Structure and electron affinity of the 4H-SiC (0001) surfaces: a methodological approach for polar systems.

The ability to accurately and consistently determine the surface electronic properties of polar materials is of great importance for device applications. Polar surface modelling is fundamentally limited by the spontaneous polarisation of these materials in a periodic boundary condition scheme. Surface data are sensitive to supercell parameters, including slab and vacuum thicknesses, as well as the non-equivalence of surface adsorbates on opposite surfaces. Using 4H-SiC as a specific case, this study explores calculation of electron affinities (EAs) of (0001̄) and (0001) surfaces varying chemical termination as a function of computational parameters. We report the impact in terms of band-gap, electric fields across the vacuum and slab for single and double cell slab models, where the latter is constructed with inversional symmetry to eliminate the electric field in the vacuum regions. We find that single cells are sensitive to both slab and vacuum thickness. The band-gap narrows with slab thickness, ultimately vanishing and inducing charge transfer between opposite surfaces. This has a consequence for predicted EAs. Adsorbate species are found to play a crucial role in the rate of narrowing. Back to back cells with inversional symmetry have larger electric fields present across the slab than the single slab cases, resulting in a greater band-gap narrowing effect, but the vacuum thickness dependence is completely removed. We discuss the relative merits of the two approaches.

Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation.

During simultaneous liver-kidney transplantation (SLK) in highly sensitized patients, donor specific anti-human leukocyte antigen antibodies (DSA, HLA) can be present prior to transplant leading to positive crossmatch, yet these recipients have relatively low incidences of acute rejection. The mechanisms and timing underlying immunologic changes that occur intra-operatively remain largely unknown. Therefore, we measured the intra- and peri-operative kinetics of anti-HLA antibodies in highly sensitized SLK recipients. In this study, pre- and post-operative blood samples were obtained from sensitized SLK candidates with documented DSA. Intra-operative samples were obtained from a sub-group of SLK recipients. Pretransplant anti-HLA antibody profiles were created and flow cytometry and anti-human globulin complement-dependent cytotoxic crossmatches were performed. Significant reductions in anti-HLA class I and II DSA were seen intra-operatively shortly after reperfusion of the liver allograft. This effect was most pronounced for anti-HLA class I DSA (mean change, -85%, p < 0.05); changes to anti-HLA class II DSA were less robust (mean change, -47%, p = 0.15). Importantly, non-DSA anti-HLA antibodies remained unchanged throughout the perioperative period, suggesting the mechanism(s) by which the liver lowers DSA levels are specific to the DSA. These data demonstrate the immunologic benefit of performing SLK is lasting and occurs very shortly after liver reperfusion.

Bracing for the Storm: One Health Care System's Planning for the COVID-19 Surge.

PROBLEM: University of Washington Medicine (UW Medicine), an academic health system in Washington State, was at the epicenter of the first outbreak of the COVID-19 pandemic in the United States. The extent of emergency activation needed to adequately respond to this global pandemic was not immediately known, as the evolving situation differed significantly from any past disaster response preparations in that there was potential for exponential growth of infection, unproven mitigation strategies, serious risk to health care workers, and inadequate supply chains for critical equipment. APPROACH: The rapid transition of the UW Medicine system to account for projected COVID-19 and usual patient care, while balancing patient and staff safety and conservation of resources, represents an example of an adaptive disaster response. KEY INSIGHTS: Although our organization's ability to meet the needs of the public was uncertain, we planned and implemented changes to space, supply management, and staffing plans to meet the influx of patients across our clinical entities. The surge management plan called for specific actions to be implemented based on the level of activity. This article describes the approach taken by UW Medicine as we braced for the storm.

Silicon and germanium terminated (0 0 1)-(2 [Formula: see text] 1) diamond surface.

Control over the chemical termination of diamond surfaces has shown great promise in the realization of field-emission applications, the selection of charge states of near-surface colour-centres such as NV, and the realisation of surface-conductive channels for electronic device applications. Experimental investigations of ultra-thin Si and Ge layers yield surface states both within the band-gap and resonant with the underlying diamond valence band. In this report, we report the results of density-functional simulations of a range of coverages of Si and Ge on diamond (0 0 1) surfaces. We have found that surface coverage with crystallogen:carbon ratios of 67% and 75% are more stable than both higher and lower coverages on the (0 0 1)-diamond surface, and that they can explain the observation of an occupied band around 1.7 eV below the valence band top. We also report geometries, adsorption energies and electron affinities of these surface structures, and show that the resonant state is made up from conventional spd-covalent [Formula: see text]-bonding orbitals between the surface adsorbates.

Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Surface-state dependent optical properties of OH-, F-, and H-terminated 4H-SiC quantum dots.

Density functional calculations are performed for OH-, F- and H-terminated 4H-SiC 10-20 Å diameter clusters to investigate the effect of surface species upon the optical absorption properties. H-termination results in a pronounced size-dependent quantum-confinement in the absorption, whereas F- and OH-terminations exhibit much reduced size dependent absorption due to surface states. Our findings are in good agreement with recent experimental studies, and are able to explain the little explored dual-feature photoluminescence spectra of SiC quantum dots. We propose that along with controlling the size, suitable surface termination is the key for optimizing optical properties of 4H-SiC quantum structures, such as might be exploited in optoelectronics, photovoltaics and biological applications.

Nitride superluminescent diodes with broadened emission spectrum fabricated using laterally patterned substrate.

We demonstrate InGaN/GaN superluminescent diodes with broadened emission spectra fabricated on surface-shaped bulk GaN (0001) substrates. The patterning changes the local vicinal angle linearly along the device waveguide, which results in an indium incorporation profile in InGaN quantum wells. The structure was investigated by microphotoluminescence mapping, showing a shift of central emission wavelength from 413 nm to 430 nm. Spectral full width at half maximum of processed superluminescent diodes is equal to 6.1 nm, while the reference chips show 3.4 nm. This approach may open the path for using nitride devices in applications requiring broad emission spectrum and high beam quality, such as optical coherence tomography.

Survival Outcomes Following Pediatric Liver Transplantation (Pedi-SOFT) Score: A Novel Predictive Index.

A prognostic index to predict survival after liver transplantation could address several clinical needs. Here, we devised a scoring system that predicts recipient survival after pediatric liver transplantation. We used univariate and multivariate analysis on 4565 pediatric liver transplant recipients data and identified independent recipient and donor risk factors for posttransplant mortality at 3 months. Multiple imputation was used to account for missing variables. We identified five factors as significant predictors of recipient mortality after pediatric liver transplantation: two previous transplants (OR 5.88, CI 2.88-12.01), one previous transplant (OR 2.54, CI 1.75-3.68), life support (OR 3.68, CI 2.39-5.67), renal insufficiency (OR 2.66, CI 1.84-3.84), recipient weight under 6 kilograms (OR 1.67, CI 1.12-2.36) and cadaveric technical variant allograft (OR 1.38, CI 1.03-1.83). The Survival Outcomes Following Pediatric Liver Transplant score assigns weighted risk points to each of these factors in a scoring system to predict 3-month recipient survival after liver transplantation with a C-statistic of 0.74. Although quite accurate when compared with other posttransplant survival models, we would not advocate individual clinical application of the index.

Mcph1/Brit1 deficiency promotes genomic instability and tumor formation in a mouse model.

MCPH1, also known as BRIT1, has recently been identified as a novel key regulatory gene of the DNA damage response pathway. MCPH1 is located on human chromosome 8p23.1, where human cancers frequently show loss of heterozygosity. As such, MCPH1 is aberrantly expressed in many malignancies, including breast and ovarian cancers, and the function of MCPH1 has been implicated in tumor suppression. However, it remains poorly understood whether MCPH1 deficiency leads to tumorigenesis. Here we generated and studied both Mcph1(-/-) and Mcph1(-/-)p53(-/-) mice; we showed that Mcph1(-/-) mice developed tumors with long latency, and that primary lymphoma developed significantly earlier in Mcph1(-/-)p53(-/-) mice than in Mcph11(+/+)p53(-/-) and Mcph1(+/-)p53(-/-) mice. The Mcph1(-/-)p53(-/-) lymphomas and derived murine embryonic fibroblasts (MEFs) were both more sensitive to irradiation. Mcph1 deficiency resulted in remarkably increased chromosome and chromatid breaks in Mcph1(-/-)p53(-/-) lymphomas and MEFs, as determined by metaphase spread assay and spectral karyotyping analysis. In addition, Mcph1 deficiency significantly enhanced aneuploidy as well as abnormal centrosome multiplication in Mcph1(-/-)p53(-/-) cells. Meanwhile, Mcph1 deficiency impaired double strand break (DSB) repair in Mcph1(-/-)p53(-/-) MEFs as demonstrated by neutral Comet assay. Compared with Mcph1(+/+)p53(-/-) MEFs, homologous recombination and non-homologous end-joining activities were significantly decreased in Mcph1(-/-)p53(-/-) MEFs. Notably, reconstituted MCPH1 rescued the defects of DSB repair and alleviated chromosomal aberrations in Mcph1(-/-)p53(-/-) MEFs. Taken together, our data demonstrate MCPH1 deficiency promotes genomic instability and increases cancer susceptibility. Our study using knockout mouse models provides convincing genetic evidence that MCPH1 is a bona fide tumor suppressor gene. Its deficiency leading to defective DNA repair in tumors can be used to develop novel targeted cancer therapies in the future.

Increasing Hospital Pharmacist Clinical Competence in Intensive Pharmacotherapeutics Using a Novel Pharmacist Clinical Educational Program.

BACKGROUND: Intensive pharmacotherapeutics (IP) is the application of multiple evidence-based practices applied at a patient-specific level, creating the overall best treatment plan in medically complex patients. To practice at this level, a high level of clinical knowledge and competency is paramount. OBJECTIVE: The goal of the pharmacist clinical educational program was to develop an engaging, challenging, and interactive program, which was concise but intense, to improve pharmacists' clinical knowledge and critical thinking skills. METHODS: A 12-week educational series was developed and successfully implemented. The primary outcome was a comparison of the proportion of accepted clinical interventions per total number of medication orders reviewed by hospital pharmacists during and after the pharmacist clinical educational program to a 3-month baseline. The secondary outcome was to anonymously gauge participant satisfaction with the program. RESULTS: The proportion of accepted clinical interventions increased from 6.4% (at baseline) to 9.1% and 8.7% in the 3 months during and 3 months immediately after the educational program, respectively (P < .01). The overall acceptance rate for clinical interventions remained >90% for all periods. Approximately 94% of respondents (n = 16) indicated that the program met their educational needs. CONCLUSIONS: The development of a clinical educational program to engage, challenge, and incentivize pharmacists is an essential tool to elevate the practice of IP. By maximizing existing resources, programming can be provided in an efficient and cost-effective manner. As health systems continue to merge on a national level, the methods described here demonstrate a means to provide critical education for both clinical and organizational competency.

Identification of the structure of the 3107 cm(-1) H-related defect in diamond.

A prominent hydrogen-related infrared absorption peak seen in many types of diamonds at 3107 cm(-1) has been the subject of investigation for many years. It is present in natural type-Ia material and can be introduced by heat-treating synthetic or CVD diamond. Based upon the most recent experimental data, it is thought that the defect giving rise to this vibrational mode is vacancy-related and is likely to contain nitrogen. Using first-principles simulations we present a VN3H model for the originating centre that simultaneously satisfies the different experimental observations including the strain response.

Upper extremity deep vein thrombosis in hospitalized patients: a descriptive study.

Increasingly, there is a focus on the prevention of hospital-acquired conditions including venous thromboembolism. Many studies have evaluated pulmonary embolism and lower extremity deep vein thrombosis, but less is known about upper extremity deep vein thrombosis (UEDVT) in hospitalized patients. The objective of this study was to describe UEDVT incidence, associated risks, outcomes, and management in our institution. Using an information technology tool, we reviewed records of all symptomatic adult inpatients diagnosed with UEDVT at an academic tertiary center between September 2011 and November 2012. Fifty inpatients were diagnosed with 76 UEDVTs. Their mean age was 49 years; 70% were men. Sixteen percent had a history of venous thromboembolism; 20% had a history of malignancy. The mean length of stay (LOS) was 24.6 days (range, 2-91 days); 50% were transferred from outside hospitals. Thirty-eight percent of UEDVTs were in internal jugular veins, 21% in axillary veins, and 25% in brachial veins. Forty-four percent of patients had UEDVT associated with central venous catheters (CVCs). During hospitalization, 78% were fully anticoagulated; 75% of survivors at discharge. Only 38% were discharged to self-care; 10% died during hospitalization. Patients with UEDVT were more likely to have CVCs, malignancy, and severe infection. Many patients were transferred critically ill with prolonged LOS and high in-hospital mortality. Most UEDVTs were treated even in the absence of concurrent lower extremity deep vein thrombosis or pulmonary embolism. Additional research is needed to modify risks and optimize outcomes. Journal of Hospital Medicine 2014;9:48-53. © 2013 Society of Hospital Medicine.

Hyperfine interactions at nitrogen interstitial defects in diamond.

Diamond has many extreme physical properties and it can be used in a wide range of applications. In particular it is a highly effective particle detection material, where radiation damage is an important consideration. The WAR9 and WAR10 are electron paramagnetic resonance centres seen in irradiated, nitrogen-containing diamond. These S = 1/2 defects have C(2v) and C(1h) symmetry, respectively, and the experimental spectra have been interpreted as arising from nitrogen split-interstitial centres. Based upon the experimental and theoretical understanding of interstitial nitrogen defect structures, the AIMPRO density functional code has been used to assess the assignments for the structures of WAR9 and WAR10. Although the calculated hyperfine interaction tensors are consistent with the measured values for WAR9, the thermal stability renders the assignment problematic. The model for the WAR10 centre yields principal directions of the hyperfine tensor at variance with observation. Alternative models for both centres are discussed in this paper, but no convincing structures have been found.

Extended point defects in crystalline materials: Ge and Si.

B diffusion measurements are used to probe the basic nature of self-interstitial point defects in Ge. We find two distinct self-interstitial forms--a simple one with low entropy and a complex one with entropy ∼30 k at the migration saddle point. The latter dominates diffusion at high temperature. We propose that its structure is similar to that of an amorphous pocket--we name it a morph. Computational modeling suggests that morphs exist in both self-interstitial and vacancylike forms, and are crucial for diffusion and defect dynamics in Ge, Si, and probably many other crystalline solids.

Effect of herpes simplex virus vector-mediated interleukin-4 gene therapy on bladder overactivity and nociception.

We investigated the effects of replication-defective herpes simplex virus (HSV) vector expression of interleukin-4 (IL-4) on bladder overactivity and nociception. HSV vector expressing murine interleukin-4 (S4IL4) or the control vector expressing ß-galactosidase (SHZ) were injected to the rat bladder wall. At 1 week after viral injection, in cystometry performed under urethane anesthesia, the S4IL4-treated group did not show the intercontraction intervals reduction during intravesical administration of 10 nM resiniferatoxin (RTx). At 2 weeks after viral injection, behavioral studies were performed on vector-injected animals in an awakened state. Freezing behavior induced by 3 µM RTx, administered for 1 min into the bladder, was significantly suppressed in the S4IL4 group compared with the SHZ group. Murine IL-4 levels examined by ELISA were significantly increased in bladder and bladder afferent dorsal root ganglia at 2 weeks after viral injection. The expression of IL-1ß and IL-2 and bladder inflammatory responses were significantly suppressed in the RTx-irritated bladder of S4IL4-injected rats. These results indicate that HSV vector-mediated interleukin-4 expression in the bladder and bladder afferent pathways reduces the inflammatory response, bladder overactivity and nociceptive behavior induced by bladder irritation in the rat model. Therefore, IL-4 gene therapy could be a new strategy for treating urinary frequency and/or bladder pain.

Improving resident engagement in quality improvement and patient safety initiatives at the bedside: the Advocate for Clinical Education (ACE).

Quality improvement (QI) and patient safety (PS) are essential competencies in residency training; however, the most effective means to engage physicians remains unclear. The authors surveyed all medicine and surgery physicians at their institution to describe QI/PS practices and concurrently implemented the Advocate for Clinical Education (ACE) program to determine if a physician-centered program in the context of educational structures and at the point of care improved performance. The ACE rounded with medicine and surgery teams and provided individual and team-level education and feedback targeting 4 domains: professionalism, infection control, interpreter use, and pain assessment. In a pilot, the ACE observed 2862 physician-patient interactions and 178 physicians. Self-reported compliance often was greater than the behaviors observed. Following ACE implementation, observed professionalism behaviors trended toward improvement; infection control also improved. Physicians were highly satisfied with the program. The ACE initiative is one coaching/feedback model for engaging residents in QI/PS that may warrant further study.

Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain.

Peripheral neuropathic pain is one of the most common and debilitating complications of diabetes. Several genes have been shown to be effective in reducing neuropathic pain in animal models of diabetes after transfer to the dorsal root ganglion using replication-defective herpes simplex virus (HSV)1-based vectors, yet there has never been a comparative analysis of their efficacy. We compared four different HSV1-based vectors engineered to produce one of two opioid receptor agonists (enkephalin or endomorphin), or one of two isoforms of glutamic acid decarboxylase (GAD65 or GAD67), alone and in combination, in the streptozotocin-induced diabetic rat and mouse models. Our results indicate that a single subcutaneous hindpaw inoculation of vectors expressing GAD65 or GAD67 reduced diabetes-induced mechanical allodynia to a degree that was greater than daily injections of gabapentin in rats. Diabetic mice that developed thermal hyperalgesia also responded to GAD65 or endomorphin gene delivery. The results suggest that either GAD65 or GAD67 vectors are the most effective in the treatment of diabetic pain. The vector combinations, GAD67+endomorphin, GAD67+enkephalin or endomorphin+enkephalin also produced a significant antinociceptive effect but the combination did not appear to be superior to single gene treatment. These findings provide further justification for the clinical development of antinociceptive gene therapies for the treatment of diabetic peripheral neuropathies.

Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial.

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.