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.

A low-charge Na-montmorillonite (SWy-2) was exchanged with hexadecyltrimethyl-ammonium (HDTMA) at levels equal to 20, 40, 60, 70, 80, 90, 100, 150 and 200% of the cation exchange capacity (819 mmol(+)/kg) to determine the nature of adsorption and the ionic composition of the clay interlayers. In contrast with earlier work with smaller aliphatic cations, which suggested random interstratification of interlayers occupied by either organic or metallic cations, there was no evidence of cation segregation into homogeneous interlayers. Instead, X-ray analysis indicated that the organic cations assumed two dominant configurations which were roughly equivalent in prevalence at ∼70% coverage of the CEC. Below 70% exchange the organocations existed predominantly in heterogeneous monolayers with Na+, attaining basal spacings of between 1.41 and 1.44 nm which were sensitive to changes in relative humidity. Relative humidity effects indicated that Na+ and HDTMA occupied functionally discrete domains within the interlayer as shown by the free interaction of water and a neutral organic solute, naphthalene, with Na+ and HDTMA, respectively. At greater levels of HDTMA exchange (up to 100% of the CEC), the organocations assumed a predominantly bilayer configuration. Transition to a fully-developed bilayer indicated by a 1.77 nm d-spacing at 100% coverage was gradual, suggesting some interstratification of the monolayers and bilayer configurations between 70 and 100% exchange. Sorption of naphthalene to the organoclays within this range of coverage was well correlated with clay organic carbon content, consistent with relatively unimpeded interlayer access of neutral organic molecules.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

Greenhouse experiments in central Texas assessed the relative importance of above- and belowground interactions of semidwarf Mit wheat and Marshall ryegrass during vegetative growth. One experiment used partitions to compare the effect of no (controls), aboveground only, belowground only, and full interaction for 75 d after planting (DAP) one wheat and nine ryegrass plants in soil volumes of 90, 950, and 3,800 ml. The results with the different soil volumes were similar. Wheat growth in the aboveground interaction only did not differ from controls. However, the full or belowground only interaction of wheat with ryegrass reduced wheat height, leaf number, tillering, leaf area, percent total nonstructural carbohydrates in shoot, and dry weights of leaves, stems, and roots 45 and 75 DAP compared to controls. Wheat in full and belowground interaction only did not differ from one another in growth. A replacement series experiment of 56 d also showed that the competitive advantage of ryegrass was relatively greater in root than in shoot growth. No allelopathic response of wheat to ryegrass occurred. While the tallness of the semidwarf wheat minimized aboveground interference by ryegrass, the root growth of the thinner and more fibrous roots of ryegrass greatly enhanced its belowground competitiveness.

A greenhouse experiment compared the vegetative growth in pure cultures and mixtures of winter Triticum aestivum cultivar ‘Mit’ and Lolium multiflorum cultivar ‘Marshall’ in continuously watered controls and drought treatments. Control L. multiflorum in pure culture 14 wk after planting produced more leaf area, tillers, and dry weights of stem and root than control T. aestivum in pure culture. The greater seed size, larger initial leaf area, and height allowed T. aestivum to produce greater final leaf area and dry stem weight in control mixtures than L. multiflorum. Watering following drought shifted the relative performance of the two species in pure cultures and mixtures compared to controls. The ability of T. aestivum to maintain a greater leaf expansion rate during drought and a greater leaf area afterward than L, multiflorum allowed T. aestivum to attain greater growth than L. multiflorum in pure cultures exposed to temporary drought followed by watering. Conversely, drought and its relief enhanced the relative competitiveness of L. multiflorum compared to controls in mixtures with T. aestivum. During 4 wk of watering following the drought, L. multiflorum in mixtures grew vigorously and was similar to T. aestivum in all measures except in height and dry stem weight. Thus, L. multiflorum was similar in root growth with T. aestivum in control and drought mixtures and had its aboveground competitiveness amplified by the cycle of drought and watering in this study. There was no evidence of an allelopathic interaction between the two species.

A greenhouse experiment used a replacement series design to compare the vegetative growth 6 wk after emergence in pure cultures and mixtures of winter wheat and Italian ryegrass, with phosphorus (P) levels recommended by soil testing. The planting proportions of wheat and Italian ryegrass were 100 and 0%, 75 and 25%, 50 and 50%, 25 and 75%, and 0 and 100%, respectively. There was no alleopathic interaction between the species. Both species in all pure and mixed cultures had substantially less growth in the low-P than in the recommended P treatment. However, the relative performance of the two species differed between P treatments. In the recommended P treatment in pure culture, Italian ryegrass had more tillers and greater root weight and length than wheat. Pure culture wheat in the low-P treatment exceeded pure culture Italian ryegrass in leaf area, weights of leaves, stems, and roots, and root length. Thus, the growth of wheat was inhibited less by P deficiency than the growth of Italian ryegrass in pure culture. In the 50:50 mixture of the recommended P treatment, wheat had greater leaf, stem, and root weights than Italian ryegrass. In the 50:50 mixture of the low-P treatment, the two species were very similar in growth, except that Italian ryegrass had about three times more tillers than did wheat. Whereas P deficiency limited the growth of wheat less than Italian ryegrass in pure culture, P deficiency did not affect the relative competitiveness of Italian ryegrass as much as wheat in mixed cultures. The ability of Italian ryegrass to compete with wheat when P was limiting may result from a difference in root growth. Italian ryegrass had a greater fresh root length to fresh root weight ratio than did wheat in the low-P treatment in pure culture and in the 50:50 mixture. The greater surface area of Italian ryegrass roots likely enhanced the competitiveness of Italian ryegrass relative to wheat under P-deficit conditions. Thus, the use of the recommended P nutrition from soil testing may be a key component to diminish Italian ryegrass competition in wheat fields.

Managers of business firms, large or small, farm or nonfarm, must make investment decisions under conditions of risk and uncertainty. However, in evaluating investments, the assumption of perfect knowledge has often been used to simplify the analysis. For example, an estimate of average annual net returns is frequently discounted into perpetuity to evaluate a real estate investment alternative. Capital budgeting literature suggests a number of approaches to evaluating alternative investments. However, use of concepts such as the payback period, average rate of return, internal rate of return and net present value embodies the assumption of perfect knowledge.

There are many biological macro-molecules such as nucleic acids, lipids, carbohydrates and proteins. While each of them plays a vital (and interesting) part in life but there is something special about the proteins. Proteins are the key link between the processes of information and replication that take place on a genetic level and the infrastructure of living features. Understanding the properties of proteins is the key to understanding the spark of the life. In this paper we describe our study of various electrical properties of protein when performing measurements at the nanoscale. To achieve this goal we designed and fabricated a nanoelectronic probe. This nano structure consists of four thin film layers. There are two conductive layers and an insulative layer in between. There is also a protective oxide layer as the top most layer. This layer is to prevent the exposure of conductive electrodes to the solution. Underneath the bottom electrode, there is another oxide layer, which can be a thermally grown oxide. This layer insulates the first electrode from the substrate. In this study, while we use non-specific detection of streptavidin protein as a proof of concept, we emphasize that the findings of this study can be extended to specific detection of target proteins, where in this case a specific probe molecule would also be immobilized on the sensor surface.

Here we present the development of an array of electrical nano-biosensors in a microfluidic channel, called Nanoneedle biosensors. Then we present the proof of concept study for protein detection. A Nanoneedle biosensor is a real-time, label-free, direct electrical detection platform, which is capable of high sensitivity detection, measuring the change in ionic current and impedance modulation, due to the presence or reaction of biomolecules such as proteins or nucleic acids. We show that the sensors which have been fabricated and characterized for the protein detection. We have functionalized Nanoneedle biosensors with receptors specific to a target protein using physical adsorption for immobilization. We have used biotinylated bovine serum albumin as the receptor and sterptavidin as the target analyte. The detection of streptavidin binding to the receptor protein is also presented.