Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

Alzheimer\u27s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer\u27s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N = 88), both plaque and tangle density contributed independently to higher P-tau217, but P-tau217 was not elevated in patients with non-Alzheimer\u27s disease tauopathies (N = 9). Several findings were replicated in a cohort with PET imaging ( BioFINDER-2 , N = 426), where β-amyloid and tau PET were independently associated with P-tau217. P-tau217 concentrations correlated with β-amyloid PET (but not tau PET) in early disease stages and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 concentration is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles

Tau-PET is superior to phospho-tau when predicting cognitive decline in symptomatic AD patients

Introduction: Biomarkers for the prediction of cognitive decline in patients with amnestic mild cognitive impairment (MCI) and amnestic mild dementia are needed for both clinical practice and clinical trials. Methods: We evaluated the ability of tau-PET (positron emission tomography), cortical atrophy on magnetic resonance imaging (MRI), baseline cognition, apolipoprotein E gene (APOE) status, plasma and cerebrospinal fluid (CSF) levels of phosphorylated tau-217, neurofilament light (NfL), and amyloid beta (Aβ)42/40 ratio (individually and in combination) to predict cognitive decline over 2 years in BioFINDER-2 and Alzheimer's Disease Neuroimaging Initiative (ADNI). Results: Baseline tau-PET and a composite baseline cognitive score were the strongest independent predictors of cognitive decline. Cortical thickness and NfL provided some additional information. Using a predictive algorithm to enrich patient selection in a theoretical clinical trial led to a significantly lower required sample size. Discussion: Models including baseline tau-PET and cognition consistently provided the best prediction of change in cognitive function over 2 years in patients with amnestic MCI or mild dementia

Diversity of Zoanthids (Anthozoa: Hexacorallia) on Hawaiian Seamounts: Description of the Hawaiian Gold Coral and Additional Zoanthids

The Hawaiian gold coral has a history of exploitation from the deep slopes and seamounts of the Hawaiian Islands as one of the precious corals commercialised in the jewellery industry. Due to its peculiar characteristic of building a scleroproteic skeleton, this zoanthid has been referred as Gerardia sp. (a junior synonym of Savalia Nardo, 1844) but never formally described or examined by taxonomists despite its commercial interest. While collection of Hawaiian gold coral is now regulated, globally seamounts habitats are increasingly threatened by a variety of anthropogenic impacts. However, impact assessment studies and conservation measures cannot be taken without consistent knowledge of the biodiversity of such environments. Recently, multiple samples of octocoral-associated zoanthids were collected from the deep slopes of the islands and seamounts of the Hawaiian Archipelago. The molecular and morphological examination of these zoanthids revealed the presence of at least five different species including the gold coral. Among these only the gold coral appeared to create its own skeleton, two other species are simply using the octocoral as substrate, and the situation is not clear for the final two species. Phylogenetically, all these species appear related to zoanthids of the genus Savalia as well as to the octocoral-associated zoanthid Corallizoanthus tsukaharai, suggesting a common ancestor to all octocoral-associated zoanthids. The diversity of zoanthids described or observed during this study is comparable to levels of diversity found in shallow water tropical coral reefs. Such unexpected species diversity is symptomatic of the lack of biological exploration and taxonomic studies of the diversity of seamount hexacorals

Teacher resilience in adverse contexts: issues of professionalism and professional identity

Teacher resilience is a construct that is relative, developmental and dynamic; it is socially constructed and depends on personal and professional dispositions. Issues of commitment, professionalism, and professional identity, for instance, need to be taken into account if teacher resilience is to be fully understood. In this chapter I draw upon a larger piece of research aimed at investigating teachers’ work and lives in challenging circumstances. Data were collected through a national survey (n=2702 teachers), focus group (n=99 teachers) and interviews to 11 school principals. Findings suggest the connection between teacher commitment and resilience which are associated with issues of school culture and leadership, a sense of vocation, and teachers’ beliefs and professional values. Factors and sources of teacher motivation and resilience are also identified within a context marked by teacher intensification, lack of trust, worsening of teaching conditions, lower social and economic status and legislative “tsunami”. The chapter ends with the discussion of the importance of relationships in the teaching profession and issues of motivation and professionalism which entails given ways of being and feeling as a teacher.Financial Support by CIEC (Research Centre on Child Studies, IE, UMinho; FCT R&D unit 317, Portugal) by the Strategic Project UID/CED/00317/2013, with financial support of National Funds through the FCT (Foundation for Science and Technology) and co-financed by European Regional Development Funds (FEDER) through the COMPETE 2020 - Competitiveness and Internationalization Operational Program (POCI) with the reference POCI-01-0145-FEDER-00756

Evaluation of changes in postnatal care using the "Parents' Postnatal Sense of Security" instrument and an assessment of the instrument's reliability and validity

<p>Abstract</p> <p>Background</p> <p>A sense of security is important for experiences of parenthood in the early postpartum period. The objectives of this study were to evaluate two models of postnatal care using a questionnaire incorporating the Parents' Postpartum Sense of Security (<it>PPSS</it>) instrument and to test the validity of the <it>PPSS </it>instrument.</p> <p>Methods</p> <p>Postal surveys were sent to 234 mothers who had experienced two different forms of postnatal care (study group and control group) and returned by 86.8%. These two groups of mothers were compared for total scores on the <it>PPSS </it>instrument. Demographic variables and mothers' opinions about care interventions were also compared and these variables were tested for correlations with the total <it>PPSS </it>score. A regression analysis was carried out to assess areas of midwifery care which might affect a sense of security. The internal consistency and concurrent validity of the instrument were tested for the total population.</p> <p>Results</p> <p>there were no significant differences between the groups for scores on the <it>PPSS </it>instrument. A total of three variables predicted 26% of the variability on the <it>PPSS </it>scores for the study group and five variables predicted 37% of the variability in the control group. One variable was common to both: "<it>The midwives on the postnatal ward paid attention to the mother as an individual"</it>. There were significant correlations between the total <it>PPSS </it>scores and scores for postpartum talks and visits to the breastfeeding clinic. There was also a significant correlation between the single question: "<it>I felt secure during the first postpartum week</it>" and the total <it>PPSS </it>score. Tests for internal consistency and concurrent validity were satisfactory.</p> <p>Conclusion</p> <p>The proposed new model of care neither improved nor impaired mothers' feelings of security the week following birth. Being seen as an individual by the midwife who provides postnatal care may be an important variable for mothers' sense of postnatal security. It is possible that postpartum talks may encourage the processing of childbirth experiences in a positive direction. Availability of breastfeeding support may also add to a sense of security postpartum. The <it>PPSS </it>instrument has shown acceptable reliability and validity.</p

Absorbing customer knowledge: how customer involvement enables service design success

Customers are a knowledge resource outside of the firm that can be utilized for new service success by involving them in the design process. However, existing research on the impact of customer involvement (CI) is inconclusive. Knowledge about customers’ needs and on how best to serve these needs (articulated in the service concept) is best obtained from customers themselves. However, codesign runs the risk of losing control of the service concept. This research argues that of the processes of external knowledge, acquisition (via CI), customer knowledge assimilation, and concept transformation form a capability that enables the firm to exploit customer knowledge in the form of a successful new service. Data from a survey of 126 new service projects show that the impact of CI on new service success is fully mediated by customer knowledge assimilation (the deep understanding of customers’ latent needs) and concept transformation (the modification of the service concept due to customer insights). However, its impact is more nuanced. CI exhibits an “∩”-shaped relationship with transformation, indicating there is a limit to the beneficial effect of CI. Its relationship with assimilation is “U” shaped, suggesting a problem with cognitive inertia where initial learnings are ignored. Customer knowledge assimilation directly impacts success, while concept transformation only helps success in the presence of resource slack. An evolving new service design is only beneficial if the firm has the flexibility to adapt to change

Tiny Sea Anemone from the Lower Cambrian of China

Background Abundant fossils from the Ediacaran and Cambrian showing cnidarian grade grossly suggest that cnidarian diversification occurred earlier than that of other eumetazoans. However, fossils of possible soft-bodied polyps are scanty and modern corals are dated back only to the Middle Triassic, although molecular phylogenetic results support the idea that anthozoans represent the first major branch of the Cnidaria. Because of difficulties in taxonomic assignments owing to imperfect preservation of fossil cnidarian candidates, little is known about forms ancestral to those of living groups. Methods and Findings We have analyzed the soft-bodied polypoid microfossils Eolympia pediculata gen. et sp. nov. from the lowest Cambrian Kuanchuanpu Formation in southern China by scanning electron microscopy and computer-aided microtomography after isolating fossils from sedimentary rocks by acetic acid maceration. The fossils, about a half mm in body size, are preserved with 18 mesenteries including directives bilaterally arranged, 18 tentacles and a stalk-like pedicle. The pedicle suggests a sexual life cycle, while asexual reproduction by transverse fission also is inferred by circumferential grooves on the body column. Conclusions The features found in the present fossils fall within the morphological spectrum of modern Hexacorallia excluding Ceriantharia, and thus Eolympia pediculata could be a stem member for this group. The fossils also demonstrate that basic features characterizing modern hexacorallians such as bilateral symmetry and the reproductive system have deep roots in the Early Cambrian.Funding was provided by the National Science Foundation of China (http://www.nsfc.gov.cn/) grants 40830208, 40602003, 50702005 to J. Han and D. G. Shu, and by MOST Special Fund from the State Key Laboratory of Continental Dynamics, Northwest University, China (http://sklcd.nwu.edu.cn/) to J. Han and D. G. Shu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Towards Design Thinking as a Management Practice: A Learning Experiment in Teaching Innovation

There is an increasing need to make management knowledge more consistent with the “messiness” and complexity of actual organizational phenomena and contexts in today’s world, calling for a refoundation of mainstream management theories. The paper focuses on the contribution of design thinking approaches in this sense, particularly addressing the question of how the predisposition for a design thinking approach can be shaped in management education. Following a qualitative inductive research design, it will report the experience of the introduction of new teaching practices inspired by design thinking in a class of students from a Master program on Innovation and Marketing in an Italian University. Based on the empirical findings, the challenges and opportunities of innovating business school teaching towards the construction of a design thinking mentality will be discussed

A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings

Memory clinic patients are a heterogeneous population representing various aetiologies of pathological ageing. It is not known whether divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± standard deviation, age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (n = 342), mild cognitive impairment (n = 118) or dementia of the Alzheimer’s type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid Alzheimer’s disease biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5) as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test whether baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and mild cognitive impairment conversion rates of cognitively unimpaired participants and those with subjective cognitive decline. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy initially affected the medial temporal lobes, followed by further temporal regions and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological Alzheimer’s disease biomarker levels, APOE ε4 carriership and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe, with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive Alzheimer’s disease biomarkers and was associated with more generalized cognitive impairment. Limbic-predominant atrophy, in all participants and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of mild cognitive impairment conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, at both the subject and the group level, was excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for Alzheimer’s disease in applied settings. The implementation of atrophy subtype- and stage-specific end points might increase the statistical power of pharmacological trials targeting early Alzheimer’s disease