Search

Objective Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysis A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed.Results The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4+CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA−CCR7− T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes.Conclusion Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.

Abstract Vascular and neural structures of the retina can be visualized non-invasively and used to predict ocular and systemic pathologies. We set out to evaluate the association of hemoglobin (Hb) levels within the national reference interval with retinal vascular caliber, optical coherence tomography (OCT) and visual field (VF) parameters in the Northern Finland 1966 Birth Cohort (n = 2319, 42.1% male, average age 47 years). The studied parameters were evaluated in Hb quintiles and multivariable linear regression models. The lowest Hb quintile of both sexes presented the narrowest central retinal vein equivalent (CRVE) and the healthiest cardiometabolic profile compared to the other Hb quintiles. In the regression models, CRVE associated positively with Hb levels in both sexes, (B males = 0.068 [0.001; 0.135], B females = 0.087 [0.033; 0.140]), after being adjusted for key cardiometabolic and inflammatory parameters, smoking status, and fellow vessel caliber. No statistically significant associations of Hb levels with central retinal artery equivalent, OCT or VF parameters were detected. In conclusion, Hb levels were positively and specifically associated with CRVE, indicating that Hb levels are an independent factor affecting CRVE and the effect is in parallel with established risk factors for cardiometabolic diseases.

Abstract Acute myeloid leukemia (AML), a heterogeneous and aggressive blood cancer, does not respond well to single-drug therapy. A combination of drugs is required to effectively treat this disease. Computational models are critical for combination therapy discovery due to the tens of thousands of two-drug combinations, even with approved drugs. While predicting synergistic drugs is the focus of current methods, few consider drug efficacy and potential toxicity, which are crucial for treatment success. To find effective new drug candidates, we constructed a bipartite network using patient-derived tumor samples and drugs. The network is based on drug-response screening and summarizes all treatment response heterogeneity as drug response weights. This bipartite network is then projected onto the drug part, resulting in the drug similarity network. Distinct drug clusters were identified using community detection methods, each targeting different biological processes and pathways as revealed by enrichment and pathway analysis of the drugs’ protein targets. Four drugs with the highest efficacy and lowest toxicity from each cluster were selected and tested for drug sensitivity using cell viability assays on various samples. Results show that ruxolitinib-ulixertinib and sapanisertib-LY3009120 are the most effective combinations with the least toxicity and the best synergistic effect on blast cells. These findings lay the foundation for personalized and successful AML therapies, ultimately leading to the development of drug combinations that can be used alongside standard first-line AML treatment.

ABSTRACTOrphans are at higher risk of HIV infection and several important HIV risk factors than non-orphans; however, this may be due to a combination of related social, psychological, and economic factors, as well as care environment, rather than orphan status alone. Understanding these complex relationships may aid policy makers in supporting evidence-based, cost-effective programming for this vulnerable population. This longitudinal study uses a causal effect model to examine, through decomposition, the relationship between care environment and HIV risk factors in orphaned and separated adolescents and youths (OSAY) in Uasin Gishu County, Kenya; considering resilience, social, peer, or family support, volunteering, or having one's material needs met as potential mediators. We analysed survey responses from 1105 OSAY age 10–26 living in Charitable Children's Institutions (CCI) (orphanages) and family-based care settings (FBS). Follow-up time was 7–36 months. Care in CCIs (vs. FBS) was associated with a decreased likelihood of engaging in forced, exchange, and consensual sex. Excess relative risks (ERR) attributable to the indirect pathway, mediation, or interaction were not significant in any model. Care environment was not statistically associated with differences in substance use. Our findings support the direct, unmediated, association between institutional care and HIV risk factors.

Abstract Background The aim of this study was to evaluate how diagnostic practice in congenital ichthyoses has evolved during the years 2000–2020 and what kind of gene variants of congenital ichthyosis have been found. Methods The study cohort of this register‐based research consisted of a total of 88 patients, whose diagnostic testing was conducted, and ichthyosis diagnoses set at the Department of Dermatology and the Department of Clinical Genetics at Tampere University Hospital during the years 2000–2020. Results Diagnosis of ichthyosis was confirmed with genetic testing in 33 cases, and with conventional diagnostic methods, such as clinical findings, skin biopsy and family history of ichthyoses, in 55 cases. We observed four novel variants in patients with the clinical diagnoses of congenital ichthyoses. Conclusion When genetic testing became available, it was offered primarily to patients with severe forms of ichthyosis. During the study period next‐generation sequencing became the genetic testing method of choice providing new opportunities in diagnostics.

BackgroundBased on Finnish LDLR-founder variations, the prevalence of familial hypercholesterolemia (FH) in Finland is estimated to be at least 1:600. Patients with FH have increased risk of premature coronary artery disease (CAD) and thus the prevalence of FH is expected to be higher in this subgroup.ObjectiveTo assess the prevalence of monogenic FH in a Finnish cohort of patients with premature CAD and elevated low-density lipoprotein cholesterol (LDL-C) levels.MethodsAmong 28,295 patients undergoing angiography at Heart Hospital at Tampere University Hospital between 2007 and 2017, we identified 162 patients diagnosed with premature CAD (men aged

Atualmente os sistemas agroalimentares têm sido analisados em diversas perspetivas, tanto em termos da eficiência da utilização dos recursos naturais, como pela aplicação de boas práticas na produção de alimentos, a influência das mesmas ao nível da qualidade e segurança alimentar, como também ao nível da sustentabilidade. Contudo, há um elemento fundamental que muitas vezes é negligenciado nesse contexto, designadamente a Ética.

Abstract Rare or novel missense variants in large genes such as TTN and NEB are frequent in the general population, which hampers the interpretation of putative disease-causing biallelic variants in patients with sporadic neuromuscular disorders. Often, when the first initial genetic analysis is performed, the reconstructed haplotype, i.e. phasing information of the variants is missing. Segregation analysis increases the diagnostic turnaround time and is not always possible if samples from family members are lacking. To overcome this difficulty, we investigated how well the linked-read technology succeeded to phase variants in these large genes, and whether it improved the identification of structural variants. Linked-read sequencing data of nemaline myopathy, distal myopathy, and proximal myopathy patients were analyzed for phasing, single nucleotide variants, and structural variants. Variant phasing was successful in the large muscle genes studied. The longest continuous phase blocks were gained using high-quality DNA samples with long DNA fragments. Homozygosity increased the number of phase blocks, especially in exome sequencing samples lacking intronic variation. In our cohort, linked-read sequencing added more information about the structural variation but did not lead to a molecular genetic diagnosis. The linked-read technology can support the clinical diagnosis of neuromuscular and other genetic disorders.

Abstract The eye possesses a paravascular solute transport pathway that is driven by physiological pulsations, resembling the brain glymphatic pathway. We developed synchronous multimodal imaging tools aimed at measuring the driving pulsations of the human eye, using an eye-tracking functional eye camera (FEC) compatible with magnetic resonance imaging (MRI) for measuring eye surface pulsations. Special optics enabled integration of the FEC with MRI-compatible video ophthalmoscopy (MRcVO) for simultaneous retinal imaging along with functional eye MRI imaging (fMREye) of the BOLD (blood oxygen level dependent) contrast. Upon optimizing the fMREye parameters, we measured the power of the physiological (vasomotor, respiratory, and cardiac) eye and brain pulsations by fast Fourier transform (FFT) power analysis. The human eye pulsated in all three physiological pulse bands, most prominently in the respiratory band. The FFT power means of physiological pulsation for two adjacent slices was significantly higher than in one-slice scans (RESP1 vs. RESP2; df = 5, p = 0.045). FEC and MRcVO confirmed the respiratory pulsations at the eye surface and retina. We conclude that in addition to the known cardiovascular pulsation, the human eye also has respiratory and vasomotor pulsation mechanisms, which are now amenable to study using non-invasive multimodal imaging of eye fluidics.

Abstract Background The objectives of this study were to compare oral frailty (OFr) among edentate and dentate older adults living in long-term care facilities (LTCF) and to clarify how edentulism and oral disease burden (ODB) of dentate older adults are associated with OFr. Methods The population of this study comprised 94 edentate and 209 dentate residents in LTCF in Helsinki, Finland, who had previously participated in a nutritional study. The participants underwent a clinical oral examination. The dentate residents were further divided into three ODB groups based on asymptotic dental score. The edentate and different ODB groups were compared with each other regarding demographics and oral and medical findings. OFr was defined as ≥ 2 of following: having a diet of soft/pureed food, residue of food in the oral cavity, inability to keep the mouth open during examination, unclearness of speech, dry mouth. The association between OFr and edentulousness and various levels of ODB was analyzed by a multivariate logistic model. Results Participants with low ODB had significantly less OFr than their edentate peers (p = 0.009). Furthermore, the edentate and dentate with high ODB had similar odds for OFr. Conclusions Edentulousness and high ODB are equally harmful conditions and may predispose to OFr. This study suggests that maintaining healthy natural teeth and good oral health (low ODB) may protect against OFr. Trial registration The Ethics Committee of the Hospital District of Helsinki and Uusimaa approved the protocols for the nutritional status and oral healthcare studies and the merging of the data, including patient medical records (Register number HUS/968/2017).

This systematic literature review employs the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to investigate recent applications of explainable AI (XAI) over the past three years. From an initial pool of 664 articles identified through the Web of Science database, 512 peer-reviewed journal articles met the inclusion criteria—namely, being recent, high-quality XAI application articles published in English—and were analyzed in detail. Both qualitative and quantitative statistical techniques were used to analyze the identified articles: qualitatively by summarizing the characteristics of the included studies based on predefined codes, and quantitatively through statistical analysis of the data. These articles were categorized according to their application domains, techniques, and evaluation methods. Health-related applications were particularly prevalent, with a strong focus on cancer diagnosis, COVID-19 management, and medical imaging. Other significant areas of application included environmental and agricultural management, industrial optimization, cybersecurity, finance, transportation, and entertainment. Additionally, emerging applications in law, education, and social care highlight XAI’s expanding impact. The review reveals a predominant use of local explanation methods, particularly SHAP and LIME, with SHAP being favored for its stability and mathematical guarantees. However, a critical gap in the evaluation of XAI results is identified, as most studies rely on anecdotal evidence or expert opinion rather than robust quantitative metrics. This underscores the urgent need for standardized evaluation frameworks to ensure the reliability and effectiveness of XAI applications. Future research should focus on developing comprehensive evaluation standards and improving the interpretability and stability of explanations. These advancements are essential for addressing the diverse demands of various application domains while ensuring trust and transparency in AI systems.

Background/Objectives: Many older adults living in long-term care (LTC) environments have varying numbers of retained natural teeth. The objective of this study was to assess the disease findings based on tooth type and estimate the role of tooth types in occlusion. Methods: We conducted clinical oral examinations of 276 LTC residents. The disease findings were analyzed for each tooth type and to determine their associations with dementia. Results: In total, 67.8% of the participants had molar teeth. Premolars/canines were often present as residual roots and had caries. Deepened periodontal pockets and higher plaque index (PI) values for molars had odds ratios of 2.5 (95% confidence interval [CI] of 1.59–3.91) and 1.61 (95% CI of 1.29–2.02), respectively. Participants with dementia were more likely to have incisors and premolars/canines in the form of root remnants and higher PI scores for all tooth types (p ≤ 0.01), as well as more deepened periodontal pockets in all teeth (p = 0.029), than those without dementia. The median number of remaining molars per participant was 3 out of a maximum of 12 (95% CI 3.4–4.0); thus, they often lacked occlusal contact. Conclusions: The LTC residents’ molars were more prone to periodontal problems, whereas their premolars/canines often had caries or were present in the form of root remnants, especially in the participants with dementia. People’s teeth should be treated in an easy-to-maintain way before they move into LTC to enable daily oral hygiene measures and maintain oral health.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application of renewal of Limosilactobacillus fermentum NCIMB 30169 as a technological feed additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers, and the environment. Regarding user safety, the additive should be considered a skin and respiratory sensitiser. No conclusions can be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lentilactobacillus buchneri ATCC PTA‐6138 as a technological additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the additive should be considered as a skin and respiratory sensitiser. No conclusions could be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lentilactobacillus buchneri ATCC PTA‐2494 as a technological additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the Panel considers that any exposure through skin and respiratory tract is considered a risk. The Panel cannot conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of 6‐phytase (Quantum® Blue) as a zootechnical feed additive for fin fish. The additive is authorised for use in poultry and pigs. The additive is available in solid and liquid forms, and the 6‐phytase contained in the product is produced by fermentation with a genetically modified strain of Trichoderma reesei. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the genetic modification of the production strain does not give rise to safety concerns; viable cells of the production strain and its DNA were not detected in the final products. The FEEDAP Panel concluded that, based on the data available, the additive tested is safe for fin fish at the highest recommended level of 2500 phytase activity unit (FTU)/kg complete feed. The Panel concluded that Quantum® Blue is not an irritant to skin and eyes nor a skin sensitiser. Owing to the proteinaceous nature of the active substance, 6‐phytase (Quantum® Blue) is considered a respiratory sensitiser. The use of Quantum® Blue as a feed additive is considered safe for the environment. The additive is considered to be efficacious as a zootechnical additive for salmonids and ornamental fish at 500 FTU/kg complete feed and other fin fish at 2500 FTU/kg complete feed.

Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. Given that current treatments for advanced disease have shown limited efficacy, alternative therapies need to be identified. In rare diseases, patient-derived cell models are crucial for screening anti-tumour activity. In this study, cell line models were characterised in 2D and 3D cultures. The cell lines’ growth, migration and invasion capabilities were explored, confirming them as useful tools for preclinical angiosarcoma studies. By screening a drug library, we identified potentially effective compounds: 8-amino adenosine impacted cell growth and inhibited migration and invasion at considerably low concentrations as a single agent. No synergistic effect was detected when combining with paclitaxel, gemcitabine or doxorubicin. These results suggest that this compound could be a potentially useful drug in the treatment of AGS.

IntroductionThis was a secondary analysis aiming to assess whether hydrophilic or hydrophobic statins have a differential effect on urinary retention (UR) and lower urinary tract symptoms (LUTS) in men following a prostate biopsy (PBx), who were at risk for prostate cancer development.MethodsThis was a population-based cohort study with data incorporated from the Institute for Clinical and Evaluative Sciences database to identify all Ontarian men aged 66 and above with a history of a single negative PBx between 1994 and 2016, with no drug prescription history of any of several putative chemo-preventative medications (statins, proton pump inhibitors, five-alpha-reductase inhibitors, and alpha-blockers). Multivariable Cox regression models with time-dependent covariates were used to assess the association of hydrophilic and hydrophobic statins with UR and LUTS within 30 days of a PBx. All models were adjusted for other known putative chemopreventive medications, age, rurality, pharmacologically treated diabetes, comorbidity score, and study inclusion year.ResultsOverall, 21 512 men were included, with a median followup time of 9.4 years (interquartile range [IQR] 5.4-13.4 years). Hydrophobic and hydrophilic statins were initiated by 30.7% and 19.6% of men, respectively, after the first negative PBx. UR and LUTS were experienced by 2.2% and 10% of men, respectively. Cox models demonstrated hydrophilic statins were associated with a lower risk of UR (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.38-0.83, p=0.0038) and LUTS (HR 0.86, 95% CI 0.76-0.98, p=0.022), while no such association was shown for hydrophobic statins.ConclusionsInitiation of hydrophilic statins in men older than 66 appears to be inversely associated with the risk of UR and LUTS within 30 days of a PBx.

NASA's Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass density (AGBD). This paper presents the development of the models used to create GEDI's footprint-level (~25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI's waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available.

IntroductionDespite the association between cannabis use and higher prevalence of suicidal ideation and attempt, the effect of cannabis legalization and regulation in Canada on intentional self-harm has not been determined. MethodsWe used an interrupted time series of population-based rates of emergency department (ED) visits and hospitalizations for intentional self-harm per 100 000 in Ontario and Alberta from January/April 2010 to February 2020. Aggregate monthly counts of ED visits and hospitalizations for intentional self-harm (ICD-10 codes X60–X84, R45.8) were obtained from the National Ambulatory Care Reporting System and Discharge Abstract Database, respectively. ResultsThe legalization and regulation of cannabis in Canada was not significantly associated with a change in rates of ED visits for intentional self-harm in Ontario (level = 0.58, 95% CI: −1.14 to 2.31; trend = −0.17, 95% CI: −0.35 to 0.01) or Alberta (level = −0.06, 95% CI: −2.25 to 2.12; trend = −0.07, 95% CI: −0.27 to 0.13). Hospitalizations for intentional self-harm also remained unchanged in Ontario (level = −0.14, 95% CI: −0.48 to 0.20; trend = 0.01, 95% CI: −0.03 to 0.04) and Alberta (level = −0.41, 95% CI: −1.03 to 0.21; trend = −0.03, 95% CI: −0.08 to 0.03). ConclusionLegalization and regulation of cannabis in Canada has not increased rates of ED visits or hospitalizations for intentional self-harm in Ontario and Alberta. Individual-level analyses that account for demographic characteristics and include other provinces and territories are needed.

IntroductionMalgré l’association connue entre consommation de cannabis et prévalence accrue d’idées suicidaires et de tentatives de suicide, on n’a pas encore mesuré l’effet de la légalisation et de la réglementation du cannabis au Canada sur les lésions auto-infligées. MéthodologieNous avons utilisé des séries chronologiques interrompues des taux de consultation aux urgences et d’hospitalisation pour lésions auto-infligées pour 100 000 habitants en Ontario et en Alberta entre janvier ou avril 2010 et février 2020. Les effectifs mensuels globaux de consultations aux urgences et d’hospitalisations pour lésions auto-infligées (codes X60-X84 et R45.8 selon la CIM-10) ont été obtenus grâce respectivement au Système national d’information sur les soins ambulatoires et à la Base de données sur les congés des patients. RésultatsLa légalisation et la réglementation du cannabis au Canada n’ont pas été associées de manière statistiquement significative à une modification des taux de consultation aux urgences pour lésions auto-infligées en Ontario (niveau = 0,58 avec IC à 95 % : −1,14 à 2,31; tendance = −0,17 avec IC à 95 % : −0,35 à 0,01) ou en Alberta (niveau = −0,06 avec IC à 95 % : −2,25 à 2,12; tendance = −0,07 avec IC à 95 % : −0,27 à 0,13). Les hospitalisations pour lésions auto-infligées sont également demeurées inchangées en Ontario (niveau = −0,14 avec IC à 95 % : −0,48 à 0,20; tendance = 0,01 avec IC à 95 % : −0,03 à 0,04) et en Alberta (niveau = −0,41 avec IC à 95 % : −1,03 à 0,21; tendance = −0,03 avec IC à 95 % : −0,08 à 0,03). ConclusionLa légalisation et la réglementation du cannabis au Canada n’ont pas entraîné d’augmentation des taux de consultation aux urgences ou d’hospitalisation pour lésions auto-infligées en Ontario ou en Alberta. Des analyses à l’échelle individuelle tenant compte des caractéristiques individuelles et incluant d’autres provinces et territoires sont nécessaires.

Technology integration promises better quality in education. This integration is challenging to accomplish, especially for teachers in a developing country like Nigeria where the demand for education remains a struggle in the face of dwindling resources. The technological pedagogical content knowledge (TPACK) framework promotes designing strategies suitable for the teachers' needs. Therefore, in order to determine the readiness of the Nigerian teachers for technology integration, this study examines the Nigerian teacher educators' (N=136) TPACK and the relationship among the constructs using self-completion survey and partial least square techniques. The results reveal that among the seven knowledge constructs, the teachers' technological, pedagogical, and technological pedagogical knowledge are the most significant predictors of their TPACK. The theoretical and practical implications of the result are discussed thereafter.

Abstract Background Falls in long-term care are common. The aim of our study was to explore how medication use is associated with incidence of falls, related consequences, and all-cause mortality among long-term care residents. Methods Five hundred thirty two long-term care residents aged 65 years or older participated in this longitudinal cohort study in 2018–2021. Data on medication use were retrieved from medical records. Polypharmacy was defined as use of 5–10 medications and excessive polypharmacy as use of > 10 medications. The numbers of falls, injuries, fractures, and hospitalizations were collected from medical records over 12 months following baseline assessment. Participants were followed for three years for mortality. All analysis were adjusted for age, sex, Charlson Comorbidity Index, Clinical dementia rating, and mobility. Results A total of 606 falls occurred during the follow-up. Falls increased significantly with the number of medications used. Fall rate was 0.84/person-years (pyrs) (95% CI 0.56 to 1.13) for the non-polypharmacy group, 1.13/pyrs (95% CI 1.01 to 1.26) for the polypharmacy group, and 1.84/pyrs (95% CI 1.60 to 2.09) for the excessive polypharmacy group. Incidence rate ratio for falls was 1.73 (95% CI 1.44 to 2.10) for opioids, 1.48 (95% CI 1.23 to 1.78) for anticholinergic medication, 0.93 (95% CI 0.70 to 1.25) for psychotropics, and 0.91 (95% CI 0.77 to 1.08) for Alzheimer medication. The three-year follow-up showed significant differences in mortality between the groups, the lowest survival rate (25%) being in the excessive polypharmacy group. Conclusion Polypharmacy, opioid and anticholinergic medication use predicted incidence of falls in long-term care. The use of more than 10 medications predicted all-cause mortality. Special attention should be paid to both number and type of medications when prescribing in long-term care.

Remotely sensed data are frequently used for predicting and mapping ecosystem characteristics, and spatially explicit wall-to-wall information is sometimes proposed as the best possible source of information for decision-making. However, wall-to-wall information typically relies on model-based prediction, and several features of model-based prediction should be understood before extensively relying on this type of information. One such feature is that model-based predictors can be considered both unbiased and biased at the same time, which has important implications in several areas of application. In this discussion paper, we first describe the conventional model-unbiasedness paradigm that underpins most prediction techniques using remotely sensed (or other) auxiliary data. From this point of view, model-based predictors are typically unbiased. Secondly, we show that for specific domains, identified based on their true values, the same model-based predictors can be considered biased, and sometimes severely so.We suggest distinguishing between conventional model-bias, defined in the statistical literature as the difference between the expected value of a predictor and the expected value of the quantity being predicted, and design-bias of model-based estimators, defined as the difference between the expected value of a model-based estimator and the true value of the quantity being predicted. We show that model-based estimators (or predictors) are typically design-biased, and that there is a trend in the design-bias from overestimating small true values to underestimating large true values. Further, we give examples of applications where this is important to acknowledge and to potentially make adjustments to correct for the design-bias trend. We argue that relying entirely on conventional model-unbiasedness may lead to mistakes in several areas of application that use predictions from remotely sensed data.