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Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
The increased use of insecticide seed treatments in rice has raised many questions about the potential benefits of these products. In 2014 and 2015, a field experiment was conducted near Stuttgart and Lonoke, AR, to evaluate whether an insecticide seed treatment could possibly lessen injury from acetolactate synthase (ALS)–inhibiting herbicides in imidazolinone-resistant (IR) rice. Two IR cultivars were tested (a hybrid, ‘CLXL745’, and an inbred, ‘CL152’), with and without an insecticide seed treatment (thiamethoxam). Four different herbicide combinations were evaluated: a nontreated control, two applications of bispyribac-sodium (hereafter bispyribac), two applications of imazethapyr, and two applications of imazethapyr plus bispyribac. The first herbicide application was to two- to three-leaf rice, and the second immediately prior to flooding (one- to two-tiller). At both 2 and 4 wk after final treatment (WAFT), the sequential applications of imazethapyr or bispyribac plus imazethapyr were more injurious to CLXL745 than CL152. This increased injury led to decreased groundcover 3 WAFT. Rice treated with thiamethoxam was less injured than nontreated rice and had improved groundcover and greater canopy heights. Even with up to 32% injury, the rice plants recovered by the end of the growing season, and yields within a cultivar were similar with and without a thiamethoxam seed treatment across all herbicide treatments. Based on these results, thiamethoxam can partially protect rice from injury caused by ALS-inhibiting herbicides as well as increase groundcover and canopy height; that is, the injury to rice never negatively affected yield.
Each year there are multiple reports of drift occurrences, and the majority of drift complaints in rice are from imazethapyr or glyphosate. In 2014 and 2015, multiple field experiments were conducted near Stuttgart, AR, and near Lonoke, AR, to evaluate whether insecticide seed treatments would reduce injury from glyphosate or imazethapyr drift or decrease the recovery time following exposure to a low rate of these herbicides. Study I was referred to as the “seed treatment study,” and Study II was the “drift timing study.” In the seed treatment study the conventional rice cultivar ‘Roy J’ was planted, and herbicide treatments included imazethapyr at 10.5 g ai ha–1, glyphosate at 126 g ae ha–1, or no herbicide. Each plot had either a seed treatment of thiamethoxam, clothianidin, chlorantraniliprole, or no insecticide seed treatment. The herbicides were applied at the two- to three-leaf growth stage. Crop injury was assessed 1, 3, and 5 wk after application. Averaged over site-years, thiamethoxam-treated rice had less injury than rice with no insecticide seed treatment at each rating, along with an increased yield. Clothianidin-treated rice had an increased yield over no insecticide seed treatment, but the reduction in injury for both herbicides was less pronounced than in the thiamethoxam-treated plots. Overall, chlorantraniliprole was generally the least effective of the three insecticides in reducing injury from either herbicide and in protecting rice yield potential. A second experiment conducted at Stuttgart, AR, was meant to determine whether damage to rice from glyphosate and imazethapyr was influenced by the timing (15, 30, and 45 d after planting) of exposure to herbicides for thiamethoxam-treated and nontreated rice. There was an overall reduction in injury with the use of thiamethoxam, but the reduction in injury was not dependent on the timing of the drift event. Reduction in damage from physical drift of glyphosate and imazethapyr as well as increased yields over the absence of an insecticide seed treatment appear to be an added benefit.
OBJECTIVES/SPECIFIC AIMS: Focal cartilage injuries of the knee joint are common and present a treatment challenge due to minimal intrinsic repair. Cartilage tissue engineering techniques currently used in clinical practice are expensive, cumbersome, and often ineffective in patients with mechanical or medical comorbidities. To address these issues, we developed an acellular nanofibrous scaffold with encapsulated growth factors designed to enhanced articular cartilage repair. Our goal is to evaluate this technology in vitro and pilot a large animal model for eventual translation into human subjects. METHODS/STUDY POPULATION: Hyaluronic acid (HA, 65 kDa) will be methacrylated (~40% modification, MeHA) and conjugated with cell-adhesive (RGD) groups. A solution of 4% wt/vol MeHA, 2% wt/vol polyethylene oxide (900 kDa), 0.05% wt/vol Irgacure 2959, and 0.005% wt/vol stromal cell-derived factor-1α (SDF-1α) and/or transforming growth factor-β3 (TGF-β3) will be prepared in ddH2O. The solution will be electrospun onto a rotating mandrel to achieve a dry scaffold thickness of 0.5 mm. The scaffold matt will be UV cross-linked and 5 mm-diameter samples will be cut out. Four groups of scaffolds will be prepared: MeHA, MeHA+SDF, MeHA+TGF, MeHA+SDF+TGF. All groups will be evaluated for fiber diameter, swell thickness, equilibrium compressive modulus, degradation rate, and growth factor release rate over 4 weeks (n=10). Scaffolds will also be seeded with juvenile porcine MSCs (5×104) in 200 μL of medium incubated for 24 hours. Seeded scaffolds will be evaluated for equilibrium compressive modulus, cell infiltration, and chondrogenesis at 4 and 8 weeks (n=10). Scaffolds will then be evaluated in a juvenile Yucatan minipig cartilage defect model. In total, 6 animals will undergo bilateral knee surgery to create four 4 mm-diameter full-thickness cartilage defects in each trochlear grove. All defects will receive microfracture to release marrow elements. Each knee will receive 2 scaffolds of the same group (replicates) with paired microfracture controls, resulting in a sample size of 3. Animals will be sacrificed at 12 weeks and defects will be evaluated via non-destructive indentation testing for mechanical properties, microCT for defect fill and subchondral bone morphology, and histology for ICRS II Visual Histological Assessment Scoring. RESULTS/ANTICIPATED RESULTS: Our preliminary studies have shown reliable replication of electrospun MeHA scaffolds. We anticipate cross-linking density to correlate positively with compressive modulus, and negatively with swell thickness, degradation rate, and growth factor release rate. We anticipate the addition of SDF-1α and TGF-β3 to increase cell infiltration and chondrogenesis, respectively, within seeded scaffolds. Similarly, we expect minipig defects treated with growth factor-releasing scaffolds to show greater mechanical properties, defect fill, and ICRS II score compared with MeHA scaffolds without growth factor. DISCUSSION/SIGNIFICANCE OF IMPACT: This study has the potential to show how an HA-based cell-free scaffold can be augmented with 2 growth factors that act synergistically to improve cartilage repair in a large animal model. This technology would improve upon the cell-free scaffolds already used clinically for autologous matrix-induced chondrogenesis and is directly translatable.
The re-emergence of debates on the decolonisation of knowledge has revived interest in the National Question, which began over a century ago and remains unresolved. Tensions that were suppressed and hidden in the past are now being openly debated. Despite this, the goal of one united nation living prosperously under a constitutional democracy remains elusive. This edited volume examines the way in which various strands of left thought have addressed the National Question, especially during the apartheid years, and goes on to discuss its relevance for South Africa today and in the future. Instead of imposing a particular understanding of the National Question, the editors identified a number of political traditions and allowed contributors the freedom to define the question as they believed appropriate – in other words, to explain what they thought was the Unresolved National Question. This has resulted in a rich tapestry of interweaving perceptions. The volume is structured in two parts. The first examines four foundational traditions: Marxism-Leninism (the Colonialism of a Special Type thesis); the Congress tradition; the Trotskyist tradition; and Africanism. The second part explores the various shifts in the debate from the 1960s onwards, and includes chapters on Afrikaner nationalism, ethnic issues, black consciousness, feminism, workerism and constitutionalism. The editors hope that by revisiting the debates not popularly known among the scholarly mainstream, this volume will become a catalyst for an enriched debate on our identity and our future.
Glyphosate-resistant populations of Conyza canadensis have been spreading at a rapid rate in Ontario, Canada, since first being documented in 2010. Determining the genetic relationship among existing Ontario populations is necessary to understand the spread and selection of the resistant biotypes. The objectives of this study were to: (1) characterize the genetic variation of C. canadensis accessions from the province of Ontario using simple sequence repeat (SSR) markers and (2) investigate the molecular mechanism (s) conferring resistance in these accessions. Ninety-eight C. canadensis accessions were genotyped using 8 SSR markers. Germinable accessions were challenged with glyphosate to determine their dose response, and the sequences of 5-enolpyruvylshikimate-3-phosphate synthase genes 1 and 2 were obtained. Results indicate that a majority of glyphosate-resistant accessions from Ontario possessed a proline to serine substitution at position 106, which has previously been reported to confer glyphosate resistance in other crop and weed species. Accessions possessing this substitution demonstrated notably higher levels of resistance than non–target site resistant (NTSR) accessions from within or outside the growing region and were observed to form a subpopulation genetically distinct from geographically proximate glyphosate-susceptible and NTSR accessions. Although it is unclear whether other non–target site resistance mechanisms are contributing to the levels of resistance observed in target-site resistant accessions, these results indicate that, at a minimum, selection for Pro-106-Ser has occurred in addition to selection for non–target site resistance and has significantly enhanced the levels of resistance to glyphosate in C. canadensis accessions from Ontario.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.