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Association of polygenic risk scores for depression, anxiety, and neuroticism with lower urinary tract symptoms in women
No full textBackground and objective:
Observational studies find that depression, anxiety, and neuroticism are prospectively associated with lower urinary tract symptoms (LUTS) in women, but face limitations from confounding and measurement error. We examined whether genetic liability for these psychiatric traits is associated with LUTS in women.
Methods:
Participants were from the Mothers cohort of the Avon Longitudinal Study of Parents and Children. Polygenic risk scores (PRS) for depression, anxiety, and neuroticism were calculated using genome-wide association study summary data.
LUTS were assessed using validated questionnaires at two timepoints: 2002-04 (n=4,758, median [IQR] age=40 [37-43]) and 2011-12 (n=3,026, age=50 [47-53]). Separate logistic regression models, adjusted for age and population structure, were fitted to examine associations of each PRS with each LUTS.
Key findings and limitations:
The neuroticism PRS was associated with nocturia at both timepoints [odds ratio and 95% confidence intervals=1.24 (1.10,1.40) and 1.21 (1.07,1.37)], and with any urinary incontinence (UI), any urgency, and mixed UI (2002-04) [1.14 (1.05,1.23), 1.12 (1.02,1.23), and 1.23 (1.07,1.43), respectively]. The depression PRS was associated with nocturia [1.33 (1.17,1.50) and 1.24 (1.09,1.40)] and any UI [1.09 (1.01,1.18); 1.11 (1.02,1.20)] at both timepoints, and with any urgency (2011-12) [1.13 (1.03,1.24)]. The anxiety PRS was associated with mixed UI (2002-04) [1.20 (1.03,1.39)].
Limitations include PRS not capturing all genetic liability, potential pleiotropic effects, and restriction of the cohort to parous women of predominantly European ancestry.
Conclusions and clinical implications:
Genetic liability for depression, anxiety and neuroticism is associated with increased risk of LUTS in women, indicating potential shared aetiology or possible contribution of mental health problems in the development of LUTS.
Advancing Practice:
Psychiatric traits are associated with increased risk of specific lower urinary tract symptoms (LUTS). Women with a high genetic risk of neuroticism and depression are more likely to develop nocturia or urinary incontinence. Mental health is not routinely assessed in current clinical evaluations of LUTS, despite its potential influence on LUTS.
Patient summary:
In this study we examined if parous women with a high genetic risk of mental health problems and neuroticism (a personality trait associated with negative emotions) are more likely to have urinary symptoms. We found that genetic liability to depression, anxiety and neuroticism increased the risk of urinary symptoms. Notably, we found strong evidence that genetic liability to depression and neuroticism increased the risk of nocturia (waking during the night to pass urine). Our findings suggest that mental health is important to consider in the development of urinary symptoms, and more research is needed to find out if these associations apply to other demographics
Growing trees on farms: navigating the goals and values of farmers
No full text1. Agricultural landscapes represent critical contexts for advancing policy objectives related to tree cover expansion. This paper explores how farmers' values influence their willingness or ability to grow trees on farms.
2. Research is based on 49 interviews and two focus groups with farmers in England and draws on two social science research traditions to devise an analytical framework based on four value orientations—instrumental, relational, expressive and intrinsic.
3. Analysing the data through the lens of these value orientations reveals how tree growing both aligns with and diverges from farmers' values. While growing trees is not a primary occupational goal for most farmers, neither is it inconsistent with the worldviews of farmers navigating the realities of an agricultural landscape increasingly oriented towards the provision of public goods.
4. Instrumental values, particularly economic considerations, play a prominent role in farmers' decisions about growing trees. However, relational and expressive dimensions—including affiliations with particular trees, landscape aesthetics and opportunities for personal fulfilment—significantly shape farmers' perspectives. Intrinsic values, linked to an appreciation for the natural world and the farming way of life, further enrich these dynamics.
5. Policy and practice implications. Our findings emphasise the importance of engaging with the full spectrum of values that underpin farmers' decision-making about trees. The four value orientations provide a framework for understanding where, how and why trees matter to farmers. Policymakers and practitioners can use this framework to align initiatives, communications and support mechanisms with farmers' priorities, fostering greater integration of trees into agricultural landscapes
Nursing shortages and patient outcomes
No full textThis paper examines the effect of nurse shortages on healthcare production. Employing novel high-frequency data, we examine what effect the absence of nursing staff has on inpatient mortality and other outcomes associated with nursing care. We find significant adverse mortality impacts of shortages of nurses with degree-level qualifications: for the average ward, the absence of a nurse with university degree-equivalent level training increases the odds of a patient death by approximately 10%, while there is no effect of shortages of less qualified nursing assistants. For qualified nurses, there are returns to firm (hospital) specific human capital: increasing the average firm-specific experience among degree qualified nurses by one year is associated with an 8% reduction in the odds of a patient death, the equivalent to adding three-quarters of an extra qualified nurse to the ward. Adverse mortality impacts of shortages are particularly concentrated among patients of relatively low, rather than high, clinical severity. The largest impacts are for those diagnosed with sepsis, a condition where early detection is important for survival and where nurses have a central role in detection and subsequent control
Innate iNKT cells: from biological insight to clinical impact
No full textOver the past 30 years, work of immunologists worldwide has phenotypically and
functionally defined “Natural Killer T cells” (NKT) and their subsets, including
“invariant Natural Killer T cells” (iNKT). NKT cells make up a substantial fraction of
T cells that express NK cell markers and have TCRs restricted to either
conventional MHC molecules or the monomorphic CD1d molecule. Among
these, iNKT cells are CD1d-restricted and more common within NKT cells than T
cells without NK markers. While the definition of NKT cells, whether based on
phenotype, function, or both, remains a topic of debate, iNKT cells represent a
distinct T cell population characterized by a recurrent, conserved TCR
rearrangement (TRAV10–TRAJ18 in humans) paired with a limited Vb repertoire
(mostly encoded by TRBV25-1 in humans). iNKT cells are restricted by CD1d,
which, unlike CD1a-c molecules, is expressed not only on professional antigen presenting cells and thymocytes but also on certain non-hematopoietic somatic
tissues, both normal and neoplastic. Like all CD1 family members, CD1d presents
various lipid antigens by accommodating their long hydrophobic tails in deep
binding pockets, in contrast to the shallow peptide grooves of conventional MHC
molecules. However, the ligand repertoire of CD1d is distinct from that of CD1a c. This review focuses on CD1d-restricted iNKT cells. Activation of iNKT cells via
their semi-invariant TCR, often in synergy with NK receptors and other co stimulatory molecules, triggers a rapid, polyfunctional response. Unlike
conventional MHC-restricted T cells, individual iNKT cells can simultaneously
produce both Th1- and Th2-type cytokines and exert cytotoxic activity in an
immune synapse-directed fashion. Through this combination of direct
cytotoxicity and cytokine-mediated immunomodulation, iNKTs can eliminate
target cells while activating myeloid and other lymphoid populations to amplify
immune responses. Their versatility has fueled growing interest in harnessing
iNKT cells across inflammatory, infectious, and oncological diseases, where
early-phase studies have demonstrated their safety and preliminary efficacy.
Moreover, because they are restricted by the non-polymorphic CD1d molecule
and possess immune-regulatory properties, iNKT cells lack graft-versus-host
potential, making them ideal candidates for allogeneic, off-the-shelf therapies.
This review summarizes how iNKT cells are being reimagined as innovative tools
for immune intervention across a range of clinical settings
If rockets are reusable, why not buildings? Reuse evaluation for cold-formed steel unequal-leg lipped angle columns
No full textWithin the drive for achieving Circularity in Construction, this paper examines the reusability of cold-formed steel (CFS) unequal-leg lipped angle columns through experimental and design assessments. In the absence of explicit design guidelines for the reuse of CFS structural members, this investigation focuses on four main tasks: (i) evaluation of the design strength of CFS unequal-leg lipped angle columns; (ii) development of a proposed reuse design approach for CFS structural members to determine the remaining strength based on repeated reuse test cycles; (iii) assessment of the influence of long-term corrosion on the reuse potential of CFS columns and; (iv) comparison of material properties of used and unused structural members to determine the material characteristics for reuse design. To achieve these tasks, a total of 154 tests, including repeated tests for reuse, on 48 CFS unequal-leg lipped angle columns are carried out in the present study. Irrespective of reuse, it is found that modifications to the classical fixed-end boundary conditions need to be incorporated in the local-global interaction design of CFS columns. Overall, the experimental results show that, apart from the first use, CFS columns can be further reused up to two times, in conjunction with a proposed “safe reuse resistance factor” and in combination with the original characteristic material properties
Stability and design of fixed-ended stainless steel unequal-leg angle section columns
No full textThe stability and design of fixed-ended stainless steel unequal-leg angle section members subjected to axial compression are studied herein. The critical buckling behaviour is first described; existing experimental data on stainless steel and aluminium alloy unequal-leg angle section columns collected from the literature are then employed to validate nonlinear finite element models developed within the commercial package ABAQUS. A comprehensive numerical parametric study is subsequently conducted considering members made from the three main families of stainless steel (austenitic, ferritic and duplex) with a broad spectrum of geometric configurations and slenderness values. The behaviour and load-carrying capacity of the studied columns are shown to depend not only on the global slenderness, but also on the ratio of the elastic torsional-flexural to minor-axis flexural buckling loads. The collected experimental data and generated numerical results are employed to evaluate the ultimate resistance predictions given by the current Eurocode 3 design provisions, revealing an excessive level of conservatism, particularly for cases where torsional-flexural buckling is dominant. A new design approach for fixed-ended stainless steel unequal-leg angle section columns, suitable for incorporation into future revisions of Eurocode 3, is subsequently proposed, reflecting the aforementioned observations. The proposed approach significantly improves the accuracy and consistency of the resistance predictions compared to the current design provisions. Finally, a reliability analysis is conducted following the EN 1990 procedure, resulting in a recommended partial safety factor of 1.1
Designing Co–N/C cathode catalysts with dense atomic cobalt sites for enhanced PEMFC performance
No full textMetal-nitrogen/carbon (M-N/C) catalysts, particularly those incorporating Fe, Co, or Mn, are among the most promising non-platinum group catalysts for the acidic oxygen reduction reaction (ORR) in fuel cells. This study reports a Co-N/C catalyst featuring high (3 wt%) cobalt content exclusively present as atomic sites. Extended X-ray absorption fine structure analysis confirms a tetrapyridinic Co-N4 coordination environment in the optimized (3.0)Co-N/CΔ catalyst. The high cobalt loading leads to a significant density of electrochemically accessible active sites, 3.58 × 1019 sites g−1, quantified via the nitrite stripping method. The catalyst demonstrates excellent ORR activity in a rotating ring-disk electrode setup, achieving a half-wave potential (E1/2) of 0.76 V at a low loading of 0.2 mg cm−2 and a mass activity of 3.5 A g−1 at 0.80 VRHE. Single-cell hydrogen-oxygen PEMFC tests achieve a peak power density exceeding 1.3 W cm−2 (iR-corrected). Under hydrogen-air condition, the catalyst delivers 0.54 A cm−2 at 0.60 V (0.39 W cm−2). Despite the intrinsically higher turnover frequency of Fe-based sites, the optimized (3.0)Co-N/CΔ catalyst achieves similar fuel cell performance to that of Fe-N/C, highlighting the critical role of site density in overall activity
Impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases: a systematic review and meta-analysis
No full textWhile numerous studies have extensively documented the pleiotropic effects of statins, including their capacity to reduce inflammation, there is a lack of research estimating the anti-inflammatory effectiveness of statins among individuals with chronic diseases. This meta-analysis evaluates the effect of statin therapy on inflammatory markers and the lipid profile in patients with chronic diseases by analysing evidence from randomized controlled trials (RCTs). We conducted a systematic review and searched articles published between 1st January 1999 and 31st December 2023 in databases including PubMed, Web of Science, Scopus, and Cochrane. The meta-analysis was performed using random effects models and inverse variance. Effect measures were mean differences (MD) and 95% confidence intervals (CI). Collectively, statins significantly reduced IL-6 (MD = -0.24 ng/dL [95% CI, -0.36 to -0.13], I2 = 98.3%, p < 0.001), TNF-α (MD = -0.74 ng/dL [95% CI, -1.08 to -0.40], I2 = 98.8%, p < 0.001); and CRP (MD = -1.58 mg/L [95% CI, -2.22 to -0.94], I2 = 86.5%, p < 0.001). Notably, atorvastatin demonstrated the most significant reduction in IL-6 and TNF-α levels, while fluvastatin and rosuvastatin displayed the greatest impact on decreasing CRP and LDL-C levels, respectively. Stratification by a longer treatment duration of more than four months revealed that atorvastatin achieved the most significant reduction in IL-6 and TNF-α. In conclusion, statin therapy not only regulates the lipid profile but also reduces systemic inflammatory biomarkers. Prolonged administration of statins led to a more substantial reduction in IL-6 and TNF-α, with atorvastatin exhibiting the greatest effect in our analysis
Ion-scale solitary structures in the solar wind observed by solar orbiter and parker solar probe
No full textWe investigate a class of ion-scale magnetic solitary structures in the solar wind, characterized by distinct magnetic field enhancements and bipolar rotations over spatial scales of several proton inertial lengths. These structures are revisited using high-resolution data from the Solar Orbiter and Parker Solar Probe missions. Using a machine learning-based method, we identified nearly a thousand such structures, providing new insights into their evolution and physical properties. Statistical analysis shows that these structures are more abundant closer to the Sun, with occurrence rates peaking around 30 - 40 Rsun and decreasing farther out. High-cadence measurements reveal that these structures are predominantly found in low-beta (beta <1) environments, with consistent fluctuations in density, velocity, and magnetic field. Magnetic field enhancements are often accompanied by plasma density drops, which, under near pressure balance, limit field increases. This leads to small fractional field enhancements near the Sun (approximately 0.01 at 20 Rsun), making detection challenging. Magnetic field variance analysis indicates that these structures are primarily oblique to the local magnetic field. Alfvénic velocity-magnetic field correlations suggest that most of these structures, unlike most near-Sun solar wind fluctuations, exhibit sunward-directed Alfvenic polarization in the plasma frame. We compare these findings with previous studies, discussing possible generation mechanisms and their implications for the turbulent cascade in the near-Sun Alfvénic solar wind. While these structures might be Alfvénic solitons, vortices, or flux ropes, we refrain from a definitive classification pending further evidence. Further high-resolution observations and simulations are needed to fully understand their origins and impacts