Background Scintigraphy using technetium-99m labelled dimercaptosuccinic acid ([ 99m Tc]Tc-DMSA), taken up in the proximal tubules, is the standard in functional imaging of the renal cortex. Recent guidelines recommend performing [ 99m Tc]Tc-DMSA scintigraphy with single photon emission computed tomography (SPECT). Prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) is used for staging and localization of recurrence in prostate cancer. A high renal uptake is often seen on PSMA PET, concordant with known PSMA expression in proximal tubules. This suggests PSMA PET could be used analogous to [ 99m Tc]Tc-DMSA scintigraphy for renal cortical imaging. [ ¹⁸ F]PSMA-1007 is a promising radiopharmaceutical for this purpose due to low urinary clearance. In this study, we aimed to compare [ ¹⁸ F]PSMA-1007 PET to [ 99m Tc]Tc-DMSA SPECT regarding split renal uptake and presence of renal uptake defects, in patients with prostate cancer. Three readers interpreted PET and SPECT images regarding presence of renal uptake defects, with each kidney split into cranial, mid and caudal segments. Kidneys were segmented in PET and SPECT images, and left renal uptake as a percentage of total renal uptake was measured. Results Twenty patients with prostate cancer were included. 2 participants had single kidneys; thus 38 kidneys were evaluated. A total of 29 defects were found on both [ 99m Tc]Tc-DMSA SPECT and [ ¹⁸ F]PSMA-1007 PET. Cohen’s kappa for concordance regarding presence of any defect was 0.76 on a per-segment basis and 0.67 on a per-kidney basis. Spearman’s r for left renal uptake percentage between [ 99m Tc]Tc-DMSA SPECT and [ ¹⁸ F]PSMA-1007 PET was 0.95. Conclusions [ ¹⁸ F]PSMA-1007 PET is comparable to [ 99m Tc]Tc-DMSA SPECT for detection of uptake defects in this setting. Measurements of split renal function made using [ ¹⁸ F]PSMA-1007 PET are valid and strongly correlated to measurements made with [ 99m Tc]Tc-DMSA SPECT.
Introduction Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using ¹³³ Ba as a surrogate for ¹³¹ I imaging. Materials and methods Two sets of four traceable ¹³³ Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68–107.4 mL). Corresponding hollow cylinders to be filled with liquid ¹³¹ I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of ¹³³ Ba sources and liquid ¹³¹ I. Results As anticipated, the ¹³¹ I pseudo-image calibration factors (cps/MBq) were higher than those for ¹³³ Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12–1.5%. The site-specific cross-calibration method also showed agreement between ¹³³ Ba and ¹³¹ I for all cylinder volumes, which highlights the potential use of ¹³³ Ba sources to calculate recovery coefficients for partial volume correction. Conclusion This comparison exercise demonstrated that traceable solid ¹³³ Ba sources can be used as surrogate for liquid ¹³¹ I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with ¹³¹ I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.
Archamoebae comprises free-living or endobiotic amoebiform protists that inhabit anaerobic or microaerophilic environments and possess mitochondrion-related organelles (MROs) adapted to function anaerobically. We compared in silico reconstructed MRO proteomes of eight species (six genera) and found that the common ancestor of Archamoebae possessed very few typical components of the protein translocation machinery, electron transport chain and tricarboxylic acid cycle. On the other hand, it contained a sulphate activation pathway and bacterial iron–sulphur (Fe-S) assembly system of MIS-type. The metabolic capacity of the MROs, however, varies markedly within this clade. The glycine cleavage system is widely conserved among Archamoebae, except in Entamoeba , probably owing to its role in catabolic function or one-carbon metabolism. MRO-based pyruvate metabolism was dispensed within subgroups Entamoebidae and Rhizomastixidae, whereas sulphate activation could have been lost in isolated cases of Rhizomastix libera , Mastigamoeba abducta and Endolimax sp. The MIS (Fe-S) assembly system was duplicated in the common ancestor of Mastigamoebidae and Pelomyxidae, and one of the copies took over Fe-S assembly in their MRO. In Entamoebidae and Rhizomastixidae, we hypothesize that Fe-S cluster assembly in both compartments may be facilitated by dual localization of the single system. We could not find evidence for changes in metabolic functions of the MRO in response to changes in habitat; it appears that such environmental drivers do not strongly affect MRO reduction in this group of eukaryotes.
Objectives The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours. Design Cross-sectional. Setting Multisite study at university hospitals. Participants A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer. Primary and secondary outcomes Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound. Results High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61–0.67), CACS (OR range 0.71–0.75) and CarA (OR range 0.72–0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73). Conclusions MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.
Objective: This Swedish study aimed to assess the prevalence, associated clinical factors, and mortality rates of heart failure patients diagnosed without echocardiograms in both hospital and primary care settings. Design: We conducted a retrospective population-based study using data from the Region Halland healthcare database in Sweden covering 330,000 residents. Subjects: From 2013-2019, 3,903 patients received an incidental heart failure diagnosis without an echocardiogram and they were followed for one year. Main outcome measures: Using logistic and Cox regression analyses, we evaluated the prevalence, clinical characteristics, and all-cause mortality at intervals of 30, 100, and 365 days post-diagnosis. Results: In this Swedish cohort, the one-year all-cause mortality rate was markedly higher for patients diagnosed in hospitals (42%) compared to those in primary care (20%, p < 0.001). Patients diagnosed in primary care were older and had fewer comorbidities and lower NT-proBNP levels. Hospital-diagnosed patients faced a significantly higher mortality rate in the initial 30 days but saw similar rates to primary care patients thereafter. Conclusion: In a Swedish region, heart failure diagnoses without echocardiograms were more common in hospitals, and these patients initially faced worse prognoses. After the first month, however, the prognosis of hospital-diagnosed patients mirrored that of those diagnosed in primary care. These findings emphasize the need for improved diagnostic and treatment approaches in both care settings to enhance outcomes.
Background In January 2010, the choice reform was instituted in Swedish primary health care establishing free entry for private primary health care providers and enabling patients to choose freely among primary health care centers. The motivation behind the reform was to improve access to primary care and responsiveness to patient expectations. Reform effects on health care utilization have previously been investigated by using subgroup analyses assuming a pattern of homogeneous subgroups of the population. By using a different methodological approach, the aim of this study was to, from an equity perspective, investigate long term trends of primary health care utilization following the choice reform. Method A closed cohort was created based on register data from Region Skåne, the third most populated region in Sweden, describing individuals’ health care utilization between 2007–2017. Using a novel approach, utilization data, measured as primary health care visits, was matched with socioeconomic and geographic determinants, and analyzed using logistic regression models. Results A total of 659,298 individuals were included in the cohort. Sex differences in utilization were recorded to decrease in the older age group and to increase in the younger age group. Multivariable logistic regression showed increasing utilization in older men to be associated with higher socioeconomic position, while in women it was associated with lower socioeconomic position. Furthermore, groups of becoming high utilizers were all associated with lower socioeconomic position and with residence in urban areas. Conclusion The impact of demographic, socioeconomic and geographic determinants on primary health care utilization varies in magnitude and direction between groups of the population. As a result, the increase in utilization as observed in the general population following the choice reform is unevenly distributed between different population groups.
Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral bleeding: the AF SPICE protocol
Introduction Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity. Methods and analysis AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24–72 hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3 months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023–2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up. Ethics and dissemination Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021–02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice. Trial registration number NCT05134454 .
Terahertz (THz) technologies provide opportunities ranging from calibration targets for satellites and telescopes to communication devices and biomedical imaging systems. A main component will be broadband THz absorbers with switchability. However, optically switchable materials in THz are scarce and their modulation is mostly available at narrow bandwidths. Realizing materials with large and broadband modulation in absorption or transmission forms a critical challenge. This study demonstrates that conducting polymer‐cellulose aerogels can provide modulation of broadband THz light with large modulation range from ≈ 13% to 91% absolute transmission, while maintaining specular reflection loss < −30 dB. The exceptional THz modulation is associated with the anomalous optical conductivity peak of conducting polymers, which enhances the absorption in its oxidized state. The study also demonstrates the possibility to reduce the surface hydrophilicity by simple chemical modifications, and shows that broadband absorption of the aerogels at optical frequencies enables de‐frosting by solar‐induced heating. These low‐cost, aqueous solution‐processable, sustainable, and bio‐friendly aerogels may find use in next‐generation intelligent THz devices.
We investigate network nonlocality in the triangle scenario when all three parties have no input and binary outputs. Through an explicit example, we prove that this minimal scenario supports nonlocal correlations compatible with no-signaling and independence of the three sources, but not with realisations based on independent quantum or classical sources. This nonlocality is robust to noise. Moreover, we identify the equivalent to a Popescu-Rohrlich box in the minimal triangle scenario.
Invasive species are predicted to adjust their morphological, physiological and life‐history traits to adapt to their non‐native environments. Although a loss of genetic variation during invasion may restrict local adaptation, introduced species often thrive in novel environments. Despite being founded by just a few individuals, Bombus terrestris (Hymenoptera: Apidae) has in less than 30 years successfully spread across the island of Tasmania (Australia), becoming abundant and competitive with native pollinators. We use RADseq to investigate what neutral and adaptive genetic processes associated with environmental and morphological variation allow B. terrestris to thrive as an invasive species in Tasmania. Given the widespread abundance of B. terrestris , we expected little genetic structure across Tasmania and weak signatures of environmental and morphological selection. We found high gene flow with low genetic diversity, although with significant isolation‐by‐distance and spatial variation in effective migration rates. Restricted migration was evident across the mid‐central region of Tasmania, corresponding to higher elevations, pastural land, low wind speeds and low precipitation seasonality. Tajima's D indicated a recent population expansion extending from the south to the north of the island. Selection signatures were found for loci in relation to precipitation, wind speed and wing loading. Candidate loci were annotated to genes with functions related to cuticle water retention and insect flight muscle stability. Understanding how a genetically impoverished invasive bumblebee has rapidly adapted to a novel island environment provides further understanding about the evolutionary processes that determine successful insect invasions, and the potential for invasive hymenopteran pollinators to spread globally.
In most non‐fullerene organic solar cells comprising bulk‐heterojunction active layers, the inter‐domain connectivity of small‐molecule acceptors is generally inferior to those of polymeric donors due to their intrinsic short‐range ordering. This issue is even exacerbated by the physiochemical mismatch between acceptor‐phases and metal‐oxide electron transport layers in most inverted n‐i‐p devices, leading to inefficient electron collection. By pre‐depositing an ultra‐thin acceptor primer layer, it develops a novel acceptor‐enriched‐bottom active layer to reinforce the acceptor‐phase continuity. It is however challenging to preserve the primer layer during non‐orthogonal solvent processing. Thus, sequential n‐type doping is implemented on the surface of the primer layer, which allows to slightly reduce the acceptor solubility by polarity regulation, as well as stabilize the film structure via strong π–π interaction between dopant/host acceptor. Upon acceptor enrichment, higher interfacial electron density enhances the built‐in potential while the enlarged domains suppress both charge‐transfer state and bimolecular recombination. Consequently, the champion device efficiency is greatly improved from ca. 16.1% to 18.0%, mainly resulting from the simultaneously elevated fill factor and short‐circuit current density.
Purpose To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. Results During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14–1.34) and OAC (HR = 1.24, 95% CI 1.05–1.47). WHR mediated 5% (95% CI 3–10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6–53%) and 15% (95% CI 8–72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. Conclusions We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).
Purpose To report on the ophthalmic findings in children with tuberous sclerosis complex (TSC) in southern Sweden, and to investigate the frequency of refractive errors, strabismus and cerebral visual impairment associated with this condition. Methods This was a retrospective cohort study including all paediatric patients with TSC in southern Sweden born between 1983 and 2020. Medical records were reviewed regarding retinal findings, visual acuity, refractive error, strabismus, full‐field electroretinography results and cerebral visual impairment. Results Ophthalmological records were available for 50 of the 52 children in the region diagnosed with TSC. The mean age at the last visit was 12.4 (SD 7.2) years. Monocular visual acuity had been measured in 38 patients, and the median value did not deviate from that expected for their age in the better eye, but by −0.2 Snellen decimal acuity in the worse eye. Refractive errors were found in 62% of the patients, and strabismus in 16%. Retinal astrocytic hamartomas were found in 34% and achromatic patches in 34%. Ten of the patients on medication with vigabatrin were examined with full‐field electroretinography and treatment had to be stopped or lowered in three (30%), due to a reduced response. Investigation of cerebral visual impairment had not been conducted in any of the children. Conclusion Refractive errors and strabismus were common among children with TSC. None of the patients in this cohort had undergone investigation for cerebral visual impairment. The general awareness of cerebral visual impairment among ophthalmologists is poor and constitutes an important area for improvement.
Genetic technologies are revolutionizing human health. In parallel, geopolitical instability has prompted renewed discussions on the risks of DNA technology being weaponized in international conflict. With today’s changing security environment, we argue that risk assessments must be broadened from genetically targeted weapons to a series of new domains. In this comment article, we reflect on possible scenarios and solutions to emerging problems.
Luminescence dating is a widely used method in combination with sedimentological analysis for reconstructing the landscape development of the Quaternary period. In this study, quartz and K-feldspar measurements were used to evaluate the luminescence characteristics with the aim of dating the deposits. The sediments were sampled from an abandoned gravel pit in the Biely Váh valley and eight sites in the lower part of the Velická dolina valley, High Tatra Mountains, Slovakia. Optically stimulated luminescence (OSL) showed that quartz had an unstable weak signal, and standard single aliquot regeneration (SAR) dose estimates were unreliable, as were doses from pulsed OSL and differential OSL. Infrared (IR 50 ) and post-IR IR 225 stimulation (pIRIR 225 ) signals from K-feldspar grains, on the other hand, gave stronger signals but were, to various extents, influenced by incomplete bleaching, fading and uncertainty due to high (>2D 0 ) doses. We find the uncorrected pIRIR 225 ages most reliable, though modern analogues indicate that there may be significant residual from incomplete bleaching for some of the samples. The results of the luminescence analyses, ages and sedimentology are put in the context of landscape dynamics and compared to the known glacial history of the Tatra Mountains.
Nitrogenase is the only enzyme that can cleave the strong triple bond in N2, making nitrogen available for biological life. There are three isozymes of nitrogenase, differing in the composition of the active site, viz., Mo, V, and Fe-nitrogenase. Recently, the first crystal structure of Fe-nitrogenase was presented. We have performed the first combined quantum mechanical and molecular mechanical (QM/MM) study of Fe-nitrogenase. We show with QM/MM and quantum-refinement calculations that the homocitrate ligand is most likely protonated on the alcohol oxygen in the resting E0 state. The most stable broken-symmetry (BS) states are the same as for Mo-nitrogenase, i.e., the three Noodleman BS7-type states (with a surplus of β spin on the eighth Fe ion), which maximize the number of nearby antiferromagnetically coupled Fe–Fe pairs. For the E1 state, we find that protonation of the S2B μ2 belt sulfide ion is most favorable, 14–117 kJ/mol more stable than structures with a Fe-bound hydride ion (the best has a hydride ion on the Fe2 ion) calculated with four different density-functional theory methods. This is similar to what was found for Mo-nitrogenase, but it does not explain the recent EPR observation that the E1 state of Fe-nitrogenase should contain a photolyzable hydride ion. For the E1 state, many BS states are close in energy, and the preferred BS state differs depending on the position of the extra proton and which density functional is used.
This paper explores the potential of blockchain technology (BCT) in promoting sustainable food production and consumption (SFPC) from a consumer perspective. India, a significant global food producer, faces challenges related to affordability and food logistics due to transport and labour constraints. Food safety concerns, i.e., foodborne illnesses and quality issues, alongside unexpected events like COVID-19 and geopolitical conflicts, threaten SFPC. In recent times, consumer focus has shifted a lot towards food safety and security. The study adopted exploratory factor analysis (EFA) to identify the factors strengthening consumer trust through BCT. The EFA helped classify the items into five factors, i.e., reliability, sustainability, impact on health, trust, and switching intentions. The results reveal that these factors are the most significant reasons consumers are willing to accept a blockchain-enabled food system over a traditional system. The study findings will benefit organisations willing to introduce blockchain within their operations to improve the consumer base. It will also prove to be helpful for researchers and academicians to understand consumer perspectives towards BCT for SFPC.
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