OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.

Priorities in Medical Research (PMR) was published in 1988 by a select committee of the House of Lords. The report ushered in an era of NHS research and development (R & D) that lasted from 2001 to 2006. The inquiry's origins lay in concerns about academic medicine in the United Kingdom, yet PMR gave relatively little attention to this subject. Instead the report focused critically on the disconnect between the Department of Health and the NHS in R & D. This, the committee argued, had led to the neglect of research into health services and public health. To sidestep the report's unwelcome proposal for a National Health Research Agency, the department eventually grafted R & D management onto structures created as part of wider NHS reforms. The Medical Research Council successfully pursued a strategy of keeping the committee's attention away from sensitive aspects of its own programme. The final focus of PMR was shaped by an alignment between committee members with an industrial view of research and champions of health services research. The actions of the various actors involved are interpreted using elite models of the state, and the applicability of these models is critically examined.

This study provides a morphological and phylogenetic characterization of two novel species of the order Haplosporida (Haplosporidium carcini n. sp., and H. cranc n. sp.) infecting the common shore crab Carcinus maenas collected at one location in Swansea Bay, South Wales, UK. Both parasites were observed in the haemolymph, gills and hepatopancreas. The prevalence of clinical infections (i.e. parasites seen directly in fresh haemolymph preparations) was low, at ~1%, whereas subclinical levels, detected by polymerase chain reaction, were slightly higher at ~2%. Although no spores were found in any of the infected crabs examined histologically (n = 334), the morphology of monokaryotic and dikaryotic unicellular stages of the parasites enabled differentiation between the two new species. Phylogenetic analyses of the new species based on the small subunit (SSU) rDNA gene placed H. cranc in a clade of otherwise uncharacterized environmental sequences from marine samples, and H. carcini in a clade with other crustacean-associated lineages.

The ‘Rothschild reforms’ of the early 1970s established a new framework for the management of government-funded science. The subsequent dismantling of the Rothschild system for biomedical research and the return of funds to the Medical Research Council (MRC) in 1981 were a notable departure from this framework and ran contrary to the direction of national science policy. The exceptionalism of these measures was justified at the time with reference to the ‘particular circumstances’ of biomedical research. Conventional explanations for the reversal in biomedical research include the alleged greater competence and higher authority of the MRC, together with its claimed practical difficulties. Although they contain some elements of truth, such explanations are not wholly convincing. Alternative explanations hinge on the behaviour of senior medical administrators, who closed ranks to ensure that de facto control was yielded to the MRC. This created an accountability deficit, which the two organizations jointly resolved by dismantling the system for commissioning biomedical research. The nature and working of medical elites were central to this outcome.

This notice describes a correction to the above mentioned paper.

The increased accessibility of soft-tissue data through diffusible iodine-based contrast-enhanced computed tomography (diceCT) enables comparative biologists to increase the taxonomic breadth of their studies with museum specimens. However, it is still unclear how soft-tissue measurements from preserved specimens reflect values from freshly collected specimens and whether diceCT preparation may affect these measurements. Here, we document and evaluate the accuracy of diceCT in museum specimens based on the soft-tissue reconstructions of brains and eyes of five bats. Based on proxies, both brains and eyes were roughly 60% of the estimated original sizes when first imaged. However, these structures did not further shrink significantly over a 4-week staining interval, and 1 week in 2.5% iodine-based solution yielded sufficient contrast for differentiating among soft-tissues. Compared to six “fresh” bat specimens imaged shortly after field collection (not fixed in ethanol), the museum specimens had significantly lower relative volumes of the eyes and brains. Variation in field preparation techniques and conditions, and long-term storage in ethanol may be the primary causes of shrinkage in museum specimens rather than diceCT staining methodology. Identifying reliable tissue-specific correction factors to adjust for the shrinkage now documented in museum specimens requires future work with larger samples.

The growth regulator herbicides 2,4-D and dicamba are used to control glyphosate-resistant horseweed before crops are planted. With the impending release of 2,4-D–resistant and dicamba-resistant crops, use of these growth regulator herbicides postemergence will likely increase. The objective of this study was to determine the effectiveness of various growth regulators on Indiana horseweed populations. A greenhouse dose–response study was conducted to evaluate the effectiveness of 2,4-D ester, diglycolamine salt of dicamba, and dimethylamine salt of dicamba on control of four populations of horseweed in the greenhouse. Population 66 expressed twofold levels of tolerance to 2,4-D ester and diglycolamine salt of dicamba. Population 43 expressed an enhanced level of tolerance to diglycolamine salt of dicamba but not to the other herbicides. Diglycolamine salt of dicamba provided the best overall control of populations 3 and 34. Additionally, a field study was conducted to evaluate standard use rates of 2,4-D amine, 2,4-D ester, diglycolamine salt of dicamba, and dimethylamine salt of dicamba on control of various sized glyphosate-resistant horseweed plants. Control of plants 30 cm or less in height was 90% or greater for all four herbicides. On plants greater than 30 cm tall, diglycolamine salt of dicamba provided 97% control while 2,4-D amine provided 81% control. Diglycolamine salt of dicamba provided the highest level of control of glyphosate-resistant horseweed, followed by dimethylamine salt of dicamba, 2,4-D ester and 2,4-D amine, respectively. This research demonstrates that horseweed populations respond differently to the various salts of 2,4-D and dicamba, and it will be important to determine the appropriate use rates of each salt to control glyphosate-resistant horseweed.

Horseweed can be a problematic weed in no-till soybean fields and populations can vary in their response to 2,4-D. The objective of this study was to evaluate the growth and seed production of four horseweed populations after exposure to 2,4-D. 2,4-D amine was applied at 0, 140, 280, and 560 g ae ha−1 to 5- to 10-cm-tall horseweed plants. An additional treatment of 280 g ha−1 of 2,4-D + 840 g ae ha−1 of glyphosate was included in the study. At 2 wk after treatment (WAT), injury ranged from 47 to 98%, but by 6 WAT the injury ranged from 89 to 100% for all four populations. Between 6 and 12 WAT some individual horseweed plants started to recover. No differences in dry weights were observed between the four populations in the untreated checks at 0, 2, 6, and 12 WAT. At 280 g ha−1 of 2,4-D amine, seed production was reduced by greater than 95%. However, three of the four horseweed populations had plants that survived and produced seed after exposure to 840 g ha−1 of glyphosate + 280 g ha−1 of 2,4-D. One plant produced seed after exposure to 560 g ha−1 of 2,4-D. These results suggest that horseweed can evolve resistance to 2,4-D and no fitness penalities were observed in populations that had higher levels of tolerance to 2,4-D.

Horseweed is an increasingly problematic weed in soybean because of the frequent occurrence of glyphosate-resistant (GR) biotypes. The objective of this study was to determine the influence of crop rotation, winter wheat cover crops (WWCC), residual nonglyphosate herbicides, and preplant herbicide application timing on the population dynamics of GR horseweed and crop yield. A field study was conducted at a site with a moderate infestation of GR horseweed (approximately 1 plant m−2) with crop rotation (soybean–corn or soybean–soybean) as main plots and management systems as subplots. Management systems were evaluated by quantifying horseweed plant density, seedbank density, and crop yield. Crop rotation did not influence in-field horseweed or seedbank densities at any data census timing. Preplant herbicides applied in the spring were more effective at reducing horseweed plant densities than when applied in the previous fall. Spring-applied, residual herbicide systems were the most effective at reducing season long horseweed densities and protecting crop yield because horseweed in this region behaves primarily as a summer annual weed. Horseweed seedbank densities declined rapidly in the soil by an average of 76% for all systems over the first 10 mo before new seed rain. Despite rapid decline in total seedbank density, seed for GR biotypes remained in the seedbank for at least 2 yr. Therefore, to reduce the presence of GR horseweed biotypes in a local no-till weed flora, integrated weed management (IWM) systems should be developed to reduce total horseweed populations based on the knowledge that seed for GR biotypes are as persistent in the seed bank as glyphosate-sensitive (GS) biotypes.

Greenhouse studies were conducted to determine the prevalence of resistance to acetolactate synthase (ALS)-inhibiting herbicides in 266 Indiana horseweed populations, both glyphosate-susceptible and glyphosate-resistant, and to characterize the response of selected biotypes to combinations of glyphosate and cloransulam. Populations with individuals resistant to ALS inhibitors were more frequent in the northern half (38% of the populations in the NW and 50% of the populations in the NE) of Indiana than in the southern half (26% of the populations in the SW and 5% of the populations in the SE). Only 2% of the populations appeared to be resistant to both glyphosate and ALS inhibitors in an initial greenhouse study. Horseweed populations with resistance to ALS inhibitors exhibited herbicide doses required for 50% reduction in plant growth (GR50) values ranging from 14 to 255 g ai ha−1 of cloransulam. The resistant : susceptible (R : S) ratio for four horseweed populations with suspected resistance to glyphosate and ALS inhibitors ranged from 0.3 to 50 and from 2.5 to 8.1 for cloransulam and glyphosate, respectively. The tank mixtures exhibited an antagonistic response to 3 of the 16 combinations of cloransulam and glyphosate on the susceptible population. The tank mixtures exhibited primarily an additive response to those same combinations in the multiple-resistant populations, but the response was occasionally synergistic for two of the four populations. The additive response between glyphosate and cloransulam indicates that, where the level of resistance is fairly low, combinations of these herbicides should be more effective for control of multiple-resistant populations compared with application of a single herbicide.

Horseweed is an increasingly common and problematic weed in no-till soybean production in the eastern cornbelt due to the frequent occurrence of biotypes resistant to glyphosate. The objective of this study was to determine the influence of crop rotation, winter wheat cover crops (WWCC), residual non-glyphosate herbicides, and preplant application timing on the population dynamics of glyphosate-resistant (GR) horseweed and crop yield. A field study was conducted from 2003 to 2007 in a no-till field located at a site that contained a moderate infestation of GR horseweed (approximately 1 plant m−2). The experiment was a split-plot design with crop rotation (soybean–corn or soybean–soybean) as main plots and management systems as subplots. Management systems were evaluated by quantifying in-field horseweed plant density, seedbank density, and crop yield. Horseweed densities were collected at the time of postemergence applications, 1 mo after postemergence (MAP) applications, and at the time of crop harvest or 4 MAP. Viable seedbank densities were also evaluated from soil samples collected in the fall following seed rain. Soybean–corn crop rotation reduced in-field and seedbank horseweed densities vs. continuous soybean in the third and fourth yr of this experiment. Preplant herbicides applied in the spring were more effective at reducing horseweed plant densities than when applied in the previous fall. Spring-applied, residual herbicide systems were the most effective at reducing season-long in-field horseweed densities and protecting crop yields since the growth habit of horseweed in this region is primarily as a summer annual. Management systems also influenced the GR and glyphosate-susceptible (GS) biotype population structure after 4 yr of management. The most dramatic shift was from the initial GR : GS ratio of 3 : 1 to a ratio of 1 : 6 after 4 yr of residual preplant herbicide use followed by non-glyphosate postemergence herbicides.

Late-season field surveys conducted in Indiana from 2003 to 2005 showed that common lambsquarters and giant ragweed plants were present in 11 and 22%, respectively, of randomly sampled soybean fields that also contained glyphosate-resistant horseweed. In the fall of 2005 and 2006, seed from 13 common lambsquarters and 22 giant ragweed populations were collected from previously surveyed fields that had confirmed glyphosate-sensitive or -resistant horseweed. The objective of this study was to determine whether the presence of glyphosate-resistant horseweed was correlated with the presence of common lambsquarters and giant ragweed biotypes with elevated tolerance to glyphosate. Through a series of greenhouse screens, 57% of common lambsquarters and 31% of giant ragweed populations collected from fields that had glyphosate-resistant horseweed expressed elevated levels of glyphosate tolerance. However, elevated tolerance to glyphosate was expressed by 33% of giant ragweed and 100% of common lambsquarters populations collected in fields that had glyphosate-sensitive horseweed. Therefore, under the parameters of this experiment and through different types of analyses, we concluded there was not a strong correlation between the late-season presence of glyphosate-resistant horseweed and common lambsquarters and giant ragweed populations with elevated glyphosate tolerance in the same field. A number of the weed populations expressed significant stunting from exposure to glyphosate, but were able to resume growth. Thus, researchers should evaluate plant regrowth in addition to biomass suppression when making assessments of glyphosate resistance in weed populations through greenhouse and field screening.

2,4-D is often used as a preplant burndown herbicide to help control horseweed and other broadleaf weeds before planting in no-till corn and soybean production. Isolated instances of poor horseweed control have occurred in production fields. The objective of this research was to evaluate the response of various horseweed populations to 2,4-D. In the first study, 478 horseweed populations from Indiana were subjected to 280 g ae ha−1 of 2,4-D amine in the greenhouse. This rate of 2,4-D caused visible injury and prevented all biotypes from forming new leaves for 28 days. There were specific populations where all plants sprayed were alive at 28 days after treatment (DAT), and approximately 10% of all populations had a least one plant that survived 280 g ae ha−1 2,4-D, resumed growth, and produced seed. In a dose-response study, we observed populations with three-fold more tolerance to 2,4-D. The most tolerant population had a GR90 of 513 g ae ha−1 and the most susceptible population had a GR90 of 121 g ae ha−1 based on dry weights. Growth suppression with 2,4-D was not affected by rosette size for rosettes between 0.5 and 10 cm in width.