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The influence of professionals’ personal views and values in the development of guidelines for rare diseases: an example from phenylketonuria
Get PDFBackground: In the process of guideline development, expert opinion is introduced when there is low-quality or no scientific evidence available. During the first revision of the European phenylketonuria guidelines, the limited data regarding adult treatment targets was interpreted and weighted in different ways by different professionals. In this study, we have recorded and analyzed personal experience and views that may affect decisions. Methods: A web-based questionnaire was sent to all panelists involved in the revision of the guidelines (n = 23), evaluating demographics, opinion about treatment targets, interpretation of scientific data and general views to establish adult specific treatment guidelines. Results: 19 panelists responded. Most acknowledged the importance of maintaining metabolic control even in adulthood with target levels in line with previous recommendations, but that dietary treatment is a limiting factor for social life. 68% preferred the risk of over-treatment rather than undertreatment. The great majority considered cognitive, behavioral and wellbeing measures to be critical to measure treatment success. 58% considered significant group differences of 1 SD or less in neuropsychological tasks to be clinically significant. Conclusion: Results highlight differences in expert opinions and the importance of making them more transparent to reach less-biased recommendations
Green Cold Chain Logistics: Minimising Greenhouse Gas Emissions of Fresh Food Products in Transport Refrigeration Units
Get PDFBackground: The growing demand for fresh food leads to extensive use of cold chain logistics (CCL) that significantly contributes to greenhouse gas (GHG) emissions due to its dependence on energy-intensive transport refrigeration units (TRUs). Understanding the need to balance food preservation with environmental sustainability, this paper explores practical strategies for reducing GHG emissions in CCL, focusing on fresh food products. Methods: The quantitative and qualitative analyses are applied to analyse data from Transport for London and Transport Scotland. Emission data were assessed to evaluate the impact of alternative TRU technologies and route optimisation practices. Results: The findings reveal that electric and cryogenic TRUs, along with improved route planning and operational practices, can significantly reduce the emissions of carbon dioxide, nitrogen oxides and particulate matter. These results highlight the potential strategy for industry-led emission reductions without compromising food quality. Conclusions: This paper recommends the coordination of government policy and industry to support technological adaptation and infrastructure upgrades and to research into real-time monitoring and renewable energy integration in CCL systems
Outcome measures in CIDP: A scoping and mapping review
Get PDFBackground: CIDP is a rare autoimmune disorder with varying symptom presentations. This heterogenous nature challenges standardizing disease monitoring and assessing treatment response. This study aimed to provide a comprehensive overview of clinical outcome assessments (COAs) used in CIDP. Methods: A structured literature review and mapping exercise was conducted to identify COAs reported in CIDP literature published between 2010 and 2023. Supplementary searches were conducted in other relevant sources. Key publications pre-2010 were identified through handsearching or consultation with clinical experts. Clinical experts assisted with prioritization of identified COAs to those clinically relevant to CIDP. Results: Overall, 2027 records were included, with 904 prioritized for COA mapping, and 524 reporting on relevant CIDP COAs. Overall, 99 different COAs were captured; the most frequent related to functional impairment, followed by humanistic burden. Three COAs were most prominent: INCAT, MRC score and I-RODS (reported in 45.6 %, 37.4 % and 29.2 % of publications respectively). Numerous CIDP biomarkers were identified; 21 publications reported on neurofilament light chain (NfL). Conclusion: Substantial heterogeneity in CIDP COAs use exists. This review identified the INCAT, I-RODs, and MRC score as core measures that evaluate important, although not exhaustive, aspects of CIDP disease experience. The absence of validated CIDP biomarkers, and the heterogeneity of available COAs, may impact the assessment of CIDP treatment effectiveness. More research is needed to establish a set of comprehensive outcome measures, that are relevant to clinicians and patients with CIDP
ESG Performance of Firms and the Structure of Loan Syndicates: Moderating Role of Relationship
No full textThis study examines the impact of firms' environmental, social and governance (ESG) performance on borrower–lender relationships within syndicated loans. Analyzing a global panel of contracts, we examine the impact of ESG scores on the number of lenders and the ownership of lead arrangers. Utilizing theories of information asymmetry, agency, relational lending, and resource dependence, our findings indicate that high ESG performance decreases lead bank retention, thus broadening syndicates and distributing risk. However, prior borrower–led relationships can reverse this effect, emphasizing that ESG and relational trust act as complementary governance channels, shaping modern global credit markets and capital allocation across sectors
Statistical asymmetry: an entropic measure of symmetry
Get PDFThis work introduces formally the concept of statistical asymmetry (SA) of a system as an entropic measure of how much it fails to be fully symmetric under a given group of transformations. It is shown that it is able to provide an alternative classification of one-dimensional elementary cellular automata that closely aligns with known others only by measuring symmetry. The behaviour of SA can also be an useful indicator of complex behaviour on two-dimensional discrete processes by following the dynamics of configurations, which is demonstrated in the case of the Geenberg–Hastings model, Conway’s game of life, and the random evolution of discrete square matrices
Use of GLP-1 receptor agonists and risks of suicide attempts or self-harm in patients with type 2 diabetes: a multicountry self-control case series study
Get PDFBackground: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies. Methods: This was a multinational self-controlled case series analysis using Hong Kong’s Clinical Data Analysis and Reporting System (2008−2023), Taiwan’s National Health Insurance Research Database (2012−2020) and the UK’s IQVIA Medical Research Database with The Health Improvement Network (2000−2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95% CIs. Results: The pooled IRR (95% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1−30, Days 31−90, Days 91−180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively. Conclusions: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings
Reinforcing the Path: The Paradox of Failed Reform in India’s Minority Policies (2004-2024)
Get PDFThe article analyses the trajectory of minority-related policies in India between 2004 and 2024, using the United Progressive Alliance (UPA) government’s experience (2004–2014) as a context for understanding the Bharatiya Janata Party’s (BJP) policy stance since taking power in 2014, highlighting the contrasting approaches of the two administrations. It uses the concepts of path dependence and punctuated equilibrium, well-established in political science and public policy studies, but which are under-utilised in examining India’s minority policies. The article explores why minority-related policies remained largely unchanged during the UPA’s tenure, despite its attempts to restructure institutional arrangements. Paradoxically, the UPA’s failed effort reinforced existing policy frameworks, enabling the BJP to pursue policies that prioritised Hindu majority interests while weakening protections for minorities. Understanding this background is essential for analysing the BJP’s stance on minority issues since 2014. The UPA’s failed reforms inadvertently created conditions that allowed the BJP to advance majoritarian agendas with relatively little institutional resistance. This article demonstrates how these policy failures consolidated pre-existing institutional patterns and highlights the self-reinforcing nature of political and institutional paths in India. This study offers a nuanced account of institutional dynamics that have shaped India’s political landscape, particularly concerning minority rights and secular governance
Experiments on contaminant transport from sewer infrastructure within shallow floodwater
Get PDFUnderstanding the transport of soluble contamination in urban floodwater is an important aspect of public health risk assessment. However due to significant measurement complexity, there is a current lack of datasets to elucidate the associated relevant flow pathways, local velocity fields and turbulent diffusion processes. This paper evaluates three alternate experimental methodologies to quantify 2D contaminant transport at scales typical of shallow urban floodwater. It further provides a new open access dataset describing transport processes from an experimental scale model of floodwater under sewer surcharge conditions, featuring different geometrical and hydraulic configurations. Results show broad agreement between the different experimental techniques, with small but notable differences associated with measurement and experimental limitations. Results and datasets also demonstrate the considerable influence of hydraulic and geometrical complexity on transport processes, and sensitivity of the concentration levels in model street networks to heterogeneous flow pathways and velocity gradients
A comparative study of effect of polyol-based and acid-based deep eutectic solvents pretreatment of rice straw under autoclave conditions on cellulose enrichment and digestibility
Get PDFDeep eutectic solvents (DESs) are attractive for lignocellulosic biomass deconstruction because of their easy synthesis, reusability, inexpensive nature, and eco-friendliness. Pretreatment of rice straw was carried out using three types of DES: choline chloride:glycerol (ChCl:Gly), choline chloride:ethylene glycol (ChCl:EG), and choline chloride:formic acid (ChCl:FA) at 120 °C, 1.5 bars in an autoclave for 1 h. Enzymatic digestibility of pretreated samples was assessed at 10% solids loading and 9.0 filter paper units g−1 cellulose of enzyme loading. A delignification efficiency of 51.6% was obtained with ChCl:FA compared to 30.4% and 36.1% obtained with ChCl:Gly and ChCl:EG respectively. The cellulose content of 58.4% was obtained from ChCl:FA pretreated samples compared to cellulose contents of < 48% from ChCl:Gly and ChCl:EG pretreated samples; cellulose content of pretreated and untreated samples correlated with their crystallinity indexes. The lowest hemicellulose content of 9.5% was obtained from the ChCl:FA pretreated sample, while ChCl:Gly and ChCl:EG were like the untreated (around 22%). As indicated by spectroscopic, microscopic, and thermogravimetric analysis, DES pretreatment caused alterations in chemical composition, structure, and surface morphology. ChCl:FA pretreated sample (Ac-PT4) was significantly hydrolysed, resulting in a glucose yield of 79.7% and a concentration of 45.56 gLl−1 after 72 h of hydrolysis. The glucose yield obtained from ChCl:Gly and ChCl:EG pretreated samples ranged from 32 to 36%, while the glucose concentrations ranged from 14 to 16 gL−1. Pretreatment using ChCl:FA effectively delignified rice straw and led to a threefold increase in enzymatic digestibility compared to untreated; hence, pretreatment using ChCl:FA could support a biorefinery concept
The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies
Get PDFThe global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised
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