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Engineering design methods are typically evaluated via case studies, surveys, and experiments. Meanwhile, domains such as the health sciences as well as software engineering have developed further powerful evaluation approaches. The objective of this paper is to show how evaluation approaches from the health sciences and software engineering might further the evaluation of engineering design methods. We survey these approaches and show which approaches could be transferred to the evaluation of engineering design methods.
The identification of new genetic variants underlying psychosis is crucial to improve its molecular diagnosis and to determine the disease etiology, which is necessary to develop new therapeutic targets.
Aim
To identify novel rare genetic variants associated to mental disorders, using whole exome sequencing (WES).
Methods
Two families with high prevalence of mental disease were genotyped using WES. The first family has 5 members affected, the mother with a bipolar disorder, three sons, two with schizophrenia and one with schizoaffective disorder, and a cousin with major depression and psychotic symptoms. The second family is constituted by 38 members affected by major mental diseases in three generations. Key affected members of each family were genotyped by WES. Shared rare variants, with allelic frequencies below 0.5% in general population, were identified among the affected members of the family. The segregation of those variants was confirmed by Sanger sequencing.
Results
In family 1, thirty-seven genetic variants related to neurodevelopment were identified. Two of those variants in the genes TRIP12 and RNF25 segregated with psychosis. In family 2, seven rare genetic variants contained in genes related to neurodevelopment were identified. A mutation in the gene ARHGAP19 segregated with psychosis.
Conclusions
Three new genes have been found to be associated with psychosis. TRIP12 and RNF25 encode two E3-ubiquitin ligases which modulate the Wnt pathway, mutations in which lead to neurodevelopmental defects. ARHGAP19 encodes a GTPase which regulates the RhoA protein, involved in the regulation of the cytoskeleton.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
To develop a proactive person-centered care approach for persons with (multiple) chronic diseases in general practice, and to explore the impact on ‘Quadruple aims’: experiences of patients and professionals, patient outcomes and costs of resources use.
Background:
The management of people with multiple chronic diseases challenges health care systems designed around single disease. Patients with multimorbidity often receive highly fragmented care that may lead to inefficient, ineffective and potentially harmful treatments and neglect of essential health needs. A more comprehensive, person-centered approach is advocated for persons with multiple morbidities. However, examples on how to provide more person-centered care and evidence of its impact are scarce. A group of Dutch general practitioners (GPs) took the initiative to develop such a care approach.
Methods/Design:
Mixed methods with a development and pilot-testing phase. The proactive person-centered approach will be developed using an action-based research design consisting of multiple plan-act-observe-reflect-adjust cycles. In each cycle, experiences of patients and primary care professionals from 13 practices will be collected via interviews, observations and focus groups. Starting point for the first cycle is a ‘person-centered consultation’ of up to 1 h in which the GP discusses the health status and health care needs of the patient. Furthermore, shared decisions between GP and patient are made on treatment goals and follow-up. In the pilot-test phase, a nested case cohort study allows to explore the impact of the new approach on ‘Quadruple aim’ outcomes comparing persons with and without exposure to the new care approach.
Discussion:
This study will provide a proactive person-centered approach for persons with multimorbidity in primary care and estimate its potential impact on quadruple outcomes.
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of
${>}200~\text{TW}$
was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
Identifying characteristics of individuals at greatest risk for prolonged grief disorder (PGD) can improve its detection and elucidate the etiology of the disorder. The Safe Passage Study, a study of women at high risk for sudden infant death syndrome (SIDS), prospectively examined the psychosocial functioning of women while monitoring their healthy pregnancies. Mothers whose infants died of SIDS were followed in bereavement.
Methods
Pre-loss data were collected from 12 000 pregnant mothers and analyzed for their associations with grief symptoms and PGD in 50 mothers whose infants died from SIDS, from 2 to 48 months after their infant's death, focusing on pre-loss risk factors of anxiety, depression, alcohol use, maternal age, the presence of other living children in the home, and previous child loss.
Results
The presence of any four risk factors significantly predicted PGD for 24 months post-loss (p < 0.003); 2–3 risk factors predicted PGD for 12 months (p = 0.02). PGD rates increased in the second post-loss year, converging in all groups to approximately 40% by 3 years. Pre-loss depressive symptoms were significantly associated with PGD. Higher alcohol intake and older maternal age were consistently positively associated with PGD. Predicted risk scores showed good discrimination between PGD and no PGD 6–24 months after loss (C-statistic = 0.83).
Conclusions
A combination of personal risk factors predicted PGD in 2 years of bereavement. There is a convergence of risk groups to high rates at 2–3 years, marked by increased PGD rates in mothers at low risk. The risk factors showed different effects on PGD.
Karlsruhe Institute of Technology (KIT) is doing research and development in the field of megawatt-class radio frequency (RF) sources (gyrotrons) for the Electron Cyclotron Resonance Heating (ECRH) systems of the International Thermonuclear Experimental Reactor (ITER) and the DEMOnstration Fusion Power Plant that will follow ITER. In the focus is the development and verification of the European coaxial-cavity gyrotron technology which shall lead to gyrotrons operating at an RF output power significantly larger than 1 MW CW and at an operating frequency above 200 GHz. A major step into that direction is the final verification of the European 170 GHz 2 MW coaxial-cavity pre-prototype at longer pulses up to 1 s. It bases on the upgrade of an already existing highly modular short-pulse (ms-range) pre-prototype. That pre-prototype has shown a world record output power of 2.2 MW already. This paper summarizes briefly the already achieved experimental results using the short-pulse pre-prototype and discusses in detail the design and manufacturing process of the upgrade of the pre-prototype toward longer pulses up to 1 s.
The Amsterdam glacial basin was a major sedimentary sink from late Saalian until late Eemian (Picea zone, E6) times. The basin’s exemplary record makes it a potential reference area for the last interglacial stage. The cored Amsterdam-Terminal borehole was drilled in 1997 to provide a record throughout the Eemian interglacial. Integrated facies analysis has resulted in a detailed reconstruction of the sedimentary history.
After the Saalian ice mass had disappeared from the area, a large, deep lake had come into being, fed by the Rhine river. At the end of the glacial, the lake became smaller because it was cut off from the river-water supply, and eventually only a number of shallow pools remained in the Amsterdam basin. During the early Eemian (Betula zone, El), a seepage lake existed at the site. The lake deepened under the influence of a steadily rising sea level and finally evolved into a silled lagoon (late Quercus zone, E3). Initially, the lagoon water had fairly stable stratification, but as the sea level continued to rise the sill lost its significance, the lagoon becoming well mixed by the middle of the Corylus/Taxus zone (E4b). The phase of free exchange with the open sea ended in the early Carpinus zone (E5), when barriers developed in the sill area causing the lagoon to become stratified again. During the Late Eemian (late E5), a more dynamic system developed. The sandy barriers that had obstructed exchange with the open sea were no longer effective, and a tidally-influenced coastal lagoon formed.
The Eemian sedimentary history shown in the Amsterdam-Terminal borehole is intimately connected with the sea-level history. Because the site includes both a high-resolution pollen signal and a record of sea-level change, it has potential for correlation on various scales. Palaeomagnetic results show that the sediments predate the Blake Event, which confirms that this reversal excursion is relatively young. The U/Th age of the uppermost part of the Eemian sequence is 118.2±6.3 ka.
CuxO thin films have been deposited on a quartz substrate by reactive radio frequency (rf) magnetron sputtering at different target powers Pt (140-190 W) while keeping other growth process parameters fixed. Room-temperature photoluminescence (PL) measurements indicate considerable improvement of crystallinity for the films deposited at Pt>170 W, with most pronounced excitonic features being observed in the film grown using Pt=190 W. These results corroborate well with the surface morphology of the films, which was found more flat, smooth and homogeneous for Pt >170 W films in comparison with those deposited at lower powers.
A load moving on sea ice, whether the weight of a vehicle or the pressure exerted by a low-flying aircraft, produces a deflection which can in extreme cases cause ice failure. The magnitude and shape of the deflection profile depends on the weight and speed of the vehicle) and also the the ice thickness and properties, with flexuralgraviry waves radiating from the source at speeds above a critical value. This wave pattern was studied in detail on flat, snow-free sea ice in McMurdo Sound, Antarctica. Surface strain was measured directly and microcracking activity monitored to correlate measured strain with possible generation of dangerous cracks. Speeds of up to 28 m sec-1 (60 mph) were achieved with a pickup truck, and up to 80 m sec-1 with a US Navy C131 aircraft. Initial comparison between theory and experimental results is very encouraging.
Background: The aging society will bring an increase in the number of people with dementia living in the community. This will mean a greater demand on care and welfare services to deliver efficient and customized care, which requires a thorough understanding of subjective and objective care needs. This study aims to assess the needs of community-dwelling people with dementia as reported by themselves and by their informal carers. The study also aims to give insight into the service use and gaps between needs and the availability of services.
Methods: 236 community-dwelling people with dementia and 322 informal carers were interviewed separately. (Un)met needs were assessed using the Camberwell Assessment of Needs for the Elderly (CANE).
Results: Most unmet needs were experienced in the domains of memory, information, company, psychological distress and daytime activities. People with dementia reported fewer (unmet) needs than their carers. Type and severity of dementia, living situation and informal carer characteristics were related to the number of reported needs.
Conclusions: This study showed a large number of unmet needs in dementia. Reasons for unmet needs are lack of knowledge about the existing service offer, a threshold to using services and insufficient services offer. These results provide a good starting point for improving community care for people with dementia.
Background: Tailor-made care in dementia requires an individual needs assessment. The Camberwell Assessment of Need for the Elderly (CANE) was developed to assess needs of older people with mental disorders. In this study the validity and reliability of the Dutch version of the CANE were studied among community-dwelling persons with dementia and their informal carers.
Method: Interviews were carried out with 236 people with mild to severe dementia and 322 informal carers; 69 informal carers were interviewed twice. Construct and criterion validity and test-retest reliability of the CANE were studied using data for informal carers. Construct validity was also studied for CANE ratings of people with dementia.
Results: The construct validity of the CANE was good among people with dementia and informal carers. Criterion validity could be studied for 76.9% of the CANE items, and all significant correlations were convergent. Test-retest reliability of the CANE varied from poor to very good and was best on domains where needs were explicit and problems well defined.
Conclusions: Use of the Dutch version of the CANE among community-dwelling people with dementia and their carers is supported by the study results, with the study showing acceptable construct and criterion validity and test-retest reliability of the CANE.
The present study investigates the benefits of the dietary intake of chia seed (Salvia hispanica L.) rich in α-linolenic acid and fibre upon dyslipidaemia and insulin resistance (IR), induced by intake of a sucrose-rich (62·5 %) diet (SRD). To achieve these goals two sets of experiments were designed: (i) to study the prevention of onset of dyslipidaemia and IR in Wistar rats fed during 3 weeks with a SRD in which chia seed was the dietary source of fat; (ii) to analyse the effectiveness of chia seed in improving or reversing the metabolic abnormalities described above. Rats were fed a SRD during 3 months; by the end of this period, stable dyslipidaemia and IR were present in the animals. From months 3–5, half the animals continued with the SRD and the other half were fed a SRD in which the source of fat was substituted by chia seed (SRD+chia). The control group received a diet in which sucrose was replaced by maize starch. The results showed that: (i) dietary chia seed prevented the onset of dyslipidaemia and IR in the rats fed the SRD for 3 weeks – glycaemia did not change; (ii) dyslipidaemia and IR in the long-term SRD-fed rats were normalised without changes in insulinaemia when chia seed provided the dietary fat during the last 2 months of the feeding period. Dietary chia seed reduced the visceral adiposity present in the SRD rats. The present study provides new data regarding the beneficial effect of chia seed upon lipid and glucose homeostasis in an experimental model of dislipidaemia and IR.
Quantum Hall (QH) systems can work as very sensitive THz detectors. In this work we report on the spectral and temporal resolution of the QH THz photodetectors with different geometries. The spectral resolution of THz QH detectors is of the order of 1-3 meV depending on bias conditions. The temporal resolution of QH detectors depends on the device geometry. For Corbino-shaped detectors we have demonstrated the devices with response times from 10 ns to over 200 ns.
Canada thistle is a serious perennial weed found throughout the northern regions of the United States and Canada. The weevil, Ceutorhynchus litura (F.), was first released in Canada in 1965 as a potential biological control agent for Canada thistle; however, its impact as a control agent has been sporadic. The objective of this study was to characterize C. litura impacts on the carbohydrate profile in Canada thistle roots through the growing season and to evaluate the potential for this biological control agent in causing stress to Canada thistle. Field plots, infested with C. litura, were established and extensively sampled for C. litura infestations. By sampling C. litura–damaged and undamaged Canada thistle shoots–roots through the season, we were able to establish the profile of free sugars and fructans in the roots and compare these levels to the presence and extent of insect damage. Levels of all free sugars and fructans were consistently found to be depressed in roots from C. litura–damaged shoots early in the summer during and shortly after the larval feeding period. Ceutorhynchus litura feeding in Canada thistle shoots appears to disrupt the movement of photoassimilates from leaves to roots. Late-season levels of free sugars and fructans indicate that roots do recover from these depressed levels, and in several instances, significant overcompensation occurred in the damaged roots. Measurement of free sugars and fructans to identify sublethal impacts of control tactics may allow the strategic combining of complementary tactics to maximize the impact of stresses on Canada thistle.
Sixty-six broiler flocks were sampled to determine the presence of Campylobacter spp. at slaughter in 1998. Thirty flocks (45%) tested positive and C. jejuni was identified in all isolates. Combined pulsed-field gel electrophoresis/amplified fragment length polymorphism (PFGE/AFLP) subtyping of 177 isolates from 24 positive flocks revealed 62 subtypes; 16 flocks harboured more than one subtype. When subtyping 101 clinical C. jejuni isolates collected in the same time period and area, 60 PFGE/AFLP types were identified. Comparison of subtypes from poultry and human isolates revealed three shared PFGE/AFLP types, which were present in 11 human isolates. Fifty per cent of all poultry isolates and 39% of all human isolates were resistant to ciprofloxacin. The present study confirms the increase in ciprofloxacin resistance in both human and poultry C. jejuni isolates in Austria, as observed in several countries worldwide. A small number of human isolates shared PFGE/AFLP types with poultry isolates, however, further studies should also focus on the identification of other sources of C. jejuni infection in humans.
As a tribute to the scientific work of Professor Gareth Thomas
in the field of structure-property relationships this paper
delineates a new possibility of Lorentz transmission electron
microscopy (LTEM) to study the magnetic properties of soft magnetic
films. We show that in contrast to the traditional point of
view, not only does the direction of the magnetization vector
in nano-crystalline films make a correlated small-angle wiggling,
but also the magnitude of the magnetization modulus fluctuates.
This fluctuation produces a rapid modulation in the LTEM image.
A novel analysis of the ripple structure in nano-crystalline
Fe-Zr-N film corresponds to an amplitude of the transversal
component of the magnetization ΔMy
of 23 mT and a longitudinal fluctuation of the magnetization of the
order of ΔMx = 30 mT. The nano-crystalline
(Fe99Zr1)1−xNx
films have been prepared by DC magnetron reactive sputtering with
a thickness between 50 and 1000 nm. The grain size decreased
monotonically with N content from typically 100 nm in the case
of N-free films to less than 10 nm for films containing 8 at%.
The specimens were examined with a JEOL 2010F 200 kV transmission
electron microscope equipped with a post column energy filter
(GIF 2000 Gatan Imaging Filter). For holography, the microscope
is mounted with a biprism (JEOL biprism with a 0.6 μm diameter
platinum wire).