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 no-reply@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.
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.
Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.
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.
Despite extensive paleoenvironmental research on the postglacial history of the Kenai Peninsula, Alaska, uncertainties remain regarding the region's deglaciation, vegetation development, and past hydroclimate. To elucidate this complex environmental history, we present new proxy datasets from Hidden and Kelly lakes, located in the eastern Kenai lowlands at the foot of the Kenai Mountains, including sedimentological properties (magnetic susceptibility, organic matter, grain size, and biogenic silica), pollen and macrofossils, diatom assemblages, and diatom oxygen isotopes. We use a simple hydrologic and isotope mass balance model to constrain interpretations of the diatom oxygen isotope data. Results reveal that glacier ice retreated from Hidden Lake's headwaters by ca. 13.1 cal ka BP, and that groundwater was an important component of Kelly Lake's hydrologic budget in the Early Holocene. As the forest developed and the climate became wetter in the Middle to Late Holocene, Kelly Lake reached or exceeded its modern level. In the last ca. 75 years, rising temperature caused rapid changes in biogenic silica content and diatom oxygen isotope values. Our findings demonstrate the utility of mass balance modeling to constrain interpretations of paleolimnologic oxygen isotope data, and that groundwater can exert a strong influence on lake water isotopes, potentially confounding interpretations of regional climate.
The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic.
Methods:
The TIN’s three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic’s rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned.
Results:
The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement.
Conclusions:
Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.
Ambulatory healthcare-associated infections (HAIs) occur frequently in children and are associated with morbidity. Less is known about ambulatory HAI costs. This study estimated additional costs associated with pediatric ambulatory central-line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTI), and surgical site infections (SSIs) following ambulatory surgery.
Design:
Retrospective case-control study.
Setting:
Four academic medical centers.
Patients:
Children aged 0–22 years seen between 2010 and 2015 and at risk for HAI as identified by electronic queries.
Methods:
Chart review adjudicated HAIs. Charges were obtained for patients with HAIs and matched controls 30 days before HAI, on the day of, and 30 days after HAI. Charges were converted to costs and 2015 USD. Mixed-effects linear regression was used to estimate the difference-in-differences of HAI case versus control costs in 2 models: unrecorded charge values considered missing and a sensitivity analysis with unrecorded charge considered $0.
Results:
Our search identified 177 patients with ambulatory CLABSIs, 53 with ambulatory CAUTIs, and 26 with SSIs following ambulatory surgery who were matched with 382, 110, and 75 controls, respectively. Additional cost associated with an ambulatory CLABSI was $5,684 (95% confidence interval [CI], $1,005–$10,362) and $6,502 (95% CI, $2,261–$10,744) in the 2 models; cost associated with a CAUTI was $6,660 (95% CI, $1,055, $12,145) and $2,661 (95% CI, −$431 to $5,753); cost associated with an SSI following ambulatory surgery at 1 institution only was $6,370 (95% CI, $4,022–$8,719).
Conclusions:
Ambulatory HAI in pediatric patients are associated with significant additional costs. Further work is needed to reduce ambulatory HAIs.
Catheter-associated urinary tract infections (CAUTIs) occur frequently in pediatric inpatients, and they are associated with increased morbidity and cost. Few studies have investigated ambulatory CAUTIs, despite at-risk children utilizing home urinary catheterization. This retrospective cohort and case-control study determined incidence, risk factors, and outcomes of pediatric patients with ambulatory CAUTI.
Design:
Broad electronic queries identified potential patients with ambulatory urinary catheters, and direct chart review confirmed catheters and adjudicated whether ambulatory CAUTI occurred. CAUTI definitions included clean intermittent catheterization (CIC). Our matched case-control analysis assessed risk factors.
Setting:
Five urban, academic medical centers, part of the New York City Clinical Data Research Network.
Patients:
Potential patients were age <22 years who were seen between October 2010 and September 2015.
Results:
In total, 3,598 eligible patients were identified; 359 of these used ambulatory catheterization (representing186,616 ambulatory catheter days). Of these, 63 patients (18%) experienced 95 ambulatory CAUTIs. The overall ambulatory CAUTI incidence was 0.51 infections per 1,000 catheter days (1.35 for indwelling catheters and 0.47 for CIC; incidence rate ratio, 2.88). Patients with nonprivate medical insurance (odds ratio, 2.5; 95% confidence interval, 1.1–6.3) were significantly more likely to have ambulatory CAUTIs in bivariate models but not multivariable models. Also, 45% of ambulatory CAUTI resulted in hospitalization (median duration, 3 days); 5% resulted in intensive care admission; 47% underwent imaging; and 88% were treated with antibiotics.
Conclusions:
Pediatric ambulatory CAUTIs occur in 18% of patients with catheters; they are associated with morbidity and healthcare utilization. Ambulatory indwelling catheter CAUTI incidence exceeded national inpatient incidence. Future quality improvement research to reduce these harmful infections is warranted.
Estimates of the proportion of illness transmitted by food for different enteric pathogens are essential for foodborne burden-of-disease studies. Owing to insufficient scientific data, a formal synthesis of expert opinion, an expert elicitation, is commonly used to produce such estimates. Eleven experts participated in an elicitation to estimate the proportion of illnesses due to food in Australia for nine pathogens over three rounds: first, based on their own knowledge alone; second, after being provided with systematic reviews of the literature and Australian data; and finally, at a workshop where experts reflected on the evidence. Estimates changed significantly across the three rounds (P = 0·002) as measured by analysis of variance. Following the workshop in round 3, estimates showed smoother distributions with significantly less variation for several pathogens. When estimates were combined to provide combined distributions for each pathogen, the width of these combined distributions reflected experts’ perceptions of the availability of evidence, with narrower intervals for pathogens for which evidence was judged to be strongest. Our findings show that the choice of expert elicitation process can significantly influence final estimates. Our structured process – and the workshop in particular – produced robust estimates and distributions appropriate for inclusion in burden-of-disease studies.
A survey of the Milky Way disk and the Magellanic System at the wavelengths of the 21-cm atomic hydrogen (H i) line and three 18-cm lines of the OH molecule will be carried out with the Australian Square Kilometre Array Pathfinder telescope. The survey will study the distribution of H i emission and absorption with unprecedented angular and velocity resolution, as well as molecular line thermal emission, absorption, and maser lines. The area to be covered includes the Galactic plane (|b| < 10°) at all declinations south of δ = +40°, spanning longitudes 167° through 360°to 79° at b = 0°, plus the entire area of the Magellanic Stream and Clouds, a total of 13 020 deg2. The brightness temperature sensitivity will be very good, typically σT≃ 1 K at resolution 30 arcsec and 1 km s−1. The survey has a wide spectrum of scientific goals, from studies of galaxy evolution to star formation, with particular contributions to understanding stellar wind kinematics, the thermal phases of the interstellar medium, the interaction between gas in the disk and halo, and the dynamical and thermal states of gas at various positions along the Magellanic Stream.
Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex.
Method
Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions.
Results
While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus.
Conclusions
These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.
We ask if Earth-like planets (terrestrial mass and habitable-zone orbit) can be detected in multi-planet systems, using astrometric and radial velocity observations. We report here the preliminary results of double-blind calculations designed to answer this question.
In an inter-laboratory survey, the pour plate, surface spread, agar droplet and spiral plate methods were used in parallel with the surface drop method for enumeration of micro-organisms in foods. Good agreement was obtained between all surface methods of enumeration, but there was poor agreement between molten agar methods and the surface drop method.
A total of 1143 samples of food that were ready for consumption at the point of retail sale were examined. Eight types of food products were chosen: meat pasties, sausage rolls, real-cream slices, synthetic-cream slices, mayonnaise-based coleslaws, faggots, patés and continental sausages. The results of this survey suggest that the upper limit for an acceptable viable count should vary according to the food product. Salmonellae were not isolated on any occasion. Potentially harmful organisms were not isolated at levels expected to constitute a public health hazard.
Information concerning the nature of the product, the total viable count, the presence or absence of pathogenic, toxigenic or indicator organisms, the spectrum of the bacterial flora and the relative predominance of each organism must all be considered when assessing the microbiological acceptability of retail ‘ready to eat’ products.