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Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
This article reports on an evaluation of the Keeping Children Safe parent education programme run in Central West New South Wales. The programme, conducted since 2004, and continuing today, primarily targets parents of children at risk and other vulnerable and disadvantaged families. The evaluation covers a 13-year period, from the first group held in May 2004 to February 2017. From the beginning, the authors strategically endeavoured to recruit and retain parents from the target group. Findings from the literature indicate that this group is difficult to engage and retain in parent education groups. Parents targeted for the groups in this study were generally not receiving parent education elsewhere. Using mixed methods, the facilitators have continuously evaluated the programme in terms of attendance rates, process and impact. The results of these evaluations show successful recruitment and retention of participants from the target group over the 13 years of the evaluation reporting period and indicate that the programme’s immediate impact on participants has been favourable. The findings complement other programme evaluations focusing on recruitment and retention to programmes in the child protection context and on hard-to-reach clients. The authors also argue the importance of education for parents about child abuse and neglect.
In this note we consider parabolic subroot systems of a complex simple Lie Algebra. We describe root theoretic data of the subroot systems in terms of that of the root system and we give a selection of applications of our results to the study of generalized flag manifolds.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Attendance at overnight school camp is an integral component of the Australian educational landscape. However, some students are reluctant to attend camp, while others refuse to attend at all. School psychologists play an important part in supporting these students and their families, and teachers. While much is published about general school refusal, there is surprisingly little attention given to the specific management of school camp refusal and reluctance. This article summarises the contribution of the related theoretical areas of childhood anxiety, school refusal, and homesickness. It then outlines, through a case study example, a management approach for school psychologists, from presentation of the problem to assessment, through to informed intervention, including a suite of strategies to support the student, parents and teachers, who have duty of care during camps.
There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.
To determine the association between gestational vitamin D status and ASD.
Based on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).
Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.
Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.
Objectives: The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Methods: Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Results: Latent class analysis categorized participants into “high” (44%) and “low” (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (ps<.001). Hierarchical logistic regression indicated that, of the above, self-reported symptoms and executive dysfunction accounted for the most variance in the prediction of self-reported academic problems. Conclusions: Post-concussion symptom severity and executive dysfunction significantly predict perceived post-injury academic problems. EBA modeling identified the strongest set of predictors of academic challenges, offering an important perspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038–1049)
The problem of active feedback control of fluid flows falls into a class of problems in the area of distributed parameter control. Distributed parameter systems are typically defined by partial differential equations that model the time and spatial evolution of the process. We consider the problem of locating sensors for effective feedback control of a fluid flow problem described by the Navier–Stokes equations. In this setting, the state of the system is the velocity field
, and hence all feedback laws are a function of this velocity field or, in most practical settings, a function of sensor outputs. In many designs, the feedback control law can be represented as a linear function of the state defined by an integral operator with a kernel function called the functional gain. In this paper we show that these functional gains can be used to determine effective sensor placement in complex flow control applications. The approach is to choose measurements of the state that would provide good quadrature points for the integral operator. We provide a computational validation of this approach by controlling the vortex shedding in a two-dimensional cylinder flow using a pair of fluid actuators on the cylinder surface. This model is linearized about the mean flow and a feedback control is designed by pole placement. Distributed parameter control theory yields the existence and form of the functional gains which are used to locate sensors. In particular, we use the location of the supports of the functional gains to determine two sets of four sensor locations in the wake. One of these measurement sets coincides with large magnitudes of the gain and the other set coincides with small magnitudes. Numerical experiments with a reduced-order model confirm superior performance of the closed-loop (CL) system using the former sensor set. We also show that choosing sensor locations associated with small magnitudes of the functional gains actually destabilizes the CL system.
In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute, to describe the “state of the art” of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure.
Scholarly work in the 1990s indicated that the values of civil servants in late colonial Hong Kong were evolving from those of classical bureaucrats to those of more political bureaucrats as the political and social environment changed. Based on in-depth interviews with 58 politicians and senior civil servants carried out between 2009 and 2012, we argue that Hong Kong civil service values have adapted owing in part to external shocks such as regime change and governance reform. Still, traditional civil service values such as fiscal prudence and balancing various community interests continue to be prominent. We illustrate the influence of civil service values in two policymaking cases: small-class teaching and minimum-wage legislation.
Using Burgers’ equation with mixed Neumann–Dirichlet boundary conditions, we highlight a
problem that can arise in the numerical approximation of nonlinear dynamical systems on
computers with a finite precision floating point number system. We describe the dynamical
system generated by Burgers’ equation with mixed boundary conditions, summarize some of
its properties and analyze the equilibrium states for finite dimensional dynamical systems
that are generated by numerical approximations of this system. It is important to note
that there are two fundamental differences between Burgers’ equation with mixed
Neumann–Dirichlet boundary conditions and Burgers’ equation with both Dirichlet boundary
conditions. First, Burgers’ equation with homogenous mixed boundary conditions on a finite
interval cannot be linearized by the Cole–Hopf transformation. Thus, on finite intervals
Burgers’ equation with a homogenous Neumann boundary condition is truly nonlinear. Second,
the nonlinear term in Burgers’ equation with a homogenous Neumann boundary condition is
not conservative. This structure plays a key role in understanding the complex dynamics
generated by Burgers’ equation with a Neumann boundary condition and how this structure
impacts numerical approximations. The key point is that, regardless of the particular
numerical scheme, finite precision arithmetic will always lead to numerically generated
equilibrium states that do not correspond to equilibrium states of the Burgers’ equation.
In this paper we establish the existence and stability properties of these numerical
stationary solutions and employ a bifurcation analysis to provide a detailed mathematical
explanation of why numerical schemes fail to capture the correct asymptotic dynamics. We
extend the results in [E. Allen, J.A. Burns, D.S. Gilliam, J. Hill and V.I. Shubov,
Math. Comput. Modelling 35 (2002) 1165–1195] and prove
that the effect of finite precision arithmetic persists in generating a nonzero numerical
false solution to the stationary Burgers’ problem. Thus, we show that the results obtained
in [E. Allen, J.A. Burns, D.S. Gilliam, J. Hill and V.I. Shubov, Math. Comput.
Modelling 35 (2002) 1165–1195] are not dependent on a specific
time marching scheme, but are generic to all convergent numerical approximations of
Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes.
To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia.
A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0–13 weeks and 0–39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods.
There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively.
In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.
Background: Cognitive impairment and depression are common and disabling non-motor symptoms of Parkinson's disease (PD). Previous studies have shown associations between them but the nature of the relationship remains unclear. In chronic illness, problem- or task-oriented coping strategies are associated with better outcome but often require higher level cognitive functioning. The present study investigated, in a sample of patients with PD, the relationships between cognitive function, choice of coping strategies, and a broad index of outcome including depression, anxiety, and health-related quality of life (QoL). It was hypothesized that the coping strategy used could mediate the association between cognition and outcome.
Methods: 347 participants completed the Coping Inventory for Stressful Situations, the Hospital Anxiety and Depression Scale, the Parkinson's Disease Questionnaire-8, the Unified Parkinson's Disease Rating Scale, and the Addenbrooke's Cognitive Examination–Revised. Structural Equation Modeling was used to test the hypothesized model of cognition, coping, and outcome based on a direct association between cognition and outcome and an indirect association mediated by coping.
Results: Overall, poorer cognition predicted less use of task-oriented coping, which predicted worse outcome (a latent variable comprised of higher depression and anxiety and lower QoL). The analyses suggested a small indirect effect of cognition on outcome mediated by coping.
Conclusions: The findings suggest that patients who fail to employ task-oriented coping strategies may be at greater risk of depression, anxiety, and poor health-related QoL. Even mild to moderate cognitive impairment may contribute to reduced use of task-oriented coping. Suitably adapted cognitive–behavioral approaches may be useful to enable the use of adaptive coping strategies in such patients.
This paper describes a semi-automated conductive ink process used for packaging MEMS devices. The method is applied to packaging of MEMS sensors for wind tunnel testing. The primary advantage of the method is a reduction in surface topology between the package and the integrated MEMS sensors. In this paper we explore the relationship between trace dimensions, resistivity, and deposition parameters such as feed rate, tip-substrate separation and tip diameter. Using this procedure it is possible to generate interconnects between a PC board and MEMS sensor chip with a topology of less than 25 micrometers.
Many metallic actinide systems host partially filled 5f electrons in the low-energy spectrum. Consequently, they exhibit diverse quantum mechanical phenomena such as magnetism, superconductivity, a mysterious hidden-order phase, or heavy-fermion behavior. Here we present results of a unified theoretical method based on the self-consistent GW formalism for the electronic many-body self-energy. We calculate the dynamic electronic correlation spectra starting from materials specific first-principles electronic band-structure. In particular, we present results for four isostructural intermetallic actinides PuCoIn5, PuCoGa5, PuRhGa5, and UCoGa5. A common underlying property of these materials is a strong spin–orbit coupling split band structure that enables substantial spin fluctuations. In a feedback effect on the electronic structure they create electronic ‘hot spots’, where the single-particle spectral weight is maximum, resulting in a universal peak-dip-hump feature. These results are in good agreement with experiments, suggesting that actinides are adequately described by the intermediate Coulomb interaction regime, where both itinerant (peak) and localized (hump) features coexist.
The electronic structure of delta plutonium (δ-Pu) and plutonium compounds is investigated using photoelectron spectroscopy (PES). Results for δ-Pu show a small component of the valence electronic structure which might reasonably be associated with a 5f6 configuration. PES results for PuTe are used as an indication for the 5f6 configuration due to the presence of atomic multiplet structure. Temperature dependent PES data on δ-Pu indicate a narrow peak centered 20 meV below the Fermi energy and 100 meV wide. The first PES data for PuCoIn5 indicate a 5f electronic structure more localized than the 5fs in the closely related PuCoGa5. There is support from the PES data for a description of Pu materials with an electronic configuration of 5f5 with some admixture of 5f6 as well as a localized/delocalized 5f5 description.