Analytical evaluations of the path integral Monte Carlo thermodynamic and Hamiltonian energies for the harmonic oscillator.

By using the recently derived universal discrete imaginary-time propagator of the harmonic oscillator, both thermodynamic and Hamiltonian energies can be given analytically and evaluated numerically at each imaginary time step for any short-time propagator. This work shows that, using only currently known short-time propagators, the Hamiltonian energy can be optimized to the twelfth-order, converging to the ground state energy of the harmonic oscillator in as few as three beads. This study makes it absolutely clear that the widely used second-order primitive approximation propagator, when used in computing thermodynamic energy, converges extremely slowly with an increasing number of beads.

Anatomy of path integral Monte Carlo: Algebraic derivation of the harmonic oscillator's universal discrete imaginary-time propagator and its sequential optimization.

The direct integration of the harmonic oscillator path integral obscures the fundamental structure of its discrete, imaginary time propagator (density matrix). This work, by first proving an operator identity for contracting two free propagators into one in the presence of interaction, derives the discrete propagator by simple algebra without doing any integration. This discrete propagator is universal, having the same two hyperbolic coefficient functions for all short-time propagators. Individual short-time propagator only modifies the coefficient function's argument, its portal parameter, whose convergent order is the same as the thermodynamic energy. Moreover, the thermodynamic energy can be given in a closed form for any short-time propagator. Since the portal parameter can be systematically optimized by matching the expansion of the product of the two coefficients, any short-time propagator can be optimized sequentially, order by order, by matching the product coefficient's expansion alone, without computing the energy. Previous empirical findings on the convergence of fourth and sixth-order propagators can now be understood analytically. An eight-order convergent short-time propagator is also derived.

No sign problem in one-dimensional path integral Monte Carlo simulation of fermions: A topological proof.

This paper shows that, in one dimension, due to its topology, a closed-loop product of short-time propagators is always positive, despite the fact that each antisymmetric free fermion propagator can be of either sign.

Rapid synthesis of drug-encapsulated films by evaporation-induced self-assembly for highly-controlled drug release from biomaterial surfaces.

Infection at the surgical site for dental implants results in failed procedures, patient pain, burdensome economic impact, and the over-prescription of prophylactic antibiotics. Mesoporous silica films as coatings for implants may provide an ideal antimicrobial drug storage and local release vector to the site of infection, however traditional drug loading techniques result in insufficient drug load and short-term release kinetics. In this work, we have applied a method to use a surfactant-antimicrobial drug octenidine dihydrochloride (OCT) as a template for mesostructured silica, to demonstrate silica-OCT composite films. The films are synthesized by evaporation induced self-assembly (EISA) and we explore the effects of synthesis parameters on porous film structure, OCT incorporation, and OCT drug release rates. Drug micelle incorporation into the silica mesostructure was highly dependent on silica precursor pre-reaction to form silica oligomers before film spin-casting. The OCT drug concentration of the synthesis solution dictated the time required for effective incorporation (without phase separation), with total loading in the film of up to 90% by mass. The OCT content in the films was found to directly determine the timescale of drug release, from 2 to 8 h for a single layer film. The total release timescale was increased by the addition of multiple layers of OCT-silica films to nearly 2 weeks. Drug release from films completely inhibited Streptococcus mutans (UA159) growth, while drug-free porous silica films showed no increase in bacterial growth over non-porous control. These OCT-silica films have a significant potential to store and release antimicrobial drugs from dental implant surfaces.

Fundamental derivation of two Boris solvers and the Ge-Marsden theorem.

It has been known for some time that when one uses the Lorentz force law, rather than Hamilton's equation, one can derive two basic algorithms for solving trajectories in a magnetic field formally similar to the velocity-Verlet (VV) and position-Verlet (PV) symplectic integrators independent of any finite-difference approximation. Because the Lorentz force law uses the mechanical rather than the canonical momentum, the resulting magnetic field algorithms are exact energy conserving, rather than symplectic. In general, both types of algorithms can only yield the exact trajectory in the limit of vanishing small time steps. This work shows that, for a constant magnetic field, both magnetic algorithms can be further modified so that their trajectories are exactly on the gyrocircle at finite time steps. The magnetic form of the PV integrator then becomes the well-known Boris solver, while the VV form yields a second, previously unknown Boris-type algorithm, unrelated to any finite-difference scheme. Remarkably, the modification needed for the trajectory to be exact is a reparametrization of the time step, reminiscent of the Ge-Marsden theorem.

Solving fermion problems without solving the sign problem: Symmetry-breaking wave functions from similarity-transformed propagators for solving two-dimensional quantum dots.

It is well known that the use of the primitive second-order propagator in path-integral Monte Carlo calculations of many-fermion systems leads to the sign problem. This work will show that by using the similarity-transformed Fokker-Planck propagator, it is possible to solve for the ground state of a large quantum dot, with up to 100 polarized electrons, without solving the sign problem. These similarity-transformed propagators naturally produce rotational symmetry-breaking ground-state wave functions previously used in the study of quantum dots and quantum Hall effects. However, instead of localizing the electrons at positions that minimize the potential energy, this derivation shows that they should be located at positions that maximize the bosonic ground-state wave function. Further improvements in the energy can be obtained by using these as initial wave functions in a ground-state path-integral Monte Carlo calculation with second- and fourth-order propagators.

Hong Kong needs a territory-wide registry for out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) is an urgent disease entity, and the outcomes of OHCA are poor. This causes a significant public health burden, with loss of life and productivity throughout society. Internationally, successful programmes have adopted various survival enhancement measures to improve outcomes of OHCA. A territory-wide organised survival enhancement campaign is required in Hong Kong to maintain OHCA survival rates that are comparable to those of other large cities. One key component is to establish an OHCA registry, such as those in Asia, the United States, Europe, Australia, and New Zealand. An OHCA registry can provide benchmarking, auditing, and surveillance for identification of weak points within the chain of survival and evaluation of the effectiveness of survival enhancement measures. In Hong Kong, digitisation of records in prehospital and in-hospital care provides the infrastructure for an OHCA registry. Resources and governance to maintain a sustainable OHCA registry are necessary in Hong Kong as the first step to improve survival and outcomes of OHCA.

Low rates of osteoporosis treatment after hospitalization for hip fracture in Hawaii.

We evaluated osteoporosis treatment and DEXA utilization rates of patients who were admitted for hip fracture in a single healthcare system in Hawaii from 2015 to 2016. We found that osteoporosis treatment and DEXA utilization rates were low, highlighting a critical gap in osteoporosis care after admission for hip fracture. INTRODUCTION: The objective of this study was to evaluate osteoporosis care after an admission for hip fracture at three community hospitals within a single healthcare system in Hawaii. METHODS: A retrospective chart review was conducted (n = 428) of patients ≥ 50 years and hospitalized for hip fractures between January 1, 2015, and May 31, 2016, at three major hospitals within Hawaii Pacific Health, a large healthcare system in Hawaii. Basic demographics were collected, and medications prescribed were quantified and described within 1 year of hip fracture. Logistic regression was used to evaluate the association between collected variables and the odds of osteoporosis treatment. RESULTS: Only 115 (26.9%) patients were prescribed a medication for osteoporosis as a secondary prevention within a year of hospitalization for hip fracture. DEXA scans were performed in 137 (32.0%) patients. Most of the treated patients were prescribed oral bisphosphonates. Treatment facility, female gender, and higher BMI were found to be predictive factors for osteoporosis treatment. CONCLUSION: The use of osteoporosis medication for secondary prevention after admission for hip fracture in Hawaii is low. Efforts need to be made to improve treatment rates, especially among males.

Peak-height formula for higher-order breathers of the nonlinear Schrödinger equation on nonuniform backgrounds.

Given any background (or seed) solution of the nonlinear Schrödinger equation, the Darboux transformation can be used to generate higher-order breathers with much greater peak intensities. In this work, we use the Darboux transformation to prove, in a unified manner and without knowing the analytical form of the background solution, that the peak height of a high-order breather is just a sum of peak heights of first-order breathers plus that of the background, irrespective of the specific choice of the background. Detailed results are verified for breathers on a cnoidal background. Generalizations to more extended nonlinear Schrödinger equations, such as the Hirota equation, are indicated.

A distinct pre-existing inflammatory tumour microenvironment is associated with chemotherapy resistance in high-grade serous epithelial ovarian cancer.

BACKGROUND: Chemotherapy resistance is a major determinant of poor overall survival rates in high-grade serous ovarian cancer (HGSC). We have previously shown that gene expression alterations affecting the NF-κB pathway characterise chemotherapy resistance in HGSC, suggesting that the regulation of an immune response may be associated with this phenotype. METHODS: Given that intrinsic drug resistance pre-exists and is governed by both tumour and host factors, the current study was performed to examine the cross-talk between tumour inflammatory microenvironment and cancer cells, and their roles in mediating differential chemotherapy response in HGSC patients. Expression profiling of a panel of 184 inflammation-related genes was performed in 15 chemoresistant and 19 chemosensitive HGSC tumours using the NanoString nCounter platform. RESULTS: A total of 11 significantly differentially expressed genes were found to distinguish the two groups. As STAT1 was the most significantly differentially expressed gene (P=0.003), we validated the expression of STAT1 protein by immunohistochemistry using an independent cohort of 183 (52 resistant and 131 sensitive) HGSC cases on a primary tumour tissue microarray. Relative expression levels were subjected to Kaplan-Meier survival analysis and Cox proportional hazard regression models. CONCLUSIONS: This study confirms that higher STAT1 expression is significantly associated with increased progression-free survival and that this protein together with other mediators of tumour-host microenvironment can be applied as a novel response predictive biomarker in HGSC. Furthermore, an overall underactive immune microenvironment suggests that the pre-existing state of the tumour immune microenvironment could determine response to chemotherapy in HGSC.

High-order path-integral Monte Carlo methods for solving quantum dot problems.

The conventional second-order path-integral Monte Carlo method is plagued with the sign problem in solving many-fermion systems. This is due to the large number of antisymmetric free-fermion propagators that are needed to extract the ground state wave function at large imaginary time. In this work we show that optimized fourth-order path-integral Monte Carlo methods, which use no more than five free-fermion propagators, can yield accurate quantum dot energies for up to 20 polarized electrons with the use of the Hamiltonian energy estimator.

Anatomy of the Akhmediev breather: Cascading instability, first formation time, and Fermi-Pasta-Ulam recurrence.

By invoking Bogoliubov's spectrum, we show that for the nonlinear Schrödinger equation, the modulation instability (MI) of its n=1 Fourier mode on a finite background automatically triggers a further cascading instability, forcing all the higher modes to grow exponentially in locked step with the n=1 mode. This fundamental insight, the enslavement of all higher modes to the n=1 mode, explains the formation of a triangular-shaped spectrum that generates the Akhmediev breather, predicts its formation time analytically from the initial modulation amplitude, and shows that the Fermi-Pasta-Ulam (FPU) recurrence is just a matter of energy conservation with a period twice the breather's formation time. For higher-order MI with more than one initial unstable mode, while most evolutions are expected to be chaotic, we show that it is possible to have isolated cases of "super-recurrence," where the FPU period is much longer than that of a single unstable mode.

Surfer's myelopathy: a radiologic study of 23 cases.

BACKGROUND AND PURPOSE: Surfing is an uncommon cause of an acute nontraumatic myelopathy. This study describes the MR imaging characteristics and clinical correlates in 23 subjects with surfer's myelopathy. MATERIALS AND METHODS: This was a retrospective review of 23 cases of surfer's myelopathy from 2003-2012. Spinal cord MR imaging characteristics and neurologic examinations with the use of the American Spinal Injury Association scale were reviewed. Logistic regression was used to determine associations between MR imaging characteristics, American Spinal Injury Association scale, and clinical improvement. RESULTS: All subjects (19 male, 4 female; mean age, 26.3 ± 7.4 years) demonstrated "pencil-like," central T2-hyperintense signal abnormalities in the spinal cord extending from the midthoracic region to the conus with associated cord expansion and varying degrees of conus enlargement on spinal cord MR imaging within 24 hours of symptom onset. T1 signal was normal. Faint gadolinium enhancement was present in a minority. Although there was a strong correlation between initial American Spinal Injury Association score and clinical improvement (P = .0032), MR imaging characteristics were not associated with American Spinal Injury Association score or clinical improvement. CONCLUSIONS: Surfer's myelopathy should be considered in the radiographic differential diagnosis of a longitudinally extensive T2-hyperintense spinal cord lesion. MR imaging characteristics do not appear to be associated with severity on examination or clinical improvement.

Update on the pharmacologic management of neonatal abstinence syndrome.

Although a statement on Neonatal Drug Withdrawal was published in 1998 by the American Academy of Pediatrics, pharmacologic management of neonatal abstinence syndrome (NAS) remains a challenge. Published clinical trials are limited, restricting treatment decision making to practitioner's experience and preference rather than evidence-based medicine. To optimize withdrawal symptom prevention, drug selection is often based on the offending agent (opioids versus polysubstance exposure), clinical presentation, mechanism of action (agonist versus partial agonist/antagonist, receptor effects), pharmacokinetic parameters and available drug formulations. This review addresses risk factors and pathophysiology of NAS, summarizes parameters of common drugs used for the management of NAS, and reviews published literature of standard therapies as well as newer agents. Based on the current literature, paregoric is no longer recommended and oral morphine solutions remain the mainstay of therapy for opiate withdrawal. Other potential therapies include methadone, buprenorphine, phenobarbital and clonidine with the latter two agents as adjunctive therapies.

Electronic health records and adverse drug events after patient transfer.

BACKGROUND: Our objective was to examine the frequencies of medication error and adverse drug events (ADEs) at the time of patient transfer in a system with an electronic health record (EHR) as compared with a system without an EHR. It was hypothesised that the frequencies of these events would be lower in the EHR system because of better information exchange across sites of care. METHODS: 469 patients transferred between seven nursing homes and three hospitals in New York and Connecticut between 1999 and 2005 were followed retrospectively. Two groups of patients were compared: US Veterans Affairs (VA) patients, with an EHR, and non-VA patients, without an EHR, on the following measures: (1) medication prescribing discrepancies at nursing home/hospital transfer, (2) high-risk medication discrepancies and (3) ADEs caused by medication discrepancies according to structured medical record review by pairs of physician and pharmacist raters. RESULTS: The overall incidence of ADE caused by medication discrepancies was 0.20 per hospitalisation episode. After controlling for demographic and clinical covariates, there were no significant differences between VA and non-VA groups in medication discrepancies (mean difference 0.02; 95% CI -0.81 to 0.85), high-risk medication discrepancies (-0.18; 95%CI -0.22 to 0.58) or occurrence of an ADE caused by a medication discrepancy (OR 0.96; 95% CI 0.18 to 5.01). CONCLUSIONS: There was no difference, with and without an EHR, in the occurrence of medication discrepancies or ADEs caused by medication discrepancies at the time of transfer between sites of care. Reducing such problems may require specialised computer tools to facilitate medication review.

Task-specificity vs. ceiling effect: step-training in shallow water after spinal cord injury.

While activity-based rehabilitation is one of the most promising therapeutic approaches for spinal cord injury, the necessary components for optimal locomotor retraining have not yet been determined. Currently, a number of different activity-based approaches are being investigated including body weight-supported treadmill training (with and without manual assistance), robotically-assisted treadmill training, bicycling and swimming, among others. We recently showed, in the adult rat, that intensive rehabilitation based on swimming brought about significant improvements in hindlimb performance during swimming but did not alter the normal course of recovery of over-ground walking (Smith et al., 2006a,b, 2009). However, swimming lacks the phasic limb-loading and plantar cutaneous feedback thought to be important for weight-supported step training. So, we are investigating an innovative approach based on walking in shallow water where buoyancy provides some body weight support and balance while still allowing for limb-loading and appropriate cutaneous afferent feedback during retraining. Thus, the aim of this study is to determine if spinal cord injured animals show improved overground locomotion following intensive body weight-supported locomotor training in shallow water. The results show that training in shallow water successfully improved stepping in shallow water, but was not able to bring about significant improvements in overground locomotion despite the fact that the shallow water provides sufficient body weight support to allow acutely injured rats to generate frequent plantar stepping. These observations support previous suggestions that incompletely injured animals retrain themselves while moving about in their cages and that daily training regimes are not able to improve upon this already substantial functional improvement due to a ceiling effect, rather than task-specificity, per se. These results also support the concept that moderately-severe thoracic contusion injuries decrease the capacity for body weight support, but do not decrease the capacity for pattern generation. In contrast, animals with severe contusion injuries could not support their body weight nor could they generate a locomotor pattern when provided with body weight support via buoyancy.

Extrapolated high-order propagators for path integral Monte Carlo simulations.

We present a new class of high-order imaginary time propagators for path integral Monte Carlo simulations that require no higher order derivatives of the potential nor explicit quadratures of Gaussian trajectories. Higher orders are achieved by an extrapolation of the primitive second-order propagator involving subtractions. By requiring all terms of the extrapolated propagator to have the same Gaussian trajectory, the subtraction only affects the potential part of the path integral. The resulting violation of positivity has surprisingly little effects on the accuracy of the algorithms at practical time steps. Thus in principle, arbitrarily high order algorithms can be devised for path integral Monte Carlo simulations. We verified the fourth, sixth, and eighth order convergences of these algorithms by solving for the ground state energy and pair distribution function of liquid (4)He, which is representative of a dense, and strongly interacting, quantum many-body system.

CSF neutrophils are implicated in the development of vasospasm in subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is a significant cause of morbidity in patients after aneurysmal subarachnoid hemorrhage (aSAH). There are few effective treatments. The search for new treatments has focused predominantly on dilating cerebral blood vessels. Growing evidence supports a role for inflammation in its pathogenesis but no potential target for intervention has emerged. METHODS: CSF and clinical information from patients with aSAH were collected. Additionally, tyrosine modifications by stable isotope dilution HPLC with online tandem mass spectrometry were quantified in CSF samples. RESULTS: We report an association between neutrophil accumulation in the cerebrospinal fluid of patients with aSAH and the development of vasospasm. In particular, CSF neutrophil content of >62% on the third day after aSAH is an independent predictor of the later development of vasospasm (OR 6.8, 95% CI 2.0-23.3, P = 0.002). Further, activity of myeloperoxidase and NADPH oxidase is elevated in aSAH suggesting a role for modification of CSF proteins by reactive oxidant species. CONCLUSIONS: Neutrophil percentage is an independent predictor of vasospasm in aSAH patients, days prior to its onset suggesting a role of neutrophils in vasospasm. The activity of neutrophil enzymes is also increased suggesting a mechanism for blood vessel damage. Inflammation mediated by neutrophils is a potential target for therapies in vasospasm. More study is necessary to determine the mechanism by which neutrophils damage cerebral blood vessels.