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OBJECTIVE The aims of this study were to quantify inpatient healthcare costs, describe patient demographics, and analyze variables influencing costs for pediatric and adult hydrocephalus shunt-related admissions in the US. METHODS A cross-sectional study was performed using the 2019 Healthcare Cost and Utilization Project Kids’ Inpatient Database (KID) and National Inpatient Sample (NIS), nationally representative weighted data sets of hospital discharges for pediatric and adult patients, respectively. International Classification of Diseases, 10th Revision, Clinical Modification and Procedure Coding System (ICD-10-CM/PCS) code filters for data extraction were queried for admission information. Age at admission was categorized into five groups (≤ 28 days, 29 days to < 1 year, 1–18 years, 19–64 years, and ≥ 65 years). RESULTS In 2019, there were 36,898 shunt-related hospital admissions accounting for 495,138 hospital days and a total cost of more than $2.06 billion. Initial shunt placements accounted for 53.5% of all admissions and nearly 60% of the total cost. The median cost per admission was $22,700 and the median length of stay was 5 days. Admissions for shunt infection requiring revision had the highest median cost at $71,300 (p < 0.001) and the longest median length of stay at 25 days (p < 0.001) compared with initial shunt placements. By age, admissions that occurred in the first 28 days of life cost almost 5 times more than the median, $110,500 versus $22,700, respectively, and resulted in hospital stays that were 8 times longer than the median, 41 versus 5 days, respectively. Individuals aged ≥ 65 years accounted for 28% of the total shunt-related admissions. Almost two-thirds (65.3%) of shunt-related admissions were classified as nonelective. The median cost of nonelective procedures was double that of elective admissions, $33,900 versus $15,100, respectively (p < 0.001), and resulted in almost 5 times longer hospital stays, 9 versus 2 days, respectively (p < 0.001). Shunt-related admissions were predominantly male across all age groups (54.7%–57.4% male) except the 19- to 64-year age group. In the 19- to 64-year age group, females accounted for 51.1% of admissions. Insurance status was largely age dependent. Of all admissions, 33.1% used private insurance, 32.9% Medicare, and 27.7% Medicaid. CONCLUSIONS This is the first study to quantify the patient demographics and cost of hydrocephalus shunt-related admissions across the entire age spectrum. Shunt-related admissions cost the US more than $2.06 billion dollars per year and represent only a fraction of the total cost of hydrocephalus care.

Background Patients experiencing systemic patterns of disadvantage, such as racial/ethnic minorities and those with limited English proficiency, are underrepresented in research. This is particularly true for large pragmatic trials of potentially sensitive research topics, such as advance care planning (ACP). It is unclear how phone outreach may affect research participation by underrepresented individuals. Objective To assess the effect of phone outreach, in addition to standard mail survey recruitment, in a population-based ACP pragmatic trial at three academic health systems in California. Design Retrospective cohort study Patients Primary care patients with serious illness were mailed a survey in their preferred language. Patients who did not initially respond by mail received up to three reminder phone calls with the option of survey completion by phone. Main measures Effect of phone outreach on survey response rate associated with respondent demographic characteristics (e.g., Social Vulnerability Index [SVI], range 0 (low) to 1 (high)). Results Across the health systems, 5998 seriously ill patients were mailed surveys. We obtained completed surveys from 1215 patients (20% response rate); 787 (65%) responded after mail alone and 428 (35%) participated only after phone outreach. Patients recruited after phone outreach compared to mail alone were more socially vulnerable (SVI 0.41 v 0.35, P < 0.001), were more likely to report being a racial/ethnic minority (35% v 28%, P = 0.006), and non-English speaking (16% v 10%, P = 0.005). Age and gender did not differ significantly. The inclusion of phone outreach resulted in a sample that better represented the baseline population than mail alone in racial/ethnic minority (28% mail alone, 30% including phone outreach, 36% baseline population), non-English language preference (10%, 12%, 15%, respectively), and SVI (0.35, 0.37, 0.38, respectively). Conclusions Phone outreach for a population-based survey in a pragmatic trial concerning a potentially sensitive topic significantly enhanced recruitment of underrepresented seriously ill patients.

All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance use disorders. Here, we demonstrate that dopaminergic neuronal activity-regulated myelin plasticity is a key modulator of dopaminergic circuit function and opioid reward. Oligodendroglial lineage cells respond to dopaminergic neuronal activity evoked by either optogenetic stimulation or by morphine administration specifically within the reward center ventral tegmental area (VTA), but not along the axonal projections in the medial forebrain bundle nor within the target nucleus accumbens (NAc). Genetic blockade of oligodendrogenesis dampens NAc dopamine release dynamics, which is critical for reward learning, and impairs behavioral conditioning to morphine. Our findings identify dopaminergic neuronal activity-regulated myelin plasticity as an important circuit modification that is required for opioid reward.One-Sentence SummaryActivity-dependent myelin plasticity in the ventral tegmental area modulates dopaminergic circuit function and opioid reward

Optical forces are used to accelerate and trap water droplets in applications such as remote spectroscopy and noninvasive surgery. However, the microscopic deformation of droplets is difficult to predict. In this work, the local electrodynamic impulse imparted by a focused laser beam to a water droplet is numerically modeled via a simulation that invokes intensive conservation of electrodynamic and kinetic momentum. Electrodynamic momentum is modeled locally using a D3Q7 electrodynamic lattice-Boltzmann method, and kinetic momentum is modeled locally using a multi-phase D3Q27 weighted-orthogonal lattice-Boltzmann method. Six different electrodynamic theories are implemented in the simulation domain predicting three unique types of droplet dynamics driven by differences in the direction and distribution of force density. The unique water droplet morphology affects the center-of-mass acceleration of the droplet. This study suggests that empirical measurement of the light-driven acceleration of a droplet may help to validate a single electrodynamic theory.

This study aimed to examine whether and how organizational factors (i.e., procedural justice) are associated with psychological flourishing, an optimal mental state. Path analysis was conducted among 195 Chinese mental health professionals (females = 69%; Mean age = 30 years) in Macao, and results showed that emotional exhaustion partially mediated the positive association between procedural justice and psychological flourishing, whereas emotion regulation significantly diminished the effects of procedural injustice on emotional exhaustion. Our findings highlight the emotional mechanisms underlying the influence of organizational procedures on employees' wellbeing, and wellness programs for enhancing employees' emotional regulation skills are recommended.

ObjectiveTo evaluate the interim feasibility, safety and clinical measures data of direct delivery of regenerating peripheral nerve tissue (PNT) to the substantia nigra (SN) in participants with Parkinson’s disease (PD).MethodsEighteen (13 men/5 women) participants were unilaterally implanted with PNT to the SN, contralateral to the most affected side during the same surgery they were receiving deep brain stimulation (DBS) surgery. Autologous PNT was collected from the sural nerve. Participants were followed for safety and clinical outcomes for 2 years (including off-state Unified Parkinson’s Disease Rating Scale (UPDRS) Part III assessments) with study visits every 6 months.ResultsAll 18 participants scheduled to receive PNT implantation received targeted delivery to the SN in addition to their DBS. All subjects were discharged the following day except for two: post-op day 2; post-op day 3. The most common study-related adverse events were hypoaesthesia and hyperaesthesias to the lateral aspect of the foot and ankle of the biopsied nerve (6 of 18 participants experienced). Clinical measures did not identify any hastening of PD measures providing evidence of safety and tolerability. Off-state UPDRS Part III mean difference scores were reduced at 12 months compared with baseline (difference=−8.1, 95% CI −2.4 to −13.9 points, p=0.005). No complications involving dyskinesias were observed.ConclusionsTargeting the SN for direct delivery of PNT was feasible with no serious adverse events related to the study intervention. Interim clinical outcomes show promising results meriting continued examination of this investigational approach.Trial registration numberNCT02369003.

Microscopic Lorentz and Einstein & Laub theories predict unique deformation and acceleration of a water droplet subjected to a tightly-focused 532 nm wavelength Gaussian beam, which can be simulated using coupled electrodynamic and kinetic lattice- Boltzmann methods.

We explore photorealistic computational visualization using electrodynamic simulations and physically based rendering (PBR) to render the iridescent colors of large objects coated with periodic metallic nanostructures supporting plasmonic effects.

Recent advances in DNA sequencing technologies include the generation of long reads, with lengths from tens to hundreds of thousands of base pairs each. State-of-the-art algorithm Minimap2 is able to process these data and the most commonly used short reads, but is memory- and computationally-intensive: to process a human genome, its running times can reach up to several hours in powerful machines. As a means of making this technology more available to hospitals and clinics, hardware accelerators have addressed these shortcomings with many short read mappers in the past, and their application to this new generation of softwares is an area of active research. Here we present a FPGA-based accelerator for Minimap2 with focus on its operation for short reads. We gathered profiling behaviors to determine the algorithm's bottleneck. We generated a hardware block for one recurrent loop in the critical function that can be integrated into a parallelizable architecture. Execution with short reads has shown a reduction of 155x in terms of required clock cycles in the accelerated section. Data transfer overhead is measured and discussed.

Conflicting formalisms for dielectric electromagnetic momentum and stress are implemented in a simulation engine to simulate radiation pressure on a nanometric single-component multiphase fluid. Non-relativistic deformations of the liquid-vapour interface, simulated using the pseudopotential Lattice-Boltzmann-method, are distinct for each formalism. These distinct deformations suggest optical pressure on liquids and gases may be used to empirically validate a single electrodynamic theory to describe light momentum in dielectrics.

Tomato is an agronomically important crop that can be infected by Pseudomonas syringae, a Gram-negative bacterium, resulting in bacterial speck disease. The tomato-P. syringae pv. tomato pathosystem is widely used to dissect the genetic basis of plant innate responses and disease resistance. While disease was successfully managed for many decades through the introduction of the Pto/Prf gene cluster from Solanum pimpinellifolium into cultivated tomato, race 1 strains of P. syringae have evolved to overcome resistance conferred by the Pto/Prf gene cluster and occur worldwide. Wild tomato species are important reservoirs of natural diversity in pathogen recognition, because they evolved in diverse environments with different pathogen pressures. In typical screens for disease resistance in wild tomato, adult plants are used, which can limit the number of plants that can be screened due to their extended growth time and greater growth space requirements. We developed a method to screen 10-day-old tomato seedlings for resistance, which minimizes plant growth time and growth chamber space, allows a rapid turnover of plants, and allows large sample sizes to be tested. Seedling outcomes of survival or death can be treated as discrete phenotypes or on a resistance scale defined by amount of new growth in surviving seedlings after flooding. This method has been optimized to screen 10-day-old tomato seedlings for resistance to two P. syringae strains and can easily be adapted to other P. syringae strains.

CRISPR-Cas technologies have provided programmable gene editing tools that have revolutionized research. The leading CRISPR-Cas9 and Cas12a enzymes are ideal for programmed genetic manipulation, however, they are limited for genome-scale interventions. Here, we utilized a Cas3-based system featuring a processive nuclease, expressed endogenously or heterologously, for genome engineering purposes. Using an optimized and minimal CRISPR-Cas3 system (Type I-C) programmed with a single crRNA, large deletions ranging from 7 - 424 kb were generated in Pseudomonas aeruginosa with high efficiency and speed. By comparison, Cas9 yielded small deletions and point mutations. Cas3-generated deletion boundaries were variable in the absence of a homology-directed repair (HDR) template, and successfully and efficiently specified when present. The minimal Cas3 system is also portable; large deletions were induced with high efficiency in Pseudomonas syringae and Escherichia coli using an “all-in-one” vector. Notably, Cas3 generated bi-directional deletions originating from the programmed cut site, which was exploited to iteratively reduce a P. aeruginosa genome by 837 kb (13.5%) using 10 distinct crRNAs. We also demonstrate the utility of endogenous Cas3 systems (Type I-C and I-F) and develop an “anti-anti-CRISPR” strategy to circumvent endogenous CRISPR-Cas inhibitor proteins. CRISPR-Cas3 could facilitate rapid strain manipulation for synthetic biological and metabolic engineering purposes, genome minimization, and the analysis of large regions of unknown function.

Electromagnetic momentum carried by light is observable through the mechanical effects radiation pressure exerts on illuminated objects. Momentum conversion from electromagnetic fields to elastic waves within a solid object proceeds through a string of electrodynamic and elastodynamic phenomena, collectively bound by momentum and energy continuity. The details of this conversion predicted by theory have yet to be validated by experiments, as it is difficult to distinguish displacements driven by momentum from those driven by heating due to light absorption. Here, we have measured temporal variations of the surface displacements induced by laser pulses reflected from a solid dielectric mirror. Ab initio modelling of momentum flow describes the transfer of momentum from the electromagnetic field to the dielectric mirror, with subsequent creation/propagation of multicomponent elastic waves. Complete consistency between predictions and absolute measurements of surface displacements offers compelling evidence of elastic transients driven predominantly by the momentum of light., The exact mechanism of momentum conversion from light to an object has varied descriptions in the literature and experimental verifications are difficult. Here the authors do an in-depth experimental and numerical study of the momentum dynamics of elastic waves in a dielectric mirror hit by a pulsed laser beam.

We present a surface plasmon resonance (SPR) sensor for crude oils that can be used to directly measure asphaltene deposition onset. Surface plasmon resonance describes a condition in which light incident onto a highly conductive metallic film couples into resonant charge oscillations of the metal. The SPR condition is highly sensitive to slight perturbations in the dielectric environment in the immediate vicinity of the thin-film, less than 1 μm away at visible frequencies. Here, we show that shifts in the peak surface plasmon resonant wavelength can be used to measure the onset of deposition of asphaltenes from a titration experiment. Initially, the SPR peak wavelength of the neat crude oil is measured. Next, the gradual addition of n-heptane dilutes the crude oil and produces a lower SPR peak wavelength, which results from the lower refractive index of the mixture. When the amount of added n-heptane approaches the deposition onset point, asphaltenes precipitate and are deposited onto the thin-film surf...

This study evaluated the short-term cost-effectiveness of the Patient Empowerment Programme (PEP) for diabetes mellitus (DM) in Hong Kong. Propensity score matching was used to select a matched group of PEP and non-PEP subjects. A societal perspective was adopted to estimate the cost of PEP. Outcome measures were the cumulative incidence of all-cause mortality and diabetic complication over a 5-year follow-up period and the number needed to treat (NNT) to avoid 1 event. The incremental cost-effectiveness ratio (ICER) of cost per event avoided was calculated using the PEP cost per subject multiplied by the NNT. The PEP cost per subject from the societal perspective was US$247. There was a significantly lower cumulative incidence of all-cause mortality (2.9% vs 4.6%, P < .001), any DM complication (9.5% vs 10.8%, P = .001) and CVD events (6.8% vs 7.6%, P = .018), in the PEP group. The costs per death from any cause, DM complication or case of CVD avoided were US$14 465, US$19 617 and US$30 796, respectively. The extra amount allocated to managing PEP was small and it appears cost-effective in the short-term as an addition to RAMP.

In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Check point inhibitors targeting CTLA4 (Cytotoxic T-lymphocyte antigen-4), PD-1 (programmed death1) on lymphocytes and PD-L1 (programmed death ligand1) on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust anti-tumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities. These adverse toxicities are frequent if patients have active auto-immune disorders. Here, we report a rare case of quiescent bullous pemphigoid which flared after initiation of pembrolizumab, a PD-L1 inhibitor.

Superlenses are imaging components that can overcome the diffraction limit associated with conventional dielectric lenses. An ideal superlens is a flat infinite slab of homogeneous double-negative material with $\ensuremath{\varepsilon}\phantom{\rule{0.16em}{0ex}}=\phantom{\rule{0.16em}{0ex}}\ensuremath{\mu}\phantom{\rule{0.16em}{0ex}}=\phantom{\rule{0.16em}{0ex}}\ensuremath{-}1$ embedded in air, which achieves perfect imaging by restoring all the spatial frequency components of an object to the image plane. It has been shown that any deviation from these homogeneous material parameter values limits the resolution of the lens and introduces a surface mode resonance with fields that dominate the image. While material loss can suppress the resonant mode, loss also reduces spatial resolution. In this paper, we investigate resonant modes arising in metamaterial superlenses of infinite and finite extent and show how they cause imaging artifacts and reduce imaging fidelity. We choose a well-studied periodic structure consisting of an array of magnetodielectric cylinders for the lens medium under test. We demonstrate that the presence of these artifacts can lead to erroneous interpretation of the standard two-source resolution test for lenses. We show that artifacts can be mitigated by introducing point defects into the array, which move the resonant modes to higher spatial frequencies and, in the case of finite lenses, suppress their amplitudes through radiation losses. This strategy enables more robust and reliable subwavelength imaging performance, improves the spatial resolution of the metamaterial lens, and reduces the deleterious effects of material losses.

Plasmonic color generation describes structural color arising from resonant interaction between visible light and metallic nanostructures, causing selective frequencies of light to be scattered and/or absorbed [Kristensen et al. 2017; Sun and Xia 2003]. The perceived color from such metallic nanostructures is highly dependent on viewing angle and the color appearance can change with color of the viewing background. Plasmonic color generation is a rapidly emerging research area with potential advantages over conventional pigment printing technology including higher printing resolution and robustness, greater compatibility for integration and functionalization, and reduced resource requirements [Mudachathi and Tanaka 2017; Zhu et al. 2017]. Structural color from plasmonic nanostructures has already been used to improve security measures in currency notes and credit cards [Lee et al. 2018].

Additional file 1. Outline of the content of the guided participation discharge intervention.

Superlens slabs rely on the coherent superposition of multiply reflected evanescent waves to amplify and restore the fine details of an object at the image plane. If a superlens slab is placed in close proximity to a source object and image detector, similar interactions with these external components can introduce resonances outside of the superlens. In this work, we explore the role of external resonances on single-negative slab superlens performance by considering a complete electromagnetic imaging system containing a physical source object and image detector, each modeled as a planar dielectric half-space. In studying the transmission of spectral components that carry real power through this system, we find that resonances outside the lens can have a dramatic impact on single-negative superlens performance. In particular, we find that the resonances external to a μ-negative lens can be used to extend the imaging range beyond the extreme near field and maintain super-resolution even in the presence of loss.

Aim To evaluate the long-term cost-effectiveness of a Patient Empowerment Programme (PEP) for type 2 diabetes mellitus (DM) in primary care. Materials and methods PEP participants were subjects with type 2 DM who enrolled into PEP in addition to enrolment in the Risk Assessment and Management Programme for DM (RAMP-DM) at primary care level. The comparison group was subjects who only enrolled into RAMP-DM without participating in PEP (non-PEP). A cost-effectiveness analysis was conducted using a patient-level simulation model (with fixed-time increments) from a societal perspective. We incorporated the empirical data from a matched cohort of PEP and non-PEP groups to simulate lifetime costs and outcomes for subjects with DM with or without PEP. Incremental cost-effectiveness ratios (ICER) in terms of cost per quality adjusted life year (QALY) gained were calculated. Probabilistic sensitivity analysis was conducted with results presented as a cost-effectiveness acceptability curve. Results With an assumption that the PEP effect would last for 5 years as shown by the empirical data, the incremental cost per subject was US $197 and the incremental QALYs gained were 0.06 per subject, which resulted in an ICER of US $3290 per QALY gained compared with no PEP across the lifetime. Probabilistic sensitivity analysis showed 66% likelihood that PEP is cost-effective compared with non-PEP when willingness-to-pay for a QALY is ≥US $46 153 (based on per capita GDP 2017). Conclusions Based on this carefully measured cost of PEP and its potentially large benefits, PEP could be highly cost-effective from a societal perspective as an adjunct intervention for patients with DM.

Upregulation of selenium binding protein 1 (SELENBP1) mRNA expression has been reported in schizophrenia, primarily in the dorsolateral prefrontal cortex. However, peripheral blood studies are limited and results are inconsistent. In this study, we examined SELENBP1 mRNA expression in whole blood and protein expression in plasma from patients with recent-onset schizophrenia (n = 30), treatment-resistant schizophrenia (n = 71) and healthy controls (n = 57). We also examined the effects of SELENBP1 genetic variation on gene and protein expression. We found lower SELENBP1 plasma protein levels in patients with recent-onset schizophrenia (p = 0.042) but not in treatment-resistant schizophrenia (p = 0.81). Measurement of peripheral mRNA levels showed no difference between treatment-resistant schizophrenia and healthy controls (p = 0.234) but clozapine plasma levels (p = 0.036) and duration of illness (p = 0.028) were positively correlated with mRNA levels. Genetic variation was not associated with mRNA or protein expression. Our data represent the first peripheral proteomic study of SELENBP1 in schizophrenia and suggest that plasma SELENBP1 protein is downregulated in patients with recent-onset schizophrenia.

Iridescent colours have been observed to be reflected from specially designed droplets of colourless liquids, with the reflected colour depending on the viewing angle. The finding reveals a curious mechanism for creating coloration. Scattered light produces coloured haloes.