Prospects of Single-Cell NMR Spectroscopy with Quantum Sensors

Single-cell analysis can unravel functional heterogeneity within cell populations otherwise obscured by ensemble measurements. However, non-invasive techniques that probe chemical entities and their dynamics are still lacking. This challenge could be overcome by novel sensors based on nitrogen-vacancy (NV) centers in diamond, which enable nuclear magnetic resonance (NMR) spectroscopy on unprecedented sample volumes. In this perspective, we briefly introduce NV-based quantum sensing and review the progress made in microscale NV-NMR spectroscopy. Lastly, we discuss approaches to enhance the sensitivity of NV ensemble magnetometers to detect biologically relevant concentrations and provide a roadmap towards their application in single-cell analysis.Comment: 13 Pages, 3 Figures, 1 Tabl

Premature Discontinuation of Pediatric Randomized Controlled Trials : A Retrospective Cohort Study

Objectives To determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs. Study design A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists. Results We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants). Conclusion Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.Peer reviewe

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

UV-Induced Charge Transfer States in DNA Promote Sequence Selective Self-Repair

Absorption of UV-radiation in nucleotides initiates a number of photophysical and photochemical processes, which may finally cause DNA damage. One major decay channel of photoexcited DNA leads to reactive charge transfer states. This study shows that these states trigger self-repair of DNA photolesions. The experiments were performed by UV spectroscopy and HPLC on different single and double stranded oligonucleotides containing a cyclobutane pyrimidine dimer (CPD) lesion. In a first experiment we show that photoexcitation of adenine adjacent to a CPD has no influence on this lesion. However, excitation of a guanine (G) adenine (A) sequence leads to reformation of the intact thymine (T) bases. The involvement of two bases for the repair points to a long-living charge transfer state between G and A to be responsible for the repair. The negatively charged A radical anion donates an electron to the CPD, inducing ring splitting and repair. In contrast, a TA sequence, having an inverted charge distribution (T radical anion, A radical cation), is not able to repair the CPD lesion. The investigations show that the presence of an adjacent radical ion is not sufficient for repair. More likely it is the driving power represented by the oxidation potential of the radical ion, which controls the repair. Thus, repair capacities are strongly sequence-dependent, creating DNA regions with different tendencies of self-repair. This self-healing activity represents the simplest sequence-dependent DNA repair system

Surface NMR Using Quantum Sensors in Diamond

Characterization of the molecular properties of surfaces under ambient or chemically reactive conditions is a fundamental scientific challenge. Nuclear magnetic resonance (NMR) spectroscopy would be the ideal technique, however it lacks the sen-sitivity to probe the small number of spins at interfaces. Here we use nitrogen vacancy (NV) centers in diamond as quantum sensors to optically detect NMR signals from chemically modified thin films. Aluminum oxide (Al2O3) layers, common supports in catalysis and materials science, are prepared by atomic layer deposition and are subsequently functionalized by phosphonate chemistry to form self-assembled monolayers (SAMs). The surface NV-NMR technique detects NMR signals from the monolayer, indicates chemical binding, and quantifies molecular coverage. In addition, it can monitor in real-time the formation kinetics at the solid-liquid interface. This work demonstrates the capability of NV quantum sensors as a sur-face-sensitive (femtomole) NMR tool for in-situ analysis in catalysis, materials and biological research

Decay Pathways of Thymine Revisited

The decay of electronically excited states of thymine (Thy) and thymidine 5′-monophosphate (TMP) was studied by time-resolved UV/vis and IR spectroscopy. In addition to the well-established ultrafast internal conversion to the ground state, a so far unidentified UV-induced species is observed. In D₂O, this species decays with a time constant of 300 ps for thymine and of 1 ns for TMP. The species coexists with the lowest triplet state and is formed with a comparably high quantum yield of about 10% independent of the solvent. The experimentally determined spectral signatures are discussed in the light of quantum chemical calculations of the singlet and triplet excited states of thymine

Microfluidic quantum sensing platform for lab-on-a-chip applications

Lab-on-a-chip (LOC) applications have emerged as invaluable physical and life sciences tools. The advantages stem from advanced system miniaturization, thus, requiring far less sample volume while allowing for complex functionality, increased reproducibility, and high throughput. However, LOC applications necessitate extensive sensor miniaturization to leverage these inherent advantages fully. Atom-sized quantum sensors are highly promising to bridge this gap and have enabled measurements of temperature, electric and magnetic fields on the nano- to microscale. Nevertheless, the technical complexity of both disciplines has so far impeded an uncompromising combination of LOC systems and quantum sensors. Here, we present a fully integrated microfluidic platform for solid-state spin quantum sensors, such as the nitrogen-vacancy (NV) center in diamond. Our platform fulfills all technical requirements, such as fast spin manipulation, enabling full quantum sensing capabilities, biocompatibility, and easy adaptability to arbitrary channel and chip geometries. To illustrate the vast potential of quantum sensors in LOC systems, we demonstrate various NV center-based sensing modalities for chemical analysis in our microfluidic platform, ranging from paramagnetic ion detection to high-resolution microscale NV-NMR. Consequently, our work opens the door for novel chemical analysis capabilities within LOC devices with applications in electrochemistry, high throughput reaction screening, bioanalytics, organ-on-a-chip, or single-cell studies

Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study).

BACKGROUND: Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. METHODS/DESIGN: Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs.We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. DISCUSSION: Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements

Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study)

Abstract Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.</p