Diagnostic accuracy of the Brief Assessment of Impaired Cognition case-finding instrument in a general practice setting and comparison with other widely used brief cognitive tests-a cross-validation study.

BACKGROUND AND PURPOSE: The aim of this study was to examine the discriminative validity of the Brief Assessment of Impaired Cognition (BASIC) case-finding instrument in a general practice (GP) setting and compare it with other widely used brief cognitive instruments. METHODS: Patients aged ≥70 years were prospectively recruited from 14 Danish GP clinics. Participants were classified as having either normal cognition (n = 154) or cognitive impairment (n = 101) based on neuropsychological test performance, reported instrumental activities of daily living, and concern regarding memory decline. Comparisons involved the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Rowland Universal Dementia Assessment Scale (RUDAS), the Mini-Cog, the 6-item Clock Drawing Test (CDT-6) and the BASIC Questionnaire (BASIC-Q). RESULTS: BASIC demonstrated good overall classification accuracy with an area under the receiver operating characteristic curve (AUC) of 0.88 (95% confidence interval [CI] 0.84-0.92), a sensitivity of 0.72 (95% CI 0.62-0.80) and a specificity of 0.86 (95% CI 0.79-0.91). Pairwise comparisons of the AUCs of BASIC, MMSE, MoCA and RUDAS produced non-significant results, but BASIC had significantly higher classification accuracy than Mini-Cog, BASIC-Q and CDT-6. Depending on the pretest probability of cognitive impairment, the positive predictive validity of BASIC varied from 0.83 to 0.36, and the negative predictive validity from 0.97 to 0.76. CONCLUSIONS: BASIC demonstrated good discriminative validity in a GP setting. The classification accuracy of BASIC is equivalent to more complex, time-consuming instruments, such as the MMSE, MoCA and RUDAS, and higher than very brief instruments, such as the CDT-6, Mini-Cog and BASIC-Q.

Diagnostic accuracy of BASIC-Q for detection of cognitive impairment in a primary care setting - a cross-validation study.

OBJECTIVES: This study aims to evaluate the diagnostic accuracy and reliability of a new, brief questionnaire, 'Brief Assessment of Impaired Cognition- Questionnaire' (BASIC-Q) for detection of cognitive impairment, primarily developed for use in primary care. BASIC-Q has three components: Self-report, Informant report, and Orientation. Self-report and Orientation are completed by the individual and Informant report is answered by a close relative. METHODS: We included 275 participants ≥ 70 years, without a prior diagnosis of dementia, and with a close relative who agreed to participate as an informant. Participants were included prospectively in 14 general practices in urban and rural Denmark using a convenience sampling method. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the informant-completed Functional Activities Questionnaire (FAQ) and reported memory concern were used as a reference standard for the classification of the participants' cognitive function. RESULTS: BASIC-Q demonstrated a fair to good diagnostic accuracy to differentiate between people with cognitive impairment and normal cognition with an area under the ROC curve (AUC) of 0.84 (95% CI 0.79-0.89) and a sensitivity and specificity of 0.80 (95% CI 0.72-0.87) and 0.71 (95% CI 0.63-0.78). A prorated BASIC-Q score derived from BASIC-Q without Informant report had significantly lower classification accuracy than the full BASIC-Q. The test-retest reliability of BASIC-Q was good with an intraclass correlation coefficient of 0.84. CONCLUSION: BASIC-Q is a brief, easy-to-use questionnaire for identification of cognitive impairment in older adults. It demonstrated fair to good classification accuracy in a general practice setting and can be a useful case-finding tool when suspecting dementia in primary health care.

The copenhagen cross-linguistic naming test (C-CLNT): Development and validation in a multicultural memory clinic population.

OBJECTIVE: Despite recent advances in cross-cultural neuropsychological test development, suitable tests for cross-linguistic assessment of language functions are not widely available. The aims of this study were to develop and validate a brief naming test, the Copenhagen Cross-Linguistic Naming Test (C-CLNT), for the assessment of culturally, linguistically, and educationally diverse older adult populations in Europe. METHOD: The C-CLNT was based on a set of standardized color drawings. Items for the C-CLNT were selected by considering name agreement and frequency across five European and two non-European languages. Ambiguities in some of the selected items and scoring criteria were resolved after pilot testing in 10 memory clinic patients. The final 30-item C-CLNT was validated by verifying its psychometric properties in 24 controls and 162 diverse memory clinic patients with affective disorder, mild cognitive impairment, and with dementia. RESULTS: The C-CLNT had acceptable scale reliability (coefficient alpha = .67) and good construct validity, with moderate to strong correlations with traditional language tests (r = .42- .75). Diagnostic accuracy for dementia was good and significantly better than that of the Boston Naming Test (areas under the curve of .80 vs .64, p < .001), but was poor for mild cognitive impairment. Only 3% of the variance in C-CLNT test scores was explained by immigrant background, while 6% was explained by age and years of education. In comparison, these proportions were 34 and 22% for the BNT. CONCLUSIONS: The C-CLNT has promising clinical utility for cross-linguistic assessment of naming impairment in culturally, linguistically, and educationally diverse older adults.

Do normative data specific to Greek Australian older adults improve validity of neuropsychological assessment results?

OBJECTIVE: This study aimed to compare Greek Australian and English language normative data with regard to impairment rates yielded within a healthy Greek Australian older adult sample. We also examined whether optimal cut scores could be identified and capable of sensitively and specifically distinguishing between healthy Greek Australians from those with a diagnosis of Alzheimer's disease (AD). METHOD: Ninety healthy Greek Australian older adults and 20 demographically matched individuals with a diagnosis of AD completed a range of neuropsychological measures, including the Wechsler Adult Intelligence Scale-Fourth Edition, Greek Adaptation (WAIS-IV GR), verbal and visual memory, language and naming, and executive functions. Impairment rates derived from the use of either Greek Australian or English language normative data were calculated and compared, using a 1.5 standard deviation criterion to denote impairment. Receiver operating characteristics curve analysis was used to investigate the sensitivity and specificity of alternate cut scores. RESULTS: Impairment rates derived from the Greek Australian normative data showed that rates of impairment generally fell within the expected 7% range. In contrast, impairment rates for all tests derived using English language normative data were significantly higher and ranged from 11%-66%. Comparisons between healthy and AD participants with moderate dementia showed significant differences across all measures. Area under the curve results ranged from .721 to .999 across all measures, with most tests displaying excellent sensitivity and specificity. CONCLUSIONS: English language normative data were found to be inappropriate for use with Greek Australian elders, potentially leading to erroneous diagnostic outcomes. The use of minority group specific normative data and associated cut points appear to partially ameliorate this issue. Clinical implications are discussed alongside future research directions.

Potential for prevention of dementia in Denmark.

INTRODUCTION: According to previous estimates, 40% of dementia cases globally may be attributed to 12 potentially modifiable risk factors. METHODS: We calculated national population attributable fractions (PAFs) for each risk factor and modeled the effects of proportional reductions in risk factor prevalence on dementia prevalence by calculating potential impact fractions (PIFs) for each factor. RESULTS: The overall adjusted PAF for all risk factors was 35.2%. Physical inactivity, hearing loss, hypertension, and obesity accounted for 64% of the total prevention potential. The overall adjusted PIF was 4.1% at 10% risk factor prevalence reduction and 8.1% at 20% risk factor reduction. DISCUSSION: Estimates of the potential for the prevention of dementia should be based on country-specific data on risk factor prevalence, as estimates based on global risk factor prevalence have limited relevance from a national perspective. Physical inactivity, hearing loss, hypertension, and obesity could be primary targets for prevention of dementia in Denmark. HIGHLIGHTS: Overall adjusted PAF for potentially modifiable dementia risk factors was 35%. Physical inactivity, hearing loss, hypertension, and obesity had the largest prevention potential. Estimates of prevention potential should be based on national risk factor prevalence.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Cognitive assessment of literacy learning difficulties in adult non- or low-literate second language learners.

The population of non- or low-literate adult immigrants studying a new language is large and growing in many countries. The aim of this study was to develop and validate a new instrument for the assessment of cognitive impairment that may hinder literacy learning in adult non- or low-literate L2 learners, the Cognitive Assessment of Literacy Learning Difficulties (CALL), in a language center setting. This was a case-control study in which the CALL was validated in adult non- or low-literate students, or students who were not literate in the Latin alphabet, in nine Danish language centers. Educator classification of students with very slow progression in learning basic Danish literacy was used as a benchmark for literacy learning difficulties. Classification was further based on the number of lessons participants had required to pass tests during Danish language program levels. An acceptable discriminative validity (AUC 0.76; specificity 0.94, sensitivity 0.64) for literacy learning difficulties (n = 32) versus schooling and sex matched control participants (n = 28) was found. In comparison, years of formal schooling had an AUC of 0.58. Age had a small effect on the ability of the CALL to predict literacy learning difficulties (OR = 1.097, p = 0.013), whereas sex and years of schooling did not. CALL was found to be a valid instrument for identification of cognitive impairment that may hinder literacy learning in adult non- or low-literate L2 learners in a Danish language center setting.

Danish Prostate Registry (DanProst) - an Updated Version of the Danish Prostate Cancer Registry, Methodology, and Early Results.

In 2016, we introduced the Danish Prostate Cancer Registry (DaPCaR) which was built on the National Pathology Register from 1995 to 2011. DaPCaR was laborious to use as most data had to be manually imputed with no regular updates. In here we present a new comprehensive centralized prostate registry called the Danish Prostate Registry (DanProst), which includes all men having undergone any histological evaluation of prostate tissue merged with laboratory-, treatment-, prescription data as well as vital status. Here the data included and the methodology of DanProst are described. DanProst is built upon all men with a histological assessment of the prostate from the Danish National Registry for Pathology. The primary histology and potential prostate cancer histological diagnosis for each unique individual is extracted and translated by newly made algorithms for topography, procedure, diagnostic conclusion, and pathological staging. Further information is added from DaPCaR, the CPR Registry, the Danish Cause of Death Registry, the Danish Cancer Registry, the National Patient Registry, the Danish Register of Laboratory Results for Research, and the Danish National Prescription Registry. The translation algorithms were validated based on the comparison with DaPCaR in the period 2010-2016. DanProst includes 190,422 men. A total of 95,152 (50%) men are diagnosed with prostate cancer until 2021. Median diagnostic PSA was 11 ng/ml, most men are diagnosed by ultrasound-guided biopsy (N = 63,751; 67%), and most frequently defined primary treatment was radical prostatectomy (N = 14,778; 19%). DanProst to DaPCaR coherency was > 99%, 95%, and 94% for the primary histological procedure, primary histological conclusion, and diagnostic histological conclusion, respectively. DanProst is a continuously updated, centrally kept, validated registry with automatic integration of data from other national registries, allowing for contemporary nationwide analysis in men with histological assessment of the prostate.

Feasibility of a culturally tailored dementia information program for minority ethnic communities in Denmark.

OBJECTIVES: Proactive efforts that take language and cultural barriers into consideration may be needed to raise awareness of dementia and improve access to services in minority ethnic communities. The aim of this study was to assess the feasibility of a culturally tailored dementia information program and the immediate effects on participants' intention to seek help for memory problems, their knowledge and beliefs about dementia, and their knowledge about options for support. METHODS: A novel dementia information program, consisting of one 2-h session, was developed through a collaborative research process with primary care dementia coordinators and multicultural link workers as co-researchers. It provides basic knowledge about dementia to minority ethnic communities and can be delivered in a community setting by non-specialists. RESULTS: Six information program sessions were conducted with a total of 110 participants; 65 Turkish, 19 Pakistani, 20 Arabic-speaking, and 6 with another minority ethnic heritage. The program had a significant effect on participants' immediate knowledge and beliefs about dementia as measured with a quiz (z = -2.02, p = 0.04, d = 0.90). In a post-program focus group meeting, facilitating multicultural link workers reported satisfaction with facilitator training, adopted recruitment strategies, and content and delivery of the information sessions and provided feedback on improving the program. CONCLUSIONS: The results provide support for the feasibility of the culturally tailored dementia information program. The program has the potential to improve knowledge and beliefs about dementia and options for formal support in minority ethnic communities and seems easily implemented in existing services, and at a low cost.

European Academy of Neurology/European Alzheimer's Disease Consortium position statement on diagnostic disclosure, biomarker counseling, and management of patients with mild cognitive impairment.

BACKGROUND AND PURPOSE: Careful counseling through the diagnostic process and adequate postdiagnostic support in patients with mild cognitive impairment (MCI) is important. Previous studies have indicated heterogeneity in practice and the need for guidance for clinicians. METHODS: A joint European Academy of Neurology/European Alzheimer's Disease Consortium panel of dementia specialists was appointed. Through online meetings and emails, positions were developed regarding disclosing a syndrome diagnosis of MCI, pre- and postbiomarker sampling counseling, and postdiagnostic support. RESULTS: Prior to diagnostic evaluation, motives and wishes of the patient should be sought. Diagnostic disclosure should be carried out by a dementia specialist taking the ethical principles of "the right to know" versus "the wish not to know" into account. Disclosure should be accompanied by written information and a follow-up plan. It should be made clear that MCI is not dementia. Prebiomarker counseling should always be carried out if biomarker sampling is considered and postbiomarker counseling if sampling is carried out. A dementia specialist knowledgeable about biomarkers should inform about pros and cons, including alternatives, to enable an autonomous and informed decision. Postbiomarker counseling will depend in part on the results of biomarkers. Follow-up should be considered for all patients with MCI and include brain-healthy advice and possibly treatment for specific underlying causes. Advice on advance directives may be relevant. CONCLUSIONS: Guidance to clinicians on various aspects of the diagnostic process in patients with MCI is presented here as position statements. Further studies are needed to enable more evidence-based and standardized recommendations in the future.

Barriers in access to dementia care in minority ethnic groups in Denmark: a qualitative study.

OBJECTIVES: To explore barriers in access to dementia care in Turkish, Pakistani and Arabic speaking minority ethnic groups in Denmark. METHOD: Semi-structured qualitative individual- and group interviews with minority ethnic family carers, primary care dementia coordinators, staff in elderly daycare, and multicultural link workers. Hermeneutic phenomenology was used as theoretical framework. RESULTS: A total of 21 individual- and 6 group interviews were conducted, including a total of 35 participants. On the service user side, barriers in access to dementia care were related to lacking language proficiency and strong cultural norms, including familial responsibility for the care of older family members and stigma associated with mental illness and dementia. On the care provider side, the available formal services were rarely tailored to the specific needs of minority ethnic service users and were often considered inadequate or unacceptable. CONCLUSION: Care practices and perceived consequences of dementia in minority ethnic communities were heavily influenced by cultural factors leading to a number of persisting barriers to accessing dementia care services. There is a simultaneous need to raise awareness about dementia and the existence of dementia care services in minority ethnic groups, to reduce stigma, and to develop culturally appropriate dementia care options.

Efficacy and safety of topical delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study.

BACKGROUND: Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids. OBJECTIVES: To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE. METHODS: In this randomized, double-blind, phase IIa study, patients with CHE received delgocitinib ointment 30 mg g-1 or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA). RESULTS: Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4·89, 95% confidence interval (CI) 1·49-16·09; P = 0·009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13·0) than with vehicle (25·8) (adjusted mean difference -12·88, 95% CI -21·47 to -4·30; P = 0·003). More patients receiving delgocitinib than vehicle achieved treatment success by PaGA, but this did not reach statistical significance. The incidence of adverse events was similar with delgocitinib and vehicle; none led to discontinuation of delgocitinib. CONCLUSIONS: Delgocitinib ointment was efficacious and well tolerated. As a plateau of efficacy was not observed, a longer treatment period may lead to increased efficacy. Further clinical studies are warranted to confirm these findings in patients with CHE. What's already known about this topic? Chronic hand eczema (CHE) has a significant burden. Few randomized controlled studies have evaluated current treatments for CHE; only limited data are available to inform and guide clinical practice decisions. There is currently an unmet need for efficacious and well-tolerated topical treatment options for patients with CHE. What does this study add? Delgocitinib is a novel, pan-Janus kinase (JAK) inhibitor specific for JAK1, JAK2, JAK3 and tyrosine kinase 2. Topical use of delgocitinib ointment resulted in clearance of CHE after 8 weeks of treatment in a significantly greater number of patients than vehicle; delgocitinib was also well tolerated. Results from this proof-of-concept clinical study suggest that topical delgocitinib may provide therapeutic benefit to patients with CHE with inadequate responses to topical corticosteroids.

A Systematic Review of Neuropsychological Tests for the Assessment of Dementia in Non-Western, Low-Educated or Illiterate Populations.

OBJECTIVE: Neuropsychological tests are important instruments to determine a cognitive profile, giving insight into the etiology of dementia; however, these tests cannot readily be used in culturally diverse, low-educated populations, due to their dependence upon (Western) culture, education, and literacy. In this review we aim to give an overview of studies investigating domain-specific cognitive tests used to assess dementia in non-Western, low-educated populations. The second aim was to examine the quality of these studies and of the adaptations for culturally, linguistically, and educationally diverse populations. METHOD: A systematic review was performed using six databases, without restrictions on the year or language of publication. RESULTS: Forty-four studies were included, stemming mainly from Brazil, Hong Kong, Korea, and considering Hispanics/Latinos residing in the USA. Most studies focused on Alzheimer's disease (n = 17) or unspecified dementia (n = 16). Memory (n = 18) was studied most often, using 14 different tests. The traditional Western tests in the domains of attention (n = 8) and construction (n = 15), were unsuitable for low-educated patients. There was little variety in instruments measuring executive functioning (two tests, n = 13), and language (n = 12, of which 10 were naming tests). Many studies did not report a thorough adaptation procedure (n = 39) or blinding procedures (n = 29). CONCLUSIONS: Various formats of memory tests seem suitable for low-educated, non-Western populations. Promising tasks in other cognitive domains are the Stick Design Test, Five Digit Test, and verbal fluency test. Further research is needed regarding cross-cultural instruments measuring executive functioning and language in low-educated people.

Brief Assessment of Impaired Cognition Questionnaire (BASIC-Q)-Development and validation of a new tool for identification of cognitive impairment in community settings.

OBJECTIVES: Brief Assessment of Impaired Cognition (BASIC), which combines self- and informant report with cognitive testing, was previously found to be highly accurate in identification of dementia and cognitive impairment. The aim of the present study was to develop and validate a questionnaire version of BASIC, the BASIC-Q, for use in community settings. METHODS: In order to construct a questionnaire version of BASIC, we substituted cognitive testing with questions regarding orientation. BASIC-Q was validated based on further analysis of data from the primary BASIC validation study, where patients consecutively referred from general practice were tested at their first memory clinic admission prior to diagnosis. Control participants were primarily recruited among participating patients' relatives. Expert clinical diagnosis was subsequently used as reference standard for estimation of classification accuracy. RESULTS: A high discriminative validity (sensitivity 0.92, specificity 0.97) for cognitive impairment (n = 159) vs socio-demographically matched control participants (n = 109) was found. In comparison, the MMSE had 0.76 sensitivity and 0.81 specificity. Administration time for BASIC-Q was less than 5 minutes compared to approximately 10 minutes for the MMSE. CONCLUSIONS: BASIC-Q is a brief, efficient and valid tool for identification of cognitive impairment in a clinical setting. Further validation in a community setting is needed.

Cross-cultural dementia screening using the Rowland Universal Dementia Assessment Scale: a systematic review and meta-analysis.

OBJECTIVES: To quantitatively synthesize data on the accuracy of the Rowland Universal Dementia Assessment Scale (RUDAS) in different sociocultural settings and compare its performance to other brief screening instruments for the detection of dementia. DESIGN: Systematic review and meta-analysis. Literature searches were performed in PubMed, EMBASE, and CINAHL from January 1, 2004 until September 1, 2019. SETTING: Community, outpatient clinic, and hospital settings in high-, and low- and middle-income countries. PARTICIPANTS: Twenty-six studies reporting diagnostic accuracy of the RUDAS were included with almost 4000 participants, including approximately 1700 patients with dementia. MEASUREMENTS: Procedures for translation and cultural adaption of the RUDAS, and influence of demographic variables on diagnostic accuracy, were compared across studies. Bivariate random-effects models were used to pool sensitivity and specificity results, and diagnostic odds-ratios and the area under the hierarchical summary receiver operator characteristic curve were used to present the overall performance. RESULTS: The pooled sensitivity and specificity for the detection of dementia were .82 (95% CI, .78-.86) and .83 (95% CI, .78-.87), respectively, with an area under the curve of .89. Subgroup analyses revealed that the RUDAS had comparable diagnostic performances across high-, and low- and middle-income settings (z = .63, P = .53) and in samples with a lower and higher proportion of participants with no formal education (z = -.15, P = .88). In 11 studies making direct comparison, the diagnostic performance of the RUDAS was comparable to that of the Mini-Mental State Examination (z = -.82, P = .41), with areas under the curve of .88 and .84, respectively. CONCLUSIONS: The RUDAS has good diagnostic performance for detecting dementia in different sociocultural settings. Compared to other brief screening instruments, advantages of the RUDAS include its limited bias in people with limited or no formal education and a minimal need for cultural or language adaptation.

Quantitative trait loci (QTL) associated with resistance of rainbow trout Oncorhynchus mykiss against the parasitic ciliate Ichthyophthirius multifiliis.

The parasitic ciliate Ichthyophthirius multifiliis has a low host specificity eliciting white spot disease (WSD) in a wide range of freshwater fishes worldwide. The parasite multiplies rapidly whereby the infection may reach problematic levels in a host population within a few days. The parasite targets both wild and cultured fish but the huge economic impact of the protozoan is associated with mortality, morbidity and treatment in aquacultural enterprises. We have investigated the potential for genetic selection of WSD-resistant strains of rainbow trout. Applying the DNA typing system Affymetrix® and characterizing the genome of the individual fish by use of 57,501 single nucleotide polymorphisms (SNP) and their location on the rainbow trout chromosomes, we have genetically characterized rainbow trout with different levels of natural resistance towards WSD. Quantitative trait loci (QTL) used for the selection of breeders with specific markers for resistance are reported. We found a significant association between resistance towards I. multifiliis infection and SNP markers located on the two specific rainbow trout chromosomes Omy 16 and Omy 17. Comparing the expression of immune-related genes in fish-with and without clinical signs-we recorded no significant difference. However, trout surviving the infection showed high expression levels of genes encoding IgT, T-cell receptor TCRß, C3, cathelicidins 1 and 2 and SAA, suggesting these genes to be associated with protection.

Integrated model predictive control of water resource recovery facilities and sewer systems in a smart grid: example of full-scale implementation in Kolding.

An integrated model predictive control (MPC) strategy to control the power consumption and the effluent quality of a water resource recovery facility (WRRF) by utilizing the storage capacity from the sewer system was implemented and put into operation for a 7-day trial period. This price-based MPC reacted to electricity prices and forecasted pollutant loads 24 hours ahead. The large storage capacity available in the sewer system directly upstream from the plant was used to control the incoming loads and, indirectly, the power consumption of the WRRF during dry weather operations. The MPC balances electricity costs and treatment quality based on linear dynamical models and predictions of storage capacity and effluent concentrations. This article first shows the modelling results involved in the design of this MPC. Secondly, results from full-scale MPC operation of the WRRF are shown. The monetary savings of the MPC strategy for the specific plant were quantified around approximately 200 DKK per day when fully exploiting the allowed storage capacity. The developed MPC strategy provides a new option for linking WRRFs to smart grid electricity systems.

Scoring of tumor-infiltrating lymphocytes: From visual estimation to machine learning.

The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other biomarkers, has been demonstrated to be a marker of response to immune-checkpoint therapy in several cancers. Pathologists have therefore started to devise standardized visual approaches to quantify TILs for therapy prediction. However, despite successful standardization efforts visual TIL estimation is slow, with limited precision and lacks the ability to evaluate more complex properties such as TIL distribution patterns. Therefore, computational image analysis approaches are needed to provide standardized and efficient TIL quantification. Here, we discuss different automated TIL scoring approaches ranging from classical image segmentation, where cell boundaries are identified and the resulting objects classified according to shape properties, to machine learning-based approaches that directly classify cells without segmentation but rely on large amounts of training data. In contrast to conventional machine learning (ML) approaches that are often criticized for their "black-box" characteristics, we also discuss explainable machine learning. Such approaches render ML results interpretable and explain the computational decision-making process through high-resolution heatmaps that highlight TILs and cancer cells and therefore allow for quantification and plausibility checks in biomedical research and diagnostics.

Associations between maternal socioeconomic position and psoriasis: a cohort study among the offspring of the Danish National Birth Cohort.

BACKGROUND: The socioeconomic determinants of paediatric-onset psoriasis have not been previously investigated. OBJECTIVE: To identify whether a social gradient exists for paediatric-onset psoriasis, using measures of maternal socioeconomic position. METHODS: Data on paediatric-onset psoriasis from 36 003 Danish National Birth Cohort offspring were cross-linked with nationwide registry data on maternal age and three measures of maternal socioeconomic position: maternal educational attainment, maternal labour market attachment and equivalized household income. Univariable and multivariable logistic regression analyses were conducted to estimate the odds ratios (ORs) of psoriasis in the offspring, in cohort analyses for data from the year of enrolment and cross-sectional analyses from the year of the 11-year follow-up. RESULTS: Maternal age at birth, maternal educational attainment and equivalized household income were inversely associated with psoriasis in the offspring. Low maternal educational attainment was associated with offspring psoriasis [adjusted OR 1·62, 95% confidence interval (CI) 1·20-2·18] after adjusting for maternal psoriasis and age in the cohort analysis. The crude OR of psoriasis in offspring of mothers in the highest quartile compared with mothers in the lowest quartile of equivalized household income was 0·57 (95% CI 0·43-0·76), and the adjusted OR was 0·59 (95% CI 0·44-0·80) after adjusting for maternal psoriasis and age. Similar results were observed for data on maternal socioeconomic position at enrolment and at follow-up. CONCLUSIONS: A steep social gradient in paediatric-onset psoriasis was observed. Maternal socioeconomic position may play a role in early-life exposure to modifiable risk factors for psoriasis. Future studies may help to elucidate which biological factors mediate the social gradient observed in our study.

Safety of percutaneous renal cryoablation: an international multicentre experience from the EuRECA retrospective percutaneous database.

OBJECTIVE: To investigate the safety profile of percutaneous cryoablation of renal tumours < 7 cm, utilising data extracted from an international multicentre registry. MATERIALS AND METHODS: A retrospective review of all immediate and delayed complications from a multicentre database was performed and was categorised according to the Clavien-Dindo classification. Statistical analysis was performed for both overall complications (all Clavien-Dindo) and major complications (Clavien-Dindo 3 to 5). The following criteria were identified as potential predictive factors for complications: centre number, modality of image guidance, tumour size (≤ 4 cm vs. > 4 cm), number of tumours treated in the same session (1 vs. > 1) and tumour histology. RESULTS: A total of 713 renal tumours underwent ablation in 647 individual sessions. In 596 of the cases, one tumour was treated; in the remaining 51 cases, several tumours were treated per session. Mean lesion size was 2.8 cm. Fifty-four complications (Clavien-Dindo 1 to 5) occurred as a result of the 647 procedures, corresponding to an overall complication rate of 8.3%. The most frequent complication was bleeding (3.2%), with 9 cases (1.4%) requiring subsequent treatment. The rate of major complication was 3.4%. The only statistically significant prognostic factor for a major complication was a tumour size > 4 cm. CONCLUSION: Percutaneous renal cryoablation is associated with a low rate of complications. Tumours measuring more than 4 cm are associated with a higher risk of major complications. KEY POINTS: • Percutaneous kidney cryoablation has a low rate of complications. • Bleeding is the most frequent complication. • A tumour size superior to 4 cm is a predictive factor of major complication.