Boltzmann's equation at 150: Traditional and modern solution techniques for charged particles in neutral gases.

Seminal gas discharge experiments of the late 19th and early 20th centuries laid the foundations of modern physics, and the influence of this "golden era" continues to resonate well into the 21st century through modern technologies, medical applications, and fundamental scientific investigations. Key to this continuing success story has been the kinetic equation formulated by Ludwig Boltzmann in 1872, which provides the theoretical foundations necessary for analyzing such highly non-equilibrium situations. However, as discussed here, the full potential of Boltzmann's equation has been realized only in the past 50 years or so, with modern computing power and analytical techniques facilitating accurate solutions for various types of charged particles (ions, electrons, positrons, and muons) in gases. Our example of thermalization of electrons in xenon gas highlights the need for such accurate methods-the traditional Lorentz approximation is shown to be hopelessly inadequate. We then discuss the emerging role of Boltzmann's equation in determining cross sections by inverting measured swarm experiment transport coefficient data using machine learning with artificial neural networks.

Practice variation in the diagnosis of acute rejection among pediatric heart transplant centers: An analysis of the pediatric heart transplant society (PHTS) registry.

BACKGROUND: Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. METHODS: The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. RESULTS: A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival. CONCLUSIONS: Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

Reduced model of plasma evolution in hydrogen discharge capillary plasmas.

A model describing the evolution of the average plasma temperature inside a discharge capillary device including Ohmic heating, heat loss to the capillary wall, and ionization and recombination effects is developed. Key to this approach is an analytic quasistatic description of the radial temperature variation which, under local thermal equilibrium conditions, allows the radial behavior of both the plasma temperature and the electron density to be specified directly from the average temperature evolution. In this way, the standard set of coupled partial differential equations for magnetohydrodynamic (MHD) simulations is replaced by a single ordinary differential equation, with a corresponding gain in simplicity and computational efficiency. The on-axis plasma temperature and electron density calculations are benchmarked against existing one-dimensional MHD simulations for hydrogen plasmas under a range of discharge conditions and initial gas pressures, and good agreement is demonstrated. The success of this simple model indicates that it can serve as a quick and easy tool for evaluating the plasma conditions in discharge capillary devices, particularly for computationally expensive applications such as simulating long-term plasma evolution, performing detailed input parameter scans, or for optimization using machine-learning techniques.

Combining laser interferometry and plasma spectroscopy for spatially resolved high-sensitivity plasma density measurements in discharge capillaries.

Precise characterization and tailoring of the spatial and temporal evolution of plasma density within plasma sources are critical for realizing high-quality accelerated beams in plasma wakefield accelerators. The simultaneous use of two independent diagnostics allowed the temporally and spatially resolved detection of plasma density with unprecedented sensitivity and enabled the characterization of the plasma temperature in discharge capillaries for times later than 0.5 µs after the initiation of the discharge, at which point the plasma is at local thermodynamic equilibrium. A common-path two-color laser interferometer for obtaining the average plasma density with a sensitivity of 2 × 1015 cm-2 was developed together with a plasma emission spectrometer for analyzing spectral line broadening profiles with a resolution of 5 × 1015 cm-3. Both diagnostics show good agreement when applying the spectral line broadening analysis methodology of Gigosos and Cardeñoso in the temperature range of 0.5 eV-5.0 eV. For plasma with densities of 0.5-2.5 × 1017 cm-3, temperatures of 1 eV-7 eV were indirectly measured by combining the diagnostic information. Measured longitudinally resolved plasma density profiles exhibit a clear temporal evolution from an initial flat-top to a Gaussian-like shape in the first microseconds as material is ejected out from the capillary. These measurements pave the way for highly detailed parameter tuning in plasma sources for particle accelerators and beam optics.

Self-consistency of electron-THF cross sections using electron swarm techniques.

The drift velocity and first Townsend ionization coefficient of electrons in gaseous tetrahydrofuran are measured over the range of reduced electric fields 4-1000 Td using a pulsed-Townsend technique. The measured drift velocities and Townsend ionization coefficients are subsequently used, in conjunction with a multi-term Boltzmann equation analysis, as a further discriminative assessment on the accuracy and completeness of a recently proposed set of electron-THF vapor cross sections. In addition, the sensitivity of the transport coefficients to uncertainties in the existing cross sections is presented. As a result of that analysis, a refinement of the momentum transfer cross section for electron-THF scattering is presented, along with modifications to the neutral dissociation and dissociative electron attachment cross sections. With these changes to the cross section database, we find relatively good self-consistency between the measured and simulated drift velocities and Townsend coefficients.

Monte Carlo study of coherent scattering effects of low-energy charged particle transport in Percus-Yevick liquids.

We generalize a simple Monte Carlo (MC) model for dilute gases to consider the transport behavior of positrons and electrons in Percus-Yevick model liquids under highly nonequilibrium conditions, accounting rigorously for coherent scattering processes. The procedure extends an existing technique [Wojcik and Tachiya, Chem. Phys. Lett. 363, 381 (2002)], using the static structure factor to account for the altered anisotropy of coherent scattering in structured material. We identify the effects of the approximation used in the original method, and we develop a modified method that does not require that approximation. We also present an enhanced MC technique that has been designed to improve the accuracy and flexibility of simulations in spatially varying electric fields. All of the results are found to be in excellent agreement with an independent multiterm Boltzmann equation solution, providing benchmarks for future transport models in liquids and structured systems.

Electron scattering and transport in liquid argon.

The transport of excess electrons in liquid argon driven out of equilibrium by an applied electric field is revisited using a multi-term solution of Boltzmann's equation together with ab initio liquid phase cross-sections calculated using the Dirac-Fock scattering equations. The calculation of liquid phase cross-sections extends previous treatments to consider multipole polarisabilities and a non-local treatment of exchange, while the accuracy of the electron-argon potential is validated through comparison of the calculated gas phase cross-sections with experiment. The results presented highlight the inadequacy of local treatments of exchange that are commonly used in liquid and cluster phase cross-section calculations. The multi-term Boltzmann equation framework accounting for coherent scattering enables the inclusion of the full anisotropy in the differential cross-section arising from the interaction and the structure factor, without an a priori assumption of quasi-isotropy in the velocity distribution function. The model, which contains no free parameters and accounts for both coherent scattering and liquid phase screening effects, was found to reproduce well the experimental drift velocities and characteristic energies.

Anticoagulation and incidence of late cerebrovascular accidents following the Fontan procedure.

Thromboembolic events are a well-reported complication following the Fontan procedure, but no previous studies have compared the incidence of thromboembolic events relative to the prophylactic anticoagulation strategy utilized. We examined the time-adjusted incidence of late thromboembolic events relative to chronic anticoagulation strategy. All patients who have undergone Fontan palliation and are followed at our institution were reviewed. All thromboembolic and major bleeding events were recorded and compared among different subgroups (anticoagulant medication utilized, Fontan variant, and the presence of a residual right-to-left shunt). The incidence of late cerebrovascular accidents (CVAs) per patient-year was calculated for each subgroup. The records of 132 patients were analyzed (median follow-up, 7.6 years; 1066.5 total patient-years). There were no major bleeding complications. One patient receiving no anticoagulation therapy developed a symptomatic thrombus 6 months after Fontan. Three patients suffered late CVAs (range, 3-7 years); 2 were receiving aspirin, and the other received no anticoagulation therapy. All 3 had lateral tunnel Fontan and a residual right-to-left shunt. The overall incidence of late CVA was 2.3%, with an event rate of 0.28% per patient-year. Late CVA was not related to anticoagulation strategy or time from Fontan procedure but was associated with a residual right-to-left shunt and lateral tunnel-type Fontan palliation (p < 0.001). Regardless of anticoagulation strategy utilized, symptomatic CVA is a rare long-term complication following the Fontan procedure.

The impact of pharmacogenomic factors on steroid dependency in pediatric heart transplant patients using logistic regression analysis.

Many pharmacogenomic predictors of drug response are now available, and include both drug metabolism-disposition factors and drug targets. Information on statistical approaches to analyzing large clinical data sets in relation to genetic polymorphisms is limited. The objective of this study was to evaluate whether logistic regression could identify pharmacogenomic predictors of outcome in a large data set in a complex transplant patient population. Seventy pediatric heart transplant patients were studied. Patients were followed for at least 1 yr post-transplantation as outpatients, and weaned from corticosteroids if clinically appropriate. Logistic regression analysis was used to identify the predictors of steroid dependency. The dependent variable was the presence or absence of steroid therapy at 1 yr post-transplantation. The independent variables were the patients' transplant age, gender, MDR1 C3435T and G2677T, CYP3A53B and cytokine polymorphisms. By chi-square test for the MDR1 C3435T polymorphism, 12 of 18 (67%) patients in the CC group were still on prednisone, whereas only 18 of 47 (38%) of the CT/TT group were still receiving prednisone (p = 0.04). For the IL-10 groups, two of 15 patients with the high producer genotype (13.3%) remained on prednisone, in comparison with 16 of 28 patients with the intermediate producer genotype (57.1%) and 15 of 26 patients with the low producer genotype (57.7%, p = 0.01). Logistic regression analysis confirmed MDR1 C3435T (p = 0.021), and IL-10 polymorphisms (intermediate producer genotype p = 0.015; low producer genotype p = 0.013) as independent risk factors for steroid dependency at 1 yr after transplantation. This approach identifies pharmacogenomic factors, which can be studied more extensively in larger data sets, and used in prospective studies to individualize immunosuppressive therapy following solid organ transplantation.

Adverse sexual and psychological effects of male infant circumcision.

A survey of the 35 female and 42 gay sexual partners of circumcised and genitally intact men, and a separate survey of 53 circumcised and 30 genitally intact men themselves, indicated that circumcised men experienced significantly reduced sexual sensation along with associated long-lasting negative emotional consequences.

Hematologic abnormalities in children and young adults receiving tacrolimus-based immunosuppression following cardiothoracic transplantation.

To define the incidence, course, and etiology of hematologic abnormalities in children on tacrolimus-based immunosuppression, we reviewed records of 106 transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to 1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous anemia and neutropenia with or without thrombocytopenia). Common etiologies included: infections, post-transplant lymphoproliferative disease, and medications. Eleven episodes (seven anemia, one neutropenia, and three simultaneous anemia and neutropenia) had unclear etiologies and process of elimination suggested an association with tacrolimus. Interventions included filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a median of 5 days) and epoetin alfa (effective in five of 16 patients, including four of four patients with anemia possibly related to tacrolimus). Five patients (two with neutropenia and three with simultaneous neutropenia and anemia) were switched to cyclosporin A (CsA); rapid resolution occurred in four of the five patients, suggesting a possible association of the hematologic abnormalities with tacrolimus. In summary, hematologic abnormalities are common in children on tacrolimus-based immunosuppression. Most of these hematologic abnormalities are caused by common etiologies; however, a sub-population exists where tacrolimus may be the etiologic agent. Anemia and neutropenia respond to treatment with epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA may be warranted.

A preliminary study of hormone replacement therapy and psychological mood states in perimenopausal women.

Hormone replacement therapy (HRT) for perimenopausal women has been suggested to minimize the physical symptoms of menopause and improve mood and psychological functioning; however, the therapy remains controversial. In this study the effects of such therapy (comprising tablets, patches, and implants) on mood states was investigated within a sample of 70 perimenopausal women who were attending a family planning clinic within the Brisbane metropolitan area. On a battery of standardized questionnaires, including the General Health Questionnaire, the Profile of Mood States, the Eysenck Personality Questionnaire, and the Menstrual Distress Questionnaire, those 35 women who were using hormone replacement therapy prescribed by the clinic physician reported significantly lower scores on anxiety, insomnia, and somatic symptoms than did a comparable group of 35 untreated perimenopausal women. These findings provide some tentative support for the beneficial effects of the therapy on physical symptoms and psychological mood states related to the onset of menopause. Given increased life expectancy, there is a growing need for research into issues of aging.

Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy.

Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and presence of enterovirus-specific antigens. IDC patients who underwent heart transplantation at different times after the onset of heart failure were studied. A cardiac infiltrate of CD4+ and CD8+ T cells was present together with activated macrophages. Furthermore, the same Vbeta gene families, previously found to be skewed in hearts from fulminant cases of CVB3+-IDC, together with two additional Vbeta gene families, Vbeta1 and 5B, were increased. IL-1beta, IL-2, IL-6 and IFN-gamma were expressed in the myocardium while others, like IL-4 were not. In conclusion, an orchestrated complex of immune mechanisms seems to be the basis of IDC etiopathogenesis.

Posttransplant diabetes mellitus in pediatric thoracic organ recipients receiving tacrolimus-based immunosuppression.

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a well-known complication of tacrolimus-based immunosuppression in both adult and pediatric solid organ recipients. The "natural history" of diabetes in the pediatric thoracic transplant population has not yet been described. METHODS: We identified all pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression who developed PTDM. Medical records were reviewed, with a particular focus on the clinical course of PTDM and its relationship to drug weaning. RESULTS: Diabetes developed in 24 of 143 (17%) 30-day survivors of heart (12/96, 13%) and heart-lung/lung (12/ 47, 26%) transplantation. In 17 (71%) patients, the immunosuppressive regimen at the onset of PTDM also included maintenance corticosteroids. Seventeen patients demonstrated glucose intolerance before the onset of diabetes. Nine patients (38%) developed diabetes during pulsed corticosteroid therapy. Median time of onset after transplantation was 9.0 months. All patients required s.c. insulin for glucose control. The median follow-up from transplant was 49.9 months. There was a significant decrease in mean tacrolimus dosage (P<0.01), tacrolimus level (P<0.04), and steroid dosage (P<0.02) from onset of PTDM to most recent follow-up. Despite this significant reduction in immunosuppression, only 3/24 (13%) patients were successfully weaned off insulin. CONCLUSIONS: Diabetes mellitus is a common complication in pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression. Insulin dependence in our population rarely resolved, even after lowering tacrolimus and steroid doses. Discontinuation of steroids did not guarantee resolution of diabetes.

Affective and evaluative descriptors of pain in the McGill Pain Questionnaire: reduction and reorganization.

Recent reports indicate that several descriptors of pain sensations in the McGill Pain Questionnaire (MPQ) are difficult to classify within MPQ sensory subcategories because of incomprehension, underuse, or ambiguity of usage. Adopting the same methodology of recent studies, the present investigation focused on the affective and evaluative subcategories of the MPQ. A decision rule revealed that only 6 of 18 words met criteria for the affective category and 5 of 11 words met criteria for the evaluative category, thus warranting a reduced list of words in these categories. This reduction, however, led to negligible loss of information transmitted. Despite notable changes in classification, the intensity ratings of the retained words correlated very highly with those originally reported for the MPQ. In conclusion, although the intensity ratings of MPQ affective and evaluative descriptors need no revision, selective reduction and reorganization of these descriptors can enhance the efficiency of this approach to pain assessment.

Endomyocardial biopsy in pediatric heart transplant recipients: a useful exercise? (Analysis of 1,169 biopsies).

The objective of this study was to define the diagnostic yield for endomyocardial biopsy (EMB) procedures performed for various indications in a large pediatric heart transplant population. Endomyocardial biopsy procedure has been employed as the 'gold standard' for rejection surveillance. Previous studies have questioned the value of surveillance EMB beyond the early post-transplant period. We retrospectively reviewed data on 82 pediatric heart transplant recipients with serial EMB. A total of 1,169 EMB were performed during a follow-up period of 2-149 months (median 41 months). EMB were classified by age at transplantation, time from transplant, immunosuppressive regimen used [tacrolimus vs. cyclosporin A (CsA)] and indication, i.e. surveillance, follow-up after rejection or lowering of immunosuppression, non-specific clinical symptoms and graft dysfunction. During the first year after heart transplantation, surveillance EMB demonstrated significant rejection [International Society for Heart and Lung Transplantation (ISHLT) grade > or = 3A] in 18% of biopsies with the yield being 14-43% for all other indications. Surveillance EMB 1-5 yr post-transplantation were found to have a lower diagnostic yield in infants (4%, vs. 13% in children) and in patients with favorable first-year rejection history (9% vs. 17% in 'frequent rejectors'). Tacrolimus-based immunosuppression was associated with significantly less rejection, but only in the first year post-transplantation (14% in tacrolimus vs. 24% in CsA surveillance EMB, p = 0.035). Surveillance EMB remains an important diagnostic tool for rejection surveillance during the first 5 years after pediatric heart transplantation. Endomyocardial biopsy is particularly warranted after reduction of immunosuppression and for monitoring for ongoing rejection after treatment of acute rejection episodes.