Search

Introduction: Human growth hormone (hGH) therapy in children can be administered by subcutaneous injection using either a manual non-connected device, which is a portable injection pen loaded with a pre-filled cartridge, or an electronic connected device. The electronic device is connected to a platform where adherence data is recorded and available for health care professionals (HCPs) and patient support programs. Real-world data used in the clinic, includes regular monitoring of adherence data which are shared with families during patients' visits and aim to determine the root causes of poor adherence. This study aimed to identify whether there are differences in growth during the first four years of treatment depending on the device, i.e. non-connected versus connected devices. Methods: This retrospective study reports treatment of either GH deficiency or short stature secondary to birth size small for gestational age (SGA) in 174 pediatric patients attending Miguel Servet Hospital, Zaragoza, Spain. hGH treatment was administered with manual non-connected devices in 87 patients and 87 patients used connected devices. Height was followed for 4 years after start of hGH therapy. Results: In total, 57% of subjects had GHD and 43% were SGA. Height standard deviation score (HSDS) at treatment start was higher (p<0.001) in the non-connected device group compared to the connected device group. Change of HSDS in the connected device group was significantly higher in the second (+0.13), third (+0.20) and fourth (+0.23) year of treatment compared to the non-connected group after adjustment for age and HSDS at treatment start, sex, indication, dose and Tanner stages during treatment, and timing of measurements. Discussion: These results support the use of the connected device for hGH treatment of pediatric growth disorders. [ABSTRACT FROM AUTHOR]

Summary: Phenotypic plasticity describes a genotype's ability to produce different phenotypes in response to different environments. Breeding crops that exhibit appropriate levels of plasticity for future climates will be crucial to meeting global demand, but knowledge of the critical environmental factors is limited to a handful of well‐studied major crops.Using 727 maize (Zea mays L.) hybrids phenotyped for grain yield in 45 environments, we investigated the ability of a genetic algorithm and two other methods to identify environmental determinants of grain yield from a large set of candidate environmental variables constructed using minimal assumptions.The genetic algorithm identified pre‐ and postanthesis maximum temperature, mid‐season solar radiation, and whole season net evapotranspiration as the four most important variables from a candidate set of 9150. Importantly, these four variables are supported by previous literature. After calculating reaction norms for each environmental variable, candidate genes were identified and gene annotations investigated to demonstrate how this method can generate insights into phenotypic plasticity.The genetic algorithm successfully identified known environmental determinants of hybrid maize grain yield. This demonstrates that the methodology could be applied to other less well‐studied phenotypes and crops to improve understanding of phenotypic plasticity and facilitate breeding crops for future climates. [ABSTRACT FROM AUTHOR]

A 2-D Lattice Boltzmann Method, designed to ensure stability at high Reynolds numbers, is combined with an Actuator Line Model to compute the loads on a two-bladed vertical axis wind turbine. Tests on the kernel size at a high mesh resolution reveal that a size equal to half of the full chord length yields the most accurate results. The aerodynamic load solution is validated against a fully resolved Scale-Adaptive Simulation (SAS) output, demonstrating high correlation, and enabling an assessment of near wake and downstream effects. The model's adaptability to various rotor operating conditions is confirmed through tests at high and low tip-speed ratios. Additionally, a Biot–Savart-based Vortex Model (VM) is employed for further comparison, showing good agreement with the Lattice Boltzmann output. The results indicate that the Highly Stable Lattice Boltzmann Method integrated with the Actuator Line Model enhances the accuracy of flow field resolution and effectively captures complex aerodynamic phenomena, making it a valuable tool for simulating vertical axis wind turbines. [ABSTRACT FROM AUTHOR]

The Kelvin-Helmholtz Instability (KHI), arising from velocity shear across the magnetopause, plays a significant role in the viscous-like transfer of mass, momentum, and energy from the shocked solar wind into the magnetosphere. While the KHI leads to growth of surface waves and vortices, suitable detection methods for these applicable to magnetohydrodynamics (MHD) are currently lacking. A novel method is derived based on the well-established A-family of hydrodynamic vortex identification techniques, which define a vortex as a local minimum in an adapted pressure field. The J x B Lorentz force is incorporated into this method by using an effective total pressure in MHD, including both magnetic pressure and a pressure-like part of the magnetic tension derived from a Helmholtz decomposition. The AMHD method is shown to comprise of four physical effects: vortical momentum, density gradients, fluid compressibility, and the rotational part of the magnetic tension. A local three-dimensional MHD simulation representative of near-flank magnetopause conditions (plasma 's 0.5-5 and convective Mach numbers Mf ~ 0.4) under northward interplanetary magnetic field (IMF) is used to validate AMHD. Analysis shows it correlates well with hydrodynamic vortex definitions, though the level of correlation decreases with vortex evolution. Overall, vortical momentum dominates AMHD at all times. During the linear growth phase, density gradients act to oppose vortex formation. By the highly nonlinear stage, the formation of small-scale structures leads to a rising importance of the magnetic tension. Compressibility was found to be insignificant throughout. Finally, a demonstration of this method adapted to tetrahedral spacecraft observations is performed. [ABSTRACT FROM AUTHOR]

The dynamics of Earth's magnetopause, driven by several different external/internal physical processes, plays a major role in the geospace energy budget. Given magnetopause motion couples across many space plasma regions, numerous forms of observations may provide valuable information in understanding these dynamics and their impacts. In-situ multi-point spacecraft measurements measure the local plasma environment, dynamics and processes; with upcoming swarms providing the possibility of improved spatiotemporal reconstruction of dynamical phenomena, and multi-mission conjunctions advancing understanding of the "mesoscale" coupling across the geospace "system of systems." Soft X-ray imaging of the magnetopause should enable boundary motion to be directly remote sensed for the first time. Indirect remote sensing capabilities might be enabled through the field-aligned currents associated with disturbances to the magnetopause; by harnessing data from satellite mega-constellations in low-Earth orbit, and taking advantage of upgraded auroral imaging and ionospheric radar technology. Finally, increased numbers of closely-spaced ground magnetometers in both hemispheres may help discriminate between high-latitude processes in what has previously been a "zone of confusion." Bringing together these multiple modes of observations for studying magnetopause dynamics is crucial. These may also be aided by advanced data processing techniques, such as physics-based inversions and machine learning methods, along with comparisons to increasingly sophisticated geospace assimilative models and simulations. [ABSTRACT FROM AUTHOR]

The prevalence of obesity globally has tripled over the last half century, and currently affects around 650 million adults and 340 million children and adolescents (ages 5–19 years). Obesity contributes towards >50 co-morbidities and premature mortality. Obesity is a highly stigmatised condition that is associated with much mental and emotional distress and dysfunction. Thus, obesity is a major contributor to healthcare expenditure globally. Traditionally, the management of obesity stratifies into three major groups that include metabolic (bariatric) surgery, pharmacotherapies, and lifestyle (primarily dietary) strategies. Although listed as a separate category, dietary strategies for obesity remain a central component of any management plan, and often complement other surgical and pharmacotherapeutic options. Indeed, the effectiveness of any management approach for obesity relies upon successful behavioural changes, particularly relating to eating behaviours. In this concise review, we explore the foundational pillars of dietary strategies for obesity: sleep, listening, routine, de-stressing and optimisation of social conditions. We then discuss the importance of balancing dietary macronutrients (including dietary fibre, carbohydrates, protein and ultra-processed foods [UPFs]) as a key dietary strategy for obesity. Although we focus on general principles, we should provide bespoke dietary strategies for our patients, tailored to their individual needs. Rather than judging the utility of a diet based simply on its associated magnitude of weight loss, we should adopt a more holistic perspective in which a dietary strategy is valued for its overall health benefits, including the nurturing of our gut microbiota, to enable them to nurture and protect us. [ABSTRACT FROM AUTHOR]

Correction for 'Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms' by Lydia W. Njenga et al., Dalton Trans., 2023, 52, 5823–5847, https://doi.org/10.1039/D3DT00366C. [ABSTRACT FROM AUTHOR]

Sodium-ion battery technology is a promising and more sustainable alternative to its more conventional lithium-ion based counterpart. The most common anode material for these systems is a disordered form of graphite known as hard carbon. The inherent disorder in these carbons results in multiple possible pathways for sodium storage making the characterisation of sodiation mechanisms during cycling highly challenging. Here, we report an operando small angle neutron scattering (SANS) investigation of sodiation in a commercial hard carbon using a custom electrochemical cell. We demonstrate that it is possible to discern different sodiation mechanisms throughout cycling and provide supporting evidence for a three-stage model in which sodium ions are first adsorbed onto the surface of particles, then intercalated into the graphene layers, and finally inserted into the nanopores during the electrochemical stage known as the plateau region. This study showcases the unique capabilities of operando SANS for the characterisation of sodiation mechanisms of carbon-based, disordered, porous materials. [ABSTRACT FROM AUTHOR]

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen‐agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator‐led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)‐induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U‐shaped response curve with the greatest effect seen at 0.1 μM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen‐agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models. [ABSTRACT FROM AUTHOR]

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in prediabetes. We assessed whether these markers also predict the success of lifestyle interventions, thereby possibly guiding personalized strategies. We analyzed the fasting serum levels of IGF-1, IGFBP-1, and Insulin-like growth factor binding protein 2 (IGFBP-2) in relation to changes in metabolic and anthropometric parameters, including intrahepatic lipids (IHLs) and visceral adipose tissue (VAT) volume, measured by magnetic resonance imaging (MRI), in 345 participants with a high risk for prediabetes (54% female; aged 36–80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), and significance was set at p < 0.05. Within the 1-year intervention, overall significant improvements were observed. Stratifying individuals by baseline IGF-1 and IGFBP-1 percentiles revealed significant differences: higher IGF-1 levels were associated with more favorable changes compared to lower levels, especially in VAT and IHL. Lower baseline IGFBP-1 levels were associated with greater improvements, especially in IHL and 2 h glucose. Higher bioactive IGF-1 levels might predict better metabolic outcomes following lifestyle interventions in prediabetes, potentially serving as biomarkers for personalized interventions. [ABSTRACT FROM AUTHOR]

Sharp boundaries are a key feature of space plasma environments universally, with their wave-like motion (driven by pressure variations or flow shears) playing a key role in mass, momentum, and energy transfer. This review summarises magnetohydrodynamic surface wave theory with particular reference to Earth's magnetopause, due to its mediation of the solar-terrestrial interaction. Basic analytic theory of propagating and standing surface waves within simple models are presented, highlighting many of the typically-used assumptions. We raise several conceptual challenges to understanding the nature of surface waves within a complex environment such as a magnetosphere, including the effects of magnetic topology and curvilinear geometry, plasma inhomogeneity, finite boundary width, the presence of multiple boundaries, turbulent driving, and wave nonlinearity. Approaches to gain physical insight into these challenges are suggested. We also discuss how global simulations have proven a fruitful tool in studying surface waves in more representative environments than analytic theory allows. Finally, we highlight strong interdisciplinary links with solar physics which might help the magnetospheric community. Ultimately several upcoming missions provide motivation for advancing magnetopause surface wave theory towards understanding their global role in filtering, accumulating, and guiding turbulent solar wind driving. [ABSTRACT FROM AUTHOR]

Substance use is a growing problem in Nigeria. The present study extended recent work documenting the importance of parenting as protective against substance use in Nigerian youth by testing a model linking parenting, additional protective factors and polysubstance use. Public school students (N = 1607; 56% female; M age = 14.88; SD =.44 years) living in the greater Lagos region participated in school‐based data collection. Lifetime polysubstance use, defined as use of two or more substances including alcohol or illicit drugs, or misuse of over‐the‐counter medications, was reported by 5.2% of the sample. Structural equation modelling that accounted for adolescent age and sex on all constructs revealed good model fit. Positive parenting (support and solicitation) was significantly associated with higher perceived harmfulness of substance use, religiosity and positive relationships at school. Positive school relationships were associated with a decreased likelihood of polysubstance use. Multiple group analysis revealed no overall sex differences in the model paths. Strengthening parent–adolescent relationships may have a cascading effect on protective factors and subsequent substance use, and should be included in youth substance use prevention programmes. [ABSTRACT FROM AUTHOR]

According to cohort studies, cereal fiber, and whole-grain products might decrease risk for type 2 diabetes (T2DM), inflammatory processes, cancer, and cardiovascular diseases. These associations, mainly affect insoluble, but not soluble cereal fiber. In intervention studies, soluble fiber elicit anti-hyperglycemic and anti-inflammatory short-term effects, partially explained by fermentation to short-chain fatty acids, which acutely counteract insulin resistance and inflammation. ß-glucans lower cholesterol levels and possibly reduce liver fat. Long-term benefits are not yet shown, maybe caused by T2DM heterogeneity, as insulin resistance and fatty liver disease – the glycometabolic points of action of soluble cereal fiber – are not present in every patient. Thus, only some patients might be susceptive to fiber. Also, incretin action in response to fiber could be a relevant factor for variable effects. Thus, this review aims to summarize the current knowledge from human studies on the impact of soluble cereal fiber on glycometabolic gastrointestinal hormones. Effects on GLP-1 appear to be highly contradictory, while these fibers might lower GIP and ghrelin, and increase PYY and CCK. Even though previous results of specific trials support a glycometabolic benefit of soluble fiber, larger acute, and long-term mechanistic studies are needed in order to corroborate the results. [ABSTRACT FROM AUTHOR]

Introduction: We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST). Methods: We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0 Results: Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH. Conclusion: We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis. [ABSTRACT FROM AUTHOR]

Advanced Geothermal Systems (AGS) may in principle be able to satisfy the global energy demand using standard continental-crust geothermal temperature gradients of 25–35 ∘ C/km. However, conventional mechanical rotary drilling is still too expensive to cost-competitively provide the required borehole depths and lengths for AGS. This highlights the need for a new, cheaper drilling technology, such as Plasma-Pulse Geo-Drilling (PPGD), to improve the economic feasibility of AGS. PPGD is a rather new drilling method and is based on nanoseconds-long, high-voltage pulses to fracture the rock without mechanical abrasion. The absence of mechanical abrasion prolongs the bit lifetime, thereby increasing the penetration rate. Laboratory experiments under ambient-air conditions and comparative analyses (which assume drilling at a depth between 3.5 and 4.5 km) have shown that PPGD may reduce drilling costs by approximately 17–23%, compared to the costs of mechanical drilling, while further research and development are expected to reduce PPGD costs further. However, the performance of the PPGD process under deep wellbore conditions, i.e., at elevated temperatures as well as elevated lithostatic and hydrostatic pressures, has yet to be systematically tested. In this paper, we introduce a standard experiment parameter to examine the impact of deep wellbore conditions on PPGD performance, namely the productivity (the excavated rock volume per pulse) and the specific energy (the amount of energy required to drill a unit volume of rock). We employ these parameters to investigate the effect of temperature on PPGD performance, with temperatures increasing up to 80 ∘ C, corresponding to a drilling depth of up to approximately 3 km. Highlights: This study introduces an experiment protocol for studying the impact of deep wellbore conditions on Plasma-Pulse Geo-Drilling performance. When deionized water is used, increasing the temperature decreases Plasma-Pulse Geo-Drilling productivity and increases the specific energy. The effect of increasing temperature on Plasma-Pulse Geo-Drilling depends significantly on the drilling fluid used. Deionized water negatively affects Plasma-Pulse Geo-Drilling, while other studies have shown that the effect of oil-based drilling muds is negligible. [ABSTRACT FROM AUTHOR]

1H‐magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single‐voxel MRS (point‐resolved single‐voxel spectroscopy sequence, 1.5 T: echo time [TE] 23–37 ms/135–144 ms, repetition time [TR] 1500 ms; 3 T: TE 37–41 ms/135–144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann–Whitney U‐tests and Kruskal–Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours. [ABSTRACT FROM AUTHOR]

We use molecular dynamics computer simulations to investigate complexation and clustering of branched polymers. In this study, we focus on star and bottle-brush polymers. In our investigation, we identify key factors governing cluster formation of branched amphiphilic polymers and provide guidance for designing and preparing various types of polymer clusters for applications, e.g., in drug delivery or materials science. We observe different kinds of clustering in the polymer systems. Our star polymers consist of several arms of hydrophilic core particles with hydrophobic particles attached to the end of each star arm. We observe that amphiphilic star polymers generally tend to form spherical complexes. In contrast to this, bottle-brush polymers exhibit a larger variety of complex structures. With large grafting density and large side arms, we also observe spherical polymer clusters; however, for low grafting density and shorter side chains, distinct clusters connected by bridging particles are formed. Furthermore, we observe membrane-like clustering of bottle-brush polymers. We employ two different clustering algorithms for further analysis of the obtained structures with respect to shape factors, pair correlation functions, and radii of gyration. We find that the hydrophobic parts of polymers play a crucial role in the formation of the resulting structures during self-assembly. The hydrophilic core parts in star polymers along with steric hindrance lead to a screening effect for the hydrophobic parts of the polymers. With bottle-brush copolymers, the hydrophilic parts of the polymers exhibit a screening effect that is sensitive to the grafting density and side chain lengths along the backbone. [ABSTRACT FROM AUTHOR]

Boundary dynamics are crucial for the transport of energy, mass, and momentum in geospace. The recently discovered plasmapause surface wave (PSW) plays a key role in the inner magnetosphere dynamics. However, a comprehensive investigation of spatial variations of the PSW remains absent. In this study, we elucidate the spatial characteristics of a PSW through observations from multiple spacecrafts in the magnetosphere. Following the initiation of the PSW, quasi‐periodic injections of energetic ions, rather than electrons, are suggested to serve as energy source of the PSW. Based on the distinct wave and particle signatures, we categorize the PSW into four regions: seed region, growth region, stabilization region and decay region, spanning from nightside to afternoon plasmapause. These findings advance our understanding of universal boundary dynamics and contribute to a deeper comprehension of the pivotal roles of surface waves in the energy couplings within the magnetosphere‐plasmasphere‐ionosphere system. Plain Language Summary: Much like the rhythmic beating of a drum, boundaries within the terrestrial system, which delimit distinct plasmas with varying temperatures and densities, can oscillate due to external impulses or internal instabilities, giving rise to surface waves. These surface waves travel along the boundary surface and establish standing wave structures in magnetic field lines. In the terrestrial space environment, two types of surface waves have been identified: the magnetopause surface wave and the plasmapause surface wave (PSW). These waves typically have frequencies ranging from fractions of milli Hertz to a few milli Hertz, with periods spanning from several to tens of minutes. They are believed to play a vital role in mass, energy, and momentum transport within Earth's magnetosphere. However, the exact source that excites the waves and the manner in which the waves evolve along the boundary remain elusive. In this study, we, for the first time, unveil the spatial evolutionary signatures of the PSW during a moderate geomagnetic storm accompanied by substorms, utilizing data from six magnetospheric spacecrafts positioned near the plasmapause. This research contributes to a better understanding of the physical mechanisms underlying the widespread existence of surface waves in the universe, shedding light on the processes of magnetosphere‐plasmasphere‐ionosphere energy couplings and wave‐particle interactions associated with surface waves. Key Points: Spatial characteristics of plasmapause surface wave (PSW) are elucidate with multiple‐spacecraft observations in the magnetosphereIt is suggested that quasi‐periodic injections of energetic ions rather than electrons sustain the PSW during the substormThe PSW is categorized into seed region, growth region, stabilization region, and decay region with different wave and particle properties [ABSTRACT FROM AUTHOR]

Patients with neuroendocrine tumours located in the gastroenteropancreatic tract (GEP‐NETs) and treatment with somatostatin analogues (SSA's) are at risk of malnutrition which has been reported previously evaluating weight loss or body mass index (BMI) only. The global leadership into malnutrition (GLIM) criteria include weight loss, BMI, and sarcopenia, for diagnosing malnutrition. These GLIM criteria have not been assessed in patients with GEP‐NETs on SSA. The effect of malnutrition on overall survival has not been explored before. The aim of this study is to describe the presence of malnutrition in patients with GEP‐NET on SSA based on the GLIM criteria and associate this with overall survival. Cross‐sectional study screening all patients with GEP‐NETs on SSA's for malnutrition using the GLIM criteria. Body composition analysis for sarcopenia diagnosis were performed. Bloods including vitamins, minerals, and lipid profile were collected. Overall survival since the date of nutrition screening was calculated. Uni‐ and multivariate Cox regression analysis were performed to identify malnutrition as risk factor for overall survival. A total of 118 patients, 47% male, with median age 67 years (IQR 56.8–75.0) were included. Overall, malnutrition was present in 88 patients (75%); based on low BMI in 26 (22%) patients, based on weight loss in 35 (30%) patients, and based on sarcopenia in 83 (70%) patients. Vitamin deficiencies were present for vitamin D in 64 patients (54%), and vitamin A in 29 patients (25%). The presence of malnutrition demonstrated a significantly worse overall survival (p‐value =.01). In multivariate analysis meeting 2 or 3 GLIM criteria was significantly associated with worse overall survival (HR 2.16 95% CI 1.34–3.48, p‐value =.002). Weight loss was the most important risk factor out of the 3 GLIM criteria (HR 3.5 95% CI 1.14–10.85, p‐value =.03) for worse overall survival. A high percentage (75%) of patients with GEP‐NETs using a SSA meet the GLIM criteria for malnutrition. Meeting more than 1 GLIM criterium, especially if there is weight loss these are risk factors for worse overall survival. [ABSTRACT FROM AUTHOR]

The interaction of a solar wind discontinuity with the backstreaming particles of the Earth's ion foreshock can generate hot, tenuous plasma transients such as foreshock bubbles (FB) and hot flow anomalies (HFA). These transients are known to have strong effects on the magnetosphere, distorting the magnetopause (MP), either locally during HFAs or globally during FBs. However, previous studies on the global impact of FBs have not been able to determine whether the response stems directly from the transverse scale size of the phenomenon or its fast motion over the magnetosphere. Here we present the observation of an FB and its impact on the magnetosphere from different spacecraft scattered over the dayside magnetosphere. We are able to constrain the size of the transverse scale of an FB from direct observations to be about 10 RE. We go on to discuss how the magnetosphere responds to this transient, which seems to have a similar scale across the dayside. Plain Language Summary: The solar wind is a fast plasma flow of charged particles originating from the Sun. Earth's magnetic field diverts this flow around the planet forming the magnetosphere. The bow shock forms upstream of Earth to decelerate the solar wind and deflect the flow around Earth's magnetic field. A fraction of the solar wind particles are reflected back into the solar wind stream, forming the foreshock. Discontinuities in the solar wind can concentrate these backstreaming particles forming a bubble of hot and tenuous plasma called a foreshock bubble. These transients structures move with the solar wind, arriving at and modifying the bow shock and leading to an expansion of the magnetosphere due to lower pressure within the transients' core. Such a response was reported before in different studies which conclude that foreshock bubbles have a global impact on the magnetosphere. In our study we report on another foreshock bubble observed by a multi‐spacecraft constellation. The observations allowed us to constrain the size of the foreshock bubble. We observe that the large scale response of the magnetosphere seems to reflect with the size of the FB. Key Points: Multi satellite observation of a large foreshock bubble (FB) hitting Earth's magnetosphereThe transverse (y − z) scale size of the FB can be constrained from observations to be at least 8–10 RE fitting with simulationsThe magnetospheric response to the FB seems to be visible across almost 10 RE of the dayside, matching the FB size [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) in medicine is transforming healthcare by automating system tasks, assisting in diagnostics, predicting patient outcomes and personalising patient care, founded on the ability to analyse vast datasets. In paediatric endocrinology, AI has been developed for diabetes, for insulin dose adjustment, detection of hypoglycaemia and retinopathy screening; bone age assessment and thyroid nodule screening; the identification of growth disorders; the diagnosis of precocious puberty; and the use of facial recognition algorithms in conditions such as Cushing syndrome, acromegaly, congenital adrenal hyperplasia and Turner syndrome. AI can also predict those most at risk from childhood obesity by stratifying future interventions to modify lifestyle. AI will facilitate personalised healthcare by integrating data from 'omics' analysis, lifestyle tracking, medical history, laboratory and imaging, therapy response and treatment adherence from multiple sources. As data acquisition and processing becomes fundamental, data privacy and protecting children's health data is crucial. Minimising algorithmic bias generated by AI analysis for rare conditions seen in paediatric endocrinology is an important determinant of AI validity in clinical practice. AI cannot create the patient–doctor relationship or assess the wider holistic determinants of care. Children have individual needs and vulnerabilities and are considered in the context of family relationships and dynamics. Importantly, whilst AI provides value through augmenting efficiency and accuracy, it must not be used to replace clinical skills. [ABSTRACT FROM AUTHOR]

Homograft heart valves may have significant advantages and are preferred for the repair of congenital valve malformations, especially in young women of childbearing age, athletes and in patients with active endocarditis. A growing problem, however, is the mismatch between tissue donation and the increasing demand. The aim of this paper is to describe the initiation process of a homograft procurement program to attenuate the shortage of organs. A comprehensive description of the infrastructure and procedural steps required to initiate a cardiac and vascular tissue donation program combined with a prospective follow-up of all homografts explanted at our institution. Between January 2020 and May 2022, 28 hearts and 12 pulmonary bifurcations were harvested at our institution and delivered to the European homograft bank. Twenty-seven valves (19 pulmonary valves, 8 aortic valves) were processed and allocated for implantation. The reasons for discarding a graft were either contamination (n = 14), or morphology (n = 13) or leaflet damage (n = 2). Five homografts (3 PV, 2 AV) have been cryopreserved and stored while awaiting allocation. One pulmonary homograft with a leaflet cut was retrieved by bicuspidization technique and awaits allocation, as a highly requested small diameter graft. The implementation of a tissue donation program in cooperation with a homograft bank can be achieved with reasonable additional efforts at a transplant center with an in-house cardiac surgery department. Challenging situations with a potential risk of tissue injury during procurement include re-operation, harvesting by a non-specialist surgeon and prior central cannulation for mechanical circulatory support. [ABSTRACT FROM AUTHOR]

Purpose: PREF-NET reported patients’ experience of Somatuline® (lanreotide) Autogel® (LAN) administration at home and in hospital among patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Methods: PREF-NET was a multicentre, cross-sectional study of UK adults (aged ≥ 18 years) with GEP-NETs receiving a stable dose of LAN, which comprised of (1) a quantitative online survey, and (2) qualitative semi-structured interviews conducted with a subgroup of survey respondents. The primary objective was the description of overall patient preference for home versus hospital administration of LAN. Secondary objectives included describing patient-reported opinions on the experience and associated preference for each administration setting, and the impact on healthcare utilisation, societal cost, activities of daily living and health-related quality of life (HRQoL). Results: In the primary analysis (80 patients; mean age 63.9 years), 98.7% (95% confidence interval [CI]: 96.1–100.0) of patients preferred to receive LAN at home, compared with 1.3% (95% CI: 0.0–3.9) who preferred the hospital setting. Among participants, over half (60.3%) received their injection from a non-healthcare professional. Most patients (79.5% [95% CI: 70.5–88.4]) reported a positive effect on HRQoL after the switch from hospital to home administration. Qualitative interviews (20 patients; mean age 63.6 years) highlighted that patients preferred home administration because it improved overall convenience; saved time and costs; made them feel more comfortable and relaxed, and less stressed; and increased confidence in their ability to self-manage their treatment. Conclusion: Almost all patients preferred to receive LAN treatment at home rather than in hospital with increased convenience and psychological benefits reported as key reasons for this preference. [ABSTRACT FROM AUTHOR]

Terahertz time-domain spectroscopy (THz-TDS) can be used to map spatial variations in electrical properties such as sheet conductivity, carrier density, and carrier mobility in graphene. Here, we consider wafer-scale graphene grown on germanium by chemical vapor deposition with non-uniformities and small domains due to reconstructions of the substrate during growth. The THz conductivity spectrum matches the predictions of the phenomenological Drude–Smith model for conductors with non-isotropic scattering caused by backscattering from boundaries and line defects. We compare the charge carrier mean free path determined by THz-TDS with the average defect distance assessed by Raman spectroscopy, and the grain boundary dimensions as determined by transmission electron microscopy. The results indicate that even small angle orientation variations below 5° within graphene grains influence the scattering behavior, consistent with significant backscattering contributions from grain boundaries. [ABSTRACT FROM AUTHOR]

Paediatric Cushing's disease (CD) is characterized by excess ACTH secretion froma pituitary adenoma, leading to hypercortisolism. It has approximately 5% of the incidence of adult CD and is a rare disorder in the paediatric age range. The four most specific presenting features of hypercortisolism are: change in facial appearance, weight gain, decreased linear growth and virilisation shown by advanced pubic hair for the stage of breast development or testicular volume. The main diagnostic priority is the demonstration of hypercortisolism followed by distinction between its ACTH-dependent and ACTH-independent origin, thus leading to identification of aetiology. All treatment options aim to resolve or control hypercortisolism. Consensus favours transsphenoidal (TSS) pituitary surgery with selective removal of the corticotroph adenoma. TSS in children with CD is now well established and induces remission in 70-100% of cases. External pituitary radiotherapy and bilateral adrenalectomy are second-line therapeutic approaches in subjects not responding to TSS. Long-term medical treatment is less frequently adopted. Recurrence in paediatric CD cases is low with factors predicting relapse being higher post-TSS cortisol and ACTH levels and rapid recovery of the hypothalamic-pituitary-adrenal axis after TSS. In summary, complete excision of the microadenoma with histological and biochemical evidence for this, predicts a low rate of recurrence of CD. Due to the need for rapid diagnosis and management to avoid the burden of prolonged exposure to hypercortisolism, tertiary university centres comprising both paediatric and adult endocrinology specialists together with experienced pituitary surgery and, eventually, radiotherapy units are recommended for referral of these patients. [ABSTRACT FROM AUTHOR]

The global lack of donor shortage poses a major limitation for heart transplantation. New concepts with expanded donor inclusion criteria comprise extended transport distances and prolonged ischemic times with the aim of reaching a larger number of potential donors. Recent developments in cold storage solutions may allow more donor hearts with prolonged ischemic times to be use for transplantation in the future. We present our experience during a long-distance donor heart procurement with the longest reported transport distance and transport time in the current literature. This was made possible through the use of SherpaPak™, an innovative cold storage system which allows for controlled temperatures during transportation. [ABSTRACT FROM AUTHOR]

Background: Paediatric endocrinology became recognised in Western European countries in the 1960s and 1970s. It is now a thriving paediatric sub-speciality in many countries but remains non-existent or in its infancy in others. We have had the privilege to work in Western centres of excellence, and this review outlines the key stages in the development of modern centres, discussing the human and organisational issues that have underpinned progress in the establishment of this paediatric sub-speciality. Summary: Human determination, vision, and ambition to create a modern centre and become a national flag bearer in the field are key components of success. The realisation that learning by spending time as a fellow away from one's home institution, so that knowledge can be acquired and brought back home, is also a key factor. Career structures should be designed to mentor and guide the trainee returning from a fellowship abroad. Scientific societies such as the European Society for Paediatric Endocrinology (ESPE) are key resources for networking, support, and discussion with experienced colleagues who may have faced similar challenges. Training and acquisition of knowledge through on-site or e-learning initiatives are beneficial and numerous examples exist, including the telemedicine model of store-and-forward consultations. Leadership skills can be learnt, and good working relationships with adult endocrinology colleagues result in benefits and political support. Key Messages: The development of paediatric endocrinology in a region with hitherto no such facilities constitutes a major contribution to local, regional, and, in all likelihood, national patient care. [ABSTRACT FROM AUTHOR]

This article describes the forecasting system urbanAQF, which incorporates several developments to deal with the complexities of air pollution in cities, including the adaptation of high-resolution numerical weather prediction data to the urban canopy, the coupling with regional forecast data, and an interactive web service for public dissemination of urban air quality information. The system applies a unique bias correction algorithm that adjusts boundary conditions and traffic emissions to observations of the previous days. An evaluation of the air quality forecasts during 2021 for Hamburg, Germany, against a comprehensive dataset of the administrative monitoring network and meteorological data, demonstrated the system's capability to describe space and time variations of NO2 and PM10. At traffic sites, the high number of missed alerts in relation to exceedance of the daily mean limit for NO2 indicates the need to improve the simulation of traffic emissions. The forecast of PM2.5 alerts was affected by the time lag of the automatic correction, leading to a low number of correct alerts. The overall performance for O3 was very good, despite frequent false alarms connected to the prediction of unstable atmospheric conditions. The urbanAQF system empowers policymakers to implement effective measures for improving air quality in cities. [ABSTRACT FROM AUTHOR]

The colloidal synthesis of CdSe/ZnSe core/shell quantum dots (QDs) under nitrogen gas flow is presented in this study. The optical, morphology and structural properties of CdSe/ZnSe core/shell QDs are varied by changing the growth temperature and the cadmium source (Cd2+). The Fourier transform infra‐red studies validate that CdSe/ZnSe QDs capped with functional −COOH groups were formed. The morphological and composition studies conducted using high resolution transmission microscope, selected area electron diffraction andenergy dispersive spectroscope confirmed the formation of pure and mono‐disperse QDs while photoluminescence and ultra‐violet visible spectroscopy displayed their improved fluorescent properties. Caco‐2 cell line was cultured from colon cancer and cytotoxic studies were conducted to test for cell viability of various capped 3‐MPA CdSe/ZnSe QDs at various concentrations. The formed CdSe/ZnSe QDs prominently bear the zinc‐blende structure with their particle size lying well below the Bohr excitation radii. Their hydrophilic nature and the availability of functional groups on the CdSe/ZnSe QDs makes them excellent potential labeling and therapeutic agents for the colon cancer disease diagnosis. [ABSTRACT FROM AUTHOR]

Background: Despite global tuberculosis (TB) interventions, the disease remains one of the major public health concerns. Kenya is ranked 15th among 22 high burden TB countries globally. Methods: A cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling two high volume health facility from each sub-county. Identification of spoligotype profiles and their family distribution and lineage level were achieved by comparison with SITVIT database. Results: Lineage distribution pattern revealed that the most predominant lineage was CAS 220 (39.8%) followed by Beijing 128 (23.1%). The other lineages identified were T, LAM, H, X, S and MANU which were quantified as 87 (15.7%), 67 (12.1%), 16 (2.8%), 10 (1.8%), 8 (1.4%) and 5 (0.9%) respectively. CAS and Beijing strains were the most predominant lineage in both HIV negative and positive TB patients. The Beijing lineage was also the most predominant in resistant M. tuberculosis strains as compared to wild type. A total of 12 (2.0%) were orphaned M. tuberculosis strains which were spread across all the 10 counties of the study site. In multivariate logistic regression adjusting for potential cofounders three potential risk factors were significant. HIV status (OR = 1.52, CI = 0.29–3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43–3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49–3.87 and P value = 0.026). Most M. tuberculosis clinical isolates showed genetic clustering with multivariate logistic regression indicating three potential risk factors to clustering. HIV status (OR = 1.52, CI = 0.29–3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43–3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49–3.87 and P value = 0.026). Conclusion: There exist diverse strains of M. tuberculosis across the 10 counties of Western Kenya. Predominant distribution of clustered genotype points to the fact that most TB cases in this region are as a result of resent transmission other than activation of latent TB. [ABSTRACT FROM AUTHOR]

Participatory breeding and crop selection can satisfy the needs of underserved groups of farmers (e.g., organic producers, farmers producing specialty grain for niche markets) neglected by the modern global seed industry. Participatory research methods that value local knowledge and facilitate Interest includes re-engagement in the development of maize hybrids that perform well in a diverse range of heterogeneous growing environments and that are better suited for sustainabilityminded producers, buyers, and consumers. Systems-based breeding aimed at protecting the environment and providing food, fiber, and energy while considering equity issues, has been proposed as a way to overcome the shortcomings of privatized approaches. In this article, we consider recent projects that use collaborative methods for hybrid maize breeding, cultivar testing, and genetic research to develop, identify, and deliver traits associated with crop performance, quality, and sustainability. Three case studies consider the efforts focused on developing non-GMO varieties for organic and specialty markets. We find that, unlike many successful efforts focused on the improvement of other crops, there are few promising models for participatory breeding of hybrid maize. Even though many projects have sought to involve stakeholders with a variety of methods, all have struggled to meaningfully engage farmers in maize hybrid improvement. Still, our reflection of case studies calls for systems-based breeding and suggests a path forward. This route would seek to address the needs, perspectives, and values of a broader range of actors participating in the food system by leveraging technologies and infrastructure in service of the public. Land-grant universities are well positioned to play a crucial role in coordinating efforts, facilitating partnerships, and supporting breeding programs that satisfy societal wants that include health, equity, and care. [ABSTRACT FROM AUTHOR]

Key message: We demonstrate potential for improved multi-environment genomic prediction accuracy using structural variant markers. However, the degree of observed improvement is highly dependent on the genetic architecture of the trait. Breeders commonly use genetic markers to predict the performance of untested individuals as a way to improve the efficiency of breeding programs. These genomic prediction models have almost exclusively used single nucleotide polymorphisms (SNPs) as their source of genetic information, even though other types of markers exist, such as structural variants (SVs). Given that SVs are associated with environmental adaptation and not all of them are in linkage disequilibrium to SNPs, SVs have the potential to bring additional information to multi-environment prediction models that are not captured by SNPs alone. Here, we evaluated different marker types (SNPs and/or SVs) on prediction accuracy across a range of genetic architectures for simulated traits across multiple environments. Our results show that SVs can improve prediction accuracy, but it is highly dependent on the genetic architecture of the trait and the relative gain in accuracy is minimal. When SVs are the only causative variant type, 70% of the time SV predictors outperform SNP predictors. However, the improvement in accuracy in these instances is only 1.5% on average. Further simulations with predictors in varying degrees of LD with causative variants of different types (e.g., SNPs, SVs, SNPs and SVs) showed that prediction accuracy increased as linkage disequilibrium between causative variants and predictors increased regardless of the marker type. This study demonstrates that knowing the genetic architecture of a trait in deciding what markers to use in large-scale genomic prediction modeling in a breeding program is more important than what types of markers to use. [ABSTRACT FROM AUTHOR]

This document is a compilation of research articles on the topic of CART (Cocaine- and Amphetamine-regulated Transcript) peptides. The articles cover a range of subjects, including the role of CART in the enteric nervous system, its involvement in stress response and body weight homeostasis, and its activation of signaling pathways. Other articles explore the implications of CART in diabetes, breast cancer, anxiety, depression, ethanol consumption, and feeding behavior. The document provides a comprehensive overview of the multifaceted nature of CART peptides and their potential implications in various physiological and pathological processes. Further research is needed to confirm and expand upon these findings. [Extracted from the article]

Global ultra‐low frequency (ULF) oscillations are believed to play a significant role in the mass, energy, and momentum transport within the Earth's magnetosphere. In this letter, we observe a ∼1.2 mHz radial standing wave in the dusk‐sector magnetosphere accompanied by the field line resonance (FLR) on 16 July 2017. The frequency estimation from the simple box model also confirms the radial standing wave. The essential characteristics of FLR are concurrently identified at the dusk‐sector magnetosphere and the conjugated ground location. Further, the radial standing wave dissipates energy into upper atmosphere to enhance the local aurora by coupling itself to the FLR. The magnetospheric dominant 1.2/1.1 mHz ULF waves plausibly correspond well with the discrete ∼1 mHz magnetosheath ion dynamic pressure/velocity oscillation, suggesting this radial standing wave and FLR in the flank magnetosphere may be triggered by the solar‐wind and/or magnetosheath dynamic pressure/velocity fluctuations. Plain Language Summary: Just like thumping the strings, the Earth's magnetic field line can also be disturbed by the external impulses or internal instability, generating the rich ultra‐low frequency (ULF) oscillations with period of 1–1,000 s. They are believed to play a significant role in the mass, energy, and momentum transport within the Earth's magnetosphere. But the question of how an external driving mechanism can produce field line disturbances deep inside the magnetosphere is a topic of much debate. One classical global mode resonance model suggests that the magnetospheric space sometimes acts as a huge closed or semi‐closed cavity, where the ULF waves form the radial standing wave structure. So far, the observational evidence of radial standing waves with period of above 8 min accompanied by the field line disturbance in the flank magnetosphere is sparse. In this letter, we report a radial standing wave with period of ∼14 min within dusk‐sector magnetosphere accompanied by the field line disturbance phenomenon by multiple‐satellite observations. The radial standing wave energy sinks down to upper atmosphere to light the local aurora by coupling itself to the field line resonance. We conclude the radial standing wave may be caused by the solar‐wind and/or magnetosheath dynamic pressure/velocity fluctuations. Key Points: A radial standing Pc5‐6 ultra‐low frequency wave is identified within the dusk‐sector magnetosphereRadial standing wave dissipates energy into upper atmosphere by coupling itself to the field line resonanceSolar‐wind and/or magnetosheath dynamic pressure/velocity fluctuations possibly trigger this radial standing wave [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD. [ABSTRACT FROM AUTHOR]

Although the task-specific robot treadmill therapies can improve gait performance of children with cerebral palsy, not all the institutions have the possibility to access to the sensor robot information to obtain quantitative measures related actual progress of the children. The aim of this study is to propose a computer vision system to investigate the effort of children with cerebral palsy during robot treadmill therapy. Ten participants diagnosed with cerebral palsy underwent single robot therapy sessions consisting of a motivated period (active: kicking a ball), followed by an unmotivated period (passive: simple walking). The outcome measure was the ankle trajectory recorded by a video camera. Indexes based on the ankle trajectory between active and passive therapy were computed: (a) the gait analysis based on the difference on a sample-by-sample manner, and b) the step cycles with dynamic time warping (DTW). Inference statistical analysis shows that the robot trajectories for passive and active therapies with the gait analysis presents statistical differences (p- value < 0. 0 1)). Likewise, DTW showed significant differences in robot trajectories related to passive and active therapy (p- value < 0. 0 1)). We found that the statistical differences are independent of the severity of central gait impairment. This suggests that information about patient involvement could be given to the therapist and could be used to assess patient participation. The method showed the potential to be used as a tool for the assessment the improvement progress. [ABSTRACT FROM AUTHOR]

Aims Enhancing SIRT1 activity exerts beneficial cardiovascular effects. In diabetes, plasma SIRT1 levels are reduced. We aimed to investigate the therapeutic potential of chronic recombinant murine SIRT1 (rmSIRT1) supplementation to alleviate endothelial and vascular dysfunction in diabetic mice (db/db). Methods and results Left internal mammary arteries obtained from patients undergoing coronary artery bypass grafting with or without a diagnosis of diabetes were assayed for SIRT1 protein levels. Twelve-week-old male db/db mice and db/+ controls were treated with vehicle or rmSIRT1 intraperitoneally for 4 weeks, after which carotid artery pulse wave velocity (PWV) and energy expenditure/activity were assessed by ultrasound and metabolic cages, respectively. Aorta, carotid, and mesenteric arteries were isolated to determine endothelial and vascular function using the myograph system. Arteries obtained from diabetic patients had significantly lower levels of SIRT1 relative to non-diabetics. In line, aortic SIRT1 levels were reduced in db/db mice compared to db/+ mice, while rmSIRT1 supplementation restored SIRT1 levels. Mice receiving rmSIRT1 supplementation displayed increased physical activity and improved vascular compliance as reflected by reduced PWV and attenuated collagen deposition. Aorta of rmSIRT1-treated mice exhibited increased endothelial nitric oxide (eNOS) activity, while endothelium-dependent contractions of their carotid arteries were significantly decreased, with mesenteric resistance arteries showing preserved hyperpolarization. Ex vivo incubation with reactive oxygen species (ROS) scavenger Tiron and NADPH oxidase inhibitor apocynin revealed that rmSIRT1 leads to preserved vascular function by suppressing NADPH oxidase (NOX)-related ROS synthesis. Chronic rmSIRT1 treatment resulted in reduced expression of both NOX1 and NOX4, in line with a reduction in aortic protein carbonylation and plasma nitrotyrosine levels. Conclusions In diabetic conditions, arterial SIRT1 levels are significantly reduced. Chronic rmSIRT1 supplementation improves endothelial function and vascular compliance by enhancing eNOS activity and suppressing NOX-related oxidative stress. Thus, SIRT1 supplementation may represent novel therapeutic strategy to prevent diabetic vascular disease. [ABSTRACT FROM AUTHOR]

Reactive transport processes in natural environments often involve many ionic species. The diffusivities of ionic species vary. Since assigning different diffusivities in the advection–diffusion equation leads to charge imbalance, a single diffusivity is usually used for all species. In this work, we apply the Nernst–Planck equation, which resolves unequal diffusivities of the species in an electroneutral manner, to model reactive transport. To demonstrate the advantages of the Nernst–Planck model, we compare the simulation results of transport under reaction-driven flow conditions using the Nernst–Planck model with those of the commonly used single-diffusivity model. All simulations are also compared to well-defined experiments on the scale of centimeters. Our results show that the Nernst–Planck model is valid and particularly relevant for modeling reactive transport processes with an intricate interplay among diffusion, reaction, electromigration, and density-driven convection. [ABSTRACT FROM AUTHOR]

To first order, the magnetopause (MP) is defined by a pressure balance between the solar wind and the magnetosphere. The boundary moves under the influence of varying solar wind conditions and transient foreshock phenomena, reaching unusually large and small distances from the Earth. We investigate under which solar wind conditions such extreme MP distortions occur. Therefore, we construct a database of magnetopause crossings (MPCs) observed by the THEMIS spacecraft in the years 2007 to mid‐2022 using a simple Random Forest Classifier. Roughly 7% of the found crossing events deviate beyond reported errors in the stand‐off distance from the Shue et al. (1998, https://doi.org/10.1029/98JA01103) MP model and thus are termed extreme distortions. We find the occurrence of these extreme events in terms of expansion or compression of the MP to be linked to different solar wind parameters, most notably to the IMF magnitude, cone angle, velocity, Alfvén Mach number and temperature. Foreshock transients like hot‐flow anomalies and foreshock bubbles could be responsible for extreme magnetospheric expansions. The results should be incorporated into future magnetopause models and may be helpful for the reconstruction of the MP locations out of soft x‐ray images, relevant for the upcoming SMILE mission. Key Points: More than 160.000 magnetopause crossings (MPCs) identified in THEMIS data between 2007 and 2022 using a Random Forest ClassifierMagnetopause crossings that extremely deviate in location from the Shue et al. (1998, https://doi.org/10.1029/98JA01103) model are quite commonImportant solar wind parameters associated with deviations include the interplanetary magnetic field cone angle, solar wind velocity and Alfvén Mach number [ABSTRACT FROM AUTHOR]

To analyse the strength and mechanical behaviour of hip implants, it is essential to employ an appropriate loading model. Generating computational models supplemented with muscle forces is a complicated task, especially in the initial phase of implant development. This research aims to expand the possibilities of the simpler acetabular cage model based on joint loads without significantly increasing the demand for computing resources. A Python script covered and grouped the loads from daily activities. The ten calculated major loads were compared with the maximum of the walking and stair climbing loads through the finite element analyses of a custom-made acetabular cage. Sensitivity analyses were performed for the surrounding bones' elastic modulus and the pelvis boundary conditions. The major loads can geometrically cover the entire load spectrum of daily activities. The effect of many high-magnitude force vectors is uncertain in the approach that uses the most common maximum loads. Using these resultant major loads, a new stress concentration area could be detected on the acetabular cage, besides the stress concentration areas induced by the loads reported in the literature. The qualitative correctness of the results is also supported by a control computed tomography scan: a fracture occurred in an extensive, high-stress zone. The results are not sensitive to changes in the elastic modulus of the surrounding bone and the boundary conditions of the model. The presented load vectors and the algorithm make more extensive static analyses possible with little computational overhead. The proposed method can be used for checking the static strength of similar implants. [ABSTRACT FROM AUTHOR]

Aims: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular–vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. Methods and results: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near‐normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = −0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e′) on echocardiography (r = −0.307, P = 0.014). Conclusions: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at‐risk intermediate phenotypes (e.g. pre‐HFpEF) before overt HFpEF occurs. [ABSTRACT FROM AUTHOR]

Eye movement perimetry (EMP) is a paradigm developed to assess the visual field without the necessity of suppressing the natural eye movements during the test. Unlike the standard automated perimetry (SAP) where the patient's responses are recorded using a button, EMP uses the natural eye movements reflex as responses during the evaluation. The reliability of EMP depends on correctly determining whether a stimulus is seen or not which, in turn, depends on an adequate analysis of the eye movement data. However, many studies in EMP have focused on characterizing eye movements and only a few authors have documented their methods to determine whether a peripheral stimulus was seen during the test. Furthermore, many of them use static thresholds to perform the classification, but it is not clear how these threshold values were obtained. Based on the foregoing, we develop a threshold test based on FASTPAC C24-2 and EMP for the visual field assessment. Our method uses two machine learning techniques: (1) cascaded K-Means and Bayesian classifiers (KBC) and (2) an Artificial Neural Network (ANN) to classify whether a stimulus was seen or not. Our method was validated with twenty healthy participants (13 women and 7 men) aged 19–43 years (µ = 26 ± 5 years), where the participants performed both an EMP test and an SAP emulation test. Results were compared with gaze trajectories annotations performed by an expert, obtaining accuracy values between 96.8% and 98.9% for KBC and ANN, and values between 90.5% and 92% for SAP emulation. [ABSTRACT FROM AUTHOR]

Myeloid cells form an essential component of initial responses to environmental hazards and toxic exposures. The ability to model these responses in vitro is central to efforts tasked with identifying hazardous materials and understanding mechanisms of injury and disease. Induced pluripotent stem cell (iPSC) derived cells have been suggested as alternatives to more established primary cell testing systems for these purposes. iPSC derived macrophage and dendritic like cells were compared to CD34+ haematopoietic stem cell derived populations using transcriptomic analysis. Using single cell sequencing-based characterisation of iPSC derived myeloid cells, we identified transitional, mature and M2 like macrophages as well as dendritic like antigen presenting cells and fibrocytes. Direct transcriptomic comparisons between iPSC and CD34+ cell derived populations revealed higher expression of myeloid differentiation genes such as MNDA, CSF1R and CSF2RB in CD34+ cells, while iPSC populations had higher fibroblastic and proliferative markers. Exposure of differentiated macrophage populations to nanoparticle alone or in combination with dust mite, resulted in differential gene expression on combination only, with responses markedly absent in iPSC compared to CD34+ derived cells. The lack of responsiveness in iPSC derived cells may be attributable to lower levels of dust mite component receptors CD14, TLR4, CLEC7A and CD36. In summary, iPSC derived myeloid cells display typical characteristics of immune cells but may lack a fully mature phenotype to adequately respond to environmental exposures. [ABSTRACT FROM AUTHOR]

This paper investigates the effect of education of firm managers on labour productivity in Uganda's manufacturing sector using enterprise survey data. Like in many Sub-Saharan economies, Uganda is grappling with labour productivity associated with deficiencies and mismatch in skills, which limit the adaptation of new production technologies. The human capital theory (HCT) and the endogenous growth theory (EGT) underpinned this investigation. On the basis of a Cobb-Douglas function we estimated a labour productivity equation. The paper found that attainment of higher levels of education by firm managers improved labour productivity, and mean productivity of individual workers at firm level. The strong linkage between managers' education and labour productivity implies that the government should focus on policies that improve higher education. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD) has now surpassed alcohol excess as the most common cause of chronic liver disease globally, affecting one in four people. Given its prevalence, MAFLD is an important cause of cirrhosis, even though only a small proportion of patients with MAFLD ultimately progress to cirrhosis. MAFLD suffers as a clinical entity due to its insidious and often asymptomatic onset, lack of an accurate and reliable non-invasive diagnostic test, and lack of a bespoke therapy that has been designed and approved for use specifically in MAFLD. MAFLD sits at a crossroads between the gut and the periphery. The development of MAFLD (including activation of the inflammatory cascade) is influenced by gut-related factors that include the gut microbiota and intactness of the gut mucosal wall. The gut microbiota may interact directly with the liver parenchyma (through translocation via the portal vein), or indirectly through the release of metabolic metabolites that include secondary bile acids, trimethylamine, and short-chain fatty acids (such as propionate and acetate). In turn, the liver mediates the metabolic status of peripheral tissues (including insulin sensitivity) through a complex interplay of hepatokines, liver-secreted metabolites, and liver-derived micro RNAs. As such, the liver plays a key central role in influencing overall metabolic status. In this concise review, we provide an overview of the complex mechanisms whereby MAFLD influences the development of insulin resistance within the periphery, and gut-related factors impact on the development of MAFLD. We also discuss lifestyle strategies for optimising metabolic liver health. [ABSTRACT FROM AUTHOR]