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Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to assess the efficacy of combined AF and NP repairs to prevent degenerative changes and restore native disc morphology in an in vivo large animal model. We hypothesize that combined repairs will prevent disc degeneration following injury to a greater extent than the individual repairs after 6 weeks in vivo, as demonstrated through disc height measurements and disc morphology. METHODS/STUDY POPULATION: A total of 8 skeletally mature female Finn sheep were used in this study. Following a previously described method, IVDs from L1 to L6 of the lumbar spine were exposed using a lateral access, extraperitoneal approach5. IVDs were randomized into 5 treatment groups: 1) intact discs, 2) discs injured via a 3 cm x 1 cm box annulotomy and partial nucleotomy, 3) injury followed by a high density collagen (HDC) AF patch, 4) injury followed by injection of a modified hyaluronic acid (HA) into the NP, and 5) injury followed by both the HDC AF patch and HA NP injection. The HDC treatment was 15 mg/mL type-I collagen mixed with 0.06mM riboflavin, injected at the defect site and crosslinked in situ with blue light. The NP injection was HA modified with C16 side chains to increase the viscosity of the hydrogel (HYADD 4®)6. At 6 weeks post-operatively, sheep were sacrificed and had 3T magnetic resonance images (MRI) taken of their lumbar spine. Disc height analysis and Pfirrmann grading were performed on each segment using MR images. Additionally, quantitative MRI analyses were performed using a custom MATLAB algorithm that segments NP from the surrounding tissue and directly measures the NP volume. ANOVA with Tukey’s HSD was used to determine statistical significance between groups for disc height and quantitative MRI analyses, and the Kruskal-Wallis test with Mann-Whitney tests was used to statistically analyze Pfirrmann Grades. All animal use followed approved IACUC protocol. RESULTS/ANTICIPATED RESULTS: As shown in axial MR images (Figure 1A), intact discs had hyperintense NP with a distinct border to the AF. The discs receiving injury with no treatment had hypointense NP with no distinct border between the AF and NP. Individual and combined treatment with the HA NP injection and HDC AF patch appeared to preserve the hyperintense NP signal and AF/NP border. Intact control discs were not degenerated and had an average Pfirrmann grade of 1 (Figure 1B), while injured, untreated discs had significant degeneration with an average Pfirrmann grade of 3. Discs receiving the HA NP injection and collagen AF patch individually showed fewer signs of degeneration than the injured alone, and the combined treatment resulted in the least amount of degeneration with Pfirrmann grades not significantly different than the intact controls. Disc height index confirmed the trends seen in the Pfirrmann grades (Figure 1C), where injured discs lost 20% of the intact disc height, the individual NP and AF repairs restored 5-10% of intact disc height, and the combined repairs preserved 90% of the intact disc height. The NP voxel count of all treatment groups were similar to the intact controls (Figure 1D). DISCUSSION/SIGNIFICANCE OF IMPACT: The objective of this study was to determine how combined AF and NP can prevent degenerative changes to the disc in a large animal in vivo model. Pfirrmann grading and disc height index results show that the greatest preservation of disc morphology was seen with combined AF and NP repairs, while the individual strategies prevented degenerative changes better than injury with no treatment. It appears the HA NP injection restores lost water content to the disc following injury, and the AF collagen patch plays a role in maintaining the NP repair within the disc. This is the first study to our knowledge to attempt combined AF and NP repairs in an in vivo large animal model. Combining NP and AF repairs leads to significantly improved outcomes following disc injury, which warrants the translation of combined repairs into the clinic to improve patient outcomes with degenerative disc disease involving NP and AF.
Adverse events during the perinatal period have traditionally been thought to contribute to the risk of febrile seizures although an association has not been found in large epidemiological studies. Disease-discordant twins provide a means to assess the role of non-shared environmental factors while matching for confounding factors and avoiding difficulties of epidemiological studies in singletons. This study aimed to examine the association of obstetric events and febrile seizures in a community-based twin study. Twenty-one twin pairs discordant for febrile seizures were ascertained from a community-based twin register. Obstetric events were scored using the McNeil-Sjöström Scale for Obstetric Complications and expressed as a summary score (OC score). The frequency of individual obstetric events in affected and unaffected twins, the within-pair differences in OC scores and other markers of perinatal risk including birthweight, birth order and Apgar scores were examined. No significant difference was found in the frequency of individual obstetric events, nor in OC scores between affected and unaffected twins. No differences in birth weight, birth order, 1- or 5-minute Apgar scores were observed. Our results confirm previous findings that obstetric events are not associated with the risk of febrile seizures.
Forensic science error rates are needlessly high. Applying the perspective of veritistic social epistemology to forensic science could produce new institutional designs that would lower forensic error rates. We make such an application through experiments in the laboratory with human subjects. Redundancy is the key to error prevention, discovery, and elimination. In the “monopoly epistemics” characterizing forensics today, one privileged actor is asked to identify the truth. In “democratic epistemics,” several independent parties are asked. In an experiment contrasting them, democratic epistemics reduced the rate at which biased observers obscured the truth by two-thirds. These results highlight, first, the potential of “epistemic systems design,” which employs the techniques of economic systems design to address issues of veracity rather than efficiency, and second, the value of “experimental epistemology,” which employs experimental techniques in the study of science.
Not all disturbances cause a loss of fertility. Disturbances typically include events that cause a loss of biomass (plant and animal tissues, or merely some organic matter). However, disturbances can also involve the displacement of biomass across the landscape. When biomass floats downstream, the areas where that biomass is deposited can become more fertile than they were before the disturbance. Ocean currents, tides and storm surges, and the seasonal turnover of lake waters also redistribute biomass and nutrients. Many civilizations have depended on such redistribution of nutrients. River floodplains have supported mighty cultures in Egypt along the Nile and in western Asia along the Tigris and Euphrates and still periodically fertilize many agricultural hotspots with organic and mineral-rich sediments. Coastal cultures have long depended on the bountiful products of cold, upwelling ocean currents that bring nutrient-rich waters to coastlines such as Peru and Norway.
This chapter explores how humans interact with fertile, unstable habitats after sudden or chronic disasters. These habitats include unstable slopes that result in landslides, river floodplains, lakeshores and estuaries. Landslides may be hard to farm and build on, but the burgeoning human population and increasingly sophisticated building technology have led to intensive human activities, both urban and agricultural, in these habitats. It is appreciated that living on a floodplain carries dangers, but floodplains are among the most fertile agricultural sites. Thus, while humans would prefer to live on stable sites that do not flood, they often rely on floods to deposit nutrients on their fields.
Each day we are bombarded with news of natural disturbances. Volcanoes rain unimaginable destruction down on mountain villages, hurricanes and tsunamis ravage coastal communities and fires turn lush forests into ashen specters. Such violent events are fundamental, unavoidable parts of the global environment that in the long term restore and rejuvenate the landscape. In the short term, societies must respond to mitigate the devastation.
Human societies are also assailed by silent disturbances that rarely merit mention in the media. Dunes creep out of a desert to swallow an oasis. Exotic species of shrubs invade grazing land. Lake levels slowly fall, eliminating unique biota and cultures. As our numbers increase, humans have unavoidably become a new form of disturbance. We rival volcanoes, floods, dunes and glaciers in the intensity of our impacts. Our actions magnify other disturbances. Grazing gradually turns steppes to deserts and agriculture impoverishes the land. Our industries pollute in both subtle and more blatant ways that merely reduce productivity or poison ecosystems.
Unlike most natural disturbances, human impacts continue to intensify and become more widespread. Worse, as populations burgeon into ever more sensitive habitats, the effects of natural disasters are becoming increasingly devastating.
We are both academic plant ecologists who have spent most of our careers studying ecosystems damaged by nature and by man. We worry greatly that the natural world is shrinking, losing its ability to sustain biodiversity and, indeed, the human species.
Hard rock surfaces abound in nature, but they eventually develop a cover of vegetation. External forces soon begin to alter them by increasing their permeability to water and susceptibility to erosion. Even the slightest roughness or a small crack will allow plants to colonize such hard surfaces. Surface heterogeneity is caused by rapid temperature changes or by differential erosion of rock minerals. Most of these surfaces are created by lava (from Italian, labes, a falling, coined by Francesco Serao upon observing Vesuvius erupting in 1737), but steady erosion can also expose other types of rocks over time. Abrupt exposure of rock surfaces comes from sudden events such as landslides. Although hard surfaces are infertile, their stability allows slow-growing lichens to establish in dry habitats and mosses in wetter habitats. Cracks allow long-rooted woody plants, like trees, to gain a foothold. If successful, these large plants soon dominate exposed rocky surfaces, covering them with their dead leaves and accelerating the process of soil development and successional change in plant composition. On gentle terrain, succession may be slow, but it is inexorable. On steep slopes, gravity chronically removes nascent plant life, exposing new, abiotic surfaces. How plants cope with such stresses in natural habitats provides unique lessons for rehabilitation of analogous habitats caused by humans such as abandoned roads, parking lots and industrial rubble, quarries and walls. In this chapter, we will discuss two very different kinds of hard surfaces: lava and cliffs.
Dramatic natural disturbances are sometimes so incomprehensible and so destructive to humans that we blame supernatural beings: lightning is Thor striking his hammer, hurricanes are controlled by Hanaka, volcanoes erupt capriciously at the whim of deities such as Vulcan or Pele, while Poseidon wreaks havoc by flooding dry land. As our understanding of cataclysmic forces such as hurricanes, volcanoes and flooding grows, we begin to grasp some of the mechanics of a disturbance. Progress has been made in predicting weather (especially hurricane trajectories), the likelihood of volcanic eruptions and even the timing and extent of floods. However, there is still much to learn about where, why and when disturbances occur. Some answers lie in global weather patterns or wobbles in the tilt of the earth. Yet, enough mysteries remain that supernatural causes provide attractive explanations for some. Whatever their mechanics, timing or ultimate causes, disturbances are as much a part of our lives as dawn and dusk, as inevitable as winter following autumn. It behooves us to try to understand disturbances in order to mitigate their negative impacts, or at least to learn when it is best to run away and when it is best to stay. Disturbances vary widely in size and destructiveness. They can be as small as one tree falling in your backyard or as large as the 2004 tsunami in the Indian Ocean. In this chapter, we outline the types of disturbance and clarify the definitions of disturbance.
The pristine world of the past was filled with cataclysms. Volcanoes, earthquakes, floods and fires shaped today's landscapes and every living organism evolved in response to natural disturbance. What we call Nature survived in a finely tuned balancing act between the forces of destruction and recovery. Recovery of Nature after destruction was inevitable, but it occurred at variable rates and with a constantly evolving mix of plants and animals. Occasionally natural disturbances were so violent that many species became extinct. Today, the rules have changed; humans have profoundly altered the balance of destruction and recovery, by intensifying natural disturbances and creating many novel ones, without an equal emphasis on recovery. What are the consequences of this meddling by humans with the future of this planet?
Humans have always been at the mercy of large natural disturbances, though we try to forget this fact. The Minoans left little but legends (e.g. Atlantis) after the massive eruption of Santorini (Thera) in about 1623 BC. Agriculture in Japan suffered terrible blows from sixth century volcanic eruptions, as did the economies of both Iceland and Europe by the eruptions of Laki in 1783. Yet we continue to build on active volcanoes, steep slopes prone to erosion and floodplains subject to flooding. Recently, we have felt a growing, yet false, sense of protection from the natural forces of destruction because many of us now live in safe, artificially created environments.
Natural disasters destroy more property and kill more people with each passing year. Volcanic eruptions, earthquakes, hurricanes, tsunamis, floods, landslides, fires and other natural events are becoming more frequent and their consequences more devastating. Del Moral and Walker provide a comprehensive summary of the diverse ways in which natural disasters disrupt humanity and how humans cope. Burgeoning human numbers, shrinking resources and intensification of the consequences of natural disasters have produced a crisis of unparalleled proportions. Through this detailed study, the authors provide a template for improving restoration to show how relatively simple approaches can enhance both human well-being and that of the other species on the planet. This book will appeal to ecologists, land managers as well as anyone curious about the natural world and natural disasters.
Some of the most dramatic landscapes on earth scarcely support life because they are infertile and unstable. Infertility limits growth and instability limits establishment. These neglected, barren habitats of our world once escaped human impact because of their isolation and because productive habitats were more profitable. Today, humans are creating similarly impoverished habitats, but unlike natural ones, human-created barrens are close to human habitats and less productive. Due to the continuing global loss of usable habitat, these unproductive environments could be restored for human use.
Volcanoes, moving sands and glaciers all form infertile and unstable habitats. In the aftermath of violent cataclysms, volcanoes can create unstable surfaces such as lahars and scoria. The slow advance of sterile sand dunes across the landscape has both beneficial and catastrophic aspects. While coastal dunes protect the shores, interior dunes are expanding at alarming rates to threaten many communities and ruin pastoral lands. However, many interior dunes also support rare and complex ecosystems. The grinding, global retreat of glacial ice reveals jumbled barrens. The biota colonizes these inhospitable sites only with difficulty and persistence. Plants and animals eventually colonize the empty habitats formed by volcanoes, dunes and melting glaciers and when they do their success offers lessons for restoration of similar infertile and unstable habitats. In this chapter, we explore the constraints to establishment on these severely altered ecosystems and suggest that even they have value for sustaining economies and easing pressure on other habitats.
Disturbances of fertile, stable habitats are often caused by natural events including fire, hurricanes, intense rainfall events and strong winds or by human activities that include intentionally set fires, agriculture, logging and grazing. Recovery following mild disturbances is normally rapid compared to intensely damaged sites because there is residual soil, vegetation and fauna and because the disturbance was not severe. However, wildfire, strong winds and human actions can lead to dramatic or subtle degradation of ecosystem properties on a site. When these more intense disturbances occur or chronic disturbances cease, the functioning of the system may have changed permanently and a return to productive ecosystems is not assured. The recovery then occurs in a new context, often quite different from that under which the ecosystem developed.
Today, many natural ecosystems across the world are in crisis. It is as if their immune systems have been compromised as combinations of natural and man-made disturbances become increasingly severe. How to manipulate the aftermath of these disturbances without loss of fertility or stability are lessons that silviculture and agriculture can learn from natural processes. Given that world agricultural production contributes about three quarters of global soil erosion, those lessons appear not yet to have been mastered.
How do ecosystems and humans respond to disturbances in stable habitats that cause relatively little loss of fertility?
The earth has provided many lessons for humanity in the form of how to repair damage from natural disasters. Landscapes formed by natural calamities provide a theater for evolution (e.g. endemism on dunes and volcanoes, biodiversity enhancements following fires and variable landscapes created by glaciers, floods and landslides). These natural disasters are part of the environment, but their effects are ephemeral in the grand scheme of things … ecosystems do recover. However, natural processes are often slow, leaving unproductive land that causes long-term privations, and a return to the previous status quo is never certain. We no longer have the luxury to wait for a natural recovery that, if it comes at all, will not produce welcome results. We face huge problems that challenge our ability to cope with complex, interacting systems. Social, political and economic problems are intensified by damage and destruction of the natural systems that support human populations. Addressing problems of resource supply and habitat restoration by applying lessons provided by natural recovery will improve our collective well-being and effectively promote security.
Natural disturbances are an integral part of the physical and biological processes on Earth, and natural recovery ensures the continued health of the planet. Long before humans arrived, species evolved in the context of a constantly changing environment. The rich variety of plants, animals and microbes is a direct result of disturbance, followed by multiple patterns of evolution, each leading to a unique, successful way to cope with the environmental changes.