bluuebunny/crossref_metadata_2025 huggingface dataset:
How much protected? Assessment of cardiovascular risk factors in patients with previous cardiovascular events admitted for acute coronary syndrome
Authors: Gregorio Antunes Coelho R , Quintal J , Pohle C , Silva Ferreira J , Bernardes P , Goncalves S , Seixo F
Published: June 2024

Background

The 2021 ESC guidelines on cardiovascular disease prevention recommend that all patients with a prior history of atherosclerotic cardiovascular disease (ASCVD) - with a history of acute coronary syndromes, coronary heart disease, surgical or percutaneous myocardial revascularization, stroke or peripheral arterial disease - are considered to have very high risk of cardiovascular events (class I, level A evidence). Despite having an increased residual risk, optimization and control of cardiovascular risk factors (diabetes, dyslipidemia, high blood pressure and smoking) is often suboptimal.

Purpose

The aim of this study is to evaluate the control of modifiable cardiovascular risk factors in patients with history of cardiovascular disease and admitted for acute coronary syndrome. Furthermore, understand the impact of follow-up in primary care (vs hospital follow-up) on this control.

Methods

We retrospectively evaluated patients admitted for acute coronary syndrome between November 2021 and October 2022 with history of cardiovascular disease, with or without hospital follow-up. Previous control of the main cardiovascular risk factors was assessed, as well as compliance with other secondary prevention measures (smoking abstinence, compliance with antithrombotic therapy).

Results

Between November 2021 and October 2022, 395 patients were admitted to our center due to acute coronary syndrome. 111 (30%) had a previous history of cardiovascular events, and of these, 41 (37%) remained under hospital follow-up. 66 patients (59%) were taking statins, but only 15 (14%) had LDL cholesterol levels <55 mg/dl and 28 (25%) LDL-C <70 mg/dl. 41 patients (37%) were diabetic, but only 35 (85%) had a previous known diagnosis and 12 (29%) were under control (HbA1c <7.0%). 97 patients (87%) had high blood pressure and 91 had systolic BP values >135 mmHg (82%). 33 patients (30%) were former smokers but 20 (18%) maintained smoking habits. 26 patients (23%) were obese (BMI >30 kg/m2). 28 patients (25%) were not taking any antithrombotic therapy.

The adherence to statins was higher in patients that kept hospital follow up (50% in primary care vs 76% in hospital follow-up; p = 0.008) with no diferences regarding other risk factos.

Conclusions

Patients with established cardiovascular disease are a subgroup at high risk of recurrent events. Despite this, compliance with control measures is often suboptimal. It's urgent to establish multidisciplinar care programs in order to reduce their residual risk.
High-dose statins are associated with increased aortic valve calcium load in patients with severe stenosis
Authors: Poggio P , Moschetta D , De Giorgi D , Rusconi V , Bertolini F , Massaiu I , Valerio V , Myasoedova V A
Published: June 2024

Background

AS represents the predominant valvular pathology, marked by the progressive fibro-calcific remodeling of aortic valve leaflets. This condition poses a significant clinical burden due to its association with increased morbidity and mortality. In recent years, emerging research has shed light on the potential role of statins in influencing the pathogenesis of AS. Statins, known primarily for their lipid-lowering properties, have been found to modulate the production of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism. This novel avenue of investigation into the interplay between statins, PCSK9, and aortic valve calcification holds considerable therapeutic implications and warrants further exploration for the development of targeted interventions in the management of AS.

Purpose

To investigate the dose-dependent impact of statins on aortic valve calcification in patients with AS.

Methods

We enrolled 194 AS patients (87 no, 34 low-dose, and 73 high-dose statins) who underwent contrast-enhanced computed tomography (CT). Atorvastatin (A:0.1uM and 1uM) and pravastatin (P:1uM and 100uM) treatments were used to evaluate valve interstitial cells (VIC) calcification potential and PCSK9 secretion.

Results

CT quantifications showed that patients taking high-dose statins had significantly higher AVC content compared to low-dose (903.8±601 vs.526.8±403 mm3/cm2, respectively; p<0.0001), while no difference in AVC was observed between patients with low-dose statins and no-statins (p=0.226). Of note, low-density lipoprotein cholesterol (LDL-C) levels were comparable between low- and high-dose statins’ groups (p=0.255). We confirmed our observation in vitro, showing that treatment with low-dose satins did not stimulate calcification nor PCSK9 secretion. While high-dose statins significantly increased VICs extracellular calcification (A:+4.3±2.6 fold-change (FC), P:+3.2±1.2FC, respectively; p<0.0001) and PCSK9 secretion (A:+3.3±1.9FC, P:+2.5FC, respectively; p<0.0001).

Conclusion

Patients with severe AS who receive high-dose statins compared with those receiving low-dose statins, both of whom achieve the target for LDL-C, had higher AVC load. An in vitro model confirms increased intracellular calcification and PCSK9 secretion upon treatment with high-dose statins only. To achieve lipid targeting in AS patients, it is important to consider this phenomenon, giving preference to other types of drugs, which do not exhibit similar effects.
Coordinated regulation of osmotic imbalance by c-di-AMP shapes ß-lactam tolerance in Group B Streptococcus
Authors: Brissac Terry , Guyonnet Cécile , Sadouni Aymane , Hernández-Montoya Ariadna , Jacquemet Elise , Legendre Rachel , Sismeiro Odile , Trieu-Cuot Patrick , Lanotte Philippe , Tazi Asmaa , Firon Arnaud
Published: June 2024

Streptococcus agalactiae is among the few pathogens that have not developed resistance to ß-lactam antibiotics despite decades of clinical use. The molecular basis of this long-lasting susceptibility has not been investigated, and it is not known whether specific mechanisms constrain the emergence of resistance. In this study, we first report ß-lactam tolerance due to the inactivation of the c-di-AMP phosphodiesterase GdpP. Mechanistically, tolerance depends on antagonistic regulation by the repressor BusR, which is activated by c-di-AMP and negatively regulates ß-lactam susceptibility through the BusAB osmolyte transporter and the AmaP/Asp23/GlsB cell envelope stress complex. The BusR transcriptional response is synergistic with the simultaneous allosteric inhibition of potassium and osmolyte transporters by c-di-AMP, which individually contribute to low-level ß-lactam tolerance. Genome-wide transposon mutagenesis confirms the role of GdpP and highlights functional interactions between a lysozyme-like hydrolase, the KhpAB RNA chaperone and the protein S immunomodulator in the response of GBS to ß-lactam. Overall, we demonstrate that c-di-AMP acts as a turgor pressure rheostat, coordinating an integrated response at the transcriptional and post-translational levels to cell wall weakening caused by ß-lactam activity, and reveal additional mechanisms that could foster resistance.
Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients
Authors: Hernández-Vega Ana M , Llorente Itzel , Sánchez-Hernández Raúl , Segura Yayoi , Tusié-Luna Teresa , Morales-Buenrostro Luis E , García-Villegas Refugio , Islas León D , Rosenbaum Tamara
Published: June 2024

Polycystic kidney disease (PKD), a disease characterized by the enlargement of the kidney through cystic growth is the fourth leading cause of end-stage kidney disease world-wide. Transient receptor potential Vanilloid 4 (TRPV4), a calcium-permeable TRP, channel participates in kidney cell physiology and since TRPV4 forms complexes with another channel whose malfunction is associated to PKD, TRPP2 (or PKD2), we sought to determine whether patients with PKD, exhibit previously unknown mutations in TRPV4. Here, we report the presence of mutations in the TRPV4 gene in patients diagnosed with PKD and determine that they produce gain-of-function (GOF). Mutations in the sequence of the TRPV4 gene have been associated to a broad spectrum of neuropathies and skeletal dysplasias but not PKD, and their biophysical effects on channel function have not been elucidated. We identified and examined the functional behavior of a novel E6K mutant and of the previously known S94L and A217S mutant TRVP4 channels. The A217S mutation has been associated to mixed neuropathy and/or skeletal dysplasia phenotypes, however, the PKD carriers of these variants had not been diagnosed with these reported clinical manifestations. The presence of certain mutations in TRPV4 may influence the progression and severity of PKD through GOF mechanisms. PKD patients carrying TRVP4 mutations are putatively more likely to require dialysis or renal transplant as compared to those without these mutations.
Seismic and acoustic signals from the 2014 ‘interstellar meteor’
Authors: Fernando Benjamin , Mialle Pierrick , Ekström Göran , Charalambous Constantinos , Desch Steven , Jackson Alan , Sansom Eleanor K
Published: June 2024

We conduct a thorough analysis of seismic and acoustic data purported to be from the so-called ‘interstellar meteor’ which entered the Earth’s atmosphere off the coast of Papua New Guinea on 2014 January 08. Previous work had suggested that this meteor may have been caused by an alien spacecraft burning up in the atmosphere. We conclude that both previously reported seismic signals are spurious—one has characteristics suggesting a local vehicular-traffic-based origin; whilst the other is statistically indistinguishable from the background noise. As such, previously reported localizations based on this data are unreliable. Analysis of acoustic data provides a best-fitting location estimate which is very far ($\sim$170 km) from the reported fireball location. Accordingly, we conclude that material recovered from the seafloor and purported to be from this event is almost certainly unrelated to it, and is likely of more mundane (non-interstellar) origin.
Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry
Authors: Rujchanarong Denys , Spruill Laura , Sandusky George E , Park Yeonhee , Mehta Anand S , Drake Richard R , Ford Marvella E , Nakshatri Harikrishna , Angel Peggi M
Published: June 2024

Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast tissue and how they associate with breast cancer risk factors remains unknown. N-glycans, a glucose metabolism-linked post-translational modification, has not been characterized in normal breast tissue. We hypothesized that normal female breast tissue with distinct Breast Imaging and Reporting Data Systems (BI-RADS) categories have unique microenvironments based on N-glycan signatures that varies with genetic ancestries. Profiles of N-glycans were characterized in normal breast tissue from BW (n = 20) and WW (n = 20) at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). A total of 176 N-glycans (32 core-fucosylated and 144 noncore-fucosylated) were identified in the NME. We found that certain core-fucosylated, outer-arm fucosylated and high-mannose N-glycan structures had specific intensity patterns and histological distributions in the breast NME dependent on BI-RADS densities and ancestry. Normal breast tissue from BW, and not WW, with heterogeneously dense breast densities followed high-mannose patterns as seen in invasive ductal and lobular carcinomas. Lastly, lifestyles factors (e.g. age, menopausal status, Gail score, BMI, BI-RADS) differentially associated with fucosylated and high-mannose N-glycans based on ancestry. This study aims to decipher the molecular signatures in the breast NME from distinct ancestries towards improving the overall disparities in breast cancer burden.
Impact of institutional variables on centre performance in long-term survival after heart transplant
Authors: McDonald Weston E , Shorbaji Khaled , Kilcoyne Maxwell , Few William , Welch Brett , Hashmi Zubair , Kilic Arman
Published: June 2024

OBJECTIVES

The gold standard metric for centre-level performance in orthotopic heart transplantation (OHT) is 1-year post-OHT survival. However, it is unclear whether centre performance at 1 year is predictive of longer-term outcomes. This study evaluated factors impacting longer-term centre-level performance in OHT.

METHODS

Patients who underwent OHT in the USA between 2010 and 2021 were identified using the United Network of Organ Sharing data registry. The primary outcome was 5-year survival conditional on 1-year survival following OHT. Multivariable Cox proportional hazard models assessed the impact of centre-level 1-year survival rates on 5-year survival rates. Mixed-effect models were used to evaluate between-centre variability in outcomes.

RESULTS

Centre-level risk-adjusted 5-year mortality conditional on 1-year survival was not associated with centre-level 1-year survival rates [hazard ratio: 0.99 (0.97–1.01, P = 0.198)]. Predictors of 5-year mortality conditional on 1-year survival included black recipient race, pre-OHT serum creatinine, diabetes and donor age. In mixed-effect modelling, there was substantial variability between centres in 5-year mortality rates conditional on 1-year survival, a finding that persisted after controlling for recipient, donor and institutional factors (P < 0.001). In a crude analysis using Kaplan–Meier, the 5-year survival conditional on 1-year survival was: low volume: 86.5%, intermediate volume: 87.5%, high volume: 86.7% (log-rank P = 0.52). These measured variables only accounted for 21.4% of the between-centre variability in 5-year mortality conditional on 1-year survival.

CONCLUSIONS

Centre-level risk-adjusted 1-year outcomes do not correlate with outcomes in the 1- to 5-year period following OHT. Further research is needed to determine what unmeasured centre-level factors contribute to longer-term outcomes in OHT.
Linking epidemiological and genomic data in cases of enteric fever in England to inform clinical management and public health action
Authors: Buczkowska Matylda , Chattaway Marie A , Jenkins Claire , Hungerford Daniel , Katwa Parisha , Kirkbride Hilary , Hawker Jeremy
Published: June 2024

Objectives

To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae.

Methods

After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent.

Results

A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%).

Conclusions

Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.
Therapeutic drug monitoring of linezolid and exploring optimal regimens and a toxicity-related nomogram in elderly patients: a multicentre, prospective, non-interventional study
Authors: Liu Tingting , Yuan Yaping , Wang Chao , Wu Jionghe , Wang Yajuan , Na Peng , Chen Xiaomin , Rao Weiqiao , Zhao Jing , Wang Dan , Wang Haiyan , Duan Zhimei , Xie Fei , Fang Xiangqun , Xie Lixin , Li Hongxia
Published: June 2024

Background

The concentrations of linezolid, its optimal regimen and the associated side effects in elderly patients remain unclear.

Methods

In this multicentre, prospective study, elderly patients receiving linezolid at four tertiary hospitals in Beijing between May 2021 and December 2022 were included. Linezolid concentrations and haematological toxicity were monitored dynamically. Risk factors for linezolid overexposure and moderate-to-severe linezolid-induced thrombocytopenia (M/S LIT) were analysed, and a predictive model of M/S LIT was developed.

Results

A total of 860 linezolid concentrations were measured in 313 patients. The median trough concentrations of linezolid were 24.4 (15.3, 35.8) mg/L at 36–72 h and 26.1 (17.0, 38.1) mg/L at 5–10 days (P = 0.132). Severe linezolid exposure was independently associated with age, estimated glomerular filtration rate (eGFR) and the worst SOFA score (SOFA1), and we further recommended dose regimens for elderly patients based on these findings. The incidences of linezolid-induced thrombocytopenia(LIT) and M/S LIT were 73.5% and 47.6%, respectively. M/S LIT was independently correlated with treatment duration, average trough concentration (TDMa), baseline platelet count, eGFR and baseline SOFA score (SOFA0). The developed nomogram predicted M/S LIT with an area under the curve of 0.767 (95% CI 0.715–0.820), a sensitivity of 71.1% and a specificity of 73.2%.

Conclusions

Linezolid trough concentrations increased dramatically in the elderly, by about 10 mg/L in patients aged 65–80 years, followed by a further increase of 10 mg/L for every 10 years of age. Therapeutic drug monitoring is recommended in elderly patients receiving linezolid. The developed nomogram may predict M/S LIT and guide dosage adjustments of linezolid.

Clinical trial registration number: ChiCTR2100045707
Application of multi-component seismic data in identifying dolomite reservoirs in the Sichuan Basin
Authors: Chen Kang , Zhang Guangzhi , Di Guidong , Guo Xin , Wen Long , Ran Qi , Ma Hualing , Dai Juncheng
Published: June 2024

A comprehensive drilling of wells has been conducted in the Permian Qixia Formation in the central Sichuan Basin, revealing a significant number of dolomite reservoirs. High- and medium-porosity dolomite reservoirs are the main gas-producing reservoirs in the Qixia Formation. Seismic PP-wave data show a “bright spot” for high-porosity dolomite reservoir formations but weak responses for medium-porosity dolomite reservoir formations, which is attributed to the inability of P waves to distinguish between medium-porosity reservoirs and limestone. However, medium-porosity dolomite and limestone have different S-wave velocities. Therefore, in this study, the identification of different-porosity dolomite reservoirs using multi-component seismic data was investigated. A comprehensive analysis of the elastic waves by forward modeling shows that the PS-wave amplitude is more sensitive to medium-porosity dolomite than the PP-wave amplitude. Therefore, medium-porosity dolomite reservoirs can be predicted using the amplitude attributes of the PS-wave, and high-porosity dolomite reservoirs can be characterized using the PP-wave. Meanwhile, the elastic parameter λρ (the product of Lame constant λ and density ρ), which is highly correlated with the dolomite content, can be used as an indicator of dolomite formations. Furthermore, compared to the results of PP-wave inversion, the elastic parameters derived from the joint inversion of PP- and PS-waves exhibited a better correspondence with the well-logging results. The comprehensive use of the seismic amplitude responses of PP- and PS-waves and multi-component seismic joint inversion can effectively predict high- and medium-porosity dolomite reservoirs. The predicted results can support the exploration and development of the Qixia Formation.
SPC manufacturing and stockpiling waiver—part 1
Authors: Stief Marco
Published: June 2024

This two-part article analyzes and discusses the legal requirements of, as well as the opportunities and risks associated with the SPC Manufacturing and Stockpiling Waiver as introduced by EU Regulation 2019/933. The introduction of the SPC Manufacturing/Stockpiling Waiver on July 1, 2019 opened up opportunities for generics and biosimilars companies established in the EU to manufacture and stockpile medicinal products before expiry of the respective SPC, either for export to third countries or for timely Day-1 market entry in the EU. But unlike, for example, the bolar exemption, application of the SPC Waiver is dependent upon compliance with specific notification, due diligence and labeling obligations. Although introduced more than four years ago, there is still considerable legal uncertainty surrounding the application of the SPC Waiver, something recent court decisions in Germany and The Netherlands have exacerbated rather than clarified. In this first part, the policy background of the Regulation is explained and the territorial and temporal scope of the SPC Waiver is examined. In the second part of the article, to be published in the next edition of the Journal of Intellectual Property Law and Practice Vol.(…) Issue (…) I will take a close look at the material scope and core components of the waiver, particularly as it relates to privileged acts and the conditions under which the waiver is applicable
Metabolic Dysregulation and Cancer Risk Program (MeDOC): a transdisciplinary approach to obesity-associated cancers
Authors: Lam Tram Kim , Daschner Phil , Ishibe Naoko , Wali Anil , Hall Kara , Czajkowski Susan , Mahabir Somdat , Watson Joanna M , Nebeling Linda , Ross Sharon , Sauter Edward
Published: June 2024

With the escalating prevalence of obesity, the association between obesity and cancer is a growing public health concern. Obesity will soon surpass tobacco smoking as the most important preventable cause of cancer. Obesity-driven mechanisms can alter cell functions to induce metabolic changes, chronic inflammation, and insulin resistance that are believed to contribute to cancer risk and development; yet the specific underlying biological mechanisms of obesity-related cancer development are largely unknown. The Metabolic Dysregulation and Cancer Risk Program: a transdisciplinary approach to obesity-associated cancers (MeDOC) is a trans–National Cancer Institute research initiative supported by the Division of Cancer Control and Population Sciences, the Division of Cancer Biology, the Division of Cancer Prevention, and the Center to Reduce Cancer Health Disparities. The overall purpose of the MeDOC Program is to advance our understanding of the underlying mechanisms that connect obesity, metabolic dysregulation, and increased obesity cancer risk as well as identify markers that will enhance cancer risk prediction, improve screening for high-risk individuals, and identify targets for preventive and therapeutic interventions for cancer interception or treatment. This report describes the funded research projects, the Coordinating Center, and the goals of the MeDOC program.
Body image and psychosocial outcomes in youth and young adults with differences of sex development: a multi-method study
Authors: Crerand Canice E , Shehata Ayah , Umbaugh Hailey , Kapa Hillary M , Hansen-Moore Jennifer , Nahata Leena , Buchanan Cindy , Chen Diane , Rausch Joseph , Udaipuria Shivika , Jayanthi Venkata R , Chan Yee-Ming , Pratt Keeley J , Buschur Elizabeth , Indyk Justin , Tishelman Amy C
Published: June 2024

Objective

Differences of sex development (DSD) can affect the physical health, appearance, and psychosocial functioning of affected individuals, but little is known about how subjective appearance perceptions (body image) impact psychosocial outcomes. This study evaluated body image and its associations with psychosocial outcomes including quality of life, resilience, and psychosocial adjustment.

Methods

This cross-sectional, multi-method study assessed body image and psychosocial outcomes including quality of life, adjustment, and resilience in 97 youth and young adults with DSD (mean age = 17 ± 3.7 years; 56% assigned female in infancy) using psychometrically sound instruments. A subsample (n = 40) completed qualitative interviews.

Results

Quantitative results indicated that overall, participants were satisfied with their physical appearance, although less so with their primary sex characteristics. Body image dissatisfaction was associated with poorer psychosocial adjustment, quality of life, and resilience. Qualitatively, youth and young adults reported a variety of perceptions, both positive and negative, related to their body image and the impact of living with a DSD condition. Themes identified included appearance management; effects of DSD on body image; diagnostic factors and features; attitudes about diagnosis; and treatment.

Conclusions

Body image is significantly associated with psychosocial outcomes in youth and young adults with DSD, with qualitative findings highlighting both positive and negative body image experiences. Results have implications for clinical care including screening for appearance concerns, normalization of appearance variations, and intervention development to better support healthy body image and psychosocial functioning in youth and young adults with DSD.
Diagnosis of Coccidioidomycosis with the Second-Generation Miravista IgG and IgM Enzyme Immunoassay and the Role of Adding Miravista Coccidioides Antigen Detection to Immunodiagnostic Assays
Authors: Kassis Christelle , Eric Holbrook , Nicolas Barros , John Witt , Christopher Dailey , Cody Banks , Kendra Carlson , Shanna Noveroske , Mary Murlow , Joseph Wheat L
Published: June 2024

In the present study, we validate and compare the second-generation Miravista Coccidioides IgG and IgM enzyme immunoassays (EIA) (MiraVista Diagnostics [MVD] Ab EIA) to Meridian Diagnostics Coccidioides IgG and IgM EIA (Meridian Ab EIA), immunodiffusion (ID) and complement fixation (CF). We also evaluated whether the addition of Coccidioides antigen testing to anti-Coccidioides antibody testing increased the sensitivity for the diagnosis of currently active coccidioidomycosis. We retrospectively studied 555 patients evaluated at Valleywise Health Medical Center between January 2013 and May 2017 for whom coccidioidomycosis was suspected and samples were submitted to MVD for testing. Specimens were tested for antigen in the MVD antigen enzyme immunoassay (MVD Ag EIA) and for IgG and IgM antibodies with MVD and Meridian Diagnostics EIAs. ID and CF were obtained from medical records. Sensitivity and specificity were 83.0% and 91.1% or MVD Ab EIA, 69.3% and 99.7% for Meridian Ab EIA, 85.4% and 100% for ID and 65.5% and 100% for CF. Combined MVD antigen and antibody detection by EIA and ID resulted in increased sensitivity in disseminated and pulmonary disease (MVD Ag/MVD Ab: 100%, 88.3%; MVD Ag/Meridian Ab: 98.2%, 78.6%; and MVD Ag/ID: 100%, 91.7%). The detection of antibodies by MVD EIA was more sensitive than Meridian EIA or CF but similar to ID. This study supports the use of antigen testing in immunocompromised patients and those with suspected disseminated disease. Furthermore, the addition of antigen detection by EIA to antibody detection resulted in higher sensitivity of all serological tests.
A strong blend in the morning: studying the circumgalactic medium before cosmic noon with strong, blended Ly α forest systems
Authors: Morrison Sean , Som Debopam , Pieri Matthew M , Pérez-Ràfols Ignasi , Blomqvist Michael
Published: June 2024

We study of the properties of a new class of circumgalactic medium absorbers identified in the Ly α forest: ‘Strong, Blended Lyman-α’ (or SBLA) absorption systems. We study SBLAs at 2.4 < z < 3.1 in SDSS-IV/eBOSS spectra by their strong extended Ly α absorption complexes covering 138 $\, \, {\rm km}\, {\rm s}^{-1}$ with an integrated $\log (N_{\rm H\, {\small I}}/\mathrm{cm}^{-2}) =16.04$$\substack{+0.05 \\ -0.06}$ and Doppler parameter b = 18.1$\substack{+0.7 \\ -0.4}$$\, \, {\rm km}\, {\rm s}^{-1}$. Clustering with the Ly α forest provides a large-scale structure bias of b = 2.34 ± 0.06 and halo mass estimate of $M_h \approx 10^{12}\, h^{-1}\, {\rm M_{\odot }}$ for our SBLA sample. We measure the ensemble mean column densities of 22 metal features in the SBLA composite spectrum and find that no single-population multiphase model for them is viable. We therefore explore the underlying SBLA population by forward modelling the SBLA absorption distribution. Based on covariance measurements and favoured populations we find that ≈25 per cent of our SBLAs have stronger metals. Using silicon only we find that our strong metal SBLAs trace gas with a log (nH/cm−3) > −2.40 for T = 103.5 K and show gas clumping on <210 parsec scales. We fit multiphase models to this strong subpopulation and find a low ionization phase with nH = 1 cm−3, T = 103.5 K, and [X/H] = 0.8, an intermediate ionization phase with log (nH/cm−3) = −3.05, T = 103.5 K and [X/H] = −0.8, and a poorly constrained higher ionization phase. We find that the low ionization phase favours cold, dense super-solar metallicity gas with a clumping scale of just 0.009 parsecs.
Unveiling the 3D structure of magnetosheath jets
Authors: Fatemi S , Hamrin M , Krämer E , Gunell H , Nordin G , Karlsson T , Goncharov O
Published: June 2024

Magnetosheath jets represent localized enhancements in dynamic pressure observed within the magnetosheath. These energetic entities, carrying excess energy and momentum, can impact the magnetopause and disrupt the magnetosphere. Therefore, they play a vital role in coupling the solar wind and terrestrial magnetosphere. However, our understanding of the morphology and formation of these complex, transient events remains incomplete over two decades after their initial observation. Previous studies have relied on oversimplified assumptions, considering jets as elongated cylinders with dimensions ranging from $0.1\, R_{\rm E}$ to $5\, R_{\rm E}$ (Earth radii). In this study, we present simulation results obtained from Amitis, a high-performance hybrid-kinetic plasma framework (particle ions and fluid electrons) running in parallel on graphics processing units (GPUs) for fast and more environmentally friendly computation compared to CPU-based models. Considering realistic scales, we present the first global, three-dimensional (3D in both configuration and velocity spaces) hybrid-kinetic simulation results of the interaction between solar wind plasma and the Earth. Our high-resolution kinetic simulations reveal the 3D structure of magnetosheath jets, showing that jets are far from being simple cylinders. Instead, they exhibit intricate and highly interconnected structures with dynamic 3D characteristics. As they move through the magnetosheath, they wrinkle, fold, merge, and split in complex ways before a subset reaches the magnetopause.
Orbital evolution of LIGO/Virgo binaries in stellar clusters driven by cluster tides, stellar encounters, and general relativity
Authors: Rasskazov Alexander , Rafikov Roman R
Published: June 2024

Origin of LIGO/Virgo gravitational wave events may involve production of binaries with relativistic components in dense stellar systems – globular or nuclear star clusters – and their subsequent evolution towards merger. Orbital parameters of these binaries (the inner orbit) and their motion inside the cluster (the outer orbit) evolve due to both external agents – random encounters with cluster stars and cluster tides due to the smooth cluster potential – and the internal ones – various sources of dissipation and precession within the binary. We present a numerical framework – binary evolution in stellar clusters (besc) – that follows the evolution of the binary inner and outer orbits accounting for all these effects simultaneously, enabling efficient Monte Carlo studies. The secular effect of cluster tides is computed in the singly averaged approximation, without averaging over the outer binary orbit. As to stellar encounters, we include the effects of both close and distant flybys on the inner and outer orbits of the binary, respectively. Also, given our focus on the LIGO/Virgo sources, we include the general relativistic precession (which suppresses cluster tides at high eccentricities) and the gravitational wave emission (shrinking the binary orbit). We use besc to illustrate a number of characteristic binary evolutionary outcomes and discuss relative contributions of different physical processes. In particular, we find that stellar encounters often dominate over the cluster tides in the evolution of compact binaries. besc can also be used to study other objects in clusters, e.g. blue stragglers, hot Jupiters, X-ray binaries, etc.
The effects of the antenna power pattern uncertainty within a global 21 cm experiment
Authors: Cumner John , Pieterse Carla , de Villiers Dirk , de Lera Acedo Eloy
Published: June 2024

Measuring the redshifted sky-averaged neutral hydrogen 21 cm signal with a wide-band antenna operating at metre wavelengths can probe the thermal history of the Universe and the first star and galaxy formation during the Cosmic Dawn. Measurement of this ‘global 21 cm’ signal is extremely challenging due to foreground signals that are orders of magnitude brighter than the cosmological signal, which must be modelled and removed first. The Radio Experiment for the Analysis of Cosmic Hydrogen (REACH) aims to improve this process by simultaneously fitting the full posterior distribution of both the cosmological and foreground signals with Bayesian inference. The method, however, relies on an informed prior; partially derived from a simulated antenna power pattern. This simulated antenna power pattern will differ from the true antenna power pattern of the deployed instrument, and the impact of this uncertainty is unknown. We investigate this problem by forward modelling mock data with different levels of power pattern uncertainty through the REACH pipeline. We construct perturbed antenna power patterns through truncation of a singular-value-decomposed simulated power pattern; using one to generate mock observation data and the others to inform the prior. The power pattern uncertainty is quantified as ΔD, the absolute mean of the difference between the original and perturbed power patterns. Comparing the evidence and root-mean-square error we find that ΔD better than −35 dB, equivalent to millimetre accuracy in the antennas dimensions, is necessary for confident detection of the global signal. We discuss potential solutions to achieve this high level of accuracy.
Kidney failure from kidney stones: an ANZDATA study
Authors: Cheikh Hassan Hicham , Tunnicliffe David J , Loyd Lyn , Mullan Adam , Wickham Ieuan , Cashmore Brydee , Jose Matthew , Mallett Andrew J
Published: June 2024

Background

Kidney stones are common, with an increasing trend over time, and have been well studied in the general population. However, the incidence and outcomes of kidney stones leading to kidney failure (KF) and the receipt of kidney replacement therapy (KRT) are poorly examined. We examined the incidence of KF due to kidney stones and compared outcomes with KRT patients due to other causes.

Methods

We studied adult patients who started KRT (January 1981–December 2020) and are included in the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Exposure was KRT patients due to kidney stones, comparing them with patients with other causes. We examined incidence, prevalence, patient survival (KRT and transplant) and graft survival (transplant). Cox regression models were fitted to compare patient survival between the kidney stones and non-kidney stones groups, overall KRT, dialysis and patient and graft survival after kidney transplant.

Results

A total of 834 (1.1%) patients commenced KRT due to kidney stones. The incidence was 1.17 per million population per year and remained stable during the study period (annual change −0.3% [95% confidence interval (CI) −1.5–0.9]. Survival was higher in kidney stone patients receiving dialysis compared with the non-kidney stone group [hazard ratio (HR) 0.89 (95% CI 0.82–0.96)], with similar estimates in a matched cohort. In kidney transplant patients, time to transplant was longer for patients with kidney stones compared with non-kidney stone patients (2.5 versus 1.7 years; P = .001). There was no difference in mortality [HR 1.02 (95% CI 0.82–1.28)] or graft loss [HR 1.07 (95% CI 0.79–1.45)] between the kidney stones and non-kidney stones patients in the kidney transplant group.

Conclusion

The incidence of KF due to kidney stones was unchanged over the study period. Survival of patients with kidney stones who require KRT was better compared with patients with other causes. For the kidney transplant group, survival and risk of graft failure were similar.
Learnability with time-sharing computational resource concerns
Authors: Zhou Zhi-Hua
Published: June 2024

This article proposes `CoRE-learning' which introduces the `time-sharing' concept and enables `resource scheduling' in intelligent supercomputing facilities to be considered in machine learning theory for the first time.
Trends in occupational respiratory conditions with short latency in the UK
Authors: Barradas A , Iskandar I , Carder M , Gittins M , Fishwick D , Seed M , van Tongeren M
Published: June 2024

Background

Occupational short-latency respiratory disease (SLRD; predominantly asthma, rhinitis, hypersensitivity pneumonitis, and occupational infections) prevalence is difficult to determine but certain occupations may be associated with increased susceptibility.

Aims

This study aimed to examine which occupations and industries are currently at high risk for SLRD and determine their respective suspected causal agents.

Methods

SLRD cases reported to the SWORD scheme between 1999 and 2019 were analysed to determine directly standardized rate ratios (SRR) by occupation against the average rate for all other occupations combined.

Results

‘Bakers and flour confectioners’ and ‘vehicle spray painters’ showed significantly raised SRR for SLRD in general, mostly due to occupational rhinitis (234.4; 95% CI 200.5–274.0) and asthma (63.5; 95% CI 51.5–78.3), respectively. Laboratory technicians also showed significantly raised SRR for occupational rhinitis (18.7; 95% CI 15.1–23.1), primarily caused by laboratory animals and insects. Metal machining setters and setter-operators showed increased SRR for occupational hypersensitivity pneumonitis (42.0; 95% CI 29.3–60.3), largely due to cutting/soluble oils. The occupation mostly affected by infectious disease was welding trades (12.9; 95% CI 5.7–29.3), mainly attributable to microbial pathogenicity.

Conclusions

This study identified the occupational groups at increased risk of developing an SLRD based on data recorded over a recent two-decade period in the UK. Occupational asthma and rhinitis were identified as the prevailing conditions and hypersensitivity pneumonitis as a potentially rising respiratory problem in the metalworking industry.
Degassing-Driven Oxidation Promotes HREE Enrichment in South China Granites
Authors: Xu Cheng , Shi Aiguo , Brenna Marco , Liu Pingping , Li Qiuli , Fan Chaoxi
Published: June 2024

Heavy rare earth elements (HREEs) are critical metals in advanced technologies. Here, we report unusual REE patterns and O–Hf–Nd isotopic compositions of composite granites from the Zhaibei HREE deposit. The complex consists of two Mesozoic granites with ages of 188 and 170 Ma. The older granites are characterized by higher HREE contents and negative Ce anomaly and contain cerianite veinlets. Their REE-rich minerals also show strong Ce depletion, indicating a high oxidation state. Magmatic zircons have variables δ18O (6.1–9.4‰) and εHf(t) (−6 to 0), towards a depleted mantle contribution. Lower δ18O (~5.4 vs 6.6‰) and higher εNd(t) (approximately −3 vs −11) values in the altered apatite rim compared to the core and primary phase result from subduction-derived fluids. In contrast, the younger granites have lower REE contents and lack a Ce anomaly. They show mantle-derived Nd (apatite εNd(t) = 1–2), Hf (zircon εHf(t) = 3–8), and O (zircon and apatite δ18O = 4.6–5.7‰) isotopic compositions. Therefore, we infer that a REE-rich fluid migrated from the flat subducting slab and flushed the subsolidus granitic mush in the Early Jurassic. This caused volatile saturation and degassing, leading to the generation of highly oxidized fluids. These processes may cause temporary oxidizing conditions in post-magmatic hydrothermal stages, resulting in the oxidation of Ce3+ to Ce4+. The resulting Ce fractionation from other REE3+ promoted HREE enrichment in the granites.
Learning optimal integration of spatial and temporal information in noisy chemotaxis
Authors: Alonso Albert , Kirkegaard Julius B
Published: June 2024

We investigate the boundary between chemotaxis driven by spatial estimation of gradients and chemotaxis driven by temporal estimation. While it is well known that spatial chemotaxis becomes disadvantageous for small organisms at high noise levels, it is unclear whether there is a discontinuous switch of optimal strategies or a continuous transition exists. Here, we employ deep reinforcement learning to study the possible integration of spatial and temporal information in an a priori unconstrained manner. We parameterize such a combined chemotactic policy by a recurrent neural network and evaluate it using a minimal theoretical model of a chemotactic cell. By comparing with constrained variants of the policy, we show that it converges to purely temporal and spatial strategies at small and large cell sizes, respectively. We find that the transition between the regimes is continuous, with the combined strategy outperforming in the transition region both the constrained variants as well as models that explicitly integrate spatial and temporal information. Finally, by utilizing the attribution method of integrated gradients, we show that the policy relies on a nontrivial combination of spatially and temporally derived gradient information in a ratio that varies dynamically during the chemotactic trajectories.
Increasing the use of telemedicine: A field experiment
Authors: González Maria Patricia , Scartascini Carlos
Published: June 2024

Patients are reluctant to use telemedicine health services, compared to its substitute in-person visits. One reason is that telemedicine can be accurately evaluated and compared to its substitute only after the product has been adopted and experienced. As such, an intervention that increases the probability of a first experience can have lasting effects. This article reports the results of a randomized field experiment conducted in collaboration with a health insurance company. During the intervention, half of the households out of 3,469 in the sample received periodic e-mails with information about the available services. It effectively increased the take-up and demand for telemedicine. Within the first 8 months of the experiment, patients assigned to the treatment group were 6 percentage points more likely to have used the service at least once (and had about five times the odds of using telemedicine compared to those in the control group). Eight months after the start of the intervention, the number of virtual consultations by the treatment group was six times larger than that of the control group. These results, even if limited by the sample and context in which the intervention took place, provide additional evidence about how information interventions can increase technological take-up within the health sector and could serve as the stepping stone for evaluating the impact of telemedicine on health outcomes causally.
Evolution vs. Creationism in the Classroom: The Lasting Effects of Science Education
Authors: Arold Benjamin W
Published: June 2024

Anti-scientific attitudes can impose substantial costs on societies. Can schools be an important agent in mitigating the propagation of such attitudes? This article investigates the effect of the content of science education on anti-scientific attitudes, knowledge, and choices. The analysis exploits staggered reforms that reduce or expand the coverage of evolution theory in U.S. state science education standards. I compare adjacent student cohorts in models with state and cohort fixed effects. There are three main results. First, expanded evolution coverage increases students’ knowledge about evolution. Second, the reforms translate into greater evolution belief in adulthood, but do not crowd out religiosity or affect political attitudes. Third, the reforms affect high-stakes life decisions, namely, the probability of working in life sciences.
Effects of institutional distrust on value estimates of stated preference surveys in developing countries: A choice experiment on conserving biodiversity within agricultural landscapes in a biodiversity hotspot
Authors: Manhique Henrique , Wätzold Frank
Published: June 2024

The use of stated preference surveys for the valuation of environmental goods in developing countries has to take into account that there is substantial public distrust towards institutions providing environmental goods under valuation. Thus, high protest responses and low-value estimates may indicate rejection/protest against the institutional setting of the survey, rather than the dislike or low welfare effects of these goods. In this context, we investigate the effects of institutional trust on value estimates by examining the performance of three different institutions—government, conservation NGO, and farmers—in a case study aimed at eliciting preferences for conserving different types of biodiversity within orchards in the Cape Floristic Region—a biodiversity hotspot in South Africa threatened by the expansion and intensification of agriculture. We find that institutional trust has an effect on preferences and willingness to pay, with farmers leading to the highest level of trust and value estimates, followed rather closely by a conservation NGO, and, with some distance, by the government with the lowest trust level and value estimates. In terms of preferences for biodiversity conservation, our results show that respondents prefer measures to conserve endangered and endemic species over measures primarily aimed at providing ecosystem services. For future studies in developing countries, we recommend selecting an institutional setting based on the study's purpose: institutions with high levels of trust should be prioritised for studies aiming to value a good per se, while existing institutions should be prioritised for studies valuing a policy to provide a good within an existing institutional framework.
Recent trust cases in the Cayman Islands
Authors: Pursall Tony , Ostick William
Published: June 2024

This article discusses some of the trust cases that have come before the Cayman Islands Grand Court in 2023. It provides detailed summaries of the cases, which will be helpful for those needing to consider recent developments in particular areas of trust law in the Cayman Islands. The cases cover issues in relation to rectification, the continuation of proprietary injunctions, applications for directions when there is uncertainty as to the beneficial ownership of assets, the new statutory Hastings-Bass jurisdiction and the application of principles in determining the establishment of a Quistclose trust.