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A relationship between characteristics of gut microbiota and obesity are now well-established(1). However, less well-understood is the extent to which these microbiological features change during periods of weight loss. This study aimed to investigate the relationship between gut microbiota and weight loss in adults (aged 25 to 65 years, BMI of 27.5 to 34.9 kg/m2) enrolled in a 9-month randomised controlled trial(2). Participants were randomised to consume an energy-restricted diet that was either almond-enriched (30–50 g/daily) or nut-free (carbohydrate-rich snack foods). Data were collected at baseline (BL, n = 108), 3 months (3M, weight loss, n = 87) and 9 months (9M, weight maintenance, n = 82) for body weight, diet composition (weighed food diaries) and faecal microbiota composition (16S rRNA V4 amplicon sequencing). Paired data were analysed using mixed-effects models adjusted for baseline BMI, age, sex, dietary fibre. As reported previously, significant weight loss occurred for both diet groups to an equal extent(3). Significant inverse relationships were observed at BL between BMI and both microbiota richness (number of unique bacterial taxa detected) (estimate = −6.56, 95% CI = −9.9 to −3.19, p = 0.0002) and diversity (Shannon’s index) (−0.06, −0.1 to −0.02, p < 0.001). The strongest relationship at BL involved members of the Christensenellaceae bacterial family, which negatively correlated with BMI (r = −0.26, p = 0.007), consistent with prior studies(3,4). Microbiota richness (8.79, −0.73 to 18.34, p = 0.024) and diversity (0.08, −0.01 to 0.18, p = 0.019) were significantly higher at 9M compared to BL but not at 3M (p > 0.05). Compared to BL, microbiota composition (the taxa detected and their relative abundance) was significantly at 3M (p < 0.001) and 9M (p = 0.007). Following weight loss at 3M, significant increases in the relative abundance of members of the Christensenellaceae and Ruminococcaceae families were observed (log2 fold change > 1, FDR p < 0.05). Positive associations between weight loss and an increase in the relative abundance of Christensenellaceae family was evident at 3M (0.001, 0.0002 to 0.002, p = 0.010), but did not remain significant at 9M. Additionally, weight loss at 3M (0.0002, 1.3 × 10-5 to 0.0005, p = 0.038) and at 9M (0.0002, 4.6 × 10-6 to 0.0005, p = 0.045) was positively associated with an increase in the relative abundance of Lachnospiraceae ND3007, a bacterial genus associated with improved diet quality(5). Our findings demonstrate that the abundance of specific bacterial populations within the gut microbiota change in a manner that is proportionate to weight loss resulting from an energy-restricted diet. The extent to which these microbes are simply markers of altered diet, or whether they contribute in a causal manner to weight loss, as suggested by emerging preclinical data(3), is yet unknown.
Herbaceous perennials must annually rebuild the aboveground photosynthetic architecture from carbohydrates stored in crowns, rhizomes, and roots. Knowledge of carbohydrate utilization and storage can inform management decisions and improve control outcomes for invasive perennials. We monitored the nonstructural carbohydrates in a population of the hybrid Bohemian knotweed [Polygonum ×bohemicum (J. Chrtek & Chrtková) Zika & Jacobson [cuspidatum × sachalinense]; syn.: Fallopia ×bohemica (Chrtek and Chrtková) J.P. Bailey] and in Japanese knotweed [Polygonum cuspidatum Siebold & Zucc.; syn.: Fallopia japonica (Houtt.) Ronse Decr.]. Carbohydrate storage in crowns followed seasonal patterns typical of perennial herbaceous dicots corresponding to key phenological events. Starch was consistently the highest nonstructural carbohydrate present. Sucrose levels did not show a consistent inverse relationship with starch levels. Lateral distribution of starch in rhizomes and, more broadly, total nonstructural carbohydrates sampled before dormancy break showed higher levels in rhizomes compared with crowns. Total nonstructural carbohydrate levels in crowns reached seasonal lows at an estimated 22.6% of crown dry weight after accumulating 1,453.8 growing degree days (GDD) by the end of June, mainly due to depleted levels of stored starch, with the estimated minimum of 12.3% reached by 1,220.3 GDD accumulated by mid-June. Depletion corresponded to rapid development of vegetative canopy before entering the reproductive phase in August. Maximum starch accumulation in crowns followed complete senescence of aboveground tissues by mid- to late October. Removal of aboveground shoot biomass in late June to early July with removal of vegetation regrowth in early September before senescence would optimize the use of time and labor to deplete carbohydrate reserves. Additionally, foliar-applied systemic herbicide translocation to belowground tissue should be maximized with applications in late August through early fall to optimize downward translocation with assimilate movement to rebuild underground storage reserves. Fall applications should be made before loss of healthy leaf tissue, with the window for control typically ending by late September in Minnesota.
The growing popularity of home-sharing platforms such as Airbnb, partly fueled by hosts’ ability to evade local taxes and regulations, has been shown to elevate housing costs by reallocating long-term housing units to the short-term rental market. This study assesses whether enhanced tax enforcement can mitigate this trend. We analyze staggered tax collection agreements between Airbnb and Florida counties, wherein Airbnb collects taxes from the hosts directly. Using a difference-in-differences methodology, we find these agreements significantly slow the growth of housing costs, highlighting the importance of tax policy in addressing the sharing economy’s influence on housing affordability.
Malignant plasma cell proliferations are characterised by specific clinical, immunophenotypic and genetic features. Multiparameter flow cytometry (MFC) is an essential component of the diagnosis of these diseases. Clonal proliferations can be identified through their aberrant cell-surface immunophenotype or, more precisely, by demonstrating monotypy, i.e. selective expression of the same light chain in the cytoplasm of plasma-cells. This chapter reviews these immunophenotypic features, the technical points of caution to observe for proper use of MFC at diagnosis and during therapy to assess measurable residual disease.
At the start of the twentieth century, few Americans ever imagined getting a college degree. Less than 5 percent of children made it through high school, and approximately 1 percent of high school graduates enrolled in college. Two-year institutions were still a novelty, and four-year colleges catered to the 1 percent.1 Those numbers have changed dramatically. We now live in a world where 94 percent of Americans believe some college is “very important” to their lives and future prospects.2 Scholars tend to point to midcentury legislation—i.e., the GI Bill and Higher Education Act—as well as “College for All” movements as key drivers for the change. But the US isn’t alone. Globally, college-going has undergone a fundamental transformation during the past century. And the future promises the further expansion and reimagining of postsecondary education, though no doubt with surprising twists along the way.
For this policy dialogue, we asked Roger Geiger and Philip Altbach to discuss the past, present, and future of higher education in the US and abroad. Roger Geiger is a distinguished professor emeritus of higher education at Penn State University. He has written extensively on higher education history, with particular attention to research universities. His recent works include The History of American Higher Education: Learning and Culture from the Founding to World War II and American Higher Education since World War II: A History. Philip Altbach is a professor emeritus at Boston College, where he was a research professor and distinguished fellow at the Center for International Higher Education. He has received the NAFSA: Association of International Educators Houlihan Award for Distinguished Service and the Association for the Study of Higher Education’s Howard R. Bowen Distinguished Career Award. Both bring decades of research experience, professional expertise, and personal insight to this discussion.
HEQ policy dialogues are, by design, intended to promote an informal, free exchange of ideas between scholars. At the end of the exchange, we offer a list of references for readers who wish to follow up on sources relevant to the discussion.
Northern Arizona University, Flagstaff, Arizona, USA, recently installed a MIni CArbon DAting System (MICADAS) with a gas interface system (GIS) for determining the 14C content of CO2 gas released by the acid dissolution of biogenic carbonates. We compare 48 paired graphite, GIS, and direct carbonate 14C determinations of individual mollusk shells and echinoid tests. GIS sample sizes ranged between 0.5 and 1.5 mg and span 0.1 to 45.1 ka BP (n = 42). A reduced major axis regression shows a strong relationship between GIS and graphite percent Modern Carbon (pMC) values (m = 1.011; 95% CI [0.997–1.023], R2 = 0.999) that is superior to the relationship between the direct carbonate and graphite values (m = 0.978; 95% CI [0.959-0.999], R2 = 0.997). Sixty percent of GIS pMC values are within ±0.5 pMC of their graphite counterparts, compared to 26% of direct carbonate pMC values. The precision of GIS analyses is approximately ±70 14C yrs to 6.5 ka BP and decreases to approximately ±130 14C yrs at 12.5 ka BP. This precision is on par with direct carbonate and is approximately five times larger than for graphite. Six Plio-Pleistocene mollusk and echinoid samples yield finite ages when analyzed as direct carbonate but yield non-finite ages when analyzed as graphite or as GIS. Our results show that GIS 14C dating of biogenic carbonates is preferable to direct carbonate 14C dating and is an efficient alternative to standard graphite 14C dating when the precision of graphite 14C dating is not required.
Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
Bentonites are readily available clays used in the livestock industry as feed additives to reduce aflatoxin (AF) exposure; their potential interaction with nutrients is the main concern limiting their use, however. The objective of the present study was to determine the safety of a dietary sodium-bentonite (Na-bentonite) supplement as a potential AF adsorbent, using juvenile Sprague Dawley (SD) rats as a research model. Animals were fed either a control diet or a diet containing Na-bentonite at 0.25% and 2% (w/w) inclusion rate. Growth, serum, and blood biochemical parameters, including selected serum vitamins (A and E) and elements such as calcium (Ca), potassium (K), iron (Fe), and zinc (Zn) were measured. The mineral characteristics and the aflatoxin B1 sorption capacity of Na-bentonite were also determined. By the end of the study, males gained more weight than females in control and Na-bentonite groups (p ≤ 0.0001); the interaction between treatment and sex was not significant (p = 0.6780), however. Some significant differences between the control group and bentonite treatments were observed in serum biochemistry and vitamin and minerals measurements; however, parameters fell within reference clinical values reported for SD rats and no evidence of dose-dependency was found. Serum Na and Na/K ratios were increased, while K levels were decreased in males and females from Na-bentonite groups. Serum Zn levels were decreased only in males from Na-bentonite treatments. Overall, results showed that inclusion of Na-bentonite at 0.25% and 2% did not cause any observable toxicity in a 3-month rodent study.
Dicamba and 2,4-D are postemergence herbicides widely used to control broadleaf weed species in crop and non-crop areas in the United States. Currently, multiple formulations of 2,4-D and dicamba are available on the market. Even though the active ingredient is the same, the chemical formulation may vary, which can influence the volatility potential of these herbicides. Therefore, the objective of this study was to evaluate the response of soybean, cotton, and tobacco plants exposed to vapors of 2,4-D and dicamba formulations alone or mixed in humidomes for 24 h. Humidome studies were conducted in an open pavilion at the Lake Wheeler Turfgrass Field Lab of the North Carolina State University in Raleigh, NC. Dicamba and mixture treatments injured and caused a reduction in the height of soybean. Injury varied from 55% to 70%, and average plant height was 8.8 cm shorter compared with untreated control plants. Treatments with 2,4-D caused the least injury to soybean (≤21%), and differences among formulations were identified (dimethylamine > choline > dimethylamine-monomethylamine). However, soybean height was not affected by 2,4-D treatments. No differences between treatments were observed when herbicides were applied to cotton. The greatest injury to tobacco (23.3%) was caused by dicamba dimethylamine. Overall, the effect of 2,4-D and dicamba vapor was species-specific and formulation-dependent. Additionally, environmental conditions in the humidomes may have played a major role on the outcome of this study.
We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient’s staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.
Method:
423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M−/M+) and/or cannabis (C−/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.
Results:
Globally, M+C+ performed worse than M−C− but better than M+C−. M+C+ outperformed M+C− on measures of verbal fluency, information processing speed, learning, memory, and working memory. M−C+ did not display lower performance than M−C− globally or on any domain measures, and M−C+ even performed better than M−C− on measures of learning, memory, and working memory.
Conclusions:
Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.
The United States Department of Agriculture Agricultural Marketing Service (USDA AMS) began publishing formula base price information in August 2021. Considerable variation in the types of cattle priced via formula has raised questions about the level of base price transparency that can be gleaned from formula base price reports. This study employs 6 years of transactions to estimate hedonic models assessing the capability of existing data to describe variation in formula base prices. Results suggest factors beyond those reported to USDA AMS by packers influence base prices. We offer suggestions for improved data collection to make hedonic modeling of base prices more effective for reporting market information.
In patients with bipolar disorder, depression symptoms are associated with greater reduction in function and quality of life than hypomania/mania symptoms. Lumateperone (LUMA), is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder.
In a recent phase 3 clinical trial (Study 404, NCT03249376) in people with bipolar depression, LUMA 42 mg monotherapy significantly improved symptoms of depression compared with placebo (PBO). This analysis of Study 404 investigated the effects of LUMA on functional disability and quality of life as measured using the secondary outcome measure, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF).
Methods
Patients (18–75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score ≥4) were randomized to LUMA 42 mg or PBO orally, once daily in the evening for 6 weeks. The primary endpoint was the change from baseline to Day 43 in MADRS Total score, analyzed using a mixed-effects model for repeated measures (MMRM) approach in the intent-to-treat population (ITT). This post hoc analysis evaluated the mean change from baseline to Day 43 in the Q-LES-Q-SF individual item scores using an analysis of covariance with last observation carried forward (ANCOVA-LOCF) in the ITT. Categorical shifts in individual items were also analyzed.
Results
The ITT comprised 376 patients (LUMA 42 mg, 188; PBO, 188). Patients in the LUMA 42 mg group had significantly greater improvement on MADRS Total score change from baseline to Day 43 compared with PBO (least squares mean difference vs PBO [LSMD], −4.585; 95% CI, −6.344 to −2.826; effect size vs PBO [ES], −0.56; P<.0001). LUMA 42 mg treatment significantly improved Q-LES-Q-SF Total score from baseline to Day 43 compared with PBO (LSMD, 2.9; 95% CI, 1.15 to 4.59; P=.001).
The Q-LES-Q-SF items with the lowest mean scores at baseline in both groups were mood, leisure time activities, and sexual drive, interest, and/or performance. By Day 43, LUMA 42 mg treatment significantly improved 8 of the 14 items in the Q-LES-Q-SF (P<0.05). Overall life satisfaction also significantly improved with LUMA treatment (P=.0016). The largest improvements with LUMA 42 mg compared with PBO (ES>0.3,) were seen for the ability to function in daily life, family relationships, household activities, leisure time activities, and mood (all LSMD=0.3; all P<.01).
Conclusion
In patients with bipolar depression, treatment with LUMA 42 mg compared with PBO significantly improved patient quality of life and functional impairment. These results support LUMA 42 mg as treatment of MDEs associated with bipolar I or bipolar II disorder in adults.
Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of “informativeness,” highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise.
Methods and Results:
Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies.
Conclusions:
We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.
The goal of the Patient-Centered Outcomes Research Partnership was to prepare health care professionals and researchers to conduct patient-centered outcomes and comparative effectiveness research (CER). Substantial evidence gaps, heterogeneous health care systems, and decision-making challenges in the USA underscore the need for evidence-based strategies.
Methods:
We engaged five community-based health care organizations that serve diverse and underrepresented patient populations from Hawai’i to Minnesota. Each partner nominated two in-house scholars to participate in the 2-year program. The program focused on seven competencies pertinent to patient-centered outcomes and CER. It combined in-person and experiential learning with asynchronous, online education, and created adaptive, pragmatic learning opportunities and a Summer Institute. Metrics included the Clinical Research Appraisal Inventory (CRAI), a tool designed to assess research self-efficacy and clinical research skills across 10 domains.
Results:
We trained 31 scholars in 3 cohorts. Mean scores in nine domains of the CRAI improved; greater improvement was observed from the beginning to the midpoint than from the midpoint to conclusion of the program. Across all three cohorts, mean scores on 52 items (100%) increased (p ≤ 0.01), and 91% of scholars reported the program improved their skills moderately/significantly. Satisfaction with the program was high (91%).
Conclusions:
Investigators that conduct patient-centered outcomes and CER must know how to collaborate with regional health care systems to identify priorities; pose questions; design, conduct, and disseminate observational and experimental research; and transform knowledge into practical clinical applications. Training programs such as ours can facilitate such collaborations.
The Bruss–Robertson–Steele (BRS) inequality bounds the expected number of items of random size which can be packed into a given suitcase. Remarkably, no independence assumptions are needed on the random sizes, which points to a simple explanation; the inequality is the integrated form of an $\omega$-by-$\omega$ inequality, as this note proves.
Maternal protein restriction is often associated with structural and functional sequelae in offspring, particularly affecting growth and renal-cardiovascular function. However, there is little understanding as to whether hypertension and kidney disease occur because of a primary nephron deficit or whether controlling postnatal growth can result in normal renal-cardiovascular phenotypes. To investigate this, female Sprague-Dawley rats were fed either a low-protein (LP, 8.4% protein) or normal-protein (NP, 19.4% protein) diet prior to mating and until offspring were weaned at postnatal day (PN) 21. Offspring were then fed a non ‘growth’ (4.6% fat) which ensured that catch-up growth did not occur. Offspring growth was determined by weight and dual energy X-ray absorptiometry. Nephron number was determined at PN21 using the disector-fractionator method. Kidney function was measured at PN180 and PN360 using clearance methods. Blood pressure was measured at PN360 using radio-telemetry. Body weight was similar at PN1, but by PN21 LP offspring were 39% smaller than controls (Pdiet < 0.001). This difference was due to proportional changes in lean muscle, fat, and bone content. LP offspring remained smaller than NP offspring until PN360. In LP offspring, nephron number was 26% less in males and 17% less in females, than NP controls (Pdiet < 0.0004). Kidney function was similar across dietary groups and sexes at PN180 and PN360. Blood pressure was similar in LP and NP offspring at PN360. These findings suggest that remaining on a slow growth trajectory after exposure to a suboptimal intrauterine environment does not lead to the development of kidney dysfunction and hypertension.