Exceptionally Stable And Super-Efficient Electrocatalysts Derived From Semiconducting Metal Phosphonate Frameworks.

Two new isostructural semiconducting metal-phosphonate frameworks are reported. Co2 [1,4-NDPA] and Zn2 [1,4-NDPA] (1,4-NDPA4- is 1,4-naphthalenediphosphonate) have optical bandgaps of 1.7 eV and 2.5 eV, respectively. The electrocatalyst derived from Co2 [1,4-NPDA] as a precatalyst generated a low overpotential of 374 mV in the oxygen evolution reaction (OER) with a Tafel slope of 43 mV dec-1 at a current density of 10 mA cm-2 in alkaline electrolyte (1 mol L-1 KOH), which is indicative of remarkably superior reaction kinetics. Benchmarking of the OER of Co2 [1,4-NPDA] material as a precatalyst coupled with nickel foam (NF) showed exceptional long-term stability at a current density of 50 mA cm-2 for water splitting compared to the state-of-the-art Pt/C/RuO2 @NF after 30 h in 1 mol L-1 KOH. In order to further understand the OER mechanism, the transformation of Co2 [1,4-NPDA] into its electrocatalytically active species was investigated.

Using the Zeno line to assess and refine molecular models.

The Zeno line is the locus of points on the temperature-density plane where the compressibility factor of the fluid is equal to one. It has been observed to be straight for a broad variety of real fluids, although the underlying reasons for this are still unclear. In this work, a detailed study of the Zeno line and its relation to the vapor-liquid coexistence curve is performed for two simple model pair-potential fluids: attractive square-well fluids with varying well-widths λ and Mie n-6 fluids with different repulsive exponents n. Interestingly, the Zeno lines of these fluids are curved, regardless of the value of λ or n. We find that for square-well fluids, λ ≈ 1.8 presents a Zeno line, which is the most linear over the largest temperature range. For Mie n-6 fluids, we find that the straightest Zeno line occurs for n between 8 and 10. Additionally, the square-well and Mie fluids with the straightest Zeno line showed the closest quantitative agreement with the vapor-liquid coexistence curve for experimental fluids that follow the principle of corresponding states (e.g., argon, xenon, krypton, methane, nitrogen, and oxygen). These results suggest that the Zeno line can provide a useful additional feature, in complement to other properties, such as the phase envelope, to evaluate molecular models.

Tethered hard spheres: A bridge between the fluid and solid phases.

The thermodynamics of hard spheres tethered to a Face-Centered Cubic (FCC) lattice is investigated using event-driven molecular-dynamics. The particle-particle and the particle-tether collision rates are related to the phase space geometry and are used to study the FCC and fluid states. In tethered systems, the entropy can be determined by at least two routes: (i) through integration of the tether collision rates with the tether length rT or (ii) through integration of the particle-particle collision rates with the hard-sphere diameter σ (or, equivalently, the density). If the entropy were an entirely analytic function of rT and σ, these two methods for calculating the entropy should lead to the same results; however, a non-analytic region exists as an extension of the solid-fluid phase transition of the untethered hard-sphere system, and integration paths that cross this region will lead to values for the entropy that depend on the particular path chosen. The difference between the calculated entropies appears to be related to the communal entropy, and the location of the non-analytic region appears to be related to conditions where the regions of phase space associated with the FCC configuration become separated from those associated with the disordered fluid. The non-analytic region is finite in extent, vanishing below rT/a ≈ 0.55, where a is the lattice spacing, and there are many continuous paths that connect the fluid and solid phases that can be used to determine the crystal free energy with respect to the fluid.

Imaging diagnosis of aortic stenosis.

Aortic valve stenosis (AS) is the commonest primary valve disorder with increasing prevalence with age. Trans-thoracic echocardiogram is the main imaging technique used to diagnose AS, but discrepancy in diagnosis has been described in almost one third of cases. Other imaging methods, particularly electrocardiogram (ECG)-gated computed tomography, have now emerged to further clarify the diagnosis of AS by both demonstrating the degree of calcification in the valve as well as aortic valve area. Cardiac magnetic resonance imaging allows accurate quantification of ventricular function and evaluation of the myocardium. This paper provides a comprehensive review of the diagnosis of AS for the radiologist.

Tethered-particle model: The calculation of free energies for hard-sphere systems.

Two methods for computing the entropy of hard-sphere systems using a spherical tether model are explored, which allow the efficient use of event-driven molecular-dynamics simulations. An intuitive derivation is given, which relates the rate of particle collisions, either between two particles or between a particle and its respective tether, to an associated hypersurface area, which bounds the system's accessible configurational phase space. Integrating the particle-particle collision rates with respect to the sphere diameter (or, equivalently, density) or the particle-tether collision rates with respect to the tether length then directly determines the volume of accessible phase space and, therefore, the system entropy. The approach is general and can be used for any system composed of particles interacting with discrete potentials in fluid, solid, or glassy states. The entropies calculated for the liquid and crystalline hard-sphere states using these methods are found to agree closely with the current best estimates in the literature, demonstrating the accuracy of the approach.

Steatotic Livers Are More Susceptible to Ischemia Reperfusion Damage after Transplantation and Show Increased γδ T Cell Infiltration.

Liver transplantation (LTx) is often the only possible therapy for many end-stage liver diseases, but successful long-term transplant outcomes are limited by multiple factors, including ischemia reperfusion injury (IRI). This situation is aggravated by a shortage of transplantable organs, thus encouraging the use of inferior quality organs. Here, we have investigated early hepatic IRI in a retrospective, exploratory, monocentric case-control study considering organ marginality. We analyzed standard LTx biopsies from 46 patients taken at the end of cold organ preparation and two hours after reperfusion, and we showed that early IRI was present after two hours in 63% of cases. Looking at our data in general, in accordance with Eurotransplant criteria, a marginal transplant was allocated at our institution in about 54% of cases. We found that patients with a marginal-organ LTx showing evidence of IRI had a significantly worse one-year survival rate (51% vs. 75%). As we saw in our study cohort, the marginality of these livers was almost entirely due to steatosis. In contrast, survival rates in patients receiving a non-marginal transplant were not influenced by the presence or absence of IRI. Poorer outcomes in marginal organs prompted us to examine pre- and post-reperfusion biopsies, and it was revealed that transplants with IRI demonstrated significantly greater T cell infiltration. Molecular analyses showed that higher mRNA expression levels of CXCL-1, CD3 and TCRγ locus genes were found in IRI livers. We therefore conclude that the marginality of an organ, namely steatosis, exacerbates early IRI by enhancing effector immune cell infiltration. Preemptive strategies targeting immune pathways could increase the safety of using marginal organs for LTx.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Late diagnosis of chronic granulomatous disease.

Modern era advancements in medical care, with improved treatment of infections, can result in delayed diagnosis of congenital immunodeficiencies. In this study we present a retrospective cohort of 16 patients diagnosed with Chronic Granulomatous Disease (CGD) at adulthood. Some of the patients had a milder clinical phenotype, but others had a classic phenotype with severe infectious and inflammatory complications reflecting a profoundly impaired neutrophil function. It is therefore of great importance to investigate the individual journey of each patient through different misdiagnoses and the threads which led to the correct diagnosis. Currently the recommended definitive treatment for CGD is hematopoietic stem cell transplantation (HSCT). Although survival of our patients to adulthood might argue against the need for early HSCT during infancy, we claim that the opposite is correct, as most of them grew to be severely ill and diagnosed at a stage when HSCT is debatable with potentially an unfavorable outcome. This cohort stresses the need to increase awareness of this severe congenital immunodeficiency among clinicians of different specialties who might be treating undiagnosed adult patients with CGD.

A comprehensive study of the thermal conductivity of the hard sphere fluid and solid by molecular dynamics simulation.

This work reports a new set of hard sphere (HS) thermal conductivity coefficient, λ, data obtained by Molecular Dynamics (MD) computer simulation, over a density range covering the dilute fluid to near the close-packed solid, and for a large number of particles (up to N = 13 1072) and long simulation times. The N-dependence of the thermal conductivity is shown to be proportional to N-2/3 to a good approximation over a wide range of system sizes, which enabled λ values in the thermodynamic limit to be predicted accurately. The fluid and solid λ can be represented well by the Enskog theory (ET) formula, λE, times a density-dependent correction term, which is close to unity for the fluid and practically constant for the solid. The convergence of the MD λ data back towards ET in the metastable fluid starts just above the freezing density. For the HS solid and dense fluid it was found that the thermal conductivity is nearly linear in pressure, as has been observed experimentally for a number of solids. Simple excess entropy scaling over the higher density fluid phase region was found, and Rosenfeld's exponential relationship can be fitted to the simulation data for the solid to a high degree of accuracy. The simulation analysis has revealed a number of new trends in the behaviour of the HS thermal conductivity which could be useful in building more accurate models for heat conduction in experimental systems.

The impact of a nationwide hands-on workshop on the diagnostic rates and management of obstetrical anal sphincter Injuries in Israel.

AIM: The aim was to evaluate the influence of a half day, hands-on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs). METHOD: Starting in February 2011, hands-on workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands-on workshop resembles the workshop organized at the International Urogynecological Association annual conferences. Participants included medical staff, midwives and surgical residents from each medical centre. We collected data regarding the rate of OASIs, 1 year before and 1 year following the workshop, in 11 medical centres. The study population was composed of parturients with the following inclusion criteria: singleton pregnancy, vertex presentation and vaginal delivery. Pre-viable preterm gestations (< 24 weeks), birth weight < 500 g, stillborn, and those with major congenital anomalies, multifoetal pregnancies, breech presentations and caesarean deliveries were excluded from the analysis. RESULTS: In the reviewed centres, 70 663 (49.3%) women delivered prior to the workshop (pre-workshop group) and 72 616 (50.7%) women delivered following the workshop (post-workshop group). Third- or fourth-degree perineal tears occurred in 248 women (0.35%) before the workshop, and in 328 (0.45%) following the workshop, a significant increase of 28.7% (P = 0.002). The increase in diagnosis was significant also in women with third-degree tears alone, 226 women (0.32%) before the workshop and 298 (0.41%) following the workshop, an increase of 28.3% (P = 0.005). CONCLUSION: The detection rate of OASIs has significantly increased following the hands-on workshop. The implementation of such programmes is crucial for increasing awareness and detection rates of OASI following vaginal deliveries.

Definition, reasons, and risk factors for mortality of patients listed for liver transplantation - a single-center study.

BACKGROUND: In Germany, following the principle "sickest first", patients awaiting liver transplantation (LTPL) are often transplanted with high MELD score and run the risk that they can no longer be transplanted, getting "too sick for transplant". METHODS: In a retrospective single-center study, we analyzed the mortality of adult patients on the waiting list for LTPL during the years 2014 to 2017. To stratify risk factors, we compared characteristics of deceased and transplanted patients. RESULTS: The main reasons for mortality were sepsis (42.9 %), malignancy (24.3 %) and bleeding (10.0 %). Risk factors for mortality (OR, univariate logistic regression, p < 0.05) were acute on chronic liver failure (ACLF), loss of E-MELD, sepsis, pneumonia, proof of pathogens, candidemia, stay at ICU, multiple organ failure and mechanical ventilation. Multivariate analysis revealed pneumonia (p < 0.001) and high MELD (p = 0.031) as risk factors. Transplantation was more likely in patients with E-MELD. We suggest a Waiting List Mortality Index for Transplantation (WMIT), by dividing deceased patients to transplanted patients to assess mortality. Average WMIT in our cohort was 0.65. CONCLUSIONS: Mortality on the waiting list is mainly determined by pneumonia and infections in high-MELD patients. Therefore, patients with ACLF after infections should be prioritized for LTPL. A WMIT might suitably represent waiting list mortality.

Surgical Aspects of Liver Transplantation and Domino Liver Transplantation in Maple Syrup Urine Disease: Analysis of 15 Donor-Recipient Pairs.

Liver transplantation (LT) has been shown to be a feasible treatment in patients with severe forms of maple syrup urine disease (MSUD). Because of a sufficient extrahepatic enzyme activity in non-MSUD individuals, the organ of MSUD patients can be used as a domino graft. We performed a retrospective data collection of all LTs for MSUD carried out at the University Medical Center Hamburg-Eppendorf (2016-2018). Moreover, data from all consecutive domino LTs of the MSUD grafts either transplanted at our institution or allocated to other transplant centers were analyzed. During the study period, 15 LTs in MSUD patients were performed (12 children, 3 adults; median age, 10.9 years; range, 0.3-26.1 years). Biliary complications occurred in 20%, and 13.3% suffered from bleeding complications. No further surgical problems occurred. At present, all MSUD patients are alive with a well-functioning liver graft and on an unrestricted diet. In total, 14 consecutive domino LTs were performed. No surgical complications requiring intervention occurred. One patient died because of HCC relapse, and all other patients are alive with good liver graft function. In conclusion, the use of MSUD livers as domino grafts is safe and allows application of LT in MSUD patients without net extraction of a liver graft from the limited donor pool.

Tweeting the Headache Meetings: Cross-Sectional Analysis of Twitter Activity Surrounding American Headache Society Conferences.

OBJECTIVES: To describe and analyze Twitter activity associated with American Headache Society (AHS) conferences and evaluate the potential for Twitter to promote education and public outreach. BACKGROUND: Many medical and scientific conferences have adopted Twitter as a method of promoting discussion among attendees as well as increasing visibility. Relatively little is known, however, about the composition of conference Twitter activity, the participants, and the impact on broader Twitter discussions. METHODS: We analyzed Twitter data from 5 AHS conferences held from 2014 to 2016 using their respective hashtags. Using the Symplur Healthcare Hashtags open social media search platform, we gathered data on numbers of tweets, impressions, participants, and mentions during a 10-day period surrounding each conference, as well as samples of Twitter accounts participating. Prominent accounts were categorized as individual medical professionals, other individuals, host organizations, health-related organizations, medical centers, and industry by cross-checking their Twitter profiles and conference registration lists. Larger samples of accounts participating in the 2016 conferences were also obtained and categorized similarly, with individual person accounts classified by conference registration status. A related prominent hashtag (#migraine) was also identified and Twitter usage before, during, and after each conference was analyzed to evaluate the impact of conference activity on broader Twitter conversations. RESULTS: Nineteen thousand nine hundred thirty-six tweets were generated across the 5 conferences, with 11,531 (58%) created by the Top 10 participating accounts in each conference, which were primarily individual medical professionals and host organizations. Thirty-two million six hundred eighty-three thousand impressions were generated across the 5 conferences, with 24,656,000 (75%) coming from the Top 10 participants in each, particularly host organizations and other individuals. An average of 331 accounts participated in each conference. The Top 10 mentioned accounts in each conference (consisting of 21 unique accounts with 14 accounts in the Top 10 across multiple conferences, primarily individual medical professionals) received a total of 15,093 mentions. Among 135 unique accounts participating actively in the two 2016 conferences, 39% were individual medical professionals, 38% other individuals, 16% health-related organizations (including the 2 host organizations), 4% medical centers, and 2% industry. From these samples, 34 of 70 (49%) and 43 of 66 (65%) individual person accounts participating in the Twitter discussion at each conference were not registered conference attendees, indicating substantial outside participation via Twitter. #migraine usage during conferences showed a significant increase from baseline in number of tweets (6080 in a 10-day period vs 3721, P < .0001) and participants (2332 vs 1830, P < .0001) but the increase was not significant for impressions (30,155 vs 25,361, P = .240). CONCLUSIONS: Consistent with the dynamics of Twitter conversations on other topics, AHS conference discussions featured a small group of accounts creating the bulk of content, with individual medical professionals and host organizations generating the largest shares of tweets and mentions while host organizations and other individuals produced the most impressions. Participating accounts were mainly individuals and health-related organizations, with more non-attendee participants than expected. Conference Twitter activity correlated with a significant increase in #migraine usage, suggesting a perceptible influence on the discussion of health-related topics beyond the conference itself.

Thermodynamic and dynamical properties of the hard sphere system revisited by molecular dynamics simulation.

Revised thermodynamic and dynamical properties of the hard sphere (HS) system are obtained from extensive molecular dynamics calculations carried out with large system sizes (number of particles, N) and long times. Accurate formulas for the compressibility factor of the HS solid and fluid branches are proposed, which represent the metastable region and take into account its divergence at close packing. Some basic second-order thermodynamic properties are obtained and a maximum in some of their derivatives in the metastable fluid region is found. The thermodynamic parameters associated with the melting-freezing transition have been determined to four digit accuracy, which generates accurate new values for the coexistence properties of the HS system. For the self-diffusion coefficient, D, it is shown that relatively large systems (N > 104) are required to achieve an accurate linear extrapolation of D to the infinite size limit with a D vs. N-1/3 plot. Moreover, it is found that there is a density dependence of the value of the slope in the linear regime. The density dependent correction becomes practically insignificant at higher densities and the hydrodynamic formula found in the literature is still accurate. However, with decreasing density the density dependence of the size correction cannot be neglected, which indicates that other sources of N-dependence, apart from those derived on purely hydrodynamic grounds, may also be important (and as yet unaccounted for). A detailed analytic representation of the density dependence of the HS self-diffusion coefficient and the HS viscosity, η, is given. It is shown that the HS viscosity near freezing and in the metastable region can be described well by the Krieger-Dougherty equation. Both D and η start to scale at high densities and in the metastable region in such a way that Dηp = const, where p ≃ 0.97, and D → 0 and η → ∞ at a packing fraction of 0.58, which coincides with some previous predictions of the HS glass transition density.

Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial.

Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 µg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.

Selection and use of immunosuppressive therapies after liver transplantation: current German practice.

In recent years, immunosuppression (IS) after liver transplantation (LT) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors (CNIs) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin-2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure. An early addition of mycophenolate mofetil (MMF) or the mTOR inhibitor everolimus also allows for the reduction in the CNI dose. To reduce the risk of malignancy, in particular of skin tumors, as well as to prevent the deterioration of renal function, everolimus-based therapy may be advantageous. Apart from patients with autoimmune hepatitis, steroids are withdrawn within 3-6 months after transplantation. Overall, immunosuppression can only be standardized in a limited proportion of patients due to specific clinical requirements and risk factors. Future studies should attempt to refine accurate individualization of the immunosuppressive regimen in specific difficult-to-treat patient subpopulations.

Unconventional RORγt+ T cells drive hepatic ischemia reperfusion injury.

An emerging body of evidence suggests a pivotal role of CD3(+) T cells in mediating early ischemia reperfusion injury (IRI). However, the precise phenotype of T cells involved and the mechanisms underlying such T cell-mediated immune responses in IRI, as well as their clinical relevance, are poorly understood. In this study, we investigated early immunological events in a model of partial warm hepatic IRI in genetically targeted mice to study the precise pathomechanistic role of RORγt(+) T cells. We found that unconventional CD27(-)γδTCR(+) and CD4(-)CD8(-) double-negative T cells are the major RORγt-expressing effector cells in hepatic IRI that play a mechanistic role by being the main source of IRI-mediating IL-17A. We further show that unconventional IRI-mediating T cells are contingent on RORγt, as highlighted by the fact that a genetic deficiency for RORγt, or its therapeutic antagonization via digoxin, is protective against hepatic IRI. Therefore, identification of CD27(-)γδTCR(+) and CD4(-)CD8(-) double-negative T cells as the major source of IL-17A via RORγt in hepatic IRI opens new therapeutic options to improve liver transplantation outcomes.

Brain connectivity during verbal working memory in children and adolescents.

Working memory (WkM) is a fundamental cognitive process that serves as a building block for higher order cognitive functions. While studies have shown that children and adolescents utilize similar brain regions during verbal WkM, there have been few studies that evaluate the developmental differences in brain connectivity. Our goal was to study the development of brain connectivity related to verbal WkM in typically developing children and adolescents. Thirty-five healthy children and adolescents, divided into three groups: 9-12 (children), 13-16 (young adolescents), and 17-19 (older adolescents) years, were included in this functional magnetic resonance imaging (fMRI) study. The verbal WkM task involved a modified Sternberg item recognition paradigm using three different loads. Brain connectivity analysis was performed using independent component analyses and regressing the components with the design matrix to determine task-related networks. Connectivity analyses resulted in four components associated solely with encoding, four solely with recognition and two with both. Two networks demonstrated age-related differences with respect to load, (1) the left motor area and right cerebellum, and 2) the left prefrontal cortex, left parietal lobe, and right cerebellum. Post hoc analyses revealed that the first network showed significant effects of age between children and the two older groups. There was increasing connectivity with increasing load for adolescents. The second network demonstrated age-related differences between children and older adolescents. Children have higher task-related connectivity at lower loads, but they tend to equalize with the adolescents with higher loads. Finally, a non-load related network involving the orbital frontal and anterior cingulate cortices showed less connectivity in children. Hum Brain Mapp 35:698-711, 2014. © 2012 Wiley Periodicals, Inc.

Clinical management of patients receiving cell-based immunoregulatory therapy.

Administering immunoregulatory cells as medicinal agents is a revolutionary approach to the treatment of immunologically mediated diseases. Isolating, propagating, and modifying cells before applying them to patients allows complementation of specific cellular functions, which opens astonishing new possibilities for gain-of-function antigen-specific treatments in autoimmunity, chronic inflammatory disorders, and transplantation. This critical review presents a systematic assessment of the potential clinical risks posed by cell-based immunotherapy, focusing on treatment of renal transplant recipients with regulatory macrophages as a concrete example.

Mapping continuous potentials to discrete forms.

The optimal conversion of a continuous inter-particle potential to a discrete equivalent is considered here. Existing and novel algorithms are evaluated to determine the best technique for creating accurate discrete forms using the minimum number of discontinuities. This allows the event-driven molecular dynamics technique to be efficiently applied to the wide range of continuous force models available in the literature, and facilitates a direct comparison of event-driven and time-driven molecular dynamics. The performance of the proposed conversion techniques are evaluated through application to the Lennard-Jones model. A surprising linear dependence of the computational cost on the number of discontinuities is found, allowing accuracy to be traded for speed in a controlled manner. Excellent agreement is found for static and dynamic properties using a relatively low number of discontinuities. For the Lennard-Jones potential, the optimized discrete form outperforms the original continuous form at gas densities but is significantly slower at higher densities.