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OBJECTIVES/GOALS: Assess molecular and cellular mechanisms of allograft loss in kidney biopsies using digital spatial profiling and clinical outcomes data. METHODS/STUDY POPULATION: Patients with chronic allograft dysfunction (CGD), enrolled in the Deterioration of Kidney Allograft Function (DeKAF) study, with or without eventual allograft loss, were included. CGD was defined as a >25% increase in creatinine over 3 months relative to a baseline. Kidney biopsy tissue was assessed by Nanostring GeoMX digital spatial profiling (DSP) after staining with anti-pan-cytokeratin, anti-CD45, anti-CD68, Syto-13, to identify specific cell populations, and Nanostring’s Whole Transcriptome Atlas (WTA), to quantify the distribution of transcripts across the biopsy. Up to 14 regions of interest (ROIs) were selected, with or without glomerulus. CIBERSORT was used to perform cell deconvolution. Clinical and outcomes data were from the DeKAF study and United States Renal Data System. RESULTS/ANTICIPATED RESULTS: Macrophage (M1) cell population abundance was significantly different in ROIs with glomerulus between graft loss and no graft loss. Principle component analysis of differentially expressed genes resulted in transcriptomes in ROIs that cluster together by clinical outcome of graft loss or no graft loss. There were 203 DEGs in ROIs with glomerulus that were different by graft loss or no graft loss. By pathway analysis, these 203 DEGS were enriched in the T-cell activation, integrin signaling and inflammation pathways. DISCUSSION/SIGNIFICANCE: DSP of kidney allograft biopsies allows for the identification and quantification of specific cell types, such as macrophages and molecular transcripts as potential drug targets. This data can be used to understand mechanisms of kidney allograft loss and may lead to improved immune suppression in kidney transplant recipients.
Those at genetic risk for Alzheimer's Disease (AD) because of the ApoE ε4 allele show differences in activation during olfactory information processing and memory in areas such as MTL structures, entorhinal cortex, posterior cingulate, precuneus, and inferior parietal lobule, suggesting preclinical AD neuropathology and olfactory impairment as a biomarker for predicting later AD onset (Murphy, 2019). The effects of smoking on AD have varied, with early studies suggesting either no effect or protective effects, and recent studies suggesting smoking as a risk factor for AD but with the need for further investigation in preclinical stages. Therefore, this study focused on olfaction and smoking as risk factors for preclinical AD neuropathology by studying differences in fMRI BOLD signal changes in smokers and nonsmokers during olfactory tasks.
Participants and Methods:
Archival data from 25 non-demented older adults recruited from the UCSD Alzheimer's Disease Research Center who completed an Assessment Scale-Cognitive Subscale (ADAS-Cog) and functional MRI scans at 3T, acquired during performance of an odor identification task. Odor Identification (OI) measured correct (hits) or incorrect (misses) identification of odors presented by an olfactometer to deliver the odor stimuli in short, controlled durations during fMRI scanning.
Results:
fMRI data were preprocessed using fMRIprep, smoothed at 4mm, scaled, and first level analyses were conducted using 3dDeconvolve in AFNI with time points corresponding to hits and misses as regressors. Differences between smokers and nonsmokers revealed smokers show a larger difference in BOLD signal change from hits minus misses at five significant clusters (p = 0.01 with the minimum cluster size [voxels] at 42). Peak areas of significant clusters included the right precuneus, right calcarine gyrus, left inferior parietal lobule, left superior parietal lobule, and left middle occipital gyrus. Analyses suggested a greater difference in activity between hits and misses in smokers compared to nonsmokers, with more activity during hits.
Conclusions:
Differences in activation between smokers and nonsmokers during an olfactory identification task, with greater activity in smokers during hits, suggests greater effort to correctly identify an odor. These findings of hyperactivation in areas (such as the precuneus and inferior parietal lobule) are similar to findings of hyperactivation during odor memory observed in studies of ε4 carriers during preclinical stages. Results provide further insight into smoking as a risk factor for AD. Moreover, results suggest the risk of smoking could potentially be reflected in altered activity in olfactory information processing networks in preclinical stages of AD. The study highlights the need for research to further understand the role smoking plays in the development of AD and the use of olfaction as a biomarker to aid in disease detection, prevention, and stage-associated treatments.
Past research has shown that many people prefer natural foods and medicines over artificial counterparts. The present study focused on examination of aversive events and hazards. Preferences were compared by having subjects consider pairs of scenarios, one natural and one artificial, matched in negative outcome and severity. Pairings were also rated along several dimensions of risk perception such as dangerousness, scariness, likelihood, and fairness. As hypothesized, natural hazards were consistently preferred to functionally identical artificial ones. Additionally, natural hazards tended to be considered less scary and dangerous, but not necessarily more unfair or unlikely than equivalent artificial counterparts. Results are discussed in terms of risk perception, and how that can lead to people diminishing risks associated with natural hazards.
To determine the usefulness of adjusting antibiotic use (AU) by prevalence of bacterial isolates as an alternative method for risk adjustment beyond hospital characteristics.
AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum β-lactamase (ESBL)–producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal β-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared.
Results:
Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016.
Conclusions:
The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.
The role that physical attractiveness and fluctuating asymmetry (FA), a measure of developmental instability, play in self-perception and peer associations were explored in a well-studied cohort of Jamaican children using a novel research paradigm where subjects were already known to each other for extensive periods of time. The results showed that how attractive a child was perceived by others was significantly positively correlated with self-ratings of attractiveness. Contrary to findings from WEIRD (Western, Educated, Industrialized, Rich, Democratic) samples, the study found a reversal in the sex differences in self-perceived attractiveness and self-esteem, where Jamaican females rate themselves more attractive and report higher self-esteem than do males. Attractiveness also predicts overall popularity, as measured by desirability as a friend and the percentage of peers who choose an individual as a friend. Attractive individuals of both sexes were chosen more often as ‘friends’. A significant correlation was also found between an individual’s FA and the average FA of those chosen as friends. However, the effect was primarily due to preferences by males for female friends possessing similar levels of FA, which could be an effective strategy in reducing future mating effort.
The last shot of Season One of Les Revenants/The Returned (Canal+, 2012–15) finds the hit French television show's nameless mountain town suddenly, mysteriously, catastrophically flooded. Water has rushed in to a place that, for the past eight episodes, has been the site of another unruly invasion: of the dead, les revenants, come back to life. They are not violent. They just want to resume the lives they lost months or years earlier. By the beginning of Season Two, the army has come to take control, managing the double catastrophe caused by a dam that cannot hold back water and the town's returned dead.
When the show first aired, it brought the French past itself into the present, for the image of a mountain community in the Haute-Savoie threatened by water, almost vacant, and under state control recalls similar historical events of more than 50 years earlier. In March 1952, the valley containing the mountain village of Tignes was flooded to make way for a new hydroelectric dam on the Isère River. Four hundred CRS were called in to remove resisting residents and dynamite their homes to prevent them from returning. These actions were the culmination of one of the most contentious and visible battles between state technocrats and the opponents – one might say victims – of modernisation that animated the early years of France's Trente Glorieuses (Fourastié 2000; Frost 1985). Although never explicitly identified, this is the same dam that appears throughout Les Revenants. Its return to French screens underpins a broader allegory about state-sponsored modernisation and its legacy, a once-‘glorious’ project returned as a story of failure and unintended consequences.
For critics and industry professionals, the returned dead of the show represented another level of allegory: the return of French dramatic television to a level of quality it had not enjoyed for decades. LesRevenants was one of the first French shows to garner public interest and critical accolades during what critics have dubbed ‘the golden age of television’. Its first season attracted record audiences and critical praise in France before being picked up for diffusion by Swedish, British, Dutch, and American channels and winning a 2013 International Emmy for Best Dramatic Series.
Heteroplasmy is the existence of multiple mitochondrial DNA haplotypes within the cell. Although the number of reports of heteroplasmy is increasing for arthropods, the occurrence, number of variants, and origins are not well studied. In this research, the occurrence of heteroplasmy was investigated in Thrips tabaci, a putative species complex whose lineages can be distinguished by their mitochondrial DNA haplotypes. The results from this study showed that heteroplasmy was due to the occurrence of mitochondrial cytochrome oxydase I (mtCOI) haplotypes from two different T. tabaci lineages. An assay using flow cytometry and quantitative real-time PCR was then used to quantify the per cell copy number of the two mtCOI haplotypes present in individuals exhibiting heteroplasmy from nine geographically distant populations in India. All of the T. tabaci individuals in this study were found to exhibit heteroplasmy, and in every individual the per cell copy number of mtCOI from lineage 3 comprised 75–98% of the haplotypes detected and was variable among individuals tested. There was no evidence to suggest that the presense of lineage-specific haplotypes was due to nuclear introgression; however, further studies are needed to investigate nuclear introgression and paternal leakage during rare interbreeding between individuals from lineages 2 and 3.
The landscapes of northern New England and adjacent areas of Canada changed greatly between 14,000 and 9000 yr B.P.: deglaciation occurred, sea levels and shorelines shifted, and a vegetational transition from tundra to closed forest took place. Data from 51 14C-dated sites from a range of elevations were used to map ice and sea positions, physiognomic vegetational zones, and the spread of individual tree taxa in the region. A continuum of tundra-woodland-forest passed northeastward and northward without major hesitation or reversal. An increased rate of progression from 11,000 to 10,000 yr B.P. suggests a more rapid warming than in the prior 2000–3000 yr. Elevational gradients controlled the patterns of deglaciation and vegetational change. The earliest spread of tree taxa was via the lowlands of southern Vermont and New Hampshire, and along a coastal corridor in Maine. Only after 12,000 yr B.P. did the taxa spread northward through the rest of the area. Different tree species entered the southern part of the area at different times and continued their spread at different rates. The approximate order of arrival follows: poplars (13,000–12,000 yr B.P. in the south), spruces, paper birch, and jack pine, followed by balsam fir and larch, and possibly ironwood, ash, and elm, and somewhat later by oak, maple, white pine, and finally hemlock (10,000–9000 yr B.P. in the south).
The judicious selection of sites for paleovegetational and paleoclimatic studies permits paleoecologists to answer specific research questions that go beyond primary descriptions of past vegetation. We present a model that describes the relationship between basin size and pollen source area and predicts the proportions of local, extralocal, and regional pollen sampled by lake basins of different size. The distinctive sampling properties of lakes, peats, and small hollows can be exploited to provide details of pattern in paleovegetation so long as attention is given to the limitations and problems of these types of sites. Combinations of site types in a single study most fully exploit the information contained in sediments.
Fláajökull is a non-surging outlet glacier draining the south-eastern part of the Vatnajökull, southeast Iceland. Fláajökull was stationary or advanced slightly between 1966 and 1995 and formed a prominent end moraine. Glacial retreat since then has revealed a cluster of 15 drumlins. This study focuses on the morphology and sedimentology of the drumlins. They are 100–600 m long, 40–130 m wide, and have cores of glaciofluvial sediment or till. The drumlins are draped by ~1 m thick, massive subglacial traction till. The glacier forefield is characterized by a number of arcuate and saw-tooth, terminal and recessional moraine ridges, overridden moraines with fluted surfaces, and glaciofluvial outwash. Some of the drumlins extend towards the 1995 end moraine but terminate abruptly at the moraine and are not observed in front of it. This suggests that they were formed sub-marginally during the 1966–1995 terminal position. The sedimentary structure of the drumlins is best explained by the sticky spot model. Dating and dendrochronological analyses of birch logs found on the surface of one of the drumlins indicate that the valley was forested about 2100 calendar year BP, after which the glacier started to reform, possibly due to an abrupt change in climate.
Cutworms are excellent insects for investigations on physiology, behaviour, and toxicology in the laboratory. Although they are often plentiful and easily obtained in the field during outbreaks their use as laboratory animals is dependent upon satisfactory methods of rearing. Cutworms vary in life history and feeding habits, and many species require distinctive rearing techniques.
This book explores how natural hazards in the Philippines can amplify the environmental harm prevalent in mining and pose a substantial threat to the livelihoods of archipelagos poor, who depend upon subsistence agriculture and subsistence aquaculture.
Given the risks associated with locating large-scale mining projects amid the natural hazards present in the Philippines, and the reluctance of many members of that archipelago's civil society to accept technological solutions to these risks, one may wonder whether a mining-based development paradigm is an appropriate approach to be followed. Will mining-related environmental disruptions brought on by the interactions of mining's environmental effects and the natural hazards present in the Philippines only serve to disrupt the ecology of the poor and end up impoverishing vulnerable communities adjacent to mining operations? Alternatively, will mining act as an engine of economic growth and generate so much prosperity that whatever instances of environmental disruption may occur can easily be compensated for by the subsequent rising tide of prosperity that “lifts all boats?”
The Twin Pillars of Sustainable Development
In addressing the efficacy of any development strategy, the concept of sustainable development is a useful metric. In 1987, the World Commission on Environment and Development defined the now ubiquitous term “sustainable development” as being “development that meets the needs of the present without compromising the ability of future generations to meet their own needs” (World Commission on Environment and Development 1987, 43). However, this definition may only be viewed as a starting point in discussions of sustainable development because much of this discussion directs its attention not on the negative consequences of economic growth upon the environment, but on the negative consequences of environmental degradation upon economic growth (Holden 2009b).
At the outset, this book posed the question, “What are the difficulties inherent in attempting to pursue a mining-based development paradigm in a country beset by natural hazards?” The Philippines is a country plagued by widespread poverty, but also richly endowed with mineral resources. To stimulate the economic development of the country, the government has rigorously promoted large-scale mining by corporations. Mining is, however, an activity with a substantial potential for environmental degradation and the Philippines is a country subjected to numerous natural hazards such as typhoons, earthquakes, tsunamis, volcanoes and El Niño–induced drought. The Philippines is also inhabited by poor people engaged in subsistence activities who are highly vulnerable to any form of environmental degradation. These natural hazards interfere with the environmental effects of mining and worsen the conditions of the poor engaged in subsistence activities thus creating disasters. The situation that transpired after the typhoon caused the tailings spill at the Rapu-Rapu Polymetallic Project in October 2005 will play itself out over and over again, possibly with catastrophic consequences. This is the classic embodiment of a disaster: a hazard that impacts a vulnerable population. A mining-based development paradigm will not generate development lifting the poor out of poverty and it will deprive them of their basic means of survival and generate disasters. To answer the question posed by the title of this book, this is not an example of “digging to development” and this is an example of “digging to disaster.”
Natural hazards are those atmospheric, hydrologic, geologic and other naturally occurring physical phenomena that have the potential to harm humans (Punongbayan 1994). An extensive body of literature exists documenting the vulnerability of the Philippines to natural hazards (Bankoff 1999, 2003a, 2003b; Bankoff and Hilhorst 2009; Delica 1993; Holden 2011; Luna 2001; Yumul et al. 2011).
Typhoons: One of the World's Most Powerful Atmospheric Phenomena
Typhoons: Tropical cyclones in the Western Pacific
Typhoon, originating from the Chinese tai (strong) and fung (wind), is the term used to describe a tropical cyclone in the Western Pacific Ocean (Bankoff 2003a). A typhoon is one of the world's most powerful atmospheric phenomena with a fully developed typhoon releasing the energy equivalent to many Hiroshima-sized atomic bombs (Wisner et al. 2004). Typhoons develop in the northern hemisphere during the months of July to November in an area just north of the equator (Bankoff 2003a; Wisner et al. 2004). They develop when strong clusters of thunderstorms drift over warm ocean waters having a temperature of at least 26.5 degrees Celsius. Warm air from the thunderstorms combines with the warm air from the ocean surface and begins rising; as this air rises there will be a reduction in air pressure on the surface of the ocean. As these clusters of thunderstorms consolidate into one large storm, trade winds blowing in opposite directions will cause the storm to begin spinning in a counter clockwise direction, while rising warm air causes air pressure to decrease at higher altitudes (Gonzalez 1994; Van Aalst 2006).