Photoinitiated Single-Crystal to Single-Crystal Redox Transformations of Titanium-Oxo Clusters.

Titanium-oxo clusters can undergo photochemical reactions under UV light, resulting in the reduction of the titanium-oxo core and oxidation of surface ligands. This is an important step in photocatalytic processes in light-absorbing Ti/O-based clusters, metal-organic frameworks, and (nano)material surfaces; however, studying the direct outcome of this photochemical process is challenging due to the fragility of the immediate photoproducts. In this report, titanium-oxo clusters [TiO(OiPr)(L)]n (n = 4, L = O2PPh2, or n = 6, L = O2CCH2tBu) undergo a two-electron photoredox reaction in the single-crystal state via an irreversible single-crystal to single-crystal (SC-SC) transformation initiated by a UV laser. The process is monitored by single crystal X-ray diffraction revealing the photoreduction of the cluster with coproduction of an (oxidized) acetone ligand, which is retained in the structure as a ligand to Ti(3+). The results demonstrate that photochemistry of inorganic molecules can be studied in the single crystal phase, allowing characterization of photoproducts which are unstable in the solution phase.

A circumpolar study unveils a positive non-linear effect of temperature on arctic arthropod availability that may reduce the risk of warming-induced trophic mismatch for breeding shorebirds.

Seasonally abundant arthropods are a crucial food source for many migratory birds that breed in the Arctic. In cold environments, the growth and emergence of arthropods are particularly tied to temperature. Thus, the phenology of arthropods is anticipated to undergo a rapid change in response to a warming climate, potentially leading to a trophic mismatch between migratory insectivorous birds and their prey. Using data from 19 sites spanning a wide temperature gradient from the Subarctic to the High Arctic, we investigated the effects of temperature on the phenology and biomass of arthropods available to shorebirds during their short breeding season at high latitudes. We hypothesized that prolonged exposure to warmer summer temperatures would generate earlier peaks in arthropod biomass, as well as higher peak and seasonal biomass. Across the temperature gradient encompassed by our study sites (>10°C in average summer temperatures), we found a 3-day shift in average peak date for every increment of 80 cumulative thawing degree-days. Interestingly, we found a linear relationship between temperature and arthropod biomass only below temperature thresholds. Higher temperatures were associated with higher peak and seasonal biomass below 106 and 177 cumulative thawing degree-days, respectively, between June 5 and July 15. Beyond these thresholds, no relationship was observed between temperature and arthropod biomass. Our results suggest that prolonged exposure to elevated temperatures can positively influence prey availability for some arctic birds. This positive effect could, in part, stem from changes in arthropod assemblages and may reduce the risk of trophic mismatch.

Why do avian responses to change in Arctic green-up vary?

Global climate change has altered the timing of seasonal events (i.e., phenology) for a diverse range of biota. Within and among species, however, the degree to which alterations in phenology match climate variability differ substantially. To better understand factors driving these differences, we evaluated variation in timing of nesting of eight Arctic-breeding shorebird species at 18 sites over a 23-year period. We used the Normalized Difference Vegetation Index as a proxy to determine the start of spring (SOS) growing season and quantified relationships between SOS and nest initiation dates as a measure of phenological responsiveness. Among species, we tested four life history traits (migration distance, seasonal timing of breeding, female body mass, expected female reproductive effort) as species-level predictors of responsiveness. For one species (Semipalmated Sandpiper), we also evaluated whether responsiveness varied across sites. Although no species in our study completely tracked annual variation in SOS, phenological responses were strongest for Western Sandpipers, Pectoral Sandpipers, and Red Phalaropes. Migration distance was the strongest additional predictor of responsiveness, with longer-distance migrant species generally tracking variation in SOS more closely than species that migrate shorter distances. Semipalmated Sandpipers are a widely distributed species, but adjustments in timing of nesting relative to variability in SOS did not vary across sites, suggesting that different breeding populations of this species were equally responsive to climate cues despite differing migration strategies. Our results unexpectedly show that long-distance migrants are more sensitive to local environmental conditions, which may help them to adapt to ongoing changes in climate.

Genetic diversity, population structure and origin of the native goats in Central Laos.

Maintaining genetic diversity and variation in livestock populations is critical for natural and artificial selection promoting genetic improvement while avoiding problems due to inbreeding. In Laos, there are concerns that there has been a decline in genetic diversity and a rise in inbreeding among native goats in their village-based smallholder system. In this study, we investigated the genetic diversity of Lao native goats in Phin, Songkhone and Sepon districts in Central Laos for the first time using Illumina's Goat SNP50 BeadChip. We also explored the genetic relationships between Lao goats with 163 global goat populations from 36 countries. Our results revealled a close genetic relationship between Lao native goats and Chinese, Mongolian and Pakistani goats, sharing ancestries with Guangfen, Jining Grey and Luoping Yellow breeds (China) and Teddi goats (Pakistan). The observed (Ho) and expected (He) heterozygosity were 0.292 and 0.303 (Laos), 0.288 and 0.288 (Sepon), 0.299 and 0.308 (Phin) and 0.289 and 0.305 (Songkhone), respectively. There was low to moderate genetic differentiation (FST: 0.011-0.043) and negligible inbreeding coefficients (FIS: -0.001 to 0.052) between goat districts. The runs of homozygosity (ROH) had an average length of 5.92-6.85 Mb, with short ROH segments (1-5 Mb length) being the most prevalent (66.34%). Longer ROH segments (20-40 and >40 Mb length categories) were less common, comprising only 4.81% and 1.01%, respectively. Lao goats exhibit moderate genetic diversity, low-inbreeding levels and adequate effective population size. Some genetic distinctions between Lao goats may be explained by geographic and cultural features.

Brave spaces in nursing ethics education: Courage through pedagogy.

BACKGROUND: Nursing students must graduate prepared to bravely enact the art and science of nursing in environments infiltrated with ethical challenges. Given the necessity and moral obligation of nurses to engage in discourse within nursing ethics, nursing students must be provided a moral supportive learning space for these opportunities. Situating conversations and pedagogy within a brave space may offer a framework to engage in civil discourse while fostering moral courage for learners. RESEARCH OBJECTIVE: The aim of this research is to explore the influence of a structured self-assessment tool called the ESA "Engagement Self-Assessment" on the alignment and creation of a brave space in a nursing ethics course. RESEARCH DESIGN: This study used an exploratory, cross-sectional survey design. PARTICIPANTS AND STUDY SETTING: Data from 39 undergraduate nursing students enrolled in a nursing healthcare ethics & law course using the ESA were recruited. ETHICAL CONSIDERATIONS: Participation was voluntary and informed without coercion. Written consent was obtained prior to participation. Research ethics approval was obtained by the Institutional Research Ethics Board of the recruited participants (Ethics # 2022-23-03). FINDINGS: The ESA provided structured self-reflection on the impact of shared vulnerability within a brave space. However, commitment to a brave space was not strongly influenced by the ESA, but rather by a mutual "commitment to others." CONCLUSION: A teaching tool such as an ESA can be used to facilitate instructor expectations of civil discourse and discussion of difficult topics. Rules of engagement such as those found in brave spaces can help transform fear of vulnerability into authentic growth for learners. A morally supportive learning space can support critical opportunities for ethical development. This study provides insight into how self-assessment and the use of a brave space in nursing ethics education can facilitate a morally supportive learning space.

On the Precise Link between Energy and Information.

We present a modified version of the Szilard engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer's original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that approaching a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer's principle that is completely independent from the Second Law of thermodynamics.

Chemically modified dsRNA induces RNAi effects in insects in vitro and in vivo: A potential new tool for improving RNA-based plant protection.

Global agriculture loses over $100 billion of produce annually to crop pests such as insects. Many of these crop pests either are not currently controlled by artificial means or have developed resistance against chemical pesticides. Long dsRNAs are capable of inducing RNAi in insects and are emerging as novel, highly selective alternatives for sustainable insect management strategies. However, there are significant challenges associated with RNAi efficacy in insects. In this study, we synthesized a range of chemically modified long dsRNAs in an approach to improve nuclease resistance and RNAi efficacy in insects. Our results showed that dsRNAs containing phosphorothioate modifications demonstrated increased resistance to southern green stink bug saliva nucleases. Phosphorothioate-modified and 2'-fluoro-modified dsRNA also demonstrated increased resistance to degradation by soil nucleases and increased RNAi efficacy in Drosophila melanogaster cell cultures. In live insects, we found chemically modified long dsRNAs successfully resulted in mortality in both stink bug and corn rootworm. These results provide further mechanistic insight into the dependence of RNAi efficacy on nucleotide modifications in the sense or antisense strand of the dsRNA in insects and demonstrate for the first time that RNAi can successfully be triggered by chemically modified long dsRNAs in insect cells or live insects.

Surfactant like peptides for targeted gene delivery to cancer cells.

Surfactant like peptides (SLPs) are a class of amphiphilic peptides widely used for drug delivery and tissue engineering. However, there are very few reports on their application for gene delivery. The current study was aimed at development of two new SLPs, named (IA)4K and (IG)4K, for selective delivery of antisense oligodeoxynucleotides (ODNs) and small interfering RNA (siRNA) to cancer cells. The peptides were synthesized by Fmoc solid phase synthesis. Their complexation with nucleic acids was studied by gel electrophoresis and DLS. The transfection efficiency of the peptides was assessed in HCT 116 colorectal cancer cells and human dermal fibroblasts (HDFs) using high content microscopy. The cytotoxicity of the peptides was assessed by standard MTT test. The interaction of the peptides with model membranes was studied using CD spectroscopy. Both SLPs delivered siRNA and ODNs to HCT 116 colorectal cancer cells with high transfection efficiency which was comparable to the commercial lipid-based transfection reagents, but with higher selectivity for HCT 116 compared to HDFs. Moreover, both peptides exhibited very low cytotoxicity even at high concentrations and long exposure time. The current study provides more insights into the structural features of SLPs required for nucleic acid complexation and delivery and can therefore serve as a guide for the rational design of new SLPs for selective gene delivery to cancer cells to minimize the adverse effects in healthy tissues.

Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes.

Heterobifunctional chimeric degraders are a class of ligands that recruit target proteins to E3 ubiquitin ligases to drive compound-dependent protein degradation. Advancing from initial chemical tools, protein degraders represent a mechanism of growing interest in drug discovery. Critical to the mechanism of action is the formation of a ternary complex between the target, degrader and E3 ligase to promote ubiquitination and subsequent degradation. However, limited insights into ternary complex structures exist, including a near absence of studies on one of the most widely co-opted E3s, cellular inhibitor of apoptosis 1 (cIAP1). In this work, we use a combination of biochemical, biophysical and structural studies to characterize degrader-mediated ternary complexes of Bruton's tyrosine kinase and cIAP1. Our results reveal new insights from unique ternary complex structures and show that increased ternary complex stability or rigidity need not always correlate with increased degradation efficiency.

Reorganization of the Neurobiology of Language After Sentence Overlearning.

It is assumed that there are a static set of "language regions" in the brain. Yet, language comprehension engages regions well beyond these, and patients regularly produce familiar "formulaic" expressions when language regions are severely damaged. These suggest that the neurobiology of language is not fixed but varies with experiences, like the extent of word sequence learning. We hypothesized that perceiving overlearned sentences is supported by speech production and not putative language regions. Participants underwent 2 sessions of behavioral testing and functional magnetic resonance imaging (fMRI). During the intervening 15 days, they repeated 2 sentences 30 times each, twice a day. In both fMRI sessions, they "passively" listened to those sentences, novel sentences, and produced sentences. Behaviorally, evidence for overlearning included a 2.1-s decrease in reaction times to predict the final word in overlearned sentences. This corresponded to the recruitment of sensorimotor regions involved in sentence production, inactivation of temporal and inferior frontal regions involved in novel sentence listening, and a 45% change in global network organization. Thus, there was a profound whole-brain reorganization following sentence overlearning, out of "language" and into sensorimotor regions. The latter are generally preserved in aphasia and Alzheimer's disease, perhaps explaining residual abilities with formulaic expressions in both.

The relationship between single muscle fibre and voluntary rate of force development in young and old males.

PURPOSE: It is suggested that the early phase (< 50 ms) of force development during a muscle contraction is associated with intrinsic contractile properties, while the late phase (> 50 ms) is associated with maximal force. There are no direct investigations of single muscle fibre rate of force development (RFD) as related to joint-level RFD METHODS: Sixteen healthy, young (n = 8; 26.4 ± 1.5 yrs) and old (n = 8; 70.1 ± 2.8 yrs) males performed maximal voluntary isometric contractions (MVC) and electrically evoked twitches of the knee extensors to assess RFD. Then, percutaneous muscle biopsies were taken from the vastus lateralis and chemically permeabilized, to assess single fibre function. RESULTS: At the joint level, older males were ~ 30% weaker and had ~ 43% and ~ 40% lower voluntary RFD values at 0-100 and 0-200 ms, respectively, than the younger ones (p ≤ 0.05). MVC torque was related to every voluntary RFD epoch in the young (p ≤ 0.001), but only the 0-200 ms epoch in the old (p ≤ 0.005). Twitch RFD was ~ 32% lower in the old compared to young (p < 0.05). There was a strong positive relationship between twitch RFD and voluntary RFD during the earliest time epochs in the young (≤ 100 ms; p ≤ 0.01). While single fibre RFD was unrelated to joint-level RFD in the young, older adults trended (p = 0.052-0.055) towards significant relationships between joint-level RTD and Type I single fibre RFD at the 0-30 ms (r2 = 0.48) and 0-50 ms (r2 = 0.49) time epochs. CONCLUSION: Electrically evoked twitches are good predictors of early voluntary RFD in young, but not older adults. Only the older adults showed a potential relationship between single fibre (Type I) and joint-level rate of force development.

Time to change the reference ranges of children's physiological observations in emergency care? A prospective study.

AIM: High heart and respiratory rates are key indicators in many published guidelines to identify and treat serious bacterial infection and sepsis in children, but the credibility of evidence underpinning what is considered abnormal is questionable. This study established the distribution of heart and respiratory rates of children using a large data set to inform debate on what the 'normal' range of these should look like. The primary aim was to compare the distribution of heart and respiratory rates measured in children recruited from non-tertiary emergency care settings with those published by Advanced Paediatric Life Support (APLS). The secondary aim was to compare the distribution of this study's data set to other national guidance on what constitutes a severe (high-risk) measurement and previously published data sets. METHOD: Prospective study using anonymised patient data, extracted from electronic patient records of children and young people 0-16 years, recruited from three Emergency Departments and one Urgent Care Centre in Northwest England, UK. RESULTS: Heart and respiratory rates, including the reporting of values at certain centiles and comparisons of averages. Distribution of heart and respiratory rate were consistently higher than those used by the APLS guidance, resulting in a large proportion exceeding the 'severe' cut-offs proposed. This varied greatly by age. CONCLUSIONS: This study's data set suggests normal heart rate ranges proposed by the APLS and others is too low and therefore 'abnormal' measurements encompass too large a proportion. The respiratory rate of this data set was more consistent with the guidelines and other published data sets.

Video Teleconferencing for Disease Prevention, Diagnosis, and Treatment : A Rapid Review.

BACKGROUND: Video teleconferencing (VTC) as a substitute for in-person health care or as an adjunct to usual care has increased in recent years. PURPOSE: To assess the benefits and harms of VTC visits for disease prevention, diagnosis, and treatment and to develop an evidence map describing gaps in the evidence. DATA SOURCES: Systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library from 1 January 2013 to 3 March 2021. STUDY SELECTION: Two investigators independently screened the literature and identified 38 randomized controlled trials (RCTs) meeting inclusion criteria. DATA EXTRACTION: Data abstraction by a single investigator was confirmed by a second investigator; 2 investigators independently rated risk of bias. DATA SYNTHESIS: Results from 20 RCTs rated low risk of bias or some concerns of bias show that the use of VTC for the treatment and management of specific diseases produces largely similar outcomes when used to replace or augment usual care. Nine of 12 studies where VTC was intended to replace usual care and 5 of 8 studies where VTC was intended to augment usual care found similar effects between the intervention and control groups. The remaining 6 included studies (3 intended to replace usual care and 3 intended to augment usual care) found 1 or more primary outcomes that favored the VTC group over the usual care group. Studies comparing VTC with usual care that did not involve in-person care were more likely to favor the VTC group. No studies evaluated the use of VTC for diagnosis or prevention of disease. Studies that reported harms found no differences between the intervention and control groups; however, many studies did not report harms. No studies evaluated the effect of VTC on health equity or disparities. LIMITATIONS: Studies that focused on mental health, substance use disorders, maternal care, and weight management were excluded. Included studies were limited to RCTs with sample sizes of 50 patients or greater. Component analyses were not conducted in the studies. CONCLUSION: Replacing or augmenting aspects of usual care with VTC generally results in similar clinical effectiveness, health care use, patient satisfaction, and quality of life as usual care for areas studied. However, included trials were limited to a handful of disease categories, with patients seeking care for a limited set of purposes. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Factors influencing mercury exposure in Arctic-breeding shorebirds.

Mercury (Hg) pollution remains a concern to Arctic ecosystems, due to long-range transport from southern industrial regions and melting permafrost and glaciers. The objective of this study was to identify intrinsic, extrinsic, and temporal factors influencing Hg concentrations in Arctic-breeding shorebirds and highlight regions and species at greatest risk of Hg exposure. We analyzed 1094 blood and 1384 feather samples from 12 shorebird species breeding at nine sites across the North American Arctic during 2012 and 2013. Blood Hg concentrations, which reflect Hg exposure in the local area in individual shorebirds: 1) ranged from 0.01-3.52 µg/g ww, with an overall mean of 0.30 ± 0.27 µg/g ww; 2) were influenced by species and study site, but not sampling year, with birds sampled near Utqiagvik, AK, having the highest concentrations; and 3) were influenced by foraging habitat at some sites. Feather Hg concentrations, which reflected Hg exposure from the wintering grounds: 1) ranged from 0.07-12.14 µg/g fw in individuals, with an overall mean of 1.14 ± 1.18 µg/g fw; and 2) were influenced by species and year. Most Arctic-breeding shorebirds had blood and feather Hg concentrations at levels where no adverse effects of exposure were predicted, though some individuals sampled near Utqiagvik had Hg levels that would be considered of concern. Overall, these data increase our understanding of how Hg is distributed in the various shorebird breeding areas of the Arctic, what factors predispose Arctic-breeding shorebirds to Hg exposure, and lay the foundation for future monitoring efforts.

Experience influences kinematic motor synergies: an Uncontrolled manifold approach to simulated Nordic skiing.

Motor synergies are defined as central nervous system mechanisms which adjust participating degrees of freedom to ensure dynamic stability (control) of certain performance variables and have been identified during many motor tasks. The potential for synergistic control of individual segments during full-body tasks is often overlooked. Thus, this study compared individual differences in the potential stabilization of multiple performance variables on the basis of experience during a full-body sport activity. Normalized time series of synergy indices from Uncontrolled Manifold analyses on experienced (n = 9) and inexperienced (n = 19) participants were analysed using statistical parametric mapping during simulated Nordic skiing. Regardless of experience, hand, upper arm, and whole-body centre of mass (COM) kinematics were found to be stabilized by kinematic motor synergies. Only experienced Nordic skiers stabilized trunk COM position at all, while trunk COM velocity was stabilized for a longer duration than inexperienced participants. However, inexperienced participants stabilized hand velocity for a greater duration overall and to a greater magnitude during early pull phase than the experienced skiers. That motor synergies for hand and trunk COM velocity differed between experience groups suggests potential utility for these performance variables as indicators of motor skill development for full-body tasks such as Nordic skiing.

Effects of trunk extensor muscle fatigue on repetitive lift (re)training using an augmented tactile feedback approach.

Augmented tactile and performance feedback has been used to (re)train a modified lifting technique to reduce lumbar spine flexion, which has been associated with low back disorder development during occupational repetitive lifting tasks. However, it remains unknown if the presence of trunk extensor neuromuscular fatigue influences learning of this modified lifting technique. Therefore, we compared the effectiveness of using augmented tactile and performance feedback to reduce lumbar spine flexion during a repetitive lifting task, in both unfatigued and fatigued states. Participants completed repetitive lifting tests immediately before and after training, and 1-week later, with half of the participants completing training after fatiguing their trunk extensor muscles. Both groups demonstrated learning of the modified lifting technique as demonstrated by increased thorax-pelvis coordination variability and reduced lumbar range of motion variability; however, experiencing trunk extensor neuromuscular fatigue during lift (re)training may have slight negative influences on learning the modified lifting technique. Practitioner summary: An augmented lift (re)training paradigm using tactile cueing and performance feedback regarding key movement features (i.e. lumbar spine flexion) can effectively (re)train a modified lifting technique to reduce lumbar flexion and redistribute motion to the hips and knees. However, performing (re)training while fatigued could slightly hinder learning this lifting technique.

The Effects of Posture and Dynamic Stretching on the Electromechanical Delay of the Paraspinal Muscles.

Electromechanical delay (EMD) of muscle is influenced in part by its in-series arrangement with connective tissue. Therefore, studying EMD might provide a better understanding of the muscle-connective tissue interaction. Here, EMD of the thoracic and lumbar erector spinae muscles were investigated under conditions that could influence muscle-connective tissue interaction. A total of 19 participants performed isometric back extension contractions in 3 different postures that influence lumbar spine angle: sitting, standing, and kneeling. They then performed a 15-minute dynamic stretching routine and repeated the standing contractions. Mean lumbar flexion angles of 0.5°, 9.9°, and 19.8° were adopted for standing, kneeling, and sitting, respectively. No statistically significant differences in the thoracic erector spinae EMD were found between the different postures. Lumbar erector spinae EMD was significantly longer in the sitting (94.1 ms) compared to the standing (69.9 ms) condition, with no differences compared to kneeling (79.7 ms). There were no statistically significant differences of the thoracic or lumbar erector spinae EMDs before and after dynamic stretching. These results suggest that dynamic stretching does not affect the mechanical behavior of the muscle-tendon-aponeurosis units in a way that alters force generation and transmission, but a sitting posture can alter how force is transmitted through the musculotendinous complex of the lumbar erector spinae.

COVID-19 vaccine apartheid and the failure of global cooperation.

The equitable distribution of COVID-19 vaccines is one of the most important tests of global cooperation that the world has faced in recent decades. Collectively, global leaders failed that crucible abysmally, creating a 'vaccine apartheid' that divided the world according to income into countries with widespread access and those without. Why, given that leaders were fully aware of the risks and injustice of vaccine inequity, did governments of wealthy countries hoard doses, impede the expansion of vaccine manufacturing and otherwise prevent equitable access to vaccines? We argue that their decisions to act selfishly are best explained by governments' accountability to domestic constituencies, their lack of leadership and commitment to multilateralism and their adoption of short-term perspectives, as well as their unwillingness to curb the influence of profit-oriented global pharmaceutical companies and, to a certain extent, of an additional private actor, the Bill and Melinda Gates Foundation.

Review of high energy x-ray computed tomography for non-destructive dimensional metrology of large metallic advanced manufactured components.

Advanced manufacturing technologies, led by additive manufacturing, have undergone significant growth in recent years. These technologies enable engineers to design parts with reduced weight while maintaining structural and functional integrity. In particular, metal additive manufacturing parts are increasingly used in application areas such as aerospace, where a failure of a mission-critical part can have dire safety consequences. Therefore, the quality of these components is extremely important. A critical aspect of quality control is dimensional evaluation, where measurements provide quantitative results that are traceable to the standard unit of length, the metre. Dimensional measurements allow designers, manufacturers and users to check product conformity against engineering drawings and enable the same quality standard to be used across the supply chain nationally and internationally. However, there is a lack of development of measurement techniques that provide non-destructive dimensional measurements beyond common non-destructive evaluation focused on defect detection. X-ray computed tomography (XCT) technology has great potential to be used as a non-destructive dimensional evaluation technology. However, technology development is behind the demand and growth for advanced manufactured parts. Both the size and the value of advanced manufactured parts have grown significantly in recent years, leading to new requirements of dimensional measurement technologies. This paper is a cross-disciplinary review of state-of-the-art non-destructive dimensional measuring techniques relevant to advanced manufacturing of metallic parts at larger length scales, especially the use of high energy XCT with source energy of greater than 400 kV to address the need in measuring large advanced manufactured parts. Technologies considered as potential high energy x-ray generators include both conventional x-ray tubes, linear accelerators, and alternative technologies such as inverse Compton scattering sources, synchrotron sources and laser-driven plasma sources. Their technology advances and challenges are elaborated on. The paper also outlines the development of XCT for dimensional metrology and future needs.

Bridging the Gap between Digital Assays and Point-of-Care Testing: Automated, Low Cost, and Ultrasensitive Detection of Thyroid Stimulating Hormone.

Medical diagnostics is moving toward disease-related target detection at very low concentrations because of the (1) quest for early-stage diagnosis, at a point where only limited target amounts are present, (2) trend toward minimally invasive sample extraction, yielding samples containing low concentrations of target, and (3) need for straightforward sample collection, usually resulting in limited volume collected. Hence, diagnostic tools allowing ultrasensitive target detection at the point-of-care (POC) are crucial for simplified and timely diagnosis of many illnesses. Therefore, we developed an innovative, fully integrated, semi-automated, and economically viable platform based on (1) digital microfluidics (DMF), enabling automated manipulation and analysis of very low sample volumes and (2) low-cost disposable DMF chips with microwell arrays, fabricated via roll-to-roll processes and allowing digital target counting. Thyroid stimulating hormone detection was chosen as a relevant application to show the potential of the system. The assay buffer was selected using design of experiments, and the assay was optimized in terms of reagent concentration and incubation time toward maximum sensitivity. The hydrophobic-in-hydrophobic microwells showed an unparalleled seeding efficiency of 97.6% ± 0.6%. A calculated LOD of 0.0013 µIU/mL was obtained, showing the great potential of the platform, especially taking into account the very low sample volume analyzed (1.1 µL). Although validation (in biological matrix) and industrialization (full automation) steps still need to be taken, it is clear that the combination of DMF, low-cost DMF chips, and digital analyte counting in microwell arrays enables the implementation of ultrasensitive and reliable target detection at the POC.