Rhizobia-diatom symbiosis fixes missing nitrogen in the ocean.

Nitrogen (N2) fixation in oligotrophic surface waters is the main source of new nitrogen to the ocean1 and has a key role in fuelling the biological carbon pump2. Oceanic N2 fixation has been attributed almost exclusively to cyanobacteria, even though genes encoding nitrogenase, the enzyme that fixes N2 into ammonia, are widespread among marine bacteria and archaea3-5. Little is known about these non-cyanobacterial N2 fixers, and direct proof that they can fix nitrogen in the ocean has so far been lacking. Here we report the discovery of a non-cyanobacterial N2-fixing symbiont, 'Candidatus Tectiglobus diatomicola', which provides its diatom host with fixed nitrogen in return for photosynthetic carbon. The N2-fixing symbiont belongs to the order Rhizobiales and its association with a unicellular diatom expands the known hosts for this order beyond the well-known N2-fixing rhizobia-legume symbioses on land6. Our results show that the rhizobia-diatom symbioses can contribute as much fixed nitrogen as can cyanobacterial N2 fixers in the tropical North Atlantic, and that they might be responsible for N2 fixation in the vast regions of the ocean in which cyanobacteria are too rare to account for the measured rates.

Terrestrial-type nitrogen-fixing symbiosis between seagrass and a marine bacterium.

Symbiotic N2-fixing microorganisms have a crucial role in the assimilation of nitrogen by eukaryotes in nitrogen-limited environments1-3. Particularly among land plants, N2-fixing symbionts occur in a variety of distantly related plant lineages and often involve an intimate association between host and symbiont2,4. Descriptions of such intimate symbioses are lacking for seagrasses, which evolved around 100 million years ago from terrestrial flowering plants that migrated back to the sea5. Here we describe an N2-fixing symbiont, 'Candidatus Celerinatantimonas neptuna', that lives inside seagrass root tissue, where it provides ammonia and amino acids to its host in exchange for sugars. As such, this symbiosis is reminiscent of terrestrial N2-fixing plant symbioses. The symbiosis between Ca. C. neptuna and its host Posidonia oceanica enables highly productive seagrass meadows to thrive in the nitrogen-limited Mediterranean Sea. Relatives of Ca. C. neptuna occur worldwide in coastal ecosystems, in which they may form similar symbioses with other seagrasses and saltmarsh plants. Just like N2-fixing microorganisms might have aided the colonization of nitrogen-poor soils by early land plants6, the ancestors of Ca. C. neptuna and its relatives probably enabled flowering plants to invade nitrogen-poor marine habitats, where they formed extremely efficient blue carbon ecosystems7.

Impact of low-value medications on quality of life, hospitalization and costs - A longitudinal analysis of patients living with dementia.

INTRODUCTION: This study aimed to analyze the impact of low-value medications (Lvm), that is, medications unlikely to benefit patients but to cause harm, on patient-centered outcomes over 24 months. METHODS: This longitudinal analysis was based on baseline, 12 and 24 months follow-up data of 352 patients with dementia. The impact of Lvm on health-related quality of life (HRQoL), hospitalizations, and health care costs were assessed using multiple panel-specific regression models. RESULTS: Over 24 months, 182 patients (52%) received Lvm at least once and 56 (16%) continuously. Lvm significantly increased the risk of hospitalization by 49% (odds ratio, confidence interval [CI] 95% 1.06-2.09; p = 0.022), increased health care costs by €6810 (CI 95% -707€-14,27€; p = 0.076), and reduced patients' HRQoL (b = -1.55; CI 95% -2.76 to -0.35; p = 0.011). DISCUSSION: More than every second patient received Lvm, negatively impacting patient-reported HRQoL, hospitalizations, and costs. Innovative approaches are needed to encourage prescribers to avoid and replace Lvm in dementia care. HIGHLIGHTS: Over 24 months, more than every second patient received low-value medications (Lvm). Lvm negatively impact physical, psychological, and financial outcomes. Appropriate measures are needed to change prescription behaviors.

Comparing the psychometric properties of EQ-5D-3L and EQ-5D-5L proxy ratings by informal caregivers and a health professional for people with dementia.

BACKGROUND: Assessing health-related quality of life (HRQoL) among persons with dementia poses several challenges due to cognitive decline and limited perception. As a result, proxy ratings by family members or health professionals are used. The EQ-5D is the most commonly used generic and preference-based HRQoL instrument. Methodological drawbacks of the three-level version (EQ-5D-3L) prompted the development of the five-level version (EQ-5D-5L) by expanding the range in the domains. However, no comparison of the psychometric properties of both versions and different proxy ratings exist so far. Therefore, the objective of this study was to compare the psychometric properties of the EQ-5D-5L and EQ-5D-3L by application of different proxy ratings in dementia. METHODS: The EQ-5D-3L and -5L were completed by n = 52 family caregivers and one care manager at baseline and three and six months later. In total, 106 caregiver and 133 care manager proxy ratings were completed. The EQ-5D-3L and 5L were evaluated in terms of acceptability (missing values), agreement, ceiling effects, redistribution properties and inconsistency, and informativity (Shannon, H', and Shannon Evenness, J', indices) as well as convergent and discriminative validity. RESULTS: Mean proxy index scores were higher for the 5L than the 3L. Missing values occurred less frequently in both proxy ratings and versions (< 1%). Agreement between both measures was high but higher in caregiver than care-manager ratings (ICC 0.885 vs. 0.840). The relative ceiling effect decreased from the 3L to the 5L, more intensively in the care-manager (75%) than the caregiver rating (56%). Inconsistency between both versions was low. Informativity increased from the 3L to the 5L version, nearly equally in both proxy ratings. The 5L also demonstrated a better discriminative ability and convergent validity than the 3L, especially in the caregiver rating. CONCLUSION: Compared to the EQ-5D-3L, the EQ-5D-5L had higher feasibility and acceptability and was slightly superior by a reduction of ceiling effects and an improvement in informativity, discriminative ability and convergent validity. Proxy ratings by informal caregivers overall demonstrated better psychometric properties than professional care-manager ratings.

Elicitation of quantitative, choice-based preferences for Person-Centered Care among People living with Dementia in comparison to physicians' judgements in Germany: study protocol for the mixed-methods PreDemCare-study.

BACKGROUND: Person-Centered-Care (PCC) requires knowledge about patient preferences. Among People-living-with-Dementia (PlwD) data on quantitative, choice-based preferences, which would allow to quantify, weigh and rank patient-relevant elements of dementia-care, and identify most/least preferred choices, are limited. The Analytic-Hierarchy-Process (AHP) may be one approach to elicit quantitative, choice-based preferences with PlwD, due to simple pairwise comparisons of individual criteria from a complex decision-problem, e.g. health care decisions. Furthermore, data on congruence of patient preferences with physicians' judgements for PCC are missing. If patient preferences and physicians' judgements differ, provision of PCC becomes unlikely. An understanding of patient preferences compared to physician's judgements will support the implementation of truly PCC, i.e. state of the art dementia-care aligned with patient preferences. METHODS: This mixed-methods-study will be based on the results from a previous systematic review and conducted in three phases: (I) literature-based key intervention-categories of PCC will be investigated during qualitative interviews with Dementia-Care-Managers (DCMs) and PlwD to identify actually patient-relevant (sub) criteria of PCC; (II) based on findings from phase I, an AHP-survey will be designed and pre-tested for face- and content-validity, and consistency during face-to-face "thinking-aloud"-interviews with PlwD and two expert panels (DCMs and physicians); (III) the developed survey will elicit patient preferences and physicians' judgements for PCC. To assess individual importance weights for (sub) criteria in both groups, the Principal-Eigenvector-Method will be applied. Weights will be aggregated per group by Aggregation-of-Individual-Priorities-mode. Descriptive and interferential statistical analyses will be conducted to assess congruence of importance-weights between groups. Subgroup-analyses shall investigate participant-heterogeneities, sensitivity of AHP-results shall be tested by inclusion/exclusion of inconsistent respondents. DISCUSSION: Little research is published on quantitative, choice-based preferences in dementia care. We expect that (1) PlwD have preferences and can express these, (2) that the AHP is a suitable technique to elicit quantitative, choice-based preferences among PlwD, and (3) to identify a divergence between patient preferences and physicians' judgements for PCC. With the help of the AHP-technique, which supports systematic decision-making including multiple criteria, it may be possible to involve PlwD in future care decisions (patient participation) and ensure implementation of truly Person-Centered-Dementia-Care. TRIAL REGISTRATION: Approval of the study was granted by the Ethics Committee at the University Medicine Greifswald the 09Apr2021 (Reg.-Nr.: BB 018-21, BB 018-21a, BB 018-21b).

Contributions of information and communications technology to future health systems and Universal Health Coverage: application of Japan's experiences.

BACKGROUND: Demographic changes in the pattern of disease burden, escalating health expenditures and inequitable access to healthcare are global challenges. Irrespective of their level of development, all countries need to reform their health systems to prepare for the future emerging health needs, in order to meet their commitments of health systems strengthening, universal health coverage (UHC) and explicit targets in the Sustainable Development Goals (SDGs). We propose three core principles for the future health system as described herein. A health system is not simply a 'cure delivery machine' but part of a 'social security system' that engages all stakeholders through a shared vision and value of health and well-being, not merely an absence of diseases. The future health system shall provide people-centred, affordable care, tailored to the individual's needs, accessible at any time and any place, and reflect the notion of leaving no one behind through a life course approach - underpinned by the SDGs. Information and communications technology (ICT) offers the potential to facilitate the realisation of these principles by improving the information flow between different parts of the health system through electronic means. We introduce Japan's new data platform - Person-centred Open PLatform for wellbeing (PeOPLe) - planned to be introduced in 2020 as one example of an ICT-based intervention to realise the three proposed principles. PeOPLe integrates data collected throughout the life course to enable all people to receive affordable, personalised health and social care at any time and any place throughout their lifetime. Furthermore, we discuss the applicability of these principles and PeOPLe to the health systems context of Thailand and the Philippines, including elaborations on ICT transformation challenges. CONCLUSION: Current rising momentum and scale for ICTs in the UHC era offers a great opportunity to make a difference for countries. The PeOPLe concept is not only relevant to resource-rich countries; its applicability to other Asian countries could be feasible though it will need to be adapted to the various country contexts. We hope that this paper contributes to wider discussion around policy choices of ICT application for future health systems strengthening and UHC in order to achieve the SDGs.

N2 fixation in free-floating filaments of Trichodesmium is higher than in transiently suboxic colony microenvironments.

To understand the role of micrometer-scale oxygen (O2 ) gradients in facilitating dinitrogen (N2 ) fixation, we characterized O2 dynamics in the microenvironment around free-floating trichomes and colonies of Trichodesmium erythraeum IMS101. Diurnal and spatial variability in O2 concentrations in the bulk medium, within colonies, along trichomes and within single cells were determined using O2 optodes, microsensors and model calculations. Carbon (C) and N2 fixation as well as O2 evolution and uptake under different O2 concentrations were analyzed by stable isotope incubations and membrane inlet mass spectrometry. We observed a pronounced diel rhythm in O2 fluxes, with net O2 evolution restricted to short periods in the morning and evening, and net O2 uptake driven by dark respiration and light-dependent O2 uptake during the major part of the light period. Remarkably, colonies showed lower N2 fixation and C fixation rates than free-floating trichomes despite the long period of O2 undersaturation in the colony microenvironment. Model calculations demonstrate that low permeability of the cell wall in combination with metabolic heterogeneity between single cells allows for anoxic intracellular conditions in colonies but also free-floating trichomes of Trichodesmium. Therefore, whereas colony formation must have benefits for Trichodesmium, it does not favor N2 fixation.

Metabolic versatility of a novel N2 -fixing Alphaproteobacterium isolated from a marine oxygen minimum zone.

The N2 -fixing (diazotrophic) community in marine ecosystems is dominated by non-cyanobacterial microorganisms. Yet, very little is known about their identity, function and ecological relevance due to a lack of cultured representatives. Here we report a novel heterotrophic diazotroph isolated from the oxygen minimum zone (OMZ) off Peru. The new species belongs to the genus Sagittula (Rhodobacteraceae, Alphaproteobacteria) and its capability to fix N2 was confirmed in laboratory experiments. Genome sequencing revealed that it is a strict heterotroph with a high versatility in substrate utilization and energy acquisition mechanisms. Pathways for sulfide oxidation and nitrite reduction to nitrous oxide are encoded in the genome and might explain the presence throughout the Peruvian OMZ. The genome further indicates that this novel organism could be in direct interaction with other microbes or particles. NanoSIMS analyses were used to compare the metabolic potential of S. castanea with single-cell activity in situ; however, N2 fixation by this diazotroph could not be detected at the isolation site. While the biogeochemical impact of S. castanea is yet to be resolved, its abundance and widespread distribution suggests that its potential to contribute to the marine N input could be significant at a larger geographical scale.

Doubling of marine dinitrogen-fixation rates based on direct measurements.

Biological dinitrogen fixation provides the largest input of nitrogen to the oceans, therefore exerting important control on the ocean's nitrogen inventory and primary productivity. Nitrogen-isotope data from ocean sediments suggest that the marine-nitrogen inventory has been balanced for the past 3,000 years (ref. 4). Producing a balanced marine-nitrogen budget based on direct measurements has proved difficult, however, with nitrogen loss exceeding the gain from dinitrogen fixation by approximately 200 Tg N yr−1 (refs 5, 6). Here we present data from the Atlantic Ocean and show that the most widely used method of measuring oceanic N2-fixation rates underestimates the contribution of N2-fixing microorganisms (diazotrophs) relative to a newly developed method. Using molecular techniques to quantify the abundance of specific clades of diazotrophs in parallel with rates of 15N2 incorporation into particulate organic matter, we suggest that the difference between N2-fixation rates measured with the established method and those measured with the new method can be related to the composition of the diazotrophic community. Our data show that in areas dominated by Trichodesmium, the established method underestimates N2-fixation rates by an average of 62%. We also find that the newly developed method yields N2-fixation rates more than six times higher than those from the established method when unicellular, symbiotic cyanobacteria and γ-proteobacteria dominate the diazotrophic community. On the basis of average areal rates measured over the Atlantic Ocean, we calculated basin-wide N2-fixation rates of 14 ± 1 Tg N yr−1 and 24 ±1 Tg N yr−1 for the established and new methods, respectively. If our findings can be extrapolated to other ocean basins, this suggests that the global marine N2-fixation rate derived from direct measurements may increase from 103 ± 8 Tg N yr−1 to 177 ± 8 Tg N yr−1, and that the contribution of N2 fixers other than Trichodesmium is much more significant than was previously thought.

Protein stable isotope fingerprinting: multidimensional protein chromatography coupled to stable isotope-ratio mass spectrometry.

Protein stable isotope fingerprinting (P-SIF) is a method to measure the carbon isotope ratios of whole proteins separated from complex mixtures, including cultures and environmental samples. The goal of P-SIF is to expose the links between taxonomic identity and metabolic function in microbial ecosystems. To accomplish this, two dimensions of chromatography are used in sequence to resolve a sample containing ca. 5-10 mg of mixed proteins into 960 fractions. Each fraction then is split in two aliquots: The first is digested with trypsin for peptide sequencing, while the second has its ratio of (13)C/(12)C (value of δ(13)C) measured in triplicate using an isotope-ratio mass spectrometer interfaced with a spooling wire microcombustion device. Data from cultured species show that bacteria have a narrow distribution of protein δ(13)C values within individual taxa (±0.7-1.2‰, 1σ). This is moderately larger than the mean precision of the triplicate isotope measurements (±0.5‰, 1σ) and may reflect heterogeneous distribution of (13)C among the amino acids. When cells from different species are mixed together prior to protein extraction and separation, the results can predict accurately (to within ±1σ) the δ(13)C values of the original taxa. The number of data points required for this endmember prediction is ≥20/taxon, yielding a theoretical resolution of ca. 10 taxonomic units/sample. Such resolution should be useful to determine the overall trophic breadth of mixed microbial ecosystems. Although we utilize P-SIF to measure natural isotope ratios, it also could be combined with experiments that incorporate stable isotope labeling.

Methylphosphonate-driven methane formation and its link to primary production in the oligotrophic North Atlantic.

Methylphosphonate is an organic phosphorus compound used by microorganisms when phosphate, a key nutrient limiting growth in most marine surface waters, becomes unavailable. Microbial methylphosphonate use can result in the formation of methane, a potent greenhouse gas, in oxic waters where methane production is traditionally unexpected. The extent and controlling factors of such aerobic methane formation remain underexplored. Here, we show high potential net rates of methylphosphonate-driven methane formation (median 0.4 nmol methane L-1 d-1) in the upper water column of the western tropical North Atlantic. The rates are repressed but still quantifiable in the presence of in-situ or added phosphate, suggesting that some methylphosphonate-driven methane formation persists in phosphate-replete waters. The genetic potential for methylphosphonate utilisation is present in and transcribed by key photo- and heterotrophic microbial taxa, such as Pelagibacterales, SAR116, and Trichodesmium. While the large cyanobacterial nitrogen-fixers dominate in the surface layer, phosphonate utilisation by Alphaproteobacteria appears to become more important in deeper depths. We estimate that at our study site, a substantial part (median 11%) of the measured surface carbon fixation can be sustained by phosphorus liberated from phosphonate utilisation, highlighting the ecological importance of phosphonates in the carbon cycle of the oligotrophic ocean.

Do They Align? Congruence Between Patient Preferences of People Living with Cognitive Impairments and Physicians' Judgements for Person-Centered Care: An Analytic Hierarchy Process Study.

BACKGROUND: Person-centered care (PCC) requires knowledge about patient preferences. Among people living with cognitive impairments (PlwCI), evidence on quantitative, choice-based preferences, which allow to quantify, weigh, and rank care elements, is limited. Furthermore, data on the congruence of patient preferences with physicians' judgements for PCC are missing. Such information is expected to support the implementation of PCC; state-of-the-art medical care aligned with patients' preferences. OBJECTIVE: To elicit patient preferences and physicians' judgements for PCC and their congruence. METHODS: Data from the mixed-methods PreDemCare study, including a cross-sectional, paper-and-pencil, interviewer-assisted analytic hierarchy process (AHP) survey conducted with n = 50 community-dwelling PlwCI and n = 25 physicians. Individual AHP weights (preferences/judgements) were calculated with the principal eigenvector method and aggregated per group by aggregation of individual priorities mode. Individual consistency ratios (CRs) were calculated and aggregated per group. Group differences in preferences/judgements were investigated descriptively by means and standard deviations (SDs) of AHP weights, resulting ranks, and boxplots. Additionally, differences between groups were investigated with independent paired t-test/Mann Whitney U-test. Sensitivity of AHP results was tested by inclusion/exclusion of inconsistent respondents, with an accepted threshold at CR≤0.3 for patients, and CR≤0.2 for physicians, due to better cognitive fitness of the latter group. RESULTS: Patient preferences and physicians' judgements did not differ significantly, except for the criterion Memory Exercises (AHP weights (mean (SD)): 0.135 (0.066) versus 0.099 (0.068), p = 0.01). We did not see rank-reversals of criteria after exclusion of inconsistent participants. Mean CR for patients at the criteria level was 0.261, and 0.181 for physicians. CONCLUSION: Physicians' judgements in our setting aligned well with patients' preferences. Our findings may be used to guide the implementation of preference-based PCC.

Impact of Hearing Aids on Progression of Cognitive Decline, Depression, and Quality of Life Among People with Cognitive Impairment and Dementia.

BACKGROUND: Hearing loss is common in people with dementia (PwD) and a modifiable risk factor for cognitive decline. Recent studies revealed that hearing loss could cause social isolation and depression, which is associated with health-related quality of life (HRQoL). However, there is a lack of knowledge about the impact of the utilization of hearing aids on these outcomes. OBJECTIVE: To assess whether hearing aids use might be positively associated with the progression of cognitive function, depression, and HRQoL among PwD. METHODS: We analyzed two-year follow-up data from 258 PwD (≥70 years, living at home). Cognitive decline was measured with Mini-Mental Status Examination (MMSE), depression using Geriatric Depression Scale (GDS), and HRQoL with Quality of Life in Alzheimer's Disease Scale (QoL-AD). The impact of hearing aid utilization on the progression of outcomes was assessed using multivariate regression models. RESULTS: 123 patients had hearing loss (47.7%), from which n = 54 (43.9%) used hearing aids. Patients with hearing loss were older and had a lower HRQoL than those without hearing loss. Use of hearing aids in patients with hearing loss was associated with a lower increase in depressive symptoms (b = -0.74, CI95 -1.48 --0.01, p = 0.047) over time as compared to those not using hearing aids. There was no effect on PwD's cognition, and the association with higher HRQoL was significant after one, but not consistently over two years. CONCLUSION: Early detection and intervention of presbycusis using hearing aids might improve mental health and HRQoL in dementia.

Fluctuations of health states in dementia diseases and their impact on the assessment of health today using the EQ-5D-5L: Protocol of a mixed-methods study.

Introduction: The EQ-5D is a widely used health-related quality of life (HRQoL) instrument. The recall period "today" may miss out on recurrent health fluctuations often observed in people with dementia (PlwD). Thus, this study aims to assess the frequency of health fluctuations, affected HRQoL dimensions and the impact of the health fluctuations on the assessment of health today using the EQ-5D-5L. Methods and analysis: This mixed-methods study will base on n=50 patient and caregiver dyads and four main study phases: (1) Baseline assessment of patients' socio-demographic and clinical characteristics; (2) caregivers self-completion of a daily diary for 14 days, documenting patient's today's health compared to yesterday, the affected HRQoL dimensions, and events that could have caused the fluctuations; (3) administration of the EQ-5D-5L as self- and proxy-rating at baseline, day seven and day 14; (4) interviewing caregivers on patient's health fluctuation, the consideration of past fluctuations in the assessment of health today using the EQ-5D-5L, and the appropriateness of recall periods to capture health fluctuations on day 14. Qualitative semi-structured interview data will be analyzed thematically. Quantitative analyses will be used to describe the frequency and intensity of health fluctuations, affected dimensions, and the association between health fluctuation and its consideration in the assessment of health today. Discussion: This study aims to reveal insights into the health fluctuation in dementia, the affected dimensions, and underlying health events, as well as whether individuals adhere to the recall period of health today using the EQ-5D-5L. This study will also provide information about more appropriate recall periods that could better capture health fluctuations. Trial registration: This study is registered in the German Clinical Trials Register (DRKS00027956).

Tasks and Activities of an Effective Collaborative Dementia Care Management Program in German Primary Care.

BACKGROUND: Recent studies have demonstrated the efficiency of collaborative dementia care, which aims to improve post-diagnostic support. However, tasks carried out of such models are currently unknown, hindering its implementation. OBJECTIVE: To describe tasks of a collaborative model of dementia care, analyze the association between specific task subgroups and number of tasks with patients' and caregivers' characteristics and the impact of specific tasks on health-related quality of life (HRQoL). METHODS: The analysis was based on 183 persons with dementia (PwD) who received dementia care management conducted by dementia-specific qualified nurses. A standardized, computer-assisted assessment was used to identify patients' and caregivers' unmet needs. Tasks carried out to address unmet needs were documented, categorized, and descriptively analyzed. We used multivariate regression models to identify socio-demographic and clinical factors associated with a specific subgroup of tasks or a higher number of tasks. RESULTS: On average, 20.5 tasks were carried out per dyad (PwD and caregiver). 41% of tasks were categorized to cooperation with other healthcare providers, 39% to nursing care, and 19% to social support. Lower HRQoL and higher age, cognitive impairment, deficits in daily living activities, and depressive symptoms were significantly associated with a higher number of tasks. A higher number of cooperation tasks were associated with a higher gain in HRQoL. CONCLUSION: Patients' characteristics and HRQoL significantly determine the intensity of collaborative care interventions. Variability of the intensity should be considered in developing future studies and in the implementation into routine care. CLINICALTRIALS: gov Identifier: NCT01401582.

Development of a Quantitative Preference Instrument for Person-Centered Dementia Care-Stage 2: Insights from a Formative Qualitative Study to Design and Pretest a Dementia-Friendly Analytic Hierarchy Process Survey.

Person-centered care (PCC) requires knowledge about patient preferences. An analytic hierarchy process (AHP) is one approach to quantify, weigh and rank patient preferences suitable for People living with Dementia (PlwD), due to simple pairwise comparisons of individual criteria from a complex decision problem. The objective of the present study was to design and pretest a dementia-friendly AHP survey. Methods: Two expert panels consisting of n = 4 Dementia Care Managers and n = 4 physicians to ensure content-validity, and "thinking-aloud" interviews with n = 11 PlwD and n = 3 family caregivers to ensure the face validity of the AHP survey. Following a semi-structured interview guide, PlwD were asked to assess appropriateness and comprehensibility. Data, field notes and partial interview transcripts were analyzed with a constant comparative approach, and feedback was incorporated continuously until PlwD had no further comments or struggles with survey completion. Consistency ratios (CRs) were calculated with Microsoft® Excel and ExpertChoice Comparion®. Results: Three main categories with sub-categories emerged: (1) Content: clear task introduction, (sub)criteria description, criteria homogeneity, (sub)criteria appropriateness, retest questions and sociodemography for heterogeneity; (2) Format: survey structure, pairwise comparison sequence, survey length, graphical design (incl. AHP scale), survey procedure explanation, survey assistance and response perspective; and (3) Layout: easy wording, short sentences and visual aids. Individual CRs ranged from 0.08 to 0.859, and the consolidated CR was 0.37 (0.038). Conclusions: Our formative qualitative study provides initial data for the design of a dementia-friendly AHP survey. Consideration of our findings may contribute to face and content validity in future quantitative preference research in dementia.

Development of a Quantitative Instrument to Elicit Patient Preferences for Person-Centered Dementia Care Stage 1: A Formative Qualitative Study to Identify Patient Relevant Criteria for Experimental Design of an Analytic Hierarchy Process.

Background: Person-centered care (PCC) requires knowledge about patient preferences. This formative qualitative study aimed to identify (sub)criteria of PCC for the design of a quantitative, choice-based instrument to elicit patient preferences for person-centered dementia care. Method: Interviews were conducted with n = 2 dementia care managers, n = 10 People living with Dementia (PlwD), and n = 3 caregivers (CGs), which followed a semi-structured interview guide including a card game with PCC criteria identified from the literature. Criteria cards were shown to explore the PlwD's conception. PlwD were asked to rank the cards to identify patient-relevant criteria of PCC. Audios were verbatim-transcribed and analyzed with qualitative content analysis. Card game results were coded on a 10-point-scale, and sums and means for criteria were calculated. Results: Six criteria with two sub-criteria emerged from the analysis; social relationships (indirect contact, direct contact), cognitive training (passive, active), organization of care (decentralized structures and no shared decision making, centralized structures and shared decision making), assistance with daily activities (professional, family member), characteristics of care professionals (empathy, education and work experience) and physical activities (alone, group). Dementia-sensitive wording and balance between comprehensibility vs. completeness of the (sub)criteria emerged as additional themes. Conclusions: Our formative study provides initial data about patient-relevant criteria of PCC to design a quantitative patient preference instrument. Future research may want to consider the balance between (sub)criteria comprehensibility vs. completeness.

Translation of Collaborative Dementia Care Management into Different Healthcare Settings: Study Protocol for a Multicenter Implementation Trial (DCM:IMPact).

Background: Collaborative care models for people living with dementia (PwD) have been developed and evaluated, demonstrating safety, efficacy, and cost-effectiveness. However, these studies are based on heterogeneous study populations and primary care settings, limiting the generalizability of the results. Therefore, this study aims to implement and evaluate collaborative care across various healthcare settings and patient populations. Objective: To describe the study design of this multicenter implementation trial. Methods: This single-arm, multicenter, longitudinal implementation study will be conducted in five different healthcare settings, including 1) physicians' networks, 2) dementia networks, 3) counselling centers, 4) hospitals, and 5) ambulatory care services. Eligibility criteria are: having a formal dementia diagnosis or having been screened positive for dementia and living community-dwelling. The staff of each healthcare setting identifies patients, informs them about the study, and invites them to participate. Participants will receive a baseline assessment followed by collaborative individualized dementia care management, comprising proven safe, effective, and cost-effective modules. Over six months, specially-qualified nurses will assess patients' unmet needs, transfer them to individualized care plans, and address them, cooperating with various healthcare providers. A follow-up assessment is conducted six months after baseline. Approximately 60-100 PwD per setting per year are expected to participate. Differences across settings will be assessed regarding acceptability, demand, implementation success and barriers, efficacy, and cost-effectiveness. Results: We expect that acceptability, demand, implementation success and barriers, efficacy, and cost-effectiveness will vary by patients' sociodemographic and clinical characteristics and unmet needs in each setting. Conclusion: The results will provide evidence highlighting differences in the implementation of collaborative care in various healthcare settings and demonstrating the settings with the highest need, best conditions for a successful implementation, and highest (cost-)effectiveness, as well as the population group that benefits most from collaborative care. Trial registration: German Clinical Trials Register: DRKS00025074. Registered 16 April 2021-retrospectively registered.

Associations Between Low-Value Medication in Dementia and Healthcare Costs.

BACKGROUND: Low-value medications (Lvm) provide little or no benefit to patients, may be harmful, and waste healthcare resources and costs. Although evidence from the literature indicates that Lvm is highly prevalent in dementia, evidence about the financial consequences of Lvm in dementia is limited. This study analyzed the association between receiving Lvm and healthcare costs from a public payers' perspective. METHODS: This analysis is based on data of 516 community-dwelling people living with dementia (PwD). Fourteen Lvm were extracted from dementia-specific guidelines, the German equivalent of the Choosing Wisely campaign, and the PRISCUS list. Healthcare utilization was retrospectively assessed via face-to-face interviews with caregivers and monetarized by standardized unit costs. Associations between Lvm and healthcare costs were analyzed using multiple linear regression models. RESULTS: Every third patient (n = 159, 31%) received Lvm. Low-value antiphlogistics, analgesics, anti-dementia drugs, sedatives and hypnotics, and antidepressants alone accounted for 77% of prescribed Lvm. PwD who received Lvm were significantly less cognitively impaired than those not receiving Lvm. Receiving Lvm was associated with higher medical care costs (b = 2959 €; 95% CI 1136-4783; p = 0.001), particularly due to higher hospitalization (b = 1911 €; 95% CI 376-3443; p = 0.015) and medication costs (b = 905 €; 95% CI 454-1357; p < 0.001). CONCLUSION: Lvm were prevalent, more likely occurring in the early stages of dementia, and cause financial harm for payers due to higher direct medical care costs. Further research is required to derive measures to prevent cost-driving Lvm in primary care, that is, implementing deprescribing interventions and moving health expenditures towards higher value resource use.

Absence of canonical trophic levels in a microbial mat.

In modern ecosystems, the carbon stable isotope (δ13 C) ratios of consumers generally conform to the principle "you are what you eat, +1‰." However, this metric may not apply to microbial mat systems where diverse communities, using a variety of carbon substrates via multiple assimilation pathways, live in close physical association and phagocytosis is minimal or absent. To interpret the δ13 C record of the Proterozoic and early Paleozoic, when mat-based productivity likely was widespread, it is necessary to understand how a microbially driven producer-consumer structure affects the δ13 C compositions of biomass and preservable lipids. Protein Stable Isotope Fingerprinting (P-SIF) is a recently developed method that allows measurement of the δ13 C values of whole proteins, separated from environmental samples and identified taxonomically via proteomics. Here, we use P-SIF to determine the trophic relationships in a microbial mat sample from Chocolate Pots Hot Springs, Yellowstone National Park (YNP), USA. In this mat, proteins from heterotrophic bacteria are indistinguishable from cyanobacterial proteins, indicating that "you are what you eat, +1‰" is not applicable. To explain this finding, we hypothesize that sugar production and consumption dominate the net ecosystem metabolism, yielding a community in which producers and consumers share primary photosynthate as a common resource. This idea was validated by confirming that glucose moieties in exopolysaccharide were equal in δ13 C composition to both cyanobacterial and heterotrophic proteins, and by confirming that highly 13 C-depleted fatty acids (FAs) of Cyanobacteria dominate the lipid pool, consistent with flux-balance expectations for systems that overproduce primary photosynthate. Overall, the results confirm that the δ13 C composition of microbial biomass and lipids is tied to specific metabolites, rather than to autotrophy versus heterotrophy or to individual trophic levels. Therefore, we suggest that aerobic microbial heterotrophy is simply a case of "you are what you eat."