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Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.
Aims
The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.
Method
This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.
Results
Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.
Conclusions
Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha−1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha−1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha−1 and topdressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha−1) was coated on AMS and topdressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS were compared to pyroxasulfone applied POST and POST-directed. The check in both studies received non-herbicide-treated AMS (321 kg ha−1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8% to 16%), while pyroxasulfone-coated AMS resulted in ≤4% injury. Additionally, no differences in cotton lint yield were observed in either study. With the exception of the lowest rate of AMS (161 kg ha−1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥83%, comparably to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate that pyroxasulfone-coated AMS can control Palmer amaranth comparably to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.
The regent honeyeater Anthochaera phrygia is a Critically Endangered Australian songbird, with current population estimates of < 300 individuals remaining in the wild. Low nest success is a factor preventing the recovery of the population, and management remedies are needed. However, a lack of data on intervention success raises uncertainty and impedes planning. To identify management priorities under uncertainty, we engaged with conservation practitioners and key stakeholders to develop and evaluate potential nest protection interventions. Four categories of threats were considered: avian predators, mammalian predators, extreme weather events and avian competitors. The interventions with the highest predicted probabilities of nest success under each threat category were, respectively: lethal control of avian predators, the use of tree collars to control arboreal mammalian predators, the provisioning of supplementary food and nesting resources during extreme weather events, and control of the noisy miner Manorina melanocephala, a competitor species. Our analysis shows that by applying a combination of conservation actions alongside improvements in nest detection, it is possible, based on the opinion of experts, to provide a pathway for the recovery of the regent honeyeater.
Alternative proteins provide a better way to feed the world(1) and have great potential to support the United Nations’ sustainable development goals in ending hunger, promoting sustainable energy use, protecting the climate, and promoting good health(2). However, consumers’ acceptance of alternative proteins is much lower than that of conventional meat(3). With the alternative protein market consistently growing since 2021(4), it is essential to summarise and update factors affecting consumer acceptance of alternative proteins to inform relevant organisations such as the government and support industry development. Using a systematic review, this study aimed to understand and compare consumers’ acceptance of five popular alternative proteins (algae, pulses, plant-based alternative proteins, insects, and cultured meat) and identify research trends and essential factors influencing consumption of alternative protein foods. Specifically, the study compared familiarity and external factors in consumer acceptance.
Building upon an existing systematic which included studies published by 2020, five electronic databases were searched. This review followed PRISMA guidelines, covering Western and Eastern countries, and articles published between June 2020 and March 2023. A total of 112 articles from 40 countries were included. Following the innovation-decision process framework, factors between alternative protein types, products, and psychological and external variables are compared, and changes over time are identified.
Italy (n = 15), China (n = 13) and the United Kingdom (n = 12) were the top 3 in publication numbers. Surveys (n = 95) were the most used method in the studies. Insects (n = 41) and cultured meat (n = 21) were the most popular. The findings reveal that consumers show moderate acceptance of alternative proteins, but a relatively higher acceptance of food products made with these proteins. Tastiness emerged as the top concern in alternative protein consumption, highlighting the importance of sensory appeal. Environmental benefits plus health beliefs also played a significant role in consumer acceptance. Interventions to illustrate food safety and quality variables correlated to a higher willingness to consume alternative proteins. Food neophobia and diet showed distinguished value in consumer acceptance level. Participants who had experienced eating insects showed significant differences in food neophobia scores, subjective norms, attitudes, and intentions. Meal composition and trust in the chef increased consumers’ willingness to consume. Many studies focused on developing alternative protein food products and determining their appropriateness for consumption in different contexts. Consuming alternative proteins with family or friends with positive emotions was more acceptable to consumers.
Consumers’ different acceptance levels and critical factors of alternative protein consumption illustrated the essentials of focusing more on consumer categorisation. The fast expansion of the global alternative protein market and accelerated study output call for building a more complete standardised management and information supply system.
The diets of children in the UK are suboptimal(1), which may influence their immediate and future health and well-being(2). Schools offer convenient and prolonged access to children from diverse backgrounds, thus interventions within this setting have been suggested as a means to promote diet and health outcomes among this population(3). This study explored the effects of Project Daire(4), a school-based food intervention, on children’s diet diversity and diet quality as well as their attitudes towards health behaviours.
A factorial design cluster randomized controlled trial was conducted. Fifteen primary schools in Northern Ireland were randomized into one of four 6-month intervention arms: Nourish, Engage, Nourish and Engage or Control (Delayed). The Nourish intervention modified the school food environment, provided food-related experiences and increased access to local foods. The Engage intervention included educational activities on nutrition, food and agriculture. Data on food consumption at home, school and/or in total over a 24-hour period were collected using ageappropriate food frequency questionnaires at baseline, with follow-up at 6-months. Diet diversity score (DDS) and diet quality score (DQS) were developed based on adherence to the Eatwell Guide. Additionally, a Health Attitudes and Behaviour measure assessed 10-11 year old children’s attitudes towards importance of various health behaviours at both time points. Linear and logistic regression models were used to examine intervention effects and to account for school clustering.
A total of 445 children aged 6-7 and 458 aged 10-11 years old completed the trial. Results indicated that children aged 10-11 year old who received the Nourish intervention demonstrated higher school DDS (adjusted mean difference=2.79, 95% CI 1.40 – 4.19; p = 0.001) and total DDS (adjusted mean difference=1.55, 95% CI 0.66 – 2.43, p = 0.002) compared to their counterparts who did not. Subgroup analyses revealed that the increases in school DDS among 10-11 year old children in the Nourish group were apparent in both boys and girls (Boys: adjusted mean difference=2.4 95% CI 0.1 – 4.7, p = 0.04; Girls: adjusted mean difference=3.1 95% CI 1.6 – 4.6, p = 0.001). However, the increase in total DDS remained statistically significant only among girls, with an adjusted mean difference of 1.9 (95% CI 1.1-2.7, p<0.001). No statistically significant changes in DQS were detected in either age group. High levels of positive attitudes towards health behaviours were observed at baseline, with no clinically significant effects of either the Nourish or Engage interventions detected during the follow-up period.
The multi-component approach of the Nourish intervention, addressing both food provision and environment, showed promise in promoting diet diversity. Further research is warranted to develop sustainable implementation strategies for Daire, to explore additional intervention components to impact other outcomes, including diet quality, and to evaluate long-term effectiveness.
Herbicides have been placed in global Herbicide Resistance Action Committee (HRAC) herbicide groups based on their sites of action (e.g., acetolactate synthase–inhibiting herbicides are grouped in HRAC Group 2). A major driving force for this classification system is that growers have been encouraged to rotate or mix herbicides from different HRAC groups to delay the evolution of herbicide-resistant weeds, because in theory, all active ingredients within a herbicide group physiologically affect weeds similarly. Although herbicide resistance in weeds has been studied for decades, recent research on the biochemical and molecular basis for resistance has demonstrated that patterns of cross-resistance are usually quite complicated and much more complex than merely stating, for example, a certain weed population is Group 2-resistant. The objective of this review article is to highlight and describe the intricacies associated with the magnitude of herbicide resistance and cross-resistance patterns that have resulted from myriad target-site and non–target site resistance mechanisms in weeds, as well as environmental and application timing influences. Our hope is this review will provide opportunities for students, growers, agronomists, ag retailers, regulatory personnel, and research scientists to better understand and realize that herbicide resistance in weeds is far more complicated than previously considered when based solely on HRAC groups. Furthermore, a comprehensive understanding of cross-resistance patterns among weed species and populations may assist in managing herbicide-resistant biotypes in the short term by providing growers with previously unconsidered effective control options. This knowledge may also inform agrochemical company efforts aimed at developing new resistance-breaking chemistries and herbicide mixtures. However, in the long term, nonchemical management strategies, including cultural, mechanical, and biological weed management tactics, must also be implemented to prevent or delay increasingly problematic issues with weed resistance to current and future herbicides.
An experiment was conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to evaluate residual herbicide-coated fertilizer for cotton tolerance and Palmer amaranth control. Treatments included acetochlor, atrazine, dimethenamid-P, diuron, flumioxazin, fluometuron, fluridone, fomesafen, linuron, metribuzin, pendimethalin, pyroxasulfone, pyroxasulfone + carfentrazone, S-metolachlor, and sulfentrazone. Each herbicide was individually coated on granular ammonium sulfate (AMS) and top-dressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf cotton. The check plots received the equivalent rate of nonherbicide-treated AMS. Before top-dress, all plots (including the check) were treated with glyphosate and glufosinate to control previously emerged weeds. All herbicides except metribuzin resulted in transient cotton injury. Cotton response to metribuzin varied by year and location. In 2022, metribuzin caused 11% to 39% and 8% to 17% injury at the Clayton and Rocky Mount locations, respectively. In 2023, metribuzin caused 13% to 32% injury at Clayton and 73% to 84% injury at Rocky Mount. Pyroxasulfone (91%), pyroxasulfone + carfentrazone (89%), fomesafen (87%), fluridone (86%), flumioxazin (86%), and atrazine (85%) controlled Palmer amaranth ≥85%. Pendimethalin and fluometuron were the least effective treatments, resulting in 58% and 62% control, respectively. As anticipated, early season metribuzin injury translated into yield loss; plots treated with metribuzin yielded 640 kg ha−1 and were comparable to yields after linuron (790 kg ha−1) was used. These findings suggest that with the exception of metribuzin, residual herbicides coated onto AMS may be suitable and effective in cotton production, providing growers with additional modes of action for late-season control of multiple herbicide–resistant Palmer amaranth.
Most of the Ross Sea has been designated a marine protected area (MPA), proposed ‘to protect ecosystem structure and function’. To assess effectiveness, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) selected Adélie (Pygoscelis adeliae) and emperor (Aptenodytes forsteri) penguins, Weddell seals (Leptonychotes weddellii) and Antarctic toothfish (Dissostichus mawsoni) as ecosystem change ‘indicator species’. Stable for decades, penguin and seal populations increased during 1998–2018 to surpass historical levels, indicating that change in ecosystem structure and function is underway. We review historical impacts to population trends, decadal datasets of ocean climate and fishing pressure on toothfish. Statistical modelling for Adélie penguins and Weddell seals indicates that variability in climate factors and cumulative extraction of adult toothfish may explain these trends. These mesopredators, and adult toothfish, all prey heavily on Antarctic silverfish (Pleuragramma antarcticum). Toothfish removal may be altering intraguild predation dynamics, leading to competitive release of silverfish and contributing to penguin and seal population changes. Despite decades of ocean/weather change, increases in indicator species numbers around Ross Island only began once the toothfish fishery commenced. The rational-use, ecosystem-based viewpoint promoted by CCAMLR regarding toothfish management needs re-evaluation, including in the context of the Ross Sea Region MPA.
Type 1 diabetes mellitus (T1DM) patients are treated via insulin which could result in weight gain. Studies have coined a new term, “Diabulimia” which refers to the limitation or skipping of insulin doses, with the objective of weight control. A previous meta-analysis has found that eating disorders (ED) are significantly associated with T1DM (Mannucci, E et al. J Endocrinol Invest 2005; 417-9), while a more recent one, has shown an insignificant association between ED and T1DM on analysis of diabetes-adapted questionnaires only (Young V, et al. Diabet Med. 2013:189-198)
Objectives
We aimed to re-analyze the association between ED and T1DM, whilst taking into account recently published literature and the type of questionnaire utilized.
Methods
A literature search of PubMed, Scopus, and Web of Science was conducted on 17th January 2023, using the key terms “ T1DM”, “Eating Disorders”, and “ Bulimia”. Only Observational controlled studies were included.
Results
T1DM was associated with increased risk of ED compared to non-diabetic individuals (RR = 2.47, 95% CI = 1.84 to 3.32, p-value < 0.00001), especially bulimia nervosa (RR = 2.80, 95% CI = 1.18 to 6.65, p-value = 0.02) and binge eating (RR = 1.53, 95% CI = 1.18 to 1.98, p-value = 0.001), while no significant association was seen between T1DM and anorexia nervosa. Our sensitivity analysis has shown that increased risk of ED among T1DM persisted regardless of the questionnaire used to diagnose ED; DM-validated questionnaires (RR = 2.80, 95% CI = 1.91 to 4.12, p-value <0.00001) and generic questionnaires (RR = 2.03, 95% CI = 1.27 to 3.23, p-value = 0.003). Furthermore, the Eating Attitudes Test-26 (EAT) showed a significant increase in the dieting subscale (MD = 2.95, 95% CI = 1.84 to 4.06, p-value < 0.00001) and bulimia subscale (MD = 0.78, 95% CI = 0.12 to 1.44, p-value = 0.02) among T1DM patients. Additionally, the Bulimic Investigatory Test, Edinburg (BITE) showed a significant increase in the symptom subscale (MD = 0.31, 95% CI = 0.12 to 0.50, p-value = 0.001), however, no significant difference was detected between T1DM and controls in the severity subscale. Prevalence of insulin omission/misuse was 10.3% (95% CI = 8.1-13); diabetic females demonstrated significantly higher risk of insulin omission (RR = 14.21, 95% CI = 2.66 to 76.04, p-value = 0.002) and insulin misuse (RR = 6.51, 95% CI = 1.14 to 37.31, p-value = 0.04) compared with diabetic males. Analysis of other potentially unhealthy weight control behaviors showed insignificant associations between fasting, excessive exercise, dieting pills misuse, diuretics misuse, and T1DM.
Conclusions
T1DM patients are at higher risk of developing ED according to both generic and diabetes-validated questionnaires. Moreover, female diabetics are at higher risk of insulin misuse/omission. Subsequently, patients should be regularly screened and early psychiatric management is warranted.
Workplace sugar-sweetened beverage (SSB) sales bans can reduce SSB consumption. Because stress and anxiety can promote sugar consumption, we examined whether anxiety among hospital employees during the COVID-19 pandemic was associated with changes in SSB consumption and explored whether this relationship varied by exposure to a workplace SSB sales ban.
Design:
In a prospective, controlled trial of workplace SSB sales bans, we examined self-reported anxiety (generalised anxiety disorder-7) and self-reported SSB consumption (fluid ounces/d) before (July 2019) and during (May 2020) the COVID-19 pandemic.
Setting:
Hospital sites in two conditions (four with SSB sales bans and three without sales bans) in Northern California.
Participants:
We sampled 580 participants (hospital employees) from a larger trial of sales bans; all were regular consumers of SSB (minimum 3/week at main trial enrollment). This subsample was chosen based on having appropriately timed data for our study questions.
Results:
Across conditions, participants reduced SSB consumption over the study period. However, participants with higher pandemic-era anxiety scores experienced smaller reductions in SSB consumption after 9 months compared with those with lower anxiety scores (β = 0·65, P < 0·05). When the sample was disaggregated by sales ban condition, this relationship held for participants in the control group (access to SSB at work, β = 0·82, P < 0·05), but not for those exposed to an SSB sales ban (β = 0·42, P = 0·25).
Conclusions:
SSB sales bans likely reduce SSB consumption through multiple pathways; buffering stress-related consumption may be one mechanism.
Understanding particle motion in narrow channels can guide progress in numerous applications, from filtration to vascular transport. Thermal or active fluctuations of fluid-filled channel walls can slow down or increase the dispersion of tracer particles via entropic trapping in the wall bulges or hydrodynamic flows induced by wall fluctuations, respectively. Previous studies concentrated primarily on the case of a single Brownian tracer. Here, we address what happens when there is a large ensemble of interacting Brownian tracers – a common situation in applications. Introducing repulsive interactions between tracer particles, while ignoring the presence of a background fluid, leads to an effective flow field. This flow field enhances tracer dispersion, a phenomenon reminiscent of that seen for single tracers in incompressible background fluid. We characterise the dispersion by the long-time diffusion coefficient of tracers numerically and analytically with a mean-field density functional analysis. We find a surprising effect where an increased particle density enhances the diffusion coefficient, challenging the notion that crowding effects tend to reduce diffusion. Here, inter-particle interactions push particles closer to the fluctuating channel walls. Interactions between the fluctuating wall and the now-nearby particles then drive particle mixing. Our mechanism is sufficiently general that we expect it to apply to various systems. In addition, our perturbation theory quantifies dispersion in generic advection–diffusion systems.
Aerial application of an herbicide mixture of triclopyr, dicamba, picloram, and aminopyralid is used to control dense infestations of exotic conifers, notably lodgepole pine (Pinus contorta Douglas ex Loudon), in New Zealand. The rates of herbicide applied to control these tree weeds has the potential for off-target impacts through persistence in the forest floor, soil, and water. Persistence of three of these herbicides was investigated in cast needles, forest floor (litter, fermented humic layer [LFH]), and soil following their operational aerial application (triclopyr: 18 kg ai ha−1; dicamba: 5 kg ai ha−1; picloram: 2 kg ai ha−1) at three sites across New Zealand (KF, MD, GE) with dense invasions of P. contorta. Water was collected from a local stream at two sites (KF, MD) in the days/months after spraying. Active ingredients detected across all sites in cast needles, LFH, and mineral soil generally reflected their application rates, with total amounts comprising 81% triclopyr, 14% dicamba, and 5% picloram. Most of the active ingredients were detected in the LFH (59%), a heavy lignin-rich layer of dead needles overlaying the soil. All three herbicides persisted in this layer, at all sites, for up to 2 yr (at study termination). Only triclopyr was detected in mineral soil, where it declined to below detection levels (0.2 mg kg−1) within 1 yr. All three herbicides were detected in stream water on the day of spray application at KF, and during a rainfall event 1 mo later. However, amounts did not exceed New Zealand environmental and drinking water standards, an outcome attributed to a 30-m no-spray buffer zone used at this site. At MD, herbicides were detectable in water up to 4 mo after spraying, with amounts exceeding New Zealand drinking water standards on one occasion, 1 mo after spray application. No spray buffer zones were used at the MD site.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
Planetary Protection (PP) is the practice of safeguarding solar system bodies from terrestrial biological contamination and screening the Earth against potentially harmful extraterrestrial biological contamination. On Earth, cleanrooms and spacecraft surfaces are assayed using swabs and wipes that are then heat shocked for 15 min at 80°C to select for spores. The samples are further processed using the pour-plate method and Petri plates (TSA plates), with trypticase soy agar (TSA) serving as the growth medium. This sampling and processing procedure, called the NASA Standard Assay (NSA), is used by PP engineers around the world. Recent years have seen an increase in the incorporation of state-of-the-art technology, such as membrane filtration, into the NSA, with a push for implementing environmentally friendly technology into day-to-day activities. Dehydrated thin film media, such as Petrifilm Rapid Aerobic Count (RAC) plates, suit these goals as an alternative method to TSA plates. RAC plates show bacterial growth (and distinguish colonies from foreign particles such as bubbles) faster than TSA plates due to the incorporation of chromogenic colour indicators in the media. RAC plates also possess a much smaller environmental footprint than TSA plates, and are designed to evaluate even some of the challenging-to-detect environmental organisms, including spreaders that fill over 25% of the plate area in only a few hours. With these benefits in mind the PP Group at the NASA Jet Propulsion Laboratory took on the task of comparing RAC plates directly to TSA plates within the context of the NSA. Not only were the RAC plates able to detect surface environmental samples and in vitro spiked samples equivalent to NSA-processed TSA plates, but spreader organisms were countable on RAC plates at culture densities 10- to 100-fold greater than on TSA plates. In addition, RAC plates showed a robust, linear detection capability when challenged with membrane filter incorporation and organisms were easily acquired from RAC plates for archiving or post-processing experiments including MALDI-TOF bacterial identification. With their ease of use, small footprint, and both rapid and accurate bioburden measurements, RAC plates have the potential to overcome limitations posed by current PP culturing protocols.
One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.
Deciding whether or not eradication of an invasive species has been successful is one of the main dilemmas facing managers of eradication programmes. When the species is no longer being detected, a decision must be made about when to stop the eradication programme and declare success. In practice, this decision is usually based on ad hoc rules, which may be inefficient. Since surveillance undertaken to confirm species absence is imperfect, any declaration of eradication success must consider the risk and the consequences of being wrong. If surveillance is insufficient, then eradication may be falsely declared (a Type I error), whereas continuation of surveillance when eradication has already occurred wastes resources (a Type II error). We review the various methods that have been developed for quantifying these errors and incorporating them into the decision-making process. We conclude with an overview of future developments likely to improve the practice of determining invasive species eradication success.