Small Volume Research Articles

Nurses’ preferences regarding MenACWY conjugate vaccines attributes: a discrete choice experiment in Spain

ObjectivesImmunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. Study designA national-level discrete choice experiment (DCE) was conducted. MethodsA literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). ResultsThirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210–3.002), smaller volumes (OR = 1.494, 95%CI = 1.264–1.767), liquid formulations (OR = 1.283, 95%CI = 1.108–1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108–1.486). No statistical evidence was found for the remaining attributes. ConclusionsEvidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses’ preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.

Review of Operation Performance and Application Status of Pulsating Heat Pipe

Due to the rapid development of science and technology in today’s era, electronic equipment is constantly upgrading. Today, the developmental trend of electronic equipment is miniaturization, portability and multi-functionality. However, multi-functionality often means multi-components, so it is undoubtedly a great test of heat dissipation ability to accommodate more components in a smaller volume. Without sufficient heat dissipation capacity, a large number of components will stop working or even be damaged because of the heat generated during operation. As a new passive cooling and heat exchange technology, pulsating heat pipes have many advantages, such as having no external energy input, a simple structure, changeable installation forms and low installation requirements. They have shown great potential in the field of thermal management, and have attracted a lot of scholars’ attention since they were put forward. Because of their operational stability and heat exchange ability in high heat flux environments, they are the best choice for cooling electronic equipment at present. If they can be fully studied and utilized, pulsating heat pipes can not only reduce the consumption of heat dissipation resources but also reuse heat energy to realize the sustainable utilization of resources. This paper briefly introduces the demand background and structural principle of pulsating heat pipes, and summarizes the research on the parameters of pulsating heat pipes and the application status of pulsating heat pipes. The parameters involve working fluid type, pipe diameter, elbow number, liquid filling rate, inclination angle, etc. After classifying the parameters that affect the operation results of pulsating heat pipes, this paper summarizes the research at this stage, and points out the lack of research fields, such as heat flux density, and new application fields of unconventional gravity environment by combining the literature content with the current scientific and technological development trends and experimental parameters, such as thermodynamics.

Hippocampal subfield volumetric changes after radiotherapy for brain metastases.

Changes in the hippocampus after brain metastases radiotherapy can significantly impact neurocognitive functions. Numerous studies document hippocampal atrophy correlating with the radiation dose. This study aims to elucidate volumetric changes in patients undergoing whole-brain radiotherapy (WBRT) or targeted stereotactic radiotherapy (SRT) and to explore volumetric changes in the individual subregions of the hippocampus. Ten patients indicated to WBRT and 18 to SRT underwent brain magnetic resonance before radiotherapy and after 4 months. A structural T1-weighted sequence was used for volumetric analysis, and the software FreeSurfer was employed as the tool for the volumetry evaluation of 19 individual hippocampal subregions. The volume of the whole hippocampus, segmented by the software, was larger than the volume outlined by the radiation oncologist. No significant differences in volume changes were observed in the right hippocampus. In the left hippocampus, the only subregion with a smaller volume after WBRT was the granular cells and molecular layers of the dentate gyrus (GC-ML-DG) region (median change -5mm3, median volume 137 vs. 135mm3; P = .027), the region of the presumed location of neuronal progenitors. Our study enriches the theory that the loss of neural stem cells is involved in cognitive decline after radiotherapy, contributes to the understanding of cognitive impairment, and advocates for the need for SRT whenever possible to preserve cognitive functions in patients undergoing brain radiotherapy.

Effects of adaptive or fixed thresholds and different platforms on the assessment of plaque characteristics using coronary computed tomography angiography

BackgroundCoronary computed tomography angiography (CCTA) is used to evaluate components of atherosclerosis. Either adaptive or diverse, fixed Hounsfield Units (HU) are used to define components such as low attenuation (LAP), mixed (MP) and calcified plaque (CP). Comparisons of different platforms and different thresholding approaches have not been extensively evaluated. We compare two fixed threshold options to an adaptive threshold option within a specific platform and to fixed threshold options measured with another platform. MethodsCoronary segments (n ​= ​24) of good image quality, with well-defined boundaries and representing a broad range of atheroma were analyzed for LAP, MP and CP. Thresholds for LAP vs MP and MP vs CP were either Fixed30/350, Fixed75/350 or based on an automatically determined Adaptive option. Pearson correlation and Bland-Altman analyses were undertaken. ResultsWithin a single platform, measures were highly correlated irrespective of use of Adaptive or Fixed30/350 and Fixed75/350 thresholds (R ​≥ ​0.819, p ​< ​0.000001). The correlation slope for measures of LAP progressively diminished comparing the Adaptive versus Fixed30/350 and the Fixed75/350 versus the Fixed30/350 approaches but bias was small. Between-platform comparisons yielded less optimal results, particularly with respect to measures of LAP and with one platform yielding both very small LAP volumes and very small ranges of volumes. ConclusionMeasures of plaque components are highly correlated irrespective of use of Adaptive or Fixed threshold approaches within a given platform. But measures are more affected by the specific proprietary algorithms employed than by specific thresholding options, especially for LAP.

ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells

Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.

Cosmic variance suppression in radiation-hydrodynamic modelling of the reionization-era 21-cm signal

ABSTRACT The 21-cm line emitted by neutral hydrogen is the most promising probe of the Epoch of Reionization (EoR). Multiple radio interferometric instruments are on the cusp of detecting its power spectrum. It is therefore essential to deliver robust theoretical predictions, enabling sound inference of the coeval Universe properties. The nature of this signal traditionally required the modelling of $\mathcal {O}(10^{7-8} \, {\rm Mpc}^3)$ volumes to suppress the impact of cosmic variance. However, the recently proposed Fixed &amp; Paired (F&amp;P) approach uses carefully crafted simulation pairs to achieve equal results in smaller volumes. In this work, we thoroughly test the applicability of and improvement granted by this technique to different observables of the 21-cm signal from the EoR. We employ radiation-magneto-hydrodynamics simulations to ensure the most realistic physical description of this epoch, greatly improving over previous studies using a seminumerical approach without accurate galaxy formation physics and radiative transfer. We estimate the statistical improvement granted by the F&amp;P technique on predictions of the skewness, power spectrum, bispectrum, and ionized regions size distribution of the 21-cm signal at redshift 7 ≤ z ≤ 10 (corresponding to ${\ge}80{{\ \rm per\ cent}}$ of the gas being neutral). We find that the effective volume of F&amp;P simulations is at least 3.5 times larger than traditional simulations. This directly translates into an equal improvement in the computational cost (in terms of time and memory). Finally, we confirm that a combination of different observables like skewness, power spectrum, and bispectrum across different redshifts can be utilized to maximize the improvement.

Double-Bubble Technique Assisted by Holding Forceps: A Modified Technique in Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes With Scleral Fixated Intraocular Lens.

Several techniques have been developed for graft unfolding approaches in Descemet membrane endothelial keratoplasty (DMEK). However, despite these techniques, graft deployment and configuration in eyes with deep anterior chambers remain challenging in some cases. Therefore, in this study, we described a modified technique for DMEK, known as the "double-bubble technique assisted by holding forceps." This was a retrospective interventional case series. Patients who underwent DMEK between August 2022 and July 2023, including cases with a history of vitrectomy and scleral fixation of intraocular lens, were enrolled in this study. Two experienced surgeons performed DMEK. In brief, after graft insertion into the anterior chamber, the first bubble with a small volume of air was injected above the graft to open the tight roll, and the graft edge was held using a 25-gauge graft manipulator. The second bubble was injected underneath the graft for fixation, while the graft edge was grasped using forceps during gas injection. The graft was released from the forceps. Best spectacle corrected visual acuity, central corneal thickness, endothelial cell density, and incidence of postoperative complications were measured before and after DMEK. Eleven eyes of 11 patients were included in this study (mean follow-up period, 4.5 ± 4.4 months). Best spectacle corrected visual acuity and central corneal thickness significantly improved postoperatively ( P < 0.001). Rebubbling was required in 2 eyes; no other postoperative complications or primary graft failure were observed. The present technique enables safe and feasible DMEK surgery in vitrectomized eyes with scleral fixated IOLs and in those with a deep anterior chamber.

Changes in masseter muscle morphology after surgical-orthodontic treatment in patients with skeletal Class III malocclusion with mandibular asymmetry: The automatic masseter muscle segmentation model

This study evaluated the masseter muscle changes after surgical-orthodontic treatment in patients with a skeletal Class III malocclusion using automatic segmentation. Images of 120 patients with skeletal Class III malocclusion were obtained and reconstructed at T0 (pretreatment), T1 (presurgery), and T2 (6-12-month postsurgery). The patients were divided into symmetrical and asymmetrical groups. The volume, major axis length, maximum cross-sectional area, horizontal cross-sectional area 5 mm above the mandibular foramen (CSAF), and orientation were calculated automatically. In the asymmetrical group, the volume and major axis length on the deviated side were lower than on the nondeviated side at T0, T1, and T2 (P<0.05). There were no significant differences in maximum cross-sectional area and CSAF bilaterally. The orientation was coronally more vertical and sagittally more forward on the deviated side (both P<0.001). In the symmetrical group, there were no significant bilateral differences at T0, T1, and T2. The volume, major axis length, and CSAF decreased, and the coronal orientation was more vertical on the nondeviated side at T2 than at T0 in both groups (P<0.05). The coronal plane orientation was more inclined on the deviated side at T2 than at T0 in the asymmetrical group (P<0.05). The smaller volume on the deviated side at T2 indicates the need for myofunctional training after surgery. The masseter muscle volume and the cross-sectional area did not recover to the preorthodontic levels. Studies with longer follow-up durations are needed to confirm these findings.

Translating myosin-binding protein C and titin abnormalities to whole-heart function using a novel calcium-contraction coupling model

Mutations in cardiac myosin-binding protein C (cMyBP-C) or titin may respectively lead to hypertrophic (HCM) or dilated (DCM) cardiomyopathies. The mechanisms leading to these phenotypes remain unclear because of the challenge of translating cellular abnormalities to whole-heart and system function.We developed and validated a novel computer model of calcium-contraction coupling incorporating the role of cMyBP-C and titin based on the key assumptions: 1) tension in the thick filament promotes cross-bridge attachment mechanochemically, 2) with increasing titin tension, more myosin heads are unlocked for attachment, and 3) cMyBP-C suppresses cross-bridge attachment.Simulated stationary calcium-tension curves, isotonic and isometric contractions, and quick release agreed with experimental data. The model predicted that a loss of cMyBP-C function decreases the steepness of the calcium-tension curve, and that more compliant titin decreases the level of passive and active tension and its dependency on sarcomere length. Integrating this cellular model in the CircAdapt model of the human heart and circulation showed that a loss of cMyBP-C function resulted in HCM-like hemodynamics with higher left ventricular end-diastolic pressures and smaller volumes. More compliant titin led to higher diastolic pressures and ventricular dilation, suggesting DCM-like hemodynamics.The novel model of calcium-contraction coupling incorporates the role of cMyBP-C and titin. Its coupling to whole-heart mechanics translates changes in cellular calcium-contraction coupling to changes in cardiac pump and circulatory function and identifies potential mechanisms by which cMyBP-C and titin abnormalities may develop into HCM and DCM phenotypes. This modeling platform may help identify distinct mechanisms underlying clinical phenotypes in cardiac diseases.

Local Anesthesia During Operations on the Cervix, Vagina, and Vulva

Introduction. Operations under general anesthesia carry risks to the patient’s health, require appropriate equipment of the operating room, additional personnel in the team. This was the impetus for the active dissemination of local anesthesia technologies in the obstetric and gynecological community. The purpose of the study is to determine the current state of the issue of the use of local anesthesia in gynecology in outpatient settings during operations on the cervix, vagina and vulva.Materials and methods. Publications freely available from databases were used to prepare the work еLibrary.Ru, PubMed, in Russian and foreign specialized journals on obstetrics and gynecology, anesthesiology, textbooks, the predominant period of publication 2016–2023.Results and discussion. In the XIX century, scientists actively worked on the issue of finding an effective anesthetic and a method of anesthesia, the XX century shows that research continued in the direction of identifying the safest drug for anesthesia. In the XXI century, an obstetrician-gynecologist has a huge arsenal of anesthesia techniques, in which it is enough only to choose those techniques that can be used effectively, safely and financially affordable in his medical institution. The literature review shows the high efficiency of infiltration anesthesia during cervical biopsy, excision and conization, as well as a reduction in the number of complications associated with anesthesia. At the same time, for a small volume cervical biopsy, application anesthesia (10% lidocaine aerosol) can be used, but for conization with curettage of the cervical canal (and maybe even with aspiration biopsy), regional anesthesia (paracervical blockade) can be used — the technique of which is described in detail. Local anesthesia of the vagina can be performed using both infiltrative and application anesthesia. Local anesthesia of the vulva is replete with information about the widespread use, effectiveness and safety of application methods of anesthesia, not only in diagnosis, but also for the purpose of treatment.Conclusion. Despite the wide variety of techniques of local anesthesia, as well as the exclusion of adverse events associated with anesthesia, any obstetrician-gynecologist should understand that local anesthesia can also lead to various complications, and be ready to eliminate them.

Crustal evolution of a continental magmatic arc from subduction to collision: A case study in the Gangdese arc, southern Tibetan Plateau

Magmatic arcs are the main environment where continental crust is created on the post-Archean Earth; however, how juvenile arc crust evolves into mature continental crust is still controversial. In this study, we report new bulk-rock major and trace elements, Sr-Nd isotopes, and zircon U-Pb ages and Hf isotopes from a large suite of granites collected from the eastern segment of the Gangdese arc, southern Tibetan Plateau, which record a complete history of arc crust evolution from Mesozoic subduction to Cenozoic collision. These new data show that Gangdese crust-derived granites generated during the subduction to collisional stages record significant geochemical changes with age, indicating that the bulk composition, lithological makeup, and thicknesses of the arc crust evolved over time. Here, we propose that the Gangdese arc had a thick juvenile crust with a small volume of ancient crustal components during late-stage subduction of the Neo-Tethys Ocean, a thin juvenile crust with heterogeneously distributed ancient crustal materials during early collision, and a thick juvenile crust with minor proportions of ancient rocks during late collision. This implies that the arc experienced episodes of crustal thickening during the Late Cretaceous and Eocene, interspersed by periods of thinning during the Paleocene and Miocene, and several discrete episodes of partial melting in the lower arc crust, and cycling or recycling of juvenile and ancient crustal materials within the arc crust and between the crust and mantle. We suggest that shallow subduction of the Neo-Tethys during the Late Cretaceous promoted tectonic thickening of the arc crust, partial melting of lower crust, and formation of high Sr/Y granites. After the onset of the Indo-Asian collision, breakoff of the subducted Neo-Tethyan oceanic slab during the Paleocene/early Eocene allowed thinning of the overlying arc crust and generation of granites derived from juvenile and ancient crustal sources. Continued underthrusting of the Indian continental crust and subsequent delamination of thickened lithospheric mantle led to thickening and thinning of the arc crust, respectively, and partial melting of thickened lower crust and generation of high Sr/Y granites during the Oligocene and Miocene. Using the Gangdese as an analogue for post-Archean continental margins, we suggest that the repeated thickening and thinning of arc crust, and associated multistage remelting of the lower arc crust, and material cycling or recycling within the crust and between the crust and mantle from subduction to collision are common processes that drive maturation of juvenile arc crust.

Unraveling the Intraday Variations in the Tear Fluid Proteome.

Tear fluid is a complex and dynamic biological fluid that plays essential roles in maintaining ocular homeostasis and protecting against the external environment. Owing to the small sample volume, studying the tear proteome is challenging. However, advances in high-resolution mass spectrometry have expanded tear proteome profiling, revealing >500 unique proteins. Tears are emerging as a noninvasive source of biomarkers for both ocular and systemic diseases; nevertheless, intraday variability of proteins in tear fluid remains questionable. This study investigates intraday variations in the tear fluid proteome to identify stable proteins that could act as candidate biomarkers. Tear samples from 15 individuals at four time points (10 am, 12 pm, 2 pm, and 4 pm) were analyzed using mass spectrometry to evaluate protein variation during these intervals. Technical variation was assessed by analyzing pooled samples and was subtracted from the total variation to isolate biological variability. Owing to high technical variation, low-abundant proteins were filtered, and only 115 proteins met the criteria for further analysis. These criteria include being detected at all four time points in at least eight subjects, having a mean peptide-spectrum match count greater than 5, and having a technical variation less than 0.10. Lactotransferrin, lipocalin-1, and several immunoglobulins were among the 51 stable proteins (mean biological coefficient of variation < 0.10). Additionally, 43 proteins displayed significant slopes across the 4 time points, with 17 increasing and 26 decreasing over time. These findings contribute to the understanding of tear fluid dynamics and further expand our knowledge of the tear proteome.

Microfluidic System Consisting of a Magnetic 3D-Printed Microchannel Filter for Isolation and Enrichment of Circulating Tumor Cells Targeted by Anti-HER2/MOF@Ferrite Core-Shell Nanostructures: A Theranostic CTC Dialysis System.

Low number of circulating tumor cells (CTCs) in the blood samples and time-consuming properties of the current CTC isolation methods for processing a small volume of blood are the biggest obstacles to CTC usage in practice. Therefore, we aimed to design a CTC dialysis system with the ability to process cancer patients' whole blood within a reasonable time. Two strategies were employed for developing this dialysis setup, including (i) synthesizing novel in situ core-shell Cu ferrites consisting of the Cu-CuFe2O4 core and the MIL-88A shell, which are targeted by the anti-HER2 antibody for the efficient targeting and trapping of CTCs; and (ii) fabricating a microfluidic system containing a three-dimensional (3D)-printed microchannel filter composed of a polycaprolactone/Fe3O4 nanoparticle composite with pore diameter less than 200 μm on which a high-voltage magnetic field is focused to enrich and isolate the magnetic nanoparticle-targeted CTCs from a large volume of blood. The system was assessed in different aspects including capturing the efficacy of the magnetic nanoparticles, CTC enrichment and isolation from large volumes of human blood, side effects on blood cells, and the viability of CTCs after isolation for further analysis. Under the optimized conditions, the CTC dialysis system exhibited more than 80% efficacy in the isolation of CTCs from blood samples. The isolated CTCs were viable and were able to proliferate. Moreover, the CTC dialysis system was safe and did not cause side effects on normal blood cells. Taken together, the designed CTC dialysis system can process a high volume of blood for efficient dual diagnostic and therapeutic purposes.

The Adhesive Capsulitis Corticosteroid and Dilation (ACCorD) randomized controlled trial.

Is it feasible to conduct a definitive multicentre trial in community settings of corticosteroid injections (CSI) and hydrodilation (HD) compared to CSI for patients with frozen shoulder? An adequately powered definitive randomized controlled trial (RCT) delivered in primary care will inform clinicians and the public whether hydrodilation is a clinically and cost-effective intervention. In this study, prior to a full RCT, we propose a feasibility trial to evaluate recruitment and retention by patient and clinician willingness of randomization; rates of withdrawal, crossover and attrition; and feasibility of outcome data collection from routine primary and secondary care data. In the UK, the National Institute for Health and Care Excellence (NICE) advises that prompt early management of frozen shoulder is initiated in primary care settings with analgesia, physiotherapy, and joint injections; most people can be managed without an operation. Currently, there is variation in the type of joint injection: 1) CSI, thought to reduce the inflammation of the capsule reducing pain; and 2) HD, where a small volume of fluid is injected into the shoulder joint along with the steroid, aiming to stretch the capsule of the shoulder to improve pain, but also allowing greater movement. The creation of musculoskeletal hubs nationwide provides infrastructure for the early and effective management of frozen shoulder. This potentially reduces costs to individuals and the wider NHS perhaps negating the need for a secondary care referral. We will conduct a multicentre RCT comparing CSI and HD in combination with CSI alone. Patients aged 18 years and over with a clinical diagnosis of frozen shoulder will be randomized and blinded to receive either CSI and HD in combination, or CSI alone. Feasibility outcomes include the rate of randomization as a proportion of eligible patients and the ability to use routinely collected data for outcome evaluation. This study has involved patients and the public in the trial design, dissemination methods, and how to include groups who are underserved by research. We will disseminate findings among musculoskeletal clinicians via the British Orthopaedic Association, the Chartered Society of Physiotherapy, the Royal College of Radiologists, and the Royal College of General Practitioners. To ensure wide reach we will communicate findings through our established network of charities and organizations, in addition to preparing dissemination findings in Bangla and Urdu (commonly spoken languages in northeast London). If a full trial is shown to be feasible, we will seek additional National Institute for Health and Care Research funding for a definitive RCT. This definitive study will inform NICE guidelines for the management of frozen shoulder.

Translating evidence: pain treatment in newborns, infants, and toddlers during needle-related procedures : German version

Treatment of pain in preterm, sick, and healthy newborns and infants and toddlers (up to 2years of age) is consistently reported to be inadequate, and effective strategies are poorly implemented. To present existing evidence of effective pain treatment strategies during needle-related procedures and to highlight initiatives focused on translating evidence into practice. This Clinical Update focuses on the 2022 International Association for the Study of Pain Global Year for Translating Pain Knowledge to Practice in the specific population of newborns, infants, and toddlers. Best evidence is reviewed, and existing knowledge translation strategies and programs available to implement evidence into practice are presented. Effective strategies for newborn and young infants during frequently occurring needle procedures include small volumes of sweet solutions, breastfeeding, or skin-to-skin care when feasible and culturally acceptable. In addition, strategies such as nonnutritive sucking, positioning, swaddling, gentle touch, facilitated tucking, and secure holding can be used. For toddlers, the evidence is less robust, and discerning between pain and distress is challenging. However, strategies recommended for needlerelated procedures include upright secure comfort holding by parents/caregivers, age-appropriate distraction, and topical anesthetics. Translation of effective pain management needs to involve the family, who need to be supported and empowered to comfort their child during painful procedures. Organizational, nationwide, and global initiatives aimed at improving implementation of effective pain treatments exist. There is evidence of effective pain management strategies for newborns, infants, and toddlers, and agreat deal of effort is being made to translate knowledge into action.

Effect of Sample Preprocessing and Size-Based Extraction Methods on the Physical and Molecular Profiles of Extracellular Vesicles.

Extracellular vesicles (EVs) are nanometric lipid vesicles that shuttle cargo between cells. Their analysis could shed light on health and disease conditions, but EVs must first be preserved, extracted, and often preconcentrated. Here we first compare plasma preservation agents, and second, using both plasma and cell supernatant, four EV extraction methods, including (i) ultracentrifugation (UC), (ii) size-exclusion chromatography (SEC), (iii) centrifugal filtration (LoDF), and (iv) accousto-sorting (AcS). We benchmarked them by characterizing the integrity, size distribution, concentration, purity, and expression profiles for nine proteins of EVs, as well as the overall throughput, time-to-result, and cost. We found that the difference between ethylenediaminetetraacetic acid (EDTA) and citrate anticoagulants varies with the extraction method. In our hands, ultracentrifugation produced a high yield of EVs with low contamination; SEC is low-cost, fast, and easy to implement, but the purity of EVs is lower; LoDF and AcS are both compatible with process automation, small volume requirement, and rapid processing times. When using plasma, LoDF was susceptible to clogging and sample contamination, while AcS featured high purity but a lower yield of extraction. Analysis of protein profiles suggests that the extraction methods extract different subpopulations of EVs. Our study highlights the strengths and weaknesses of sample preprocessing methods, and the variability in concentration, purity, and EV expression profiles of the extracted EVs. Preanalytical parameters such as collection or preprocessing protocols must be considered as part of the entire process in order to address EV diversity and their use as clinically actionable indicators.

Volumetric analysis of hippocampal subregions and subfields in left and right semantic dementia.

Two variants of semantic dementia are recognized based on the laterality of temporal lobe involvement: a left-predominant variant associated with verbal knowledge impairment and a right-predominant variant associated with behavioural changes and non-verbal knowledge loss. This cross-sectional clinicoradiologic study aimed to assess whole hippocampal, subregion, and/or subfield volume loss in semantic dementia versus controls and across its variants. Thirty-five semantic dementia participants and 15 controls from the Neurodegenerative Research Group at Mayo Clinic who had completed 3.0-T volumetric magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography were included. Classification as left-predominant (n = 25) or right-predominant (n = 10) variant was based on temporal lobe hypometabolism. Volumes of hippocampal subregions (head, body, and tail) and subfields (parasubiculum, presubiculum, subiculum, cornu ammonis 1, cornu ammonis 3, cornu ammonis 4, dentate gyrus, molecular layer, hippocampal-amygdaloid transition area, and fimbria) were obtained using FreeSurfer 7. Subfield volumes were measured separately from head and body subregions. We fit linear mixed-effects models using log-transformed whole hippocampal/subregion/subfield volumes as dependent variables; age, sex, total intracranial volume, hemisphere and a group-by-hemisphere interaction as fixed effects; and subregion/subfield nested within hemisphere as a random effect. Significant results (P < 0.05) are hereby reported. At the whole hippocampal level, the dominant (predominantly involved) hemisphere of both variants showed 23-27% smaller volumes than controls. The non-dominant (less involved) hemisphere of the right-predominant variant also showed volume loss versus controls and the left-predominant variant. At the subregional level, both variants showed 17-28% smaller dominant hemisphere head, body, and tail than controls, with the right-predominant variant also showing 8-12% smaller non-dominant hemisphere head than controls and left-predominant variant. At the subfield level, the left-predominant variant showed 12-36% smaller volumes across all dominant hemisphere subfields and 14-15% smaller non-dominant hemisphere parasubiculum, presubiculum (head and body), subiculum (head) and hippocampal-amygdaloid transition area than controls. The right-predominant variant showed 16-49% smaller volumes across all dominant hemisphere subfields and 14-22% smaller parasubiculum, presubiculum, subiculum, cornu ammonis 3, hippocampal-amygdaloid transition area (all from the head) and fimbria of non-dominant hemisphere versus controls. Comparison of dominant hemispheres showed 16-29% smaller volumes of the parasubiculum, presubiculum (head) and fimbria in the right-predominant than left-predominant variant; comparison of non-dominant hemispheres showed 12-15% smaller cornu ammonis 3, cornu ammonis 4, dentate gyrus, hippocampal-amygdaloid transition area (all from the head) and cornu ammonis 1, cornu ammonis 3 and cornu ammonis 4 (all from the body) in the right-predominant variant. All hippocampal subregion/subfield volumes are affected in semantic dementia, although some are more affected in both dominant and non-dominant hemispheres of the right-predominant than the left-predominant variant by the time of presentation. Involvement of hippocampal structures is apparently more subregion dependent than subfield dependent, indicating possible superiority of subregion volumes as disease biomarkers.

An Efficient Low‐Cost Device for Sampling Exhaled Breath Condensate EBC

AbstractWhile exhaled breath condensate EBC is not yet used in routine clinical diagnostics and disease monitoring, recent publications indicate that exhaled air and EBC contain a wide range of molecular biomarkers that are characteristic of various medical conditions. This includes evidently lung disorders such as asthma, COPD, and cystic fibrosis, but also diabetes and several types of cancer go along with specific biomarkers exhaled from the airways. In addition, EBC samples can be collected in a non‐invasive way and, due to their small volume, they can be easily stored frozen between collection and analysis. Several home‐made EBC‐collection systems for research purposes are documented in literature while there are also a few systems from commercial suppliers that are not yet certified as medical products. In this work, a novel collection device is presented in which the EBC is condensed and frozen inside stainless steel tubes, tightly surrounded by an aluminum cylinder that is precooled in a kitchen freezer. The device is low cost, easy to use by patients at home or in a clinic, and its collection efficiency of up to 500 µL min−1 of respiration is on the high side.

Multi-objective optimization research of open and closed air brayton cycle

Air Brayton cycle obtains the significant advantages of high efficiency, compact structure, easy medium requirement and so on, which is one of the most suitable choices for the mobile nuclear power conversion system. In this paper, system-component combined design method is used to establish the open and closed air Brayton cycle of diverse configurations. Based on performance and compactness targets, the multi-objective optimization is carried out to find the optimal design by nondominated sorting genetic algorithm II and entropy weight method. According to the analysis, the closed intercooling reheating recuperating cycle is the configuration with the best comprehensive performance, with cycle efficiency of 33.58 %, power density of 175.39 kW m−3 and power mass ratio of 68.60 kW t−1. The open simple recuperating cycle is the configuration with the smallest volume and mass, with cycle efficiency of 20.01 %, system volume of 6.56 m3 and system mass of 19.98 t. The closed intercooling recuperating cycle is the most balanced configuration, with cycle efficiency of 31.33 %, volume of 9.06 m3 and system mass of 24.97 t. Based on the optimal results, off-design performance analysis of different environmental conditions is also carried out for the configurations above.

Seismic motion incoherency effects on SSSI responses of nuclear buildings

AbstractThe spatial variation of ground motion may significantly aggravate the seismic damage of large‐scale structures such as nuclear buildings. Establishing the seismic wave field with spatial features is the basis and key to seismic analysis of large‐scale complex structures. For the nuclear island buildings, which are arranged close to each other, the influence of structure–soil–structure interaction (SSSI) and incoherent motion on the structural seismic response should be considered. Taking a domestic nuclear power project as an example, the seismic response analyses under incoherent seismic motion and coherent seismic motion are carried out respectively. The seismic motion incoherency effects on the nuclear island buildings on the common raft and the adjacent seismic category I structure are explored by comparing the results of the in‐structure response spectrum (ISRS) at key elevations. The results indicate that the seismic motion incoherency does not change the trend of the response spectrum curve and the dominant frequency. Both the peak acceleration and zero‐period acceleration of ISRS are changed to some extent. Overall, seismic motion incoherency has a more significant impact on the ISRS of nuclear buildings with smaller volumes.