Analysis of gas chromatography/mass spectrometry data for catalytic lignin depolymerization using positive matrix factorization

Various catalytic technologies are being developed to efficiently convert lignin into renewable chemicals. However, due to its complexity, catalytic lignin depolymerization often generates a wide and complex distribution of product compounds. Gas chromatography/mass spectrometry (GC-MS) is a common analytical technique to profile the compounds that comprise lignin depolymerization products. GC-MS is applied not only to determine the product composition, but also to develop an understanding of the catalytic reaction pathways and of the relationships among catalyst structure, reaction conditions, and the resulting compounds generated. Although a very useful tool, the analysis of lignin depolymerization products with GC-MS is limited by the quality and scope of the available mass spectral libraries and the ability to correlate changes in GC-MS chromatograms to changes in lignin structure, catalyst structure, and other reaction conditions. In this study, the GC-MS data of the depolymerization products generated from organosolv hybrid poplar lignin using a copper-doped porous metal oxide catalyst and a methanol/dimethyl carbonate co-solvent was analyzed by applying a factor analysis technique, positive matrix factorization (PMF). Several different solutions for the PMF model were explored. A 13-factor solution sufficiently explains the chemical changes occurring to lignin depolymerization products as a function of lignin, reaction time, catalyst, and solvent. Overall, seven factors were found to represent aromatic compounds, while one factor was defined by aliphatic compounds

The frail-LESS (LEss sitting and sarcopenia in frail older adults) remote intervention to improve sarcopenia and maintain independent living via reductions in sedentary behaviour: findings from a randomised controlled feasibility trial

The datasets supporting the conclusions of this article are available in Figshare, https://doi.org/10.17633/rd.brunel.26028892.v1. The raw qualitative data (transcripts) are not publicly available due to privacy restrictions. Further detail on the qualitative data and analysis that supports the findings of this study are available upon request to the corresponding author.Electronic supplementary material is available online at: https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-024-05310-9#Sec40 .Background: Sarcopenia leads to functional disability, dependence in activities of daily living (ADL), and is a key contributor to frailty. Reducing and breaking up sedentary time is associated with improved sarcopenia and frailty-related outcomes. The aim of this study was to determine the feasibility of delivering and evaluating a remote sedentary behaviour intervention to improve sarcopenia and independent living in older adults with frailty. Methods: A two-arm randomised controlled feasibility trial was conducted with a target of 60 older adults (mean age 74 ± 6 years) with very mild or mild frailty. Participants were randomised to the Frail-LESS (LEss Sitting and Sarcopenia in Frail older adults) intervention or usual care control group for six months. The intervention included tailored feedback on sitting, standing and stepping; an education workbook that included goal setting and action planning; one-to-one health coaching; peer support; and a wearable device to self-monitor sedentary behaviour. Participant recruitment (percentage of eligible individuals recruited), retention and data completion rates were used to assess trial feasibility. Acceptability of the trial was explored through interviews and safety was evaluated via unplanned healthcare utilisation and number of falls. Sitting, standing, stepping and sarcopenia were measured to evaluate potential intervention effects. Results: Sixty participants were recruited. Recruitment and retention rates were 72% and 83%, respectively. Completion rates for outcome measures ranged from 70 to 100%. The trial was safe (< 1 fall per participant on average at each timepoint) and trial procedures were acceptable. Descriptive analysis (mean ± SD) showed that daily sitting was 25.1 ± 82.1 min/day lower in the intervention group, and 6.4 ± 60.5 min/day higher in the control group, at 6 months compared with baseline. Hand grip strength and sit-to-stand score were improved by 1.3 ± 2.4 kg and 0.7 ± 1.0, respectively, in the intervention group. Conclusions: This study demonstrates the feasibility and safety of delivering and evaluating a remote intervention to reduce and break up sitting in older adults with frailty. The intervention showed evidence towards reducing daily sitting and improving sarcopenia, supporting its evaluation in a definitive randomised controlled trial. Trial registration: ISRCTN registry (registration number: ISRCTN17158017). Registered 6th August 2021.Abbeyfield Research Foundatio

Yoga programme for type-2 diabetes prevention (YOGA-DP) among high risk people in India: a multicentre feasibility randomised controlled trial protocol.

INTRODUCTION: A huge population in India is at high risk of type-2 diabetes (T2DM). Physical activity and a healthy diet (healthy lifestyle) improve blood glucose levels in people at high risk of T2DM. However, an unhealthy lifestyle is common among Indians. Yoga covers physical activity and a healthy diet and can help to prevent T2DM. The research question to be addressed by the main randomised controlled trial (RCT) is whether a Yoga programme for T2DM prevention (YOGA-DP) is effective in preventing T2DM among high risk people in India as compared with enhanced standard care. In this current study, we are determining the feasibility of undertaking the main RCT. INTERVENTION: YOGA-DP is a structured lifestyle education and exercise programme. The exercise part is based on Yoga and includes Shithilikarana Vyayama (loosening exercises), Surya Namaskar (sun salutation exercises), Asana (Yogic poses), Pranayama (breathing practices) and Dhyana (meditation) and relaxation practices. METHODS AND ANALYSIS: This is a multicentre, two-arm, parallel-group, feasibility RCT with blinded outcome assessment and integrated mixed-methods process evaluation. Eligible participants should be aged 18-74 years, at high risk of T2DM (fasting plasma glucose level 5.6-6.9 mmol/L) and safe to participate in physical activities. At least 64 participants will be randomised to intervention or control group with final follow-up at 6 months. Important parameters, needed to design the main RCT, will be estimated, such as SD of the outcome measure (fasting plasma glucose level at 6-month follow-up), recruitment, intervention adherence, follow-up, potential contamination and time needed to conduct the study. Semistructured qualitative interviews will be conducted with up to 20-30 participants, a sample of those declining to participate, four YOGA-DP instructors and around eight study staff to explore their perceptions and experiences of taking part in the study and of the intervention, reasons behind non-participation, experiences of delivering the intervention and running the study, respectively. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the following Research Ethics Committees: Faculty of Medicine and Health Sciences, University of Nottingham (UK); Centre for Chronic Disease Control (CCDC, India); Bapu Nature Cure Hospital and Yogashram (BNCHY, India) and Swami Vivekananda Yoga Anusandhana Samsthana (S-VYASA, India). The results will be widely disseminated among key stakeholders through various avenues. TRIAL REGISTRATION NUMBER: CTRI/2019/05/018893

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $\mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j \sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_\infty$ as $t\to\infty$, and the stochastic growth rate $\lim_{t\to\infty}t^{-1}\log S_t$ equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of $Y_\infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Fluorescence Lifetime Imaging Unravels C. trachomatis Metabolism and Its Crosstalk with the Host Cell

Chlamydia trachomatis is an obligate intracellular bacterium that alternates between two metabolically different developmental forms. We performed fluorescence lifetime imaging (FLIM) of the metabolic coenzymes, reduced nicotinamide adenine dinucleotides [NAD(P)H], by two-photon microscopy for separate analysis of host and pathogen metabolism during intracellular chlamydial infections. NAD(P)H autofluorescence was detected inside the chlamydial inclusion and showed enhanced signal intensity on the inclusion membrane as demonstrated by the co-localization with the 14-3-3β host cell protein. An increase of the fluorescence lifetime of protein-bound NAD(P)H [τ2-NAD(P)H] inside the chlamydial inclusion strongly correlated with enhanced metabolic activity of chlamydial reticulate bodies during the mid-phase of infection. Inhibition of host cell metabolism that resulted in aberrant intracellular chlamydial inclusion morphology completely abrogated the τ2-NAD(P)H increase inside the chlamydial inclusion. τ2-NAD(P)H also decreased inside chlamydial inclusions when the cells were treated with IFNγ reflecting the reduced metabolism of persistent chlamydiae. Furthermore, a significant increase in τ2-NAD(P)H and a decrease in the relative amount of free NAD(P)H inside the host cell nucleus indicated cellular starvation during intracellular chlamydial infection. Using FLIM analysis by two-photon microscopy we could visualize for the first time metabolic pathogen-host interactions during intracellular Chlamydia trachomatis infections with high spatial and temporal resolution in living cells. Our findings suggest that intracellular chlamydial metabolism is directly linked to cellular NAD(P)H signaling pathways that are involved in host cell survival and longevity

What is theoretical progress of science?

The epistemic conception of scientific progress equates progress with accumulation of scientific knowledge. I argue that the epistemic conception fails to fully capture scientific progress: theoretical progress, in particular, can transcend scientific knowledge in important ways. Sometimes theoretical progress can be a matter of new theories ‘latching better onto unobservable reality’ in a way that need not be a matter of new knowledge. Recognising this further dimension of theoretical progress is particularly significant for understanding scientific realism, since realism is naturally construed as the claim that science makes theoretical progress. Some prominent realist positions (regarding fundamental physics, in particular) are best understood in terms of commitment to theoretical progress that cannot be equated with accumulation of scientific knowledge

Effect of private insurance incentive policy reforms on trends in coronary revascularisation procedures in the private and public health sectors in Western Australia: A cohort study

Background: The Australian federal government introduced private health insurance incentive policy reforms in 2000 that increased the uptake of private health insurance in Australia. There is currently a lack of evidence on the effect of the policy reforms on access to cardiovascular interventions in public and private hospitals in Australia. The aim was to investigate whether the increased private health insurance uptake influenced trends in emergency and elective coronary artery revascularisation procedures (CARPs) for private and public patients. Methods: We included 34,423 incident CARPs from Western Australia during 1995-2008 in this study. Rates of emergency and elective CARPs were stratified for publicly and privately funded patients. The average annual percent change (AAPC) in trend was calculated before and after 2000 using joinpoint regression. Results: The rate of emergency CARPs, which were predominantly percutaneous coronary interventions (PCIs) with stenting, increased throughout the study period for both public and private patients (AAPC=12.9%, 95% CI=5.0,22.0 and 14.1%, 95% CI=9.8,18.6, respectively) with no significant difference in trends before and after policy implementation. The rate of elective PCIs with stenting from 2000 onwards remained relatively stable for public patients (AAPC=−6.0, 95% C= −16.9,6.4), but increased by 4.1% on average annually (95% CI=1.8,6.3) for private patients (Pdifference=0.04 between groups). This rate increase for private patients was only seen in people aged over 65 years and people residing in high socioeconomic areas.Conclusions: The private health insurance incentive policy reforms are a likely contributing factor in the shift in 2000 from public to privately-funded elective PCIs with stenting. These reforms as well as the increasing number of private hospitals may have been successful in increasing the availability of publicly-funded beds since 2000

Adaptation and validation of the Charlson Index for Read/OXMIS coded databases

BACKGROUND: The Charlson comorbidity index is widely used in ICD-9 administrative data, however, there is no translation for Read/OXMIS coded data despite increasing use of the General Practice Research Database (GPRD). Our main objective was to translate the Charlson index for use with Read/OXMIS coded data such as the GPRD and test its association with mortality. We also aimed to provide a version of the comorbidity index for other researchers using similar datasets. METHODS: Two clinicians translated the Charlson index into Read/OXMIS codes. We tested the association between comorbidity score and increased mortality in 146 441 patients from the GPRD using proportional hazards models. RESULTS: This Read/OXMIS translation of the Charlson index contains 3156 codes. Our validation showed a strong positive association between Charlson score and age. Cox proportional models show a positive increasing association with mortality and Charlson score. The discrimination of the logistic regression model for mortality was good (AUC = 0.853). CONCLUSION: We have translated a commonly used comorbidity index into Read/OXMIS for use in UK primary care databases. The translated index showed a good discrimination in our study population. This is the first study to develop a co-morbidity index for use with the Read/OXMIS coding system and the GPRD. A copy of the co-morbidity index is provided for other researchers using similar database