Biomarkers and Risk Factors of Dementia

Dementia is a devastating disease that is common in elderly people. The prevalence increases from almost 1% at age 65 to over 40% of people older than 90 years.1 Because the population is aging, the number of people living with dementia world- wide is expected to double every 20 years with an expected number of 81 million people with dementia in 2040.2 Currently, dementia is still a clinical diagnosis of disturbances in cognitive functions that interfere with normal daily functioning.3,4 The major subtype of dementia is Alzheimer disease, which based on a clinical diag- nosis, accounts for around 70% of all dementia. The second most common subtype is vascular dementia, which is diagnosed in about 15% of dementia cases.1 Nowadays, however, we know that most patients with dementia have a mix of the neurodegen- erative changes that typically occur in Alzheimer disease, vascular pathology and other pathological signs, like Lewy bodies.5,6 In addition, vascular risk factors have repeatedly been associated with not only vascular dementia, but also with Alzheim- er disease,7 supporting the neuropathological findings of mixed brain pathologies. Although many risk factors for dementia have been identified in the past decades, the exact mechanisms that lead to dementia are still unclear. When the clinical di- agnosis of dementia is made, the actual neuropathological processes that have lead to dementia have already been ongoing for many years. Biomarkers that can detect these processes before a clinical diagnosis can be made are strongly needed in order to identify persons who will develop dementia, to gain more insight in the pathogen- esis of dementia and ultimately to help find new therapeutic agents that may alter or stop the disease. Currently, the most explored biomarkers are imaging markers and the proteins β-Amyloid (Aβ)-42 and tau that are altered in the cerebrospinal fluid of patients with Alzheimer disease early in the disease process.8,9 A lumbar puncture, required to obtain cerebrospinal fluid, is a relative invasive procedure that is not easily performed on large numbers of patients or in the general population, and imaging methods such as PET are not routinely available in all clinical settings. Less invasive biomarkers of dementia are therefore wanted

Multidisciplinary integrated parent and child centres in Amsterdam: a qualitative study

Background: In several countries centres for the integrated delivery of services to the parent and child have been established. In the Netherlands family health care service centres, called Parent and Child Centres (PCCs) involve multidisciplinary teams. Here doctors, nurses, midwives, maternity help professionals and educationists are integrated into multidisciplinary teams in neighbourhood-based centres. To date there has been little research on the implementation of service delivery in these centres. Study Design: A SWOT analysis was performed by use of triangulation data; this took place by integrating all relevant published documents on the origin and organization of the PCCs and the results from interviews with PCC experts and with PCC professionals (N=91). Structured interviews were performed with PCC-professionals (health care professionals (N=67) and PCC managers N=12)) and PCC-experts (N=12) in Amsterdam and qualitatively analysed thematically. The interview themes were based on a pre-set list of codes, derived from a prior documentation study and a focus group with PCC experts. Results: Perceived advantages of PCCs were more continuity of care, shorter communication lines, low-threshold contact between professionals and promising future perspectives. Perceived challenges included the absence of uniform multidisciplinary guidelines, delays in communication with hospitals and midwives, inappropriate accommodation for effective professional integration, differing expectations regarding the PCC-manager role among PCC-partners and the danger of professionals' needs dominating clients' needs. Conclusions: Professionals perceive PCCs as a promising development in the integration of services. Remaining challenges involved improvements at the managerial and organizational level. Quantitative research into the improvements in quality of care and child health is recommended

The Essence of Nested Composition

Calculi with disjoint intersection types support an introduction form for intersections called the merge operator, while retaining a coherent semantics. Disjoint intersections types have great potential to serve as a foundation for powerful, flexible and yet type-safe and easy to reason OO languages. This paper shows how to significantly increase the expressive power of disjoint intersection types by adding support for nested subtyping and composition, which enables simple forms of family polymorphism to be expressed in the calculus. The extension with nested subtyping and composition is challenging, for two different reasons. Firstly, the subtyping relation that supports these features is non-trivial, especially when it comes to obtaining an algorithmic version. Secondly, the syntactic method used to prove coherence for previous calculi with disjoint intersection types is too inflexible, making it hard to extend those calculi with new features (such as nested subtyping). We show how to address the first problem by adapting and extending the Barendregt, Coppo and Dezani (BCD) subtyping rules for intersections with records and coercions. A sound and complete algorithmic system is obtained by using an approach inspired by Pierce\u27s work. To address the second problem we replace the syntactic method to prove coherence, by a semantic proof method based on logical relations. Our work has been fully formalized in Coq, and we have an implementation of our calculus

Medical Specialists' Perspectives on the Influence of Electronic Medical Record Use on the Quality of Hospital Care:Semistructured Interview Study

Objective: The aim of this study was to examine how, and by which aspects, the relationship between EMR use and the quality of care in hospitals is influenced according to medical specialists. Methods: To answer this question, a qualitative study was conducted in the period of August-October 2018. Semistructured interviews of around 90 min were conducted with 11 medical specialists from 11 different Dutch hospitals. For analysis of the answers, we used a previously published taxonomy of factors that can influence the use of EMRs. Results: The professional experience of the participating medical specialists varied between 5 and 27 years. Using the previously published taxonomy, these medical specialists considered technical barriers the most significant for EMR use. The suboptimal change processes surrounding implementation were also perceived as a major barrier. A final major problem is related to the categories “social” (their relationships with the patients and fellow care providers), “psychological” (based on their personal issues, knowledge, and perceptions), and “time” (the time required to select, implement, and learn how to use EMR systems and subsequently enter data into the system). However, the medical specialists also identified potential technical facilitators, particularly in the assured availability of information to all health care professionals involved in the care of a patient. They see promise in using EMRs for medical decision support to improve the quality of care but consider these possibilities currently lacking. Conclusions: The 11 medical specialists shared positive experiences with EMR use when comparing it to formerly used paper records. The fact that involved health care professionals can access patient data at any time they need is considered important. However, in practice, potential quality improvement lags as long as decision support cannot be applied because of the lack of a fully coded patient record

Row and Bounded Polymorphism via Disjoint Polymorphism

Polymorphism and subtyping are important features in mainstream OO languages. The most common way to integrate the two is via ?_{< :} style bounded quantification. A closely related mechanism is row polymorphism, which provides an alternative to subtyping, while still enabling many of the same applications. Yet another approach is to have type systems with intersection types and polymorphism. A recent addition to this design space are calculi with disjoint intersection types and disjoint polymorphism. With all these alternatives it is natural to wonder how they are related. This paper provides an answer to this question. We show that disjoint polymorphism can recover forms of both row polymorphism and bounded polymorphism, while retaining key desirable properties, such as type-safety and decidability. Furthermore, we identify the extra power of disjoint polymorphism which enables additional features that cannot be easily encoded in calculi with row polymorphism or bounded quantification alone. Ultimately we expect that our work is useful to inform language designers about the expressive power of those common features, and to simplify implementations and metatheory of feature-rich languages with polymorphism and subtyping

An asteroseismic study of the beta Cephei star beta Canis Majoris

We present the results of a detailed analysis of 452 ground-based high-resolution high S/N spectroscopic measurements spread over 4.5 years for beta Canis Majoris with the aim to determine the pulsational characteristics of this star, and to use them to derive seismic constraints on the stellar parameters. We determine pulsation frequencies in the SiIII 4553 Angstrom line with Fourier methods. We identify the m-value of the modes by taking into account the photometric identifications of the degrees l. To this end we use the moment method together with the amplitude and phase variations across the line profile. The frequencies of the identified modes are used for a seismic interpretation of the structure of the star. We confirm the presence of the three pulsation frequencies already detected in previous photometric datasets: f_1 = 3.9793 c/d (46.057 microHz), f_2 = 3.9995 c/d (46.291 microHz) and f_3 = 4.1832 c/d (48.417 microHz). For the two modes with the highest amplitudes we unambiguously identify (l_1,m_1) = (2,2) and (l_2,m_2) = (0,0). We cannot conclude anything for the third mode identification, except that m_3 > 0. We also deduce an equatorial rotational velocity of 31 +/- 5 Km/s for the star. We show that the mode f_1 must be close to an avoided crossing. Constraints on the mass (13.5 +/- 0.5 Msun), age (12.4 +/- 0.7 Myr) and core overshoot (0.20 +/- 0.05 H_P) of beta CMa are obtained from seismic modelling using f_1 and f_2.Comment: Accepted for publication in A&