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Ureteroscopy is a minimally invasive surgical procedure for the removal of kidney stones. A ureteroscope, containing a hollow, cylindrical working channel, is inserted into the patient's kidney. The renal space proximal to the scope tip is irrigated, to clear stone particles and debris, with a saline solution that flows in through the working channel. We consider the fluid dynamics of irrigation fluid within the renal pelvis, resulting from the emerging jet through the working channel and return flow through an access sheath. Representing the renal pelvis as a two-dimensional rectangular cavity, we investigate the effects of flow rate and cavity size on flow structure and subsequent clearance time of debris. Fluid flow is modelled with the steady incompressible Navier–Stokes equations, with an imposed Poiseuille profile at the inlet boundary to model the jet of saline, and zero-stress conditions on the outlets. The resulting flow patterns in the cavity contain multiple vortical structures. We demonstrate the existence of multiple solutions dependent on the Reynolds number of the flow and the aspect ratio of the cavity using complementary numerical simulations and particle image velocimetry experiments. The clearance of an initial debris cloud is simulated via solutions to an advection–diffusion equation and we characterise the effects of the initial position of the debris cloud within the vortical flow and the Péclet number on clearance time. With only weak diffusion, debris that initiates within closed streamlines can become trapped. We discuss a flow manipulation strategy to extract debris from vortices and decrease washout time.
Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
To disrupt cycles of health inequity, traceable to dietary inequities in the earliest stages of life, public health interventions should target improving nutritional wellbeing in preconception/pregnancy environments. This requires a deep engagement with pregnant/postpartum people (PPP) and their communities (including their health and social care providers, HSCP). We sought to understand the factors that influence diet during pregnancy from the perspectives of PPP and HSCP, and to outline intervention priorities.
We carried out thematic network analyses of transcripts from ten focus group discussions (FGD) and one stakeholder engagement meeting with PPP and HSCP in a Canadian city. Identified themes were developed into conceptual maps, highlighting local priorities for pregnancy nutrition and intervention development.
FGD and the stakeholder meeting were run in predominantly lower socioeconomic position (SEP) neighbourhoods in the sociodemographically diverse city of Hamilton, Canada.
All local, comprising twenty-two lower SEP PPP and forty-three HSCP.
Salient themes were resilience, resources, relationships and the embodied experience of pregnancy. Both PPP and HSCP underscored that socioeconomic-political forces operating at multiple levels largely determined the availability of individual and relational resources constraining diet during pregnancy. Intervention proposals focused on cultivating individual and community resilience to improve early-life nutritional environments. Participants called for better-integrated services, greater income supports and strengthened support programmes.
Hamilton stakeholders foregrounded social determinants of inequity as main factors influencing pregnancy diet. They further indicated a need to develop interventions that build resilience and redistribute resources at multiple levels, from the household to the state.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of “false positive” prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation.
This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B.
A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B.
The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.
In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
Given the equivocal literature on the relationship between internalizing symptoms and early adolescent alcohol use (AU) and AU disorder (AUD), the present study took a developmental perspective to understand how internalizing and externalizing symptoms may operate together in the etiology of AU and AUD. We pit the delayed onset and rapid escalation hypothesis (Hussong et al., 2011) against a synthesis of the dual failure model and the stable co-occurring hypothesis (Capaldi, 1992; Colder et al., 2013, 2018) to test competing developmental pathways to adolescent AU and AUD involving problem behavior, peer delinquency, and early initiation of AU. A latent transactional and mediational framework was used to test pathways to AUD spanning developmental periods before AU initiation (Mage = 11) to early and high risk for AUD (Mage = 14–15 and Mage = 17–18). The results supported three pathways to AUD. The first started with “pure” externalizing symptoms in early childhood and involved multiple mediators, including the subsequent development of co-occurring symptoms and peer delinquency. The second pathway involved stable co-occurring symptoms. Interestingly, chronically elevated pure internalizing symptoms did not figure prominently in pathways to AUD. Selection and socialization effects between early AU and peer delinquency constituted a third pathway.
Attention deficit/hyperactivity disorder (ADHD) often presents as an impairing lifelong condition in adults, yet it is currently under-diagnosed and under-treated in many European countries.
To establish the characteristics of the European (EU) adult ADHD patient relative to adult patients outside the EU (OEU).
To compare the baseline characteristics of patients with ADHD in regions where adult ADHD is relatively well established (e.g., USA), with EU adult ADHD patients.
Baseline data was used from the open-label acute treatment period of a multicenter, randomized, withdrawal trial of atomoxetine in adult patients with ADHD (N = 2017; EU, n = 1217; OEU, n = 800). All enrolled patients were included in the baseline analyses.
The demographics for patients in the EU region and regions OEU were comparable. Patients in the EU region had a somewhat lower percentage of prior exposure to psychostimulants compared to the region OEU (32.7% versus 38.9%, p = .005). Conners’ Adult ADHD Rating Scale-Investigator Rated: Screening Version with adult ADHD prompts (18 item total, inattentive and hyperactive/impulsive subscales, and index) were comparable. The adult ADHD Quality of Life life outlook and life productivity domain scores were different between groups (p ≤ .0004). The EuroQol-5 Dimension UK and US population-based Index score, and health state score were comparable between groups.
There were some subtle differences between study groups; however, overall, the adult ADHD patients were not substantially different between the EU region and regions OEU, suggesting that baseline features of ADHD in adult EU patients manifest comparable to those in patients OEU.
The role of APOE in Alzheimer’s disease and other dementias has been intensively investigated. However APOE in delirium has only recently been investigated in studies with small samples. There is evidence that APOE relates to delirium by one or more of the following pathophysiological mechanism: a) inhibition of inflammation in the CNS during acute illness, with release of inflammatory mediators, b) modification of inflammatory responses in an isoform-specific manner, c) by blocking both nicotine and acetylcholine receptors causing the anticholinergic effect which is assumed in delirium.
A meta-analysis of the published pooled data seems timely to establish any relationship between APOE and delirium, and to determine further direction of research in this topic.
To find out if there is any direct relationship between the APOE epsilon 4 and the occurrence of delirium.
Pubmed, MEDLINE, EBSCOhost and Google Scholar have been searched with the relevant keywords, and from the references of relevant papers. Nine papers were found which examined the relationship between APOE and delirium. Data were extracted from 8 of them and were pooled for meta-analysis using random effects with R software.
Data from 1762 participants showed no heterogeneity (Q=13.55, df:7, p=0.06). The possession of the APOE epsilon 4 allele has a small (OR:1.17, CI:0.77-1.80), non-significant (p=0.45) effect in the presence of delirium.
There is no association between APOE and the occurrence of delirium. Confirmation and clarification in larger studies could have important clinical implications for predicting prognosis and for treatment of delirium.
Single nucleotide polymorphisms (SNPs) contribute small increases in risk for late-onset Alzheimer's disease (LOAD). LOAD SNPs cluster around genes with similar biological functions (pathways). Polygenic risk scores (PRS) aggregate the effect of SNPs genome-wide. However, this approach has not been widely used for SNPs within specific pathways.
We investigated whether pathway-specific PRS were significant predictors of LOAD case/control status.
We mapped SNPs to genes within 8 pathways implicated in LOAD. For our polygenic analysis, the discovery sample comprised 13,831 LOAD cases and 29,877 controls. LOAD risk alleles for SNPs in our 8 pathways were identified at a P-value threshold of 0.5. Pathway-specific PRS were calculated in a target sample of 3332 cases and 9832 controls. The genetic data were pruned with R2 > 0.2 while retaining the SNPs most significantly associated with AD. We tested whether pathway-specific PRS were associated with LOAD using logistic regression, adjusting for age, sex, country, and principal components. We report the proportion of variance in liability explained by each pathway.
The most strongly associated pathways were the immune response (NSNPs = 9304, = 5.63 × 10−19, R2 = 0.04) and hemostasis (NSNPs = 7832, P = 5.47 × 10−7, R2 = 0.015). Regulation of endocytosis, hematopoietic cell lineage, cholesterol transport, clathrin and protein folding were also significantly associated but accounted for less than 1% of the variance. With APOE excluded, all pathways remained significant except proteasome-ubiquitin activity and protein folding.
Genetic risk for LOAD can be split into contributions from different biological pathways. These offer a means to explore disease mechanisms and to stratify patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Studies of the association between blood BDNF levels and delirium are very few and have yielded mixed results.
To investigate the blood BDNF levels in the occurrence and recovery of delirium.
Prospective, longitudinal study. Participants were assessed twice weekly with MoCA, DRS-R98, APACHE-II. BDNF levels of the same were estimated with ELISA method. Delirium has been define as per DRS-98R (cut-off > 16) and recovery of delirium as at least two consequently assessments without delirium prior to discharge.
No differences in the levels of BDNF between those with delirium and those who never developed it. Excluding those who never developed delirium (n = 140), we analysed the effects of BDNF and the other variables on delirium resolution and recovery. Of the 58 remained with delirium in the subsequently observations (max = 8) some of them continue to be delirious until discharge or death (n = 39) while others recovered (n = 19). BDNF levels and MoCA scores were significantly associated with both delirium cases who became non-delirious (resolution) during the assessments and with overall recovery. BDNF (Wald χ2 = 11.652, df: 1 P = .001), for resolution. For recovery Wald χ2 = 7.155; df: 1, P = .007. No significant association was found for the other variables (APACHE-II, history of dementia, age or gender)
BDNF do not have a direct effect in the occurrence of delirium but for those delirious of whom the levels are increased during the hospitalisation they are more likely to recover from delirium.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
This paper considers the significant role of cross-sectional geometry on resistance in co-axial pipe flows. We consider an axially flowing viscous fluid in between two long and thin elliptical coaxial cylinders, one inside the other. The outer cylinder is stationary, while the inner cylinder (rod) is free to move. The rod poses a resistance to the axial flow, while the viscous fluid poses a resistance to any motion of the rod. We show that the equations for flow in the axial direction – driven by a prescribed flux – and for flow within the cross-section of the domain – driven by the motion of the rod – decouple in the asymptotic limit of small cylinder aspect ratio into axial Poiseuille flow and transverse Stokes flow, respectively. The objective of this paper is to calculate numerically the axial and cross-sectional resistances and to determine their dependence on cross-sectional geometry – i.e. rod position and the ellipticities of the rod and bounding cylinder. We characterise axial resistance, first for three reduced parameter spaces that have not been fully analysed in the literature: (i) a circle in an ellipse, (ii) an ellipse in a circle and (iii) an ellipse in an ellipse of equal eccentricity and orientation, before extending our geometric parameter space to determine the overall optimal geometry to minimise axial flow resistance for fixed cross-sectional area. Cross-sectional resistance is characterised via coefficients in a Stokes resistance matrix and we highlight the interdependent effects of cross-sectional ellipticity and boundary interactions.
Chinese privet (Ligustrum sinense Lour.) is a deciduous to evergreen shrub with an expansive nonnative global range. Control costs are often high, so land managers must carefully consider whether the plant’s potential negative effects warrant active management. To help facilitate this decision-making process, we reviewed and synthesized the literature on the potential ecological effects of L. sinense invasion. We also identified research gaps in need of further study. We found ample evidence of negative relationships between L. sinense invasion and native plant communities. While observational studies are not able to confirm whether L. sinense is driving these relationships, experimental evidence suggests that there is a cause–effect relationship. Of particular concern is the possibility that L. sinense could suppress forest regeneration and cause areas to transition from forest to L. sinense–dominated shrublands. Although this outcome would obviously impact a wide variety of wildlife species, empirical evidence of negative effects of L. sinense on wildlife are limited, and some species may actually benefit from the additional cover and foraging opportunities that L. sinense can provide. Further research on the potential effects of L. sinense invasion on large-scale forest structure and wildlife populations is needed. In areas where L. sinense invasion is a concern, evidence suggests early detection and management can mitigate control costs.
Whilst aortopexy is an accepted and established procedure, there remains considerable heterogeneity within the literature, with inconsistencies in both the approach taken and the technique employed. Furthermore, limited data exist on both patient selection and long-term outcomes. This study aimed to report the experience of managing severe tracheomalacia by way of aortopexy in a large UK paediatric centre.
A retrospective case note review was conducted. Mean follow up was five years.
Twenty-five patients underwent aortopexy for severe tracheomalacia caused by external vascular compression. Acute life-threatening events precipitated investigation in 72 per cent of cases. Twenty-one patients initially presented to ENT services for investigation, which comprised upper airway endoscopy and imaging with computed tomography angiography. Post-operatively, the majority of patients demonstrated complete resolution of symptoms and were discharged from all associated services. Only four patients required a tracheostomy.
Aortopexy offers an effective method of treating severe tracheomalacia due to vascular compression.
Glyphosate-resistant (GR) canola is a widely grown crop across western Canada and has quickly become a prolific volunteer weed. Glyphosate-resistant soybean is rapidly gaining acreage in western Canada. Thus, there is a need to evaluate herbicide options to manage volunteer GR canola in GR soybean crops. We conducted an experiment to evaluate the efficacy of various PRE and POST herbicides applied sequentially to volunteer GR canola and to evaluate soybean injury caused by these herbicides. Trials were conducted across Saskatchewan and Manitoba in 2014 and 2015. All treatments provided a range of suppression (>70%) to control (>80%) of volunteer canola. All treatments with the exception of the glyphosate-treated control reduced aboveground canola biomass by an average of 96%. As well, canola seed contamination was reduced from 36% to less than 5% when a PRE and POST herbicide were both used. Moreover, all combinations of herbicides used had excellent crop safety (<10%). All PRE and POST herbicide combinations provided better control of volunteer canola compared with the glyphosate-only control, but tribenuron followed by bentazon and tribenuron followed by imazamox plus bentazon provided solutions that were low cost, currently available (registered in western Canada), and had the potential to minimize development of herbicide resistance in other weeds.
Psychotropic prescription rates continue to increase in the United States (USA). Few studies have investigated whether social-structural factors may play a role in psychotropic medication use independent of mental illness. Food insecurity is prevalent among people living with HIV in the USA and has been associated with poor mental health. We investigated whether food insecurity was associated with psychotropic medication use independent of the symptoms of depression and anxiety among women living with HIV in the USA.
We used cross-sectional data from the Women's Interagency HIV Study (WIHS), a nationwide cohort study. Food security (FS) was the primary explanatory variable, measured using the Household Food Security Survey Module. First, we used multivariable linear regressions to test whether FS was associated with symptoms of depression (Center for Epidemiologic Studies Depression [CESD] score), generalised anxiety disorder (GAD-7 score) and mental health-related quality of life (MOS-HIV Mental Health Summary score; MHS). Next, we examined associations of FS with the use of any psychotropic medications, including antidepressants, sedatives and antipsychotics, using multivariable logistic regressions adjusting for age, race/ethnicity, income, education and alcohol and substance use. In separate models, we additionally adjusted for symptoms of depression (CESD score) and anxiety (GAD-7 score).
Of the 905 women in the sample, two-thirds were African-American. Lower FS (i.e. worse food insecurity) was associated with greater symptoms of depression and anxiety in a dose–response relationship. For the psychotropic medication outcomes, marginal and low FS were associated with 2.06 (p < 0.001; 95% confidence interval [CI] = 1.36–3.13) and 1.99 (p < 0.01; 95% CI = 1.26–3.15) times higher odds of any psychotropic medication use, respectively, before adjusting for depression and anxiety. The association of very low FS with any psychotropic medication use was not statistically significant. A similar pattern was found for antidepressant and sedative use. After additionally adjusting for CESD and GAD-7 scores, marginal FS remained associated with 1.93 (p < 0.05; 95% CI = 1.16–3.19) times higher odds of any psychotropic medication use. Very low FS, conversely, was significantly associated with lower odds of antidepressant use (adjusted odds ratio = 0.42; p < 0.05; 95% CI = 0.19–0.96).
Marginal FS was associated with higher odds of using psychotropic medications independent of depression and anxiety, while very low FS was associated with lower odds. These complex findings may indicate that people experiencing very low FS face barriers to accessing mental health services, while those experiencing marginal FS who do access services are more likely to be prescribed psychotropic medications for distress arising from social and structural factors.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service.
Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test.
Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT.
NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.