Search

Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies.In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD). We excluded those who received SGLT2 or DPP-4 inhibitors as first-line treatment or insulin at the same time, had estimated glomerular filtration rate (eGFR) of less than 45 mL/min per 1·73 mAmong 10 253 patients initiating SGLT2 inhibitors and 16 624 patients initiating DPP-4 inhibitors in CPRD, baseline HbAA validated treatment selection algorithm for SGLT2 inhibitor and DPP-4 inhibitor therapies can support decisions on optimal treatment for people with type 2 diabetes.BHF-Turing Cardiovascular Data Science Award and the UK Medical Research Council.

Cell-free protein synthesis is an important tool for studying gene expression and harnessing it for applications. In cells, gene expression is regulated in part by the spatial organization of transcription and translation. Unfortunately, current cell-free approaches are unable to control the organization of molecular components needed for gene expression, which limits the ability to probe and utilize its effects. Here, we show, using complementary computational and experimental approaches, that macromolecular crowding can be used to control the spatial organization and translational efficiency of gene expression in cell-sized vesicles. Computer simulations and imaging experiments reveal that, as crowding is increased, DNA plasmids become localized at the inner surface of vesicles. Ribosomes, in contrast, remain uniformly distributed, demonstrating that crowding can be used to differentially organize components of gene expression. We further carried out cell-free protein synthesis reactions in cell-sized vesicles and quantified mRNA and protein abundance. At sufficiently high levels of crowding, we observed localization of mRNA near vesicle surfaces, a decrease in translational efficiency and protein abundance, and anomalous scaling of protein abundance as a function of vesicle size. These results are consistent with high levels of crowding causing altered spatial organization and slower diffusion. Our work demonstrates a straightforward way to control the organization of gene expression in cell-sized vesicles and provides insight into the spatial regulation of gene expression in cells.

Warfarin induces coagulopathy. Guidelines protocolize reversal of supratherapeutic international normalized ratio (INR) in patients dependent on anticoagulation, but practices vary for reversing warfarin-induced coagulopathy after overdose in non-warfarin-dependent patients.This is the report of a 15-year-old female who ingested her father's warfarin (100-200 mg) in a self-harm attempt. At hour 24 post-ingestion, her INR was 2.00 and she was admitted for monitoring. Reversal of coagulopathy was initially deferred pending the INR trend. The INR was 5.10 at hour 60 and 2.5 mg oral vitamin KA restrictive approach to coagulopathy reversal in non-warfarin-dependent patients with intentional warfarin overdose may result in worsening coagulopathy, bleeding, and lengthy hospital stay. Given the risk for significant, prolonged coagulopathy, these patients should be treated early with VK1, with subsequent serial INR monitoring and probable additional VK1 dosing. Delayed peak warfarin concentrations support consideration of gastrointestinal decontamination in late presenters.

Veno-arterial membrane oxygenation (VA-ECMO) can be used as a rescue therapy for patients in refractory cardiogenic shock. While there is experience as a bridge-to-transplant and bridge-to-ventricular assist device in the heart failure population, there are not reports of its use as a bridge to definitive valvular intervention. Here we present a case of VA-ECMO as a bridge to transcatheter mitral valve-in-valve (TMVIV) with a Sapien aortic prosthesis (Edwards Life Sciences, Irvine, CA).

OBJECTIVES The Commando technique for reconstruction of the aortomitral intervalvular fibrous body is effective to facilitate double valve surgery in cases of endocarditis or infiltrative calcification. The length of patch utilized in reconstruction of the intervalvular fibrous body has an important relationship to the geometry of the mitral and aortic valves and may impact on potential future valve-in-valve therapy. Here we report anatomic measurements after Commando reconstruction in a small group of patients and analyze the impact of reconstruction techniques on transcatheter valve-in-valve therapies. METHODS Seven patients from January 2018 to April 2022 who underwent double valve surgery with the Commando technique with postoperative computed tomography scans were identified. Computed tomographic reconstruction of the aortic and mitral valves was performed using 3mensio software and virtual transcatheter valve replacement was performed. Two of these patients who had preoperative imaging was analyzed to assess the change in aortomitral geometry resulting from reconstruction. RESULTS Measurements for each patient post-reconstruction are given in Table 1. Aortomitral length was grossly inversely proportional to aortomitral angle. Aortomitral angle and aortomitral curtain length were significantly altered post-Commando in two analyzed patients with pre- and post-operative computed tomography scan. Transcatheter aortic and mitral valve replacements were feasible in all patients post-Commando. The aortomitral angle was larger and more favorable for mitral valve-in-valve in patients in which the aortomitral curtain was short. CONCLUSIONS Aortomitral curtain length, as determined by location of aortic valve annular sutures, may be an important consideration in surgical decision-making for valve-in-valve after the Commando procedure.

To use optical modeling to compare a 6.0 mm and 7.0 mm intraocular lens (IOL) optic diameters on peripheral retinal illumination with implications for negative dysphotopsia.Mayo Clinic, Rochester, Minnesota, and Simpson Optics LLC, Arlington, Texas.Model eye.Ray-tracing software was used to simulate retinal illumination from an extended light source for a pseudophakic eye with in-the-bag biconvex IOLs (refractive index [n] = 1.46 and 1.55) and a 2.5 mm pupil. Ray-tracing diagrams and simulated retina illumination profiles were compared using the 6.0 mm and 7.0 mm optic diameter IOLs. Retinal locations were scaled to relative visual angles from 70 to 110 degrees horizontally.A 7.0 mm optic (n = 1.46) expands the image field by 2.8 degrees compared with a 6.0 mm optic. High-angle input light misses a 7.0 mm optic at a larger visual angle than a 6.0 mm optic, shifting illumination of the peripheral retina by this light anteriorly by 5.6 degrees. Consequently, a region of nonilluminated peripheral nasal retina is enlarged and shifted peripherally using a 7.0 mm optic (visual angle, 86.3 to 96.3 degrees) compared with a 6.0 mm optic (visual angle, 83.5 to 90.7 degrees). Similar illumination changes were seen modeling a 1.55 n IOL.A narrow dark region in the nasal retina when using a 6.0 mm optic is changed to a broader, more peripheral dark region when using a 7.0 mm optic. An extended, more peripheral dark nasal region may make a temporal shadow less bothersome and explain lower negative dysphotopsia rates using a 7.0 mm optic.

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT −/− mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor β1 ( TGF β 1 ) and collagen ( COL1A1 ) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.

Funding: Social Sciences and Humanities Research Council of Canada (752-2019-0520), Rothermere Foundation, Canadian Centennial Scholarship Fund, University of St Andrews. Community ownership of wind energy has been found to increase acceptance, but the reasons for this are poorly understood. Here, we compare different communities’ attitudes towards local onshore wind energy projects in order to gain a deeper understanding of the characteristics of ownership which are conducive to community acceptance. Using a postal survey in Scotland (n = 318), we compared three communities with varying degrees of ownership regarding their (1) support for the local wind project; (2) perceptions of energy justice; (3) perceived impacts; and (4) ownership and benefit preferences. One-way ANOVAs and the Potential for Conflict Index2 identified that residents in the two communities with a degree of ownership were more associated with greater acceptance, processes, and outcomes (i.e. more just and inclusive development processes and more fairly distributed benefits and impacts), than residents living near the privately-owned development. Additionally, we provide evidence that a co-operative can achieve similar acceptance and energy justice as a fully community-owned project. Overall, the results indicate that policymakers should take seriously the connection between the tenets of energy justice and ownership models in their policy and planning efforts. Publisher PDF

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection.METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis.RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives.CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.).

Objectives: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. Methods: Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)–based heritability estimate (h2SNP) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. Results: We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10−9), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10−45) and Wnt signaling (adjusted P = 9.5 × 10−58). The heritability of PsA in this cohort was found to be moderate (h2SNP = 0.63), which was similar to the heritability of PsC (h2SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. Conclusion: Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

Among left ventricular assist device patients, the most commonly infected component is the drive line, which can be managed with antibiotics and local debridement. Infection of intrathoracic device components is less common but more difficult to manage. Herein we describe the incidence of deep device infection (DDI) at our center as well as management and outcomes.We retrospectively reviewed 658 patients who underwent implantable left ventricular assist device insertion with HeartMate 2 (Abbott) or HeartMate 3 (Abbott) devices between January 2004 and June 2021. DDI was defined according to radiographic and clinical criteria. Cumulative incidence was calculated using a Fine-Gray subdistribution model; survival analysis was performed using the method of Kaplan and Meier.There were 32 (4.8%) DDIs during this study period. Drive line infection and re-exploration for bleeding were associated with development of DDI. Cumulative incidence of DDI increased over time, affecting 11% (7%-18%) at 5 years. The dominant microbes involved in DDI were Pseudomonas aeruginosa (19%) and methicillin-resistant Staphylococcus aureus (13%). Nineteen patients (59%) with device infection underwent device exchange, 6 (19%) underwent initial transplant, and 7 (22%) were treated solely with debridement and antibiotics. Of those who underwent device exchange, 12 (63%) developed reinfection of their new device and 6 underwent subsequent heart transplant. Patients who underwent transplantation for management of device infection had improved 5-year survival (80% vs 11%; P = .01) but 3 patients (25%) developed deep sternal wound infection after transplant.DDI is a rare but challenging complication in this destination era. Heart transplantation is the preferred management strategy for eligible patients but infectious complication is common.

BackgroundDespite advances in next generation sequencing technologies, the identification of variants of uncertain significance (VUS) can often hinder definitive diagnosis in patients with complex neurodevelopmental disorders.ObjectiveThe objective of this study was to identify and characterize the underlying cause of disease in a family with two children with severe developmental delay associated with generalized dystonia and episodic status dystonicus, chorea, epilepsy, and cataracts.MethodsCandidate genes identified by autozygosity mapping and whole-exome sequencing were characterized using cellular and vertebrate model systems.ResultsHomozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1. Although the patients had features of MED27-related disorder, the SLC6A7 and MPPE1 variants were functionally investigated. SLC6A7 variant in vitro overexpression caused decreased proline transport as a result of reduced cell-surface expression, and zebrafish knockdown of slc6a7 exhibited developmental delay and fragile motor neuron morphology that could not be rescued by L-proline transporter–G396S RNA. Lastly, patient fibroblasts displayed reduced cell-surface expression of glycophosphatidylinositol-anchored proteins linked to MPPE1 dysfunction.ConclusionsWe report a family harboring a homozygous MED27 variant with additional loss-of-function SLC6A7 and MPPE1 gene variants, which potentially contribute to a blended phenotype caused by multilocus pathogenic variants. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

In this study, the stability of Ag|Ag+ molten chloride reference electrodes was studied using mullite and magnesia tubes as reference electrode membrane materials in molten MgCl2-KCl-NaCl for continuous immersion up to 31 d. Two electrochemical methods were used to characterize the long-term performance of the reference electrodes at 500 °C in an inert atmosphere using a Mg rod as the working electrode: open circuit potential (OCP) and onset of Mg(II) reduction as measured by cyclic voltammetry (CV). There was only a 3% difference between the average OCP measured versus the mullite and MgO reference electrodes. Potential drift was higher for mullite (−1.34 mV d−1) than MgO (0.22 mV d−1). But both drift rates were very low compared to the OCP data standard deviation, indicating that no significant drift was measured for us to 31 d.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non‐SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2 . Conclusions This study examined one of the largest single‐center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A ; postmortem whole exome sequencing identified 18 ultrarare variants.

Funder: King’s College London, Funder: The European Union Scholarship Programme, Funder: National Institute for Health Research (NIHR), Establishing a universally applicable protocol to assess the impact of BRCA1 variants of uncertain significance (VUS) expression is a problem which has yet to be resolved despite major progresses have been made. The numerous difficulties which must be overcome include the choices of cellular models and functional assays. We hypothesised that the use of induced pluripotent stem (iPS) cells might facilitate the standardisation of protocols for classification, and could better model the disease process. We generated eight iPS cell lines from patient samples expressing either BRCA1 pathogenic variants, non-pathogenic variants, or BRCA1 VUSs. The impact of these variants on DNA damage repair was examined using a ɣH2AX foci formation assay, a Homologous Repair (HR) reporter assay, and a chromosome abnormality assay. Finally, all lines were tested for their ability to differentiate into mammary lineages in vitro. While the results obtained from the two BRCA1 pathogenic variants were consistent with published data, some other variants exhibited differences. The most striking of these was the BRCA1 variant Y856H (classified as benign), which was unexpectedly found to present a faulty HR repair pathway, a finding linked to the presence of an additional variant in the ATM gene. Finally, all lines were able to differentiate first into mammospheres, and then into more advanced mammary lineages expressing luminal- or basal-specific markers. This study stresses that BRCA1 genetic analysis alone is insufficient to establish a reliable and functional classification for assessment of clinical risk, and that it cannot be performed without considering the other genetic aberrations which may be present in patients. The study also provides promising opportunities for elucidating the physiopathology and clinical evolution of breast cancer, by using iPS cells.

ObjectiveTo establish whether clinical patient characteristics routinely measured in primary care can identify people with differing short-term benefits and risks for SGLT2-inhibitor and DPP4-inhibitor therapies, and to derive and validate a treatment selection algorithm to identify the likely optimal therapy for individual patients.DesignProspective cohort study.SettingRoutine clinical data from United Kingdom general practice (Clinical Practice Research Datalink [CPRD]), and individual-level clinical trial data from 14 multi-country trials of SGLT2-inhibitor and DPP4-inhibitor therapies.Participants26,877 new users of SGLT2-inhibitor and DPP4-inhibitor therapy in CPRD over 2013-2019, and 10,414 participants randomised to SGLT2-inhibitor or DPP4-inhibitor therapy in 14 clinical trials, including 3 head-to-head trials of the two therapies (n=2,499).Main outcome measuresThe primary outcome was achieved HbA1c 6 months after initiating therapy. Clinical features associated with differential HbA1c outcomes with SGLT2-inhibitor and DPP4-inhibitor therapies were identified in routine clinical data, with associations then tested in trial data. A multivariable treatment selection algorithm to predict differential HbA1c outcomes was developed in a CPRD derivation cohort (n=14,069), with validation in a CPRD validation cohort (n=9,376) and the head-to-head trials. In CPRD, we further explored the relationship between model predictions and secondary outcomes of weight loss and treatment discontinuation.ResultsThe final treatment selection algorithm included HbA1c, eGFR, ALT, age, and BMI, which were identified as predictors of differential HbA1c outcomes with SGLT2-inhibitor and DPP4-inhibitor therapies using both routine and trial data. In validation cohorts, patient strata predicted to have a ≥5 mmol/mol HbA1c reduction with SGLT2-inhibitor therapy compared with DPP4-inhibitor therapy (38.8% of CPRD validation sample) had an observed greater reduction of 8.8 mmol/mol [95%CI 7.8-9.8] in the CPRD validation sample, a 5.8 mmol/mol (95%CI 3.9-7.7) greater reduction in the Cantata D/D2 trials, and a 6.6 mmol/mol [95%CI 2.2-11.0]) greater reduction in the BI1245.20 trial. In CPRD, there was a greater weight reduction with SGLT2-inhibitor therapy regardless of predicted glycaemic benefit. Strata predicted to have greater reduction in HbA1c on SGLT2-inhibitor therapy had a similar risk of discontinuation as on DPP4-inhibitor therapy. In contrast, strata predicted to have greater reduction in HbA1c with DPP4-inhibitor therapy were half as likely to discontinue DPP4-inhibitor therapy than SGLT2-inhibitor therapy.ConclusionsRoutinely measured clinical features are robustly associated with differential glycaemic responses to SGLT2-inhibitor and DPP4-inhibitor therapies. Combining features into a treatment selection algorithm can inform clinical decisions concerning optimal type 2 diabetes treatment choices.Key messagesWhat is already known on this subjectDespite there being multiple glucose-lowering treatment options available for people with type 2 diabetes, current guidelines do not provide clear advice on selecting the optimal treatment for most patients.It is unknown whether routinely measured clinical features modify the risks and benefits of two common treatment options, DPP4-inhibitor or SGLT2-inhibitor therapy, and which could be used to target these treatments to those patients most likely to benefit.What this study addsUsing data from 10,414 participants in 14 randomised trials, and 26,877 patients in UK primary care, we show several routinely available clinical features, notably glycated haemoglobin (HbA1c) and kidney function, are robustly associated with differential HbA1c responses to initiating SGLT2-inhibitor and DPP4-inhibitor therapies.Combining clinical features into a multivariable treatment selection model identifies validated patient strata with 1) a >5 mmol/mol HbA1c benefit for SGLT2-i therapy compared with DPP4-inhibitor therapy ; 2) a 50% reduced risk of early treatment discontinuation with DPP4-inhibitor therapy compared with SGLT2-inhibitor therapy.Our findings demonstrate a precision medicine approach based on routine clinical features can inform clinical decisions concerning optimal type 2 diabetes treatment choices.

INTRODUCTION Explicit motor sequence learning is impaired in Parkinson's disease (PD). Transcranial direct current stimulation (tDCS) applied over the motor cortex in healthy can improve explicit motor learning, but comparative effects in PD are unknown. This exploratory study aims to examine the effect of single session tDCS on explicit motor sequence learning in PD. METHODS Thirty-three people with mild to moderate PD learnt a short and long finger tapping sequence with their right hand. Participants received either anodal, cathodal, or sham tDCS applied over the left primary motor cortex during task practice. Single- and dual-task finger tapping performance was assessed before and after task practice and functional near-infrared spectroscopy used to measure task related changes of oxygenated haemoglobin. RESULTS Finger tapping performance of short and long sequences under single-task conditions significantly improved following practice (p = 0.010 and p

Among many mixed ionic electronic conductors (MIECs), lanthanum strontium cobalt iron oxide (LSCF) has been proven as a promising material for use as cathode in SOFCs. The ion and electron conduction in LSCF need to be studied separately. To measure the ionic conductivity of LSCF, YSZ disks were applied to block the electronic current, and multilayered samples were made with YSZ disks in series with an LSCF disk. Both AC and DC techniques were used for the measurements. An LSCF(porous)/LSCF(dense)/LSCF(porous) bar-shaped sample was made to measure the electronic conductivity of LSCF. DC technique was utilized for the measurement. Results show that the ionic conductivity of LSCF is much lower than its electronic conductivity. The ionic conductivity of LSCF increases with increasing temperature (600 °C–900 °C), and the electronic conductivity decreases with increasing temperature (600 °C–900 °C). Measurements were also made on a foil of silver to investigate oxygen transport through it. From this, oxygen ion conductivity through silver was estimated.

In this paper, results from comprehensive thermoeconomic assessments of small-scale solar organic Rankine cycle (ORC) systems are presented based on weather data in London, UK, which is taken as representative of a temperate climate with modest temperature changes, mild winters and moderate summers. The assessments consider a range of: (i) solar collector types (flat-plate, evacuated-tube, and evacuated flat-plate collectors); (ii) power cycle configurations (basic/recuperative, partial/full evaporating, and subcritical/transcritical cycles); (iii) expander types (scroll, screw, and piston) and designs; and (iv) a set of suitable working fluids. All possible solar-ORC system designs are optimised by considering simultaneously key parameters in the solar field and in the power cycle in order to obtain the highest electricity generation, from which the best-performing systems are identified. Selected designs are then subjected to detailed, annual simulations considering the systems’ operation, explicitly considering off-design performance under actual varying weather conditions. The results indicate that, among all investigated designs, solar-ORC systems based on the subcritical recuperative ORC (SRORC), evacuated flat-plate collectors (EFPCs), a piston expander, and isobutane as the working fluid outperforms all the other system designs on thermodynamic performance, whilst having the highest annual electricity generation of 1,100 kW·h/year (73 kW·h/year/m2) and an overall thermal efficiency of 5.5%. This system also leads to the best economic performance with a levelised cost of energy (LCOE) of ~1 $/kW·h. Apart from the specific weather data used for these detailed system simulations, this study also proceeds to consider a wider range of climates associated with other global regions by varying the solar resource available to the system. Interestingly, it is found that the optimal solar-ORC system design remains unchanged for different conditions, however, the LCOE can drop below 0.35 $/kW·h and payback times can be shorter than 16 years in high solar-resource regions, even in the absence of incentives that would otherwise lead to even better economic performance. This work complements previous efforts in the literature by considering the full design and operational features of solar-ORC systems, thereby providing valuable guidance for selecting appropriate cycle configurations, components, working fluids and other characteristics and, for the first time, presents a comprehensive comparison of such systems in small-scale applications.