The INNODIA Type 1 Diabetes Natural History Study: a European cohort of newly diagnosed children, adolescents and adults.

AIMS/HYPOTHESIS: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual's clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis. METHODS: Data were collected from the large INNODIA cohort of individuals (aged 1.0-45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10-17 years; and ≥18 years. RESULTS: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0-382.0) pmol/l (AUC 749.3 [466.2-1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001). CONCLUSIONS/INTERPRETATION: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline.

Clinical care advice for monitoring of islet autoantibody positive individuals with presymptomatic type 1 diabetes.

BACKGROUND/AIM: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta-cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody-positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. METHODS: Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow-up strategies. RESULTS: The guidance outlines recommended monitoring approaches based on age, disease stage and clinical setting. Individuals with presymptomatic type 1 diabetes are best followed up in specialist care. For stage 1, biannual assessments of random plasma glucose and HbA1c are suggested for children, while annual assessments are recommended for adolescents and adults. For stage 2, 3-monthly clinic visits with additional home monitoring are advised. The value of repeat OGTT in stage 1 and the use of continuous glucose monitoring in stage 2 are discussed. Primary care is encouraged to monitor individuals who decline specialist care, following the guidance presented. CONCLUSIONS: As type 1 diabetes screening programs become more prevalent, effective monitoring strategies are essential to mitigate the risk of complications such as DKA. This guidance serves as a valuable resource for clinicians, providing practical recommendations tailored to an individual's age and disease stage, both within specialist and primary care settings.

Oxygen limitation may affect the temperature and size dependence of metabolism in aquatic ectotherms.

Both oxygen and temperature are fundamental factors determining metabolic performance, fitness, ecological niches, and responses of many aquatic organisms to climate change. Despite the importance of physical and physiological constraints on oxygen supply affecting aerobic metabolism of aquatic ectotherms, ecological theories such as the metabolic theory of ecology have focused on the effects of temperature rather than oxygen. This gap currently impedes mechanistic models from accurately predicting metabolic rates (i.e., oxygen consumption rates) of aquatic organisms and restricts predictions to resting metabolism, which is less affected by oxygen limitation. Here, we expand on models of metabolic scaling by accounting for the role of oxygen availability and temperature on both resting and active metabolic rates. Our model predicts that oxygen limitation is more likely to constrain metabolism in larger, warmer, and active fish. Consequently, active metabolic rates are less responsive to temperature than are resting metabolic rates, and metabolism scales to body size with a smaller exponent whenever temperatures or activity levels are higher. Results from a metaanalysis of fish metabolic rates are consistent with our model predictions. The observed interactive effects of temperature, oxygen availability, and body size predict that global warming will limit the aerobic scope of aquatic ectotherms and may place a greater metabolic burden on larger individuals, impairing their physiological performance in the future. Our model reconciles the metabolic theory with empirical observations of oxygen limitation and provides a formal, quantitative framework for predicting both resting and active metabolic rate and hence aerobic scope of aquatic ectotherms.

Fifteen-minute consultation: Management of albuminuria in children and young people with diabetes.

Albuminuria is a marker of diabetic kidney disease. Raised albuminuria in children and young people with diabetes is associated with an increased risk of microvascular and macrovascular complications. This review provides guidance for paediatricians caring for children and young people with type 1 and type 2 diabetes on screening, investigations and treatments for albuminuria in line with relevant national and international recommendations.

A Generalized Physiologically Based Kinetic Model for Fish for Environmental Risk Assessment of Pharmaceuticals.

An increasing number of pharmaceuticals found in the environment potentially impose adverse effects on organisms such as fish. Physiologically based kinetic (PBK) models are essential risk assessment tools, allowing a mechanistic approach to understanding chemical effects within organisms. However, fish PBK models have been restricted to a few species, limiting the overall applicability given the countless species. Moreover, many pharmaceuticals are ionizable, and fish PBK models accounting for ionization are rare. Here, we developed a generalized PBK model, estimating required parameters as functions of fish and chemical properties. We assessed the model performance for five pharmaceuticals (covering neutral and ionic structures). With biotransformation half-lives (HLs) from EPI Suite, 73 and 41% of the time-course estimations were within a 10-fold and a 3-fold difference from measurements, respectively. The performance improved using experimental biotransformation HLs (87 and 59%, respectively). Estimations for ionizable substances were more accurate than any of the existing species-specific PBK models. The present study is the first to develop a generalized fish PBK model focusing on mechanism-based parameterization and explicitly accounting for ionization. Our generalized model facilitates its application across chemicals and species, improving efficiency for environmental risk assessment and supporting an animal-free toxicity testing paradigm.

Ibuprofen exposure in Europe; ePiE as an alternative to costly environmental monitoring.

The EU Water Framework Directive and Priority Substance Directive provide a framework to identify substances that potentially pose a risk to surface waters and provide a legal basis whereby member states are required to monitor and comply with environmental quality standards (EQSs) set for those substances. The cost and effort to continuously measure and analyse real world concentrations in all water bodies across Europe are high. Establishing the reliability of environmental exposure models to predict concentrations of priority substances is key, both to fill data gaps left by monitoring campaigns, and to predict the outcomes of actions that might be taken to reduce exposure. In this study, we aimed to validate the ePiE model for the pharmaceutical ibuprofen by comparing predictions made using the best possible consumption data with measured river concentrations. The results demonstrate that the ePiE model makes useful, conservative exposure predictions for ibuprofen, typically within a factor of 3 of mean measured values. This exercise was performed across a number of basins within Europe, representative of varying conditions, including consumption rates, population densities and climates. Incorporating specific information pertaining to the basin or country being assessed, such as custom WWTP removal rates, was found to improve the realism and accuracy of predictions. We found that the extrapolation of consumption data between countries should be kept to a minimum when modelling the exposure of pharmaceuticals, with the per capita consumption of ibuprofen varying by nearly a factor of 10.

Plants obey (and disobey) the island rule.

The island rule predicts that small animals evolve to become larger on islands, while large animals evolve to become smaller. It has been studied for over half a century, and its validity is fiercely debated. Here, we provide a perspective on the debate by conducting a test of the island rule in plants. Results from an extensive dataset on islands in the southwest Pacific illustrate that plant stature and leaf area obey the island rule, but seed size does not. Our results indicate that the island rule may be more pervasive than previously thought and that support for its predictions varies among functional traits.

Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants.

BACKGROUND: Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. RESULTS: Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions. CONCLUSIONS: Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.

Rewilding the Sea with Domesticated Seagrass.

It is well known that seagrass meadows sequester atmospheric carbon dioxide, protect coasts, provide nurseries for global fisheries, and enhance biodiversity. Large-scale restoration of lost seagrass meadows is urgently needed to revive these planetary ecosystem services, but sourcing donor material from natural meadows would further decline them. Therefore, we advocate the domestication and mariculture of seagrasses in order to produce the large quantities of seed needed for successful rewilding of the sea with seagrass meadows. We provide a roadmap for our proposed solution and show that 44% of seagrass species have promising reproductive traits for domestication and rewilding by seeds. The principle of partially domesticating species to enable subsequent large-scale rewilding may form a successful shortcut to restore threatened keystone species and their vital ecosystem services.

Internal and Maternal Distribution of Persistent Organic Pollutants in Sea Turtle Tissues: A Meta-Analysis.

We aimed to identify patterns in the internal distribution of persistent organic pollutants (POPs) and assess contributing factors using sea turtles and their offspring as a case study of a long-lived wildlife species. We systematically synthesized 40 years of data and developed a lipid database to test whether lipid-normalized POP concentrations are equal among tissues as expected under steady state for lipophilic compounds. Results supported equal partitioning among tissues with high blood flow or perfusion including the heart, kidney, muscle, and lung. Observed differences in the brain, fat, and blood plasma, however, suggest the physiological influence of the blood-brain barrier, limited perfusion, and protein content, respectively. Polybrominated diphenyl ethers partitioned comparably to legacy POPs. Polycyclic aromatic hydrocarbons, meanwhile, partitioned more into the lung, colon, and muscle compared to the liver under chronic and acute field exposure. Partitioning ratios of individual POPs among tissues were significantly related to the lipophilicity of compounds (as estimated by Kow) in half of the observed cases, and significant differences between juveniles and adults underscore physiological differences across life stages. The comprehensive tissue partitioning patterns presented here provide a quantitative basis to support comparative assessments of POP pollution derived from biomonitoring among multiple tissues.

Do initial concentration and activated sludge seasonality affect pharmaceutical biotransformation rate constants?

Pharmaceuticals find their way to the aquatic environment via wastewater treatment plants (WWTPs). Biotransformation plays an important role in mitigating environmental risks; however, a mechanistic understanding of involved processes is limited. The aim of this study was to evaluate potential relationships between first-order biotransformation rate constants (kb) of nine pharmaceuticals and initial concentration of the selected compounds, and sampling season of the used activated sludge inocula. Four-day bottle experiments were performed with activated sludge from WWTP Groesbeek (The Netherlands) of two different seasons, summer and winter, spiked with two environmentally relevant concentrations (3 and 30 nM) of pharmaceuticals. Concentrations of the compounds were measured by LC-MS/MS, microbial community composition was assessed by 16S rRNA gene amplicon sequencing, and kb values were calculated. The biodegradable pharmaceuticals were acetaminophen, metformin, metoprolol, terbutaline, and phenazone (ranked from high to low biotransformation rates). Carbamazepine, diatrizoic acid, diclofenac, and fluoxetine were not converted. Summer and winter inocula did not show significant differences in microbial community composition, but resulted in a slightly different kb for some pharmaceuticals. Likely microbial activity was responsible instead of community composition. In the same inoculum, different kb values were measured, depending on initial concentration. In general, biodegradable compounds had a higher kb when the initial concentration was higher. This demonstrates that Michealis-Menten kinetic theory has shortcomings for some pharmaceuticals at low, environmentally relevant concentrations and that the pharmaceutical concentration should be taken into account when measuring the kb in order to reliably predict the fate of pharmaceuticals in the WWTP. KEY POINTS: • Biotransformation and sorption of pharmaceuticals were assessed in activated sludge. • Higher initial concentrations resulted in higher biotransformation rate constants for biodegradable pharmaceuticals. • Summer and winter inocula produced slightly different biotransformation rate constants although microbial community composition did not significantly change.

Towards a systematic method for assessing the impact of chemical pollution on ecosystem services of water systems.

Chemical pollution impinges on the quality of water systems and the ecosystem services (ESs) they provide. Expression of ESs in monetary units has become an essential tool for sustainable ecosystem management. However, the impact of chemical pollution on ESs is rarely quantified, and ES valuation often focuses on individual services without considering the total services provided by the ecosystem. The purpose of the study was to develop a stepwise approach to quantify the impact of sediment pollution on the total ES value provided by water systems. Thereby, we calculated the total ES value loss as a function of the multi-substance potentially affected fraction of species at the HC50 level (msPAF(HC50)). The function is a combination of relationships between, subsequently: the msPAF(HC50), diversity, productivity and total ES value. Regardless of the inherent differences between terrestrial and aquatic ecosystems, an increase of diversity generally corresponded to an increase in productivity with curvilinear or linear effects. A positive correlation between productivity and total values of ESs of biomes was observed. The combined relationships showed that 1% msPAF(HC50) corresponded to on average 0.5% (0.05-1.40%) of total ES value loss. The ES loss due to polluted sediments in the Waal-Meuse river estuary (the Netherlands) and Flemish waterways (Belgium) was estimated to be 0.3-5 and 0.6-10 thousand 2007$/ha/yr, respectively. Our study presents a novel methodology to assess the impact of chemical exposure on diversity, productivity, and total value that ecosystems provide. With sufficient monitoring data, our generic methodology can be applied for any chemical and region of interest and help water managers make informed decisions on cost-effective measures to remedy pollution. Acknowledging that the ES loss estimates as a function of PAF(HC50) are crude, we explicitly discuss the uncertainties in each step for further development and application of the methodology.

Bioconcentration of Organotin Cations during Molting Inhibits Heterocypris incongruens Growth.

The densely populated North Sea region encompasses catchments of rivers such as Scheldt and Meuse. Herein, agricultural, industrial, and household chemicals are emitted, transported by water, and deposited in sediments, posing ecological risks. Though sediment monitoring is often costly and time-intensive, modeling its toxicity to biota has received little attention. Due to high complexity of interacting variables that induce overall toxicity, monitoring data only sporadically validates current models. Via a range of concepts, we related bio-physicochemical constituents of sediment in Flanders to results from toxicity bioassays performed on the ostracod Heterocypris incongruens. Depending on the water body, we explain up to 90% of the variance in H. incongruens growth. Though variable across Flanders' main water bodies, organotin cations and ammonia dominate the observed toxicity according to toxic unit (TU) assessments. Approximately 10% relates to testing conditions/setups, species variabilities, incoherently documented pollutant concentrations, and/or bio-physicochemical sediment properties. We elucidated the influence of organotin cations and ammonia relative to other metal(oxides) and biocides. Surprisingly, the tributylin cation appeared ∼1000 times more toxic to H. incongruens as compared to "single-substance" bioassays for similar species. We inferred indirect mixture effects between organotin, ammonia, and phosphate. Via chemical speciation calculations, we observed strong physicochemical and biological interactions between phosphate and organotin cations. These interactions enhance bioconcentration and explain the elevated toxicity of organotin cations. Our study aids water managers and policy makers to interpret monitoring data on a mechanistic basis. As sampled sediments differ, future modeling requires more emphasis on characterizing and parametrizing the interactions between bioassay constituents. We envision that this will aid in bridging the gap between testing in the laboratory and field observations.

Implications of Trophic Variability for Modeling Biomagnification of POPs in Marine Food Webs in the Svalbard Archipelago.

The occurrence of persistent organic pollutants (POPs) in the Arctic has been of constant concern, as these chemicals cause reproductive effects and mortality in organisms. The Arctic acts as a chemical sink, which makes this system an interesting case for bioaccumulation studies. However, as conducting empirical studies for all Arctic species and POPs individually is unfeasible, in silico methods have been developed. Existing bioaccumulation models are predominately validated for temperate food chains, and do not account for a large variation in trophic levels. This study applies Monte Carlo simulations to account for variability in trophic ecology on Svalbard when predicting bioaccumulation of POPs using the optimal modeling for ecotoxicological applications (OMEGA) bioaccumulation model. Trophic magnification factors (TMFs) were calculated accordingly. Comparing our model results with monitored POP residues in biota revealed that, on average, all predictions fell within a factor 6 of the monitored POP residues in biota. Trophic variability did not affect model performance tremendously, with up to a 25% variability in performance metrics. To our knowledge, we were the first to include trophic variability in predicting biomagnification in Arctic ecosystems using a mechanistic biomagnification model. However, considerable amounts of data are required to quantify the implications of trophic variability on biomagnification of POPs in Arctic food webs.

Proxy reporting of health-related quality of life for people with dementia: a psychometric solution.

BACKGROUND: The growing move towards personalised health and social care systems means that every effort needs to be made to generate patient-reported outcome data. However, the deteriorating nature of dementia can make it difficult for people with dementia to complete self-reported questionnaires and it is often necessary to rely on a family member (proxy) to report on their behalf. There is little evidence to guide how the difference between self- and proxy-reports of health reported quality of life (HRQL) in dementia can be interpreted. METHODS: We recruited people with dementia and their family carers from 78 memory Assessment Services in the UK. We used Rasch measurement methods to investigate whether a HRQL questionnaire known as DEMQOL (self-reported by the person with dementia) and DEMQOL-Proxy (proxy-reported by a family carer) can be placed on the same continuum and whether a revised scoring algorithm, based on this equated model, can be developed that takes account of the relationship between self- and proxy-reports. RESULTS: In a sample of 1434 patients and 1030 carers, our findings supported equating DEMQOL/DEMQOL-Proxy (overall fit to the model; no mis-fitting items) after addressing specific issues (eight disordered items requiring re-scoring, four pairs locally dependent items, and five items showing DIF). Cross walk tables have been produced. CONCLUSIONS: We have established for the first time that DEMQOL and DEMQOL-Proxy can be placed on the same continuum and that patients and carer proxies are reporting on the same construct when they complete these questionnaires. Where possible both DEMQOL and DEMQOL-Proxy should still be administered together, using the improved scoring algorithm reported here. Where only DEMQOL-Proxy is available, the cross walk tables provide an estimate of DEMQOL for a particular person from their DEMQOL-Proxy score.

Thermochemical unification of molecular descriptors to predict radical hydrogen abstraction with low computational cost.

Chemistry describes transformation of matter with reaction equations and corresponding rate constants. However, accurate rate constants are not always easy to get. Here we focus on radical oxidation reactions. Analysis of over 500 published rate constants of hydroxyl radicals led us to hypothesize that a modified linear free-energy relationship (LFER) could be used to predict rate constants speedily, reliably and accurately. LFERs correlate the Gibbs activation-energy with the Gibbs energy of reaction. We calculated the latter as the sum of one-electron transfer and, if appropriate, proton transfer. We parametrized specific transition state effects to orbital delocalizability and the polarity of the reactant. The calculation time for 500 reactions is less than 8 hours on a standard desktop-PC. Rate constants were also calculated for hydrogen and methyl radicals; these controls show that the predictions are applicable to a broader set of oxidizing radicals. An accuracy of 30-40% (standard deviation) with reference to reported experimental values was found suitable for the screening of complex chemical systems for possibly relevant reactions. In particular, potentially relevant reactions can be singled out and scrutinized in detail when prioritizing chemicals for environmental risk assessment.

Family-based social capital of emerging adults with and without mild intellectual disability.

BACKGROUND: Family is recognised as an important context for the self-development of young adults in emerging adulthood, although very little research has addressed the perspective of young people with intellectual disability about their families by using self-report. This study examined how emerging adults with mild intellectual disability define their family support networks, compared with definitions of students without intellectual disability, within a social capital theoretical framework. METHODS: Fifty-three participants with mild intellectual disability and 53 students without intellectual disability were interviewed individually using the Family Network Method - Intellectual Disability (FNM-ID). Data from the FNM-ID relate to key social network measures on how individuals define their family groups, and how they perceive existing supportive relationships within their families. Participants with mild intellectual disability and students were compared on the FNM-ID social network measures. RESULTS: Participants with mild intellectual disability reported fewer family members who they considered significant to them than students without intellectual disability. They were less likely to include peers (i.e. friends and partners) and siblings in their significant family networks, had fewer relationships with family members in which they received or gave support, had fewer reciprocal support relationships and had a less central position in their family network. DISCUSSION: The family-based social capital of emerging adults with mild intellectual disability differed from that of students without intellectual disability. They may remain more dependent on their natural family for emotional support as their supportive networks have not necessarily made the transition to networks with emotionally close peer relationships.

Comparing the genetic architecture of childhood behavioral problems across socioeconomic strata in the Netherlands and the United Kingdom.

Socioeconomic status (SES) affects the development of childhood behavioral problems. It has been frequently observed that children from low SES background tend to show more behavioral problems. There also is some evidence that SES has a moderating effect on the causes of individual differences in childhood behavioral problems, with lower heritability estimates and a stronger contribution of environmental factors in low SES groups. The aim of the present study was to examine whether the genetic architecture of childhood behavioral problems suggests the presence of protective and/or harmful effects across socioeconomic strata, in two countries with different levels of socioeconomic disparity: the Netherlands and the United Kingdom. We analyzed data from 7-year-old twins from the Netherlands Twin Register (N = 24,112 twins) and the Twins Early Development Study (N = 19,644 twins). The results revealed a nonlinear moderation effect of SES on the contribution of genetic and environmental factors to individual differences in childhood behavioral problems. The heritability was higher, the contribution of the shared environment was lower, and the contribution of the nonshared environment was higher, for children from high SES families, compared to children from low or medium SES families. The pattern was similar for Dutch and UK families. We discuss the importance of these findings for prevention and intervention goals.

Pre-procedural image-guided versus non-image-guided ventricular tachycardia ablation-a review.

BACKGROUND: Magnetic resonance imaging and computed tomography in patients with ventricular tachycardia (VT) after myocardial infarction (MI) helps to delineate scar from healthy tissue. Image-guided VT ablation has not yet been studied on a large scale. OBJECTIVE: The aim of the meta-analysis was to compare the long-term outcome of image-guided VT ablation with a conventional approach for VT after MI. METHODS: Eight electronic bibliographic databases were searched to identify all relevant studies from 2012 until 2018. The search for scientific literature was performed for studies that described the outcome of VT ablation in patients with an ischaemic substrate. The outcome of image-guided ablation was compared with the outcome of conventional ablations. RESULTS: Of the 2990 citations reviewed for eligibility, 38 articles-enrolling a total of 7748 patients-were included into the meta-analysis. Five articles included patients with image-guided ablation. VT-free survival was 82% [74-90] in the image-guided VT ablation versus 59% [54-64] in the conventional ablation group (p < 0.001) during a mean follow-up of 35 months. Overall survival was 94% [90-98] in the image-guided versus 82% [76-88] in the conventional VT ablation group (p < 0.001). CONCLUSIONS: Image-guided VT ablation in ischaemic VT was associated with a significant benefit in VT-free and overall survival as compared with conventional VT ablation. Visualising myocardial scar facilitates substrate-guided ablation procedures, pre-procedurally and by integrating imaging during the procedure, and may consequently improve long-term outcome.

DEMQOL and DEMQOL-Proxy: a Rasch analysis among those diagnosed with dementia.

BACKGROUND: In previous work we concluded that DEMQOL and DEMQOL-Proxy can provide robust measurement of HRQL in dementia when scores are derived from analysis using the Rasch model. As the study sample included people with mild cognitive impairment, we undertook a replication study in the subsample with a diagnosis of dementia (PWD). PWD constitute the population for whom DEMQOL and DEMQOL-Proxy were originally developed. METHODS: We conducted a Rasch model analysis using the RUMM2030 software to re-evaluate DEMQOL (441 PWD) and DEMQOL-Proxy (342 family carers). We evaluated scale to sample targeting, ordering of item thresholds, item fit to the model, and differential item functioning (sex, age, severity, relationship), local independence, unidimensionality and reliability. RESULTS: For both DEMQOL and DEMQOL-Proxy, results were highly similar to the results in the original sample. We found the same problems with content and response options. CONCLUSIONS: DEMQOL and DEMQOL-Proxy can provide robust measurement of HRQL in people with a diagnosis of dementia when scores are derived from analysis using the Rasch model. As in the wider sample, the problems identified with content and response options require qualitative investigation in order to improve the scoring of DEMQOL and DEMQOL-Proxy.