Mechanical Properties of MiniBars™ Basalt Fiber-Reinforced Geopolymer Composites.

Fly ash-based geopolymers represent a new material, which can be considered an alternative to ordinary Portland cement. MiniBars™ are basalt fiber composites, and they were used to reinforce the geopolymer matrix for the creation of unidirectional MiniBars™ reinforced geopolymer composites (MiniBars™ FRBCs). New materials were obtained by incorporating variable amount of MiniBars™ (0, 12.5, 25, 50, 75 vol.% MiniBars™) in the geopolymer matrix. Geopolymers were prepared by mixing fly ash powder with Na2SiO3 and NaOH as alkaline activators. MiniBars™ FRBCs were cured at 70 °C for 48 h and tested for different mechanical properties. Optical microscopy and SEM were employed to investigate the fillers and MiniBars™ FRBC. MiniBars™ FRBC showed increasing mechanical properties by an increased addition of MiniBars™. The mechanical properties of MiniBars™ FRBC increased more than the geopolymer wtihout MiniBars™: the flexural strength > 11.59-25.97 times, the flexural modulus > 3.33-5.92 times, the tensile strength > 3.50-8.03 times, the tensile modulus > 1.12-1.30 times, and the force load at upper yield tensile strength > 4.18-7.27 times. SEM and optical microscopy analyses were performed on the fractured surface and section of MiniBars™ FRBC and confirmed a good geopolymer network around MiniBars™. Based on our results, MiniBars™ FRBC could be a very promising green material for buildings.

Radiofrequency Microneedling: Technology, Devices, and Indications in the Modern Plastic Surgery Practice.

Background: Since the initial invention of microneedling, advancements have been made to improve the desired effects. The addition of radiofrequency to microneedling devices was developed within the past decade as a way to induce thermal injury and increase dermal heating to enhance the dermal wound healing cascade. Objectives: With an overabundance of literature and mainstream media focused on microneedling and radiofrequency microneedling, this review aims to focus on the available high-quality evidence. Methods: A comprehensive review of the literature was performed across PubMed (National Institutes of Health, Bethesda, MD) and Embase (Elsevier, Amsterdam, the Netherlands) databases. Attention was focused on manuscripts that provided objective data with respect to clinical application, innovation, anatomy, and physiology. Results: Optimal outcomes are achieved when needle depth is targeted to the reticular dermis. Needle depth should reflect the relative differences in epidermal and dermal thickness throughout the face. A depth of at least 1.5 mm should be used for the forehead and temporal skin, 1.0 mm for the malar region, 2.0 mm (maximum depth for radiofrequency microneedling) for the nasal side walls, 0.5 mm for the perioral skin, and 1.5 mm for the neck. Deeper settings can be used with care to provide some fat reduction in the submentum. Conclusions: The authors find herein that radiofrequency microneedling is a safe adjunctive tool to surgical aesthetic procedures. The addition of radiofrequency poses an advance over traditional microneedling devices for skin tightening, with improvements in both safety and efficacy over time.

Effects of global and domestic tobacco control policies on cigarette consumption per capita: an evaluation using monthly data in China.

INTRODUCTION: China consumes 44% of the world's cigarettes. Robust tobacco control measures are needed to contain the trend of increasing cigarette consumption. This paper examines the effectiveness of policy interventions introduced in China on reducing the country's tobacco use. METHODS: The paper uses data on China's monthly cigarette consumption per capita from January 2000 to June 2017 to estimate the impact of specific policies on China's tobacco consumption. Tobacco consumption is calculated from monthly sales data from the China National Tobacco Corporation and demographic data from the China National Bureau of Statistics. The policies studied include the WHO Framework Convention on Tobacco Control (FCTC), national tobacco-related policy changes and two tobacco tax increases implemented in China during the study period. Segmented regression analysis is used to estimate the immediate effects of the policies studied and changes in the time trends resulted from these policy changes. FINDINGS: The impact of national policy changes in China is almost 20 times greater than the impact of the WHO FCTC treaty itself, and national policy changes in tobacco control are a determining factor in reversing the trend of increasing tobacco consumption in China. The 2015 tax increase, which raised retail cigarette prices, produced both immediate and trend effects, with a total incremental effect 7.8 times that of the 2009 tax increase, which did not result in higher cigarette prices for the consumer. INTERPRETATIONS: Translating global tobacco control policies into domestic policies will generate a much greater impact on reducing average cigarette consumption, and tobacco taxes that are reflected in the retail prices of cigarettes will be more effective in reducing cigarette consumption.

Fucosylation Enhances the Efficacy of Adoptively Transferred Antigen-Specific Cytotoxic T Lymphocytes.

PURPOSE: Inefficient homing of adoptively transferred cytotoxic T lymphocytes (CTLs) to tumors is a major limitation to the efficacy of adoptive cellular therapy (ACT) for cancer. However, through fucosylation, a process whereby fucosyltransferases (FT) add fucose groups to cell surface glycoproteins, this challenge may be overcome. Endogenously fucosylated CTLs and ex vivo fucosylated cord blood stem cells and regulatory T cells were shown to preferentially home to inflamed tissues and marrow. Here, we show a novel approach to enhance CTL homing to leukemic marrow and tumor tissue. EXPERIMENTAL DESIGN: Using the enzyme FT-VII, we fucosylated CTLs that target the HLA-A2-restricted leukemia antigens CG1 and PR1, the HER2-derived breast cancer antigen E75, and the melanoma antigen gp-100. We performed in vitro homing assays to study the effects of fucosylation on CTL homing and target killing. We used in vivo mouse models to demonstrate the effects of ex vivo fucosylation on CTL antitumor activities against leukemia, breast cancer, and melanoma. RESULTS: Our data show that fucosylation increases in vitro homing and cytotoxicity of antigen-specific CTLs. Furthermore, fucosylation enhances in vivo CTL homing to leukemic bone marrow, breast cancer, and melanoma tissue in NOD/SCID gamma (NSG) and immunocompetent mice, ultimately boosting the antitumor activity of the antigen-specific CTLs. Importantly, our work demonstrates that fucosylation does not interfere with CTL specificity. CONCLUSIONS: Together, our data establish ex vivo CTL fucosylation as a novel approach to improving the efficacy of ACT, which may be of great value for the future of ACT for cancer.

Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation.

Delayed engraftment is a major limitation of cord blood transplantation (CBT), due in part to a defect in the cord blood (CB) cells' ability to home to the bone marrow. Because this defect appears related to low levels of fucosylation of cell surface molecules that are responsible for binding to P- and E-selectins constitutively expressed by the marrow microvasculature, and thus for marrow homing, we conducted a first-in-humans clinical trial to correct this deficiency. Patients with high-risk hematologic malignancies received myeloablative therapy followed by transplantation with 2 CB units, one of which was treated ex vivo for 30 minutes with the enzyme fucosyltransferase-VI and guanosine diphosphate fucose to enhance the interaction of CD34(+) stem and early progenitor cells with microvessels. The results of enforced fucosylation for 22 patients enrolled in the trial were then compared with those for 31 historical controls who had undergone double unmanipulated CBT. The median time to neutrophil engraftment was 17 days (range, 12-34 days) compared with 26 days (range, 11-48 days) for controls (P = .0023). Platelet engraftment was also improved: median was 35 days (range, 18-100 days) compared with 45 days (range, 27-120 days) for controls (P = .0520). These findings support ex vivo fucosylation of multipotent CD34(+) CB cells as a clinically feasible means to improve engraftment efficiency in the double CBT setting. The trial is registered to www.clinicaltrials.gov as #NCT01471067.

Ex vivo fucosylation of third-party human regulatory T cells enhances anti-graft-versus-host disease potency in vivo.

Adoptive therapy with regulatory T cells (Tregs) to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation. We hypothesized that adding fucose to human Tregs, forming the Sialyl Lewis X moiety on P-selectin glycoprotein ligand-1, would improve their trafficking pattern. The selectin pathway recruiter, α-1,3-fucosyltransferase-VI enzyme, significantly increased Treg surface fucosylation (66% vs 8%). In a xenogenic GVHD mouse model, fucosylated Tregs showed prolonged periods of in vivo persistence. When given at a lower dose compared with the untreated Tregs, the murine recipients of fucosylated Tregs maintained weight, had ameliorated clinical GVHD, and improved survival (70% vs 30%; P < .0001). These preclinical data indicate that fucosylated human Tregs is an effective strategy for prevention of GVHD and, as such, warrants consideration for future clinical trials.

Homing of neural stem cells from the venous compartment into a brain infarct does not involve conventional interactions with vascular endothelium.

Human neural stem cells (hNSCs) hold great potential for treatment of a wide variety of neurodegenerative and neurotraumatic conditions. Heretofore, administration has been through intracranial injection or implantation of cells. Because neural stem cells are capable of migrating to the injured brain from the intravascular space, it seemed feasible to administer them intravenously if their ability to circumvent the blood-brain barrier was enhanced. In the present studies, we found that interactions of hNSCs in vitro on the luminal surface of human umbilical vein endothelial cells was enhanced following enforced expression of cutaneous lymphocyte antigen on cell surface moieties by incubation of hNSCs with fucosyltransferase VI and GDP-fucose (fhNSCs). Interestingly, ex vivo fucosylation of hNSCs not only did not improve the cells homing into the brain injured by stroke following intravenous administration but also increased mortality of rats compared with the nonfucosylated hNSC group. Efforts to explain these unexpected findings using a three-dimensional flow chamber device revealed that transmigration of fhNSCs (under conditions of physiological shear stress) mediated by stromal cell-derived factor 1α was significantly decreased compared with controls. Further analysis revealed that hNSCs poorly withstand physiological shear stress, and their ability is further decreased following fucosylation. In addition, fhNSCs demonstrated a higher frequency of cellular aggregate formation as well as a tendency for removal of fucose from the cell surface. In summary, our findings suggest that the behavior of hNSCs in circulation is different from that observed with other cell types and that, at least for stroke, intravenous administration is a suboptimal route, even when the in vitro rolling ability of hNSCs is optimized by enforced fucosylation.

Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment.

BACKGROUND AIMS: Advantages associated with the use of cord blood (CB) transplantation include the availability of cryopreserved units, ethnic diversity and lower incidence of graft-versus-host disease compared with bone marrow or mobilized peripheral blood. However, poor engraftment remains a major obstacle. We and others have found that ex vivo fucosylation can enhance engraftment in murine models, and now ex vivo treatment of CB with fucosyltransferase (FT) VI before transplantation is under clinical evaluation (NCT01471067). However, FTVII appears to be more relevant to hematopoietic cells and may alter acceptor substrate diversity. The present study compared the ability of FTVI and FTVII to improve the rapidity, magnitude, multi-lineage and multi-tissue engraftment of human CB hematopoietic stem and progenitor cells (HSPCs) in vivo. METHODS: CD34-selected CB HSPCs were treated with recombinant FTVI, FTVII or mock control and then injected into immunodeficient mice and monitored for multi-lineage and multi-tissue engraftment. RESULTS: Both FTVI and FTVII fucosylated CB CD34⁺ cells in vitro, and both led to enhanced rates and magnitudes of engraftment compared with untreated CB CD34⁺ cells in vivo. Engraftment after treatment with either FT was robust at multiple time points and in multiple tissues with similar multi-lineage potential. In contrast, only FTVII was able to fucosylate T and B lymphocytes. CONCLUSIONS: Although FTVI and FTVII were found to be similarly able to fucosylate and enhance the engraftment of CB CD34⁺ cells, differences in their ability to fucosylate lymphocytes may modulate graft-versus-tumor or graft-versus-host effects and may allow further optimization of CB transplantation.

Fucosyltransferase VII improves the function of selectin ligands on cord blood hematopoietic stem cells.

Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands on HSPCs by α1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with α1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34(+) cells, was used for these experiments. In vitro, FUT7-treated CB CD34(+) cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34(+) cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34(+) cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2Rγ(null) (NSG) mice. FUT7 also exhibited marginally-yet statistically significant-increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34(+) cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients.

Circulating mononuclear progenitor cells: differential roles for subpopulations in repair of retinal vascular injury.

PURPOSE: We examined effect on retinal vascular homing of exogenous CD34(+) and CD14(+) progenitor cells using mouse models of chronic (streptozotocin [STZ]-induced diabetes) and acute (ischemia-reperfusion [I/R]) ocular vascular injury. METHODS: STZ-treated mice of short or long duration (≤4, ≥11 months) diabetes, along with age- and sex-matched controls, were given intravitreous injections of human CD34(+) and CD14(+) cells isolated from healthy or diabetic donors alone or in combination. I/R injured mice were given diabetic or nondiabetic CD34(+) cells with mesenchymal stem cells (MSCs) or diabetic CD34(+) cells manipulated by ex vivo fucosylation with ASC-101. Injected cells were localized by fluorescent immunocytochemistry, and the degree of retinal vascular colocalization quantified morphometrically. Permeability was assessed by fluorescent albumin leakage. RESULTS: Diabetic CD14(+) cells associated with vessels to a greater degree than diabetic CD34(+) cells. Vascular permeability was reduced only by nondiabetic cells and only at the highest number of cells tested. Diabetic CD34(+) cells consistently demonstrated reduced migration. There was a 2-fold or 4-fold increase over control in the specific localization of diabetic CD34(+) cells within the vasculature when these cells were co-administered with MSCs or ex vivo fucosylated prior to injection, respectively. CONCLUSIONS: Diabetic CD14(+) cells, unlike diabetic CD34(+) cells, retain robust homing characteristics. CD34(+) or CD14(+) subsets rather than whole bone marrow or peripheral blood cells may prove more beneficial in autologous cell therapy for diabetics. Co-administration with MSCs or ex vivo fucosylation may enhance utility of CD34(+) cells in cell therapy for diabetic ocular conditions like macular ischemia and retinal nonperfusion.

Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ(null) mice.

Delayed engraftment remains a major hurdle after cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the bone marrow microenvironment. Because fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the bone marrow microvasculature can occur, a simple 30-minute ex vivo incubation of CB hematopoietic progenitor cells with fucosyltransferase-VI and its substrate (GDP-fucose) was performed to increase levels of fucosylation. The physiologic impact of CB hematopoietic progenitor cell hypofucosylation was investigated in vivo in NOD-SCID interleukin (IL)-2Rγ(null) (NSG) mice. By isolating fucosylated and nonfucosylated CD34(+) cells from CB, we showed that only fucosylated CD34(+) cells are responsible for engraftment in NSG mice. In addition, because the proportion of CD34(+) cells that are fucosylated in CB is significantly less than in bone marrow and peripheral blood, we hypothesize that these combined observations might explain, at least in part, the delayed engraftment observed after CB transplantation. Because engraftment appears to be correlated with the fucosylation of CD34(+) cells, we hypothesized that increasing the proportion of CD34(+) cells that are fucosylated would improve CB engraftment. Ex vivo treatment with fucosyltransferase-VI significantly increases the levels of CD34(+) fucosylation and, as hypothesized, this was associated with improved engraftment. Ex vivo fucosylation did not alter the biodistribution of engrafting cells or pattern of long-term, multilineage, multi-tissue engraftment. We propose that ex vivo fucosylation will similarly improve the rate and magnitude of engraftment for CB transplant recipients in a clinical setting.

Evaluation of the economic impact of California's Tobacco Control Program: a dynamic model approach.

OBJECTIVE: To evaluate the long-term net economic impact of the California Tobacco Control Program. METHODS: This study developed a series of dynamic models of smoking-caused mortality, morbidity, health status and healthcare expenditures. The models were used to evaluate the impact of the tobacco control programme. Outcomes of interest in the evaluation include net healthcare expenditures saved, years of life saved, years of treating smoking-related diseases averted and the total economic value of net healthcare savings and life saved by the programme. These outcomes are evaluated to 2079. Due to data limitations, the evaluations are conducted only for men. RESULTS: The California Tobacco Control Program resulted in over 700,000 person-years of life saved and over 150,000 person-years of treatment averted for the 14.7 million male California residents alive in 1990. The value of net healthcare savings and years of life saved resulting from the programme was $22 billion or $107 billion in 1990 dollars, depending on how a year of life is discounted. If women were included, the impact would likely be much greater. CONCLUSIONS: The benefits of California's Tobacco Control Program are substantial and will continue to accrue for many years. Although the programme has resulted in increased longevity and additional healthcare resources for some, this impact is more than outweighed by the value of the additional years of life. Modelling the programme's impact in a dynamic framework makes it possible to evaluate the multiple impacts that the programme has on life, health and medical expenditures.

Patterns of recovery from severe mental illness: a pilot study of outcomes.

We performed a pilot study examining the patterns of recovery from severe mental illness in a model integrated service delivery system using measures from the Milestones of Recovery Scale (MORS), a valid and reliable measure of recovery outcomes which ranges from 1 to 8 (8 levels). For purposes of presentation, we constructed an aggregate MORS (6 levels) where the levels are described as follows: (1) extreme risk; (2) unengaged, poorly self-coordinating; (3) engaged, poorly self-coordinating; (4) coping and rehabilitating; (5) early recovery, and (6) self reliant. We analyzed MORS data on individuals followed over time from The Village in Long Beach, California (658 observations). Using Markov Chains, we estimated origin-destination transition probabilities, simulating recovery outcomes for 100 months. Our models suggest that after 12 months only 8% of "extreme risk" clients remain such. Over 40% have moved to "engaged, poorly self-coordinating." After 2 years, almost half of the initial "extreme Risk" clients are "coping/rehabilitating", "early recovery" or "Self reliant." Most gains occur within 2 years.

Transformation of the California mental health system: stakeholder-driven planning as a transformational activity.

OBJECTIVE: This study describes strategies developed by California counties to transform their mental health systems under the 2004 Mental Health Services Act (MHSA). This voter initiative places a 1% tax on annual incomes over $1 million; tax monies are earmarked to transform county-operated mental health services into systems that are oriented more toward recovery. MHSA implementation itself can be considered "transformational" by balancing greater standardization of mental health service delivery in the state with a locally driven planning process. METHODS: A qualitative content analysis of the three-year plans submitted by 12 counties to receive funds under MHSA was conducted to identify common themes, as well as innovative approaches. These 12 (out of 58) counties were chosen to represent both small and large counties, as well as geographic diversity, and they represent 62.3% of the state population. RESULTS: This analysis showed that the state guidelines and local planning process generated consistency across counties in establishing full-service partnerships with a "whatever it takes" approach to providing goal-directed services and supports to consumers and their families. There was, however, little convergence around the specific strategies to achieve this vision, reflecting both the local planning process and a relative lack of clear policy and guidance on evidence-based practices. CONCLUSIONS: There are many obstacles to the successful implementation of these ambitious plans. However, the state-guided, but stakeholder-driven, transformation in California appears to generate innovative approaches to recovery-oriented services, involve consumers and family members in service planning and delivery, and build community partnerships that create new opportunities for consumers to meet their recovery goals.

Social climate and workplace drinking among women in a male-dominated occupation.

OBJECTIVE: This study applies Gilligan's relational theory to an exploration of the influence of the social climate at work on workplace drinking in a male-dominated occupation. METHODS: Data used in this analysis were originally collected from a random sample of employees at a heavy machinery assembly plant (N = 984, women = 121). Because reciprocal relationships between workplace drinking and social climate were hypothesized, the parameters were estimated using simultaneous equation modeling. RESULTS: Women who reported a negative social climate at work also had a greater propensity to drink at work. There was no similar relationships between social climate and workplace drinking for men. CONCLUSIONS: Workplace drinking prevention programs in male-dominated occupations may need to address the social climate at work, particularly for women.

On the Stability of Exponential Backoff.

Random access schemes for packet networks featuring distributed control require algorithms and protocols for resolving packet collisions that occur as the uncoordinated terminals contend for the channel. A widely used collision resolution protocol is the exponential backoff (EB). New analytical results for the stability of the (binary) EB are given. Previous studies on the stability of the (binary) EB have produced contradictory results instead of a consensus: some proved instability, others showed stability under certain conditions. In these studies, simplified and/or modified models of the backoff algorithm were used. In this paper, care is taken to use a model that reflects the actual behavior of backoff algorithms. We show that EB is stable under a throughput definition of stability; the throughput of the network converges to a non-zero constant as the offered load N goes to infinity. We also obtain the analytical expressions for the saturation throughput for a given number of nodes, N. The analysis considers the general case of EB with backoff factor r, where BEB is the special case with r = 2. We show that r = 1/(1 - e(-1)) is the optimum backoff factor that maximizes the throughput. The accuracy of the analysis is checked against simulation results.