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Meeting physical activity guidelines in conjunction with higher protein intake: associations with appendicular lean soft tissue index in middle aged adults with cancer
No full textAbstract
Background
Loss of muscle mass is a common concern among patients with cancer. The aim of this study was to examine whether meeting the World Health Organization physical activity guidelines in combination with a higher vs. lower than the recommended daily allowance (RDA) protein intake is associated with greater appendicular lean soft tissue index (ALSTI) in adults aged 40–59 years with cancer from the National Health and Nutrition Examination Survey.
Methods
Participants were categorized by physical activity levels (moderate ≥ 150 min/week or vigorous ≥ 75 min/week) and protein intake (> 0.8 vs. ≤ 0.8 g/kg/day) assessed via two interviewer-administered 24-h dietary recalls. ALSTI was calculated using dual-energy X-ray absorptiometry (kg/m
2
). Linear regression models estimated associations, adjusting for demographic, clinical, and dietary covariates.
Results
Among 169 participants (mean age 51.0 ± 5.6 years; 69% women, mean ALSTI 7.74 ± 1.66 kg/m
2
), those meeting vigorous or moderate physical activity guidelines with higher protein intake did not show a significant association with ALSTI in the fully adjusted models (vigorous: β = 0.08, standard error (SE) 0.12,
p
= 0.53; moderate: β = -0.05, SE 0.15,
p
= 0.76). However, a significantly positive link was found in those meeting both vigorous and moderate physical activity (β = 0.40, b SE 0.02, p < 0.01).
Conclusions
Meeting vigorous or moderate physical activity guidelines in combination with higher vs. lower protein intake was not associated with ALSTI in adults with cancer. However, meeting both was positively linked to ALSTI. Longitudinal and interventional studies using objective measures and longitudinal designs are needed to clarify the role of physical activity with adequate protein intake in preserving muscle health in this clinical population.
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Monitoring and analysis of excess pore water pressure response during jet grouting installation in liquefiable silty sand soils
Get PDFThe Yellow River floodplain, characterized by poor geotechnical properties and high liquefaction potential, is commonly treated using double-fluid and triple-fluid system jet grouting. However, poor column quality is often encountered due to complex hydrogeological conditions and highly permeable soil characteristics. This study investigates the failure mechanisms of jet grouting column formation through pore pressure monitoring and comprehensive quality evaluation. Furthermore, a parametric study was conducted by varying key construction parameters, including grouting pressure in the double-fluid system, as well as grouting pressure and nozzle spacing in the triple-fluid system. For this purpose, field tests were performed on nine columns constructed using double and triple-fluid jet grouting techniques. The accumulation and dissipation of excess pore water pressure (EPWP) govern both the liquefaction extent and the resulting column quality. In the double-fluid system, the liquefaction extent increases with grouting pressure, leading to a larger column diameter but a reduction in unconfined compressive strength (UCS). In the triple-fluid system, besides grouting pressure, nozzle spacing plays a critical role in controlling liquefaction; increasing the spacing from 0.3 m to 0.7 m decreases the liquefaction extent and enhances UCS by 2.81 MPa by minimizing overlap of the disturbance zones. The difference between liquefaction extent and column radius ( Δ l ) exhibits a linear negative correlation with UCS in the double-fluid system, whereas a nonlinear correlation is observed in the triple-fluid system. Furthermore, in both cases, EPWP decays exponentially with an influence range of about 10 times the column diameter. An energy waste assessment framework is developed by quantifying over-liquefied zones relative to the final pile structure, enabling systematic evaluation of energy waste rate (EWR) across different construction configurations. Additionally, this study proposes a novel strategy for liquefiable silty sand foundations by linking EPWP to column quality, enabling optimization of construction parameters. The findings highlight that increasing nozzle spacing in the triple-fluid system can effectively improve column integrity by reducing the affected zone
Thriving or surviving: Understanding the geography of financial precarity in Great Britain
No full textFinancial precarity, the state of economic insecurity characterised by unpredictable employment and declining social protection significantly impacts cognitive functioning, emotional stability and social inclusion. This condition stems from multiple interconnected factors: poor quality and unpredictable work, unmanaged debt, insecure asset wealth and insufficient financial resource. Despite extensive research on financial precarity's individual impacts, its geographical distribution and associated social-spatial inequalities remain poorly understood. This paper addresses this gap by introducing a new geodemographic classification of financial precarity across Great Britain. Our classification system uses small-area measurements encompassing employment patterns, income levels, asset holdings, debt obligations, and lifestyle characteristics at the neighbourhood level. By mapping financial precarity at a fine spatial scale, this research reveals how economic vulnerability varies across different localities, highlighting the uneven geography of financial insecurity between rural and urban areas, city centres and peripheries, coastal and inland communities, and how the classification groups are interwoven to the variegated patterns in and around major urban areas. This small-area approach provides sufficient detail to identify spatial patterns while enabling comparisons between local areas, offering new insights into the geographic dimensions of economic precarity in contemporary Britain
The dangers of feudal escheat, being the two pipe problem of the Baglan Operations Ltd liquidation and post disclaimer responsibility
No full textThe dangers of feudal escheat, being the two pipe problem of the Baglan Operations Ltd liquidation and post disclaimer responsibilit
Accelerating Generic Long-Acting Antiretrovirals for Global HIV Treatment: Workshop Findings and a Roadmap to Access
No full textThe global HIV response aims for widespread availability of affordable, quality-assured long-acting antiretroviral (LA ARV) drugs to achieve sustained epidemic control, particularly in low- and middle-income countries. This report summarizes key discussion points, findings, and outcomes from an international workshop on generic LA ARVs, held in Liverpool, United Kingdom, and co-organized by the Long-Acting/Extended-Release Antiretroviral Resource Program (LEAP) and the Centre of Excellence for Long-acting Therapeutics (CELT). The workshop brought together experts from across disciplines to evaluate the multifaceted challenges and opportunities for faster development and regulatory approval of affordable and accessible generic LA ARVs. Key topics included the application of novel pharmacokinetic end points to reduce study duration, the integration of community preferences into practice-based research in resource-limited settings, intellectual property considerations, formulation and manufacturing complexities that affect cost, scalability and implementation, and the growing role of model-integrated evidence in streamlining bioequivalence assessments. To reach the goal of timely and equitable global access to long-acting medicines, this workshop emphasized the need for strategic public-private engagement to promote data sharing, enhance regulatory efficiencies, and develop robust in vitro–in vivo correlation strategies that meet regulatory guidance for LAI products
Ferroelectricity through Reversible Anion-Relay Polarization Switching in a Two-Dimensional Metal–Organic Framework
No full textFerroelectric materials are central to next-generation electronics and energy technologies because of their ability to couple electrical, mechanical, and thermal signals. Metal–organic frameworks (MOFs) provide a versatile platform for such functionalities owing to their structural tunability; however, despite notable examples, the microscopic mechanisms governing polarization switching in MOFs remain poorly understood. Here we report a Cu(II)-based polar two-dimensional metal–organic framework [Cu(PhPO(NHCH23Py)2)](NO3)2·2H2O (1·2H2O), constructed from a low-symmetric flexible dipodal phosphoramide ligand, PhPO(NHCH23Py)2. Compound 1·2H2O exhibits robust ferroelectricity, confirmed by a well-defined rectangular P–E hysteresis loop with a saturation polarization of 1.2 μC/cm2. The ferroelectric polar domains, along with bias-dependent amplitude-butterfly and phase-hysteresis loops, were characterized by piezoresponse force microscopy (PFM). First-principles calculations uncover an unusual displacive polarization-switching pathway, in which two nitrate ions displace together along a field-defined direction, enabling reversible 180° dipole reversal through bonding reorganization at the Cu(II) center. This reversible anion-relay mechanism expands the catalog of microscopic ferroelectric processes and represents a new paradigm for MOFs. To demonstrate practical utility, flexible piezoelectric nanogenerators (PENGs) were fabricated by embedding 1·2H2O in thermoplastic polyurethane composites. The champion 10 wt % device delivered an open-circuit voltage of 25.1 V and a maximum power density of 48.7 μW/cm2, highlighting the potential of MOF-based ferroelectrics for piezoelectric energy harvesting applications
MicroAge mission: experimental design and hardware for a bespoke culture system supporting tissue-engineered skeletal muscle.
No full textMicrogravity provides a unique model for accelerated skeletal muscle loss and potentially muscle ageing. During spaceflight, astronauts experience pronounced muscle atrophy, similar to age-related decline on Earth but over a much shorter timescale. Despite daily aerobic and resistance exercise on the International Space Station (ISS), countermeasures remain suboptimal, reflecting similar challenges seen in ageing populations. The MicroAge Mission used microgravity on the ISS to assess whether the molecular mechanisms behind reduced adaptive responses to contractile activity during ageing resemble those triggered by spaceflight. It also tested proof-of-concept genetic interventions, including Heat Shock Protein 10 (HSP10) overexpression, to mitigate muscle atrophy and functional loss. A tissue-engineering approach was used to fabricate human skeletal muscle constructs secured to 3D-printed scaffolds. These scaffolds incorporated microfluidic channels to interface with the flight hardware's fluid-handling system. The hardware, developed by Kayser Space Ltd, was designed to operate with the European Space Agency's (ESA) Kubik incubator on the ISS. This research addresses key methodological constraints in low Earth orbit (LEO) experimentation, outlining pre-flight protocol development, muscle construct biofabrication methods, and operational considerations. The findings provide a translational framework for future studies on musculoskeletal degeneration, with implications for therapies targeting both terrestrial ageing and astronaut musculoskeletal health
Altered cholesterol immunometabolism activates the macrophage NLRP3-inflammasome in lung fibrosis.
No full textPrevious research has highlighted dysregulation in lipid metabolism during lung fibrosis. However, the impact of cholesterol immunometabolism during lung fibrosis progression remains unclear but has been related to the NLRP3-inflammasome activation in cardiovascular diseases. The main objective of this work was to investigate the link between altered cholesterol metabolism and NLRP3 inflammasome activation in fibrotic lungs. Different pulmonary fibrosis patient cohorts (from 2 centers and a publicly available dataset) and a murine model of lung fibrosis (aged SP-C-/-) were included. Expression of cholesterol metabolism proteins and cholesterol content were determined in lungs from patients and bronchoalveolar lavage fluid (BALF) cells of aging SP-C-/- mice. Metabolomic and lipidomic analyses were conducted in BALF and BALF cells of SP-C-/- versus wild-type (WT) mice. NLRP3 inflammasome components were assessed by immunoblotting, ELISA, and immunofluorescence. Lung samples from fibrosis patients showed higher cholesterol content, altered cholesterol metabolism and higher IL-18 levels, compared to controls. Moreover, key genes related to inflammasome activation and cholesterol metabolism were differentially expressed in alveolar macrophages from IPF patients. Accordingly, BALF cells of SP-C-/- mice showed alteration of their cholesterol metabolism and inflammasome activation with age and fibrosis development. Lipidomic analysis pointed at cholesterol esters as potential activating agent. The molecular mechanism linking cholesterol esters to NLRP3 inflammasome and fibrosis markers was confirmed in vitro in a human macrophage model. In conclusion, altered cholesterol esterification activates the NLRP3 inflammasome in AM during pulmonary fibrosis in a murine model and fibrosis patients
Feasibility and outcomes of robotic colorectal cancer surgery in patients with high body mass index.
No full textBackgroundMinimally invasive techniques are the standard of care in colorectal surgery. However, high body mass index (BMI) presents technical and anaesthetic challenges. Robotic-assisted surgery offers potential advantages in this population; however, given its relatively recent adoption, outcome data remain limited. This article presents a single-centre case series evaluating the short-term surgical and anaesthetic outcomes of obese patients undergoing robotic colorectal resections.MethodsA retrospective review was performed of patients with BMI > 30 kg/m2 who underwent robotic colorectal cancer resection at Liverpool University Hospital NHS Trust between July 2019 and April 2024. Demographic, surgical, anaesthetic, and clinical outcome data were collected from a prospectively maintained database. Key measures included operative time, Trendelenburg positioning, critical care admissions, complications, and mortality.ResultsSeventy-five patients [mean BMI 35.8 (range 30.0-66.1) kg/m2] underwent robotic resection. Conversion to open surgery occurred in one case (1.3%). Mean operative time was 380 min for rectal and 289 min for colonic resections. The average Trendelenburg tilt was 20o (range 15-22), with an average lateral tilt of 15o (range 10-20), and mean head down duration was 225 (range 120-320) min. Fifty-six (74.7%) patients had primary anastomosis; the anastomotic leak rate was 9.3%. Thirty-two per cent of patients were electively admitted to the critical care as part of our institutional pathway for high BMI-cases. Of these, three patients (4.0%) required overnight mechanical ventilation and were both extubated the following morning without further organ support. One case of postoperative visual disturbance, attributed to positioning, resolved fully. The 30- and 90-day mortality rate was 1.3%.ConclusionRobotic colorectal surgery is a feasible and safe option in elevated BMI patients, with low conversion rates and acceptable morbidity. Importantly, prolonged Trendelenburg position did not appear to increase anaesthetic risk, with only one reversible positioning-related complication observed
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