Advances in digital anthropometric body composition assessment: neural network algorithm prediction of appendicular lean mass.

Currently available anthropometric body composition prediction equations were often developed on small participant samples, included only several measured predictor variables, or were prepared using conventional statistical regression methods. Machine learning approaches are increasingly publicly available and have key advantages over statistical modeling methods when developing prediction algorithms on large datasets with multiple complex covariates. This study aimed to test the feasibility of predicting DXA-measured appendicular lean mass (ALM) with a neural network (NN) algorithm developed on a sample of 576 participants using 10 demographic (sex, age, 7 ethnic groupings) and 43 anthropometric dimensions generated with a 3D optical scanner. NN-predicted and measured ALM were highly correlated (n = 116; R2, 0.95, p < 0.001, non-significant bias) with small mean, absolute, and root-mean square errors (X ± SD, -0.17 ± 1.64 kg and 1.28 ± 1.04 kg; 1.64). These observations demonstrate the application of NN body composition prediction algorithms to rapidly emerging large and complex digital anthropometric datasets. Clinical Trial Registration: NCT03637855, NCT05217524, NCT03771417, and NCT03706612.

Measuring acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans using TD-fNIRS.

Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n = 15, 8 females, 7 males, age 32.4 ± 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations, and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our study demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine in humans, and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings.

Change in brain asymmetry reflects level of acute alcohol intoxication and impacts on inhibitory control.

Alcohol is one of the most commonly used substances and frequently abused, yet little is known about the neural underpinnings driving variability in inhibitory control performance after ingesting alcohol. This study was a single-blind, placebo-controlled, randomized design with participants (N = 48 healthy, social drinkers) completing three study visits. At each visit participants received one of three alcohol doses; namely, a placebo dose [equivalent Blood Alcohol Concentration (BAC) = 0.00%], a low dose of alcohol (target BAC = 0.04%), or a moderate dose of alcohol (target BAC = 0.08%). To measure inhibitory control, participants completed a Go/No-go task paradigm twice during each study visit, once immediately before dosing and once after, while their brain activity was measured with time-domain functional near-infrared spectroscopy (TD-fNIRS). BAC and subjective effects of alcohol were also assessed. We report decreased behavioral performance for the moderate dose of alcohol, but not the low or placebo doses. We observed right lateralized inhibitory prefrontal activity during go-no-go blocks, consistent with prior literature. Using standard and novel metrics of lateralization, we were able to significantly differentiate between all doses. Lastly, we demonstrate that these metrics are not only related to behavioral performance during inhibitory control, but also provide complementary information to the legal gold standard of intoxication (i.e. BAC).

Joint modelling of longitudinal processes and time-to-event outcomes in heart failure: systematic review and exemplar examining the relationship between serum digoxin levels and mortality.

BACKGROUND: Joint modelling combines two or more statistical models to reduce bias and increase efficiency. As the use of joint modelling increases it is important to understand how and why it is being applied to heart failure research. METHODS: A systematic review of major medical databases of studies which used joint modelling within heart failure alongside an exemplar; joint modelling repeat measurements of serum digoxin with all-cause mortality using data from the Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure (DIG) trial. RESULTS: Overall, 28 studies were included that used joint models, 25 (89%) used data from cohort studies, the remaining 3 (11%) using data from clinical trials. 21 (75%) of the studies used biomarkers and the remaining studies used imaging parameters and functional parameters. The exemplar findings show that a per unit increase of square root serum digoxin is associated with the hazard of all-cause mortality increasing by 1.77 (1.34-2.33) times when adjusting for clinically relevant covariates. CONCLUSION: Recently, there has been a rise in publications of joint modelling being applied to heart failure. Where appropriate, joint models should be preferred over traditional models allowing for the inclusion of repeated measures while accounting for the biological nature of biomarkers and measurement error.

FAIR data pipeline: provenance-driven data management for traceable scientific workflows.

Modern epidemiological analyses to understand and combat the spread of disease depend critically on access to, and use of, data. Rapidly evolving data, such as data streams changing during a disease outbreak, are particularly challenging. Data management is further complicated by data being imprecisely identified when used. Public trust in policy decisions resulting from such analyses is easily damaged and is often low, with cynicism arising where claims of 'following the science' are made without accompanying evidence. Tracing the provenance of such decisions back through open software to primary data would clarify this evidence, enhancing the transparency of the decision-making process. Here, we demonstrate a Findable, Accessible, Interoperable and Reusable (FAIR) data pipeline. Although developed during the COVID-19 pandemic, it allows easy annotation of any data as they are consumed by analyses, or conversely traces the provenance of scientific outputs back through the analytical or modelling source code to primary data. Such a tool provides a mechanism for the public, and fellow scientists, to better assess scientific evidence by inspecting its provenance, while allowing scientists to support policymakers in openly justifying their decisions. We believe that such tools should be promoted for use across all areas of policy-facing research. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Kernel Flow: a high channel count scalable time-domain functional near-infrared spectroscopy system.

SIGNIFICANCE: Time-domain functional near-infrared spectroscopy (TD-fNIRS) has been considered as the gold standard of noninvasive optical brain imaging devices. However, due to the high cost, complexity, and large form factor, it has not been as widely adopted as continuous wave NIRS systems. AIM: Kernel Flow is a TD-fNIRS system that has been designed to break through these limitations by maintaining the performance of a research grade TD-fNIRS system while integrating all of the components into a small modular device. APPROACH: The Kernel Flow modules are built around miniaturized laser drivers, custom integrated circuits, and specialized detectors. The modules can be assembled into a system with dense channel coverage over the entire head. RESULTS: We show performance similar to benchtop systems with our miniaturized device as characterized by standardized tissue and optical phantom protocols for TD-fNIRS and human neuroscience results. CONCLUSIONS: The miniaturized design of the Kernel Flow system allows for broader applications of TD-fNIRS.

Following the science? Comparison of methodological and reporting quality of covid-19 and other research from the first wave of the pandemic.

BACKGROUND: Following the initial identification of the 2019 coronavirus disease (covid-19), the subsequent months saw substantial increases in published biomedical research. Concerns have been raised in both scientific and lay press around the quality of some of this research. We assessed clinical research from major clinical journals, comparing methodological and reporting quality of covid-19 papers published in the first wave (here defined as December 2019 to May 2020 inclusive) of the viral pandemic with non-covid papers published at the same time. METHODS: We reviewed research publications (print and online) from The BMJ, Journal of the American Medical Association (JAMA), The Lancet, and New England Journal of Medicine, from first publication of a covid-19 research paper (February 2020) to May 2020 inclusive. Paired reviewers were randomly allocated to extract data on methodological quality (risk of bias) and reporting quality (adherence to reporting guidance) from each paper using validated assessment tools. A random 10% of papers were assessed by a third, independent rater. Overall methodological quality for each paper was rated high, low or unclear. Reporting quality was described as percentage of total items reported. RESULTS: From 168 research papers, 165 were eligible, including 54 (33%) papers with a covid-19 focus. For methodological quality, 18 (33%) covid-19 papers and 83 (73%) non-covid papers were rated as low risk of bias, OR 6.32 (95%CI 2.85 to 14.00). The difference in quality was maintained after adjusting for publication date, results, funding, study design, journal and raters (OR 6.09 (95%CI 2.09 to 17.72)). For reporting quality, adherence to reporting guidelines was poorer for covid-19 papers, mean percentage of total items reported 72% (95%CI:66 to 77) for covid-19 papers and 84% (95%CI:81 to 87) for non-covid. CONCLUSIONS: Across various measures, we have demonstrated that covid-19 research from the first wave of the pandemic was potentially of lower quality than contemporaneous non-covid research. While some differences may be an inevitable consequence of conducting research during a viral pandemic, poor reporting should not be accepted.

Association between patterns of alcohol consumption (beverage type, frequency and consumption with food) and risk of adverse health outcomes: a prospective cohort study.

BACKGROUND: Alcohol consumption is a leading contributor to death and disability worldwide, but previous research has not examined the effects of different patterns of alcohol consumption. The study objective was to understand the relationship between different alcohol consumption patterns and adverse health outcomes risk, adjusting for average amount consumed among regular drinkers. METHODS: This was a prospective cohort study of UK Biobank (UKB) participants. Abstainers, infrequent alcohol consumers or those with previous cancer, myocardial infarction (MI), stroke or liver cirrhosis were excluded. We used beverage type, consumption with food and consumption frequency as exposures and adjusted for potential confounding. All-cause mortality, major cardiovascular events-MACE (MI/stroke/cardiovascular death), accidents/injuries, liver cirrhosis, all-cause and alcohol-related cancer incidence over 9-year median follow-up period were outcomes of interest. RESULTS: The final sample size for analysis was N = 309,123 (61.5% of UKB sample). Spirit drinking was associated with higher adjusted mortality (hazard ratio (HR) 1.25; 95% confidence intervals (CI) 1.14-1.38), MACE (HR 1.31; 95% CI 1.15-1.50), cirrhosis (HR 1.48; 95% CI 1.08-2.03) and accident/injuries (HR 1.10; 95% CI 1.03-1.19) risk compared to red wine drinking, after adjusting for the average weekly alcohol consumption amounts. Beer/cider drinkers were also at a higher risk of mortality (HR 1.18; 95% CI 1.10-1.27), MACE (HR 1.16; 95% CI 1.05-1.27), cirrhosis (HR 1.36; 95% CI 1.06-1.74) and accidents/injuries (HR 1.11; 95% CI 1.06-1.17). Alcohol consumption without food was associated with higher adjusted mortality (HR 1.10; 95% CI 1.02-1.17) risk, compared to consumption with food. Alcohol consumption over 1-2 times/week had higher adjusted mortality (HR 1.09; 95% CI 1.03-1.16) and MACE (HR 1.14; 95% CI 1.06-1.23) risk, compared to 3-4 times/week, adjusting for the amount of alcohol consumed. CONCLUSION: Red wine drinking, consumption with food and spreading alcohol intake over 3-4 days were associated with lower risk of mortality and vascular events among regular alcohol drinkers, after adjusting for the effects of average amount consumed. Selection bias and residual confounding are important possible limitations. These findings, if replicated and validated, have the potential to influence policy and practice advice on less harmful patterns of alcohol consumption.

Intravenous lidocaine in spine surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: This study aimed to evaluate the role of intravenous lidocaine as a supplemental pain control modality in patients undergoing spine surgery. METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) involving the use of supplemental intravenous lidocaine in spine surgery. We developed a comprehensive search strategy to adequately screen for randomized controlled trials involving intravenous lidocaine in spine surgery. Continuous outcomes included postoperative opiate consumption and postoperative pain scores. Dichotomous outcomes included nausea, vomiting, pneumonia, delirium, and wound infection. RESULTS: A total of 3 RCTs comprising 235 patients were selected for inclusion in the meta-analysis. Cumulative morphine consumption at 48 h was not statistically significant between lidocaine and control groups. Postoperative pain was not statistically significant at any measured time points in the first and second day postoperatively. There was no statistical difference in postoperative complications including nausea, vomiting, pneumonia, delirium, or surgical site infection. CONCLUSION: Our results indicated that current literature does not support the use of intravenous lidocaine as an adjunctive measure of pain management after spine surgery. Given the relatively few numbers of studies in this field, further randomized controlled trials are needed to make a definitive conclusion on the effectiveness of lidocaine in spine surgery patients.

Direct observation of nuclear reorganization driven by ultrafast spin transitions.

One of the most basic molecular photophysical processes is that of spin transitions and intersystem crossing between excited states surfaces. The change in spin states affects the spatial distribution of electron density through the spin orbit coupling interaction. The subsequent nuclear reorganization reports on the full extent of the spin induced change in electron distribution, which can be treated similarly to intramolecular charge transfer with effective reaction coordinates depicting the spin transition. Here, single-crystal [FeII(bpy)3](PF6)2, a prototypical system for spin crossover (SCO) dynamics, is studied using ultrafast electron diffraction in the single-photon excitation regime. The photoinduced SCO dynamics are resolved, revealing two distinct processes with a (450 ± 20)-fs fast component and a (2.4 ± 0.4)-ps slow component. Using principal component analysis, we uncover the key structural modes, ultrafast Fe-N bond elongations coupled with ligand motions, that define the effective reaction coordinate to fully capture the relevant molecular reorganization.

Perioperative Ketamine for Analgesia in Spine Surgery: A Meta-analysis of Randomized Controlled Trials.

STUDY DESIGN: A meta-analysis of randomized controlled trials (RCTs). OBJECTIVE: The aim of this study was to evaluate the effectiveness of perioperative supplemental ketamine to reduce postoperative opioid analgesic consumption following spine surgery. SUMMARY OF BACKGROUND DATA: Although low-dose supplemental ketamine has been known to reduce pain after surgery, there is conflicting evidence regarding whether ketamine can be effective to reduce opioid consumption following spine surgery. METHODS: Comprehensive search of PubMed, the Cochrane Central Register of Controlled Trials for prospective RCTs, Web of Science, and Scopus. Patients who received supplemental ketamine were compared with the control group in terms of postoperative morphine equivalent consumption, pain scores, and adverse events. Mean differences (MDs) and 95% confidence intervals (CIs) were used to describe continuous outcomes. Odds ratios (ORs) and 95% CIs were applied to dichotomous outcomes. RESULTS: A total of 14 RCTs comprising 649 patients were selected for inclusion into the meta-analysis. Patients who were administered adjunctive ketamine exhibited less cumulative morphine equivalent consumption at 4, 8, 12, and 24 hours following spine surgery (all Ps < 0.05). The ketamine group also reported lower postoperative pain scores at 6, 12, and 24 hours (all Ps < 0.05). None of the adverse events studied attained statistical significance (all Ps > 0.05). CONCLUSION: Supplemental perioperative ketamine reduces postoperative opioid consumption up to 24 hours following spine surgery. LEVEL OF EVIDENCE: 1.

CMOS-Integrated Low-Noise Junction Field-Effect Transistors for Bioelectronic Applications.

In this work, we present a CMOS-integrated low-noise junction field-effect transistor (JFET) developed in a standard 0.18 pm CMOS process. These JFETs reduce input-referred flicker noise power by more than a factor of 10 when compared to equally sized n-channel MOS devices by eliminating oxide interfaces in contact with the channel. We show that this improvement in device performance translates into a factor-of-10 reduction in the input-referred noise of integrated CMOS operational amplifiers when JFET devices are used at the input, significant for many applications in bioelectronics.

Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on Patients Undergoing Curative Intent Liver Surgery.

BACKGROUND: Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the current study was to define the association of primary tumor location on prognosis of patients undergoing curative intent liver resection for NELM. METHODS: Between 1990 and 2014, 421 patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified and analyzed by location of the primary tumor (PNET vs. non-PNET). A propensity score-matched analysis was utilized to assess the impact of primary tumor location on long-term survival. RESULTS: Among the 421 patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). There were no differences in tumor burden and tumor site, while presence of extrahepatic disease was more common among patients with non-PNET NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29 72.5%; p = 0.010). Patients with PNET NELM were more likely to have non-functional disease compared with patients who had non-PNET NELM (non-functional, PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the final pathological specimen of the resected NELM, patients with PNET NELM were more likely to have a moderately differentiated tumor (59.3%), while patients with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%) (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%; p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5% vs. non-PNET 84.3%; p = 0.19). CONCLUSION: PNET patients more often present with non-functional NELM and moderately differentiated tumors. On propensity-matched analysis, factors such as extrahepatic disease and tumor grade, but not primary tumor location, were associated with prognosis of patients undergoing curative intent liver surgery for NELM.

Structural Dynamics upon Photoexcitation in a Spin Crossover Crystal Probed with Femtosecond Electron Diffraction.

Photoexcitation of spin crossover (SCO) complexes can trigger extensive electronic spin transitions and transformation of molecular structure. However, the precise nature of the associated ultrafast structural dynamics remains elusive, especially in the solid state. Here, we studied a single-crystal SCO material with femtosecond electron diffraction (FED). The unique capability of FED allows us to directly probe atomic motions and to track ultrafast structural changes within a crystal lattice. By monitoring the time-dependent changes of the Bragg reflections, we observed the formation of a photoinduced structure similar to the thermally induced high-spin state. The data and refinement calculations indicate the global structural reorganization within 2.3 ps, as the metal-ligand bond distribution narrows during intramolecular vibrational energy redistribution (IVR) driving the intermolecular rearrangement. Three independent dynamical group are identified to model the structural dynamics upon photoinduced SCO.

Development of Expectancies About Own- and Other-Gender Group Interactions and Their School-Related Consequences.

This study examined children's expectancies about interactions with own- and other-gender peers. Goals were to examine expectancies about the outcomes related to own- versus other-gender group interactions, assess cohort and temporal changes in expectancies, and assess the effect of expectancies on school-related outcomes. Students in second and fourth grades (N = 412, 47% girls, Mage  = 7.15 and 9.10 years, respectively) were followed longitudinally for 1 year. Results supported hypotheses that social costs and inclusion-enjoyment that children expect in interactions with own- and other-gender peers represent four constructs. Expectancies varied by gender, age, and differentially predicted school outcomes with inclusion expectancies more strongly relating to outcomes than cost expectancies. Implications of children's expectancies about gendered contexts are discussed.

Spectral Signatures of Ultrafast Spin Crossover in Single Crystal [Fe(II)(bpy)3](PF6)2.

Solvated iron(II)-tris(bipyridine) ([Fe(II)(bpy)3](2+)) has been extensively studied with regard to the spin crossover (SCO) phenomenon. Herein, the ultrafast spin transition dynamics of single crystal [Fe(II)(bpy)3](PF6)2 was characterized for the first time using femtosecond transient absorption (TA) spectroscopy. The single crystal environment is of interest for experiments that probe the nuclear motions involved in the SCO transition, such as femtosecond X-ray and electron diffraction. We found that the TA at early times is very similar to what has been reported in solvated [Fe(II)(bpy)3](2+), whereas the later dynamics are perturbed in the crystal environment. The lifetime of the high-spin state is found to be much shorter (100 ps) than in solution due to chemical pressure exerted by the lattice. Oscillatory behavior was observed on both time scales. Our results show that single crystal [Fe(II)(bpy)3](PF6)2 serves as an excellent model system for localized molecular spin transitions.

An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics.

Considerable effort has recently been directed toward the miniaturization of quantitative-polymerase-chain-reaction (qPCR) instrumentation in an effort to reduce both cost and form factor for point-of-care applications. Considerable gains have been made in shrinking the required volumes of PCR reagents, but resultant prototypes retain their bench-top form factor either due to heavy heating plates or cumbersome optical sensing instrumentation. In this paper, we describe the use of complementary-metal-oxide semiconductor (CMOS) integrated circuit (IC) technology to produce a fully integrated qPCR lab-on-chip. Exploiting a 0.35 µm high-voltage CMOS process, the IC contains all of the key components for performing qPCR. Integrated resistive heaters and temperature sensors regulate the surface temperature of the chip to an accuracy of 0.45 °C. Electrowetting-on-dielectric microfluidics are actively driven from the chip surface, allowing for droplet generation and transport down to volumes less than 1.2 nanoliter. Integrated single-photon avalanche diodes (SPADs) are used for fluorescent monitoring of the reaction, allowing for the quantification of target DNA with more than four-orders-of-magnitude of dynamic range and sensitivities down to a single copy per droplet. Using this device, reliable and sensitive real-time proof-of-concept detection of Staphylococcus aureus (S. aureus) is demonstrated.

Gender-based relationship efficacy: children's self-perceptions in intergroup contexts.

This research introduces a new construct, gender-based relationship efficacy, which refers to beliefs about one's ability to relate to own- and other-gender peers. Study 1 investigated 204 fourth graders (M age = 9.56) and confirmed that own-gender and other-gender relationship efficacy represent distinguishable aspects of preadolescents' social competency beliefs that are differentially related to outcomes with own- and other-gender peers, including outcome expectancies and friendships with own- and other-gender peers. Study 2 provided further evidence of the distinctiveness of relationship efficacy for own- and other-gender peers among 403 seventh (M age = 12.48) and 453 eighth (M age = 13.50) graders and found gender and age differences. Developmental changes and implications for research on intergroup relationships are discussed.