Effect of BMI and hemoglobin A1c on survival of veterans with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

BACKGROUND: Abiraterone acetate and enzalutamide are two common therapies for metastatic castration-resistant prostate cancer (mCRPC) that have shown improved overall survival (OS). The drugs have different mechanisms of action with limited comparative trials to evaluate treatment in patients with comorbidities such as obesity and diabetes. This is important since abiraterone requires the co-administration of prednisone. We assessed the relationship between body mass index (BMI), hemoglobin A1c (HbA1c), treatment, and survival in mCRPC. METHODS: Veterans treated with abiraterone or enzalutamide within the Veterans Health Administration between September 10, 2014 and June 2, 2017 with BMI and HbA1c were identified. Additional variables included age, baseline prostate-specific antigen at first treatment for mCRPC, race, and the Charlson comorbidity index. Differences in survival were compared using the Kaplan-Meier method. Cox proportional hazards regression modeling was used to assess the association between initial treatment, BMI, and HbA1c while adjusting for confounding variables. RESULTS: A total of 5231 patients were identified with a mean age of 75.2 years and 1241 (23.7%) were of black race. BMI was associated with OS with longest median survival of 29.8 months in BMI ≥ 30 (n = 1903), 23.9 months in BMI 25-30 (n = 1879), 15.9 months in BMI 18.5-25 (n = 1336), and 9.2 months in BMI < 18.5 (n = 113, p < 0.001). In a multivariable model compared to normal BMI, increased mortality was observed in BMI < 18.5 (adjusted hazard ratio (aHR) = 1.583, 95% confidence interval [CI]: 1.29-1.94) and a decreased mortality in BMI 25-30 (aHR = 0.751, 95% CI: 0.69-0.81) and BMI > 30 (aHR = 0.644, 95% CI: 0.59-0.70). In 3761 patients with BMI > 25, there was longer OS in patients treated with enzalutamide (28.4 months, n = 1615) compared to abiraterone (25.8 months, n = 2146, p = 0.002). In 1470 patients with BMI < 25, there was no difference in OS between patients treated with enzalutamide (16.0 months, n = 597, p = 0.513) or abiraterone (16.1 months, n = 873). In 1333 veterans with HbA1c ≥ 6.5%, initial prescription of enzalutamide was associated with longer OS compared with abiraterone (24.4 vs. 20.5 months, p = 0.0005). In 2088 patients with HbA1c < 6.5%, there was no difference in OS in patients who were initially prescribed enzalutamide versus abiraterone (25.7 vs. 23.5 months, p = 0.334). CONCLUSIONS: In veterans with mCRPC, increased BMI was associated with longer survival. Veterans with BMI > 25 had longer survival with enzalutamide compared to abiraterone. In patients with HbA1c ≥ 6.5%, enzalutamide was associated with longer survival compared to abiraterone. These results may facilitate prognostication of survival and improve treatment selection based on patient comorbidities.

Assessment of Duration of Smoking Cessation Prior to Surgical Treatment of Non-small Cell Lung Cancer.

OBJECTIVE: To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment. BACKGROUND: Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear. METHODS: Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions. RESULTS: The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). CONCLUSION: Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.

Comparison Between Veteran and Non-Veteran Populations With Clinical Stage I Non-small Cell Lung Cancer Undergoing Surgery.

OBJECTIVE: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). BACKGROUND: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. METHODS: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). RESULTS: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). CONCLUSIONS: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.

Development and Validation of the VA Lung Cancer Mortality (VALCAN-M) Score for 90-Day Mortality Following Surgical Treatment of Clinical Stage I Lung Cancer.

OBJECTIVE: The aim was to develop and validate the Veterans Administration (VA) Lung Cancer Mortality (VALCAN-M) score, a risk prediction model for 90-day mortality following surgical treatment of clinical stage I nonsmall-cell lung cancer (NSCLC). BACKGROUND: While surgery remains the preferred treatment for functionally fit patients with early-stage NSCLC, less invasive, nonsurgical treatments have emerged for high-risk patients. Accurate risk prediction models for postoperative mortality may aid surgeons and other providers in optimizing patient-centered treatment plans. METHODS: We performed a retrospective cohort study using a uniquely compiled VA data set including all Veterans with clinical stage I NSCLC undergoing surgical treatment between 2006 and 2016. Patients were randomly split into derivation and validation cohorts. We derived the VALCAN-M score based on multivariable logistic regression modeling of patient and treatment variables and 90-day mortality. RESULTS: A total of 9749 patients were included (derivation cohort: n=6825, 70.0%; validation cohort: n=2924, 30.0%). The 90-day mortality rate was 4.0% (n=390). The final multivariable model included 11 factors that were associated with 90-day mortality: age, body mass index, history of heart failure, forced expiratory volume (% predicted), history of peripheral vascular disease, functional status, delayed surgery, American Society of Anesthesiology performance status, tumor histology, extent of resection (lobectomy, wedge, segmentectomy, or pneumonectomy), and surgical approach (minimally invasive or open). The c statistic was 0.739 (95% CI=0.708-0.771) in the derivation cohort. CONCLUSIONS: The VALCAN-M score uses readily available treatment-related variables to reliably predict 90-day operative mortality. This score can aid surgeons and other providers in objectively discussing operative risk among high-risk patients with clinical stage I NSCLC considering surgery versus other definitive therapies.

Medicare Spending on Drugs With Accelerated Approval.

BACKGROUND: The U.S. Food and Drug Administration provides accelerated approval to drugs on the basis of surrogate end points deemed to be "reasonably likely" to predict clinical benefit. To receive full approval, drugs must complete a confirmatory trial. Although most accelerated approved drugs ultimately receive full approval, others remain on the market without full approval for many years, and some are withdrawn before full approval is granted. Until confirmatory trials are completed and full approval is granted, there is uncertainty surrounding each drug's clinical benefits. OBJECTIVE: To estimate fee-for-service Medicare payments on accelerated approved drugs without full approvals. DESIGN: Cross-sectional analysis. SETTING: Fee-for-service Medicare Part B and Part D drug claims in 2019. PARTICIPANTS: Beneficiaries enrolled in Medicare Part B and Part D plans. MEASUREMENTS: Medicare spending for drugs treating accelerated approved indications without full approval, beneficiary spending, and drug characteristics. RESULTS: In 2019, 45 drugs associated with 69 accelerated approved indications lacked full approval. Of those, the fee-for-service Medicare program spent $1.2 billion on 36 drugs across 55 indications. Medicare beneficiaries had $209 million in out-of-pocket spending on these drugs. Oncology drugs represented 82% of these indications and 72% of the Medicare spending. Extrapolating to Medicare Advantage, total Medicare spending on these drugs in 2019 was $1.8 billion. LIMITATIONS: The study drugs may have clinical benefit and may come to receive full approval after this analysis. The algorithm used to identify accelerated approved indications is novel. Generalizability to other years is unclear. CONCLUSION: In 2019, fee-for-service Medicare spent $1.2 billion on accelerated approved drugs without full approval. Medicare should adjust incentives to encourage sponsors to complete confirmatory trials as soon as possible. PRIMARY FUNDING SOURCE: Laura and John Arnold Foundation.

The First 2 Years of Biosimilar Epoetin for Cancer and Chemotherapy-Induced Anemia in the U.S.: A Review from the Southern Network on Adverse Reactions.

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.

Flow-assisted self-healing of the helical structure in a cholesteric liquid crystal.

We employ nonequilibrium molecular dynamics simulations to investigate the structure and dynamics of a cholesteric liquid crystal confined between atomically corrugated solid walls. By choosing walls normal to the helical axis, we can study systems with an arbitrary cholesteric pitch without exposing the cholesteric helix to a spurious stress. We investigate the effects of local heating and flow and their joint effects. A steady-state laminar Poiseuille flow is initiated by means of an external body force. Flow alone (i.e., without local heating) in a direction normal to the helical axis does not affect the cholesteric pitch. If the liquid crystal is heated in a small region, the cholesteric helix becomes unstable and melts locally. However, if local heating and flow are combined, a nontrivial synergistic effect is observed in that the helical structure recuperates the better, the higher the speed of the flow is.

Improving oncology biosimilar launches in the EU, the USA, and Japan: an updated Policy Review from the Southern Network on Adverse Reactions.

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.

End of an era for erythropoiesis-stimulating agents in oncology.

Erythropoiesis-stimulating agents (ESAs) are available to treat chemotherapy-induced anemia (CIA). In 2007-2008, regulatory notifications advised of venous thromboembolism and mortality risks while the Center for Medicare and Medicaid Services' restricted ESA initiation to patients with hemoglobin <10 g/dl. In 2010, a Risk Evaluation and Mitigation Strategies required consent prior to administration. We evaluated ESA utilization from 2003 to 2012 and obtained private health insurer claims data for persons with lung, colorectal, or breast cancer from 2001 to 2012. ESA use for CIA was determined by an ESA claim after chemotherapy, up to 6 months after treatment. We identified 839,948 commercially insured patients, including 24,785 patients with ESA-treated CIA (3.2%). Darbepoetin use increased 3.9-fold from 2003 to 2007 (12.3% to 48.7%) and then decreased 95% to 2.6% by 2012. Epoetin use decreased 90% from 2003 to 2012 (30.3% to 3.1%). Between 2003 and 2012, mean epoetin dosing decreased 0.8-fold (244,979 in 2003 vs. 196,216 units in 2012), but increased 1.8-fold for darbepoetin-treated CIA (262 in 2003 to 467 µg in 2012). Among CIA patients, transfusions were low (4.5%) in 2002-2007, then increased 2.2-fold between 2008 and 2012. Safety initiatives between 2007 and 2010 facilitated reductions in ESA use combined with changes in coverage. These data show the efficacy of regulatory efforts, publication of adverse events and changes in reimbursement in reducing use of ESAs. Future studies are warranted to optimize deimplementation strategies to improve patient safety.

Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis, in those identified at high-risk of VTE by the presence of risk factors. The National Comprehensive Cancer Network (NCCN) has adopted these guidelines; however, they lack validation. We sought to develop and validate a risk prediction score for VTE in MM and to evaluate the performance of the current IMWG/NCCN guidelines. Using 4446 patients within the Veterans Administration Central Cancer Registry, we used time-to-event analyses to develop a risk score for VTE in patients with newly diagnosed MM starting chemotherapy. We externally validated the score using the Surveillance, Epidemiology, End Results (SEER)-Medicare database (N = 4256). After identifying independent predictors of VTE, we combined the variables to develop the IMPEDE VTE score (Immunomodulatory agent; Body Mass Index ≥25 kg/m2 ; Pelvic, hip or femur fracture; Erythropoietin stimulating agent; Dexamethasone/Doxorubicin; Asian Ethnicity/Race; VTE history; Tunneled line/central venous catheter; Existing thromboprophylaxis). The score showed satisfactory discrimination in the derivation cohort, c-statistic = 0.66. Risk of VTE significantly increased as score increased (hazard ratio 1.20, P = <.0001). Within the external validation cohort, IMPEDE VTE had a c-statistic of 0.64. For comparison, when evaluating the performance of the IMWG/NCCN guidelines, the c-statistic was 0.55. In summary, the IMPEDE VTE score outperformed the current IMWG/NCCN guidelines and could be considered as the new standard risk stratification for VTE in MM.

Description of Venous Thromboembolism in Hospitalized Patients With Metastatic Cancer: A National Sample.

Background: This study aimed to determine patient-, tumor-, and hospital-level characteristics associated with venous thromboembolism (VTE), and to assess the impact of VTE on in-hospital mortality and length of hospital stay in hospitalized patients with metastatic cancer. Methods: Using the Nationwide Inpatient Sample database, a cross-sectional analysis was performed of patients aged ≥18 years with at least 1 diagnosis of primary solid tumor and subsequent secondary or metastatic tumor between 2008 and 2013. Results: Among 850,570 patients with metastatic cancer, 6.6% were diagnosed with VTE. A significant trend for increasing VTE rates were observed from 2008 to 2013 (5.7%-7.2%; P<.0001). Using an adjusted multilevel hierarchical regression model, higher odds of VTE were seen among women (odds ratio [OR], 1.04; 95% CI, 1.02-1.06), black versus white patients (OR, 1.14; 95% CI, 1.11-1.18), and those with an Elixhauser comorbidity index score of ≥3 (OR, 2.50; 95% CI, 2.38-2.63). Hospital-level correlates of VTE included treatment in a teaching hospital (OR, 1.05; 95% CI, 1.01-1.11) and an urban location (OR, 1.18; 95% CI, 1.09-1.27), and admission to hospitals in the Northeast (OR, 1.16; 95% CI, 1.08-1.24) and West (OR, 1.09; 95% CI, 1.03-1.16) versus the South. Patients with metastasis to the liver, brain, or respiratory organs and those with multiple (≥2) metastatic sites had higher odds of VTE, whereas those with metastasis to lymph nodes and genital organs had lower odds. Patients diagnosed with versus without VTE had higher odds of in-hospital mortality (OR, 1.50; 95% CI, 1.38-1.63) and prolonged hospital stay (OR, 1.65; 95% CI, 1.57-1.73). Conclusions: The frequency of VTE in patients with metastatic cancer is increasing. Patient characteristics, hospital factors, and site of metastasis independently predict the occurrence of VTE and allow for better stratification of patients with cancer according to their VTE risk.

Mean-field density functional theory of a nanoconfined classical, three-dimensional Heisenberg fluid. II. The interplay between molecular packing and orientational order.

As in Paper I of this series of papers [S. M. Cattes et al., J. Chem. Phys. 144, 194704 (2016)], we study a Heisenberg fluid confined to a nanoscopic slit pore with smooth walls. The pore walls can either energetically discriminate specific orientations of the molecules next to them or are indifferent to molecular orientations. Unlike in Paper I, we employ a version of classical density functional theory that allows us to explicitly account for the stratification of the fluid (i.e., the formation of molecular layers) as a consequence of the symmetry-breaking presence of the pore walls. We treat this stratification within the White Bear version (Mark I) of fundamental measure theory. Thus, in this work, we focus on the interplay between local packing of the molecules and orientational features. In particular, we demonstrate why a critical end point can only exist if the pore walls are not energetically discriminating specific molecular orientations. We analyze in detail the positional and orientational order of the confined fluid and show that reorienting molecules across the pore space can be a two-dimensional process. Last but not least, we propose an algorithm based upon a series expansion of Bessel functions of the first kind with which we can solve certain types of integrals in a very efficient manner.

Perturbation Theory versus Thermodynamic Integration. Beyond a Mean-Field Treatment of Pair Correlations in a Nematic Model Liquid Crystal.

The phase behavior and structure of a simple square-well bulk fluid with anisotropic interactions is described in detail. The orientation dependence of the intermolecular interactions allows for the formation of a nematic liquid-crystalline phase in addition to the more conventional isotropic gas and liquid phases. A version of classical density functional theory (DFT) is employed to determine the properties of the model, and comparisons are made with the corresponding data from Monte Carlo (MC) computer simulations in both the grand canonical and canonical ensembles, providing a benchmark to assess the adequacy of the DFT results. A novel element of the DFT approach is the assumption that the structure of the fluid is dominated by intermolecular interactions in the isotropic fluid. A so-called augmented modified mean-field (AMMF) approximation is employed accounting for the influence of anisotropic interactions. The AMMF approximation becomes exact in the limit of vanishing density. We discuss advantages and disadvantages of the AMMF approximation with respect to an accurate description of isotropic and nematic branches of the phase diagram, the degree of orientational order, and orientation-dependent pair correlations. The performance of the AMMF approximations is found to be good in comparison with the MC data; the AMMF approximation has clear advantages with respect to an accurate and more detailed description of the fluid structure. Possible strategies to improve the DFT are discussed.

Phase Behavior of Magnetic Nanocolloids of Different Sizes Suspended in an Apolar Solvent.

We employ classical density functional theory (DFT) to investigate the phase behavior and composition of binary mixtures; each compound consists of hard spheres of different sizes with superimposed dispersion attraction. In addition to the dispersion attraction, molecules of one component carry an additional three-dimensional magnetic "spin" where the orientation-dependent spin-spin interaction is accounted for by the Heisenberg model. We are treating the excess free energy using a modified mean-field approximation (second virial coefficient) for the orientation-dependent pair correlation function. Depending on the concentration of the magnetic particles, the strength of the spin-spin coupling, and the size ratio of the particles, the model predicts the formation of ordered (polar) phases in addition to the more conventional gas and isotropic liquid phases. Key features of our model are a particle-size dependent shift of the gas-liquid critical point (critical temperature and density) and a change in the width of the phase diagram. In the near-critical region, the latter can be analyzed quantitativly in terms of an effective critical exponent ßeff that may differ from the classical critical exponent [Formula: see text]; the classical value is attained in the immediate vicinity of the critical point as it must. The deviation between ßeff and ß can be linked to nontrivial composition effects along the phase boundaries.

Adsorption and Depletion Regimes of a Nonionic Surfactant in Hydrophilic Mesopores: An Experimental and Simulation Study.

Adsorption and aggregation of nonionic surfactants at oxide surfaces has been studied extensively in the past, but only for concentrations below and near the critical micelle concentration. Here we report an adsorption study of a short-chain surfactant (C6E3) in porous silica glass of different pore sizes (7.5 to 50 nm), covering a wide composition range up to 50 wt % in a temperature range from 20 °C to the LCST. Aggregative adsorption is observed at low concentrations, but the excess concentration of C6E3 in the pores decreases and approaches zero at higher bulk concentrations. Strong depletion of surfactant (corresponding to enrichment of water in the pores) is observed in materials with wide pores at high bulk concentrations. We propose an explanation for the observed pore-size dependence of the azeotropic point. Mesoscale simulations based on dissipative particle dynamics (DPD) were performed to reveal the structural origin of this transition from the adsorption to the depletion regime. The simulated adsorption isotherms reproduce the behavior found in the 7.5 nm pores. The calculated bead density profiles indicate that the repulsive interaction of surfactant head groups causes a depletion of surfactant in the region around the corona of the surface micelles.

The Impact of Colloidal Surface-Anchoring on the Smectic A Phase.

Liquid-crystalline phases are known for their unique properties, i.e., the combination of fluidity and long-range orientational and/or positional order. The presence of a colloidal particle gives rise to perturbations of this order locally. These perturbations are the origin of intercolloidal forces driving the colloidal self-assembly in a directed manner. Hence, the understanding of these perturbations is the first step in understanding and controlling the self-assembly process. Here, we perform Monte Carlo simulations to investigate the perturbations of orientational and positional order in a smectic A phase caused by a spherical colloid. We model the host phase via an interaction potential that reproduces characteristic features of phase behavior, structure, dynamics, and elasticity [S. Püschel-Schlotthauer et al. J. Chem. Phys. 2016, 145, 164903]. For strong homeotropic anchoring conditions, we find a Saturn ring defect and an onion structure in the smectic A phase; the latter has never been reported for colloids so far. For strong planar anchoring conditions, we find Boojum defects that become elongated at low temperature, similar to what is observed in experiments. However, for weak planar anchoring conditions, a double surface ring defect is exhibited in the smectic A phase.

Coarse-grained treatment of the self-assembly of colloids suspended in a nematic host phase.

The complex interplay of molecular scale effects, nonlinearities in the orientational field and long-range elastic forces makes liquid-crystal physics very challenging. A consistent way to extract information from the microscopic, molecular scale up to the meso- and macroscopic scale is still missing. Here, we develop a hybrid procedure that bridges this gap by combining extensive Monte Carlo (MC) simulations, a local Landau-de Gennes theory, classical density functional theory, and finite-size scaling theory. As a test case to demonstrate the power and validity of our novel approach we study the effective interaction among colloids with Boojum defect topology immersed in a nematic liquid crystal. In particular, at sufficiently small separations colloids attract each other if the angle between their center-of-mass distance vector and the far-field nematic director is about 30°. Using the effective potential in coarse-grained two-dimensional MC simulations we show that self-assembled structures formed by the colloids are in excellent agreement with experimental data.

Mean-field density functional theory of a nanoconfined classical, three-dimensional Heisenberg fluid. I. The role of molecular anchoring.

In this work, we employ classical density functional theory (DFT) to investigate for the first time equilibrium properties of a Heisenberg fluid confined to nanoscopic slit pores of variable width. Within DFT pair correlations are treated at modified mean-field level. We consider three types of walls: hard ones, where the fluid-wall potential becomes infinite upon molecular contact but vanishes otherwise, and hard walls with superimposed short-range attraction with and without explicit orientation dependence. To model the distance dependence of the attractions, we employ a Yukawa potential. The orientation dependence is realized through anchoring of molecules at the substrates, i.e., an energetic discrimination of specific molecular orientations. If the walls are hard or attractive without specific anchoring, the results are "quasi-bulk"-like in that they can be linked to a confinement-induced reduction of the bulk mean field. In these cases, the precise nature of the walls is completely irrelevant at coexistence. Only for specific anchoring nontrivial features arise, because then the fluid-wall interaction potential affects the orientation distribution function in a nontrivial way and thus appears explicitly in the Euler-Lagrange equations to be solved for minima of the grand potential of coexisting phases.

A novel model for smectic liquid crystals: Elastic anisotropy and response to a steady-state flow.

By means of a combination of equilibrium Monte Carlo and molecular dynamics simulations and nonequilibrium molecular dynamics we investigate the ordered, uniaxial phases (i.e., nematic and smectic A) of a model liquid crystal. We characterize equilibrium behavior through their diffusive behavior and elastic properties. As one approaches the equilibrium isotropic-nematic phase transition, diffusion becomes anisotropic in that self-diffusion D⊥ in the direction orthogonal to a molecule's long axis is more hindered than self-diffusion D∥ in the direction parallel to that axis. Close to nematic-smectic A phase transition the opposite is true, D∥ < D⊥. The Frank elastic constants K1, K2, and K3 for the respective splay, twist, and bend deformations of the director field n̂ are no longer equal and exhibit a temperature dependence observed experimentally for cyanobiphenyls. Under nonequilibrium conditions, a pressure gradient applied to the smectic A phase generates Poiseuille-like or plug flow depending on whether the convective velocity is parallel or orthogonal to the plane of smectic layers. We find that in Poiseuille-like flow the viscosity of the smectic A phase is higher than in plug flow. This can be rationalized via the velocity-field component in the direction of the flow. In a sufficiently strong flow these smectic layers are not destroyed but significantly bent.

Defect topologies in chiral liquid crystals confined to mesoscopic channels.

We present Monte Carlo simulations in the grand canonical and canonical ensembles of a chiral liquid crystal confined to mesochannels of variable sizes and geometries. The mesochannels are taken to be quasi-infinite in one dimension but finite in the two other directions. Under thermodynamic conditions chosen and for a selected value of the chirality coupling constant, the bulk liquid crystal exhibits structural characteristics of a blue phase II. This is established through the tetrahedral symmetry of disclination lines and the characteristic simple-cubic arrangement of double-twist helices formed by the liquid-crystal molecules along all three axes of a Cartesian coordinate system. If the blue phase II is then exposed to confinement, the interplay between its helical structure, various anchoring conditions at the walls of the mesochannels, and the shape of the mesochannels gives rise to a broad variety of novel, qualitative disclination-line structures that are reported here for the first time.