A machine learning approach for potential Super-Agers identification using neuronal functional connectivity networks.

INTRODUCTION: Aging is often associated with cognitive decline. Understanding neural factors that distinguish adults in midlife with superior cognitive abilities (Positive-Agers) may offer insight into how the aging brain achieves resilience. The goals of this study are to (1) introduce an optimal labeling mechanism to distinguish between Positive-Agers and Cognitive Decliners, and (2) identify Positive-Agers using neuronal functional connectivity networks data and demographics. METHODS: In this study, principal component analysis initially created latent cognitive trajectories groups. A hybrid algorithm of machine learning and optimization was then designed to predict latent groups using neuronal functional connectivity networks derived from resting state functional magnetic resonance imaging. Specifically, the Optimal Labeling with Bayesian Optimization (OLBO) algorithm used an unsupervised approach, iterating a logistic regression function with Bayesian posterior updating. This study encompassed 6369 adults from the UK Biobank cohort. RESULTS: OLBO outperformed baseline models, achieving an area under the curve of 88% when distinguishing between Positive-Agers and cognitive decliners. DISCUSSION: OLBO may be a novel algorithm that distinguishes cognitive trajectories with a high degree of accuracy in cognitively unimpaired adults. Highlights: Design an algorithm to distinguish between a Positive-Ager and a Cognitive-Decliner.Introduce a mathematical definition for cognitive classes based on cognitive tests.Accurate Positive-Ager identification using rsfMRI and demographic data (AUC = 0.88).Posterior default mode network has the highest impact on Positive-Aging odds ratio.

Evoking stress reactivity in virtual reality: A systematic review and meta-analysis.

BACKGROUND: Virtual reality (VR) research probes stress environments that are infeasible to create in the real world. However, because research simulations are applied to narrow populations, it remains unclear if VR simulations can stimulate a broadly applicable stress-response. This systematic review and meta-analysis was conducted on studies using VR stress tasks and biomarkers. METHODS: Included papers (N = 52) measured cortisol, heart rate (HR), galvanic skin response (GSR), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory sinus arrhythmia (RSA), parasympathetic activity (RMSSD), sympathovagal balance (LF/HF), and/or salivary alpha-amylase (sAA). Effect sizes (ES) and confidence intervals (CI) were calculated based on standardized mean change of baseline-to-peak biomarker levels. RESULTS: From baseline-to-peak (ES, CI), analyses showed a statistically significant change in cortisol (0.56, 0.28-0.83), HR (0.68, 0.53-0.82), GSR (0.59, 0.36-0.82), SBP (.55, 0.19-0.90), DBP (.64, 0.23-1.05), RSA (-0.59, -0.88 to -0.30), and sAA (0.27, 0.092-0.45). There was no effect for RMSSD and LF/HF. CONCLUSION: VR stress tasks elicited a varied magnitude of physiological stress reactivity. VR may be an effective tool in stress research.

The Tandem Photoredox Catalysis Mechanism of [Ir(ppy)2(dtb-bpy)]+ Enabling Access to Energy Demanding Organic Substrates.

We report the discovery of a tandem catalytic process to reduce energy demanding substrates, using the [Ir(ppy)2(dtb-bpy)]+ (1+) photocatalyst. The immediate products of photoinitiated electron transfer (PET) between 1+ and triethylamine (TEA) undergo subsequent reactions to generate a previously unknown, highly reducing species (2). Formation of 2 occurs via reduction and semisaturation of the ancillary dtb-bpy ligand, where the TEA radical cation serves as an effective hydrogen atom donor, confirmed by nuclear magnetic resonance, mass spectrometry, and deuterium labeling experiments. Steady-state and time-resolved luminescence and absorption studies reveal that upon irradiation, 2 undergoes electron transfer or proton-coupled electron transfer (PCET) with a representative acceptor (N-(diphenylmethylene)-1-phenylmethanamine; S). Turnover of this new photocatalytic cycle occurs along with the reformation of 1+. We rationalize our observations by proposing the first example of a mechanistic pathway where two distinct yet interconnected photoredox cycles provide access to an extended reduction potential window capable of engaging a wide range of energy demanding and synthetically relevant organic substrates including aryl halides.

Adrenocortical and autonomic attunement between romantic partners in emerging adulthood.

Parent-child physiological attunement, particularly during stressful situations, appears adaptive as shared stress reactivity may promote dyadic engagement. Romantic partners eventually replace parents as the primary support figure, yet it remains unclear whether romantic partners buffer physiological stress or display physiological attunement as most studies on adults examine attunement during conflict paradigms. The present study examined physiological attunement in 63 emerging adult romantic partner dyads (one partner was the active participant, the other the observer) during the Trier Social Stress Task (TSST). Heart rate (HR) and respiratory sinus arrhythmia (RSA) were continuously monitored across the visit. Repeated saliva samples were assayed for cortisol. Physiological attunement was operationalized as a correlation in biomarkers between the TSST participant and their partner; sex, social support, and physical proximity were examined as moderators. We then compared the biomarker profiles of partnered-TSST participants to individuals who participated in the TSST solo (n = 63) to determine if partner presence buffered stress biomarker reactivity during the TSST. RSA attunement between partners was found but was not further moderated by social support or sex. Adrenocortical attunement was moderated, such that lower social support and increased proximity resulted in higher attunement. HR attunement was higher when the participant was male and when partners were in close physical proximity. Compared to TSST solo, romantic partner presence increased participant cortisol levels and altered HR reactivity, suggesting that emerging adult romantic partners do not buffer physiological stress reactivity. Future research should examine whether physiological attunement and partner presence is protective in more established relationships.

Evaluation of coloured materials in microfluidic flow-cells for chemiluminescence detection.

Recent advances in the construction of chemiluminescence flow-cells has included high precision milling of channels into a range of different polymer materials, in efforts to maximise the transfer of light from the chemical reaction to the photodetector. However, little is known of the extent that the colour of polymer materials will influence this transfer. This may become increasingly important as chemiluminescence detection zones are integrated with other operations within microfluidic devices or micro total analysis systems (µTAS). Herein, we compare microfluidic flow-cells fabricated from five polymer sheets (clear, white, black, red, blue), using two flow-cell designs (spiral and serpentine), two modes of photodetection, and four chemiluminescence reactions that provide a range of different emission colours. The direct transfer of light from the reaction within the white flow-cell channel to the photodetector made only minor contributions (10%-20%) to the measured intensity, with the majority of the measured light first interacting with the polymer material into which the channels were machined. The extent that the emitted light was absorbed or reflected by the coloured polymer materials was dependent on not only the properties of the polymer, but also the spectral distribution of the chemiluminescence. The changes in chemiluminescence intensities from absorption of light by the flow-cell materials can be accompanied by distortion of the spectral distribution.

Application of 2D-HPLC coupled with principal component analysis to study an industrial opiate processing stream.

Principal component analysis (PCA) loading plots were used to elucidate key differences between two-dimensional high performance liquid chromatography (2D-HPLC) fingerprint data from samples collected from stages along the Papaver somniferum industrial process chemistry workflow. Data reduction was completed using a 2D-HPLC peak picking approach as a precursor to chemometric analysis. Using comparisons of the final stages of product extraction as an example, PCA analysis of characteristic 2D-HPLC fingerprints accounted for 84.9% of variation between the two sample sets measured in triplicate, with 64.7% explained by PC1. Loadings plots of PC1 on each sample set identified where the significant changes were occurring and normalised bubble plots provided an indication of the relative importance of each of these changes. These findings highlight 2D-HPLC with appropriate chemometric analysis as a useful tool for the exploration of bioactive molecules within biomass.

Blind column selection protocol for two-dimensional high performance liquid chromatography.

The selection of two orthogonal columns for two-dimensional high performance liquid chromatography (LC×LC) separation of natural product extracts can be a labour intensive and time consuming process and in many cases is an entirely trial-and-error approach. This paper introduces a blind optimisation method for column selection of a black box of constituent components. A data processing pipeline, created in the open source application OpenMS®, was developed to map the components within the mixture of equal mass across a library of HPLC columns; LC×LC separation space utilisation was compared by measuring the fractional surface coverage, fcoverage. It was found that for a test mixture from an opium poppy (Papaver somniferum) extract, the combination of diphenyl and C18 stationary phases provided a predicted fcoverage of 0.48 and was matched with an actual usage of 0.43. OpenMS®, in conjunction with algorithms designed in house, have allowed for a significantly quicker selection of two orthogonal columns, which have been optimised for a LC×LC separation of crude extractions of plant material.

Analytically useful blue chemiluminescence from a water-soluble iridium(III) complex containing a tetraethylene glycol functionalised triazolylpyridine ligand.

We examine [Ir(df-ppy)2(pt-TEG)](+) as the first highly water soluble, blue-luminescent iridium(III) complex for chemiluminescence detection. Marked differences in selectivity were observed between the new complex and the conventional [Ru(bpy)3](2+) reagent, which will enable this mode of detection to be extended to new areas of application.

Probing the tunable surface chemistry of graphene oxide.

The determination of oxygen content, hydrophobicity and reduction efficiency of graphene oxide (GO) are difficult tasks because of its heterogeneous structure. Herein, we describe a novel approach for the detailed understanding of the surface chemistry of GO by studying the interactions between [Ru(bpy)3](2+) and GO.

Screening of cannabinoids in industrial-grade hemp using two-dimensional liquid chromatography coupled with acidic potassium permanganate chemiluminescence detection.

Widely known for its recreational use, the cannabis plant also has the potential to act as an antibacterial agent in the medicinal field. The analysis of cannabis plants/products in both pharmacological and forensic studies often requires the separation of compounds of interest and/or accurate identification of the whole cannabinoid profile. In order to provide a complete separation and detection of cannabinoids, a new two-dimensional liquid chromatography method has been developed using acidic potassium permanganate chemiluminescence detection, which has been shown to be selective for cannabinoids. This was carried out using a Luna 100 Å CN column and a Poroshell 120 EC-C18 column in the first and second dimensions, respectively. The method has utilized a large amount of the available separation space with a spreading angle of 48.4° and a correlation of 0.66 allowing the determination of more than 120 constituents and mass spectral identification of ten cannabinoids in a single analytical run. The method has the potential to improve research involved in the characterization of sensitive, complex matrices.

Assessing the detectability of antioxidants in two-dimensional high-performance liquid chromatography.

This paper explores the analytical figures of merit of two-dimensional high-performance liquid chromatography for the separation of antioxidant standards. The cumulative two-dimensional high-performance liquid chromatography peak area was calculated for 11 antioxidants by two different methods--the areas reported by the control software and by fitting the data with a Gaussian model; these methods were evaluated for precision and sensitivity. Both methods demonstrated excellent precision in regards to retention time in the second dimension (%RSD below 1.16%) and cumulative second dimension peak area (%RSD below 3.73% from the instrument software and 5.87% for the Gaussian method). Combining areas reported by the high-performance liquid chromatographic control software displayed superior limits of detection, in the order of 1 × 10(-6) M, almost an order of magnitude lower than the Gaussian method for some analytes. The introduction of the countergradient eliminated the strong solvent mismatch between dimensions, leading to a much improved peak shape and better detection limits for quantification.

Chemiluminescence detection of MDMA in street drug samples using tris(2,2'-bipyridine)ruthenium(III).

Tris(2,2'-bipyridine)ruthenium(II) chemiluminescence was investigated for the detection of 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds in street drug samples. Optimization using flow injection analysis showed that the selectivity of the reagent can be targeted towards the detection of secondary amines by altering the pH of the reaction environment. The greater selectivity of this mode of detection, compared to UV-absorbance, reduces the probability of false positive results from interfering compounds. The detection limit for MDMA under these conditions was 0.48 µM. A HPLC method incorporating post-column tris(2,2'-bipyridine)ruthenium(II) chemiluminescence detection was applied to the determination of MDMA in five street drug samples. The results obtained were in good agreement with quantification performed using traditional UV-absorbance detection, which demonstrates the viability of this method for confirmatory analysis of drug samples. This is the first report of tris(2,2'-bipyridine)ruthenium(II) chemiluminescence for the detection of MDMA and related amphetamine derivatives.

Protocols for finding the most orthogonal dimensions for two-dimensional high performance liquid chromatography.

The selection of two high performance liquid chromatography (HPLC) columns with vastly different retention mechanisms is vital for performing effective two-dimensional (2D-) HPLC. This paper reports on a systematic method to select a pair of HPLC columns that provide the most different separations for a given sample. This was completed with the aid of a HPLC simulator that predicted retention profiles on the basis of real experimental data, which is difficult when the contents of sample matrices are largely-or completely-unknown. Peaks from the same compounds must first be matched between chromatograms to compare the retention profiles and optimised 2D-HPLC column selection. In this work, two methods of matching peaks between chromatograms were explored and an optimal pair of chromatography columns was selected for 2D-HPLC. First, a series of 17 antioxidants were selected as an analogue for a coffee extract. The predicted orthogonality of the standards was 39%, according to the fractional surface coverage 'bins' method, which was close to the actual space utilisation of the standard mixture, 44%. Moreover, the orthogonality for the 2D-HPLC of coffee matched the predicted value of 38%. The second method employed a complex sample matrix of urine to optimise the column selections. Seven peaks were confidently matched between chromatograms by comparing relative peak areas of two detection strategies: UV absorbance and potassium permanganate chemiluminescence. It was found that the optimal combinations had an orthogonality of 35% while the actual value was closer to 30%.

Chemiluminescence detection with water-soluble iridium(III) complexes containing a sulfonate-functionalised ancillary ligand.

The chemiluminescence from four cyclometalated iridium(III) complexes containing an ancillary bathophenanthroline-disulfonate ligand exhibited a wide range of emission colours (green to red), and in some cases intensities that are far greater than the commonly employed benchmark reagent, [Ru(bpy)3](2+). A similar complex incorporating a sulfonated triazolylpyridine-based ligand enabled the emission to be shifted into the blue region of the spectrum, but the responses with this complex were relatively poor. DFT calculations of electronic structure and emission spectra support the experimental findings.

A review of recent advances in chemiluminescence detection using nano-colloidal manganese(IV).

The application of 'soluble' (colloidal) manganese(IV) for chemiluminescence detection is reviewed, focussing on papers published since the last comprehensive review of the subject in 2008. Advances in this reagent system include: the on-line formation of manganese(IV); new insight into the light-producing pathway and selectivity of the reagent; its application to assess total antioxidants in plant derived samples and oxidative stress in biological fluids and tissues; and the replacement of the formaldehyde enhancer with ethanol.

Ethanol as an alternative to formaldehyde for the enhancement of manganese(IV) chemiluminescence detection.

Previous applications of manganese(IV) as a chemiluminescence reagent have required the use of formaldehyde to enhance the emission intensity to analytically useful levels. However, this known human carcinogen (by inhalation) is not ideal for routine application. A wide range of alternative enhancers have been examined but to date none have been found to provide the dramatic increase in chemiluminescence intensities obtained using formaldehyde. Herein, we demonstrate that ethanol offers a simple, safe and inexpensive alternative to the use of formaldehyde for manganese(IV) chemiluminescence detection, without compromising signal intensity or sensitivity. For example, chemiluminescence signals for opiate alkaloids using 50-100% ethanol were 0.8-1.6-fold those using 2M formaldehyde. This innocuous alternative enhancer is shown to be a particularly effective for the direct detection of thiols and disulfides by manganese(IV) chemiluminescence, which we have applied to a simple HPLC procedure to determine a series of biomarkers of oxidative stress.

The importance of chain length for the polyphosphate enhancement of acidic potassium permanganate chemiluminescence.

Sodium polyphosphate is commonly used to enhance chemiluminescence reactions with acidic potassium permanganate through a dual enhancement mechanism, but commercially available polyphosphates vary greatly in composition. We have examined the influence of polyphosphate composition and concentration on both the dual enhancement mechanism of chemiluminescence intensity and the stability of the reagent under analytically useful conditions. The average chain length (n) provides a convenient characterisation, but materials with similar values can exhibit markedly different distributions of phosphate oligomers. There is a minimum polyphosphate chain length (∼6) required for a large enhancement of the emission intensity, but no further advantage was obtained using polyphosphate materials with much longer average chain lengths. Providing there is a sufficient average chain length, the optimum concentration of polyphosphate is dependent on the analyte and in some cases, may be lower than the quantities previously used in routine detection. However, the concentration of polyphosphate should not be lowered in permanganate reagents that have been partially reduced to form high concentrations of the key manganese(III) co-reactant, as this intermediate needs to be stabilised to prevent formation of insoluble manganese(IV).

3D-printed and CNC milled flow-cells for chemiluminescence detection.

Herein we explore modern fabrication techniques for the development of chemiluminescence detection flow-cells with features not attainable using the traditional coiled tubing approach. This includes the first 3D-printed chemiluminescence flow-cells, and a milled flow-cell designed to split the analyte stream into two separate detection zones within the same polymer chip. The flow-cells are compared to conventional detection systems using flow injection analysis (FIA) and high performance liquid chromatography (HPLC), with the fast chemiluminescence reactions of an acidic potassium permanganate reagent with morphine and a series of adrenergic phenolic amines.

Investigating retention characteristics of a mixed-mode stationary phase and the enhancement of monolith selectivity for high-performance liquid chromatography.

The synthesis and chromatographic behavior of an analytical size mixed-mode bonded silica monolith was investigated. The monolith was functionalized by an in situ modification process of a bare silica rod with chloro(3-cyanopropyl)dimethyl silane and chlorodimethyl propyl phenyl silane solutions. These ligands were selected in order to combine both resonance and nonresonance π-type bonding within a single separation environment. Selectivity studies were undertaken using n-alkyl benzenes and polycyclic aromatic hydrocarbons in aqueous methanol and acetonitrile mobile phases to assess the methylene and aromatic selectivities of the column. The results fit with the linear solvent strength theory suggesting excellent selectivity of the column was achieved. Comparison studies were performed on monolithic columns that were functionalized separately with cyano and phenyl ligands, suggesting highly conjugated molecules were able to successfully exploit both of the π-type selectivities afforded by the two different ligands on the mixed-mode column.

Enhancing permanganate chemiluminescence detection for the determination of glutathione and glutathione disulfide in biological matrices.

Acidic potassium permanganate chemiluminescence enables direct post-column detection of glutathione, but its application to assess the redox state of a wider range of biological fluids and tissues is limited by its sensitivity. Herein we show that the simple on-line addition of an aqueous formaldehyde solution not only enhances the sensitivity of the procedure by two orders of magnitude, but also provides a remarkable improvement in the selectivity of the reagent towards thiols such as glutathione (compared to phenols and amino acids that do not possess a thiol group). This enhanced mode of detection was applied to the determination of glutathione and its corresponding disulfide species in homogenised striatum samples taken from both wild type mice and the R6/1 transgenic mouse model of Huntington's disease, at both 8 and 12 weeks of age. No significant difference was observed between the GSH/GSSG ratios of wild type mice and R6/1 mice at either age group, suggesting that the early disease progression had not significantly altered the intracellular redox environment.