Programming patchy particles to form three-dimensional dodecagonal quasicrystals

Model patchy particles have been shown to be able to form a wide variety of structures, including symmetric clusters, complex crystals and even two-dimensional quasicrystals. Here, we investigate whether we can design patchy particles that form three-dimensional quasicrystals, in particular targeting a quasicrystal with dodecagonal symmetry that is made up of stacks of two-dimensional quasicrystalline layers. We obtain two designs that are able to form such a dodecagonal quasicrystal in annealing simulations. The first is a one-component system of 7-patch particles but with wide patches that allow them to adopt both 7- and 8-coordinated environments. The second is a ternary system that contains a mixture of 7- and 8-patch particles, and is likely to be more realizable in experiments, for example, using DNA origami. One interesting feature of the first system is that the resulting quasicrystals very often contain a screw dislocation.Comment: 10 pages, 6 figure

Deriving a preference-based measure for cancer using the EORTC QLQ-C30 : a confirmatory versus exploratory approach

Background: To derive preference-based measures from various condition-specific descriptive health-related quality of life (HRQOL) measures. A general 2-stage method is evolved: 1) an item from each domain of the HRQOL measure is selected to form a health state classification system (HSCS); 2) a sample of health states is valued and an algorithm derived for estimating the utility of all possible health states. The aim of this analysis was to determine whether confirmatory or exploratory factor analysis (CFA, EFA) should be used to derive a cancer-specific utility measure from the EORTC QLQ-C30. Methods: Data were collected with the QLQ-C30v3 from 356 patients receiving palliative radiotherapy for recurrent or metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter based on a conceptual model (the established domain structure of the QLQ-C30: physical, role, emotional, social and cognitive functioning, plus several symptoms) and clinical considerations (views of both patients and clinicians about issues relevant to HRQOL in cancer). The dimensions determined by each method were then subjected to item response theory, including Rasch analysis. Results: CFA results generally supported the proposed conceptual model, with residual correlations requiring only minor adjustments (namely, introduction of two cross-loadings) to improve model fit (increment χ2(2) = 77.78, p 75% observation at lowest score), 6 exhibited misfit to the Rasch model (fit residual > 2.5), none exhibited disordered item response thresholds, 4 exhibited DIF by gender or cancer site. Upon inspection of the remaining items, three were considered relatively less clinically important than the remaining nine. Conclusions: CFA appears more appropriate than EFA, given the well-established structure of the QLQ-C30 and its clinical relevance. Further, the confirmatory approach produced more interpretable results than the exploratory approach. Other aspects of the general method remain largely the same. The revised method will be applied to a large number of data sets as part of the international and interdisciplinary project to develop a multi-attribute utility instrument for cancer (MAUCa)

Single-Lung Transplantation in the Setting of Aborted Bilateral Lung Transplantation

Background. The outcome of patients undergoing a single-lung transplant in the setting of an aborted bilateral lung transplant is unclear. Methods. A retrospective review of single lung transplants at an institutional program. Results. Of the 543 lung transplants performed over the last 10 years, 31 (5.7%) were single-lung transplants. Nineteen of 31 (61%) were planned single-lung transplants, while 12/31 (39%) were intraoperatively aborted, double lung transplants converted to single-lung transplants. The aborted and planned groups were similar in age, lung allocation score and NYHA status. The reasons for aborted double lung transplantation were cardiac/hemodynamic instability 4/12 (33%), difficult pneumonectomy 3/12 (25%), size mismatch 4/12(33%), and technical issues 1/12 (8%). The aborted group had higher CPB utilization (5/12 versus 1/19, P = .02), similar ischemic times (260 versus 234 min) and similar incidence of grade 3 primary graft dysfunction (6/12 versus 3/19, P = .13). ECMO was required for graft dysfunction in 2 patients in the aborted group. The one and two-year survival was 84% and 79% in the planned group and 62% and 52% in the aborted group, respectively. Conclusions. Patients undergoing single-lung transplantation in the setting of an aborted bilateral lung transplant may be at a higher risk of worse outcomes

Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor

Macrophage CSF (M-CSF) regulates monocyte differentiation, activation, and foam cell formation. We have observed that it is elevated in human pulmonary alveolar proteinosis (PAP) and in the GMCSF knockout mouse, a murine model for PAP. A potential regulator of M-CSF, peroxisome proliferator-activated receptor-γ (PPARγ), is severely deficient in both human PAP and the GM-CSF knockout mouse. To investigate the role of PPARγ in alveolar macrophage homeostasis, we generated myeloidspecific PPARγ knockout mice using the Lys-Cre method to knock out the floxed PPARγ gene. Similar to the GM-CSF-deficient mouse, absence of alveolar macrophage PPARγ resulted in development of lung pathology resembling PAP in 16-wk-old mice, along with excess M-CSF gene expression and secretion. In ex vivo wild-type alveolar macrophages, we observed that M-CSF itself is capable of inducing foam cell formation similar to that seen in PAP. Overexpression of PPARγ prevented LPS-stimulated M-CSF production in RAW 264.7 cells, an effect that was abrogated by a specific PPARγ antagonist, GW9662. Use of proteasome inhibitor, MG-132 or a PPARγ agonist, pioglitazone, prevented LPS-mediated M-CSF induction. Using chromatin immunoprecipitation, we found that PPARγ is capable of regulating M-CSF through transrepression of NF-κB binding at the promoter. Gel-shift assay experiments confirmed that pioglitazone is capable of blocking NF-κB binding. Taken together, these data suggest that M-CSF is an important mediator of alveolar macrophage homeostasis, and that transcriptional control of M-CSF production is regulated by NF-κB and PPARγ

Panel: Collective Licensing for Digitizing Analog Materials

Question and answer session

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Clinical Study Single-Lung Transplantation in the Setting of Aborted Bilateral Lung Transplantation

Background. The outcome of patients undergoing a single-lung transplant in the setting of an aborted bilateral lung transplant is unclear. Methods. A retrospective review of single lung transplants at an institutional program. Results. Of the 543 lung transplants performed over the last 10 years, 31 (5.7%) were single-lung transplants. Nineteen of 31 (61%) were planned singlelung transplants, while 12/31 (39%) were intraoperatively aborted, double lung transplants converted to single-lung transplants. The aborted and planned groups were similar in age, lung allocation score and NYHA status. The reasons for aborted double lung transplantation were cardiac/hemodynamic instability 4/12 (33%), difficult pneumonectomy 3/12 (25%), size mismatch 4/12(33%), and technical issues 1/12 (8%). The aborted group had higher CPB utilization (5/12 versus 1/19, P = .02), similar ischemic times (260 versus 234 min) and similar incidence of grade 3 primary graft dysfunction (6/12 versus 3/19, P = .13). ECMO was required for graft dysfunction in 2 patients in the aborted group. The one and two-year survival was 84% and 79% in the planned group and 62% and 52% in the aborted group, respectively. Conclusions. Patients undergoing single-lung transplantation in the setting of an aborted bilateral lung transplant may be at a higher risk of worse outcomes

The impact of the lung allocation score on short-term transplantation outcomes: A multicenter study

ObjectiveThe lung allocation score restructured the distribution of scarce donor lungs for transplantation. The algorithm ranks waiting list patients according to medical urgency and expected benefit after transplantation. The purpose of this study was to evaluate the impact of the lung allocation score on short-term outcomes after lung transplantation.MethodsA multicenter retrospective cohort study was performed with data from 5 academic medical centers. Results of patients undergoing transplantation on the basis of the lung allocation score (May 4, 2005 to May 3, 2006) were compared with those of patients receiving transplants the preceding year before the lung allocation score was implemented (May 4, 2004, to May 3, 2005).ResultsThe study reports on 341 patients (170 before the lung allocation score and 171 after). Waiting time decreased from 680.9 ± 528.3 days to 445.6 ± 516.9 days (P < .001). Recipient diagnoses changed with an increase in idiopathic pulmonary fibrosis and a decrease in emphysema and cystic fibrosis (P = .002). Postoperatively, primary graft dysfunction increased from 14.1% (24/170) to 22.9% (39/171) (P = .04) and intensive care unit length of stay increased from 5.7 ± 6.7 days to 7.8 ± 9.6 days (P = .04). Hospital mortality and 1-year survival were the same between groups (5.3% vs 5.3% and 90% vs 89%, respectively; P > .6)ConclusionsThis multicenter retrospective review of short-term outcomes supports the fact that the lung allocation score is achieving its objectives. The lung allocation score reduced waiting time and altered the distribution of lung diseases for which transplantation was done on the basis of medical necessity. After transplantation, recipients have significantly higher rates of primary graft dysfunction and intensive care unit lengths of stay. However, hospital mortality and 1-year survival have not been adversely affected

Near real-time bed modelling feasibility study

Hospital bed management is crucial to ensure that patients do not have to wait for the right bed for their care. A simulation model has been developed that mimics the bed management rules applied to the Trauma & Orthopaedic wards of a busy Welsh hospital. The model includes forecasting methodologies to predict the number of emergency admissions, split by gender. The model uses near real-time admission data to see whether patients will be admitted to a given ward on a given day in a 7-day planning horizon. The one-week feasibility pilot study examined the accuracy and usability of the tool. The study has shown that it is possible to correctly predict the short-term processes of a Trauma & Orthopaedic bed management system by accurately forecasting arrivals, using known data and statistical distributions to predict patient length of stay, and applying generic bed management rules to dictate their placement