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In this paper, we investigate the impingement of a two-dimensional (2-D) vortex pair translating downwards onto a horizontal wall with a wavy surface. A principal purpose is to compare the vortex dynamics with the complementary case of a wavy vortex pair (deformed by the long-wavelength Crow instability) impinging onto a flat surface. The simpler case of a 2-D vortex pair descending onto a flat horizontal ground plane leads to the well known ‘rebound’ effect, wherein the primary vortex pair approaches the wall but subsequently advects vertically upwards, due to the induced velocity of secondary vorticity. In contrast, a wavy vortex pair descending onto a flat plane leads to ‘rebounding’ vorticity in the form of vortex rings. A descending 2-D vortex pair, impinging on a wavy wall, also generates ‘rebounding’ vortex rings. In this case, we observe that the vortex pair interacts first with the ‘hills’ of the wavy wall before the ‘valleys’. The resulting secondary vorticity rolls up into a concentrated vortex tube, ultimately forming a vortex loop along each valley. Each vortex loop pinches off to form a vortex ring, which advects upwards. Surprisingly, these rebounding vortex rings evolve without the strong axial flows fundamental to the wavy vortex case. The present research is relevant to wing tip trailing vortices interacting with a non-uniform ground plane. A non-flat wall is shown to accelerate the decay of the primary vortex pair. Such a passive, ground-based method to diminish the wake vortex hazard close to the ground is consistent with Stephan et al. (J. Aircraft, vol. 50 (4), 2013a, pp. 1250–1260; CEAS Aeronaut. J., vol. 5 (2), 2013b, pp. 109–125).
Nearly half of care home residents with advanced dementia have clinically significant agitation. Little is known about costs associated with these symptoms toward the end of life. We calculated monetary costs associated with agitation from UK National Health Service, personal social services, and societal perspectives.
Prospective cohort study.
Thirteen nursing homes in London and the southeast of England.
Seventy-nine people with advanced dementia (Functional Assessment Staging Tool grade 6e and above) residing in nursing homes, and thirty-five of their informal carers.
Data collected at study entry and monthly for up to 9 months, extrapolated for expression per annum. Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI). Health and social care costs of residing in care homes, and costs of contacts with health and social care services were calculated from national unit costs; for a societal perspective, costs of providing informal care were estimated using the resource utilization in dementia (RUD)-Lite scale.
After adjustment, health and social care costs, and costs of providing informal care varied significantly by level of agitation as death approached, from £23,000 over a 1-year period with no agitation symptoms (CMAI agitation score 0–10) to £45,000 at the most severe level (CMAI agitation score >100). On average, agitation accounted for 30% of health and social care costs. Informal care costs were substantial, constituting 29% of total costs.
With the increasing prevalence of dementia, costs of care will impact on healthcare and social services systems, as well as informal carers. Agitation is a key driver of these costs in people with advanced dementia presenting complex challenges for symptom management, service planners, and providers.
Congenital renal and urinary tract anomalies are common, accounting for up to 21% of all congenital abnormalities . The reported incidence is approximately 1:250–1:1000 pregnancies  and the routine use of prenatal ultrasonography allows relatively early detection, particularly for the obstructive uropathies, which account for the majority. According to the latest UK renal registry report in 2015, ‘obstructive uropathy’ was the second leading cause (19%) of chronic renal failure in children under 16 years of age after renal dysplasia +/− reflux . The obstructions may occur within the upper or lower urinary tract, and their prognosis varies significantly, with obstructions at the level of the bladder neck being associated with the majority of neonatal mortality and renal failure. In untreated cases, perinatal mortality is high (up to 45%, often because of associated severe oligohydramnios and pulmonary hypoplasia) , and 30% of the survivors suffer from end-stage renal failure (ESRF) requiring dialysis and renal transplantation before the age of 5 . The overall chance of survival in childhood is lowest if renal support therapy or transplantation is commenced before 2 years old when compared with starting at 12–16 years old (hazard ratio [HR] of 4.1, 95% confidence interval [CI] 1.7–9.9, P = 0.002) . Therefore, in utero intervention, by the insertion of a vesicoamniotic shunt, or therapeutic treatment by fetal cystoscopy and valvular ablation, has been attempted to attenuate in utero progression of these pathologies (and their consequences) and to alter the natural history of congenital bladder neck obstruction in childhood. In this chapter, we discuss the etiology, pathophysiology, prenatal presentation and diagnosis of congenital bladder neck obstruction. Suggested algorithms for screening and the prenatal prognostic evaluation in selecting candidates for in utero therapy will be discussed.
Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson’s disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurodegenerative and neuroprogressive disorders, there are detrimental effects of oxidative stress, mitochondrial dysfunction, and neuroinflammation on neuronal function. However, they also adversely impact on neurone–glia interactions, disrupting the role of microglia and astrocytes in central nervous system (CNS) homeostasis. Astrocytes are the main site of CNS fatty acid oxidation; the resulting ketone bodies constitute an important source of oxidative fuel for neurones in an environment of glucose restriction. Importantly, the lactate shuttle between astrocytes and neurones is dependent on glycogenolysis and glycolysis, resulting from the fact that the astrocytic filopodia responsible for lactate release are too narrow to accommodate mitochondria. The entry into the CNS of ketone bodies and fatty acids, as a result of nutritional ketosis, has effects on the astrocytic glutamate–glutamine cycle, glutamate synthase activity, and on the function of vesicular glutamate transporters, EAAT, Na+, K+-ATPase, Kir4.1, aquaporin-4, Cx34 and KATP channels, as well as on astrogliosis. These mechanisms are detailed and it is suggested that they would tend to mitigate the changes seen in many neurodegenerative and neuroprogressive disorders. Hence, it is hypothesized that nutritional ketosis may have therapeutic applications in such disorders.
Introduction: Transcutaneous cardiac pacing (TCP) is recommended for the treatment of symptomatic bradycardia, a life-threatening condition. Although TCP is taught in ACLS (advanced cardiac life support) courses, it is a difficult skill to master for junior residents. The main objective of this study is to measure the impact of having access to a checklist on successful TCP implementation. Our hypothesis was that the availability of a CL would improve performance of junior residents in the management of symptomatic bradycardia by facilitating TCP. Methods: We conducted a prospective, randomized, single-site study. First-year residents entering postgraduate programs and taking a mandatory ACLS course were enrolled. Students had didactic sessions on the management of symptomatic bradycardia followed by hands-on teaching on a low-fidelity manikin (ALS® simulator, Laerdal) using a CL conceived for this project as a teaching tool. Study participants were then assessed with a simulation scenario requiring TCP. Participants were randomly assigned to groups with and without CL accessibility. Performances were graded on six critical tasks. The primary outcome was the successful use of TCP, defined as having completed all tasks. Participants then completed a post-test questionnaire. Sample size estimation was based on a previous project (Ranger et al., 2018). Accepting an alpha error of 0.05 and a power of 80%, 45 participants in each group would permit the detection of 26.5% in performance gain. Results: Of 250 residents completing the ACLS course in 2017, 85 voluntary participants were randomized to a control group (no CL available during testing, n = 42) or an experimental group (CL available during testing, n = 43). Six participants in the experimental group adequately used TCP compared to five participants in the control group (p = 0.81, chi-squared test). Out of the 43 participants who had access to the CL, only 2 (5%) used it. Reasons why the CL was infrequently used were stated as the following: 24 participants (56%) mentioned not realizing it was available, 8 (19%) considered it was of little to no utility and 5 (19%) forgot a CL existed. Conclusion: Availability of a checklist previously used during simulation teaching did not increase junior residents’ capacity to correctly apply TCP. Non-recognition of CL availability and decreased perceived need for it were the main reasons for marginal use. Our results suggest that there are many limiting factors to CL effectiveness.
Introduction: Individualizing risk for stroke following a transient ischemic attack (TIA) is a topic of intense research, as existing scores are context-dependent or have not been well validated. The Canadian TIA Score stratifies risk of subsequent stroke into low, moderate and high risk. Our objective was to prospectively validate the Canadian TIA Score in a new cohort of emergency department (ED) patients. Methods: We conducted a prospective cohort study in 14 Canadian EDs over 4 years. We enrolled consecutive adult patients with an ED visit for TIA or nondisabling stroke. Treating physicians recorded standardized clinical variables onto data collection forms. Given the ability of prompt emergency carotid endarterectomy (CEA) to prevent stroke (NNT = 3) in high risk patients, our primary outcome was the composite of subsequent stroke or CEA ≤7 days. We conducted telephone follow-up using the validated Questionnaire for Verifying Stroke Free Status at 7 and 90 days. Outcomes were adjudicated by panels of 3 local stroke experts, blinded to the index ED data collection form. Based on prior work, we estimated a sample size of 5,004 patients including 93 subsequent strokes, would yield 95% confidence bands of +/− 10% for sensitivity and likelihood ratio (LR). Our analyses assessed interval LRs (iLR) with 95% CIs. Results: We prospectively enrolled 7,569 patients with mean 68.4 +/−14.7 years and 52.4% female, of whom 107 (1.4%) had a subsequent stroke and 74 (1.0%) CEA ≤7 days (total outcomes = 181). We enrolled 81.2% of eligible patients; missed patients were similar to enrolled. The Canadian TIA Score stratified the stroke/CEA ≤7days risk as: Low (probability <0.2%, iLR 0.20 [95%CI 0.091-0.44]; Moderate (probability 1.3%, iLR 0.79 [0.68-0.92]; High (probability 2.6%, iLR 2.2 [1.9-2.6]. Sensitivity analysis for just stroke ≤7 days yielded similar results: Low iLR 0.17 [95%CI 0.056-0.52], Medium iLR 0.89 [0.75-1.1], High iLR 2.0 [1.6-2.4]. Conclusion: The Canadian TIA Score accurately identifies TIA patients risk for stroke/CEA ≤7 days. Patients classified as low risk can be safely discharged following a careful ED assessment with elective follow-up. Patients at moderate risk can undergo additional testing in the ED, have antithrombotic therapy optimized, and be offered early stroke specialist follow-up. Patients at high risk should in most cases be fully investigated and managed ideally in consultation with a stroke specialist during their index ED visit.
Important ear problems can affect the outer ear, the middle ear and the inner ear. Globally, the greatest burden of disease is due to ear conditions that are associated with otorrhoea and hearing loss.
This study reviewed the literature on the prevention and treatment of common ear conditions that are most relevant to settings with high rates of ear disease and limited resources. The grading of recommendations assessment, development and evaluation (‘GRADE’) approach was utilised to assess interventions.
Accurate diagnosis of ear disease is challenging. Much of the preventable burden of ear disease is associated with otitis media. Nine otitis media interventions for which there is moderate to high certainty of effect were identified. While most interventions only provide modest benefit, the impact of treatment is more substantial in children with acute otitis media with perforation and chronic suppurative otitis media.
Disease prevention through good hygiene practices, breastfeeding, reducing smoke exposure, immunisation and limiting noise exposure is recommended. Children with acute otitis media with perforation, chronic suppurative otitis media, complications of otitis media, and significant hearing loss should be prioritised for medical treatment.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.
Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.
We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).
These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
To assess relationships between mothers’ feeding practices (food as a reward, food for emotion regulation, modelling of healthy eating) and mothers’ willingness to purchase child-marketed foods and fruits/vegetables (F&V) requested by their children during grocery co-shopping.
Cross-sectional. Mothers completed an online survey that included questions about feeding practices and willingness (i.e. intentions) to purchase child-requested foods during grocery co-shopping. Feeding practices scores were dichotomized at the median. Foods were grouped as nutrient-poor or nutrient-dense (F&V) based on national nutrition guidelines. Regression models compared mothers with above-the-median v. at-or-below-the-median feeding practices scores on their willingness to purchase child-requested food groupings, adjusting for demographic covariates.
Participants completed an online survey generated at a public university in the USA.
Mothers (n 318) of 2- to 7-year-old children.
Mothers who scored above-the-median on using food as a reward were more willing to purchase nutrient-poor foods (β=0·60, P<0·0001), mothers who scored above-the-median on use of food for emotion regulation were more willing to purchase nutrient-poor foods (β=0·29, P<0·0031) and mothers who scored above-the-median on modelling of healthy eating were more willing to purchase nutrient-dense foods (β=0·22, P<0·001) than were mothers with at-or-below-the-median scores, adjusting for demographic covariates.
Mothers who reported using food to control children’s behaviour were more willing to purchase child-requested, nutrient-poor foods. Parental feeding practices may facilitate or limit children’s foods requested in grocery stores. Parent–child food consumer behaviours should be investigated as a route that may contribute to children’s eating patterns.
Rapid weight gain in infancy and low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) at birth are associated with increased adiposity later in life. The association between placental LCPUFA delivery and weight gain in infancy is poorly understood. We sought to determine the relationships between maternal phenotype, placental fatty acid transporter expression and offspring growth patterns over the first 6 months. Placental tissue and cord blood were collected at term delivery from women with uncomplicated pregnancies. Offspring body composition measurements were recorded 1 day and 6 months after birth. Body mass index (BMI) z-scores were determined using World Health Organization 2006 reference data. Body phenotype patterns were compared among offspring who had an increase in BMI z-score and those who had a decrease. High skinfold thickness at birth and positive change in BMI z-scores during infancy were associated with low neonatal n-3 LCPUFA plasma levels (r=−0.46, P=0.046) and high saturated fatty acids levels (r=0.49, P=0.034). Growth of skinfolds over 6 months of age was associated with placental fatty acid transporter gene expression. Change in BMI z-score in the first 6 months of life correlated with arm muscle area growth, a measure of lean mass (r=0.62, P=0.003), but not with growth in skinfold thickness. Early infancy weight gain was associated with poor plasma LCPUFA status at birth, and fat deposition in infancy was related to changes in placental lipid handling. Thus, neonatal fatty acid profiles may influence the trajectory of infant growth and fat and lean mass deposition.
Functional neurological disorders (FNDs), also known as conversion disorder, are unexplained neurological symptoms unrelated to a neurological cause. The disorder is common, yet poorly understood. The symptoms are experienced as involuntary but have similarities to voluntary processes. Here we studied intention awareness in FND.
A total of 26 FND patients and 25 healthy volunteers participated in this functional magnetic resonance study using Libet's clock.
FND is characterized by delayed awareness of the intention to move relative to the movement itself. The reporting of intention was more precise, suggesting that these findings are reliable and unrelated to non-specific attentional deficits. That these findings were more prominent with aberrant positive functional movement symptoms rather than negative symptoms may be relevant to impairments in timing for an inhibitory veto process. Attention towards intention relative to movement was associated with lower right inferior parietal cortex activity in FND, a region early in the processing of intention. During rest, aberrant functional connectivity was observed with the right inferior parietal cortex and other motor intention regions.
The results converge with observations of low inferior parietal activity comparing involuntary with voluntary movement in FND, emphasizing core deficiencies in intention. Heightened precision of this impaired intention is consistent with Bayesian theories of impaired top-down priors that might influence the sense of involuntariness. A primary impairment in voluntary motor intention at an early processing stage might explain clinical observations of slowed effortful voluntary movement, heightened self-directed attention and underlie functional movements. These findings further suggest novel therapeutic targets.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Late Medieval Castles is a companion to Anglo-Norman Castles (2003), a volume that brought together a series of historiographically significant articles on castles and castle-building in the period from the Norman Conquest to the early thirteenth century. The format and themes of the present collection are broadly comparable with the earlier book, but with the focus on those castles dating to the period c.1250–1500.
In the course of bringing Anglo-Norman Castles to publication the somewhat arbitrary cut-off date of c.1225 seemed unsatisfactory for a number of reasons. On a practical level, there were highly relevant articles that could not be included because the subject matter fell outside the chronological range of the volume. A more scholarly concern was the fact that a number of issues pertinent to castle-building in the eleventh and twelfth centuries could not be satisfactorily addressed without reference to subsequent developments in the thirteenth and fourteenth. Allied to this, a focus on Anglo-Norman building (no matter how justifiable in historical terms) does perhaps contribute, albeit unwittingly, to the erroneous idea that the eleventh and twelfth centuries are the most important centuries for castle-building, a time when the ‘true’ castle is to be found, and that the period that follows, particularly after 1300, is something of an anti-climax. The present volume should therefore be seen as a continuation of the broad themes discussed in the introduction to Anglo-Norman Castles, with the aim of pursuing them in a late medieval context.
In the years since 2003 there have been a number of important publications in the field of castle studies, and castles continue to be a source of controversy and to provoke debate. Despite the fact that the availability of some secondary material has been made easier through electronic access, I have been consistently reminded by academic colleagues that a compilation such as this is worthwhile, both for the student reader and those seeking a path into the specialist secondary literature. This author at least also believes that there is value in bringing together in one place a series of important contributions that have defined the subject and which also illustrate a diversity of approaches.