Characterization of a Human Powered Nebulizer Compressor for Resource Poor Settings

Background Respiratory disease accounts for three of the ten leading causes of death worldwide. Many of these diseases can be treated and diagnosed using a nebulizer. Nebulizers can also be used to safely and efficiently deliver vaccines. Unfortunately, commercially available nebulizers are not designed for use in regions of the world where lung disease is most prevalent: they are electricity-dependent, cost-prohibitive, and not built to be reliable in harsh operating conditions or under frequent use. To overcome these limitations, the Human Powered Nebulizer compressor (HPN) was developed. The HPN does not require electricity; instead airflow is generated manually through a hand-crank or bicycle-style pedal system. A health care worker or other trained individual operates the device while the patient receives treatment. This study demonstrates functional specifications of the HPN in comparison with a standard commercially available electric jet nebulizer compressor, the DeVilbiss Pulmo-Aide 5650D (Pulmo-Aide). Methods Pressure and flow characteristics were measured with a rotameter and pressure transducer, respectively. Volume nebulized by each compressor was determined by mass, and particle size distribution was determined via laser diffraction. The Hudson RCI Micro Mist nebulizer mouthpiece was used with both compressors. Results The pressure and flow generated by the HPN and Pulmo-Aide were: 15.17 psi and 10.5 L/min; and 14.65 psi and 11.2 L/min, respectively. The volume of liquid delivered by each was equivalent, 1.097 ± 0.107 mL (mean ± s.e.m., n = 13) for the HPN and 1.092 ± 0.116 mL for the Pulmo-Aide. The average particle size was also equivalent, 5.38 ± 0.040 micrometers (mean ± s.e.m., n = 7) and 5.40 ± 0.025 micrometers, respectively. Conclusions Based on these characteristics, the HPN’s performance is equivalent to a popular commercially available electric nebulizer compressor. The findings presented in this paper, combined with the results of two published clinical studies, suggest that the HPN could serve as an important diagnostic and therapeutic tool in the fight against global respiratory health challenges including: tuberculosis, chronic obstructive pulmonary disease, asthma, and lower respiratory infections

Thermomechanical properties of polyhedral oligomeric silsequioxane- poly(methyl methacrylate) nanocomposites

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005.Includes bibliographical references.Poly(methyl methacrylate)s (PMMA) containing polyhedral oligomeric silsesquioxane (POSS) nanoparticles (d [approx.] 1.5 nm) were subjected to heological, mechanical, and morphological tests to determine the effects that POSS has on the melt-state and solid-state properties of this commercially important amorphous polymer. The effect of POSS on the rheological properties varied depending on the type of POSS cage and whether the POSS was covalently tethered to the PMMA backbone. A highly miscible acrylic-POSS species plasticizes PMMA, decreasing the glass transition temperature by approximately 10⁰C at a loading of 10 vol%. An essentially immiscible POSS species (cyclohexyl-POSS) does not alter the ... of PMMA but is able to decrease slightly the zero shear-rate viscosity at low loadings. Incorporating a POSS filler (isobutyl-POSS) into an isobutyl-POSS-PMMA copolymer causes a significant increase in viscosity at all loadings. The addition of POSS fillers to PMMA leads to an enhancement in the toughness in both slow-speed tension (strain rate = ... ) and high rate split-Hopkinson pressure bar tests (strain rate = ... ). In particular, the combined addition of two distinct POSS species - one miscible, one immiscible - led to the greatest enhancement in toughness and excellent reproducibility. A four-fold increase in tensile toughness was observed through the use of these two disparate POSS species.(cont.) Polyhedral oligomeric silsesquioxane macromers were copolymerized separately with a glassy polymer [PMMA, ... = 104⁰C] and a rubbery polymer [Poly(n-butyl acrylate), ... = -52⁰C] to determine the effect of the polymer glass transition temperature on the ultimate properties of an acrylic copolymer. Copolymers of POSS and PMMA show a significant decrease in ... . Conversely, copolymers of POSS and poly(n-butyl acrylate) have significantly higher glass transition temperatures than the pure PBA. These also exhibit a more than two order of magnitude increase in the room temperature modulus measured in DMA and tensile tests. The increase in modulus was due to nanocrystallites of POSS within the butyl acrylate matrix.by Edward Thomas Kopesky.Ph.D

Self-assembling peptide hydrogels promote in vitro chondrogenesis of bone marrow-derived stromal cells : effects of peptide sequence, cell donor age, and method of growth factor delivery

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 108-115).The inability of articular cartilage to heal after damage or disease has motivated investigation of novel cartilage tissue engineering technologies. The objective of this thesis was to advance the use of self-assembling peptide hydrogel scaffolds for cartilage repair by encapsulating bone-marrow-stromal cells (BMSCs) and incorporating chondrogenic cues to stimulate differentiation and neotissue production. To test the hypothesis that self-assembling peptide hydrogels provide cues which enhance the chondrogenic differentiation of BMSCs, a technique for rapid, high-viability BMSC encapsulation was developed. BMSCs were cultured in two peptide hydrogel sequences and compared to agarose hydrogels. BMSCs in all three hydrogels underwent TGF-3 1-mediated chondrogenesis as demonstrated by comparable gene expression and ECM biosynthesis. Cell proliferation occurred only in the peptide hydrogels, not in agarose, resulting in higher sulfated-glycosaminoglycan content and more spatially uniform proteoglycan and type II collagen deposition. These data showed that self-assembling peptide hydrogels enhance chondrogenesis compared to agarose. To evaluate the capacity for BMSCs from young and adult equine donors to produce cartilage-like ECM, neotissue formation was compared to that for animal-matched primary chondrocytes. Young chondrocytes stimulated by TGF-PlI accumulated ECM with higher sulfated-glycosaminoglycan content than adult chondrocytes and BMSCs of either age. BMSCs produced neotissue with higher dynamic stiffness than young chondrocytes. Measurement of aggrecan core-protein and chondroitin-sulfate length by atomic-force microscopy revealed BMSCs produce longer core protein and chondroitin-sulfate, and fewer catabolic-cleavage products than chondrocytes. Therefore, BMSC-produced aggrecan appears to have a younger phenotype than chondrocyte-produced aggrecan. These advantages make BMSCs a potentially superior cell source for peptide-hydrogel-based cartilage repair. To deliver TGF-pl to BMSCs via a bioactive scaffold, BMSCs were encapsulated in peptide hydrogels with both tethered and adsorbed TGF-p1 and cultured in TGF-p 1-free medium. Chondrogenesis was compared to that of unmodified peptide hydrogels with medium-delivered TGF-p1. Adsorbed-TGF-plI peptide hydrogels stimulated chondrogenesis of BMSCs as demonstrated by cell proliferation and cartilage-like ECM accumulation, while tethered TGF-p1 was not different from TGF-pl -free controls. TGF-p1 adsorbed to self-assembling peptide hydrogels can stimulate BMSC chondrogenesis. BMSC-seeded self-assembling peptide hydrogels, modified for controlled delivery of pro-chondrogenic factors, generate cartilage-like neotissue and are compatible with a single-surgery, autologous therapy for cartilage repair.by Paul Wayne Kopesky.Ph.D

Miscibility and Viscoelastic Properties of Acrylic Polyhedral Oligomeric Silsesquioxane-Poly(methyl methacrylate) Blends

Submitted to POLYMER, January 2005We investigate the miscibility of acrylic polyhedral oligomeric silsesquioxanes (POSS) [characteristic size d ≈ 2 nm] and poly(methyl methacrylate)(PMMA) in order to determine the effect of well-dispersed POSS nanoparticles on the thermomechanical properties of PMMA. Two different acrylic POSS species (unmodified and hydrogenated) were blended separately with PMMA at volume fractions up to φ = 0.30. Both POSS species have a plasticizing effect on PMMA by lowering the glass transition temperature Tg and decreasing the melt-state linear viscoelastic moduli measured in small amplitude oscillatory shear flow. The unmodified acrylic-POSS has better miscibility with PMMA than the hydrogenated form, approaching complete miscibility for loadings φ Tg of PMMA, far less than the 17.4°C decrease in the glass transition temperature observed in a blend of 5 vol% dioctyl phthalate (DOP) in PMMA; however, the decrease in the glass transition temperature per added plasticizer molecule is nearly the same in the unmodified acrylic-POSS-PMMA blend compared with the DOP-PMMA blend. Time-temperature superposition (TTS) was applied successfully to the storage and loss moduli data and the resulting shift factors were correlated with a significant increase in free volume of the blends. The fractional free volume f0 = 0.046 for PMMA at T0 = 170°C while for a blend of 5 vol% unmodified acrylic-POSS in PMMA f0 = 0.057, which corresponds to an addition of 0.47 nm3 per added POSS molecule at φ = 0.05. The degree of dispersion was characterized using both wide-angle x-ray diffraction (WAXD) and dynamic mechanical analysis (DMA). Diffraction patterns for both blend systems show clear evidence of phase separation at φ = 0.20 and higher, but no significant phase separation is evident at φ = 0.10 and lower. The storage modulus measured in DMA indicates appreciable phase separation for unmodified acrylic POSS loadings φ = 0.10, while no evidence of phase separation is present in the φ = 0.05 blend in DMA.AFOSR (DURINT program

Thermorheological Properties Near the Glass Transition of Oligomeric Poly(methyl methacrylate) Blended with Acrylic Polyhedral Oligomeric Silsesquioxane Nanocages

Submitted to Rheologica ActaTwo distinct oligomeric species of similar mass and chemical functionality (Mw ≈ 2,000 g/mol), one a linear methyl methacrylate oligomer (radius of gyration Rg ≈ 1.1 nm) and the other a hybrid organic-inorganic polyhedral silsesquioxane nanocage (methacryl-POSS, r ≈ 1.0 nm), were subjected to thermal and rheological tests to compare the behaviors of these geometrically dissimilar molecules over the entire composition range. The glass transition temperatures of the blends varied monotonically between the glass transition temperatures of the pure oligomer (Tg = â47.3°C) and the pure POSS (Tg = â61.0°C). Blends containing high POSS contents (with volume fraction φ_POSS ⥠0.90) exhibited enhanced enthalpy relaxation in DSC measurements, and the degree of enthalpy relaxation was used to calculate the kinetic fragility indices m of the oligomeric MMA (m = 59) and the POSS (m = 74). The temperature dependences of the viscosities were fitted by the free volume-based WLF-VFT framework and a dynamic scaling relation. The calculated values of the fragility from the WLF-VFT fits were similar for the POSS (m = 82) and for the oligomer (m = 76), and the dynamic scaling exponent was similar for the oligomeric MMA and the POSS. Within the range of known fragilities for glass-forming liquids, the temperature dependence of the viscosity was found to be similarly fragile for the two species. The difference in shape of the nanocages and oligomer chains is unimportant in controlling the glass-forming properties of the blends at low volume fractions ( φPOSS < 0.20); however, at higher volume fractions, adjacent POSS cages begin to crowd each other, leading to an increase in the fractional free volume at the glass transition temperature and the observed enhanced enthalpy relaxation in DSC.AFOSR (DURINT Program

Short-Term Cost-Benefits of Intensive Home Visiting

The University of Minnesota conducted this study for Dakota County in fall of 2004. The study compared rates of child maltreatmentﾗchild abuse and neglectﾗamong families involved in the Dakota Healthy Families program from July 2002 through June 2004, with a comparison group of similar families not involved in Dakota Healthy Families. The study was undertaken to determine whether Dakota Healthy Families is effective in preventing child abuse among parents at risk to perpetrate maltreatment, and at a rate sufficient to off-set program costs. Child maltreatment records for 220 home visited families were reviewed at 1 to 2.5 years of program participation. This report details the study methodology and results.Prepared in partnership with Dakota County Public Health by the Community Assistantship Program (CAP), administered by the Center for Urban and Regional Affairs (CURA) at the University of Minnesota

Sustained delivery of bioactive TGF-β1 from self-assembling peptide hydrogels induces chondrogenesis of encapsulated bone marrow stromal cells

Tissue engineering strategies for cartilage defect repair require technology for local targeted delivery of chondrogenic and anti-inflammatory factors. The objective of this study was to determine the release kinetics of transforming growth factor β1 (TGF-β1) from self-assembling peptide hydrogels, a candidate scaffold for cell transplant therapies, and stimulate chondrogenesis of encapsulated young equine bone marrow stromal cells (BMSCs). Although both peptide and agarose hydrogels retained TGF-β1, fivefold higher retention was found in peptide. Excess unlabeled TGF-β1 minimally displaced retained radiolabeled TGF-β1, demonstrating biologically relevant loading capacity for peptide hydrogels. The initial release from acellular peptide hydrogels was nearly threefold lower than agarose hydrogels, at 18% of loaded TGF-β1 through 3 days as compared to 48% for agarose. At day 21, cumulative release of TGF-β1 was 32–44% from acellular peptide hydrogels, but was 62% from peptide hydrogels with encapsulated BMSCs, likely due to cell-mediated TGF-β1 degradation and release of small labeled species. TGF-β1 loaded peptide hydrogels stimulated chondrogenesis of young equine BMSCs, a relevant preclinical model for treating injuries in young human cohorts. Self-assembling peptide hydrogels can be used to deliver chondrogenic factors to encapsulated cells making them a promising technology for in vivo, cell-based regenerative medicine.National Institutes of Health (U.S.) (NIH EB003805)National Institutes of Health (U.S.) (NIH AR60331)National Institutes of Health (U.S.). Molecular, Cell, and Tissue Biomechanics (Training Grant Fellowship)Arthritis Foundation (postdoctoral fellowship