We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Prior to the COVID-19 pandemic, our research group initiated a pediatric practice-based randomized trial for the treatment of childhood obesity in rural communities. Approximately 6 weeks into the originally planned 10-week enrollment period, the trial was forced to pause all study activity due to the COVID-19 pandemic. This pause necessitated a substantial revision in recruitment, enrollment, and other study methods in order to complete the trial using virtual procedures. This descriptive paper outlines methods used to recruit, enroll, and manage clinical trial participants with technology to obtain informed consent, obtain height and weight measurements by video, and maintain participant engagement throughout the duration of the trial.
Methods:
The study team reviewed the IRB records, protocol team meeting minutes and records, and surveyed the site teams to document the impact of the COVID-19 shift to virtual procedures on the study. The IRB approved study changes allowed for flexibility between clinical sites given variations in site resources, which was key to success of the implementation.
Results:
All study sites faced a variety of logistical challenges unique to their location yet successfully recruited the required number of patients for the trial. Ultimately, virtual procedures enhanced our ability to establish relationships with participants who were previously beyond our reach, but presented several challenges and required additional resources.
Conclusion:
Lessons learned from this study can assist other study groups in navigating challenges, especially when recruiting and implementing studies with rural and underserved populations or during challenging events like the pandemic.
Palmer amaranth is a common weed on levees in rice fields but has become increasingly problematic with the adoption of furrow-irrigated rice and lack of an established flood. Florpyrauxifen-benzyl previously has been found effective for controlling Palmer amaranth in rice, but the efficacy of low rates of florpyrauxifen-benzyl and the effect of Palmer amaranth size on controlling it is unknown. The objective of this research was to determine the level of Palmer amaranth control expected with single and sequential applications of florpyrauxifen-benzyl at varying weed heights. The first study was conducted near Marianna, AR, in 2019 and 2020, to determine the effect of florpyrauxifen-benzyl rate on control of <10 cm (labeled size) and 28- to 32-cm-tall (larger-than-labeled size) Palmer amaranth. The second experiment was conducted in 2020 at two locations in Arkansas to compare single applications of florpyrauxifen-benzyl at low rates to sequential applications at the same rates with a 14-d interval on 20- and 40-cm-tall Palmer amaranth. Results revealed that florpyrauxifen-benzyl at 15 g ae ha−1 was as effective as 30 g ae ha−1 in controlling <10-cm-tall Palmer amaranth (92% and 95% mortality in 2019). Sequential applications of florpyrauxifen-benzyl at 8 g ae ha−1 were as effective as single or sequential applications at 30 g ae ha−1. However, no rate of florpyrauxifen-benzyl applied to 20- or 40-cm-tall Palmer amaranth was sufficient to provide season-long control of the weed, with the escaping female plants producing as many as 6,120 seed per plant following a single application.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Environmental conditions surrounding herbicide applications are known to affect weed control and crop response. Variable levels of rice injury caused by florpyrauxifen-benzyl have been observed across cropping systems and environmental conditions, warranting research in which single environmental and management strategies are isolated to understand the effect of each factor on rice injury and subsequent reductions in rice growth. A field study was conducted to determine the effects of planting date, rice cultivar, and florpyrauxifen-benzyl rate on rice injury, maturity, and yield. Two greenhouse studies were conducted to determine the effect of soil moisture and time of flooding after florpyrauxifen-benzyl application on rice injury caused by the herbicide. Growth chamber experiments were conducted to isolate the effects of temperature and light intensity on rice injury caused by florpyrauxifen-benzyl. In the field study, levels of injury varied across planting dates in both years, indicating the influence of environment on the crop response to florpyrauxifen-benzyl applications. Under dry (40% soil moisture) and saturated (100%) soil conditions, rice injury increased to 36% and 35%, respectively, compared with 27% and 25% injury at 60% and 80% soil moisture, respectively. Flooding rice 0 to 6 d after florpyrauxifen-benzyl application reduced visible injury; however, a reduction in rice tiller production occurred when the rice was flooded the same day as application. Visible rice injury increased when florpyrauxifen-benzyl was applied under low light intensity (700 µmol m−2 s−1) and high temperatures (35/24 C day/night). Based on these findings, applications of florpyrauxifen-benzyl are least likely to cause unacceptable rice injury when applied to soils having 60% and 80% saturation in high light, low temperature environments, and the crop is flooded 3 to 6 d following application.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
The distinct turbulence dynamics and transport modulated by a common seagrass species were investigated experimentally using a flexible surrogate canopy in a refractive-index-matching environment that enabled full optical access. The surrogate seagrass replicated the dynamic behaviour and morphological properties of its natural counterpart. The flows studied were subcritical with Froude numbers $Fr<0.26$ and concerned five Reynolds numbers $Re\in [3.4\times 10^{4}, 1.1\times 10^{5}]$ and Cauchy numbers $Ca\in [120, 1200]$. Complementary rigid canopy experiments were also included to aid comparative insight. The flow was quantified in wall-normal planes in a developed region using high-frame-rate particle image velocimetry. Results show that the deflection and coordinated waving motion of the blades redistributed the Reynolds stresses above and below the canopy top. Critically, in-canopy turbulence associated with the seagrass lacked periodic stem wake vortex shedding present in the rigid canopy, yet the flexible canopy induced vortex shedding from the blade tips. Inspection of spatial and temporal characteristics of coherent flow structures using spectral proper orthogonal decomposition reveals that Kelvin–Helmholtz-type vortices are the dominant flow structures associated with the waving motion of the seagrass and that modulated the local flow exchange in both rigid and flexible canopies. A barrier-like effect produced by the blade deflections blocked large-scale turbulence transport, thereby reducing vortex penetration into the canopy. In addition, we uncovered a transition from sweep-dominated to ejection-dominated behaviour in the surrogate seagrass. We hypothesise that the vortices created during the upward blade motion period play a major role in the sweep-to-ejection-dominated transition. Conditionally averaged quadrant analysis on the downward and upward blade motion supports this contention.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
The first western Canadian records of the European carabid, Nebria brevicollis (Fabricius) (Coleoptera: Carabidae), are reported from Vancouver, Coquitlam, and Delta, British Columbia, Canada. A species description is provided to facilitate identification of this new invasive species. In addition, pitfall trap data are presented that demonstrate establishment of populations at four locations in Coquitlam. Trap catches were substantially higher at one anthropogenic meadow site than at three urban forest sites. Potential for further expansion of the range of N. brevicollis in British Columbia and beyond is discussed.
A growing body of research supports the value of a multimodal assessment approach, drawing on measures from different response modalities, for clarifying how core biobehavioral processes relate to various clinical problems and dimensions of psychopathology. Using data for 507 healthy adults, the current study was undertaken to integrate self-report and neurophysiological (brain potential) measures as a step toward a multimodal measurement model for the trait of affiliative capacity (AFF) – a biobehavioral construct relevant to adaptive and maladaptive social-interpersonal functioning. Individuals low in AFF exhibit a lack of interpersonal connectedness, deficient empathy, and an exploitative-aggressive social style that may be expressed transdiagnostically in antagonistic externalizing or distress psychopathology. Specific aims were to (1) integrate trait scale and brain potential indicators into a multimodal measure of AFF and (2) evaluate associations of this multimodal measure with criterion variables of different types. Results demonstrated (1) success in creating a multimodal measure of AFF from self-report and neural indicators, (2) effectiveness of this measure in predicting both clinical-diagnostic and neurophysiological criterion variables, and (3) transdiagnostic utility of the multimodal measure at both specific-disorder and broad symptom-dimension levels. Our findings further illustrate the value of psychoneurometric operationalizations of biobehavioral trait dimensions as referents for clarifying transdiagnostic relationships between biological systems variables and empirically defined dimensions of psychopathology.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
Research participants want to receive results from studies in which they participate. However, health researchers rarely share the results of their studies beyond scientific publication. Little is known about the barriers researchers face in returning study results to participants.
Methods:
Using a mixed-methods design, health researchers (N = 414) from more than 40 US universities were asked about barriers to providing results to participants. Respondents were recruited from universities with Clinical and Translational Science Award programs and Prevention Research Centers.
Results:
Respondents reported the percent of their research where they experienced each of the four barriers to disseminating results to participants: logistical/methodological, financial, systems, and regulatory. A fifth barrier, investigator capacity, emerged from data analysis. Training for research faculty and staff, promotion and tenure incentives, and funding agencies supporting dissemination of results to participants were solutions offered to overcoming barriers.
Conclusions:
Study findings add to literature on research dissemination by documenting health researchers’ perceived barriers to sharing study results with participants. Implications for policy and practice suggest that additional resources and training could help reduce dissemination barriers and increase the return of results to participants.
To determine the attributable cost and length of stay of hospital-acquired Clostridioides difficile infection (HA-CDI) from the healthcare payer perspective using linked clinical, administrative, and microcosting data.
Design:
A retrospective, population-based, propensity-score–matched cohort study.
Setting:
Acute-care facilities in Alberta, Canada.
Patients:
Admitted adult (≥18 years) patients with incident HA-CDI and without CDI between April 1, 2012, and March 31, 2016.
Methods:
Incident cases of HA-CDI were identified using a clinical surveillance definition. Cases were matched to noncases of CDI (those without a positive C. difficile test or without clinical CDI) on propensity score and exposure time. The outcomes were attributable costs and length of stay of the hospitalization where the CDI was identified. Costs were expressed in 2018 Canadian dollars.
Results:
Of the 2,916 HA-CDI cases at facilities with microcosting data available, 98.4% were matched to 13,024 noncases of CDI. The total adjusted cost among HA-CDI cases was 27% greater than noncases of CDI (ratio, 1.27; 95% confidence interval [CI], 1.21–1.33). The mean attributable cost was $18,386 (CAD 2018; USD $14,190; 95% CI, $14,312–$22,460; USD $11,046-$17,334). The adjusted length of stay among HA-CDI cases was 13% greater than for noncases of CDI (ratio, 1.13; 95% CI, 1.07–1.19), which corresponds to an extra 5.6 days (95% CI, 3.10–8.06) in length of hospital stay per HA-CDI case.
Conclusions:
In this population-based, propensity score matched analysis using microcosting data, HA-CDI was associated with substantial attributable cost.
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.
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.