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OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.
People with pancreatic cancer have poor survival, and management is challenging. Pancreatic cancer patients' perceptions of their care coordination and its association with their outcomes have not been well-studied. Our objective was to determine if perception of care coordination is associated with patient-reported outcomes or survival.
People with pancreatic cancer who were 1–8 months postdiagnosis (52 with completed resection and 58 with no resection) completed a patient-reported questionnaire that assessed their perceptions of care coordination, quality of life, anxiety, and depression using validated instruments. Mean scores for 15 care-coordination items were calculated and then ranked from highest (best experience) to lowest (worst experience). Associations between care-coordination scores (including communication and navigation domains) and patient-reported outcomes and survival were investigated using general linear regression and Cox regression, respectively. All analyses were stratified by whether or not the tumor had been resected.
In both groups, the highest-ranked care-coordination items were: knowing who was responsible for coordinating care, health professionals being informed about their history, and waiting times. The worst-ranked items related to: how often patients were asked about visits with other health professionals and how well they and their family were coping, knowing the symptoms they should monitor, having sufficient emotional help from staff, and access to additional specialist services. For people who had a resection, better communication and navigation scores were significantly associated with higher quality of life and less anxiety and depression. However, these associations were not statistically significant for those with no resection. Perception of cancer care coordination was not associated with survival in either group.
Significance of results:
Our results suggest that, while many core clinical aspects of care are perceived to be done well for pancreatic cancer patients, improvements in emotional support, referral to specialist services, and self-management education may improve patient-reported outcomes.
Over 80% of the flow of the Upper Indus River is derived from less than 20% of its area: essentially from zones of heavy snowfall and glacierized basins above 3500 m elevation. The trans-Himalayan contribution comes largely from an area of some 20 000 km2 of glacierized basins, mostly along the axis of the Greater Karakoram range and especially from 20-30 of the largest glacier basins. Very few glaciological investigations have so far been undertaken in this the major glacierized region of Central Asia. Biafo Glacier, one of the largest of the Karakoram glaciers, drains south-eastwards from the central Karakoram crest. Its basin covers a total area of 853 km2, 628 km2 of which are permanent snow and ice, with 68% of the glacier area forming the accumulation zone. This paper describes investigations of snow accumulation, ablation, glacier movement, and glacier depth undertaken in the period 1985–87, set against a background of investigations carried out over the last 130 years. Biafo Glacier differs from most of the other Karakoram glaciers in being nourished mainly by direct snowfall rather than by avalanching; this has the advantage of allowing extensive investigation of accumulation over a broad range of altitude.
Snow-accumulation studies in the Biafo Glacier basin have indicated that annual accumulation varies from 0.9 to 1.9 m of water equivalent between 4650 and 5450 m a.s.l. This suggests an annual moisture input above the equilibrium line of approximately 0.6 km3. Monopulse radar measurements indicate the presence of ice thickness as great as 1400 m at the equilibrium line, although these results may not be completely reliable. Mean surface velocity during the summer of 0.8 m d−1 has been measured near to the equilibrium line. Calculations of annual ice flux through the vertical cross-profile at the equilibrium line indicate a throughput of 0.7 km3 a−1. Estimates from stake ablation measurements also suggest that ice loss on Biafo Glacier is about 0.7 km3 a−1. The close agreement between these three sets of measurements is reassuring, indicating that the ablation zone of Biafo Glacier, whose area covers 0.09% of the whole Upper Indus basin, produces approximately 0.9% of the total run-off. However, it should be mentioned that this estimate does not include water originating from seasonal snow melt, either above or below the equilibrium line, or from rainfall. Net annual ice losses due to wastage of the glacier since 1910 are probably of the order of 0.4-0.5 m a−1; this would represent between 12 and 15% of annual water yield from melting ice.
Pigweeds are among the most abundant and troublesome weed species across Midwest and mid-South soybean production systems because of their prolific growth characteristics and ability to rapidly evolve resistance to several herbicide sites of action. This has renewed interest in diversifying weed management strategies by implementing integrated weed management (IWM) programs to efficiently manage weeds, increase soybean light interception, and increase grain yield. Field studies were conducted across 16 site-years to determine the effectiveness of soybean row width, seeding rate, and herbicide strategy as components of IWM in glufosinate-resistant soybean. Sites were grouped according to optimum adaptation zones for soybean maturity groups (MGs). Across all MG regions, pigweed density and height at the POST herbicide timing, and end-of-season pigweed density, height, and fecundity were reduced in IWM programs using a PRE followed by (fb) POST herbicide strategy. Furthermore, a PRE fb POST herbicide strategy treatment increased soybean cumulative intercepted photosynthetically active radiation (CIPAR) and subsequently, soybean grain yield across all MG regions. Soybean row width and seeding rate manipulation effects were highly variable. Narrow row width (≤ 38 cm) and a high seeding rate (470,000 seeds ha−1) reduced end-of-season height and fecundity variably across MG regions compared with wide row width (≥ 76 cm) and moderate to low (322,000 to 173,000 seeds ha−1) seeding rates. However, narrow row widths and high seeding rates did not reduce pigweed density at the POST herbicide application timing or at soybean harvest. Across all MG regions, soybean CIPAR increased as soybean row width decreased and seeding rate increased; however, row width and seeding rate had variable effects on soybean yield. Furthermore, soybean CIPAR was not associated with end-of-season pigweed growth and fecundity. A PRE fb POST herbicide strategy was a necessary component for an IWM program as it simultaneously managed pigweeds, increased soybean CIPAR, and increased grain yield.
Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
A segment of the debate surrounding the commercialization and use of glyphosate-resistant (GR) crops focuses on the theory that the implementation of these traits is an extension of the intensification of agriculture that will further erode the biodiversity of agricultural landscapes. A large field-scale study was initiated in 2006 in the United States on 156 different field sites with a minimum 3-yr history of GR-corn, -cotton or -soybean in the cropping system. The impact of cropping system, crop rotation, frequency of using the GR crop trait, and several categorical variables on seedbank weed population density and diversity was analyzed. The parameters of total weed population density of all species in the seedbank, species richness, Shannon's H′ and evenness were not affected by any management treatment. The similarity between the seedbank and aboveground weed community was more strongly related to location than management; previous year's crops and cropping systems were also important while GR trait rotation was not. The composition of the weed flora was more strongly related to location (geography) than any other parameter. The diversity of weed flora in agricultural sites with a history of GR crop production can be influenced by several factors relating to the specific method in which the GR trait is integrated (cropping system, crop rotation, GR trait rotation), the specific weed species, and the geographical location. Continuous GR crop, compared to fields with other cropping systems, only had greater species diversity (species richness) of some life forms, i.e., biennials, winter annuals, and prostrate weeds. Overall diversity was related to geography and not cropping system. These results justify further research to clarify the complexities of crops grown with herbicide-resistance traits to provide a more complete characterization of their culture and local adaptation to the weed seedbank.
A segment of the debate surrounding the commercialization of genetically
engineered (GE) crops, such as glyphosate-resistant (GR) crops, focuses on
the theory that implementation of these traits is an extension of the
intensification of agriculture that will further erode the biodiversity of
agricultural landscapes. A large field-scale study was conducted in 2006 in
the United States on 156 different field sites with a minimum 3-yr history
of GR corn, cotton, or soybean in the cropping system. The impact of
cropping system, crop rotation, frequency of using the GR crop trait, and
several categorical variables on emerged weed density and diversity was
analyzed. Species richness, evenness, Shannon's H′, proportion of forbs,
erect growth habit, and C3 species diversity were all greater in
agricultural sites that lacked crop rotation or were in a continuous GR crop
system. Rotating between two GR crops (e.g., corn and soybean) or rotating
to a non-GR crop resulted in less weed diversity than a continuous GR crop.
The composition of the weed flora was more strongly related to location
(geography) than any other parameter. The diversity of weed flora in
agricultural sites with a history of GR crop production can be influenced by
several factors relating to the specific method in which the GR trait is
integrated (cropping system, crop rotation, GR trait rotation), the specific
weed species, and the geographical location. The finding that fields with
continuous GR crops demonstrated greater weed diversity is contrary to
arguments opposing the use of GE crops. These results justify further
research to clarify the complexities of crops grown with
herbicide-resistance traits, or more broadly, GE crops, to provide a more
complete characterization of their culture and local adaptation.
In 2010, a grower survey was administered to 1,299 growers in 22 states to determine changes in weed management in the United States from 2006 to 2009. The majority of growers had not changed weed management practices in the previous 3 yr; however, 75% reported using weed management practices targeted at glyphosate-resistant (GR) weeds. Growers were asked to rate their efforts at controlling GR weeds and rate the effectiveness of various practices for controlling/preventing GR weeds regardless of whether they were personally using them. Using the herbicide labeled rate, scouting fields, and rotating crops were among the practices considered by growers as most effective in managing GR weeds. Sixty-seven percent of growers reported effective management of GR weeds. Between the 2005 and 2010 Benchmark surveys, the frequency of growers using specific actions to manage GR weeds increased markedly. Although the relative effectiveness of practices, as perceived by growers, remained the same, the effectiveness rating of tillage and the use of residual and POST herbicides increased.
Almost 1,650 corn, cotton, and soybean growers in 22 states participated in a 2010 telephone survey to determine their attitudes with regard to which weed species were most problematic in glyphosate-resistant (GR) crop production systems for corn, cotton, and soybean. The survey is a follow-up to a previous 2005 to 2006 survey that utilized a smaller set of growers from fewer states. In general, growers continued to estimate weed populations as low and few challenges have been created following adoption of GR cropping systems. Pigweed and foxtail species were dominant overall, whereas other species were more commodity and state specific. Corn, cotton, and soybean growers cited velvetleaf, annual morningglory, and waterhemp, respectively, as predominant weeds. Growers in the South region were more likely to report pigweed and waterhemp (Amaranthus spp.), whereas growers in the East and West reported horseweed. When growers were asked with which GR weeds they had experienced personally, horseweed was reported in all regions, but growers in the South more frequently reported pigweed, whereas growers in the East and West regions more frequently reported waterhemp. Comparisons with the previous 2005 survey indicated that more growers believed they were experiencing GR weeds and were more aware of specific examples in their state. In particular, the Amaranthus complex was of greatest concern in continuously cropped soybean and cotton.
Approximately 1,300 growers from 22 states were surveyed during 2010 to determine herbicide use. Cropping systems included continuous glyphosate-resistant corn, cotton, and soybean, and various combinations of these crops and rotations with non–glyphosate-resistant crops. The most commonly used herbicide for both fall and spring applications was glyphosate followed by synthetic auxin herbicides. Herbicide application in spring was favored over application in the fall. The percentage of growers in a glyphosate-only system was as high as 69% for some cropping systems. Excluding glyphosate, the most frequently used herbicides included photosystem II, mitotic, and protoporphyrinogen oxidase inhibitors. A higher percentage of growers integrated herbicides other than glyphosate during 2010 compared with 2005. Extensive educational efforts have promoted resistance management by increasing the diversity of herbicides in glyphosate-resistant cropping systems. However, a considerable percentage of growers continued use of only glyphosate from the period of 2005 to 2010, and this practice most likely will continue to exert a high level of selection for evolved glyphosate-resistant weed species.