The humidity in a Dräger Primus anesthesia workstation using low or high fresh gas flow and with or without a heat and moisture exchanger in pediatric patients.

PubMed

Bicalho, Gustavo P; Braz, Leandro G; de Jesus, Larissa S B; Pedigone, Cesar M C; de Carvalho, Lídia R; Módolo, Norma S P; Braz, José R C

2014-10-01

An inhaled gas absolute humidity of 20 mg H2O·L is the value most considered as the threshold necessary for preventing the deleterious effects of dry gas on the epithelium of the airways during anesthesia. Because children have small minute ventilation, we hypothesized that the humidification of a circle breathing system is lower in children compared with adults. The Primus anesthesia workstation (Dräger Medical, Lübeck, Germany) has a built-in hotplate to heat the patient's exhaled gases. A heat and moisture exchanger (HME) is a device that can be used to further humidify and heat the inhaled gases during anesthesia. To evaluate the humidifying properties of this circle breathing system during pediatric anesthesia, we compared the temperature and humidity of inhaled gases under low or high fresh gas flow (FGF) conditions and with or without an HME. Forty children were randomly allocated into 4 groups according to the ventilation of their lungs by a circle breathing system in a Dräger Primus anesthesia workstation with low (1 L·min) or high (3 L·min) FGF without an HME (1L and 3L groups) or with an HME (Pall BB25FS, Pall Biomedical, East Hills, NY; HME1L and HME3L groups). The temperature and absolute humidity of inhaled gases were measured at 10, 20, 40, 60, and 80 minutes after connecting the patient to the breathing circuit. The mean inhaled gas temperature was higher in HME groups (HME1L: 30.3°C ± 1.1°C; HME3L: 29.3°C ± 1.2°C) compared with no-HME groups (1L: 27.0°C ± 1.2°C; 3L: 27.1°C ± 1.5°C; P < 0.0001). The mean inhaled gas absolute humidity was higher in HME than no-HME groups and higher in low-flow than high-flow groups ([HME1L: 25 ± 1 mg H2O·L] > [HME3L: 23 ± 2 mg H2O·L] > [1L: 17 ± 1 mg H2O·L] > [3L: 14 ± 1 mg H2O·L]; P < 0.0001). In a pediatric circle breathing system, the use of neither high nor low FGF provides the minimum humidity level of the inhaled gases thought to reduce the risk of dehydration of airways. Insertion of an HME increases the humidity and temperature of the inhaled gases, bringing them closer to physiological values. The use of a low FGF enhances the HME efficiency and consequently increases the inhaled gas humidity values. Therefore, the association of an HME with low FGF in the breathing circuit is the most efficient way to conserve the heat and the moisture of the inhaled gas during pediatric anesthesia.

Cost-Effectiveness Analysis of Heat and Moisture Exchangers in Mechanically Ventilated Critically Ill Patients.

PubMed

Menegueti, Mayra Goncalves; Auxiliadora-Martins, Maria; Nunes, Altacilio Aparecido

2016-08-01

Moisturizing, heating and filtering gases inspired via the mechanical ventilation (MV) circuits help to reduce the adverse effects of MV. However, there is still no consensus regarding whether these measures improve patient prognosis, shorten MV duration, decrease airway secretion and lower the incidence of ventilator associated pneumonia (VAP) and other complications. The aim of this study was to study the incremental cost-effectiveness ratio associated with the use of heat and moisture exchangers (HME) filter to prevent VAP compared with the heated humidifiers (HH) presently adopted by intensive care unit (ICU) services within the Brazilian Healthcare Unified System. This study was a cost-effectiveness analysis (CEA) comparing HME and HH in preventing VAP (outcome) in mechanically ventilated adult patients admitted to an ICU of a public university hospital. The analysis considered a period of 12 months; MV duration of 11 and 12 days for patients in HH and HME groups, respectively and a daily cost of R$ 16.46 and R$ 13.42 for HH and HME, respectively. HME was more attractive; costs ranged from R$ 21,000.00 to R$ 22,000.00 and effectiveness was close to 0.71, compared with a cost of R$ 30,000.00 and effectiveness between 0.69 and 0.70 for HH. HME and HH differed significantly for incremental effectiveness. Even after an effectiveness gain of 1.5% in favor of HH, and despite the wide variation in the VAP rate, the HME effectiveness remained stable. The mean HME cost-effectiveness was lower than the mean HH cost-effectiveness, being the HME value close to R$ 44,000.00. Our findings revealed that HH and HME differ very little regarding effectiveness, which makes interpretation of the results in the context of clinical practice difficult. Nonetheless, there is no doubt that HME is advantageous. This technology incurs lower direct cost.

Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century.

PubMed

Tiwari, Roshan V; Patil, Hemlata; Repka, Michael A

2016-01-01

Hot-melt extrusion (HME) technology is applied successfully in the plastic, rubber and food industry. HME has also emerged as an important technology for drug delivery applications in pharmaceutical research and manufacturing because of its process automation and low-cost scale-up properties, which reduce labor costs and capital investment. There are a number of commercial FDA-approved HME-derived products, signifying the commercial feasibility of this novel technique in drug delivery applications. HME is a highly efficient, solvent-free continuous processing technique for the development of solid dispersions; thus, research efforts to develop sustained, modified and targeted drug delivery systems to improve the solubility and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) are of interest. This review focuses on both the innovations and applications of HME in the production of pharmaceutical formulations, and on the significant findings of the general principles regarding formulation and process development via HME as described in published articles. Challenges faced by pharmaceutical companies to produce efficient drug formulations may be partly overcome by HME's advantages - high drug-loading capacity, good content uniformity, cost-effectiveness, and ease of processing scale-up. Nevertheless, HME's high processing temperatures may be an obstacle if adequate knowledge about the product's formulation is lacking.

The simultaneous use of a heat and moisture exchanger and a heated humidifier causes critical airway occlusion in less than 24 hours.

PubMed

Doyle, Alexander; Mariyaselvam, Maryanne; Wijewardena, Gayathri; English, Natalie; Gent, Emma; Young, Peter

2015-08-01

Heat and moisture exchangers (HMEs) and heated humidifiers (HHs) may be used together inadvertently. Such an incident occurred at our institution resulting in airway occlusion. A bench-top study was conducted to compare the incidence of airway occlusion when using (1) no airway humidification, (2) HME alone, (3) HH alone, and (4) both HME and HH in combination as part of a standard breathing circuit. The simultaneous use of a HME and a HH was associated with a reduction in tidal volume (no airway humidification, P ≤ .05; HME alone, P ≤ .01; and HH alone, P ≤ .01) and an increased incidence of airway occlusion (no airway humidification, 0/7; HME alone, 0/7; HH alone, 0/7; and HME and HH in combination, 7/7; P < .0001). The use of a HME and a HH in combination is likely to result in airway occlusion. Precautions should be taken to ensure that both systems are not used together in clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic adherence to heat and moisture exchanger use in laryngectomized patients.

PubMed

Pedemonte-Sarrias, Gabriel; Villatoro-Sologaistoa, Juan Carlos; Ale-Inostroza, Paulina; López-Vilas, Montserrat; León-Vintró, Xavier; Quer-Agustí, Miquel

2013-01-01

Total laryngectomy leads to pulmonary problems such as excessive sputum production, forced expectoration and increased coughing. The use of a heat and moisture exchanger (Provox(®) HME) reduces these symptoms. The aim of this study was to quantify chronic adherence to HME use in laryngectomized patients. A prospective study of 115 patients laryngectomized at our centre during 2005-2011 was performed. Of the 115 patients, 90 (78.2%) used the HME consistently and 25 (21.8%) abandoned its use. The most common causes of desertion were adhesion problems due to mucus and skin irritation. Of the 30 patients with voice prostheses, 90% of them used the HME system regularly. Voice prosthesis use (P=.05) and early indication in postoperative laryngectomy (P=.001) were factors significantly associated with chronic HME use. There is high adherence (78.2%) to heat and moisture exchanger (Provox(®) HME) use in laryngectomized patients. Chronic HME use was higher in patients with voice prosthesis and the ones with early indication in postoperative period. The major causes of abandonment were related to problems with the adhesive. Copyright © 2012 Elsevier España, S.L. All rights reserved.

A new heat and moisture exchanger for laryngectomized patients: endotracheal temperature and humidity.

PubMed

Scheenstra, Renske J; Muller, Saar H; Vincent, Andrew; Ackerstaff, Annemieke H; Jacobi, Irene; Hilgers, Frans J M

2011-05-01

To assess the endotracheal temperature and humidity and clinical effects of 2 models of a new heat and moisture exchanger (HME): Rplus, which has regular breathing resistance, and Lplus, which has lower breathing resistance. We measured endotracheal temperature and humidity in 10 laryngectomized patients, for 10 min each, with and without the HMEs. We sequentially tested 4 HME models (all Atos Medical, Hörby, Sweden), in randomized order: Rplus, Lplus, Provox Normal (the HME we regularly use and which we considered the reference HME), and Stomvent (an older HME model). We also assessed the short-term clinical and practical effects of the Rplus and Lplus in a prospective 3-week trial with 13 laryngectomized patients. Rplus and Lplus had better humidification than Provox Normal (6.8 mg H(2)O/L, 4.3 mg H(2)O/L, and 3.7 mg H(2)O/L, respectively, P < .001), and no significant temperature difference. During the 3-week study period, 7 of the 13 patients reported noticeably lower mucus production with Rplus and Lplus. Rplus and Lplus had better heating and humidification than Provox Normal. Although Stomvent also performed well, its design is less convenient for laryngectomized patients. Further HME improvement is still warranted and should focus on improving the HME's heating capacity.

Hot Melt Extruded and Injection Moulded Dosage Forms: Recent Research and Patents.

PubMed

Major, Ian; McConville, Christopher

2015-01-01

Hot Melt Extrusion (HME) and Injection Moulding (IM) are becoming more prevalent in the drug delivery field due to their continuous nature and advantages over current pharmaceutical manufacturing techniques. Hot melt extrusion (HME) is a process that involves the use of at least one reciprocating screw to force a thermoplastic resin along a heated barrel and through a die, while injection moulding is a forming process were molten polymer is forced at high pressure to enter a mould. HME offers a number of advantages over conventional pharmaceutical manufacturing techniques such as increased solubility and bioavailability of poorly water soluble drugs, a solvent free and continuous process, improved content uniformity and flexibility in manufacture. Injection moulding (IM) has been recognised as a rapid and versatile manufacturing technique, which has the advantages of being a continuous process, which is easily scaled up by the use of larger equipment and moulds. However, despite their advantages and the significant number of publications and patents on HME and IM drug delivery devices there are very few marketed formulations. These marketed products range from oral dosage forms which improve bioavailability and reduce pill burden to vaginal rings which provide long-term controlled release thus improving patient compliance. The patenting strategy for IM and HME seems to be focused towards patenting the finished product, more so than patenting the manufacturing process. This is probably due to the fact that the IM and HME processes have already been patented. HME is a process where raw materials (i.e. polymer, plasticizer, drug etc.) are mixed and pumped along by a rotating screw(s) at elevated temperatures through a die to produce a product of uniform shape. IM is similar to HME except that the raw materials are pushed into a mould which is set at lower temperatures. Interest in the use of HME and IM within the pharmaceutical industry is growing with as steady increase in the number of HME patents being issued and with more than 10 products, ranging from oral dosage forms to implantable devices, currently on the market. Therefore, this review of HME and IM is important to the scientific community to further understand and advance these novel and exciting manufacturing techniques.

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME.

PubMed

Huang, Siyuan; O'Donnell, Kevin P; Keen, Justin M; Rickard, Mark A; McGinity, James W; Williams, Robert O

2016-02-01

Hypromellose is a hydrophilic polymer widely used in immediate- and modified-release oral pharmaceutical dosage forms. However, currently available grades of hypromellose are difficult, if not impossible, to process by hot melt extrusion (HME) because of their high glass transition temperature, high melt viscosity, and low degradation temperature. To overcome these challenges, a modified grade of hypromellose, AFFINISOL™ HPMC HME, was recently introduced. It has a significantly lower glass transition temperature and melt viscosity as compared to other available grades of hypromellose. The objective of this paper is to assess the extrudability and performance of AFFINISOL™ HPMC HME (100LV and 4M) as compared to other widely used polymers in HME, including HPMC 2910 100cP (the currently available hypromellose), Soluplus®, Kollidon® VA 64, and EUDRAGIT® E PO. Formulations containing polymer and carbamazepine (CBZ) were extruded on a co-rotating 16-mm twin-screw extruder, and the effect of temperature, screw speed, and feed rate was investigated. The performance of the solid dispersions was evaluated based on Flory-Huggins modeling and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and dissolution. All formulations extruded well except for HPMC 2910 100cP, which resulted in over-torqueing the extruder (machine overloading because the motor cannot provide efficient energy to rotate the shaft). Among the HME extrudates, only the EUDRAGIT® E PO formulation was crystalline as confirmed by DSC, XRD, and Raman, which agreed with predictions from Flory-Huggins modeling. Dissolution testing was conducted under both sink and non-sink conditions. Sink dissolution testing in neutral media revealed that amorphous CBZ in the HME extrudates completely dissolved within 15 min, which was much more rapid than the time for complete dissolution of bulk CBZ (60 min) and EUDRAGIT® E PO solid dispersion (more than 6 h). Non-sink dissolution in acidic media testing revealed that only CBZ contained in the AFFINISOL™ HPMC HME, and EUDRAGIT® E PO solid dispersions rapidly supersaturated after 15 min, reaching a twofold drug concentration compared to the CBZ equilibrium solubility. In summary, AFFINISOL™ HPMC HME 100LV and AFFINISOL™ HPMC HME 4M are useful in the pharmaceutical HME process to increase wetting and dissolution properties of poorly water-soluble drugs like CBZ.

Comparison of the effects of heat and moisture exchangers and heated humidifiers on ventilation and gas exchange during non-invasive ventilation.

PubMed

Jaber, Samir; Chanques, Gérald; Matecki, Stefan; Ramonatxo, Michèle; Souche, Bruno; Perrigault, Pierre-François; Eledjam, Jean-Jacques

2002-11-01

To compare the short-term effects of a heat and moisture exchanger (HME) and a heated humidifier (HH) during non-invasive ventilation (NIV). Prospective, clinical investigation. Intensive care unit of a university hospital. Twenty-four patients with acute respiratory failure (ARF). Each patient was studied with a HME and a HH in a random order during two consecutive 20min periods of NIV. Respiratory rate (RR), expiratory tidal volume (VTe) and expiratory minute ventilation (VE) were measured during the last 5 min of each period and blood gases were measured. Mean pressure support and positive end-expiratory pressure levels were, respectively, 15+/-4 and 6+/-2 cmH(2)O. VE was significantly greater with HME than with HH (14.8+/-4.8 vs 13.2+/-4.3 l/min; p<0.001). This increase in VE was the result of a greater RR for HME than for HH (26.5+/-10.6 vs 24.1+/-9.8 breaths/min; p=0.002), whereas the VT for HME was similar to that for HH (674+/-156 vs 643+/-148 ml; p=0.09). Arterial partial pressure of carbon dioxide (PaCO(2)) was significantly higher with a HME than with a HH (43.4+/-8.9 vs 40.8+/-8.2 mmHg; p<0.005), without significantly changing oxygenation. During NIV the increased dead space of a HME can negatively affect ventilatory function and gas exchange. The effect of HME dead space may decrease efficiency of NIV in patients with ARF.

Interactions between drugs and polymers influencing hot melt extrusion.

PubMed

Li, Yongcheng; Pang, Huishi; Guo, Zhefei; Lin, Ling; Dong, Yixuan; Li, Ge; Lu, Ming; Wu, Chuangbin

2014-02-01

Hot melt extrusion (HME) as a technique for producing amorphous solid dispersion (ASD) has been widely used in pharmaceutical research. The biggest challenge for the application of HME is the thermal degradation of drug, poor physical stability of ASD and precipitation of drug during dissolution. Interactions between drugs and polymers may play an important role in overcoming these barriers. In this review, influence of drug-polymer interactions on HME and the methods for characterizing the drug-polymer interactions were reviewed. Strong drug-polymer interactions, especially ionic interactions and hydrogen bonds, are helpful to improving the thermal stability of drug during HME, enhancing the physical stability of ASD during storage and maintaining supersaturated solution after dissolution in gastrointestinal tract. The interactions can be quantitatively and qualitatively characterized by many analysing methods. As many factors collectively determine the properties of HME products, drug-polymer interactions play an extremely important role. However, the action mechanisms of drug-polymer interactions need intensive investigation to provide more useful information for optimizing the formulation and the process parameters of HME. © 2013 Royal Pharmaceutical Society.

[Early functional hemispherectomy in hemimegalencephaly associated to refractory epilepsy].

PubMed

Fonseca, Luiz Fernando; Melo, Renato Pacheco de; Cukiert, Arthur; Burattini, Jose Augusto; Mariani, Pedro Paulo; Brandão, Ródio; Ceda, Lauro; Baldauf, Cristine Mella; Argentoni, Meire; Forster, Cássio; Baise, Carla

2004-12-01

Hemimegalencephaly (HME) is a rare congenital brain malformation of unknown etiology. Patients with HME can present with an early onset epileptic syndrome which is often refractory to medical treatment and associated to impaired neurological development. Functional hemispherectomy (FH) has proven to be a valuable treatment alternative in patients with refractory epilepsy in this setting. Very few children operated under the age of 6 months and bearing HME and catastrophic epilepsy (CE) have been described in the literature. This study reports on 2 kids younger than 6 months with HME and CE submitted to FH with good clinical outcome.

Osteopoikilosis and multiple exostoses caused by novel mutations in LEMD3 and EXT1 genes respectively - coincidence within one family

PubMed Central

2010-01-01

Background Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and in the carpal and tarsal bones [1]. Heterozygous LEMD3 gene mutations were shown to be the primary cause of the disease [2]. Association of the primarily asymptomatic osteopokilosis with connective tissue nevi of the skin is categorized as Buschke-Ollendorff syndrome (BOS) [3]. Additionally, osteopoikilosis can coincide with melorheostosis (MRO), a more severe bone disease characterised by the ectopic bone formation on the periosteal and endosteal surface of the long bones [4-6]. However, not all MRO affected individuals carry germ-line LEMD3 mutations [7]. Thus, the genetic cause of MRO remains unknown. Here we describe a familial case of osteopoikilosis in which a novel heterozygous LEMD3 mutation coincides with a novel mutation in EXT1, a gene involved in aetiology of multiple exostosis syndrome. The patients affected with both LEMD3 and EXT1 gene mutations displayed typical features of the osteopoikilosis. There were no additional skeletal manifestations detected however, various non-skeletal pathologies coincided in this group. Methods We investigated LEMD3 and EXT1 in the three-generation family from Poland, with 5 patients affected with osteopoikilosis and one child affected with multiple exostoses. Results We found a novel c.2203C > T (p.R735X) mutation in exon 9 of LEMD3, resulting in a premature stop codon at amino acid position 735. The mutation co-segregates with the osteopoikilosis phenotype and was not found in 200 ethnically matched controls. Another new substitution G > A was found in EXT1 gene at position 1732 (cDNA) in Exon 9 (p.A578T) in three out of five osteopoikilosis affected family members. Evolutionary conservation of the affected amino acid suggested possible functional relevance, however no additional skeletal manifestations were observed other then those specific for osteopoikilosis. Finally in one member of the family we found a splice site mutation in the EXT1 gene intron 5 (IVS5-2 A > G) resulting in the deletion of 9 bp of cDNA encoding three evolutionarily conserved amino acid residues. This child patient suffered from a severe form of exostoses, thus a causal relationship can be postulated. Conclusions We identified a new mutation in LEMD3 gene, accounting for the familial case of osteopoikilosis. In the same family we identified two novel EXT1 gene mutations. One of them A598T co-incided with the LEMD3 mutation. Co-incidence of LEMD3 and EXT1 gene mutations was not associated with a more severe skeletal phenotype in those patients. PMID:20618940

Numerical simulation of hot-melt extrusion processes for amorphous solid dispersions using model-based melt viscosity.

PubMed

Bochmann, Esther S; Steffens, Kristina E; Gryczke, Andreas; Wagner, Karl G

2018-03-01

Simulation of HME processes is a valuable tool for increased process understanding and ease of scale-up. However, the experimental determination of all required input parameters is tedious, namely the melt rheology of the amorphous solid dispersion (ASD) in question. Hence, a procedure to simplify the application of hot-melt extrusion (HME) simulation for forming amorphous solid dispersions (ASD) is presented. The commercial 1D simulation software Ludovic ® was used to conduct (i) simulations using a full experimental data set of all input variables including melt rheology and (ii) simulations using model-based melt viscosity data based on the ASDs glass transition and the physical properties of polymeric matrix only. Both types of HME computation were further compared to experimental HME results. Variation in physical properties (e.g. heat capacity, density) and several process characteristics of HME (residence time distribution, energy consumption) among the simulations and experiments were evaluated. The model-based melt viscosity was calculated by using the glass transition temperature (T g ) of the investigated blend and the melt viscosity of the polymeric matrix by means of a T g -viscosity correlation. The results of measured melt viscosity and model-based melt viscosity were similar with only few exceptions, leading to similar HME simulation outcomes. At the end, the experimental effort prior to HME simulation could be minimized and the procedure enables a good starting point for rational development of ASDs by means of HME. As model excipients, Vinylpyrrolidone-vinyl acetate copolymer (COP) in combination with various APIs (carbamazepine, dipyridamole, indomethacin, and ibuprofen) or polyethylene glycol (PEG 1500) as plasticizer were used to form the ASDs. Copyright © 2017 Elsevier B.V. All rights reserved.

Extensive Chromosomal Reorganization in the Evolution of New World Muroid Rodents (Cricetidae, Sigmodontinae): Searching for Ancestral Phylogenetic Traits

PubMed Central

Pereira, Adenilson Leão; Malcher, Stella Miranda; Nagamachi, Cleusa Yoshiko; O’Brien, Patricia Caroline Mary; Ferguson-Smith, Malcolm Andrew; Mendes-Oliveira, Ana Cristina; Pieczarka, Julio Cesar

2016-01-01

Sigmodontinae rodents show great diversity and complexity in morphology and ecology. This diversity is accompanied by extensive chromosome variation challenging attempts to reconstruct their ancestral genome. The species Hylaeamys megacephalus–HME (Oryzomyini, 2n = 54), Necromys lasiurus—NLA (Akodontini, 2n = 34) and Akodon sp.–ASP (Akodontini, 2n = 10) have extreme diploid numbers that make it difficult to understand the rearrangements that are responsible for such differences. In this study we analyzed these changes using whole chromosome probes of HME in cross-species painting of NLA and ASP to construct chromosome homology maps that reveal the rearrangements between species. We include data from the literature for other Sigmodontinae previously studied with probes from HME and Mus musculus (MMU) probes. We also use the HME probes on MMU chromosomes for the comparative analysis of NLA with other species already mapped by MMU probes. Our results show that NLA and ASP have highly rearranged karyotypes when compared to HME. Eleven HME syntenic blocks are shared among the species studied here. Four syntenies may be ancestral to Akodontini (HME2/18, 3/25, 18/25 and 4/11/16) and eight to Sigmodontinae (HME26, 1/12, 6/21, 7/9, 5/17, 11/16, 20/13 and 19/14/19). Using MMU data we identified six associations shared among rodents from seven subfamilies, where MMU3/18 and MMU8/13 are phylogenetic signatures of Sigmodontinae. We suggest that the associations MMU2entire, MMU6proximal/12entire, MMU3/18, MMU8/13, MMU1/17, MMU10/17, MMU12/17, MMU5/16, MMU5/6 and MMU7/19 are part of the ancestral Sigmodontinae genome. PMID:26800516

[Pulmonary rehabilitation after total laryngectomy using a heat and moisture exchanger (HME)].

PubMed

Lorenz, K J; Maier, H

2009-08-01

A complete removal of the larynx has profound consequences for a patient. Since laryngectomy involves the separation of the upper airway from the lower airway, it not only implies a loss of the voice organ but also leads to chronic lung problems such as increased coughing, mucus production and expectoration. In addition, laryngectomees complain of fatigue, sleeping problems, a reduced sense of smell and taste, and a loss of social contact. A heat and moisture exchanger (HME) cassette can replace a function of the upper airway which consists in conditioning inspired air. It can improve pulmonary symptoms in three ways. 1. An HME cassette heats and moisturises inhaled air and thus creates nearly physiological conditions in the region of the deep airway. 2. The use of an HME cassette leads to an increase in breathing resistance, thereby reducing dynamic airway compression and improving lung ventilation. 3. An HME cassette acts as a filter and removes larger particles from incoming air. This review examines the current understanding of lung physiology after laryngectomy and assesses the effects of HME cassettes on the conditioning of respiratory air, lung function and psychosocial problems. Georg Thieme Verlag KG Stuttgart, New York.

Small dead space heat and moisture exchangers do not impede gas exchange during noninvasive ventilation: a comparison with a heated humidifier.

PubMed

Boyer, Alexandre; Vargas, Frederic; Hilbert, Gilles; Gruson, Didier; Mousset-Hovaere, Maud; Castaing, Yves; Dreyfuss, Didier; Ricard, Jean Damien

2010-08-01

Adverse respiratory and gasometrical effects have been described in patients with acute respiratory failure (ARF) undergoing noninvasive ventilation (NIV) with standard heat and moisture exchangers (HME). We decided to evaluate respiratory parameters and arterial blood gases (ABG) of patients during NIV with small dead space HME compared with heated humidifier (HH). Prospective randomized crossover study. A 16-bed medical intensive care unit (ICU). Fifty patients receiving NIV for ARF. The effects of HME and HH on respiratory rate, minute ventilation, EtCO(2), oxygen saturation, airway occlusion pressure at 0.1 s, ABG, and comfort perception were compared during two randomly determined NIV periods of 30 min. The relative impact of HME and HH on these parameters was successively compared with or without addition of a flex tube (40 and 10 patients, respectively). No difference was observed between HME and HH regarding any of the studied parameters, whether or not a flex tube was added. If one decides to humidify patients' airways during NIV, one may do so with small dead space HME or HH without altering respiratory parameters.

Effect of heat and moisture exchanger (HME) positioning on inspiratory gas humidification.

PubMed

Inui, Daisuke; Oto, Jun; Nishimura, Masaji

2006-08-08

In mechanically ventilated patients, we investigated how positioning the heat and moisture exchanger (HME) at different places on the ventilator circuit affected inspiratory gas humidification. Absolute humidity (AH) and temperature (TEMP) at the proximal end of endotracheal tube (ETT) were measured in ten mechanically ventilated patients. The HME was connected either directly proximal to the ETT (Site 1) or at before the circuit Y-piece (Site 2: distance from proximal end of ETT and Site 2 was about 19 cm) (Figure. 1). Two devices, Hygrobac S (Mallinckrodt Dar, Mirandola, Italy) and Thermovent HEPA (Smiths Medical International Ltd., Kent, UK) were tested. AH and TEMP were measured with a hygrometer (Moiscope, MERA Co., Ltd., Tokyo, Japan). Hygrobac S provided significantly higher AH and TEMP at both sites than Thermovent HEPA. Both Hygrobac S and with Thermovent HEPA provided significantly higher AH and TEMP when placed proximally to the ETT. Although placement proximal to the ETT improved both AH and TEMP in both HMEs tested, one HME performed better in the distal position than the other HME in the proximal position. We conclude the both the type and placement of HME can make a significant difference in maintaining AH and TEMP during adult ventilation.

Effect of heat and moisture exchanger (HME) positioning on inspiratory gas humidification

PubMed Central

Inui, Daisuke; Oto, Jun; Nishimura, Masaji

2006-01-01

Background In mechanically ventilated patients, we investigated how positioning the heat and moisture exchanger (HME) at different places on the ventilator circuit affected inspiratory gas humidification. Methods Absolute humidity (AH) and temperature (TEMP) at the proximal end of endotracheal tube (ETT) were measured in ten mechanically ventilated patients. The HME was connected either directly proximal to the ETT (Site 1) or at before the circuit Y-piece (Site 2: distance from proximal end of ETT and Site 2 was about 19 cm) (Figure. 1). Two devices, Hygrobac S (Mallinckrodt Dar, Mirandola, Italy) and Thermovent HEPA (Smiths Medical International Ltd., Kent, UK) were tested. AH and TEMP were measured with a hygrometer (Moiscope, MERA Co., Ltd., Tokyo, Japan). Results Hygrobac S provided significantly higher AH and TEMP at both sites than Thermovent HEPA. Both Hygrobac S and with Thermovent HEPA provided significantly higher AH and TEMP when placed proximally to the ETT. Conclusion Although placement proximal to the ETT improved both AH and TEMP in both HMEs tested, one HME performed better in the distal position than the other HME in the proximal position. We conclude the both the type and placement of HME can make a significant difference in maintaining AH and TEMP during adult ventilation. PMID:16895607

Investigation of Thermal and Viscoelastic Properties of Polymers Relevant to Hot Melt Extrusion, IV: Affinisol™ HPMC HME Polymers.

PubMed

Gupta, Simerdeep Singh; Solanki, Nayan; Serajuddin, Abu T M

2016-02-01

Most cellulosic polymers cannot be used as carriers for preparing solid dispersion of drugs by hot melt extrusion (HME) due to their high melt viscosity and thermal degradation at high processing temperatures. Three HME-grade hydroxypropyl methylcelluloses, namely Affinisol™ HPMC HME 15 cP, Affinisol™ HPMC HME 100 cP, and Affinisol™ HPMC HME 4 M, have recently been introduced by The Dow Chemical Co. to enable the preparation of solid dispersion at lower and more acceptable processing temperatures. In the present investigation, physicochemical properties of the new polymers relevant to HME were determined and compared with that of Kollidon(®) VA 64. Powder X-ray diffraction (PXRD), modulated differential scanning calorimetry (mDSC), thermogravimetric analysis (TGA), moisture sorption, rheology, and torque analysis by melt extrusion were applied. PXRD and mDSC showed that the Affinisol™ polymers were amorphous in nature. According to TGA, the onset of degradation for all polymers was >220°C. The Affinisol™ polymers exhibited less hygroscopicity than Kollidon(®) VA 64 and another HPMC polymer, Methocel™ K100LV. The complex viscosity profiles of the Affinisol™ polymers as a function of temperature were similar. The viscosity of the Affinisol™ polymers was highly sensitive to the shear rate applied, and unlike Kollidon(®) VA 64, the viscosity decreased drastically when the angular frequency was increased. Because of the very high shear rate encountered during melt extrusion, Affinisol™ polymers showed capability of being extruded at larger windows of processing temperatures as compared to that of Kollidon(®) VA 64.

[Efficacy of heat and moisture exchangers and heated humidifiers in preventing ventilator-associated pneumonia: a meta-analysis].

PubMed

Mo, Min; Liu, Song-qiao; Yang, Yi

2011-09-01

To demonstrate the effects of heat and moisture exchangers (HME) and heated humidifiers(HH) in preventing ventilator-associated pneumonia (VAP). PubMed and Cochrane databases were searched by computer retrieval and manual retrieval to identify relevant randomized controlled trials (RCTs) using HMEs and HHs in preventing VAP from January 1st 1990 to September 1st 2010. Meta-analysis of HME and HH in preventing VAP was conducted using the methods recommended by the Cochrane Collaboration. Eleven RCTs were included. 1 121 in HME group and 1 101 in HH group. In total, the rate of VAP in HME group and HH group was 14.2% (159/1 121) and 15.9% (175/1 101) respectively, the total relative risk (RR) was 0.88, and 95% confidence interval (95%CI) 0.72-1.07, P=0.21. Compared with HH group, there was not a reduction in the risk ratio of VAP in the HME group. Even in mechanical ventilation(MV) with a duration of at least 7 days for subgroup analysis (8 RCTs, sample size: 834 in HME group and 859 in HH group), the rate of VAP in HME group and HH group was 15.2% (127/834) and 17.5% (150/859) respectively, the total RR was 0.84, 95%CI 0. 58-1.23, P=0.37, suggesting that in MV with a duration at least 7 days, there was also no reduction in the risk ratio of VAP in the HME group. This study suggests there is not a significant reduction in the incidence of VAP in patients humidified with HMEs during MV, even in patients ventilated for 7 days or longer. This finding is limited by lack of enough RCTs and blinding. Further large sample of high quality RCTs is necessary to examine the wider applicability of HMEs and their extended use.

Bony outgrowths on the jaws of an extinct sperm whale support macroraptorial feeding in several stem physeteroids

NASA Astrophysics Data System (ADS)

Lambert, Olivier; Bianucci, Giovanni; Beatty, Brian L.

2014-06-01

Several extinct sperm whales (stem Physeteroidea) were recently proposed to differ markedly in their feeding ecology from the suction-feeding modern sperm whales Kogia and Physeter. Based on cranial, mandibular, and dental morphology, these Miocene forms were tentatively identified as macroraptorial feeders, able to consume proportionally large prey using their massive teeth and robust jaws. However, until now, no corroborating evidence for the use of teeth during predation was available. We report on a new specimen of the stem physeteroid Acrophyseter, from the late middle to early late Miocene of Peru, displaying unusual bony outgrowths along some of the upper alveoli. Considering their position and outer shape, these are identified as buccal maxillary exostoses. More developed along posterior teeth and in tight contact with the high portion of the dental root outside the bony alveoli, the exostoses are hypothesized to have developed during powerful bites; they may have worked as buttresses, strengthening the teeth when facing intense occlusal forces. These buccal exostoses further support a raptorial feeding technique for Acrophyseter and, indirectly, for other extinct sperm whales with a similar oral apparatus ( Brygmophyseter, Livyatan, Zygophyseter). With a wide size range, these Miocene stem physeteroids were major marine macropredators, occupying ecological niches nowadays mostly taken by killer whales.

[Strategy Discussion for Pollution Control of Post-Consumer Home Medical Equipment].

PubMed

Zhang, Xu; Xu, Honglei; Huang, Yanhong; Peng, Xiaolong

2015-09-01

Compared with the recycle of post-consumer medical equipments in medical institutions, the treatment of post-consumer home medical equipments (HME) should be consummated in the field of academic research, policy and regulatory plus corresponding supporting industries. The HME industry situation and its classification, main components and properties are reviewed in this paper. The merits and demerits of various pollution control techniques in the recycle of post-consumer medical equipments are analysed. For instance, the source control techniques to improve the property of raw materials, the end treatment technique to recycle the HME and regenerate energy are also discussed. Further, the development prospect of pollution control technique in the recycle of HME and the challenges must face up to are also probed.

[Heat and moisture exchangers for conditioning of inspired air of intubated patients in intensive care. The humidification properties of passive air exchangers under clinical conditions].

PubMed

Rathgeber, J; Züchner, K; Kietzmann, D; Weyland, W

1995-04-01

Heat and moisture exchangers (HME) are used as artificial noses for intubated patients to prevent tracheo-bronchial or pulmonary damage resulting from dry and cold inspired gases. HME are mounted directly on the tracheal tube, where they collect a large fraction of the heat and moisture of the expired air, adding this to the subsequent inspired breath. The effective performance depends on the water-retention capacity of the HME: the amount of water added to the inspired gas cannot exceed the stored water uptake of the previous breath. This study evaluates the efficiency of four different HME under laboratory and clinical conditions using a new moisture-measuring device. METHODS. In a first step, the absolute efficiency of four different HME (DAR Hygrobac, Gibeck Humid-Vent 2P, Pall BB 22-15 T, and Pall BB 100) was evaluated using a lung model simulating physiological heat and humidity conditions of the upper airways. The model was ventilated with tidal volumes of 500, 1,000, and 1,500 ml and different flow rates. The water content of the ventilated air was determined between tracheal tube and HME using a new high-resolution humidity meter and compared with the absolute water loss of the exhaled air at the gas outlet of a Siemens Servo C ventilator measured with a dew-point hygrometer. Secondly, the moisturizing efficiency was evaluated under clinical conditions in an intensive care unit with 25 intubated patients. Maintaining the ventilatory conditions for each patient, the HME were randomly changed. The humidity data were determined as described above and compared with the laboratory findings. RESULTS AND DISCUSSION. The water content at the respirator outlet is inversely equivalent to the humidity of the inspired gases and represents the water loss from the respiratory tract if the patient is ventilated with dry gases. Moisture retention and heating capacity decreased with higher volumes and higher flow rates. These data are simple to obtain without affecting the patient and can easily be interpreted. It was demonstrated that, compared to physiological conditions, the DAR Hygrobac and Gibeck Humid Vent 2P-HME coated with hygroscopic salts-were able to maintain sufficient inspiratory humidity and heat. The Pall-HME, solely a condensation humidifier, did not meet the physiological requirements.

The effect of heat and moisture exchanger and gas flow on humidity and temperature in a circle anaesthetic system.

PubMed

Poopalalingam, R; Goh, M H; Chan, Y W

2002-11-01

The aim of the study was to measure the humidity and temperature of the inspired gas in a circle absorber system at fresh gas flows of 11/min and 31/min and assess the need of a heat and moisture exchanger (HME). This prospective randomised controlled study received the Hospital Ethics Committee approval and informed consent. Forty adult ASA 1 and 11 patients were randomised into four groups to receive with or without HME fresh gas flow of 1L/min or 3L/min. Temperature and the relative humidity readings were taken at the start and every 10 minutes for the first hour of anaesthesia. There was a significantly higher relative humidity, absolute humidity and temperatures of the inspired gases at fresh gas flow of 1L/min and 3L/min with a HME compared to 3L/min without HME. Patients receiving fresh gas flows of lL/min had higher relative and absolute humidity than patients with fresh gas flows of 3L/min. However, the addition of the HME improved the absolute and relative humidity of the inspired gas in patients receiving fresh gas flow of 3l/min to a comparable level. However, the addition of a HME to a fresh gas flow of 1L/min did not significantly improve the humidity of the inspired gas. This suggests that the inherent humidifying property of the circle system at low fresh gas flow of 1L/min was sufficient in short surgeries lasting less than one hour and that the addition of a HME may not be necessary.

Rare Earth Arylsilazido Compounds with Inequivalent Secondary Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boteju, Kasuni Chathurika; Wan, Suchen; Venkatesh, Amrit

Here, a new bulky silazido ligand, –N(SiHMe 2)Dipp (Dipp = C 6H 3-2,6- iPr 2) supports planar, three-coordinate homoleptic rare earth complexes Ln{N(SiHMe 2)Dipp} 3 (Ln = Sc, Y, Lu) that each contain three secondary Ln←HSi interactions and one agostic CH bond. Y{N(SiHMe 2)Dipp} 3 and acetophenone react via hydrosilylation, rather than by insertion into the Y–N bond or enolate formation.

Rare Earth Arylsilazido Compounds with Inequivalent Secondary Interactions

DOE PAGES

Boteju, Kasuni Chathurika; Wan, Suchen; Venkatesh, Amrit; ...

2018-06-05

Here, a new bulky silazido ligand, –N(SiHMe 2)Dipp (Dipp = C 6H 3-2,6- iPr 2) supports planar, three-coordinate homoleptic rare earth complexes Ln{N(SiHMe 2)Dipp} 3 (Ln = Sc, Y, Lu) that each contain three secondary Ln←HSi interactions and one agostic CH bond. Y{N(SiHMe 2)Dipp} 3 and acetophenone react via hydrosilylation, rather than by insertion into the Y–N bond or enolate formation.

Randomized controlled trial on postoperative pulmonary humidification after total laryngectomy: external humidifier versus heat and moisture exchanger.

PubMed

Mérol, Jean-Claude; Charpiot, Anne; Langagne, Thibault; Hémar, Patrick; Ackerstaff, Annemieke H; Hilgers, Frans J M

2012-02-01

Assessment of immediate postoperative airway humidification after total laryngectomy (TLE), comparing the use of an external humidifier (EH) with humidification through a heat and moisture exchanger (HME). Randomized controlled trial (RCT). Fifty-three patients were randomized into the standard (control) EH (N = 26) or the experimental HME arm (N = 27). Compliance, pulmonary and sleeping problems, patients' and nursing staff satisfaction, nursing time, and cost-effectiveness were assessed with trial-specific structured questionnaires and tally sheets. In the EH arm data were available for all patients, whereas in the HME arm data were incomplete for four patients. The 24/7 compliance rate in the EH arm was 12% and in the HME arm 87% (77% if the four nonevaluable patients are considered noncompliant). Compliance and patients' satisfaction were significantly better, and the number of coughing episodes, mucus expectoration for clearing the trachea, and sleeping disturbances were significantly less in the HME arm (P < .001). This was also the case for nursing time and nursing staff satisfaction and preference. This RCT clearly shows the benefits of immediate postoperative airway humidification by means of an HME over the use of an EH after TLE. This study therefore underlines that HMEs presently can be considered the better option for early postoperative airway humidification after TLE. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Hot melt extrusion of ion-exchange resin for taste masking.

PubMed

Tan, David Cheng Thiam; Ong, Jeremy Jianming; Gokhale, Rajeev; Heng, Paul Wan Sia

2018-05-30

Taste masking is important for some unpleasant tasting bioactives in oral dosage forms. Among many methods available for taste-masking, use of ion-exchange resin (IER) holds promise. IER combined with hot melt extrusion (HME) may offer additional advantages over solvent methods. IER provides taste masking by complexing with the drug ions and preventing drug dissolution in the mouth. Drug-IER complexation approaches described in literatures are mainly based either on batch processing or column eluting. These methods of drug-IER complexation have obvious limitations such as high solvent volume requirements, multiprocessing steps and extended processing time. Thus, the objective of this study was to develop a single-step, solvent-free, continuous HME process for complexation of drug-IER. The screening study evaluated drug to IER ratio, types of IER and drug complexation methods. In the screening study, a potassium salt of a weakly acidic carboxylate-based cationic IER was found suitable for the HME method. Thereafter, optimization study was conducted by varying HME process parameters such as screw speed, extrusion temperature and drug to IER ratio. It was observed that extrusion temperature and drug to IER ratio are imperative in drug-IER complexation through HME. In summary, this study has established the feasibility of a continuous complexation method for drug to IER using HME for taste masking. Copyright © 2018 Elsevier B.V. All rights reserved.

Process monitoring and visualization solutions for hot-melt extrusion: a review.

PubMed

Saerens, Lien; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

2014-02-01

Hot-melt extrusion (HME) is applied as a continuous pharmaceutical manufacturing process for the production of a variety of dosage forms and formulations. To ensure the continuity of this process, the quality of the extrudates must be assessed continuously during manufacturing. The objective of this review is to provide an overview and evaluation of the available process analytical techniques which can be applied in hot-melt extrusion. Pharmaceutical extruders are equipped with traditional (univariate) process monitoring tools, observing barrel and die temperatures, throughput, screw speed, torque, drive amperage, melt pressure and melt temperature. The relevance of several spectroscopic process analytical techniques for monitoring and control of pharmaceutical HME has been explored recently. Nevertheless, many other sensors visualizing HME and measuring diverse critical product and process parameters with potential use in pharmaceutical extrusion are available, and were thoroughly studied in polymer extrusion. The implementation of process analytical tools in HME serves two purposes: (1) improving process understanding by monitoring and visualizing the material behaviour and (2) monitoring and analysing critical product and process parameters for process control, allowing to maintain a desired process state and guaranteeing the quality of the end product. This review is the first to provide an evaluation of the process analytical tools applied for pharmaceutical HME monitoring and control, and discusses techniques that have been used in polymer extrusion having potential for monitoring and control of pharmaceutical HME. © 2013 Royal Pharmaceutical Society.

Application of hot melt extrusion for poorly water-soluble drugs: limitations, advances and future prospects.

PubMed

Lu, Ming; Guo, Zhefei; Li, Yongcheng; Pang, Huishi; Lin, Ling; Liu, Xu; Pan, Xin; Wu, Chuanbin

2014-01-01

Hot melt extrusion (HME) is a powerful technology to enhance the solubility and bioavailability of poorly water-soluble drugs by producing amorphous solid dispersions. Although the number of articles and patents about HME increased dramatically in the past twenty years, there are very few commercial products by far. The three main obstacles limiting the commercial application of HME are summarized as thermal degradation of heat-sensitive drugs at high process temperature, recrystallization of amorphous drugs during storage and dissolving process, and difficulty to obtain products with reproducible physicochemical properties. Many efforts have been taken in recent years to understand the basic mechanism underlying these obstacles and then to overcome them. This article reviewed and summarized the limitations, recent advances, and future prospects of HME.

Homoleptic organolanthanide compounds supported by the bis(dimethylsilyl)benzyl ligand

DOE PAGES

Boteju, Kasuni C.; Ellern, Arkady; Sadow, Aaron D.

2016-12-19

Here, a β-SiH functionalized benzyl anion [C(SiHMe 2) 2Ph]$-$s obtained by deprotonation of HC(SiHMe 2) 2Ph with KCH 2Ph or by reaction of KOtBu and (Me 2HSi) 3CPh; LnI 3(THF)n and three equivalents of this carbanion combine to provide homoleptic tris(alkyl)lanthanide compounds Ln{C(SiHMe 2) 2Ph} 3 (Ln = La, Ce, Pr, Nd) containing secondary metal–ligand interactions.

Design and Evaluation of Topical Diclofenac Sodium Gel Using Hot Melt Extrusion Technology as a Continuous Manufacturing Process with Kolliphor® P407.

PubMed

Pawar, Jaywant; Narkhede, Rajkiran; Amin, Purnima; Tawde, Vaishali

2017-08-01

The aim of the present context was to develop and evaluate a Kolliphor® P407-based transdermal gel formulation of diclofenac sodium by hot melt extrusion (HME) technology; central composite design was used to optimize the formulation process. In this study, we have explored first time ever HME as an industrially feasible and continuous manufacturing technology for the manufacturing of gel formulation using Kolliphor® P407 and Kollisolv® PEG400 as a gel base. Diclofenac sodium was used as a model drug. The HME parameters such as feeding rate, screw speed, and barrel temperature were crucial for the semisolid product development, and were optimized after preliminary trials. For the processing of the gel formulation by HME, a modified screw design was used to obtain a uniform product. The obtained product was evaluated for physicochemical characterization such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), pH measurement, rheology, surface tension, and texture profile analysis. Moreover, it was analyzed for general appearance, spreadibility, surface morphology, and drug content. The optimized gel formulation showed homogeneity and transparent film when applied on a glass slide under microscope, pH was 7.02 and uniform drug content of 100.04 ± 2.74 (SD = 3). The DSC and XRD analysis of the HME gel formulation showed complete melting of crystalline API into an amorphous form. The Kolliphor® P407 and Kollisolv® PEG400 formed excellent gel formulation using HME with consistent viscoelastic properties of the product. An improved drug release was found for the HME gel, which showed a 100% drug release than that of a marketed product which showed only 88% of drug release at the end of 12 h. The Flux value of the HME gel was 106 than that of a marketed formulation, which showed only about 60 value, inferring a significant difference (P < 0.05) at the end of 1 h. This study demonstrates a novel application of the hot melt extrusion process for manufacturing of topical semisolid products.

Poly(2-ethyl-2-oxazoline) as matrix excipient for drug formulation by hot melt extrusion and injection molding.

PubMed

Claeys, Bart; Vervaeck, Anouk; Vervaet, Chris; Remon, Jean Paul; Hoogenboom, Richard; De Geest, Bruno G

2012-10-15

Here we evaluate poly(2-ethyl-2-oxazoline)s (PEtOx) as a matrix excipient for the production of oral solid dosage forms by hot melt extrusion (HME) followed by injection molding (IM). Using metoprolol tartrate as a good water-soluble model drug we demonstrate that drug release can be delayed by HME/IM, with the release rate controlled by the molecular weight of the PEtOx. Using fenofibrate as a lipophilic model drug we demonstrate that relative to the pure drug the dissolution rate is strongly enhanced by formulation in HME/IM tablets. For both drug molecules we find that solid solutions, i.e. molecularly dissolved drug in a polymeric matrix, are obtained by HME/IM. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of heat and moisture exchangers on the prevention of ventilator-associated pneumonia in critically ill patients.

PubMed

Auxiliadora-Martins, M; Menegueti, M G; Nicolini, E A; Alkmim-Teixeira, G C; Bellissimo-Rodrigues, F; Martins-Filho, O A; Basile-Filho, A

2012-12-01

Ventilator-associated pneumonia (VAP) remains one of the major causes of infection in the intensive care unit (ICU) and is associated with the length of hospital stay, duration of mechanical ventilation, and use of broad-spectrum antibiotics. We compared the frequency of VAP 10 months prior to (pre-intervention group) and 13 months after (post-intervention group) initiation of the use of a heat and moisture exchanger (HME) filter. This is a study with prospective before-and-after design performed in the ICU in a tertiary university hospital. Three hundred and fourteen patients were admitted to the ICU under mechanical ventilation, 168 of whom were included in group HH (heated humidifier) and 146 in group HME. The frequency of VAP per 1000 ventilator-days was similar for both the HH and HME groups (18.7 vs 17.4, respectively; P = 0.97). Duration of mechanical ventilation (11 vs 12 days, respectively; P = 0.48) and length of ICU stay (11 vs 12 days, respectively; P = 0.39) did not differ between the HH and HME groups. The chance of developing VAP was higher in patients with a longer ICU stay and longer duration of mechanical ventilation. This finding was similar when adjusted for the use of HME. The use of HME in intensive care did not reduce the incidence of VAP, the duration of mechanical ventilation, or the length of stay in the ICU in the study population.

Effect of heat and moisture exchangers on the prevention of ventilator-associated pneumonia in critically ill patients

PubMed Central

Auxiliadora-Martins, M.; Menegueti, M.G.; Nicolini, E.A.; Alkmim-Teixeira, G.C.; Bellissimo-Rodrigues, F.; Martins-Filho, O.A.; Basile-Filho, A.

2012-01-01

Ventilator-associated pneumonia (VAP) remains one of the major causes of infection in the intensive care unit (ICU) and is associated with the length of hospital stay, duration of mechanical ventilation, and use of broad-spectrum antibiotics. We compared the frequency of VAP 10 months prior to (pre-intervention group) and 13 months after (post-intervention group) initiation of the use of a heat and moisture exchanger (HME) filter. This is a study with prospective before-and-after design performed in the ICU in a tertiary university hospital. Three hundred and fourteen patients were admitted to the ICU under mechanical ventilation, 168 of whom were included in group HH (heated humidifier) and 146 in group HME. The frequency of VAP per 1000 ventilator-days was similar for both the HH and HME groups (18.7 vs 17.4, respectively; P = 0.97). Duration of mechanical ventilation (11 vs 12 days, respectively; P = 0.48) and length of ICU stay (11 vs 12 days, respectively; P = 0.39) did not differ between the HH and HME groups. The chance of developing VAP was higher in patients with a longer ICU stay and longer duration of mechanical ventilation. This finding was similar when adjusted for the use of HME. The use of HME in intensive care did not reduce the incidence of VAP, the duration of mechanical ventilation, or the length of stay in the ICU in the study population. PMID:23044627

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.

PubMed

Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

2016-02-01

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

Heat and moisture exchanger use reduces in-hospital complications following total laryngectomy: a case-control study.

PubMed

Foreman, A; De Santis, R J; Sultanov, F; Enepekides, D J; Higgins, K M

2016-07-07

Total laryngectomy (TL) is an appropriate oncologic operation for many patients with laryngeal cancer delivering excellent oncologic outcomes, however it remains beset with significant functional consequences. Following TL, the upper and lower airways are permanently disconnected, which causes unfiltered, cold air with reduced humidity to enter the tracheobronchial tree, resulting in mucus overproduction and an increase in the viscosity of the mucus. In response to this, Heat and moisture exchangers were developed to compensate for the lost functions of the upper respiratory tract and their effect on the patients' respiratory performance in addition to their quality of life. The case records of 48 patients undergoing total laryngectomy were reviewed and data concerning demographics, surgical details, post-operative care requirements and adverse events was retrieved. Post hoc analysis of the case patients was undertaken to identify any benefit of using a heat and moisture exchanger (HME) system with particular reference to post-operative respiratory outcomes. There was no significant difference between case and control subjects based on demographics, extent of surgery or need for flap repair. 16 patients had used a HME and 32 patients had used external humidification (EH). Of those experiencing mucous plugging, only 3/24 (12.5 %) had used a HME system, in contrast to 21/24 (87.5 %) who used EH (Chi square = 9.375, p = 0.002). The odds ratio of having an adverse event if not using HME was 8.27 (CI = 1.94 - 35.71). Use of HME also significantly reduced the number of days requiring physiotherapy (1.75 days vs. 3.20 days, p = 0.034). Use of an HME system can reduce in-hospital complications, in particular episodes of mucus plugging, and post-operative care requirements. Furthermore, there is a cost benefit to using HME systems that warrants more widespread introduction of these devices in head and neck surgery centers.

Evaluation of resistance in 8 different heat-and-moisture exchangers: effects of saturation and flow rate/profile.

PubMed

Lucato, Jeanette Janaina Jaber; Tucci, Mauro Roberto; Schettino, Guilherme Paula Pinto; Adams, Alexander B; Fu, Carolina; Forti, Germano; de Carvalho, Carlos Roberto Ribeiro; de Souza, Rogério

2005-05-01

When endotracheal intubation is required during ventilatory support, the physiologic mechanisms of heating and humidifying the inspired air related to the upper airways are bypassed. The task of conditioning the air can be partially accomplished by heat-and-moisture exchangers (HMEs). To evaluate and compare with respect to imposed resistance, different types/models of HME: (1) dry versus saturated, (2) changing inspiratory flow rates. Eight different HMEs were studied using a lung model system. The study was conducted initially by simulating spontaneous breathing, followed by connecting the system directly to a mechanical ventilator to provide pressure-support ventilation. None of the encountered values of resistance (0.5\\N3.6 cm H(2)O/L/s) exceeded the limits stipulated by the previously described international standard for HMEs (International Standards Organization Draft International Standard 9360-2) (not to exceed 5.0 cm H(2)O with a flow of 1.0 L/s, even when saturated). The hygroscopic HME had less resistance than other types, independent of the precondition status (dry or saturated) or the respiratory mode. The hygroscopic HME also had a lesser increase in resistance when saturated. The resistance of the HME was little affected by increases in flow, but saturation did increase resistance in the hydrophobic and hygroscopic/hydrophobic HME to levels that could be important at some clinical conditions. Resistance was little affected by saturation in hygroscopic models, when compared to the hydrophobic or hygroscopic/hydrophobic HME. Changes in inspiratory flow did not cause relevant alterations in resistance.

Investigation of the interactions of enteric and hydrophilic polymers to enhance dissolution of griseofulvin following hot melt extrusion processing.

PubMed

Bennett, Ryan C; Keen, Justin M; Bi, Yunxia Vivian; Porter, Stuart; Dürig, Thomas; McGinity, James W

2015-07-01

This study focuses on the application of hot melt extrusion (HME) to produce solid dispersions containing griseofulvin (GF) and investigates the in-vitro dissolution performance of HME powders and resulting tablet compositions containing HME-processed dispersions. Binary, ternary and quaternary dispersions containing GF, enteric polymer (Eudragit L100-55 or AQOAT-LF) and/or vinyl pyrrolidone-based polymer (Plasdone K-12 povidone or S-630 copovidone) were processed by HME. Two plasticizers, triethyl citrate (TEC) and acetyl tributyl citrate (ATBC), were incorporated to aid in melt processing and to modify release of GF in neutral media following a pH-change in dissolution. Products were characterized for GF recovery, degrees of compositional amorphous character, intermolecular interactions and non-sink dissolution performance. Binary dispersions exhibited lower maximum observed concentration values and magnitudes of supersaturated GF in neutral media dissolution in comparison with the ternary dispersions. The quaternary HME products, 1 : 2 : 1 : 0.6 GF : L100-55 : S-630 : ATBC and GF : AQOAT-LF : K-12 : ATBC, were determined as the most optimal concentration-enhancing compositions due to increased hydrogen bonding of enteric functional groups with carbonyl/acetate groups of vinyl pyrrolidone-based polymers, reduced compositional crystallinity and presence of incorporated hydrophobic plasticizer. HME products containing combinations of concentration-enhancing polymers can supersaturate and sustain GF dissolution to greater magnitudes in neutral media following the pH-transition and be compressed into immediate-release tablets exhibiting similar dissolution profiles. © 2015 Royal Pharmaceutical Society.

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions.

PubMed

LaFountaine, Justin S; Prasad, Leena Kumari; Brough, Chris; Miller, Dave A; McGinity, James W; Williams, Robert O

2016-02-01

Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.

Bilateral external ear canal osteomas - discussion on a clinical case.

PubMed

Gheorghe, D C; Stanciu, A E; Ulici, A; Zamfir-Chiru-Anton, A

2016-01-01

Osteomas of the external ear are uncommon benign tumors that need to be differentiated from the external ear canal exostoses, bony proliferations that are linked mainly to cold-water exposure. Clinical manifestations vary from no symptoms to recurrent local infections and external ear cholesteatoma. Objective: presenting a rare case that we did not find described in the published literature. A patient with multiple long-term asymptomatic osteomas of both external ear canals presented to our department. Material: Data recorded from the patient's medical record was reviewed and analyzed. Surgery was performed and histology confirmed the presumptive diagnosis. Results: There was a discrepancy between the local severity of the disease, with a complete obstruction of his ear canals, and the long-term disease-free status of the patient. Conclusion: We hypothesized about the etiology of these multiple bilateral osteomas of the EAC, in light of the clinical and surgical findings.

The Langer-Giedion syndrome: Molecular dissection of a contiguous gene syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luedecke, H.J.; Pillo, B.L.; Nardmann, J.

The tricho-rhino-phalangeal syndromes TRPS I and II, which are characterized by craniofacial dysmorphism and skeletal abnormalities, are caused by genetic defects in 8q24.1. The presence of multiple exostoses (EXT) distinguishes TRPS II (Langer-Giedion syndrome, LGS) from TRPS I. Multiple exostoses also occur as an autosomal dominant trait displaying genetic heterogeneity. One of the EXT loci maps to 8q24.1. Previously, we had determined a probe order (cen-D8S50-D8S98-D8S51-D8S67-D8S43-tel) for the Langer-Giedion syndrome chromosome region. The shortest region of deletion overlap in LGS patients is defined by D8S51 and D8S67. Interestingly, a patient with TRPS I and a large deletion was found tomore » be intact for these two loci, but deleted for more proximal loci. We have now constructed a complete yeast artificial chromosome (YAC) contig for the entire LGCR. Some of these YACs were used to perform fluorescence in situ hybridization analyses in patients with chromosomal abnormalities associated with TRPS I, TRPS II and EXT. One YAC containing D8S98 spans the translocation breakpoint in a patient with TRPS I and (8;18)(q24.11;q13.3;q21.13). The translocation breakpoint in a patient with TRPS II and t(4;8)(p15.3;q24.1) is covered by a D8S67 YAC. Interestingly, this YAC also spans the inversion breakpoint in a patient with EXT and inv(8)(p23;q24.1). The data indicate that most of the putative TRPS I gene is located between D8S98 and D8S51, that the putative EXT gene maps to D8S67, and that both genes are 1.5 Mbp apart. We are currently analyzing putative gene sequences in the vicinity of the chromosomal breakpoints.« less

Of Brain and Bone: The Unusual Case of Dr. A

PubMed Central

Narvid, J; Gorno-Tempini, ML; Slavotinek, A; DeArmond, SJ; Cha, YH; Miller, BL; Rankin, K.P

2009-01-01

Frontotemporal dementia (FTD) is a clinical syndrome characterized by progressive decline in social conduct and a focal pattern of frontal and temporal lobe damage. Its biological basis is still poorly understood but the focality of the brain degeneration provides a powerful model to study the cognitive and anatomical basis of social cognition. Here, we present Dr. A, a patient with a rare hereditary bone disease (hereditary multiple exostoses) and FTD (pathologically characterized as Pick’s disease), who presented with a profound behavioral disturbance characterized by acquired sociopathy. We conducted a detailed genetic, pathological, neuroimaging and cognitive study, including a battery of tests designed to investigate Dr. A’s abilities to understand emotional cues and to infer mental states and intentions to others (theory of mind). Dr. A’s genetic profile suggests the possibility that a mutation causing hereditary multiple exostoses, Ext2, may play a role in the pattern of neurodegeneration in frontotemporal dementia since knockout mice deficient in the Ext gene family member, Ext1, show severe CNS defects including loss of olfactory bulbs and abnormally small cerebral cortex. Dr. A showed significant impairment in emotion comprehension, second order theory of mind, attribution of intentions, and empathy despite preserved general cognitive abilities. Voxel-based morphometry on structural MRI images showed significant atrophy in the medial and right orbital frontal and anterior temporal regions with sparing of dorsolateral frontal cortex. This case demonstrates that social and emotional dysfunction in FTD can dissociate from preserved performance on classic executive functioning tasks. The specific pattern of anatomical damage shown by VBM emphasizes the importance of the network including the superior medial frontal gyrus as well as temporal polar areas, in regulation of social cognition and theory of mind. This case provides new evidence regarding the neural basis of social cognition and suggests a possible genetic link between bone disease and FTD. PMID:20183548

Hierarchical mixture of experts and diagnostic modeling approach to reduce hydrologic model structural uncertainty: STRUCTURAL UNCERTAINTY DIAGNOSTICS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moges, Edom; Demissie, Yonas; Li, Hong-Yi

2016-04-01

In most water resources applications, a single model structure might be inadequate to capture the dynamic multi-scale interactions among different hydrological processes. Calibrating single models for dynamic catchments, where multiple dominant processes exist, can result in displacement of errors from structure to parameters, which in turn leads to over-correction and biased predictions. An alternative to a single model structure is to develop local expert structures that are effective in representing the dominant components of the hydrologic process and adaptively integrate them based on an indicator variable. In this study, the Hierarchical Mixture of Experts (HME) framework is applied to integratemore » expert model structures representing the different components of the hydrologic process. Various signature diagnostic analyses are used to assess the presence of multiple dominant processes and the adequacy of a single model, as well as to identify the structures of the expert models. The approaches are applied for two distinct catchments, the Guadalupe River (Texas) and the French Broad River (North Carolina) from the Model Parameter Estimation Experiment (MOPEX), using different structures of the HBV model. The results show that the HME approach has a better performance over the single model for the Guadalupe catchment, where multiple dominant processes are witnessed through diagnostic measures. Whereas, the diagnostics and aggregated performance measures prove that French Broad has a homogeneous catchment response, making the single model adequate to capture the response.« less

Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression.

PubMed

Avgerinos, Theodoros; Kantiranis, Nikolaos; Panagopoulou, Athanasia; Malamataris, Stavros; Kachrimanis, Kyriakos; Nikolakakis, Ioannis

2018-02-01

Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release. Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit ® RSPO the matrix former and citric acid or Lutrol ® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer's type and content on the extrusion pressure (P e ) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters. Resistance to extrusion and tablet ejection force were reduced by Lutrol ® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P e correlated with T and resistance to deformation of the corresponding pellets (r 2  = 0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r 2  = 0.990) and for HME the diffusion coefficient (D e ) and retreat rate constant (k b ) decreased linearly with T (r 2  = 0.934 and 0.972). Lutrol ® F127 and citric acid are efficient plasticizers and Lutrol ® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.

The temperature and humidity in a low-flow anesthesia workstation with and without a heat and moisture exchanger.

PubMed

de Castro, Jair; Bolfi, Fernanda; de Carvalho, Lidia R; Braz, Jose R C

2011-09-01

The Dräger Primus anesthesia workstation has a built-in hotplate to heat the patient's exhaled gas. The fresh gas flow is mixed with the heated exhaled gas as they pass through the soda lime canister. A heat and moisture exchanger (HME) may also be used to further heat and humidify the inhaled gas. In this study we measured the temperature and humidity of the inhaled gas coming from the Dräger Primus with or without a HME. Thirty female patients were randomly divided into 2 groups and their lungs ventilated by the Primus Dräger anesthesia workstation with or without a HME. The humidity and temperature of the inhaled gas were measured 15, 30, 60, 90, and 120 minutes after connecting the patient to the breathing circuit. After 120 minutes of ventilation with a low-flow breathing circuit, the temperatures of inhaled gas were 25°C ± 1°C and 30°C ± 2°C without and with HME, respectively, with a statistically significant difference between groups (P < 0.001) with 95% confidence interval (CI) of 3.80°C to 6.40°C; and the absolute humidity values of the inhaled gas were 20.5 ± 3.6 mgH(2)O · L(-1) and 30 ± 2 mgH(2)O · L(-1) without and with HME, respectively, with a statistically significant difference between groups (P < 0.001) with 95% CI of 7.37°C to 13.03°C. The Primus anesthesia workstation partially humidifies the inspired gas when a low fresh gas flow is used. Insertion of an HME increases the humidity in inhaled gas, bringing it close to physiological values.

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.

PubMed

Agrawal, Anjali; Dudhedia, Mayur; Deng, Weibin; Shepard, Kevin; Zhong, Li; Povilaitis, Edward; Zimny, Ewa

2016-02-01

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

Dissolution enhancement of a drug exhibiting thermal and acidic decomposition characteristics by fusion processing: a comparative study of hot melt extrusion and KinetiSol dispersing.

PubMed

Hughey, Justin R; DiNunzio, James C; Bennett, Ryan C; Brough, Chris; Miller, Dave A; Ma, Hua; Williams, Robert O; McGinity, James W

2010-06-01

In this study, hot melt extrusion (HME) and KinetiSol Dispersing (KSD) were utilized to prepare dissolution-enhanced solid dispersions of Roche Research Compound A (ROA), a BCS class II drug. Preformulation characterization studies showed that ROA was chemically unstable at elevated temperatures and acidic pH values. Eudragit L100-55 and AQOAT LF (HPMCAS) were evaluated as carrier polymers. Dispersions were characterized for ROA recovery, crystallinity, homogeneity, and non-sink dissolution. Eudragit L100-55 dispersions prepared by HME required the use of micronized ROA and reduced residence times in order to become substantially amorphous. Compositions containing HPMCAS were also prepared by HME, but an amorphous dispersion could not be obtained. All HME compositions contained ROA-related impurities. KSD was investigated as a method to reduce the decomposition of ROA while rendering compositions amorphous. Substantially amorphous, plasticizer free compositions were processed successfully by KSD with significantly higher ROA recovery values and amorphous character than those achieved by HME. A near-infrared chemical imaging analysis was conducted on the solid dispersions as a measure of homogeneity. A statistical analysis showed similar levels of homogeneity in compositions containing Eudragit L100-55, while differences were observed in those containing HMPCAS. Non-sink dissolution analysis of all compositions showed rapid supersaturation after pH adjustment to approximately two to three times the equilibrium solubility of ROA, which was maintained for at least 24 h. The results of the study demonstrated that KSD is an effective method of forming dissolution-enhanced amorphous solid solutions in cases where HME is not a feasible technique.

Long-term use of heat and moisture exchangers among laryngectomees: medical, social, and psychological patterns.

PubMed

Brook, Itzhak; Bogaardt, Hans; van As-Brooks, Corina

2013-06-01

After laryngectomy, pulmonary protection is mostly acquired by means of a heat and moisture exchanger (HME) that is placed on an airtight seal around the stoma. The effects of HMEs on the tracheal climate have been well described, and the filtration effect of an HME with an electrostatic filter has been described in vitro. The effects of HME use in patients have been documented in several trials in different countries. The follow-up time of the patients in these trials, however, is limited. Less is known about long-term use of HMEs, and studies describing long-term compliance with HME use are scarce. This study investigated the long-term use of HMEs in laryngectomees. Questionnaires were sent to 195 laryngectomees, and 75 questionnaires were returned. More than 85% of the respondents used an HME, of whom 77% were compliant users (ie, use for more than 20 hours per day). The incidence of pulmonary illnesses (either before or after surgery) was about 25%. More than 90% of the respondents were heavy smokers before laryngectomy. One third of the respondents are regularly exposed to dusty environments. Compliant HME users tend to make less use of external humidifiers and vaporizers, and have better pulmonary status and lower health-care costs. Regarding quality of life, patients who use a FreeHands device tended to have more frequent social contacts (r = 0.251; p = 0.030). The prevalence of depression is high, pointing to an urgent need to recognize and treat psychiatric problems such as depression and suicidal ideation in this patient group. These findings have implications for any postlaryngectomy research that uses pulmonary parameters.

49 CFR 1572.9 - Applicant information required for HME security threat assessment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... threat assessment. 1572.9 Section 1572.9 Transportation Other Regulations Relating to Transportation... TRANSPORTATION SECURITY CREDENTIALING AND SECURITY THREAT ASSESSMENTS Procedures and General Standards § 1572.9 Applicant information required for HME security threat assessment. An applicant must supply the information...

APPLICATIONS OF HOT-MELT EXTRUSION FOR DRUG DELIVERY

PubMed Central

Repka, Michael A.; Majumdar, Soumyajit; Battu, Sunil Kumar; Srirangam, Ramesh; Upadhye, Sampada B.

2018-01-01

In today’s pharmaceutical arena, it is estimated that more than 40% of new chemical entities produced during drug discovery efforts exhibit poor solubility characteristics. However, over the last decade hot-melt extrusion (HME) has emerged as a powerful processing technology for drug delivery and has opened the door to a host of such molecules previously considered unviable as drugs. HME is considered to be an efficient technique in developing solid molecular dispersions and has been demonstrated to provide sustained, modified and targeted drug delivery resulting in improved bioavailability. This article reviews the myriad of HME applications for pharmaceutical dosage forms such as tablets, capsules, films and implants for drug delivery through oral, transdermal, transmucosal, transungual, as well as other routes of administration. Interest in HME as a pharmaceutical process continues to grow and the potential of automation and reduction of capital investment and labor costs have made this technique worthy of consideration as a drug delivery solution. PMID:19040397

Postfunctionalization of periodic mesoporous silica SBA-1 with magnesium(II) and iron(II) silylamides.

PubMed

Deschner, Thomas; Klimpel, Michael; Tafipolsky, Maxim; Scherer, Wolfgang; Törnroos, Karl W; Anwander, Reiner

2012-06-28

Magnesium silylamide complexes Mg[N(SiHMe(2))(2)](2)(THF)(2) and Mg[N(SiPhMe(2))(2)](2) were synthesized according to transsilylamination and alkane elimination protocols, respectively, utilizing Mg[N(SiMe(3))(2)](2)(THF)(2) and [Mg(n-Bu)](2) as precursors. Cage-like periodic mesoporous silica SBA-1 was treated with donor solvent-free dimeric [Mg{N(SiHMe(2))(2)}(2)](2), [Mg{N(SiMe(3))(2)}(2)](2) and monomeric Mg[N(SiPhMe(2))(2)](2), producing hybrid materials [Mg(NR(2))(2)]@SBA-1 with magnesium located mainly at the external surface. Consecutive grafting of [Mg{N(SiHMe(2))(2)}(2)](2) and [Fe(II){N(SiHMe(2))(2)}(2)](2) onto SBA-1 led to heterobimetallic hybrid materials which exhibit complete consumption of the isolated surface silanol groups, evidencing intra-cage surface functionalization. All materials were characterized by DRIFT spectroscopy, nitrogen physisorption and elemental analysis.

Effectiveness of heat and moisture exchangers in preventing ventilator-associated pneumonia in critically ill patients: a meta-analysis.

PubMed

Menegueti, Mayra Gonçalves; Auxiliadora-Martins, Maria; Nunes, Altacílio Aparecido

2014-01-01

Patients may acquire ventilator-associated pneumonia (VAP) by aspirating the condensate that originates in the ventilator circuit upon use of a conventional humidifier. The bacteria that colonize the patients themselves can proliferate in the condensate and then return to the airways and lungs when the patient aspirates this contaminated material. Therefore, the use of HME might contribute to preventing pneumonia and lowering the VAP incidence. The aim of this study was to evaluate how the use of HME impacts the probability of VAP occurrence in critically ill patients. On the basis of the acronym "PICO" (Patient, Intervention, Comparison, Outcome), the question that guided this review was "Do critically ill patients under invasive mechanical ventilation present lower VAP incidence when they use HME as compared with HH?". Two of the authors of this review searched the databases PUBMED/Medline, The Cochrane Library, and Latin-American and Caribbean Literature in Health Sciences, LILACS independently; they used the following keywords: "heat and moisture exchanger", AND "heated humidifier", AND "ventilator-associated pneumonia prevention". This review included papers in the English language published from January 1990 to December 2012. This review included ten studies. Comparison between the use of HME and HH did not reveal any differences in terms of VAP occurrence (OR = 0.998; 95% CI: 0.778-1.281). Together, the ten studies corresponded to a total sample of 1077 and 953 patients in the HME and HH groups, respectively; heterogeneity among the investigations was low (I(2) < 50%). Information about the outcome mortality was available in only eight of the ten studies. The use of HME and HH did not afford different results in terms of mortality (OR = 1.09; 95% CI: 0.864-1.376). The total sample size was 884 and 762 patients, respectively. Heterogeneity among the studies was low (I(2) = 0.0%). Current meta-analysis was not sufficient to definitely exclude an associate between heat and moisture exchangers and VAP. Despite the methodological limitations found in selected clinical trials, the current meta-analysis suggests that HME does not decrease VAP incidence or mortality in critically ill patients.

Hot Melt Extrudates Formulated Using Design Space: One Simple Process for Both Palatability and Dissolution Rate Improvement.

PubMed

Malaquias, Lorena F B; Schulte, Heidi L; Chaker, Juliano A; Karan, Kapish; Durig, Thomas; Marreto, Ricardo N; Gratieri, Tais; Gelfuso, Guilherme M; Cunha-Filho, Marcilio

2018-01-01

This work aimed at obtaining an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone ® (poly(1-vinylpyrrolidone-co-vinyl acetate) [PVP/VA]), Klucel ® ELF (2-hydroxypropyl ether cellulose [HPC]), and Soluplus ® (SOL, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an e-tongue. All materials became homogeneous and dense after HME processing. Thermal and structural analyses demonstrated drug amorphization, whereas IR spectroscopy evidenced drug stability and drug-excipient interactions in HME systems. Extrudates presented a significant increase in dissolution rate compared to ITZ raw material, mainly with formulations containing PVP/VA and HPC. A pronounced improvement in taste masking was also identified for HME systems, especially in those containing higher amounts of SOL and HPC. Data showed polymers act synergistically favoring formulation functional properties. Predicted best formulation should contain ITZ 25.0%, SOL 33.2%, HPC 28.9%, and PVP/VA 12.9% (w/w). Optimized response considering dissolution rate and palatability reinforces the benefit of polymer combinations. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Implementation of transmission NIR as a PAT tool for monitoring drug transformation during HME processing.

PubMed

Islam, Muhammad T; Scoutaris, Nikolaos; Maniruzzaman, Mohammed; Moradiya, Hiren G; Halsey, Sheelagh A; Bradley, Michael S A; Chowdhry, Babur Z; Snowden, Martin J; Douroumis, Dennis

2015-10-01

The aim of the work reported herein was to implement process analytical technology (PAT) tools during hot melt extrusion (HME) in order to obtain a better understanding of the relationship between HME processing parameters and the extruded formulations. For the first time two in-line NIR probes (transmission and reflectance) have been coupled with HME to monitor the extrusion of the water insoluble drug indomethacin (IND) in the presence of Soluplus (SOL) or Kollidon VA64 hydrophilic polymers. In-line extrusion monitoring of sheets, produced via a specially designed die, was conducted at various drug/polymer ratios and processing parameters. Characterisation of the extruded transparent sheets was also undertaken by using DSC, XRPD and Raman mapping. Analysis of the experimental findings revealed the production of molecular solutions where IND is homogeneously blended (ascertained by Raman mapping) in the polymer matrices, as it acts as a plasticizer for both hydrophilic polymers. PCA analysis of the recorded NIR signals showed that the screw speed used in HME affects the recorded spectra but not the homogeneity of the embedded drug in the polymer sheets. The IND/VA64 and IND/SOL extruded sheets displayed rapid dissolution rates with 80% and 30% of the IND being released, respectively within the first 20min. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process.

PubMed

Puri, Vibha; Brancazio, Dave; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Myerson, Allan S; Trout, Bernhardt L

2017-11-01

The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

External auditory exostoses and hearing loss in the Shanidar 1 Neandertal

PubMed Central

2017-01-01

The Late Pleistocene Shanidar 1 older adult male Neandertal is known for the crushing fracture of his left orbit with a probable reduction in vision, the loss of his right forearm and hand, and evidence of an abnormal gait, as well as probable diffuse idiopathic skeletal hyperostosis. He also exhibits advanced external auditory exostoses in his left auditory meatus and larger ones with complete bridging across the porus in the right meatus (both Grade 3). These growths indicate at least unilateral conductive hearing (CHL) loss, a serious sensory deprivation for a Pleistocene hunter-gatherer. This condition joins the meatal atresia of the Middle Pleistocene Atapuerca-SH Cr.4 in providing evidence of survival with conductive hearing loss (and hence serious sensory deprivation) among these Pleistocene humans. The presence of CHL in these fossils thereby reinforces the paleobiological and archeological evidence for supporting social matrices among these Pleistocene foraging peoples. PMID:29053746

49 CFR 1572.15 - Procedures for HME security threat assessment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... completes includes a fingerprint-based criminal history records check (CHRC), an intelligence-related background check, and a final disposition. (b) Fingerprint-based check. In order to conduct a fingerprint... before the date of the expiration of the HME. (2) Where the State elects to collect fingerprints and...

49 CFR 1572.15 - Procedures for HME security threat assessment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... completes includes a fingerprint-based criminal history records check (CHRC), an intelligence-related background check, and a final disposition. (b) Fingerprint-based check. In order to conduct a fingerprint... before the date of the expiration of the HME. (2) Where the State elects to collect fingerprints and...

49 CFR 1572.15 - Procedures for HME security threat assessment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... completes includes a fingerprint-based criminal history records check (CHRC), an intelligence-related background check, and a final disposition. (b) Fingerprint-based check. In order to conduct a fingerprint... before the date of the expiration of the HME. (2) Where the State elects to collect fingerprints and...

49 CFR 1572.15 - Procedures for HME security threat assessment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... completes includes a fingerprint-based criminal history records check (CHRC), an intelligence-related background check, and a final disposition. (b) Fingerprint-based check. In order to conduct a fingerprint... before the date of the expiration of the HME. (2) Where the State elects to collect fingerprints and...

49 CFR 1572.15 - Procedures for HME security threat assessment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... completes includes a fingerprint-based criminal history records check (CHRC), an intelligence-related background check, and a final disposition. (b) Fingerprint-based check. In order to conduct a fingerprint... before the date of the expiration of the HME. (2) Where the State elects to collect fingerprints and...

Surfer's ear: external auditory exostoses are more prevalent in cold water surfers.

PubMed

Kroon, David F; Lawson, M Louise; Derkay, Craig S; Hoffmann, Karen; McCook, Joe

2002-05-01

The study goal was to demonstrate the prevalence and severity of external auditory exostoses (EAEs) in a population of surfers and to examine the relationship between these lesions and the length of time surfed as well as water temperature in which the swimmers surfed. It was hypothesized that subjects who predominantly surfed in colder waters had more frequent and more severe exostoses. Two hundred two avid surfers (91% male and 9% female, median age 17 years) were included in the study. EAEs were graded based on the extent of external auditory canal patency; grades of normal (100% patency), mild (66% to 99% patency), and moderate-severe (<66% patency) were assigned. Otoscopic findings were correlated with data collected via questionnaires that detailed surfing habits. There was a 38% overall prevalence of EAEs, with 69% of lesions graded as mild and 31% graded as moderate-severe. Professional surfers (odds ratio 3.8) and those subjects who surfed predominantly in colder waters (odds ratio 5.8) were found to be at a significantly increased risk for the development of EAEs. The number of years surfed was also found to be significant, increasing one's risk for developing an exostosis by 12% per year and for developing more severe lesions by 10% per year. Individuals who had moderate-severe EAEs were significantly more likely to be willing to surf in colder waters than were those who had mild EAEs (odds ratio 4.3). EAEs are more prevalent in cold water surfers, and additional years surfing increase one's risk not only for developing an EAE but also for developing more severe lesions.

Neutralization of Home Made Explosives (HME) Hazards

DTIC Science & Technology

2015-04-28

Octob previous wo nding levels n achieving neral . More B – Explosiv September rch Centre HME Threa ing CIED/EO . ED Disrupte e Test & Ev 1-120, 201...testing ar 204RD, and he choice of mixtures us neral observ hosen mixtu lations. are large a y of water je se of veloci ction. consistency tability

Influence of heat and moisture exchanger respiratory load on transcutaneous oxygenation in laryngectomized individuals: a randomized crossover study.

PubMed

Zuur, J Karel; Muller, Sara H; Sinaasappel, Michiel; Hart, Guus A M; van Zandwijk, Nico; Hilgers, Frans J M

2007-12-01

High-resistance heat and moisture exchangers (HMEs) have been reported to increase transcutaneous oxygenation (tcpO(2)) values in laryngectomized individuals and to negatively influence patient compliance. The goal of the present study was to validate earlier published results on short-term transcutaneous oxygenation changes by high-resistance HMEs. We conducted a randomized crossover study, monitoring the influence of an HME on tcpO(2) over a 2-hour time interval in 20 subjects. No evidence of an immediate HME effect (95% CI: -14.9-13.3 mm Hg, p = .91), or a time-dependent HME effect (95% CI: -.121 - .172 mm Hg/minute, p = .74), on tcpO(2) was found. After fitting the statistical model without time dependency, again no evidence of HME presence was seen (95% CI: -.5 mm Hg - 3.6 mm Hg, p = .15). In contrast to earlier suggestions, there is no evidence of increased tcpO(2) levels by high-resistance HMEs in laryngectomized individuals. Thus, using such HMEs has no added clinical value in this respect.

"Ein Liebhaber des Mysterii, und ein grosser Verwandter desselben." Toward the Life of Balthasar Walther: Kabbalist, Alchemist and Wandering Paracelsian Physician.

PubMed

Penman, Leigh T I

2010-01-01

Despite the attention recently paid to Jakob Böhme's life and works, the Görlitz theosopher's most famous disciple, Balthasar Walther (1558-c.1630), remains something of a historical puzzle. Utilizing several recently rediscovered print and manuscript sources located by the author, the present article seeks to provide the first detailed biographical study of Walther, highlighting his significance to sixteenth and seventeenth century history in a myriad of contexts. Far from being merely a follower of Böhme, Walther emerges as significant in his own right as a physician, Paracelsian, Kabbalist, Weigelian, religious heretic, and distributor of magical manuscripts, whose personal networks extended across Europe and beyond. In addition to providing a biography, this article seeks to discover new avenues of enquiry in which information concerning Walther's life and thought might be uncovered and contextualized. This investigation simultaneously throws light upon Walther himself, as well as Jakob Böhme's often neglected intellectual and social Umwelt. It also points to new and entirely unexamined sources for Böhme's thought.

The physiological rationale of heat and moisture exchangers in post-laryngectomy pulmonary rehabilitation: a review.

PubMed

Zuur, J K; Muller, S H; de Jongh, F H C; van Zandwijk, N; Hilgers, F J M

2006-01-01

Total laryngectomy results in a permanent disconnection of the upper and lower airways and inevitably leads to chronic pulmonary complaints like frequent involuntary coughing, increased sputum production and repeated daily forced expectoration to clean the airway. Heat and moisture exchangers (HMEs), applied in an attempt to compensate for the lost functions of the upper respiratory tract, have been found to diminish these symptoms and improve the quality of life significantly. An HME has three physical properties that might be responsible for these improvements. First, its heat and moisture exchanging capacity improves intra-airway preservation of heat and water. Since the condensation and evaporation of moisture are accompanied by the release and uptake of thermal energy, these parameters are inseparable. Secondly, the HME's resistance may reduce dynamic airway compression, thereby improving ventilation. Thirdly, to some extent, an HME might filter out particles, thereby cleaning inspiratory breathing air. This article summarizes our present knowledge of changes in respiratory physiology after total laryngectomy and the influence of the HME by reviewing the physiological impact of these three physical properties separately for in vitro and in vivo data.

The influence of a heat and moisture exchanger on tracheal climate in a cold environment.

PubMed

Zuur, J Karel; Muller, Sara H; Vincent, Andrew; Sinaasappel, Michiel; de Jongh, Frans H C; Hilgers, Frans J M

2009-09-01

The incidence of pulmonary complaints, severe tracheitis and lung function deterioration is increased during wintertime in laryngectomized individuals. We analyzed how a heat and moisture exchanger (HME) performs in cold and dry ambient circumstances, and how its efficiency in this environmental climate might be improved. Randomized crossover. Intra-tracheal temperature and humidity were measured in 10 laryngectomized patients with and without HME, in a cold (mean, 4.7 degrees C) and dry (mean, 4.5 mgH2O/L) room. Presence of an HME causes the intra-tracheal mean humidity minima and maxima to increase with 4.2 mgH2O/L (95%CI: 3.3-5.0 mgH2O/L; p<0.001) and 2.4 mgH2O/L (95%CI: 1.7-3.1 mgH2O/L; p<0.001), respectively. The intra-tracheal mean temperature minima and maxima increased with 3.9 degrees C (95%CI: 2.7-5.1 degrees C; p<0.001) and 1.2 degrees C (95%CI: 0.8-1.2 degrees C; p<0.001), respectively. In the majority of patients, the calculated relative humidity values appear to reach well above 100% during inspiration. In a cold environment, presence of an HME significantly increases both inspiratory and expiratory temperature and humidity values. Relative humidity calculations suggest the formation of condense droplets during inspiration. To further increase its effectiveness, improvement of the HME's thermal capacity should be aimed for.

Comparison of two different types of heat and moisture exchangers in ventilated patients.

PubMed

Ahmed, Syed Moied; Mahajan, Jyotsna; Nadeem, Abu

2009-09-01

To compare the efficacy of two different types of Heat and Moisture Exchangers (HME filters) in reducing transmission of infection from the patient to ventilator and vice versa and also its cost effectiveness. Randomized, controlled, double blind, prospective study. 60 patients admitted to the ICU from May 1, 2007 to July 31, 2007 of either sex, age ranging between 20 and 60 years, requiring mechanical ventilation were screened for the study. Following intubation of the patients, the HME device was attached to the breathing circuit randomly by the chit-in-a box method. The patients were divided into two groups according to the HME filters attached. Both the groups were comparable with respect to age and sex ratio. In Type A HME filters, 80% showed growth on the patient end within 24 h and in 27% filters, culture was positive both on the patient and the machine ends. The organisms detected were Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa and co-related with the endotracheal aspirate culture. After 48 h, 87% filters developed organisms on the patient end, whereas 64% filters were culture positive both on the patient and the machine end. In Type B HME filters, 70% showed growth on patient's end after 24 h. Organisms detected were S. aureus, E. coli, P. aeruginosa and Acinetobacter. Thirty percent of filters were culture negative on both the patient and machine ends. No growth was found on the machine end in any of the filters after 24 h. After 48 h, 73% of the filters had microbial growth on the patient end, whereas only 3% filters had growth (S. aureus) on the machine end only. Seven percent had growth on both the patient as well as the machine ends. The microorganisms detected on the HME filters co-related with the endotracheal aspirate cultures. HME filter Type B (study group) was significantly better in reducing contamination of ventilator from the patient as compared to Type A (control group), which was routinely used in our ICU. Type B filter was found to be effective for at least 48 h. This study can also be applied to patients coming to emergency department (ED) and requiring emergency surgery and postoperative ventilation; and trauma patients like flail chest, head injury etc. requiring ventilatory support to prevent them from acquiring ventilator-associated pneumonia (VAP).

Effects of Heat and Moisture Exchangers and Exhaled Humidity on Aerosol Deposition in a Simulated Ventilator-Dependent Adult Lung Model.

PubMed

Ari, Arzu; Alwadeai, Khalid S; Fink, James B

2017-05-01

Many in vitro models report higher inhaled dose with dry versus heated humidity. Heat-and-moisture exchangers (HMEs) provide passive humidity in ventilator-dependent patients but act as a barrier to aerosol. The HMEs designed to allow aerosol delivery (HME-ADs) have not been well described. The purpose of this study is to determine the impact on aerosol deposition of HME-ADs with and without active exhaled humidity in a simulated ventilator-dependent adult model. We used an in vitro lung model consisting of an intubated teaching mannequin with an endotracheal tube of 8.0 mm inner diameter with bronchi directly attached to a collecting filter and passive rubber test lung to provide testing without active exhaled humidity. To simulate exhaled humidity, a Cascade humidifier (37°C and 100% relative humidity) was placed between the collecting filter and test lung, simulating body temperature and pressure saturated exhaled humidity at the bronchi. Albuterol sulfate (2.5 mg/3 mL) was administered with a mesh nebulizer (Aerogen Solo) placed in the inspiratory limb of the ventilator circuit at the Y-piece, with no HME in place (control) and with 3 HME-AD devices, including the CircuVent, Humid-Flo, and AirLife, with and without exhaled humidity. Drug was eluted from the collecting filter and analyzed with spectrophotometry. Student t tests and analysis of variance were used for data analysis ( P < .05). The percentage of drug dose delivered (mean ± SD) distal to the bronchi in the control experiments was greater than all of the HME-ADs without exhaled humidity 18 ± 0.7 and with active exhaled humidity 10.8 ± 0.2% ( P < .005). Without exhaled humidity, aerosol delivery with the CircuVent (12.6 ± 0.8), Humid-Flo (15.3 ± 0.8), and AirLife (12.0 ± 0.5) was less than control ( P < .001, P = .01 and P < .001, respectively). In contrast, with exhaled humidity, no difference was found between control and HME-ADs ( P = .89). Also, a greater variation between control and the 3 HME-ADs was observed without exhaled humidity. Drug delivery without exhaled humidity exceeded aerosol deposition obtained with exhaled humidity in all conditions tested in this study. In this model simulating active exhaled humidity, aerosol drug delivery was lower and more consistent with both control and the HME-ADs than with the standard nonhumidified model. Further studies are needed to determine whether greater deposition in a dry model is an artifact of the model that does not simulate exhaled humidity. Copyright © 2017 by Daedalus Enterprises.

49 CFR 1572.403 - Procedures for collection by States.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Threat Assessment Fee and the FBI Fee. (a) Imposition of fees. (1) The following Threat Assessment Fee is... applies to obtain or renew an HME: $34. (2) The following FBI Fee is required for the FBI to process... FBI under Pub. L. 101-515. (3) An individual who applies to obtain or renew an HME, or the individual...

49 CFR 1572.403 - Procedures for collection by States.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Threat Assessment Fee and the FBI Fee. (a) Imposition of fees. (1) The following Threat Assessment Fee is... applies to obtain or renew an HME: $34. (2) The following FBI Fee is required for the FBI to process... FBI under Pub. L. 101-515. (3) An individual who applies to obtain or renew an HME, or the individual...

49 CFR 1572.403 - Procedures for collection by States.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Threat Assessment Fee and the FBI Fee. (a) Imposition of fees. (1) The following Threat Assessment Fee is... applies to obtain or renew an HME: $34. (2) The following FBI Fee is required for the FBI to process... FBI under Pub. L. 101-515. (3) An individual who applies to obtain or renew an HME, or the individual...

49 CFR 1572.11 - Applicant responsibilities for HME security threat assessment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... immigration status, and/or is ordered removed from the United States. (c) Submission of fingerprints and information. (1) An HME applicant must submit fingerprints and the information required in 49 CFR 1572.9, in a... fingerprints and the information required in 49 CFR 1572.9, the fee described in 49 CFR 1572.503 must be...

49 CFR 1572.11 - Applicant responsibilities for HME security threat assessment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... immigration status, and/or is ordered removed from the United States. (c) Submission of fingerprints and information. (1) An HME applicant must submit fingerprints and the information required in 49 CFR 1572.9, in a... fingerprints and the information required in 49 CFR 1572.9, the fee described in 49 CFR 1572.503 must be...

49 CFR 1572.11 - Applicant responsibilities for HME security threat assessment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... immigration status, and/or is ordered removed from the United States. (c) Submission of fingerprints and information. (1) An HME applicant must submit fingerprints and the information required in 49 CFR 1572.9, in a... fingerprints and the information required in 49 CFR 1572.9, the fee described in 49 CFR 1572.503 must be...

49 CFR 1572.11 - Applicant responsibilities for HME security threat assessment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... immigration status, and/or is ordered removed from the United States. (c) Submission of fingerprints and information. (1) An HME applicant must submit fingerprints and the information required in 49 CFR 1572.9, in a... fingerprints and the information required in 49 CFR 1572.9, the fee described in 49 CFR 1572.503 must be...

49 CFR 1572.11 - Applicant responsibilities for HME security threat assessment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... immigration status, and/or is ordered removed from the United States. (c) Submission of fingerprints and information. (1) An HME applicant must submit fingerprints and the information required in 49 CFR 1572.9, in a... fingerprints and the information required in 49 CFR 1572.9, the fee described in 49 CFR 1572.503 must be...

Multiple Hereditary Osteochondromatosis: A Case Report

PubMed Central

Küçükesmen, Çiḡdem; Özen, Buḡra; Akçam, Mustafa

2007-01-01

Objectives Common carious lesions owing to vomiting are not widespread in children. In this case, we aimed to report an 11-years-old male patient with common carious lesions due to repeated vomitings, chewing and eating difficulty and retarded growth with Multiple Hereditary Osteochondromatosis (MHO). Case Report An 11-years-old boy was referred to Department of Pediatric Dentistry in Faculty of Dentistry because of eating difficulty owing to common carious lesions. It was seen that the patient growth was generally retarded in extra-oral examination. Some exostoses were also present on the extremities. It was learned that he was previously diagnosed as MHO in Faculty of Medicine. Nausea and vomiting have been commonly occurring after taking of Didronat. Chewing and eating difficulty and inadequate nutrition were present because of bad oral hygiene, carious lesions and remained roots. Growth was negatively affected by malnutrition and MHO. Results Diet recommendations were given and oral hygiene behaviors were rearranged. Preventive, surgical, restorative and prosthetical dental applications were applied for dental treatments. PMID:19212564

A Quantitative and Qualitative Evaluation of an Automatic Occlusion Device for Tracheoesophageal Speech: The Provox FreeHands HME

ERIC Educational Resources Information Center

Hamade, Rachel; Hewlett, Nigel; Scanlon, Emer

2006-01-01

This study aimed to evaluate a new automatic tracheostoma valve: the Provox FreeHands HME (manufactured by Atos Medical AB, Sweden). Data from four laryngectomee participants using automatic and also manual occlusion were subjected to acoustic and perceptual analysis. The main results were a significant decrease, from the manual to automatic…

Gender Inequalities and Higher Music Education: Comparing the UK and Sweden

ERIC Educational Resources Information Center

de Boise, Sam

2018-01-01

Whilst the impact of gender inequalities has been studied in relation to music education, especially in the UK, relatively little has been written about their impact on higher music education (HME). This article compares data on HME programs and courses, in the UK and Sweden, from 2010 to 2014. It looks at similarities and differences in the…

Healthy Migrant Effect on Smoking Behavior Among Asian Immigrants in the United States.

PubMed

Kuerban, Aliya

2016-02-01

Healthy migrant effect (HME) of immigrants has been evidenced in various heath aspects. However, few studies have explored the applicability of HME on Asian immigrants' health risk behavior-smoking. This study used three waves of Current Population Survey-Tobacco Use Supplement data, 1998-1999, 2005-2006, and 2010-2011, to compare the rates of being a current smoker among Asian immigrants and United States born citizens. Further, the odds ratios of gender, age, marital status, socioeconomic status, years of migration, and citizenship status on the likelihood of being a current smoker were examined. Across the three waves, Asian immigrants smoked at a much lower rate than their native-born counterparts. The gender gap of being a current smoker was much wider among Asian immigrants. The longer the Asian immigrants stayed in the United States, the more likely they were to become current smokers. These data confirmed the association of HME and Asian immigrants' smoking behavior, and also provided strong evidence of the importance of smoking prevention among Asian immigrants. This study also implied the possibility of a decline in the effectiveness of HME on Asian immigrants as the time they spent in the United States increased.

Improving the chemical stability of amorphous solid dispersion with cocrystal technique by hot melt extrusion.

PubMed

Liu, Xu; Lu, Ming; Guo, Zhefei; Huang, Lin; Feng, Xin; Wu, Chuanbin

2012-03-01

To explore in-situ forming cocrystal as a single-step, efficient method to significantly depress the processing temperature and thus minimize the thermal degradation of heat-sensitive drug in preparation of solid dispersions by melting method (MM) and hot melt extrusion (HME). Carbamazepine (CBZ)-nicotinamide (NIC) cocrystal solid dispersions were prepared with polymer carriers PVP/VA, SOLUPLUS and HPMC by MM and/or HME. The formation of cocrystal was investigated by differential scanning calorimetry and hot stage polarized optical microscopy. State of CBZ in solid dispersion was characterized by X-ray powder diffraction and optical microscopy. Interactions between CBZ, NIC and polymers were investigated by FTIR. Dissolution behaviors of solid dispersions were compared with that of pure CBZ. CBZ-NIC cocrystal with melting point of 160°C was formed in polymer carriers during heating process, and the preparation temperature of amorphous CBZ solid dispersion was therefore depressed to 160°C. The dissolution rate of CBZ-NIC cocrystal solid dispersion was significantly increased. By in-situ forming cocrystal, chemically stable amorphous solid dispersions were prepared by MM and HME at a depressed processing temperature. This method provides an attractive opportunity for HME of heat-sensitive drugs.

Detection of the agents of human ehrlichioses in ixodid ticks from California.

PubMed

Kramer, V L; Randolph, M P; Hui, L T; Irwin, W E; Gutierrez, A G; Vugia, D J

1999-01-01

A study was conducted in northern California to estimate the prevalence and distribution in ixodid ticks of the rickettsial agents of human monocytic (HME) and human granulocytic (HGE) ehrlichioses. More than 650 ixodid ticks were collected from 17 sites in six California counties over a 15-month period. Ehrlichia chaffeensis, the causative agent of HME, was detected by a nested polymerase chain reaction (PCR) in Ixodes pacificus (minimum infection rate [MIR] = 13.3%) and Dermacentor variabilis (infection rate=20.0%) from a municipal park in Santa Cruz County. The HGE agent was detected by nested PCR in I. pacificus adults from a heavily used recreational area in Alameda County (MIR = 4.7%) and a semirural community in Sonoma County (MIR = 6.7%). Evidence of infection with Ehrlichia spp. was not detected in D. occidentalis adults or I. pacificus nymphs. This study represents the first detection of E. chaffeensis in California ticks and the first report of infection in Ixodes spp. The competency of I. pacificus to be coinfected with and to transmit multiple disease agents, including those of human ehrlichioses and Lyme disease, has yet to be determined.

[The clinical and microbiological comparison of the use of heated humidifiers and heat and moisture exchanger filters with Booster in mechanically ventilated patients].

PubMed

Nadir Oziş, Türkan; Ozcan Kanat, Derya; Oğuzülgen, Ipek Kivilcim; Aydoğdu, Müge; Hizel, Kenan; Gürsel, Gül

2009-01-01

Ventilator associated pneumonia (VAP) is the most frequent nosocomial infection in intensive care units that is associated with prolonged mechanical ventilation, hospitalization and increased health-care costs. Various humidifiers can be used for humidification during mechanical ventilation. Many studies were conducted to identify the effects of two different humidifiers, i.e. heated humidifiers and heat and moisture exchanger filters (HME), on VAP development; and HME filters were found to decrease the VAP frequency. In this study we aimed to compare the efficacy and safety of heated humidifiers and HME-Booster. Heated humidifier with conventional microbiologic filter (CMF-HH) or HME-Booster were used in randomization to 41 mechanically ventilated patients of our intensive care unit, and patients were divided into two groups as group 1 receiving CMF-HH (20 patients) and group 2 (21 patients) receiving HME-Booster. Daily secretion scores, endotracheal tube occlusion due to secretions, VAP development rate for the assessment of microbiological safety of humidifiers and differences in PETCO(2) and PaCO(2) values for the assessment of their effect on arterial blood gas were recorded prospectively. The measurement of PETCO(2) and PaCO(2) values were performed with the presence of humidifiers and after removing them in both groups. In both groups with the removal of CMF-HH and HME-Booster, a decrease in PETCO(2) value was identified, but the decrease in group 2 was statistically significant (p= 0.016). The decrease in PaCO(2) after removal of humidifiers was greater in group 2 than in group 1, but the difference was not significant (p> 0.05).The rate of VAP and endotracheal tube occlusion was not significantly different between the groups. The mean secretion score was lower in group 1 (p= 0.041). In conclusion, although both humidifiers have similar microbiological effects, heated humidifiers could be preferred particularly for the patients with an underlying chronic lung disease due to its positive effects on PETCO(2) values and secretion scores.

Randomized clinical trial of extended use of a hydrophobic condenser humidifier: 1 vs. 7 days.

PubMed

Thomachot, Laurent; Leone, Marc; Razzouk, Karim; Antonini, François; Vialet, Renaud; Martin, Claude

2002-01-01

To determine whether extended use (7 days) would affect the efficiency on heat and water preservation of a hydrophobic condenser humidifier as well as the rate of ventilation-acquired pneumonia, compared with 1 day of use. Prospective, controlled, randomized, not blinded, clinical study. Twelve-bed intensive care unit of a university hospital. One hundred and fifty-five consecutive patients undergoing mechanical ventilation for > or = 48 hrs. After randomization, patients were allocated to one of the two following groups: a) heat and moisture exchangers (HMEs) changed every 24 hrs; b) HMEs changed only once a week. Devices in both groups could be changed at the discretion of the staff when signs of occlusion or increased resistance were identified. Efficient airway humidification and heating were assessed by clinical variables (numbers of tracheal suctionings and instillations required, peak and mean airway pressures). The frequency rates of bronchial colonization and ventilation-acquired pneumonia were evaluated by using clinical and microbiological criteria. Endotracheal tube occlusion, ventilatory support variables, duration of mechanical ventilation, length of intensive care, acquired multiorgan dysfunction, and mortality rates also were recorded. The two groups were similar at the time of randomization. Endotracheal tube occlusion never occurred. In the targeted population (patients ventilated for > or = 7 days), the frequency rate of ventilation-acquired pneumonia was 24% in the HME 1-day group and 17% in the HME 7-day group (p > .05, not significant). Ventilation-acquired pneumonia rates per 1000 ventilatory support days were 16.4/1000 in the HME 1-day group and 12.4/1000 in the HME 7-day group (p > .05, not significant). No statistically significant differences were found between the two groups for duration of mechanical ventilation, intensive care unit length of stay, acquired organ system derangements, and mortality rate. There was indirect evidence of very little, if any, change in HME resistance. Changing the studied hydrophobic HME after 7 days did not affect efficiency, increase resistance, or altered bacterial colonization. The frequency rate of ventilation-acquired pneumonia was also unchanged. Use of HMEs for > 24 hrs and up to 7 days is safe.

Do heat and moisture exchangers in the anaesthesia breathing circuit preserve body temperature in dogs undergoing anaesthesia for magnetic resonance imaging?

PubMed

Khenissi, Latifa; Covey-Crump, Gwen; Knowles, Toby G; Murrell, Joanna

2017-05-01

To investigate whether the use of a heat and moisture exchanger (HME) preserves body temperature in dogs weighing <10 kg anaesthetised for magnetic resonance imaging (MRI). Prospective, randomised, clinical trial. Thirty-one client-owned dogs. Dogs were assigned randomly to a treatment group [HME (n = 16) or no HME (n = 15)]. Dogs were pseudorandomised according to the premedication they were administered, either dexmedetomidine or no dexmedetomidine. Induction agents were not standardised. General anaesthesia was maintained with isoflurane vaporised in 100% oxygen delivered using a T-piece and a fresh gas flow of 600 mL kg -1 minute -1 . Rectal temperature was measured before premedication (T1), after induction (T2), before moving to the MRI unit (T3) and at the end of the MRI scan (T4). Ambient temperatures were measured in the induction room, outside and inside the MRI unit. Data were analysed using a general linear model with T4 as the outcome variable. Linear correlations were performed between T1, T2, T3 and T4, and variables that predicted T4 were investigated. Sex, age and body mass were not significantly different between groups. There were no significant differences in rectal temperature between groups at any time point (group with HME at the end of MRI = 36.3 ± 1.1 °C; group with no HME at the end of MRI = 36.2 ± 1.4 °C) but at the end of the MRI, dogs administered dexmedetomidine (36.6 ± 0.7 °C) had a higher rectal temperature compared with dogs not administered dexmedetomidine (35.9 ± 1.6 °C) for premedication. Rectal temperature varied directly with ambient temperature in MRI scanning room and inversely with anaesthetic duration. Using an HME did not alter body temperature in dogs weighing <10 kg undergoing an MRI, but including dexmedetomidine in the premedication regimen seemed to preserve the body temperature during anaesthesia. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Chromosomal diversity and molecular divergence among three undescribed species of Neacomys (Rodentia, Sigmodontinae) separated by Amazonian rivers.

PubMed

Oliveira Da Silva, Willam; Pieczarka, Julio Cesar; Ferguson-Smith, Malcolm Andrew; O'Brien, Patricia Caroline Mary; Mendes-Oliveira, Ana Cristina; Sampaio, Iracilda; Carneiro, Jeferson; Nagamachi, Cleusa Yoshiko

2017-01-01

The Neacomys genus (Rodentia, Sigmodontinae) is distributed in the Amazon region, with some species limited to a single endemic area, while others may occur more widely. The number of species within the genus and their geographical boundaries are not known accurately, due to their high genetic diversity and difficulties in taxonomic identification. In this work we collected Neacomys specimens from both banks of the Tapajós River in eastern Amazon, and studied them using chromosome painting with whole chromosome probes of Hylaeamys megacephalus (HME; Rodentia, Sigmodontinae), and molecular analysis using haplotypes of mitochondrial genes COI and Cytb. Chromosome painting shows that Neacomys sp. A (NSP-A, 2n = 58/FN = 68) and Neacomys sp. B (NSP-B, 2n = 54/FN = 66) differ by 11 fusion/fission events, one translocation, four pericentric inversions and four heterochromatin amplification events. Using haplotypes of the concatenated mitochondrial genes COI and Cyt b, Neacomys sp. (2n = 58/FN = 64 and 70) shows a mean divergence of 6.2% for Neacomys sp. A and 9.1% for Neacomys sp. B, while Neacomys sp. A and Neacomys sp. B presents a medium nucleotide divergence of 7.4%. Comparisons were made with other published Neacomys data. The Tapajós and Xingu Rivers act as geographic barriers that define the distribution of these Neacomys species. Furthermore, our HME probes reveal four synapomorphies for the Neacomys genus (associations HME 20/[13,22]/4, 6a/21, [9,10]/7b/[9,10] and 12/[16,17]) and demonstrate ancestral traits of the Oryzomyini tribe (HME 8a and 8b, 18 and 25) and Sigmodontinae subfamily (HME 15 and 24), which can be used as taxonomic markers for these groups.

Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach.

PubMed

Patil, Hemlata; Feng, Xin; Ye, Xingyou; Majumdar, Soumyajit; Repka, Michael A

2015-01-01

This contribution describes a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME). Presently, HME technology has not been used for the manufacturing of SLN. Generally, SLN are prepared as a batch process, which is time consuming and may result in variability of end-product quality attributes. In this study, using Quality by Design (QbD) principles, we were able to achieve continuous production of SLN by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Fenofibrate (FBT), a poorly water-soluble model drug, was incorporated into SLN using HME-HPH methods. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm. The dissolution profile of the FBT SLN prepared by the novel HME-HPH method was faster than that of the crude FBT and a micronized marketed FBT formulation. At the end of a 5-h in vitro dissolution study, a SLN formulation released 92-93% of drug, whereas drug release was approximately 65 and 45% for the marketed micronized formulation and crude drug, respectively. Also, pharmacokinetic study results demonstrated a statistical increase in Cmax, Tmax, and AUC0-24 h in the rate of drug absorption from SLN formulations as compared to the crude drug and marketed micronized formulation. In summary, the present study demonstrated the potential use of hot-melt extrusion technology for continuous and large-scale production of SLN.

Chromosomal diversity and molecular divergence among three undescribed species of Neacomys (Rodentia, Sigmodontinae) separated by Amazonian rivers

PubMed Central

Oliveira Da Silva, Willam; Pieczarka, Julio Cesar; Ferguson-Smith, Malcolm Andrew; O’Brien, Patricia Caroline Mary; Mendes-Oliveira, Ana Cristina; Sampaio, Iracilda; Carneiro, Jeferson

2017-01-01

The Neacomys genus (Rodentia, Sigmodontinae) is distributed in the Amazon region, with some species limited to a single endemic area, while others may occur more widely. The number of species within the genus and their geographical boundaries are not known accurately, due to their high genetic diversity and difficulties in taxonomic identification. In this work we collected Neacomys specimens from both banks of the Tapajós River in eastern Amazon, and studied them using chromosome painting with whole chromosome probes of Hylaeamys megacephalus (HME; Rodentia, Sigmodontinae), and molecular analysis using haplotypes of mitochondrial genes COI and Cytb. Chromosome painting shows that Neacomys sp. A (NSP-A, 2n = 58/FN = 68) and Neacomys sp. B (NSP-B, 2n = 54/FN = 66) differ by 11 fusion/fission events, one translocation, four pericentric inversions and four heterochromatin amplification events. Using haplotypes of the concatenated mitochondrial genes COI and Cyt b, Neacomys sp. (2n = 58/FN = 64 and 70) shows a mean divergence of 6.2% for Neacomys sp. A and 9.1% for Neacomys sp. B, while Neacomys sp. A and Neacomys sp. B presents a medium nucleotide divergence of 7.4%. Comparisons were made with other published Neacomys data. The Tapajós and Xingu Rivers act as geographic barriers that define the distribution of these Neacomys species. Furthermore, our HME probes reveal four synapomorphies for the Neacomys genus (associations HME 20/[13,22]/4, 6a/21, [9,10]/7b/[9,10] and 12/[16,17]) and demonstrate ancestral traits of the Oryzomyini tribe (HME 8a and 8b, 18 and 25) and Sigmodontinae subfamily (HME 15 and 24), which can be used as taxonomic markers for these groups. PMID:28763510

Influence of heat and moisture exchanger use on measurements performed with manovacuometer and respirometer in healthy adults.

PubMed

Lucato, Jeanette Janaina Jaber; Nogueira da Cunha, Thiago Marraccini; Rocha, Sara Solange Oliveira Costa; Palmieri de Carvalho, Fernanda Maria; Botega, Daniele Cristina; Torquato, Jamili Anbar; Gimenes, Ana Cristina; Righetti, Renato Fraga

2015-01-01

The use of evaluation tools such as the manovacuometer and respirometer is frequent and disinfection is usually limited to the external surfaces, which is insufficient and raises concerns because of the potential spread of infectious diseases. Hydrophobic heat and moisture exchangers (HME) are used in mechanical ventilation and have microbiological filters, which can possibly reduce contamination, increasing the safety of related procedures. It is unknown, however, if the addition of an exchanger affects the measurements obtained. Aim of this study was to verify if the use of an HME interferes in maximal inspiratory and expiratory pressures assessed using the manovacuometer and vital capacity evaluated using the respirometer in healthy adults. A controlled transversal trial was carried out. Twenty healthy young adults were included in the study. Vital capacity by respirometer and, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were assessed with and without the use of HME. No significant difference was found between the values pre and post HME use in vital capacity measurements: (3878.8 ± 202.2 mL vs. 3925.5 ± 206.0 mL, p = 0.116) and the respiratory muscle strength measurements: MIP (-99.0 ± 8.9 vs -95.5 ± 9.0 cm H2O, p = 0.149) and MEP (92.5 ± 7.5 vs 92.5 ± 7.7 cm H2O, p = 1.0) respectively. We conclude that the use of HME does not modify the lung volumes or respiratory muscle strength, and can be used in order to reduce the occurrence of pulmonary infection.

Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity.

PubMed

Kassim, Mustafa; Achoui, Mouna; Mustafa, Mohd Rais; Mohd, Mustafa Ali; Yusoff, Kamaruddin Mohd

2010-09-01

Natural honey has been used in traditional medicine of different cultures throughout the world. This study looked into the extraction of Malaysian honey and the evaluation of the anti-inflammatory activity of these extracts. It was hypothesized that honey extracts contain varying amounts of phenolic compounds and that they possess different in vitro anti-inflammatory activities. Honey extracts were analyzed using liquid chromatography-mass spectrometry to identify and compare phenolic compounds, whereas high-performance liquid chromatography was used for their quantification. Subsequently, honey methanol extract (HME) and honey ethyl acetate extract (HEAE) were tested in vitro for their effect on nitric oxide production in stimulated macrophages. The extracts were also tested for their effects on tumor necrosis factor-α (TNF) cytotoxicity in L929 cells. The major phenolics in the extracts were ellagic, gallic, and ferulic acids; myricetin; chlorogenic acid; and caffeic acid. Other compounds found in lower concentrations were hesperetin, p-coumaric acid, chrysin, quercetin, luteolin, and kaempferol. Ellagic acid was the most abundant of the phenolic compounds recorded, with mean concentrations of 3295.83 and 626.74 μg/100 g of honey in HME and HEAE, respectively. The median maximal effective concentrations for in vitro nitric oxide inhibition by HEAE and HME were calculated to be 37.5 and 271.7 μg/mL, respectively. The median maximal effective concentrations for protection from TNF cytotoxicity by HEAE and HME were 168.1 and 235.4 μg/mL, respectively. In conclusion, HEAE exhibited greater activity in vitro, whereas HME contained a higher concentration of phenolic compounds per 100 g of honey. Copyright © 2010 Elsevier Inc. All rights reserved.

Taste Masking of Griseofulvin and Caffeine Anhydrous Using Kleptose Linecaps DE17 by Hot Melt Extrusion.

PubMed

Juluri, Abhishek; Popescu, Carmen; Zhou, Leon; Murthy, Reena N; Gowda, Vanaja K; Chetan Kumar, P; Pimparade, Manjeet B; Repka, Michael A; Murthy, S Narasimha

2016-02-01

The objective of this project was to investigate the potential of Kleptose Linecaps DE17 (KLD) in masking the unpleasant/bitter taste of therapeutic agents by hot melt extrusion (HME). Griseofulvin (GRI) and caffeine anhydrous (CA) were used as a bitter active pharmaceutical ingredient (API) model drugs. Thermogravimetric studies confirmed the stability of GRI, CA, and KLD at the employed extrusion temperatures. The differential scanning calorimetry (DSC) studies revealed a characteristic melting endotherm of GRI at 218-220°C and CA at 230-232°C in the physical mixtures as well as in all extrudates over the period of study, indicating the crystalline nature of drug. HME of KLD was achieved only in the presence of plasticizer. Among the several plasticizers investigated, xylitol showed improved processability of KLD at 15% w/w concentration. Dissolution studies of HME extrudates using simulated salivary medium exhibited ∼threefold less release compared to physical mixture at the end of 5 min (the lesser drug release, better the taste masking efficiency). Furthermore, the results from the sensory evaluation of products in human panel demonstrated strong bitter taste in the case of physical mixture compared to the HME formulation, suggesting the potential of Kleptose Linecaps DE17 as taste masking polymer in melt extruded form.

Angelica gigas Nakai and Soluplus-Based Solid Formulations Prepared by Hot-Melting Extrusion: Oral Absorption Enhancing and Memory Ameliorating Effects

PubMed Central

Piao, Jingpei; Lee, Jae-Young; Weon, Jin Bae; Ma, Choong Je; Ko, Hyun-Jeong; Kim, Dae-Duk; Kang, Wie-Soo; Cho, Hyun-Jong

2015-01-01

Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot-melting extrusion (HME) method. AGN was pulverized into coarse and ultrafine particles, and their particle size and morphology were investigated. Ultrafine AGN particles were used in the HME process with high shear to produce AGN-based formulations. In simulated gastrointestinal fluids (pH 1.2 and pH 6.8) and water, significantly higher amounts of the major active components of AGN, decursin (D) and decursinol angelate (DA), were extracted from the HME-processed AGN/Soluplus (F8) group than the AGN EtOH extract (ext) group (p < 0.05). Based on an in vivo pharmacokinetic study in rats, the relative oral bioavailability of decursinol (DOH), a hepatic metabolite of D and DA, in F8-administered mice was 8.75-fold higher than in AGN EtOH ext-treated group. In scopolamine-induced memory-impaired mice, F8 exhibited a more potent cognitive enhancing effect than AGN EtOH ext in both a Morris water maze test and a passive avoidance test. These findings suggest that HME-processed AGN/Soluplus formulation (F8) could be a promising therapeutic candidate for memory impairment. PMID:25915423

A novel, simplified ex vivo method for measuring water exchange performance of heat and moisture exchangers for tracheostomy application.

PubMed

van den Boer, Cindy; Muller, Sara H; Vincent, Andrew D; Züchner, Klaus; van den Brekel, Michiel W M; Hilgers, Frans J M

2013-09-01

Breathing through a tracheostomy results in insufficient warming and humidification of inspired air. This loss of air-conditioning can be partially compensated for with the application of a heat and moisture exchanger (HME) over the tracheostomy. In vitro (International Organization for Standardization [ISO] standard 9360-2:2001) and in vivo measurements of the effects of an HME are complex and technically challenging. The aim of this study was to develop a simple method to measure the ex vivo HME performance comparable with previous in vitro and in vivo results. HMEs were weighed at the end of inspiration and at the end of expiration at different breathing volumes. Four HMEs (Atos Medical, Hörby, Sweden) with known in vivo humidity and in vitro water loss values were tested. The associations between weight change, volume, and absolute humidity were determined using both linear and non-linear mixed effects models. The rating between the 4 HMEs by weighing correlated with previous intra-tracheal measurements (R(2) = 0.98), and the ISO standard (R(2) = 0.77). Assessment of the weight change between end of inhalation and end of exhalation is a valid and simple method of measuring the water exchange performance of an HME.

The Effects of Polymer Carrier, Hot Melt Extrusion Process and Downstream Processing Parameters on the Moisture Sorption Properties of Amorphous Solid Dispersions

PubMed Central

Feng, Xin; Vo, Anh; Patil, Hemlata; Tiwari, Roshan V.; Alshetaili, Abdullah S.; Pimparade, Manjeet B.; Repka, Michael A.

2017-01-01

Objective The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion (HME) and downstream processing parameters on the water uptake properties of amorphous solid dispersions. Methods Three polymers and a model drug were used to prepare amorphous solid dispersions utilizing HME technology. The sorption-desorption isotherms of solid dispersions and their physical mixtures were measured by the Dynamic Vapor Sorption system, and the effect of polymer hydrophobicity, hygroscopicity, molecular weight and the HME process were investigated. FTIR imaging was performed to understand the phase separation driven by the moisture. Key findings Solid dispersions with polymeric carriers with lower hydrophilicity, hygroscopicity, and higher molecular weight could sorb less moisture under the high RH conditions. The water uptake ability of polymer-drug solid dispersion systems were decreased compared to the physical mixture after HME, which might be due to the decreased surface area and porosity. The FTIR imaging indicated the homogeneity of the drug molecularly dispersed within the polymer matrix was changed after exposure to high RH. Conclusion Understanding the effect of formulation and processing on the moisture sorption properties of solid dispersions is essential for the development of drug products with desired physical and chemical stability. PMID:26589107

A change in humidification system can eliminate endotracheal tube occlusion.

PubMed

Doyle, Alex; Joshi, Manasi; Frank, Peter; Craven, Thomas; Moondi, Parvez; Young, Peter

2011-12-01

Inadequate airway humidification can result in endotracheal tube occlusion. There is evidence that heat and moisture exchangers (HMEs) are more prone to endotracheal tube occlusion than heated humidifiers (HHs) that contain a heated wire circuit. We aimed to compare the incidence of endotracheal tube occlusion while introducing a new dual-heated wire circuit HH in place of an established hydrophobic HME. This was a prospective observational study. All patients who required intubation were included in our analysis. Univariate statistical analysis was performed using a Fisher exact test. P < .05 was considered statistically significant. There were 158 patients in the HME group and 88 patients in the HH group. The incidence of endotracheal tube occlusion was 5.7% in the HME group and 0% in the HH group. Statistical analysis revealed a significant difference between the 2 groups (P = .02). In light of this finding, we changed our practice to provide humidification exclusively by HH. In the subsequent 18-month period, there were no further episodes of endotracheal tube occlusion. Our study demonstrates that there is a significant increase in the incidence of endotracheal tube occlusion when using a hydrophobic HME compared with an HH and that using a dual-heated wire circuit HH can eliminate endotracheal tube occlusion. Copyright © 2011 Elsevier Inc. All rights reserved.

A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties.

PubMed

Martinez-Marcos, Laura; Lamprou, Dimitrios A; McBurney, Roy T; Halbert, Gavin W

2016-02-29

The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (μ-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, μ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced in vivo absorption of CB-1 antagonist in rats via solid solutions prepared by hot-melt extrusion.

PubMed

Ranzani, L S; Font, J; Galimany, F; Santanach, A; Gomez-Gomar, A M; Casadevall, G; Gryczke, A

2011-06-01

The aim of the present work was to investigate in vitro dissolution properties of three binary solid solutions prepared by a hot-melt extrusion (HME) process with vinyl pirrolidone--vinyl acetate copolymer (Kollidon VA 64), ethyl acrylate, methyl methacrylate polymer (Eudragit E) polyetilenglicol 8000 (PEG 8000) with a cannabinoid type 1 (CB-1) antagonist. Hansen solubility parameters were calculated from the chemical structures of the drug and the individual polymers in order to predict miscibility. Solid state characterizations of drug substance, physical blends and HME formulations were performed with differential scanning calorimetry. The dissolution testing conducted under sink conditions revealed that the dissolution rate of HME formulations improved around 1.8-fold vs drug substance. Supersaturation dissolution study demonstrated that HME formulations composed by Eudragit E and Kollidon VA64 increased drug solubility between 30- and 35-fold, respectively comparing to the drug substance. Physical and chemical stability of formulations were studied at 40°C/75%HR with open dish during 15 days. The formulation composed by the drug and Eudragit E at 10:90 was evaluated for in vivo drug absorption in male Wistar-Hannover rats and it was found to increase CB-1 absorption threefold greater than pure drug oral suspension.

Humidification and secretion volume in mechanically ventilated patients.

PubMed

Solomita, Mario; Palmer, Lucy B; Daroowalla, Feroza; Liu, Jeffrey; Miller, Dori; LeBlanc, Deniese S; Smaldone, Gerald C

2009-10-01

To determine potential effects of humidification on the volume of airway secretions in mechanically ventilated patients. Water vapor delivery from devices providing non-heated-wire humidification, heated-wire humidification, and heat and moisture exchanger (HME) were quantified on the bench. Then, patients requiring 24-hour mechanical ventilation were exposed sequentially to each of these humidification devices, and secretions were removed and measured by suctioning every hour during the last 4 hours of the 24-hour study period. In vitro water vapor delivery was greater using non-heated-wire humidification, compared to heated-wire humidification and HME. In vivo, a total of 9 patients were studied. Secretion volume following humidification by non-heated-wire humidification was significantly greater than for heated-wire humidification and HME (P=.004). The volume of secretions appeared to be linked to humidification, as greater water vapor delivery measured in vitro was associated with greater secretion volume in vivo.

The Humidity in a Low-Flow Dräger Fabius Anesthesia Workstation with or without Thermal Insulation or a Heat and Moisture Exchanger: A Prospective Randomized Clinical Trial.

PubMed

de Oliveira, Sergius A R; Lucio, Lorena M C; Modolo, Norma S P; Hayashi, Yoko; Braz, Mariana G; de Carvalho, Lídia R; Braz, Leandro G; Braz, José Reinaldo C

2017-01-01

During anesthesia, as compared with intensive care, the time of the tracheal intubation is much shorter. An inhaled gas minimum humidity of 20 mgH2O.L-1 is recommended to reduce the deleterious effects of dry gas on the airways during anesthesia with tracheal intubation. The Fabius GS Premium® anesthesia workstation (Dräger Medical, Lübeck, Germany) has a built-in hotplate to heat gases in the breathing circuit. A heat and moisture exchanger (HME) is used to further heat and humidify the inhaled gas. The humidity of the gases in the breathing circuit is influenced by the ambient temperature. We compared the humidity of the inhaled gases from a low-flow Fabius anesthesia workstation with or without thermal insulation (TI) of the breathing circuit and with or without an HME. We conducted a prospective randomized trial in 41 adult female patients who underwent elective abdominal surgery. The patients were allocated into four groups according to the devices used to ventilate their lungs using a Dräger Fabius anesthesia workstation with a low gas flow (1 L.min-1): control, with TI, with an HME or with TI and an HME (TIHME). The mean temperature and humidity of the inhaled gases were measured during 2-h after connecting the patients to the breathing circuit. The mean inhaled gas temperature and absolute humidity were higher in the HME (29.2±1.3°C; 28.1±2.3 mgH2O·L-1) and TIHME (30.1±1.2°C; 29.4±2.0 mgH2O·L-1) groups compared with the control (27.5±1.0°C; 25.0±1.8 mgH2O·L-1) and TI (27.2±1.1°C; 24.9±1.8 mgH2O·L-1) groups (P = 0.003 and P<0.001, respectively). The low-flow Fabius GS Premium breathing circuit provides the minimum humidity level of inhaled gases to avoid damage to the tracheobronchial epithelia during anesthesia. TI of the breathing circuit does not increase the humidity of the inhaled gases, whereas inserting an HME increases the moisture of the inhaled gases closer to physiological values.

Homoleptic Trivalent Tris(alkyl) Rare Earth Compounds

DOE PAGES

Pindwal, Aradhana; Yan, KaKing; Patnaik, Smita; ...

2017-10-09

Homoleptic tris(alkyl) rare earth complexes Ln{C(SiHMe 2) 3} 3 (Ln = La, 1a; Ce, 1b; Pr, 1c; Nd, 1d) are synthesized in high yield from LnI 3THF n and 3 equiv of KC(SiHMe 2) 3. X-ray diffraction studies reveal 1a–d are isostructural, pseudo-C 3-symmetric molecules that contain two secondary Ln←HSi interactions per alkyl ligand (six total). Spectroscopic assignments are supported by comparison with Ln{C(SiDMe 2) 3} 3 and DFT calculations. Here, the Ln←HSi and terminal SiH exchange rapidly on the NMR time scale at room temperature, but the two motifs are resolved at low temperature. Variable-temperature NMR studies provide activationmore » parameters for the exchange process in 1a (ΔH ‡ = 8.2(4) kcal·mol –1; ΔS ‡ = –1(2) cal·mol –1K –1) and 1a-d 9 (ΔH ‡ = 7.7(3) kcal·mol –1; ΔS ‡ = –4(2) cal·mol –1K –1). Comparisons of lineshapes, rate constants (kH/kD), and slopes of ln(k/T) vs 1/T plots for 1a and 1a-d 9 reveal that an inverse isotope effect dominates at low temperature. DFT calculations identify four low-energy intermediates containing five β-Si–H→Ln and one γ-C–H→Ln. The calculations also suggest the pathway for Ln←HSi/SiH exchange involves rotation of a single C(SiHMe 2) 3 ligand that is coordinated to the Ln center through the Ln–C bond and one secondary interaction. These robust organometallic compounds persist in solution and in the solid state up to 80 °C, providing potential for their use in a range of synthetic applications. For example, reactions of Ln{C(SiHMe 2) 3} 3 and ancillary proligands, such as bis-1,1-(4,4-dimethyl-2-oxazolinyl)ethane (HMeC(Ox Me2) 2) give {MeC(Ox Me2) 2}Ln{C(SiHMe 2) 3} 2, and reactions with disilazanes provide solvent-free lanthanoid tris(disilazides).« less

Homoleptic Trivalent Tris(alkyl) Rare Earth Compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pindwal, Aradhana; Yan, KaKing; Patnaik, Smita

Homoleptic tris(alkyl) rare earth complexes Ln{C(SiHMe 2) 3} 3 (Ln = La, 1a; Ce, 1b; Pr, 1c; Nd, 1d) are synthesized in high yield from LnI 3THF n and 3 equiv of KC(SiHMe 2) 3. X-ray diffraction studies reveal 1a–d are isostructural, pseudo-C 3-symmetric molecules that contain two secondary Ln←HSi interactions per alkyl ligand (six total). Spectroscopic assignments are supported by comparison with Ln{C(SiDMe 2) 3} 3 and DFT calculations. Here, the Ln←HSi and terminal SiH exchange rapidly on the NMR time scale at room temperature, but the two motifs are resolved at low temperature. Variable-temperature NMR studies provide activationmore » parameters for the exchange process in 1a (ΔH ‡ = 8.2(4) kcal·mol –1; ΔS ‡ = –1(2) cal·mol –1K –1) and 1a-d 9 (ΔH ‡ = 7.7(3) kcal·mol –1; ΔS ‡ = –4(2) cal·mol –1K –1). Comparisons of lineshapes, rate constants (kH/kD), and slopes of ln(k/T) vs 1/T plots for 1a and 1a-d 9 reveal that an inverse isotope effect dominates at low temperature. DFT calculations identify four low-energy intermediates containing five β-Si–H→Ln and one γ-C–H→Ln. The calculations also suggest the pathway for Ln←HSi/SiH exchange involves rotation of a single C(SiHMe 2) 3 ligand that is coordinated to the Ln center through the Ln–C bond and one secondary interaction. These robust organometallic compounds persist in solution and in the solid state up to 80 °C, providing potential for their use in a range of synthetic applications. For example, reactions of Ln{C(SiHMe 2) 3} 3 and ancillary proligands, such as bis-1,1-(4,4-dimethyl-2-oxazolinyl)ethane (HMeC(Ox Me2) 2) give {MeC(Ox Me2) 2}Ln{C(SiHMe 2) 3} 2, and reactions with disilazanes provide solvent-free lanthanoid tris(disilazides).« less

Surfer's exostosis in a child who does not surf.

PubMed

Paddock, Michael; Lau, Kimberley; Raghavan, Ashok; Dritsoula, Aikaterini

2018-06-01

Surfer's exostoses are more commonly seen in adults who frequently participate in aquatic activities with repeated exposed to cold water and wind. However, this entity has not been previously reported in the pediatric population. Most patients can be managed conservatively, particularly considering that surgical removal of external auditory canal exostosis can be challenging.

External auditory exostoses in the Xuchang and Xujiayao human remains: Patterns and implications among eastern Eurasian Middle and Late Pleistocene crania

PubMed Central

2017-01-01

In the context of Middle and Late Pleistocene eastern Eurasian human crania, the external auditory exostoses (EAE) of the late archaic Xuchang 1 and 2 and the Xujiayao 15 early Late Pleistocene human temporal bones are described. Xujiayao 15 has small EAE (Grade 1), Xuchang 1 presents bilateral medium EAE (Grade 2), and Xuchang 2 exhibits bilaterally large EAE (Grade 3), especially on the right side. These cranial remains join the other eastern Eurasian later Pleistocene humans in providing frequencies of 61% (N = 18) and 58% (N = 12) respectively for archaic and early modern human samples. These values are near the upper limits of recent human frequencies, and they imply frequent aquatic exposure among these Pleistocene humans. In addition, the medial extents of the Xuchang 1 and 2 EAE would have impinged on their tympanic membranes, and the large EAE of Xuchang 2 would have resulted in cerumen impaction. Both effects would have produced conductive hearing loss, a serious impairment in a Pleistocene foraging context. PMID:29232394

External auditory exostoses in the Xuchang and Xujiayao human remains: Patterns and implications among eastern Eurasian Middle and Late Pleistocene crania.

PubMed

Trinkaus, Erik; Wu, Xiu-Jie

2017-01-01

In the context of Middle and Late Pleistocene eastern Eurasian human crania, the external auditory exostoses (EAE) of the late archaic Xuchang 1 and 2 and the Xujiayao 15 early Late Pleistocene human temporal bones are described. Xujiayao 15 has small EAE (Grade 1), Xuchang 1 presents bilateral medium EAE (Grade 2), and Xuchang 2 exhibits bilaterally large EAE (Grade 3), especially on the right side. These cranial remains join the other eastern Eurasian later Pleistocene humans in providing frequencies of 61% (N = 18) and 58% (N = 12) respectively for archaic and early modern human samples. These values are near the upper limits of recent human frequencies, and they imply frequent aquatic exposure among these Pleistocene humans. In addition, the medial extents of the Xuchang 1 and 2 EAE would have impinged on their tympanic membranes, and the large EAE of Xuchang 2 would have resulted in cerumen impaction. Both effects would have produced conductive hearing loss, a serious impairment in a Pleistocene foraging context.

Hot melt extruded and injection moulded disulfiram-loaded PLGA millirods for the treatment of glioblastoma multiforme via stereotactic injection.

PubMed

McConville, Christopher; Tawari, Patricia; Wang, Weiguang

2015-10-15

Glioblastoma multiforme (GBM) has a poor prognosis and is one of the most common primary malignant brain tumours in adults. Stereotactic injections have been used to deliver chemotherapeutic drugs directly into brain tumours. This paper describes the development of disulfiram (DSF)-loaded biodegradable millirods manufactured using hot melt extrusion (HME) and injection moulding (IM). The paper demonstrates that the stability of the DSF within the millirods is dependent on the manufacturing technique used as well as the drug loading. The physical state of the DSF within the millirods was dependent on the fabrication process, with the DSF in the HME millirods being either completely amorphous within the PLGA, while the DSF within the IM millirods retained between 54 and 66% of its crystallinity. Release of DSF from the millirods was dependent on the degradation rate of the PLGA, the manufacturing technique used as well as the DSF loading. DSF in the 10% (w/w) DSF loaded HME millirods and the 20% (w/w) DSF-loaded HME and IM millirods had a similar cytotoxicity against a GBM cell line compared to the unprocessed DSF control. However, the 10% (w/w) DSF-loaded IM millirods had a significantly lower cytotoxicity when compared to the unprocessed control. Copyright © 2015 Elsevier B.V. All rights reserved.

Fusion processing of itraconazole solid dispersions by kinetisol dispersing: a comparative study to hot melt extrusion.

PubMed

DiNunzio, James C; Brough, Chris; Miller, Dave A; Williams, Robert O; McGinity, James W

2010-03-01

KinetiSol Dispersing (KSD) is a novel high energy manufacturing process investigated here for the production of pharmaceutical solid dispersions. Solid dispersions of itraconazole (ITZ) and hypromellose were produced by KSD and compared to identical formulations produced by hot melt extrusion (HME). Materials were characterized for solid state properties by modulated differential scanning calorimetry and X-ray diffraction. Dissolution behavior was studied under supersaturated conditions. Oral bioavailability was determined using a Sprague-Dawley rat model. Results showed that KSD was able to produce amorphous solid dispersions in under 15 s while production by HME required over 300 s. Dispersions produced by KSD exhibited single phase solid state behavior indicated by a single glass transition temperature (T(g)) whereas compositions produced by HME exhibited two T(g)s. Increased dissolution rates for compositions manufactured by KSD were also observed compared to HME processed material. Near complete supersaturation was observed for solid dispersions produced by either manufacturing processes. Oral bioavailability from both processes showed enhanced AUC compared to crystalline ITZ. Based on the results presented from this study, KSD was shown to be a viable manufacturing process for the production of pharmaceutical solid dispersions, providing benefits over conventional techniques including: enhanced mixing for improved homogeneity and reduced processing times. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan.

PubMed

Lee, Jae-Young; Kang, Wie-Soo; Piao, Jingpei; Yoon, In-Soo; Kim, Dae-Duk; Cho, Hyun-Jong

2015-01-01

Soluplus(®) (SP) and D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based solid dispersion (SD) formulations were developed by hot-melt extrusion (HME) to improve oral bioavailability of valsartan (VST). HME process with twin-screw configuration for generating a high shear stress was used to prepare VST SD formulations. The thermodynamic state of the drug and its dispersion in the polymers were evaluated by solid-state studies, including Fourier-transform infrared, X-ray diffraction, and differential scanning calorimetry. Drug release from the SD formulations was assessed at pH values of 1.2, 4.0, and 6.8. Pharmacokinetic study was performed in rats to estimate the oral absorption of VST. HME with a high shear rate produced by the twin-screw system was successfully applied to prepare VST-loaded SD formulations. Drug amorphization and its molecular dispersion in the polymer matrix were verified by several solid-state studies. Drug release from SD formulations was improved, compared to the pure drug, particularly at pH 6.8. Oral absorption of drug in rats was also enhanced in SP and TPGS-based SD groups compared to that in the pure drug group. SP and TPGS-based SDs, prepared by the HME process, could be used to improve aqueous solubility, dissolution, and oral absorption of poorly water-soluble drugs.

Cavernous sinus syndrome due to osteochondromatosis in a cat.

PubMed

Perazzi, Anna; Bernardini, Marco; Mandara, Maria T; De Benedictis, Giulia M; De Strobel, Francesca; Zotti, Alessandro

2013-12-01

A 1-year-old sexually intact male Korat cat was referred for ophthalmological consultation due to anisocoria. Mydriasis with external ophthalmoplegia and absence of pupillary light responses in the right eye and nasofacial hypalgesia were seen. Cavernous sinus syndrome (CSS) was suspected. Bilateral deformities of the jaw and phalangeal bones, severe spinal pain and abnormal conformation of the lumbar spine were also present. Radiographic examination revealed several mineralised masses in the appendicular and axial skeleton, indicative of multiple cartilaginous exostoses. For further investigation of the CSS-related neurological deficits, the cat underwent computed tomography (CT) examination of the skull. CT images revealed a non-vascularised, calcified, amorphous mass originating from the right lateral skull base and superimposing on the sella turcica. Based on the severity of diffuse lesions and owing to the clinical signs of extreme pain, the cat was euthanased. A diffuse skeletal and intracranial osteochondromatosis was diagnosed histologically.

Enantioselective quantitation of the ecstasy compound (R)- and (S)-N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma and urine.

PubMed

Buechler, Jochen; Schwab, Matthias; Mikus, Gerd; Fischer, Beate; Hermle, Leo; Marx, Claudia; Grön, Georg; Spitzer, Manfred; Kovar, Karl Artur

2003-08-15

An enantioselective HPLC method has been developed and validated for the stereospecific analysis of N-ethyl-3,4-methylenedioxyamphetamine (MDE) and its major metabolites N-ethyl-4-hydroxy-3-methoxyamphetamine (HME) and 3,4-methylenedioxyamphetamine (MDA). These compounds have been analyzed both from human plasma and urine after administration of 70 mg pure MDE-hydrochloride enantiomers to four subjects. The samples were prepared by hydrolysis of the o-glucuronate and sulfate conjugates using beta-glucuronidase/arylsulfatase and solid-phase extraction with a cation-exchange phase. A chiral stationary protein phase (chiral-CBH) was used for the stereoselective determination of MDE, HME and MDA in a single HPLC run using sodium dihydrogenphosphate, ethylendiaminetetraacetic acid disodium salt and isopropanol as the mobile phase (pH 6.44) and fluorimetric detection (lambda(ex) 286 nm, lambda(em) 322 nm). Moreover, a suitable internal standard (N-ethyl-3,4-methylenedioxybenzylamine) was synthesized and qualified for quantitation purposes. The method showed high recovery rates (>95%) and limits of quantitation for MDE and MDA of 5 ng/ml and for HME of 10 ng/ml. The RSDs for all working ranges of MDE, MDA and HME in plasma and urine, respectively, were less than 1.5%. After validation of the analytical methods in plasma and urine samples pharmacokinetic parameters were calculated. The plasma concentrations of (R)-MDE exceeded those of the S-enantiomer (ratio R:S of the area under the curve, 3.1) and the plasma half time of (R)-MDE was longer than that of (S)-MDE (7.9 vs. 4.0 h). In contrast, the stereochemical disposition of the MDE metabolites HME and MDA was reversed. Concentrations of the (S)-metabolites in plasma of volunteers were much higher than those of the (R)-enantiomers.

A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices.

PubMed

Verstraete, G; Mertens, P; Grymonpré, W; Van Bockstal, P J; De Beer, T; Boone, M N; Van Hoorebeke, L; Remon, J P; Vervaet, C

2016-11-20

During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of processing on the surface physical stability of amorphous solid dispersions.

PubMed

Yang, Ziyi; Nollenberger, Kathrin; Albers, Jessica; Moffat, Jonathan; Craig, Duncan; Qi, Sheng

2014-11-01

The focus of this study was to investigate the effect of processing on the surface crystallization of amorphous molecular dispersions and gain insight into the mechanisms underpinning this effect. The model systems, amorphous molecular dispersions of felodipine-EUDRAGIT® E PO, were processed both using spin coating (an ultra-fast solvent evaporation based method) and hot melt extrusion (HME) (a melting based method). Amorphous solid dispersions with drug loadings of 10-90% (w/w) were obtained by both processing methods. Samples were stored under 75% RH/room temperatures for up to 10months. Surface crystallization was observed shortly after preparation for the HME samples with high drug loadings (50-90%). Surface crystallization was characterized by powder X-ray diffraction (PXRD), ATR-FTIR spectroscopy and imaging techniques (SEM, AFM and localized thermal analysis). Spin coated molecular dispersions showed significantly higher surface physical stability than hot melt extruded samples. For both systems, the progress of the surface crystal growth followed zero order kinetics on aging. Drug enrichment at the surfaces of HME samples on aging was observed, which may contribute to surface crystallization of amorphous molecular dispersions. In conclusion it was found the amorphous molecular dispersions prepared by spin coating had a significantly higher surface physical stability than the corresponding HME samples, which may be attributed to the increased process-related apparent drug-polymer solubility and reduced molecular mobility due to the quenching effect caused by the rapid solvent evaporation in spin coating. Copyright © 2014 Elsevier B.V. All rights reserved.

Rheology as a tool for evaluation of melt processability of innovative dosage forms.

PubMed

Aho, Johanna; Boetker, Johan P; Baldursdottir, Stefania; Rantanen, Jukka

2015-10-30

Future manufacturing of pharmaceuticals will involve innovative use of polymeric excipients. Hot melt extrusion (HME) is an already established manufacturing technique and several products based on HME are on the market. Additionally, processing based on, e.g., HME or three dimensional (3D) printing, will have an increasingly important role when designing products for flexible dosing, since dosage forms based on compacting of a given powder mixture do not enable manufacturing of optimal pharmaceutical products for personalized treatments. The melt processability of polymers and API-polymer mixtures is highly dependent on the rheological properties of these systems, and rheological measurements should be considered as a more central part of the material characterization tool box when selecting suitable candidates for melt processing by, e.g., HME or 3D printing. The polymer processing industry offers established platforms, methods, and models for rheological characterization, and they can often be readily applied in the field of pharmaceutical manufacturing. Thoroughly measured and calculated rheological parameters together with thermal and mechanical material data are needed for the process simulations which are also becoming increasingly important. The authors aim to give an overview to the basics of rheology and summarize examples of the studies where rheology has been utilized in setting up or evaluating extrusion processes. Furthermore, examples of different experimental set-ups available for rheological measurements are presented, discussing each of their typical application area, advantages and limitations. Copyright © 2015 Elsevier B.V. All rights reserved.

The Humidity in a Low-Flow Dräger Fabius Anesthesia Workstation with or without Thermal Insulation or a Heat and Moisture Exchanger: A Prospective Randomized Clinical Trial

PubMed Central

de Oliveira, Sergius A. R.; Lucio, Lorena M. C.; Modolo, Norma S. P.; Hayashi, Yoko; Braz, Mariana G.; de Carvalho, Lídia R.; Braz, Leandro G.; Braz, José Reinaldo C.

2017-01-01

Background During anesthesia, as compared with intensive care, the time of the tracheal intubation is much shorter. An inhaled gas minimum humidity of 20 mgH2O.L-1 is recommended to reduce the deleterious effects of dry gas on the airways during anesthesia with tracheal intubation. The Fabius GS Premium® anesthesia workstation (Dräger Medical, Lübeck, Germany) has a built-in hotplate to heat gases in the breathing circuit. A heat and moisture exchanger (HME) is used to further heat and humidify the inhaled gas. The humidity of the gases in the breathing circuit is influenced by the ambient temperature. We compared the humidity of the inhaled gases from a low-flow Fabius anesthesia workstation with or without thermal insulation (TI) of the breathing circuit and with or without an HME. Methods We conducted a prospective randomized trial in 41 adult female patients who underwent elective abdominal surgery. The patients were allocated into four groups according to the devices used to ventilate their lungs using a Dräger Fabius anesthesia workstation with a low gas flow (1 L.min-1): control, with TI, with an HME or with TI and an HME (TIHME). The mean temperature and humidity of the inhaled gases were measured during 2-h after connecting the patients to the breathing circuit. Results The mean inhaled gas temperature and absolute humidity were higher in the HME (29.2±1.3°C; 28.1±2.3 mgH2O·L-1) and TIHME (30.1±1.2°C; 29.4±2.0 mgH2O·L-1) groups compared with the control (27.5±1.0°C; 25.0±1.8 mgH2O·L-1) and TI (27.2±1.1°C; 24.9±1.8 mgH2O·L-1) groups (P = 0.003 and P<0.001, respectively). Conclusions The low-flow Fabius GS Premium breathing circuit provides the minimum humidity level of inhaled gases to avoid damage to the tracheobronchial epithelia during anesthesia. TI of the breathing circuit does not increase the humidity of the inhaled gases, whereas inserting an HME increases the moisture of the inhaled gases closer to physiological values. PMID:28129353

Ventilator-associated pneumonia using a heated humidifier or a heat and moisture exchanger: a randomized controlled trial [ISRCTN88724583

PubMed Central

Lorente, Leonardo; Lecuona, María; Jiménez, Alejandro; Mora, María L; Sierra, Antonio

2006-01-01

Introduction Some guidelines to prevent ventilator-associated pneumonia (VAP) do not establish a recommendation for the preferential use of either heat and moisture exchangers (HMEs) or heated humidifiers (HHs), while other guidelines clearly advocate the use of HMEs. The aim of this study was to determine the incidence of VAP associated with HHs or HMEs. Methods A randomized study was conducted in the intensive care unit of a university hospital involving patients expected to require mechanical ventilation for >5 days. Patients were assigned to two groups; one group received HH and the other group received HME. Tracheal aspirate samples were obtained on endotracheal intubation, then twice a week, and finally on extubation, in order to diagnose VAP. Throat swabs were taken on admission to the intensive care unit, then twice a week, and finally at discharge from the intensive care unit in order to classify VAP as primary endogenous, secondary endogenous, or exogenous. Results A total of 120 patients were assigned to HMEs (60 patients) and HHs (60 patients); 16 patients received mechanical ventilation for less than five days and were excluded from the analysis. Data analysis of the remaining 104 patients (53 HMEs and 51 HHs) showed no significant differences between groups regarding sex, age, Acute Physiology and Chronic Health Evaluation II score, pre-VAP use of antibiotics, days on mechanical ventilation, and diagnosis group. VAP was found in eight of 51 (15.69%) patients in the HH group and in 21 of 53 (39.62%) patients in the HME group (P = 0.006). The median time free of VAP was 20 days (95% confidence interval, 13.34–26.66) for the HH group and was 42 days (95% confidence interval, 35.62–48.37) for the HME group (P <0.001). Cox regression analysis showed the HME as a risk factor for VAP (hazard rate, 16.2; 95% confidence interval, 4.54–58.04; P < 0.001). Conclusion The patients mechanically ventilated for more than five days developed a lower incidence of VAP with a HH than with a HME. PMID:16884530

Effectiveness of Humidification with Heat and Moisture Exchanger-booster in Tracheostomized Patients.

PubMed

Gonzalez, Isabel; Jimenez, Pilar; Valdivia, Jorge; Esquinas, Antonio

2017-08-01

The two most commonly used types of humidifiers are heated humidifiers and heat and moisture exchange humidifiers. Heated humidifiers provide adequate temperature and humidity without affecting the respiratory pattern, but overdose can cause high temperatures and humidity resulting in condensation, which increases the risk of bacteria in the circuit. These devices are expensive. Heat and moisture exchanger filter is a new concept of humidification, increasing the moisture content in inspired gases. This study aims to determine the effectiveness of the heat and moisture exchanger (HME)-Booster system to humidify inspired air in patients under mechanical ventilation. We evaluated the humidification provided by 10 HME-Booster for tracheostomized patients under mechanical ventilation using Servo I respirators, belonging to the Maquet company and Evita 4. There was an increase in the inspired air humidity after 1 h with the humidifier. The HME-Booster combines the advantages of heat and moisture exchange minimizing the negatives. It increases the amount of moisture in inspired gas in mechanically ventilated tracheostomized patients. It is easy and safe to use. The type of ventilator used has no influence on the result.

Water content of delivered gases during non-invasive ventilation in healthy subjects.

PubMed

Lellouche, François; Maggiore, Salvatore Maurizio; Lyazidi, Aissam; Deye, Nicolas; Taillé, Solenne; Brochard, Laurent

2009-06-01

No clear recommendation exists concerning humidification during non-invasive ventilation (NIV) and high flow CPAP, and few hygrometric data are available. We measured hygrometry during NIV delivered to healthy subjects with different humidification strategies: heated humidifier (HH), heat and moisture exchanger, (HME) or no humidification (NoH). For each strategy, a turbine and an ICU ventilator were used with different FiO(2) settings, with and without leaks. During CPAP, two different HH and NoH were tested. Inspired gases hygrometry was measured, and comfort was assessed. On a bench, we also assessed the impact of ambient air temperature, ventilator temperature and minute ventilation on HH performances (with NIV settings). During NIV, with NoH, gas humidity was very low when an ICU ventilator was used (5 mgH(2)O/l), but equivalent to ambient air hygrometry with a turbine ventilator at minimal FiO(2) (13 mgH(2)O/l). HME and HH had comparable performances (25-30 mgH(2)O/l), but HME's effectiveness was reduced with leaks (15 mgH(2)O/l). HH performances were reduced by elevated ambient air and ventilator output temperatures. During CPAP, dry gases (5 mgH(2)O/l) were less tolerated than humidified gases. Gases humidified at 15 or 30 mgH(2)O/l were equally tolerated. This study provides data on the level of humidity delivered with different humidification strategies during NIV and CPAP. HH and HME provide gas with the highest water content. Comfort data suggest that levels above 15 mgH(2)O/l are well tolerated. In favorable conditions, HH and HMEs are capable of providing such values, even in the presence of leaks.

Heat and moisture exchangers and heated humidifiers in acute lung injury/acute respiratory distress syndrome patients. Effects on respiratory mechanics and gas exchange.

PubMed

Morán, Indalecio; Bellapart, Judith; Vari, Alessandra; Mancebo, Jordi

2006-04-01

To compare, in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, the short-term effects of heat and moisture exchangers (HME) and heated humidifiers (HH) on gas exchange, and also on respiratory system mechanics when isocapnic conditions are met. Prospective open clinical study. Intensive Care Service. Seventeen invasively ventilated ALI/ARDS patients. The study was performed in three phases: (1) determinations were made during basal ventilatory settings with HME; (2) basal ventilatory settings were maintained and HME was replaced by an HH; (3) using the same HH, tidal volume (Vt) was decreased until basal PaCO2 levels were reached. FiO2, respiratory rate and PEEP were kept unchanged. Respiratory mechanics, Vdphys, gas exchange and hemodynamic parameters were obtained at each phase. By using HH instead of HME and without changing Vt, PaCO2 decreased from 46+/-9 to 40+/-8 mmHg (p<0.001) and Vdphys decreased from 352+/-63 to 310+/-74 ml (p<0.001). Comparing the first phase with the third, Vt decreased from 521+/-106 to 440+/-118 ml (p<0.001) without significant changes in PaCO2, Vd/Vt decreased from 0.69+/-0.11 to 0.62+/-0.12 (p<0.001), plateau airway pressure decreased from 25+/-6 to 21+/-6 cmH2O (p<0.001) and respiratory system compliance improved from 35+/-12 to 42+/-15 ml/cmH2O (p<0.001). PaO2 remained unchanged in the three phases. Reducing dead space with the use of HH decreases PaCO2 and more importantly, if isocapnic conditions are maintained by reducing Vt, this strategy improves respiratory system compliance and reduces plateau airway pressure.

Rheology Guided Rational Selection of Processing Temperature To Prepare Copovidone-Nifedipine Amorphous Solid Dispersions via Hot Melt Extrusion (HME).

PubMed

Yang, Fengyuan; Su, Yongchao; Zhang, Jingtao; DiNunzio, James; Leone, Anthony; Huang, Chengbin; Brown, Chad D

2016-10-03

The production of amorphous solid dispersions via hot melt extrusion (HME) relies on elevated temperature and prolonged residence time, which can result in potential degradation and decomposition of thermally sensitive components. Herein, the rheological properties of a physical mixture of polymer and an active pharmaceutical ingredient (API) were utilized to guide the selection of appropriate HME processing temperature. In the currently studied copovidone-nifedipine system, a critical temperature, which is substantially lower (∼13 °C) than the melting point of crystalline API, was captured during a temperature ramp examination and regarded as the critical point at which the API could molecularly dissolve into the polymer. Based on the identification of this critical point, various solid dispersions were prepared by HME processing below, at, and above the critical temperature (both below and above the melting temperature (T m ) of crystalline API). In addition, the resultant extrudates along with two control solid dispersions prepared by physical mixing and cryogenic milling were assessed by X-ray diffraction, differential scanning calorimetry, hot stage microscopy, rheology, and solid-state NMR. Physicochemical properties of resultant solid dispersions indicated that the identified critical temperature is sufficient for the polymer-API system to reach a molecular-level mixing, manifested by the transparent and smooth appearance of extrudates, the absence of API crystalline diffraction and melting peaks, dramatically decreased rheological properties, and significantly improved polymer-API miscibility. Once the critical temperature has been achieved, further raising the processing temperature only results in limited improvement of API dispersion, reflected by slightly reduced storage modulus and complex viscosity and limited improvement in miscibility.

Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale.

PubMed

Agrawal, Anjali M; Dudhedia, Mayur S; Zimny, Ewa

2016-02-01

The objective of the study was to develop an amorphous solid dispersion (ASD) for an insoluble compound X by hot melt extrusion (HME) process. The focus was to identify material-sparing approaches to develop bioavailable and stable ASD including scale up of HME process using minimal drug. Mixtures of compound X and polymers with and without surfactants or pH modifiers were evaluated by hot stage microscopy (HSM), polarized light microscopy (PLM), and modulated differential scanning calorimetry (mDSC), which enabled systematic selection of ASD components. Formulation blends of compound X with PVP K12 and PVP VA64 polymers were extruded through a 9-mm twin screw mini-extruder. Physical characterization of extrudates by PLM, XRPD, and mDSC indicated formation of single-phase ASD's. Accelerated stability testing was performed that allowed rapid selection of stable ASD's and suitable packaging configurations. Dissolution testing by a discriminating two-step non-sink dissolution method showed 70-80% drug release from prototype ASD's, which was around twofold higher compared to crystalline tablet formulations. The in vivo pharmacokinetic study in dogs showed that bioavailability from ASD of compound X with PVP VA64 was four times higher compared to crystalline tablet formulations. The HME process was scaled up from lab scale to clinical scale using volumetric scale up approach and scale-independent-specific energy parameter. The present study demonstrated systematic development of ASD dosage form and scale up of HME process to clinical scale using minimal drug (∼500 g), which allowed successful clinical batch manufacture of enabled formulation within 7 months.

Earthquake-triggered landslides along the Hyblean-Malta Escarpment (off Augusta, eastern Sicily, Italy) - assessment of the related tsunamigenic potential

NASA Astrophysics Data System (ADS)

Ausilia Paparo, Maria; Armigliato, Alberto; Pagnoni, Gianluca; Zaniboni, Filippo; Tinti, Stefano

2017-02-01

Eastern Sicily is affected by earthquakes and tsunamis of local and remote origin, which is known through numerous historical chronicles. Recent studies have put emphasis on the role of submarine landslides as the direct cause of the main local tsunamis, envisaging that earthquakes (in 1693 and 1908) did produce a tsunami, but also that they triggered mass failures that were able to generate an even larger tsunami. The debate is still open, and though no general consensus has been found among scientists so far, this research had the merit to attract attention on possible generation of tsunamis by landslides off Sicily. In this paper we investigate the tsunami potential of mass failures along one sector of the Hyblean-Malta Escarpment (HME). facing Augusta. The HME is the main offshore geological structure of the region running almost parallel to the coast, off eastern Sicily. Here, bottom morphology and slope steepness favour soil failures. In our work we study slope stability under seismic load along a number of HME transects by using the Minimun Lithostatic Deviation (MLD) method, which is based on the limit-equilibrium theory. The main goal is to identify sectors of the HME that could be unstable under the effect of realistic earthquakes. We estimate the possible landslide volume and use it as input for numerical codes to simulate the landslide motion and the consequent tsunami. This is an important step for the assessment of the tsunami hazard in eastern Sicily and for local tsunami mitigation policies. It is also important in view of tsunami warning system since it can help to identify the minimum earthquake magnitude capable of triggering destructive tsunamis induced by landslides, and therefore to set up appropriate knowledge-based criteria to launch alert to the population.

PLA/PEG-PPG-PEG/dexamethasone implant prepared by hot-melt extrusion for controlled release of immunosuppressive drug to implantable medical devices, Part 2: in vivo evaluation.

PubMed

Li, DeXia; Guo, Gang; Deng, Xin; Fan, RangRang; Guo, QingFa; Fan, Min; Liang, Jian; Luo, Feng; Qian, ZhiYong

2013-01-01

Hot-melt extrusion (HME) plays an important role in preparing implants as local drug delivery systems in pharmaceutical fields. Here, a new PLA/PEG-PPG-PEG/Dexamethasone (PLA/F68/Dex) implant prepared by HME has been developed. Importantly, the implant was successfully achieved to control release of immunosuppressive drug to an implanted device. In particular, this implant has not been reported previously in pharmaceutical fields. FTIR and XRD were adopted to investigate the properties of the samples. The in vivo release study showed that the maximum value of Dex release from the implants was approximately 50% at 1 month. The in vivo degradation behavior was determined by UV spectrophotometer and scanning electron microscopy studies, and the weight loss rate of the implants were up to 25% at 1 month. Furthermore, complete blood count (CBC) test, serum chemistry and major organs were performed, and there is no significant lesion and side effects observed in these results. Therefore, the results elucidated that the new PLA/F68/Dex implant prepared by HME could deliver an immunosuppressive drug to control the inflammatory reaction at the implant site.

Evaluation of the efficiency of heat and moisture exchangers during paediatric anaesthesia.

PubMed

Luchetti, M; Pigna, A; Gentili, A; Marraro, G

1999-01-01

This study evaluates the efficiency of heat and moisture exchangers (HMEs) in allowing adequate humidification and warming during anaesthesia in children. Eighteen paediatric patients undergoing anaesthesia were divided into two groups: group A ten patients: infants up to 10 kg-->Hygrobaby HME; group B 8 patients: children above 10 kg-->Hygroboy HME. The following parameters were evaluated: body temperature (bT), room temperature (rT), fresh gas temperature, HME warm-up time, inspired and expired gases temperature and humidity, conserving efficiency, and duration of anaesthesia. Gas temperatures were recorded by means of a recorder fitted with four thermal probes. Humidity values were mathematically derived. The correlation between efficiency and rT, bT, and fresh gas temperature was computed. In both groups the inspired gases temperatures were below 30 degrees C. Inspired absolute humidity was never more than 28 mgH2O.l(-1). The conserving efficiency was good (0.93 in both groups). A positive correlation was found between efficiency and fresh gas temperature. HMEs did not meet the minimum standards for humidity and heating during anaesthesia in children, although their conserving efficiency was found to be satisfactory.

Effectiveness of Humidification with Heat and Moisture Exchanger-booster in Tracheostomized Patients

PubMed Central

Gonzalez, Isabel; Jimenez, Pilar; Valdivia, Jorge; Esquinas, Antonio

2017-01-01

Background: The two most commonly used types of humidifiers are heated humidifiers and heat and moisture exchange humidifiers. Heated humidifiers provide adequate temperature and humidity without affecting the respiratory pattern, but overdose can cause high temperatures and humidity resulting in condensation, which increases the risk of bacteria in the circuit. These devices are expensive. Heat and moisture exchanger filter is a new concept of humidification, increasing the moisture content in inspired gases. Aims: This study aims to determine the effectiveness of the heat and moisture exchanger (HME)-Booster system to humidify inspired air in patients under mechanical ventilation. Materials and Methods: We evaluated the humidification provided by 10 HME-Booster for tracheostomized patients under mechanical ventilation using Servo I respirators, belonging to the Maquet company and Evita 4. Results: There was an increase in the inspired air humidity after 1 h with the humidifier. Conclusion: The HME-Booster combines the advantages of heat and moisture exchange minimizing the negatives. It increases the amount of moisture in inspired gas in mechanically ventilated tracheostomized patients. It is easy and safe to use. The type of ventilator used has no influence on the result. PMID:28904484

Quantitation of N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma by high-performance liquid chromatography and fluorescence detection.

PubMed

Brunnenberg, M; Lindenblatt, H; Gouzoulis-Mayfrank, E; Kovar, K A

1998-11-20

A HPLC method has been developed for the analogue of Ecstasy MDE and its major metabolites N-ethyl-4-hydroxy-3-methoxyamphetamine (HME) and 3,4-methylenedioxyamphetamine (MDA) in human plasma. In the course of our investigations we found that the methylenedioxyamphetamines and HME exhibit fluorescence at 322 nm. Therefore the detection could be carried out with a fluorescence (FL) detector. Solid-phase extraction was used for sample preparation and yielded high recovery rates greater than 95%. The limit of quantitation for MDE and its metabolites in the extracts was between 1.5 and 8.9 ng/ml and the method standard deviations were less than 5%. This sensitive, rapid and reliable analytical method has been used successfully in the quantitation of the substances in plasma samples obtained from 14 volunteers in two clinical studies after p.o. administration of 100 to 140 mg MDE*HCI. The maximum plasma concentrations were 235-465 ng/ml (MDE), 67-673 ng/ml (HME) and 7-33 ng/ml (MDA), respectively. Pharmacokinetic parameters have been investigated using the plasma concentration curves.

Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

PubMed

Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

2015-12-30

The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms. Copyright © 2015. Published by Elsevier B.V.

Devices used to humidify respired gases.

PubMed

Rathgeber, Jörg

2006-06-01

The efficiency of HMEs decreases with increasing tidal volumes. HMEs always result in an elevation of the inspiratory and expiratory airway resistances; this should be considered especially in cases that involve spontaneous respiration. The pressure drop across HMEs should be less than 2 hPa for a flow of 60 L/min, a level that also has been measured for cascade humidifiers.HMEs with a hygroscopic coating of CaCl2 should be given preference over LiCl-coated ones, especially because products of the same efficiency are available with CaCl2 coating. Lithium is a potentially toxic substance that can be taken up by way of bronchopulmonary resorption after accidental washing out [37]. Therefore, a possible safety hazard cannot be eliminated, especially in neonates and babies. Not least for these reasons HMEs must never be combined with active humidification systems or medication nebulizers. Even if the reduction in functional efficiency of the HME that is caused by washing off of the coating of hygroscopic substances is disregarded, the presence of medication aerosols in the HME, in particular, can result in a dangerous increase in resistance to gas flow. The internal volumes of HMEs should be as small as possible so that they do not increase the effective deadspace too much. A combination of HMEsand catheter mounts results in a further increase in the deadspace, and there-fore, must be considered critically, especially in cases that involve spontaneous respiration. If a catheter mount is necessary to add flexibility to the breathing system, the HME preferably should be connected directly onto the tracheal tube with the catheter mount behind it; otherwise, the humidification efficiency of the HME will be reduced by condensation in the catheter mount. Children should be ventilated with special HMEs that have a small internal volume. Caution is required in patients who have elevated sputum production, pulmonary trauma with bleeding, pulmonary edema, or a similar condition;in such patients a partial obstruction of the HME with a resulting elevation of the airway resistances might occur. In patients who have very viscous secretions (eg, as a result of a primary pulmonary disease or long-term dehydration therapy), heated humidifiers with a set temperature of greater than 370 degrees C should be given preference. Several recent investigations showed that not every device that is designated as an HME is appropriate for conditioning respiratory gases (ie, it effectively humidifies the inspiratory air). Most of the products that are available on the market are, at best, adequate for anesthetic ventilation or short-term postoperative follow-up ventilation. Generally, this is true of all HMEs that have not been coated with hygroscopic substances. CoatedHMEs have a much better humidification efficiency; however, here too, the existence of substantial differences in quality among the products prohibits an uncritical application.

Heat and moisture exchange devices for patients undergoing total laryngectomy.

PubMed

Icuspit, Pearl; Yarlagadda, Bharat; Garg, Shweta; Johnson, Theresa; Deschler, Daniel

2014-01-01

Patients undergoing total laryngectomy face the challenge of an altered anatomy with the resultant changes in quality of life and significant requirements for post-operative care. Increased production of secretions and sputum, the need for ongoing suctioning, and the formation of stomal crusting require meticulous post-operative care. The use of Heat and Moisture Exchange (HME) devices has been shown to decrease the effect of these factors. This article describes the nature of these devices and their use. The literature is reviewed regarding the long term benefits and new data are presented suggesting an immediate post-operative benefit as well. Finally, costs and other considerations for successful use of HME devices are presented.

Expanding the Library of Uranyl Amide Derivatives: New Complexes Featuring the tert-Butyldimethylsilylamide Ligand.

PubMed

Pattenaude, Scott A; Coughlin, Ezra J; Collins, Tyler S; Zeller, Matthias; Bart, Suzanne C

2018-04-16

New uranyl derivatives featuring the amide ligand, -N(SiHMe 2 ) t Bu, were synthesized and characterized by X-ray crystallography, multinuclear NMR spectroscopy, and absorption spectroscopies. Steric properties of these complexes were also quantified using the computational program Solid-G. The increased basicity of the free ligand -N(SiHMe 2 ) t Bu was demonstrated by direct comparison to -N(SiMe 3 ) 2 , a popular supporting ligand for uranyl. Substitutional lability on a uranyl center was also demonstrated by exchange with the -N(SiMe 3 ) 2 ligand. The increased basicity of this ligand and diverse characterization handles discussed here will make these compounds useful synthons for future reactivity.

The Hygroscopic Condenser Humidifier. A new device for general use in anaesthesia and intensive care.

PubMed

Gedeon, A; Mebius, C

1979-01-01

The design and performance of the Hygroscopic Condenser Humidifier (HCH) are described. In principle the HCH consists of two parts, a conventional Heat-Moisture-Exchanger (HME) and a hygroscopic unit. The hygroscopic action is shown to improve the water retention efficiency of the device by about a factor of two as compared with optimal HME designs. As a result, humidification levels corresponding to around 80% relative humidity at 37 degrees C are obtained in the trachea and this is also achieved when completely dry gases are delivered to the patient. The unit can therefore be used for all procedures in anaesthesia and in intensive care.

Harnessing 3D models of mammary epithelial morphogenesis. An off the beaten path approach to identify candidate biomarkers of early stage breast cancer

PubMed Central

Rossetti, Stefano; Bshara, Wiam; Reiners, Johanna A.; Corlazzoli, Francesca; Miller, Austin; Sacchi, Nicoletta

2016-01-01

Regardless of the etiological factor, an aberrant morphology is the common hallmark of ductal carcinoma in situ (DCIS), which is a highly heterogeneous disease. To test if critical core morphogenetic mechanisms are compromised by different mutations, we performed proteomics analysis of five mammary epithelial HME1 mutant lines that develop a DCIS-like morphology in three dimensional (3D) culture. Here we show first, that all HME1 mutant lines share a common protein signature highlighting an inverse deregulation of two annexins, ANXA2 and ANXA8. Either ANXA2 downregulation or ANXA8 upregulation in the HME1 cell context are per se sufficient to confer a 3D DCIS-like morphology. Seemingly, different mutations impinged on a common mechanism that differentially regulates the two annexins. Second, we show that ANXA8 expression is significantly higher in DCIS tissue samples versus normal breast tissue and atypical ductal hyperplasia (ADH). Apparently, ANXA8 expression is significantly more upregulated in ER- negative versus ER-positive cases, and significantly correlates with tumor stage, grade and positive lymph node. Based on our study, 3D mammary morphogenesis models can be an alternate/complementary strategy for unraveling new DCIS mechanisms and biomarkers. PMID:27422542

Oecomys catherinae (Sigmodontinae, Cricetidae): Evidence for chromosomal speciation?

PubMed

Malcher, Stella Miranda; Pieczarka, Julio Cesar; Geise, Lena; Rossi, Rogério Vieira; Pereira, Adenilson Leão; O'Brien, Patricia Caroline Mary; Asfora, Paulo Henrique; Fonsêca da Silva, Victor; Sampaio, Maria Iracilda; Ferguson-Smith, Malcolm Andrew; Nagamachi, Cleusa Yoshiko

2017-01-01

Among the Oryzomyini (Sigmodontinae), Oecomys is the most speciose, with 17 species. This genus presents high karyotypic diversity (2n = 54 to 2n = 86) and many taxonomic issues at the species level because of the presence of cryptic species and the overlap of morphological characters. For these reasons the real number of species of Oecomys may be underestimated. With the aim of verifying if the taxon Oecomys catherinae is composed of more than one species, we made comparative studies on two populations from two regions of Brazil, one from the Amazon and another from the Atlantic Forest using both classical cytogenetics (G- and C-banding) and comparative genomic mapping with whole chromosome probes of Hylaeamys megacephalus (HME), molecular data (cytochrome b mitochondrial DNA) and morphology. Our results confirm that Oecomys catherinae occurs in the southeast Amazon, and reveal a new karyotype for the species (2n = 62, FNa = 62). The comparative genomic analysis with HME probes identified chromosomal homeologies between both populations and rearrangements that are responsible for the different karyotypes. We compared our results in Sigmodontinae genera with other studies that also used HME probes. These chromosomal differences together with the absence of consistent differentiation between the two populations on morphological and molecular analyses suggest that these populations may represent cryptic species.

Mucoperiosteal exostoses in the tympanic bulla of African lions (Panthera leo).

PubMed

Novales, M; Ginel, P J; Diz, A; Blanco, B; Zafra, R; Guerra, R; Mozos, E

2015-03-01

Mucoperiosteal exostoses (MpEs) of the tympanic bulla (TB), also referred as middle-ear otoliths, have been occasionally described in dogs and cats in association with clinical signs of otitis media or as an incidental finding, but they have not been recorded in other species. In this report, we describe the radiographic, gross, and histopathologic features of MpEs in 8 African lions (Panthera leo). All animals (5 males and 3 females) were adults that had been kept in captivity and had their skeletons conserved as part of an anatomic academic collection. A radiographic study revealed mineralized structures in the TB consistent with MpEs in 7 of the 16 examined TB; a computed tomography study identified MpEs in 12 of the 16 TB. Six TB from 4 lions were sectioned, and several MpEs were demineralized for histopathologic analysis. Grossly, MpEs appeared variable in number and shape. Some were globular structures that were loosely attached to the mucosal surface of the TB; others were isolated to coalescent bone spicules extending from the mucoperiosteum. Position was also variable, but MpEs frequently developed in the hypotympanum, especially on the ventromedial aspect of the TB wall. Microscopically, MpEs were composed of osteonal bone growing from the periosteum and not by dystrophic calcification of necrotic tissue debris, as is hypothesized in dogs. © The Author(s) 2014.

Downstream processing from hot-melt extrusion towards tablets: A quality by design approach.

PubMed

Grymonpré, W; Bostijn, N; Herck, S Van; Verstraete, G; Vanhoorne, V; Nuhn, L; Rombouts, P; Beer, T De; Remon, J P; Vervaet, C

2017-10-05

Since the concept of continuous processing is gaining momentum in pharmaceutical manufacturing, a thorough understanding on how process and formulation parameters can impact the critical quality attributes (CQA) of the end product is more than ever required. This study was designed to screen the influence of process parameters and drug load during HME on both extrudate properties and tableting behaviour of an amorphous solid dispersion formulation using a quality-by-design (QbD) approach. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables (barrel temperature: 160-200°C, screw speed: 50-200rpm, throughput: 0.2-0.5kg/h) and drug load (0-20%) as formulation parameter on the hot-melt extrusion (HME) process, extrudate and tablet quality of Soluplus ® -Celecoxib amorphous solid dispersions. A prominent impact of the formulation parameter on the CQA of the extrudates (i.e. solid state properties, moisture content, particle size distribution) and tablets (i.e. tabletability, compactibility, fragmentary behaviour, elastic recovery) was discovered. The resistance of the polymer matrix to thermo-mechanical stress during HME was confirmed throughout the experimental design space. In addition, the suitability of Raman spectroscopy as verification method for the active pharmaceutical ingredient (API) concentration in solid dispersions was evaluated. Incorporation of the Raman spectroscopy data in a PLS model enabled API quantification in the extrudate powders with none of the DOE-experiments resulting in extrudates with a CEL content deviating>3% of the label claim. This research paper emphasized that HME is a robust process throughout the experimental design space for obtaining amorphous glassy solutions and for tabletting of such formulations since only minimal impact of the process parameters was detected on the extrudate and tablet properties. However, the quality of extrudates and tablets can be optimized by adjusting specific formulations parameters (e.g. drug load). Copyright © 2017 Elsevier B.V. All rights reserved.

β-SiH-containing tris(silazido) rare-earth complexes as homogeneous and grafted single-site catalyst precursors for hydroamination

DOE PAGES

Eedugurala, Naresh; Wang, Zhuoran; Yan, KaKing; ...

2017-01-25

A series of homoleptic rare-earth silazido compounds and their silica-grafted derivatives were prepared to compare spectroscopic and catalytic features under homogeneous and interfacial conditions. Trivalent tris(silazido) compounds Ln{N(SiHMe 2) tBu} 3 (Ln = Sc (1), Y (2), Lu (3)) are prepared in high yield by salt metathesis reactions. Solution-phase and solid-state characterization of 1–3 by NMR and IR spectroscopy and X-ray diffraction reveals Ln←H–Si interactions. These features are retained in solvent-coordinated 2·Et 2O, 2·THF, and 3·THF. The change in spectroscopic features characterizing the secondary interactions (ν SiH, 1 J SiH) from the unactivated SiH in the silazane HN(SiHMe 2) tBumore » follows the trend 3 > 2 > 1 ≈ 2·Et 2O > 2·THF ≈ 3·THF. Ligand lability follows the same pattern, with Et 2O readily dissociating from 2·Et 2O while THF is displaced only during surface grafting reactions. 1 and 2·THF graft onto mesoporous silica nanoparticles (MSN) to give Ln{N(SiHMe 2) tBu} n@MSN (Ln = Sc (1@MSN), Y (2@MSN)) along with THF and protonated silazido as HN(SiHMe 2) tBu and H 2N tBu. The surface species are characterized by multinuclear and multidimensional solid-state (SS) NMR spectroscopic techniques, as well as diffuse reflectance FTIR, elemental analysis, and reaction stoichiometry. A key 1 J SiH SSNMR measurement reveals that the grafted sites most closely resemble Ln·THF adducts, suggesting that siloxane coordination occurs in grafted compounds. These species catalyze the hydroamination/bicyclization of aminodialkenes, and both solution-phase and interfacial conditions provide the bicyclized product with equivalent cis:trans ratios. As a result, similar diastereoselectivities mediated by catalytic sites under the two conditions suggest similar effective environments.« less

Heat and moisture exchangers versus heated humidifiers for mechanically ventilated adults and children.

PubMed

Gillies, Donna; Todd, David A; Foster, Jann P; Batuwitage, Bisanth T

2017-09-14

Invasive ventilation is used to assist or replace breathing when a person is unable to breathe adequately on their own. Because the upper airway is bypassed during mechanical ventilation, the respiratory system is no longer able to warm and moisten inhaled gases, potentially causing additional breathing problems in people who already require assisted breathing. To prevent these problems, gases are artificially warmed and humidified. There are two main forms of humidification, heat and moisture exchangers (HME) or heated humidifiers (HH). Both are associated with potential benefits and advantages but it is unclear whether HME or HH are more effective in preventing some of the negative outcomes associated with mechanical ventilation. This review was originally published in 2010 and updated in 2017. To assess whether heat and moisture exchangers or heated humidifiers are more effective in preventing complications in people receiving invasive mechanical ventilation and to identify whether the age group of participants, length of humidification, type of HME, and ventilation delivered through a tracheostomy had an effect on these findings. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL up to May 2017 to identify randomized controlled trials (RCTs) and reference lists of included studies and relevant reviews. There were no language limitations. We included RCTs comparing HMEs to HHs in adults and children receiving invasive ventilation. We included randomized cross-over studies. We assessed the quality of each study and extracted the relevant data. Where possible, we analysed data through meta-analysis. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). For continuous outcomes, we calculated the mean difference (MD) and 95% CI or standardized mean difference (SMD) and 95% CI for parallel studies. For cross-over trials, we calculated the MD and 95% CI using correlation estimates to correct for paired analyses. We aimed to conduct subgroup analyses based on the age group of participants, how long they received humidification, type of HME and whether ventilation was delivered through a tracheostomy. We also conducted sensitivity analysis to identify whether the quality of trials had an effect on meta-analytic findings. We included 34 trials with 2848 participants; 26 studies were parallel-group design (2725 participants) and eight used a cross-over design (123 participants). Only three included studies reported data for infants or children. Two further studies (76 participants) are awaiting classification.There was no overall statistical difference in artificial airway occlusion (RR 1.59, 95% CI 0.60 to 4.19; participants = 2171; studies = 15; I 2 = 54%), mortality (RR 1.03, 95% CI 0.89 to 1.20; participants = 1951; studies = 12; I 2 = 0%) or pneumonia (RR 0.93, 95% CI 0.73 to 1.19; participants = 2251; studies = 13; I 2 = 27%). There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia compared to HHs (RR 0.48, 95% CI 0.28 to 0.82; participants = 469; studies = 3; I 2 = 0%)..The overall GRADE quality of evidence was low. Although the overall methodological risk of bias was generally unclear for selection and detection bias and low risk for follow-up, the selection of study participants who were considered suitable for HME and in some studies removing participants from the HME group made the findings of this review difficult to generalize. The available evidence suggests no difference between HMEs and HHs on the primary outcomes of airway blockages, pneumonia and mortality. However, the overall low quality of this evidence makes it difficult to be confident about these findings. Further research is needed to compare HMEs to HHs, particularly in paediatric and neonatal populations, but research is also needed to more effectively compare different types of HME to each other as well as different types of HH.

Factors Affecting the Dissolution of Indomethacin Solid Dispersions.

PubMed

Zhang, Wei; Zhang, Chen-Ning; He, Yue; Duan, Ban-Yan; Yang, Guang-Yi; Ma, Wei-Dong; Zhang, Yong-Hong

2017-11-01

The aim of this study was to investigate the influence of factors such as carrier type, drug/carrier ratio, binary carriers, and preparation method on the dissolution of an insoluble drug, indomethacin (IM), under supersaturation conditions. Using a solvent evaporation (SE) method, poloxamer 188 and PVP K30 showed better dissolution among the selected carriers. Furthermore, as the ratio of carriers increased (drug/carrier ratio from 1:0.5 to 1:2), the dissolution rate increased especially in almost two times poloxamer 188 solid dispersions (SDs), while the reverse results were observed for PVP K30 SDs. For the binary carrier SD, a lower dissolution was found. Under hot melt extrusion (HME), the dissolution of poloxamer 188 SD and PVP K30 SD was 0.83- and 0.94-folds lower than that using SE, respectively, while the binary carrier SD showed the best dissolution. For poloxamer 188 SDs, the drug's crystal form changed when using SE, while no crystal form change was observed using HME. IM was amorphous in PVP K30 SDs prepared by both methods. For binary carrier systems, amorphous and crystalline drugs coexisted in SD using SE, and negligible amorphous IM was in SD using HME. This study indicated that a higher amorphous proportion in SD did not correlate with higher dissolution rate, and other factors, such as carrier type, particle size, and density, were also critical.

Determination of airway humidification in high-frequency oscillatory ventilation using an artificial neonatal lung model. Comparison of a heated humidifier and a heat and moisture exchanger.

PubMed

Schiffmann, H; Singer, S; Singer, D; von Richthofen, E; Rathgeber, J; Züchner, K

1999-09-01

Thus far only few data are available on airway humidification during high-frequency oscillatory ventilation (HFOV). Therefore, we studied the performance and efficiency of a heated humidifier (HH) and a heat and moisture exchanger (HME) in HFOV using an artificial lung model. Experiments were performed with a pediatric high-frequency oscillatory ventilator. The artificial lung contained a sponge saturated with water to simulate evaporation and was placed in an incubator heated to 37 degrees C to prevent condensation. The airway humidity was measured using a capacitive humidity sensor. The water loss of the lung model was determined gravimetrically. The water loss of the lung model varied between 2.14 and 3.1 g/h during active humidification; it was 2.85 g/h with passive humidification and 7.56 g/h without humidification. The humidity at the tube connector varied between 34. 2 and 42.5 mg/l, depending on the temperature of the HH and the ventilator setting during active humidification, and between 37 and 39.9 mg/l with passive humidification. In general, HH and HME are suitable devices for airway humidification in HFOV. The performance of the ventilator was not significantly influenced by the mode of humidification. However, the adequacy of humidification and safety of the HME remains to be demonstrated in clinical practice.

The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions.

PubMed

Guo, Zhefei; Lu, Ming; Li, Yongcheng; Pang, Huishi; Lin, Ling; Liu, Xu; Wu, Chuanbin

2014-02-01

Interactions between drugs and polymers were utilized to lower the processing temperature of hot-melt extrusion (HME), and thus minimize the thermal degradation of heat-sensitive drugs during preparation of amorphous solid dispersions. Diflunisal (DIF), which would degrade upon melting, was selected as a model drug. Hydrogen bonds between DIF and polymeric carriers (PVP K30, PVP VA64, hydroxypropyl methylcellulose and Soluplus) were revealed by differential scanning calorimetry and Fourier transform infrared spectroscopy. The hot-melt extruded solid dispersion was characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and high-performance liquid chromatography (HPLC). The results of hot-stage polar microscopy indicated that DIF was dissolved in molten polymers at 160°C, much lower than the melting point of DIF (215°C). At this temperature, amorphous solid dispersions were successfully produced by HME, as confirmed by XRD and SEM. The related impurities in amorphous solid dispersions detected by HPLC were lower than 0.3%, indicating that thermal degradation was effectively minimized. The dissolution of DIF from amorphous solid dispersions was significantly enhanced as compared with the pure crystalline drug. This technique based on drug-polymer interactions to prepare chemically stable amorphous solid dispersions by HME provides an attractive opportunity for development of heat-sensitive drugs. © 2013 Royal Pharmaceutical Society.

(Phosphinoalkyl)silanes. 4.(1) Hydrozirconation as a Non-Photochemical Route to (Phosphinopropyl)silanes: Facile Assembly of the Bis(3-(diphenylphosphino)propyl)silyl ("biPSi") Ligand Framework. Access to the Related Poly(3-(dimethylsilyl)propyl)phosphines R(n)()P(CH(2)CH(2)CH(2)SiMe(2)H)(3)(-)(n)() (n = 1, R = Ph; n = 0).

PubMed

Zhou, Xiaobing; Stobart, Stephen R.; Gossage, Robert A.

1997-08-13

Treatment of SiEt(3)(CH=CH(2)) with ZrCp(2)HCl (Schwartz's reagent) followed by reaction with PPh(2)Cl provides a high-yield (75%) route to Ph(2)PCH(2)CH(2)SiEt(3), and accordingly hydrozirconation of CH(2)=CHCH(2)SiHMe(2) affords the intermediate ZrCp(2)(CH(2)CH(2)CH(2)SiHMe(2))Cl (2). The latter, which is very sensitive to hydrolysis and reacts with HCl forming SiHMe(2)Pr(n)() and with NBS or I(2) affording SiHMe(2)CH(2)CH(2)CH(2)X (X = Br (3), I (4)), behaves similarly with PPh(2)Cl, PPhCl(2), or PBr(3) undergoing cleavage to the known Ph(2)PCH(2)CH(2)CH(2)SiMe(2)H (i.e. chelH, A) and the novel bis- and tris(silylpropyl)phosphines PhP(CH(2)CH(2)CH(2)SiMe(2)H)(2) (5) and P(CH(2)CH(2)CH(2)SiMe(2)H)(3) (6), respectively, with concomitant formation of ZrCp(2)Cl(2). Corresponding hydroboration of allylsilanes is facile, but subsequent phosphine halide cleavage yields (phosphinoalkyl)silanes only as constituents of intractable mixtures. Hydrozirconation followed by phosphination with PPh(2)Cl also converts SiHMe(CH(2)CH=CH(2))(2) to SiHMe(CH(2)CH(2)CH(2)PPh(2))(2) (i.e. biPSiH, B) together with a propyl analogue Ph(2)PCH(2)CH(2)CH(2)SiMe(Pr(n)())H (7) of A (ca. 2:1 ratio), as well as SiH(CH(2)CH=CH(2))(3) to a mixture (ca. 5:2:1 ratio) of SiH(CH(2)CH(2)CH(2)PPh(2))(3) (i.e. triPSiH, C), a new analogue SiH(Pr(n)())(CH(2)CH(2)CH(2)PPh(2))(2) (8) of B, and a further analogue Ph(2)PCH(2)CH(2)CH(2)SiHPr(n)()(2) (9) of A. A further analogue SiH(2)(CH(2)CH(2)CH(2)PPh(2))(2) (10) of biPSiH (B) is obtained similarly starting from SiH(2)(CH(2)CH=CH(2))(2). Steric control of silylalkyl cleavage from 2 is indicated by the fact that, like PPh(2)Cl (which forms B), two further biPSiH analogues SiH(Me)[CH(2)CH(2)CH(2)P(n-hex)(2)](2) (11) and SiH(Me)(CH(2)CH(2)CH(2)PPhBz)(2) (12) were obtained using P(n-hex)(2)Cl (i.e. n-hex = CH(3)(CH(2))(4)CH(2)-) or PPhBzCl (i.e. Bz = -CH(2)C(6)H(5)), respectively, whereas neither PPr(i)(2)Cl nor PBu(t)(2)Cl led to (phosphinoalkyl)silane formation. The surface-substrate linking reagent Ph(2)PCH(2)CH(2)CH(2)Si(OEt)(3) (D) is formed efficiently by similar means from Si(OEt)(3)(CH(2)CH=CH(2)). NMR data ((1)H, (13)C, (29)Si, (31)P) for 2-12 have been measured and are discussed.

Effect of Heat Moisture Exchanger on Aerosol Drug Delivery and Airway Resistance in Simulated Ventilator-Dependent Adults Using Jet and Mesh Nebulizers.

PubMed

Ari, Arzu; Dang, Truong; Al Enazi, Fahad H; Alqahtani, Mohammed M; Alkhathami, Abdulrahman; Qoutah, Rowaida; Almamary, Ahmad S; Fink, James B

2018-02-01

Placement of a heat moisture exchanger (HME) between aerosol generator and patient has been associated with greatly reduced drug delivery. The purpose of this study was to evaluate the effect of filtered and nonfiltered HMEs placed between nebulizer and patient on aerosol deposition and airway resistance (Raw) in simulated ventilator-dependent adults. An in vitro lung model was developed to simulate a mechanically ventilated adult (Vt 500 mL, RR 15/min, and PEEP 5 cmH 2 O, using two inspiratory flow rates 40 and 50 L/min) using an intubated adult manikin with an endotracheal tube (8 mmID). The bronchi of the manikin were connected to a Y-adapter through a collecting filter (Respirgard II) attached to a test lung through a heated humidifier (37°C producing 100% relative humidity) to simulate exhaled humidity. For treatment conditions, a nonfiltered HME (ThermoFlo™ 6070; ARC Medical) and filtered HMEs (ThermoFlo™ Filter; ARC Medical and PALL Ultipor; Pall Medical) were placed between the ventilator circuit at the endotracheal tube and allowed to acclimate to the exhaled heat and humidity for 30 minutes before aerosol administration. Airway resistance (cmH 2 O/L/s) was taken at 0, 10, 20, and 30 minutes after HME placement and after each of four aerosol treatments. Albuterol sulfate (2.5 mg/3 mL) was administered with jet (Misty Max 10; Airlife) and mesh (Aerogen Solo; Aerogen) nebulizers positioned in the inspiratory limb proximal to the Y-adapter. Control consisted of nebulization with no HME. Drug was eluted from filter at the end of the trachea and measured using spectrophotometry (276 nm). Greater than 60% of the control dose was delivered through the ThermoFlo. No significant difference was found between the first four treatments given by the jet (p = 0.825) and the mesh (p = 0.753) nebulizers. There is a small increase in Raw between pre- and post-four treatments with the jet (p = 0.001) and mesh (p = 0.015) nebulizers. Aerosol delivery through filtered HMEs was similar (<0.5%) across the four treatments. Airway resistance was similar using the ThermoFlo Filter. With the PALL Ultipor, changes in Raw increased with mesh nebulizer after treatment (p = 0.005). Changes in resistance pre- and post-treatment were similar with both filtered HMEs. The ThermoFlo™ nonfilter HME allowed the majority of the control dose to be delivered to the airway. Increases in Raw would likely not be outside of a tolerable range in ventilated patients. In contrast, filtered HMEs should not be placed between nebulizers and patient airways. Further research with other HMEs and materials is warranted.

Halving the Volume of AnaConDa: Evaluation of a New Small-Volume Anesthetic Reflector in a Test Lung Model.

PubMed

Bomberg, Hagen; Meiser, Franziska; Daume, Philipp; Bellgardt, Martin; Volk, Thomas; Sessler, Daniel I; Groesdonk, Heinrich V; Meiser, Andreas

2018-05-21

Volatile anesthetics are increasingly used for sedation in intensive care units. The most common administration system is AnaConDa-100 mL (ACD-100; Sedana Medical, Uppsala, Sweden), which reflects volatile anesthetics in open ventilation circuits. AnaConDa-50 mL (ACD-50) is a new device with half the volumetric dead space. Carbon dioxide (CO2) can be retained with both devices. We therefore compared the CO2 elimination and isoflurane reflection efficiency of both devices. A test lung constantly insufflated with CO2 was ventilated with a tidal volume of 500 mL at 10 breaths/min. End-tidal CO2 (EtCO2) partial pressure was measured using 3 different devices: a heat-and-moisture exchanger (HME, 35 mL), ACD-100, and ACD-50 under 4 different experimental conditions: ambient temperature pressure (ATP), body temperature pressure saturated (BTPS) conditions, BTPS with 0.4 Vol% isoflurane (ISO-0.4), and BTPS with 1.2 Vol% isoflurane. Fifty breaths were recorded at 3 time points (n = 150) for each device and each condition. To determine device dead space, we adjusted the tidal volume to maintain normocapnia (n = 3), for each device. Thereafter, we determined reflection efficiency by measuring isoflurane concentrations at infusion rates varying from 0.5 to 20 mL/h (n = 3), for each device. EtCO2 was consistently greater with ACD-100 than with ACD-50 and HME (ISO-0.4, mean ± standard deviations: ACD-100, 52.4 ± 0.8; ACD-50, 44.4 ± 0.8; HME, 40.1 ± 0.4 mm Hg; differences of means of EtCO2 [respective 95% confidence intervals]: ACD-100 - ACD-50, 8.0 [7.9-8.1] mm Hg, P < .001; ACD-100 - HME, 12.3 [12.2-12.4] mm Hg, P < .001; ACD-50 - HME, 4.3 [4.2-4.3] mm Hg, P < .001). It was greatest under ATP, less under BTPS, and least with ISO-0.4 and BTPS with 1.2 Vol% isoflurane. In addition to the 100 or 50 mL "volumetric dead space" of each AnaConDa, "reflective dead space" was 40 mL with ACD-100 and 25 mL with ACD-50 when using isoflurane. Isoflurane reflection was highest under ATP. Under BTPS with CO2 insufflation and isoflurane concentrations around 0.4 Vol%, reflection efficiency was 93% with ACD-100 and 80% with ACD-50. Isoflurane reflection remained sufficient with the ACD-50 at clinical anesthetic concentrations, while CO2 elimination was improved. The ACD-50 should be practical for tidal volumes as low as 200 mL, allowing lung-protective ventilation even in small patients.

Ventilator-associated pneumonia using a heated humidifier or a heat and moisture exchanger: a randomized controlled trial [ISRCTN88724583].

PubMed

Lorente, Leonardo; Lecuona, María; Jiménez, Alejandro; Mora, María L; Sierra, Antonio

2006-01-01

Some guidelines to prevent ventilator-associated pneumonia (VAP) do not establish a recommendation for the preferential use of either heat and moisture exchangers (HMEs) or heated humidifiers (HHs), while other guidelines clearly advocate the use of HMEs. The aim of this study was to determine the incidence of VAP associated with HHs or HMEs. A randomized study was conducted in the intensive care unit of a university hospital involving patients expected to require mechanical ventilation for >5 days. Patients were assigned to two groups; one group received HH and the other group received HME. Tracheal aspirate samples were obtained on endotracheal intubation, then twice a week, and finally on extubation, in order to diagnose VAP. Throat swabs were taken on admission to the intensive care unit, then twice a week, and finally at discharge from the intensive care unit in order to classify VAP as primary endogenous, secondary endogenous, or exogenous. A total of 120 patients were assigned to HMEs (60 patients) and HHs (60 patients); 16 patients received mechanical ventilation for less than five days and were excluded from the analysis. Data analysis of the remaining 104 patients (53 HMEs and 51 HHs) showed no significant differences between groups regarding sex, age, Acute Physiology and Chronic Health Evaluation II score, pre-VAP use of antibiotics, days on mechanical ventilation, and diagnosis group. VAP was found in eight of 51 (15.69%) patients in the HH group and in 21 of 53 (39.62%) patients in the HME group (P = 0.006). The median time free of VAP was 20 days (95% confidence interval, 13.34-26.66) for the HH group and was 42 days (95% confidence interval, 35.62-48.37) for the HME group (P <0.001). Cox regression analysis showed the HME as a risk factor for VAP (hazard rate, 16.2; 95% confidence interval, 4.54-58.04; P < 0.001). The patients mechanically ventilated during more than 5 days developed a lower incidence of VAP with a heated humidifier than heat and moisture exchanger.

Human impacts of hydrometeorological extremes in the Bohemian-Moravian Highlands derived from documentary sources in the 18th-19th centuries

NASA Astrophysics Data System (ADS)

Dolák, Lukáš; Brázdil, Rudolf; Valášek, Hubert

2014-05-01

The extent of damage caused by hydrometeorological events or extremes (HME) has risen up in the entire world in the last few years. Especially the floods, flash floods, torrential rains and hailstorms are the most typical and one of the most frequent kind of natural disasters in the central Europe. Catastrophes are a part of human history and people were forced to cope with their consequences (e. g. material damage, economical losses, impacts on agriculture and society or losses of human lives). This paper analyses the human impacts of HME in the Bohemian-Moravian Highlands (central part of the Czech Republic) on the basis of documentary sources from the 18th-19th centuries. The paper presents various negative impacts of natural disasters on lives and property and subsequent inconveniences of Czech peasants. The preserved archival documents of estates or domains became the primary sources of data (e. g. taxation reliefs, damaged records, reports of afflicted farmers, administrative correspondence etc.). Particularly taxation reliefs relate to taxation system in the Czech lands during the 17th-19th centuries allowing to farmers to ask for tax alleviation when their crops were significantly damaged by any HME. These archival documents are a highly valuable source for the study of human impacts of natural disasters. Devastating consequences of these extremes affected individual farmers much more than the aristocracy. Floods caused inundations of farmer's fields, meadows, houses and farm buildings, washed away the arable land with crops, caused losses of cattle, clogged the land with gravel and mud and destroyed roads, bridges or agricultural equipment. Afflicted fields became worthless and it took them many years to become became fertile again. Crop was also damaged by hailstorms, droughts or late/early frosts. All these events led to lack of food and seeds in the following year and it meant the decrease of living standard, misery and poverty of farmers. Acquired results could give better insight of human impacts of HME in history and help to compare the negative consequences in the past and present.

Species delimitation using Bayes factors: simulations and application to the Sceloporus scalaris species group (Squamata: Phrynosomatidae).

PubMed

Grummer, Jared A; Bryson, Robert W; Reeder, Tod W

2014-03-01

Current molecular methods of species delimitation are limited by the types of species delimitation models and scenarios that can be tested. Bayes factors allow for more flexibility in testing non-nested species delimitation models and hypotheses of individual assignment to alternative lineages. Here, we examined the efficacy of Bayes factors in delimiting species through simulations and empirical data from the Sceloporus scalaris species group. Marginal-likelihood scores of competing species delimitation models, from which Bayes factor values were compared, were estimated with four different methods: harmonic mean estimation (HME), smoothed harmonic mean estimation (sHME), path-sampling/thermodynamic integration (PS), and stepping-stone (SS) analysis. We also performed model selection using a posterior simulation-based analog of the Akaike information criterion through Markov chain Monte Carlo analysis (AICM). Bayes factor species delimitation results from the empirical data were then compared with results from the reversible-jump MCMC (rjMCMC) coalescent-based species delimitation method Bayesian Phylogenetics and Phylogeography (BP&P). Simulation results show that HME and sHME perform poorly compared with PS and SS marginal-likelihood estimators when identifying the true species delimitation model. Furthermore, Bayes factor delimitation (BFD) of species showed improved performance when species limits are tested by reassigning individuals between species, as opposed to either lumping or splitting lineages. In the empirical data, BFD through PS and SS analyses, as well as the rjMCMC method, each provide support for the recognition of all scalaris group taxa as independent evolutionary lineages. Bayes factor species delimitation and BP&P also support the recognition of three previously undescribed lineages. In both simulated and empirical data sets, harmonic and smoothed harmonic mean marginal-likelihood estimators provided much higher marginal-likelihood estimates than PS and SS estimators. The AICM displayed poor repeatability in both simulated and empirical data sets, and produced inconsistent model rankings across replicate runs with the empirical data. Our results suggest that species delimitation through the use of Bayes factors with marginal-likelihood estimates via PS or SS analyses provide a useful and complementary alternative to existing species delimitation methods.

Yet another cause for blocked sidestream capnogram--beware of the non-threaded cap mount in heat and moisture exchangers.

PubMed

Umesh, Goneppanavar; Jasvinder, Kaur; Shetty, Nanda

2009-08-01

Heat and moisture exchangers (HME) are commonly used during general anaesthesia and intensive care of patients on mechanical ventilators. Some of the HME manufacturers provide HMEs with a Luer lock fitting for connecting side stream CO(2) monitoring line, Luer lock cap, and a non-threaded cap mount. However, HMEs from different manufacturers and HMEs meant for use in children and for adults from the same manufacturer vary in the presence/absence of non-threaded cap mount. This can create confusion to the clinicians and can result in inadvertent connection of the CO(2) monitoring line to the non-threaded cap mount resulting in blocked CO(2) monitoring line and leak in the circuit. We caution all the anaesthesiologists and intensivists regarding this possibility while using HMEs from different manufacturers.

Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

PubMed

Verstraete, G; Van Renterghem, J; Van Bockstal, P J; Kasmi, S; De Geest, B G; De Beer, T; Remon, J P; Vervaet, C

2016-06-15

Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

In vitro evaluation of heat and moisture exchangers designed for spontaneously breathing tracheostomized patients.

PubMed

Brusasco, Claudia; Corradi, Francesco; Vargas, Maria; Bona, Margherita; Bruno, Federica; Marsili, Maria; Simonassi, Francesca; Santori, Gregorio; Severgnini, Paolo; Kacmarek, Robert M; Pelosi, Paolo

2013-11-01

Heat and moisture exchangers (HMEs) are commonly used in chronically tracheostomized spontaneously breathing patients, to condition inhaled air, maintain lower airway function, and minimize the viscosity of secretions. Supplemental oxygen (O2) can be added to most HMEs designed for spontaneously breathing tracheostomized patients. We tested the efficiency of 7 HMEs designed for spontaneously breathing tracheostomized patients, in a normothermic model, at different minute ventilations (VE) and supplemental O2 flows. HME efficiency was evaluated using an in vitro lung model at 2 VE (5 and 15 L/min) and 4 supplemental O2 flows (0, 3, 6, and 12 L/min). Wet and dry temperatures of the inspiratory flow were measured, and absolute humidity was calculated. In addition, HME efficiency at 0, 12, and 24 h use was evaluated, as well as resistance to flow at 0 and 24 h. The progressive increase in O2 flow from 0 to 12 L/min was associated with a reduction in temperature and absolute humidity. Under the same conditions, this effect was greater at lower VE. The HME with the best performance provided an absolute humidity of 26 mg H2O/L and a temperature of 27.8 °C. No significant changes in efficiency or resistance were detected during the 24 h evaluation. The efficiency of HMEs in terms of temperature and absolute humidity is significantly affected by O2 supplementation and V(E).

Application of film-casting technique to investigate drug-polymer miscibility in solid dispersion and hot-melt extrudate.

PubMed

Parikh, Tapan; Gupta, Simerdeep Singh; Meena, Anuprabha K; Vitez, Imre; Mahajan, Nidhi; Serajuddin, Abu T M

2015-07-01

Determination of drug-polymer miscibility is critical for successful development of solid dispersions. This report details a practical method to predict miscibility and physical stability of drug with various polymers in solid dispersion and, especially, in melt extrudates by applying a film-casting technique. Mixtures of itraconazole (ITZ) with hydroxypropylmethylcellulose phthalate (HPMCP), Kollidon(®) VA 64, Eudragit(®) E PO, and Soluplus(®) were film-casted, exposed to 40°C/75% RH for 1 month and then analyzed using differential scanning calorimetry (DSC), powder X-ray diffractometry, and polarized light microscopy (PLM). ITZ had the highest miscibility with HPMCP, being miscible at drug to polymer ratio of 6:4 (w/w). There was a downward trend of lower miscibility with Soluplus(®) (miscible at 3:7, w/w, and a few microcrystals present at 4:6, w/w), Kollidon(®) VA 64 (2:8, w/w) and Eudragit(®) E PO (<1:9, w/w). PLM was found more sensitive to detect drug crystallization than DSC and powder X-ray diffractometry. There was general correlation between results of film casting and hot-melt extrusion (HME) using a twin screw extruder. For ITZ-Soluplus(®) mixtures, HME at 4:6 (w/w) resulted in a single phase, whereas drug crystallization was observed at higher drug load. HME of ITZ-Kollidon(®) VA 64 mixtures also correlated well with the miscibility predicted by film casting. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Iron silylamide-grafted periodic mesoporous silica.

PubMed

Deschner, Thomas; Törnroos, Karl W; Anwander, Reiner

2011-08-01

The surface chemistry of a series of well-defined metalorganic ferrous and ferric iron complexes on periodic mesoporous silica (PMS) was investigated. In addition to literature known Fe(II)[N(SiMe(3))(2)](2)(THF), Fe(II)[N(SiPh(2)Me(2))(2)](2), and Fe(III)[N(SiMe(3))(2)](2)Cl(THF), the new complexes [Fe(II){N(SiHMe(2))(2)}(2)](2) and Fe(III)[N(SiHMe(2))(2)](3)(μ-Cl)Li(THF)(3) were employed as grafting precursors. Selection criteria for the molecular precursors were the molecular size (monoiron versus diiron species), the oxidation state of the iron center (II versus III), and the functionality of the silylamido ligand (e.g., built-in spectroscopic probes). Hexagonal channel-like MCM-41 and cubic cage-like SBA-1 were chosen as two distinct PMS materials. The highest iron load (12.8 wt %) was obtained for hybrid material [Fe(II){N(SiHMe(2))(2)}(2)](2)@MCM-41 upon stirring the reaction mixture iron silylamide/PMS/n-hexane for 18 h at ambient temperature. Size-selective grafting and concomitantly extensive surface silylation were found to be prominent for cage-like SBA-1. Here, the surface metalation is governed by the type of iron precursor, the pore size, the reaction time, and the solvent. The formation of surface-attached iron-ligand species is discussed on the basis of diffuse reflectance infrared Fourier transform (DRIFT) and electron paramagnetic resonance (EPR) spectroscopy, nitrogen physisorption, and elemental analysis. © 2011 American Chemical Society

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Collection Fee is required for a TSA agent to collect and transmit fingerprints and applicant information, in... renew an HME: $34. (3) The following FBI Fee is required for the FBI to process fingerprint...

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Collection Fee is required for a TSA agent to collect and transmit fingerprints and applicant information, in... renew an HME: $34. (3) The following FBI Fee is required for the FBI to process fingerprint...

49 CFR 1572.405 - Procedures for collection by TSA.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Collection Fee is required for a TSA agent to collect and transmit fingerprints and applicant information, in... renew an HME: $34. (3) The following FBI Fee is required for the FBI to process fingerprint...

Effects of different fresh gas flows with or without a heat and moisture exchanger on inhaled gas humidity in adults undergoing general anaesthesia: A systematic review and meta-analysis of randomised controlled trials.

PubMed

Braz, José R C; Braz, Mariana G; Hayashi, Yoko; Martins, Regina H G; Betini, Marluci; Braz, Leandro G; El Dib, Regina

2017-08-01

The minimum inhaled gas absolute humidity level is 20 mgH2O l for short-duration use in general anaesthesia and 30 mgH2O l for long-duration use in intensive care to avoid respiratory tract dehydration. The aim is to compare the effects of different fresh gas flows (FGFs) through a circle rebreathing system with or without a heat and moisture exchanger (HME) on inhaled gas absolute humidity in adults undergoing general anaesthesia. Systematic review and meta-analyses of randomised controlled trials. We defined FGF (l min) as minimal (0.25 to 0.5), low (0.6 to 1.0) or high (≥2). We extracted the inhaled gas absolute humidity data at 60 and 120 min after connection of the patient to the breathing circuit. The effect size is expressed as the mean differences and corresponding 95% confidence intervals (CI). PubMed, EMBASE, SciELO, LILACS and CENTRAL until January 2017. We included 10 studies. The inhaled gas absolute humidity was higher with minimal flow compared with low flow at 120 min [mean differences 2.51 (95%CI: 0.32 to 4.70); P = 0.02] but not at 60 min [mean differences 2.95 (95%CI: -0.95 to 6.84); P = 0.14], and higher with low flow compared with high flow at 120 min [mean differences 7.19 (95%CI: 4.53 to 9.86); P < 0.001]. An inhaled gas absolute humidity minimum of 20 mgH2O l was attained with minimal flow at all times but not with low or high flows. An HME increased the inhaled gas absolute humidity: with minimal flow at 120 min [mean differences 8.49 (95%CI: 1.15 to 15.84); P = 0.02]; with low flow at 60 min [mean differences 9.87 (95%CI: 3.18 to 16.57); P = 0.04] and 120 min [mean differences 7.19 (95%CI: 3.29 to 11.10); P = 0.003]; and with high flow of 2 l min at 60 min [mean differences 6.46 (95%CI: 4.05 to 8.86); P < 0.001] and of 3 l min at 120 min [mean differences 12.18 (95%CI: 6.89 to 17.47); P < 0.001]. The inhaled gas absolute humidity data attained or were near 30 mgH2O l when an HME was used at all FGFs and times. All intubated patients should receive a HME with low or high flows. With minimal flow, a HME adds cost and is not needed to achieve an appropriate inhaled gas absolute humidity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seetho, Isaac M.; Brown, William D.; Martz, Jr., Harry E.

This document is a short summary of the steps required for MicroCT evaluation of a specimen. This includes data acquisition through image analysis, for the EXD HME program. Expected outputs for each stage are provided. Data shall be shipped to LLNL as described herein.

High speed spectral measurements of IED detonation fireballs

NASA Astrophysics Data System (ADS)

Gordon, J. Motos; Spidell, Matthew T.; Pitz, Jeremey; Gross, Kevin C.; Perram, Glen P.

2010-04-01

Several homemade explosives (HMEs) were manufactured and detonated at a desert test facility. Visible and infrared signatures were collected using two Fourier transformspectrometers, two thermal imaging cameras, a radiometer, and a commercial digital video camera. Spectral emissions from the post-detonation combustion fireball were dominated by continuum radiation. The events were short-lived, decaying in total intensity by an order of magnitude within approximately 300ms after detonation. The HME detonation produced a dust cloud in the immediate area that surrounded and attenuated the emitted radiation from the fireball. Visible imagery revealed a dark particulate (soot) cloud within the larger surrounding dust cloud. The ejected dust clouds attenuated much of the radiation from the post-detonation combustion fireballs, thereby reducing the signal-to-noise ratio. The poor SNR at later times made it difficult to detect selective radiation from by-product gases on the time scale (~500ms) in which they have been observed in other HME detonations.

Detection of Ehrlichia chaffeensis in adult and nymphal stage lone star ticks (Amblyomma americanum) from Long Island, New York

USGS Publications Warehouse

Mixson, T.R.; Ginsberg, H.S.; Campbell, S.R.; Sumner, J.W.; Paddock, C.D.

2004-01-01

The lone star tick, Amblyomma americanum (L.), has increased in abundance in several regions of the northeastern United States, including areas of Long Island, NY. Adult and nymphal stage A. americanum collected from several sites on Long Island were evaluated for infection with Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME), by using a nested polymerase chain reaction assay. Fifty-nine (12.5%) of ,17.3 adults and eight of 11.3 pools of five nymphs each (estimated minimum prevalence of infection 1.4%) contained DNA of E. chaffeensis. These data, coupled with the documented expansion of lone star tick populations in the northeastern United States, confirm that E. chaffeensis is endemic to many areas of Long Island and that HME should be considered among the differential diagnoses of the many distinct tick-borne diseases that occur in this region.

Demonstration of pharmaceutical tablet coating process by injection molding technology.

PubMed

Puri, Vibha; Brancazio, David; Harinath, Eranda; Martinez, Alexander R; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Braatz, Richard D; Myerson, Allan S; Trout, Bernhardt L

2018-01-15

We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300 μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of hot-melt extrusion technology in immediate-release abuse-deterrent formulations.

PubMed

Wening, Klaus; Schwier, Sebastian; Stahlberg, Hans-J; Galia, Eric

Hot-melt extrusion (HME) technology has been used for manufacturing extended-release abuse-deterrent formulations (ADFs) of opioid-type analgesics with improved tamper-resistant properties. Our objective was to describe application of this technology to immediate-release (IR) ADFs. For development of a sample IR ADF (hydrocodone 10 mg/acetaminophen 325 mg) based on HME, feasibility studies were performed using different excipients. The formulation selected for further development was evaluated via in vitro test battery. Moreover, in vivo performance of IR ADF technologies was investigated in an open-label, randomized, cross-over, phase 1, relative oral bioavailability study with another opioid (model compound). Single-center bioavailability trial. Twenty-four healthy white male subjects. ADF IR formulation of an opioid and marketed IR formulation. For feasibility and in vitro studies, dissolution profiles, syringeability, particle size distribution after physical manipulation, and extractability were evaluated. For the phase 1 study, pharmacokinetic parameters were evaluated and compared for ADF IR and a marketed IR formulation. After manipulation, the majority of particles from the ADF IR formulation were >500µm and, thus, not considered suitable for intranasal abuse, while the majority of particles for the reference marketed IR formulation were <500µm. The ADF IR formulation was resistant to syringing and preparation for potential intravenous injection. In healthy subjects, pharmacokinetics of an ADF and marketed IR formulation of an opioid were nearly identical. Application of HME to IR formulations led to development of products with improved mechanical resistance to manipulation for intranasal or intravenous preparation, but similar bioavailability.

Clinical feasibility study of protrach dualcare a new speaking valve with heat and moisture exchanger for tracheotomized patients.

PubMed

de Kleijn, B J; van As-Brooks, C J; Wedman, J; van der Laan, B F A M

2017-12-01

The aim of this study was to evaluate the clinical feasibility of the ProTrach DualCare (Atos Medical, Hörby, Sweden), a device combining a hands-free speaking valve and a Heat and Moisture Exchanger (HME) for tracheotomized patients. A non-randomized, prospective single center feasibility study. Sixteen adult tracheotomized patients were included. Participants were asked to test the DualCare for two weeks while continuing their normal activities. After these two weeks, participants could choose whether or not to take part in the long-term evaluation. The EuroQOL-5D, Borg scale and questionnaires on speaking, pulmonary function and patient preference were used. During the long-term evaluation, a minor redesign was implemented and all participants were asked to test the new device again for one week, with a potential long-term evaluation. Eleven decided to participate. The device was well-tolerated. Speaking noise was reduced ( p  = 0.020) and speech was considered to sound more natural compared to previously used devices according to the users ( p  = 0.020). Overall 11 participants preferred the DualCare to their standard device. No serious adverse events were reported. Overall, 11 of 16 participants preferred the DualCare to their standard speaking valve or HME. Users of the DualCare were able to use hands free speech with the benefits of an HME and the device was considered clinically feasible and has the potential to improve quality of life of tracheotomized patients. 2b.

Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion.

PubMed

Silva, Luis Antonio D; Almeida, Susana L; Alonso, Ellen C P; Rocha, Priscila B R; Martins, Felipe T; Freitas, Luís A P; Taveira, Stephania F; Cunha-Filho, Marcilio S S; Marreto, Ricardo N

2018-04-25

Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ± 7.22 nm, 0.219 ± 0.011 and -9.77 ± 0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets. Copyright © 2018 Elsevier B.V. All rights reserved.

Submarine slope earthquake-induced instability and associated tsunami generation potential along the Hyblean-Malta Escarpment (offshore eastern Sicily, Italy)

NASA Astrophysics Data System (ADS)

Ausilia Paparo, Maria; Pagnoni, Gianluca; Zaniboni, Filippo; Tinti, Stefano

2016-04-01

The stability analysis of offshore margins is an important step for the assessment of natural hazard: the main challenge is to evaluate the potential slope failures and the consequent occurrence of submarine tsunamigenic landslides to mitigate the potential coastal damage to inhabitants and infrastructures. But the limited geotechnical knowledge of the underwater soil and the controversial scientific interpretation of the tectonic units make it often difficult to carry out this type of analysis reliably. We select the Hyblean-Malta Escarpment (HME), the main active geological structure offshore eastern Sicily, because the amount of data from historical chronicles, the records about strong earthquakes and tsunami, and the numerous geological offshore surveys carried out in recent years make the region an excellent scenario to evaluate slope failures, mass movements triggered by earthquakes and the consequent tsunamis. We choose several profiles along the HME and analyse their equilibrium conditions using the Minimun Lithostatic Deviation (MLD) method (Tinti and Manucci, 2006, 2008; Paparo et al. 2013), that is based on the limit-equilibrium theory. Considering the morphological and geotechnical features of the offshore slopes, we prove that large-earthquake shaking may lead some zones of the HME to instability, we evaluate the expected volumes involved in sliding and compute the associated landslide-tsunami through numerical tsunami simulations. This work was carried out in the frame of the EU Project called ASTARTE - Assessment, STrategy And Risk Reduction for Tsunamis in Europe (Grant 603839, 7th FP, ENV.2013.6.4-3).

Molecular implications of drug-polymer solubility in understanding the destabilization of solid dispersions by milling.

PubMed

Yang, Ziyi; Nollenberger, Kathrin; Albers, Jessica; Qi, Sheng

2014-07-07

The solubility of drugs in polymer matrixes has been recognized as one of the key factors governing the physical stability of solid dispersions. This study has explored the implications of drug solubility on the destabilization that occurs on milling, which is often used as an additional process for hot melt extruded (HME) solid dispersions. The theoretical drug solubility in the polymer was first predicted using various theoretical and experimental approaches. The destabilization effects of high-energy mechanical milling on the solid dispersions with drug loadings below and above the predicted solubility were then investigated using a range of thermal, microscopic, and spectroscopic techniques. Four model drug-polymer combinations were studied. The HME formulations with drug loading below the predicted solid solubility (undersaturated and true molecular dispersion) showed good stability against milling. In contrast, milling destabilized supersaturated HME dispersions via increasing molecular mobility and creating phase-separated, amorphous, drug-rich domains. However, these additional amorphous drug-rich domains created by milling show good stability under ambient conditions, though crystallization can be accelerated by additional heating. These results highlighted that the processing method used to prepare the solid dispersions may play a role in facilitating the stabilization of amorphous drug in supersaturated solid dispersions. The degree of supersaturation of the drug in the polymer showed significant impact on the destabilization behavior of milling on solid dispersions. An improved understanding of the destabilization behavior of solid dispersions upon milling can provide new insights into the processing related apparent solubility of drugs in polymers.

Distinctive Menkes disease variant with occipital horns: Delineation of natural history and clinical phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Proud, V.K.; Mussell, H.G.; Percy, A.K.

1996-10-02

To delineate further the clinical spectrum of Menkes disease, an X-linked recessive disorder of copper transport, we studied 4 related males, ranging in age from 4-38 years, with a unique phenotype that combines manifestations of classical and mild Menkes disease and occipital horn syndrome (OHS). The propositus, an 18-year-old man, was evaluated following an intracerebral hemorrhage at age 15 years and was noted to have marked hypotonia, motor delay with mental retardation, bladder diverticula, failure to thrive, and diarrhea from infancy; seizures from age 3 years; and abnormal hair (pili torti) and face, cutis laxa, and multiple joint dislocations. Radiographicmore » abnormalities included occipital exostoses, tortuous cerebral blood vessels with multiple branch occlusions, and hammer-shaped clavicles. Biochemical studies demonstrated reduced copper and ceruloplasmin levels in serum, and abnormal plasma catecholamine ratios. We reported previously the molecular defect in this family, a splice-site mutation that predicts formation of approximately 20% of the normal Menkes gene product. Here, we detail the clinical course and physical features and radiographic findings in these 4 individuals, and compare their phenotype with classical and mild Menkes and OHS. Unusual Menkes disease variants such as this may escape recognition due to anomalies that appear inconsistent with the diagnosis, particularly prolonged survival and later onset of seizures. Males with mental retardation and connective tissue abnormalities should be evaluated for biochemical evidence of defective copper transport. 28 refs., 8 figs.« less

Microsensor studies on Padina from a natural CO2 seep: implications of morphology on acclimation to low pH.

PubMed

Hofmann, Laurie C; Fink, Artur; Bischof, Kai; de Beer, Dirk

2015-12-01

Low seawater pH can be harmful to many calcifying marine organisms, but the calcifying macroalgae Padina spp. flourish at natural submarine carbon dioxide seeps where seawater pH is low. We show that the microenvironment created by the rolled thallus margin of Padina australis facilitates supersaturation of CaCO3 and calcifi-cation via photosynthesis-induced elevated pH. Using microsensors to investigate oxygen and pH dynamics in the microenvironment of P. australis at a shallow CO2 seep, we found that, under saturating light, the pH inside the microenvironment (pHME ) was higher than the external seawater (pHSW ) at all pHSW levels investigated, and the difference (i.e., pHME - pHSW ) increased with decreasing pHSW (0.9 units at pHSW 7.0). Gross photosynthesis (Pg ) inside the microenvironment increased with decreasing pHSW , but algae from the control site reached a threshold at pH 6.5. Seep algae showed no pH threshold with respect to Pg within the pHSW range investigated. The external carbonic anhydrase (CA) inhibitor, acetazolamide, strongly inhibited Pg of P. australis at pHSW 8.2, but the effect was diminished under low pHSW (6.4-7.5), suggesting a greater dependence on membrane-bound CA for the dehydration of HCO3 (-) ions during dissolved inorganic carbon uptake at the higher pHSW . In comparison, a calcifying green alga, Halimeda cuneata f. digitata, was not inhibited by AZ, suggesting efficient bicarbonate transport. The ability of P. australis to elevate pHME at the site of calcification and its strong dependence on CA may explain why it can thrive at low pHSW . © 2015 Phycological Society of America.

A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

PubMed

Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A

2016-11-01

The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

Portable standoff Raman system for fast detection of homemade explosives through glass, plastic, and water

NASA Astrophysics Data System (ADS)

Misra, Anupam K.; Sharma, Shiv K.; Acosta, Tayro E.; Porter, John N.; Lucey, Paul G.; Bates, David E.

2012-06-01

The University of Hawaii has been developing portable remote Raman systems capable of detecting chemicals in daylight from a safe standoff distance. We present data on standoff detection of chemicals used in the synthesis of homemade explosives (HME) using a portable standoff Raman system utilizing an 8-inch telescope. Data show that good-quality Raman spectra of various hazardous chemicals such as ammonium nitrate, potassium nitrate, potassium perchlorate, sulfur, nitrobenzene, benzene, acetone, various organic and inorganic chemicals etc. could be easily obtained from remote distances, tested up to 120 meters, with a single-pulse laser excitation and with detection time less than 1 μs. The system uses a frequency-doubled Nd:YAG pulsed laser source (532 nm, 100 mJ/pulse, 15 Hz, pulse width 10 ns) capable of firing a single or double pulse. The double-pulse configuration also allows the system to perform standoff LIBS (Laser-Induced Breakdown Spectroscopy) at 50 m range. In the standoff Raman detection, the doublepulse sequence simply doubles the signal to noise ratio. Significant improvement in the quality of Raman spectra is observed when the standoff detection is made with 1s integration time. The system uses a 50-micron slit and has spectral resolution of 8 cm-1. The HME chemicals could be easily detected through clear and brown glass bottles, PP and HDPE plastic bottles, and also through fluorescent plastic water bottles. Standoff Raman detection of HME chemical from a 10 m distance through non-visible concealed bottles in plastic bubble wrap packaging is demonstrated with 1 s integration time. Possible applications of the standoff Raman system for homeland security and environmental monitoring are discussed.

Effect of a heat and moisture exchanger on heat loss in isoflurane-anesthetized dogs undergoing single-limb orthopedic procedures.

PubMed

Hofmeister, Erik H; Brainard, Benjamin M; Braun, Christina; Figueiredo, Juliana P

2011-12-15

To determine whether a heat and moisture exchange device (HME) prevents a decrease in body temperature in isoflurane-anesthetized dogs undergoing orthopedic procedures. Blinded randomized controlled clinical trial. 60 privately owned dogs weighing at least 15 kg (33 lb). Dogs were randomly assigned to 1 of 3 treatment groups (n = 20/group): HME placed immediately after anesthetic induction with isoflurane, after transfer to the operating room, or not at all. The device consisted of a hygroscopic filter placed between the endotracheal tube and the Y piece of the anesthesia circuit. Each dog was positioned on a circulating warm water blanket and had a forced-air warming blanket placed over its body. Body temperature was monitored after transfer to the operating room with a probe placed in the thoracic aspect of the esophagus. Study groups did not differ significantly with respect to body weight, body condition score, reproductive status, breed, surgical procedure, preoperative sedative and opioid administration, anesthetic induction drug, local nerve block technique, or operating room assignment. There were no significant differences among groups in esophageal temperature variables, interval between anesthetic induction and surgery, surgery duration, anesthesia duration, or oxygen flow rate. However, the relationship between temperature delta and body weight was significant and relevant (R(2) = 0.23), as was the association between temperature nadir and body weight (R(2)= 0.10). As body weight increased, the temperature delta decreased and temperature nadir increased. No other significant relationships were identified. Inclusion of an HME in healthy dogs undergoing anesthesia for an elective orthopedic surgery did not facilitate maintenance of body temperature throughout the procedure.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Enhancing Cocrystal Yield.

PubMed

Li, Shu; Yu, Tao; Tian, Yiwei; Lagan, Colette; Jones, David S; Andrews, Gavin P

2017-11-22

Pharmaceutical cocrystals have attracted increasing attention over the past decade as an alternative way to modify the physicochemical properties and hence improve the bioavailability of a drug, without sacrificing thermodynamic stability. Our previous work has demonstrated the viability of in-situ formation of ibuprofen/isonicotinamide cocrystal suspensions within a matrix carrier via a single-step hot-melt extrusion (HME) process. The key aim of the current work is to establish optimised processing conditions to improve cocrystal yield within extruded matrices. The solubility of each individual cocrystal component in the matrix carrier was estimated using two different methods, calculation of Hansen solubility parameters, and Flory-Huggins solution theory using melting point depression measurement, respectively. The latter was found to be more relevant to extrusion cocrystallisation because of the ability to predict miscibility across a range of temperatures. The predictions obtained from the F-H phase diagrams were verified using ternary extrusion processing. Temperatures that promote solubilisation of the parent reagents during processing, and precipitation of the newly formed cocrystal were found to be the most suitable in generating high cocrystal yields. The incorporation of intensive mixing/kneading elements to the screw configuration was also shown to significantly improve the cocrystal yield when utilising a matrix platform. This work has shown that intensive mixing in combination with appropriate temperature selection, can significantly improve the cocrystal yield within a stable and low viscosity carrier during HME processing. Most importantly, this work reports, for the very first time in the literature, the use of the F-H phase diagrams to predict the most appropriate HME processing window to drive higher cocrystal yield.

Heat and moisture exchangers in mechanically ventilated intensive care unit patients: a plea for an independent assessment of their performance.

PubMed

Thiéry, Guillaume; Boyer, Alexandre; Pigné, Etienne; Salah, Amar; De Lassence, Arnaud; Dreyfuss, Didier; Ricard, Jean-Damien

2003-03-01

To determine whether use of a hygroscopic and hydrophobic heat and moisture exchanger (HME) for 7 days without change affects its efficiency in long-term, mechanically ventilated, chronic obstructive pulmonary disease (COPD) patients. Prospective, randomized, controlled clinical study comparing two combined HMEs. Medical intensive care unit at a university teaching hospital. Long-term, mechanically ventilated, COPD patients compared with non-COPD patients. In the first part of the study, COPD patients were studied with the Hygroster HME changed once a week. For the second part, the Hygroster was assessed in non-COPD patients and compared with the Hygrobac HME used in COPD and non-COPD patients for 1 wk without change. Devices could be changed if hygrometric measurements indicated insufficient humidity delivery. Daily measurements were recorded for inspired gas temperature and relative and absolute humidity. Ventilatory variables, clinical indicators of efficient humidification, were also recorded. No tracheal tube occlusion occurred. However, contrary to the manufacturer advertisement, the Hygroster experienced surprisingly low values for absolute humidity in both COPD and non-COPD patients. Such events did not occur with the Hygrobac. Absolute humidity with the Hygroster was constantly and significantly lower during the 7-day study period than with the Hygrobac. Absolute humidity measured in COPD patients was identical to that measured in the rest of the study population with both HMEs. Manufacturer specifications and bedside measurements of absolute humidity differed considerably for the Hygroster, which in certain instances did not achieve efficient humidification in both COPD and non-COPD patients. This did not occur with the Hygrobac, which performed well throughout the 7-day period in both COPD and non-COPD patients. Our results speak for independent and evaluation of HMEs.

A Pilot Study of the Noninvasive Assessment of the Lung Microbiota as a Potential Tool for the Early Diagnosis of Ventilator-Associated Pneumonia

PubMed Central

Brady, Jacob S.; Romano-Keeler, Joann; Drake, Wonder P.; Norris, Patrick R.; Jenkins, Judith M.; Isaacs, Richard J.; Boczko, Erik M.

2015-01-01

BACKGROUND: Ventilator-associated pneumonia (VAP) remains a common complication in critically ill surgical patients, and its diagnosis remains problematic. Exhaled breath contains aerosolized droplets that reflect the lung microbiota. We hypothesized that exhaled breath condensate fluid (EBCF) in hygroscopic condenser humidifier/heat and moisture exchanger (HCH/HME) filters would contain bacterial DNA that qualitatively and quantitatively correlate with pathogens isolated from quantitative BAL samples obtained for clinical suspicion of pneumonia. METHODS: Forty-eight adult patients who were mechanically ventilated and undergoing quantitative BAL (n = 51) for suspected pneumonia in the surgical ICU were enrolled. Per protocol, patients fulfilling VAP clinical criteria undergo quantitative BAL bacterial culture. Immediately prior to BAL, time-matched HCH/HME filters were collected for study of EBCF by real-time polymerase chain reaction. Additionally, convenience samples of serially collected filters in patients with BAL-diagnosed VAP were analyzed. RESULTS: Forty-nine of 51 time-matched EBCF/BAL fluid samples were fully concordant (concordance > 95% by κ statistic) relative to identified pathogens and strongly correlated with clinical cultures. Regression analysis of quantitative bacterial DNA in paired samples revealed a statistically significant positive correlation (r = 0.85). In a convenience sample, qualitative and quantitative polymerase chain reaction analysis of serial HCH/HME samples for bacterial DNA demonstrated an increase in load that preceded the suspicion of pneumonia. CONCLUSIONS: Bacterial DNA within EBCF demonstrates a high correlation with BAL fluid and clinical cultures. Bacterial DNA within EBCF increases prior to the suspicion of pneumonia. Further study of this novel approach may allow development of a noninvasive tool for the early diagnosis of VAP. PMID:25474571

DNA methylation epigenotype and clinical features of NRAS-mutation(+) colorectal cancer.

PubMed

Takane, Kiyoko; Akagi, Kiwamu; Fukuyo, Masaki; Yagi, Koichi; Takayama, Tadatoshi; Kaneda, Atsushi

2017-05-01

Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome-wide DNA methylation analysis to classify CRC into distinct subgroups: high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)-high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP-low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers. While BRAF- and KRAS-mutation(+) CRC strongly correlated with HME and IME, respectively, clinicopathological features of NRAS-mutation(+) CRC, including association with DNA methylation, remain unclear. To characterize NRAS-mutation(+) CRC, the methylation levels of 19 methylation marker genes (6 Group 1 and 13 Group 2) were analyzed in 61 NRAS-mutation(+) and 144 NRAS-mutation(-) CRC cases by pyrosequencing, and their correlation with clinicopathological features was investigated. Different from KRAS-mutation(+) CRC, NRAS-mutation(+) CRC significantly correlated with LME. NRAS-mutation(+) CRC showed significantly better prognosis than KRAS-mutation(+) CRC (P = 3 × 10 -4 ). NRAS-mutation(+) CRC preferentially occurred in elder patients (P = 0.02) and at the distal colon (P = 0.006), showed significantly less lymph vessel invasion (P = 0.002), and correlated with LME (P = 8 × 10 -5 ). DNA methylation significantly accumulated at the proximal colon. NRAS-mutation(+) CRC may constitute a different subgroup from KRAS-mutation(+) CRC, showing significant correlation with LME, older age, distal colon, and relatively better prognosis. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Evaluation of polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions prepared by hot-melt extrusion.

PubMed

Feng, Jia; Xu, Lishuang; Gao, Renchao; Luo, Yanfei; Tang, Xing

2012-06-01

The aim of this study was to evaluate several polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions (SD) prepared by hot-melt extrusion (HME) and select the most appropriate polymer carrier. Solid dispersions containing bifendate in different polymers, including Plasdone(®) S-630, Eudragit(®) EPO and Kollidon(®) VA 64 were prepared by hot-melt extrusion. Differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD) and dissolution testing were used to characterize the systems. Then, the thermal degradation during the HME process and the storage stability of tablets consisting of bifendate-Kollidon(®) VA 64 SD were investigated. Finally, the oral bioavailability of bifendate dosage forms with bifendate-Plasdone(®) S-630 (1/9), bifendate-Eudragit(®) EPO (1/4) and bifendate-Kollidon(®) VA 64 (1/9) SD in beagle dogs was compared with that of commercially available benfidate pills. DSC and XDR analysis showed the dispersion of the drug in the polymer on a molecular basis or in the amorphous state. The drug release from both bifendate-Plasdone(®) S-630 SD and bifendate-Eudragit(®) EPO SD was up to more than 90% with the pH 1.2 simulated gastric fluid as the dissolution medium, while the relative bioavailability was just 87.8 ± 51.8% and 110 ± 62% compared with commercial pills, respectively. The directly compressed tablets with bifendate-Kollidon(®) VA 64 SD were found to dissolve rapidly over 95% within 30 min and the relative bioavailability was 145.0 ± 35.2%. The bioavailability of water-insoluble bifendate was markedly enhanced by dispersing the drug in the polymer carrier Kollidon(®) VA 64 employing HME technology.

Physicochemical characterization and drug-release properties of celecoxib hot-melt extruded glass solutions.

PubMed

Andrews, Gavin P; Abu-Diak, Osama; Kusmanto, Febe; Hornsby, Peter; Hui, Zhai; Jones, David S

2010-11-01

The interest in hot-melt extrusion (HME) as a drug delivery technology for the production of glass solutions is growing rapidly. HME glass solutions have a tendency to recrystallize during storage and also typically have a very dense structure, restricting the ingress of dissolution fluid and retarding drug release. In this study, we have used HME to manufacture glass solutions containing celecoxib (CX) and polyvinylpyrrolidone (PVP) and have assessed the use of supercritical carbon dioxide (scCO2) as a pore-forming agent to enhance drug release. Differential scanning calorimetry confirmed the formation of glass solutions following extrusion. All extrudates exhibited a single glass transition temperature (Tg), positioned between the Tg values of CX and PVP. The instability of glass solutions is a significant problem during storage. Stabilization may be improved through the appropriate choice of excipient to facilitate drug–polymer interactions. The Gordon–Taylor equation showed that the Tg values of all extrudates expected on ideal mixing were lower than those observed experimentally. This may be indicative of drug–polymer interactions that decrease free volume and elevate the Tg. Molecular interactions between CX and PVP were further confirmed using Fourier transform infrared and Raman spectroscopy. Storage stability of the extrudates was shown to be dependent on drug loading. Samples containing a higher CX loading were less stable, which we ascribed to decreased Tg and hence increased mobility within the drug–polymer matrix. The solubility of CX was improved through the formulation of extruded glass solutions, but release rate was relatively slow. Exposure of extrudates to scCO2 had no effect on the solid-state properties of CX but did produce a highly porous structure. The drug-release rate from extrudates after scCO2 exposure was significantly higher.

dbHiMo: a web-based epigenomics platform for histone-modifying enzymes

PubMed Central

Choi, Jaeyoung; Kim, Ki-Tae; Huh, Aram; Kwon, Seomun; Hong, Changyoung; Asiegbu, Fred O.; Jeon, Junhyun; Lee, Yong-Hwan

2015-01-01

Over the past two decades, epigenetics has evolved into a key concept for understanding regulation of gene expression. Among many epigenetic mechanisms, covalent modifications such as acetylation and methylation of lysine residues on core histones emerged as a major mechanism in epigenetic regulation. Here, we present the database for histone-modifying enzymes (dbHiMo; http://hme.riceblast.snu.ac.kr/) aimed at facilitating functional and comparative analysis of histone-modifying enzymes (HMEs). HMEs were identified by applying a search pipeline built upon profile hidden Markov model (HMM) to proteomes. The database incorporates 11 576 HMEs identified from 603 proteomes including 483 fungal, 32 plants and 51 metazoan species. The dbHiMo provides users with web-based personalized data browsing and analysis tools, supporting comparative and evolutionary genomics. With comprehensive data entries and associated web-based tools, our database will be a valuable resource for future epigenetics/epigenomics studies. Database URL: http://hme.riceblast.snu.ac.kr/ PMID:26055100

Idiopathic masseter muscle hypertrophy.

PubMed

Kebede, Biruktawit; Megersa, Shimalis

2011-11-01

Benign Masseteric Hypertrophy is a relatively uncommon condition that can occur unilaterally or bilaterally. Pain may be a symptom, but most frequently a clinician is consulted for cosmetic reasons. In some cases prominent Exostoses at the angle of the mandible are noted. Although it is tempting to point to Malocclusion, Bruxism, clenching, or Temporomandibular joint disorders, the etiology in the majority of cases is unclear. Diagnosis is based on awareness of the condition, clinical and radiographic findings, and exclusion of more serious Pathology such as Benign and Malignant Parotid Disease, Rhabdomyoma, and Lymphangioma. Treatment usually involves resection of a portion of the Masseter muscle with or without the underlying bone.

49 CFR 1572.9 - Applicant information required for HME security threat assessment.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... (13) Passport number. This information is voluntary and may expedite the adjudication process for... information is voluntary and may expedite the adjudication process for applicants who are U.S. citizens born... adjudication process for applicants who have completed a TSA security threat assessment. (16) Whether the...

Improvement in antiproliferative activity of Angelica gigas Nakai by solid dispersion formation via hot-melt extrusion and induction of cell cycle arrest and apoptosis in HeLa cells.

PubMed

Jiang, Yunyao; Piao, Jingpei; Cho, Hyun-Jong; Kang, Wie-Soo; Kim, Hye-Young

2015-01-01

Angelica gigas Nakai (AGN) is one of the most popular herbal medicines and widely used as a functional food product. In this study, AGN was firstly processed by a low-temperature turbo mill and a hot melting extruder to reduce particle size and form solid dispersion (SD). Anticancer activity against HeLa cells was then examined. AGN-SD based on Soluplus was formed via hot-melt extrusion (HME) and showed the strongest cytotoxic effect on HeLa cells. In addition, the possible mechanism of cell death induced by AGN-SD on HeLa cells was also investigated. AGN-SD decreased cell viability, induced apoptosis, increased the production of reactive oxygen species, regulated the expression of Bcl-2 and Bax, and induced G2/M phase arrest in HeLa cells. This study suggested that AGN-SD based on Soluplus and the method to improve antiproliferative effect by SD formation via HME may be suitable for application in the pharmaceutical industry.

Mechanistic modeling of modular co-rotating twin-screw extruders.

PubMed

Eitzlmayr, Andreas; Koscher, Gerold; Reynolds, Gavin; Huang, Zhenyu; Booth, Jonathan; Shering, Philip; Khinast, Johannes

2014-10-20

In this study, we present a one-dimensional (1D) model of the metering zone of a modular, co-rotating twin-screw extruder for pharmaceutical hot melt extrusion (HME). The model accounts for filling ratio, pressure, melt temperature in screw channels and gaps, driving power, torque and the residence time distribution (RTD). It requires two empirical parameters for each screw element to be determined experimentally or numerically using computational fluid dynamics (CFD). The required Nusselt correlation for the heat transfer to the barrel was determined from experimental data. We present results for a fluid with a constant viscosity in comparison to literature data obtained from CFD simulations. Moreover, we show how to incorporate the rheology of a typical, non-Newtonian polymer melt, and present results in comparison to measurements. For both cases, we achieved excellent agreement. Furthermore, we present results for the RTD, based on experimental data from the literature, and found good agreement with simulations, in which the entire HME process was approximated with the metering model, assuming a constant viscosity for the polymer melt. Copyright © 2014. Published by Elsevier B.V.

Health issues for surfers.

PubMed

Zoltan, Todd B; Taylor, Kenneth S; Achar, Suraj A

2005-06-15

Surfers are prone to acute injuries as well as conditions resulting from chronic environmental exposure. Sprains, lacerations, strains, and fractures are the most common types of trauma. Injury from the rider's own surfboard may be the prevailing mechanism. Minor wound infections can be treated on an outpatient basis with ciprofloxacin or trimethoprim-sulfamethoxazole. Jellyfish stings are common and may be treated with heat application. Other treatment regimens have had mixed results. Seabather's eruption is a pruritic skin reaction caused by exposure to nematocyst-containing coelenterate larvae. Additional surfing hazards include stingrays, coral reefs, and, occasionally, sharks. Otologic sequelae of surfing include auditory exostoses, tympanic membrane rupture, and otitis externa. Sun exposure and skin cancer risk are inherent dangers of this sport.

Structural Model Error and Decision Relevancy

NASA Astrophysics Data System (ADS)

Goldsby, M.; Lusk, G.

2017-12-01

The extent to which climate models can underwrite specific climate policies has long been a contentious issue. Skeptics frequently deny that climate models are trustworthy in an attempt to undermine climate action, whereas policy makers often desire information that exceeds the capabilities of extant models. While not skeptics, a group of mathematicians and philosophers [Frigg et al. (2014)] recently argued that even tiny differences between the structure of a complex dynamical model and its target system can lead to dramatic predictive errors, possibly resulting in disastrous consequences when policy decisions are based upon those predictions. They call this result the Hawkmoth effect (HME), and seemingly use it to rebuke rightwing proposals to forgo mitigation in favor of adaptation. However, a vigorous debate has emerged between Frigg et al. on one side and another philosopher-mathematician pair [Winsberg and Goodwin (2016)] on the other. On one hand, Frigg et al. argue that their result shifts the burden to climate scientists to demonstrate that their models do not fall prey to the HME. On the other hand, Winsberg and Goodwin suggest that arguments like those asserted by Frigg et al. can be, if taken seriously, "dangerous": they fail to consider the variety of purposes for which models can be used, and thus too hastily undermine large swaths of climate science. They put the burden back on Frigg et al. to show their result has any effect on climate science. This paper seeks to attenuate this debate by establishing an irenic middle position; we find that there is more agreement between sides than it first seems. We distinguish a `decision standard' from a `burden of proof', which helps clarify the contributions to the debate from both sides. In making this distinction, we argue that scientists bear the burden of assessing the consequences of HME, but that the standard Frigg et al. adopt for decision relevancy is too strict.

Ex vivo assessment and validation of water exchange performance of 23 heat and moisture exchangers for laryngectomized patients.

PubMed

van den Boer, Cindy; Muller, Sara H; Vincent, Andrew D; van den Brekel, Michiel W M; Hilgers, Frans J M

2014-08-01

Breathing through a tracheostoma results in insufficient warming and humidification of the inspired air. This loss of air conditioning, especially humidification, can be partially restored with the application of a heat and moisture exchanger (HME) over the tracheostoma. For medical professionals, it is not easy to judge differences in water exchange performance of various HMEs owing to the lack of universal outcome measures. This study has three aims: assessment of the water exchange performance of commercially available HMEs for laryngectomized patients, validation of these results with absolute humidity outcomes, and assessment of the role of hygroscopic salt present in some of the tested HMEs. Measurements of weight and absolute humidity at end inspiration and end expiration at different breathing volumes of a healthy volunteer were performed using a microbalance and humidity sensor. Twenty-three HMEs from 6 different manufacturers were tested. Associations were determined between core weight, weight change, breathing volume, and absolute humidity, using both linear and nonlinear mixed effects models. Water exchange of the 23 HMEs at a breathing volume of 0.5 L varies between 0.5 and 3.6 mg. Both water exchange and wet core weight correlate strongly with the end-inspiratory absolute humidity values (r2 =0.89/0.87). Hygroscopic salt increases core weight. The 23 tested HMEs for laryngectomized patients show wide variation in water exchange performance. Water exchange correlates well with the end-inspiratory absolute humidity outcome, which validates the ex vivo weight change method. Wet core weight is a predictor of HME performance. Hygroscopic salt increases the weight of the core material. The results of this study can help medical professionals to obtain a more founded opinion about the performance of available HMEs for pulmonary rehabilitation in laryngectomized patients, and allow them to make an informed decision about which HME type to use.

Process design and control of a twin screw hot melt extrusion for continuous pharmaceutical tamper-resistant tablet production.

PubMed

Baronsky-Probst, J; Möltgen, C-V; Kessler, W; Kessler, R W

2016-05-25

Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most efficient production technique. The focus of this study is thus to evaluate the manufacturability of the HME process for tamper-resistant formulations. Parameters such as the specific mechanical energy (SME), as well as the melt pressure and its standard deviation, are important and will be discussed in this study. In the first step, the existing process data are analyzed by means of multivariate data analysis. Key critical process parameters such as feed rate, screw speed, and the concentration of the API in the polymers are identified, and critical quality parameters of the tablet are defined. In the second step, a relationship between the critical material, product and process quality attributes are established by means of Design of Experiments (DoEs). The resulting SME and the temperature at the die are essential data points needed to indirectly qualify the degradation of the API, which should be minimal. NIR-spectroscopy is used to monitor the material during the extrusion process. In contrast to most applications in which the probe is directly integrated into the die, the optical sensor is integrated into the cooling line of the strands. This saves costs in the probe design and maintenance and increases the robustness of the chemometric models. Finally, a process measurement system is installed to monitor and control all of the critical attributes in real-time by means of first principles, DoE models, soft sensor models, and spectroscopic information. Overall, the process is very robust as long as the screw speed is kept low. Copyright © 2015 Elsevier B.V. All rights reserved.

Gradients in precipitation and seasonality between Central and Eastern Asia (Mongolia, Northern Vietnam) during the Oligocene with implication for earlier monsoonal circulation

NASA Astrophysics Data System (ADS)

Boehme, Madelaine; Krings, Michael; Prieto, Jérome; Schneider, Simon

2010-05-01

Today Central and Eastern Asia are characterized by strong contrast in the amount and the annual distribution of rainfall as well as the seasonality in temperature, which is attributed to the uplifted Tibetian Plateau generating monsoonal circulation. Whereas Central Asia is characterized by strong continentality with cold winters and little rainfall concentrated in a short rainy season, the southern part of East Asia exhibit a paratropical climate with high amounts in precipitation distributed relatively even through the year. Palaeontological data (vertebrates and plant remains) from the Eocene and Oligocene of Mongolia and Northern Vietnam indicate that a strong gradient in precipitation and seasonality between Central Asia and East Asia was already established during the Oligocene, which emphasise the establishment of substantial monsoonal circulation at that time. Fossil amphibians and reptiles from Mongolia (45° N, 101° E; Böhme 2007) indicate a strong and abrupt drying and winter cooling at the Eocene-Oligocene boundary consistent with previous results (Dupont-Nivet et al. 2007). Late Eocene assemblages are characterized by crocodiles, salamanders and diverse aquatic turtles, whereas Early Oligocene faunas constitutes of pelobatid frogs, agamid and anguid squamates, diverse species of lizards, and an erycine boide snake. The environmental preferences of both contrasting assemblages point to a severe climate event around 34 myr ago, resulting in the lost of permanent freshwater bodies under humid and winter mild climate and the spread of open landscapes without permanent freshwater bodies under a dry arid to semi-arid climate with only a short rainy season. Oligocene reptiles, macro- and micro-botanical remains, as well as palaeosols from Northern Vietnam (22° N, 107° E; Böhme et al. subm.) suggest warm-humid, (para-) tropical climates with low seasonality in temperature and precipitation. Besides a high diversity in semi-aquatic turtles and the presence of large-sized longirostrine crocodiles we found diverse ferns, including arborescent Osmundaceae and planosol paleosoils similar to those which developed today in this region. Böhme, M. 2007. Oligocene-Miocene Vertebrates from the Valley of Lakes (Central Mongolia): Morphology, phylogenetic and stratigraphic implications - 3. Herpetofauna (Anura, Squamata) and palaeoclimatic implications: preliminary results.- Annalen des Naturhistorischen Museums Wien 108A: 43-52. Böhme, M., Prieto J., Schneider, S. (submitted): Cenozoic basins of Northern Vietnam: biostratigraphy, vertebrate and invertebrate fauna.- Journal of Asian Earth Sciences. Dupont-Nivet, G., Krijgsman, W., Langereis, C.G., Abels, H. A., Dai, S. and Fang, X. 2007. Tibetan Plateau aridification linked to global cooling at the Eocene-Oligocene transition.- Nature 445, 635-638.

Forearm lengthening by distraction osteogenesis: A report on 5 limbs in 3 cases.

PubMed

Tonogai, Ichiro; Takahashi, Mitsuhiko; Tsutsui, Takahiko; Goto, Tomohiro; Hamada, Daisuke; Suzue, Naoto; Matsuura, Tetsuya; Yasui, Natsuo; Sairyo, Koichi

2015-01-01

Radioulnar length discrepancy causes pain and decreases function of the wrist, forearm, and elbow. Limb lengthening, which has been used in the treatment of various deformities of the forearm, is necessary to restore balance between the ulna and radius. We treated 5 limbs in 3 patients (2 boys, 1 girl; mean age 9.3 years old) with radioulnar length discrepancy by distraction osteogenesis of either the ulna or radius using external fixators. We dissected the interosseous membrane between the ulna and radius in 3 limbs in 2 cases and did not do so in 2 limbs of 1 case. These cases include 2 cases with hereditary multiple exostoses, and 1 case with multiple epiphyseal dysplasia. The results were investigated and evaluated in this study, using appropriate clinical and radiographic parameters, noting the state of the interosseous membrane, which has an important role in forearm stability. The mean fixation period was 113 days. The mean distraction distance was 22.8 mm. The mean follow-up period was 637.7 days. The mean ulnar shortening and radial articular angle respectively improved from 7.4 mm and 30.2° preoperatively to -0.1 mm and 34.8° postoperatively. Balance between the ulna and radius was restored, and the results showed significant improvements in range of motion of the joints. However, 2 unintended radial head subluxations occurred in 2 limbs without dissection of the interosseous membrane. In addition, a keloid remained in 1 limb due to pin site infection. Forearm lengthening by distraction osteogenesis was useful in our cases. It is important to recognize the function of the interosseous membrane when lengthening is performed by osteotomy of the proximal ulna by gradual distraction with an external fixator.

Hull, Mechanical, and Electrical Equipment Standardization in the U.S. Navy Surface Force: A Case of Competing Objectives and Stakeholder Trade-Off Decisions

DTIC Science & Technology

2007-12-14

successful Standardization Program for Hull, Mechanical, and Electrical (HM&E) equipment and components of ships in the surface force costs the United......standardization will significantly increases the likelihood of achieving transformation successes . Properly identifying and understanding the root cause of a

Intérêt de l’imagerie dans les tumeurs osseuses bénignes chez l’enfant

PubMed Central

Traoré, Ousmane; Chban, Kamilia; Hode, Alzavine Fleur; Diarra, Yaya; Salam, Siham; Ouzidane, Lachen

2016-01-01

Les tumeurs osseuses bénignes sont beaucoup plus fréquentes que les tumeurs malignes en milieu pédiatrique. L’exostose (ostéchondrome) en est la plus fréquente. Les différentes techniques d'imagerie occupent une place déterminante dans l'étude de ses tumeurs notamment la radiographie standard. Le but de ce travail est de souligner l’intérêt de l’imagerie dans la prise en charge diagnostique des tumeurs bénignes osseuses chez l’enfant à travers une étude rétrospective portant sur 169 patients. Tous ces patients ont été explorés par la radiographie standard, un complément scanner avec reconstruction multiplanaires avant et après injection de PDC et/ouune IRM 1.5 Tesla a été réalisé en fonction de l’indication. L’âge moyen est de 6 ans avec une légère prédominance masculine. Cliniquement, la tuméfaction est présente dans 35% des cas. La douleur dans 29 %des cas. La localisation la plus fréquente est la métaphyse sur les os long: fémur: 25% des cas, humérus: 17 % des cas, tibia: 21% des cas. Les principales tumeurs bénignes retrouvées sont l’exostose (20,12 %), le kyste osseux (31,95%) et l’ostéoblastome (16, 57%). L’imagerie permet de préciser la topographie et l’extension de la lésion dans l’os, apporter des arguments en faveur de la bénignité et parfois, en faveur de l’origine de la lésion. La radiographie standard seule permet souvent de poser un diagnostic de certitude dans certains cas. PMID:27795776

Enactments of Discursive Empowerment in Narratives of Medium of Education by North Indian Women

ERIC Educational Resources Information Center

Sandhu, Priti

2010-01-01

In this study I examine how women in a north Indian city narratively construct their identities in relation to medium of education (MoE)--English only (EME), Hindi only (HME), and a combination of both. I specifically analyze how the participants discursively articulate empowerment or disempowerment while narrating stories connected to their MoEs.…

Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion.

PubMed

Patil, Hemlata; Kulkarni, Vijay; Majumdar, Soumyajit; Repka, Michael A

2014-08-25

Solid lipid nanoparticles (SLN) can either be produced by hot homogenization of melted lipids at higher temperatures or by a cold homogenization process. This paper proposes and demonstrates the formulation of SLN for pharmaceutical applications by combining two processes: hot melt extrusion (HME) technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. This work aimed at developing continuous and scalable processes for SLN by mixing a lipid and aqueous phase containing an emulsifier in the extruder barrel at temperatures above the melting point of the lipid and further reducing the particle size of emulsion by HPH linked to HME in a sequence. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm (for 60 mg/ml lipid solution at a flow rate of 100ml/min). Among the several process parameters investigated, the lipid concentration, residence time and screw design played major roles in influencing the size of the SLN. This new process demonstrates the potential use of hot melt extrusion technology for continuous and large-scale production of SLN. Copyright © 2014 Elsevier B.V. All rights reserved.

Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

PubMed

Claeys, Bart; Vervaeck, Anouk; Hillewaere, Xander K D; Possemiers, Sam; Hansen, Laurent; De Beer, Thomas; Remon, Jean Paul; Vervaet, Chris

2015-02-01

This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM. Copyright © 2014 Elsevier B.V. All rights reserved.

Application of carrier and plasticizer to improve the dissolution and bioavailability of poorly water-soluble baicalein by hot melt extrusion.

PubMed

Zhang, Yilan; Luo, Rui; Chen, Yi; Ke, Xue; Hu, Danrong; Han, Miaomiao

2014-06-01

The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.

HPLC-DAD-ESI/MS(n) analysis of phenolic compounds for quality control of Grindelia robusta Nutt. and bioactivities.

PubMed

Ferreres, Federico; Grosso, Clara; Gil-Izquierdo, Angel; Valentão, Patrícia; Azevedo, Carolina; Andrade, Paula B

2014-06-01

The phenolic composition of herbal tea (HT) and hydromethanolic extract (HME) obtained from Grindelia robusta Nutt. was studied by HPLC-DAD-ESI/MS(n). Thirty six flavonoids and hydroxycinnamic acids were detected, from which thirty are described for the first time in this species. Quantification by HPLC-DAD showed that diosmetin-7-O-glucuronide-3'-O-pentoside+apigenin-7-O-glucuronide-4'-O-pentoside, apigenin-7-O-glucuronide+diosmetin-7-O-glucuronide and 3,5-dicaffeoylquinic acid+3,4-dicaffeoylquinic acid were the major compounds. Since the health-promoting effects of natural phenolic compounds against brain disorders is of increasing interest, HT and HME were also tested against oxygen and nitrogen reactive species and against enzymes related with Alzheimer's disease and depression. Extracts displayed strong in vitro scavenging activity and monoamine oxidase-A (MAO-A) inhibitory activity. The anti-MAO-A capacity was observed at non-toxic concentrations for SH-SY5Y human neuroblastoma cell line, reinforcing the benefits of G. robusta HT. However, no protection against hydrogen peroxide treatment was observed. Copyright © 2014 Elsevier B.V. All rights reserved.

Heated humidification improves clinical outcomes, compared to a heat and moisture exchanger in children with tracheostomies.

PubMed

McNamara, David G; Asher, M Innes; Rubin, Bruce K; Stewart, Alistair; Byrnes, Catherine A

2014-01-01

The upper airway humidifies and warms inspired gases before they reach the trachea, a process bypassed by the insertion of a tracheostomy, necessitating humidification of inspired gases. The optimal method of humidification is not known. We conducted a short-term 20-hour study and a long-term 10-week randomized crossover study comparing a heated humidifier (HH) to a heat and moisture exchanger (HME) in children with established tracheostomies. Subjects were assessed for clinical events, clinical examination findings, airway cytokine levels, and airway secretion viscoelasticity. For the short-term study, 15 children were recruited; for the long-term study, 14 children were recruited. Children using the HH had decreased respiratory examination score (P < .001) but no change in clinical events over the short term. There was a decrease in acute clinical events (P = .008) in the long-term study. No differences were found in airway secretion viscoelasticity results or cytokine levels in either study, but these sample numbers were limited. Over 20 hours use, HH, compared to HME, improved work of breathing. Over a longer 10 week treatment period HH resulted in decreased adverse clinical events.

Heat and moisture exchange capacity of the upper respiratory tract and the effect of tracheotomy breathing on endotracheal climate.

PubMed

Scheenstra, Renske J; Muller, Sara H; Vincent, Andrew; Hilgers, Frans J M

2011-01-01

The aim of this study was to assess the heat and moisture exchange (HME) capacity of the upper respiratory tract and the effect of tracheotomy breathing on endotracheal climate in patients with head and neck cancer. We plotted the subglottic temperature and humidity measurements in 10 patients with head and neck cancer with a temporary precautionary tracheotomy during successive 10-minute periods of nose, mouth, and tracheotomy breathing in a randomized sequence. End-inspiratory temperatures of nose, mouth, and tracheotomy breathing were 31.1, 31.3, and 28.3°C, respectively. End-inspiratory humidity measurements of nose, mouth, and tracheotomy breathing were 29.3, 28.6, and 21.1 mgH₂O/L, respectively. There was a trend toward lower end-inspiratory humidity in patients with radiotherapy or with large surgery-induced oropharyngeal mucosal defects, whereas temperatures were similar. This study gives objective information about the HME capacity of the upper respiratory tract in patients with head and neck cancer with precautionary tracheotomy, and thus provides target values for HMEs for laryngectomized and tracheotomized patients. © 2010 Wiley Periodicals, Inc. Head Neck, 2011.

G protein-coupled receptor 30 down-regulates cofactor expression and interferes with the transcriptional activity of glucocorticoid.

PubMed

Ylikomi, Timo; Vienonen, Annika; Ahola, Tytti M

2004-11-01

G protein-coupled receptor 30 (GPR30) has previously been described to be important in steroid-mediated growth and to inhibit cell proliferation. Here we investigated whether the effect of GPR30 on cell growth is dependent on steroid hormone receptors. We stably introduced GPR30 in immortalized normal mammary epithelial (HME) cells using retroviruses for gene delivery. GPR30 inhibited the growth and proliferation of the cells. They expressed glucocorticoid receptor, but not estrogen or progesterone receptor. GPR30 down-regulated the expression of cofactor transcription intermediary factor 2 (TIF2) analyzed using quantitative RT-PCR analysis, and also diminished the expression of TIF2 at protein level analyzed by Western blotting using nuclear extracts from mammary epithelial cells. When HME cells were transiently transfected with the glucocorticoid response element MMTV-luc reporter plasmid, stable expression of GPR30 resulted in the abolition of ligand-induced transactivation of the promoter. In COS cells, transient transfection of GPR30 with glucocorticoid receptor alpha resulted in an abrogation of the MMTV-luc and GRE-luc reporter activities induced by dexamethasone. The results suggest a novel mechanism by which membrane-initiated signaling interferes with steroid signaling.

Designing of Holistic Mathematic Education Model Based-"System Among" at Low Grade Elementary School

NASA Astrophysics Data System (ADS)

Hayati, R.; Fauzan, A.; Iswari, M.; Khaidir, A.

2018-04-01

The purpose of this study was to develop a model of Holistic Mathematics Education (HME) among systems based on low-grade primary school students so that students have a solid foundation when entering a higher behavior. This type of research is desaign research developed by Plomp to have three stages, namely the preliminary research, development or prototyping phase, and assessement Phase. This research resulted in a model Holistic Mathematics Education (HME) -based system is among the primary school students low grade consists of 10 stages, namely 1) Recap through the neighborhood, 2) Discussion groups by exploiting the environment, 3) Demonstration Group, 4) Exercise individuals, 5) mathematical modeling, 6) Demonstration of individuals, 7) Reflections, 8) impressions and messages, and giving meaning, 9) Celebrations and 10) A thorough assessment. Furthermore, this model also produces 7 important components that should be developed teacher, namely 1) constructivism, 2) the nature of nature, 3) independence, 4) parable, 5) inquiry, 6) cooperation, and 7) strengthening. This model will produce a model in the form of books, student books and teacher's guide book as a support system that can help users in its application.

Stress Modulus of Cancer Cells

NASA Astrophysics Data System (ADS)

Bonin, Keith; Guthold, Martin; Guo, Xinyi; Sigley, Justin

2012-02-01

Our main goal is to study the different physical and mechanical properties of cells as they advance through different stages of neoplastic transformation from normal to the metastatic state. Since recent reports indicate there is significant ambiguity about how these properties change for different cancer cells, we plan to measure these properties for a single line of cells, and to determine whether the changes vary for different cellular components: i.e. whether the change in physical properties is due to a change in the cytoskeleton, the cell membrane, the cytoplasm, or a combination of these elements. Here we expect to present data on the stress modulus of cancer cells at different stages: normal, mortal cancerous, immortal cancerous, and tumorigenic. The cells are Weinberg cell line Human Mammary Epithelial (HME) cells. Atomic force microscope (AFM) probes with different diameters are used to push on the cell membrane to measure the local, regional and global cell stress modulus. Preliminary results on normal HME cells suggests a stress modulus of 1.5 ± 0.8 kPa when pushing with 7 μm spherical probes. We anticipate reporting an improved value for the modulus as well as results for some of the Weinberg cancer cells.

BRCA1/p220 loss triggers BRCA1-IRIS overexpression via mRNA stabilization in breast cancer cells

PubMed Central

Shimizu, Yoshiko; Mullins, Nicole; Blanchard, Zannel; ElShamy, Wael M.

2012-01-01

BRCA1/p220-assocaited and triple negative/basal-like (TN/BL) tumors are aggressive and incurable breast cancer diseases that share among other features the no/low BRCA1/p220 expression. Here we show that BRCA1/p220 silencing in normal human mammary epithelial (HME) cells reduces expression of two RNA-destabilizing proteins, namely AUF1 and pCBP2, both proteins bind and destabilize BRCA1-IRIS mRNA. BRCA1-IRIS overexpression in HME cells triggers expression of several TN/BL markers, e.g., cytokeratins 5 and 17, p-cadherin, EGFR and cyclin E as well as expression and activation of the pro-survival proteins; AKT and survivin. BRCA1-IRIS silencing in the TN/BL cell line, SUM149 or restoration of BRCA1/p220 expression in the mutant cell line, HCC1937 reduced expression of TN/BL markers, AKT, survivin, and induced cell death. Collectively, we propose that BRCA1/p220 loss of expression or function triggers BRCA1-IRIS overexpression through a post-transcriptional mechanism, which in turn promotes formation of aggressive and invasive breast tumors by inducing expression of TN/BL and survival proteins. PMID:22431556

The Empirical Canadian High Arctic Ionospheric Model (E-CHAIM): Bottomside Parameterization

NASA Astrophysics Data System (ADS)

Themens, D. R.; Jayachandran, P. T.

2017-12-01

It is well known that the International Reference Ionosphere (IRI) suffers reduced accuracy in its representation of monthly median ionospheric electron density at high latitudes. These inaccuracies are believed to stem, at least in part, from a historical lack of data from these regions. Now, roughly thirty and forty years after the development of the original URSI and CCIR foF2 maps, respectively, there exists a much larger dataset of high latitude observations of ionospheric electron density. These new measurements come in the form of new ionosonde deployments, such as those of the Canadian High Arctic Ionospheric Network, the CHAMP, GRACE, and COSMIC radio occultation missions, and the construction of the Poker Flat, Resolute, and EISCAT Incoherent Scatter Radar systems. These new datasets afford an opportunity to revise the IRI's representation of the high latitude ionosphere. Using a spherical cap harmonic expansion to represent horizontal and diurnal variability and a Fourier expansion in day of year to represent seasonal variations, we have developed a new model of the bottomside ionosphere's electron density for the high latitude ionosphere, above 50N geomagnetic latitude. For the peak heights of the E and F1 layers (hmE and hmF1, respectively), current standards use a constant value for hmE and either use a single-parameter model for hmF1 (IRI) or scale hmF1 with the F peak (NeQuick). For E-CHAIM, we have diverged from this convention to account for the greater variability seen in these characteristics at high latitudes, opting to use a full spherical harmonic model description for each of these characteristics. For the description of the bottomside vertical electron density profile, we present a single-layer model with altitude-varying scale height. The scale height function is taken as the sum three scale height layer functions anchored to the F2 peak, hmF1, and hmE. This parameterization successfully reproduces the structure of the various bottomside layers while ensuring that the resulting electron density profile is free of strong vertical gradient artifacts and is doubly differentiable.

Estimation of tracheal pressure and imposed expiratory work of breathing by the endotracheal tube, heat and moisture exchanger, and ventilator during mechanical ventilation.

PubMed

Uchiyama, Akinori; Yoshida, Takeshi; Yamanaka, Hidenori; Fujino, Yuji

2013-07-01

The resistance of the endotracheal tube (ETT), the heat and moisture exchanger (HME), and the ventilator may affect the patient's respiratory status. Although previous studies examined the inspiratory work of breathing (WOB), investigation of WOB in the expiratory phase is rare. We estimated tracheal pressure at the tip of the ETT (Ptrach) and calculated expiratory WOB imposed by the ETT, the HME, and the expiratory valve. We examined imposed expiratory WOB in patients under a continuous mandatory ventilation (CMV) mode and during spontaneous breathing trials (SBTs). We hypothesized that imposed expiratory WOB would increase with heightened ventilatory demand. We measured airway pressure (Paw) and respiratory flow (V). We estimated Ptrach using the equation Ptrach = Paw - K1 × V(K2) - 2.70 × V(L/s)(1.42). K1 and K2 were determined by the inner diameter (ID) of the ETT. Imposed expiratory WOB was calculated from the area of Ptrach above PEEP versus lung volume. We examined imposed expiratory WOB and imposed expiratory resistance in relation to mean expiratory flow. We examined 28 patients under CMV mode, and 29 during SBT. During both CMV and SBT, as mean expiratory flow increased, imposed expiratory WOB increased. The regression curves between mean expiratory flow (x) (L/s) and imposed expiratory WOB (y) (J/L) were y = 1.35x(0.83) (R(2) = 0.79) for 7 mm ID ETT under CMV, y = 1.12x(0.82) (R(2) = 0.73) for 8 mm ID ETT under CMV, y = 1.07x(1.04) (R(2) = 0.85) for 7 mm ID ETT during SBT, and y = 0.84x(0.93) (R(2) = 0.75) for 8 mm ID ETT during SBT. Levels of imposed expiratory WOB were affected by ETT diameter and ventilator mode. The reason for increasing imposed expiratory WOB was an increase in expiratory resistance imposed by the ETT and HME. Under mechanical ventilation, imposed expiratory WOB should be considered in patients with higher minute ventilation.

Back-scattered electron imaging of a non-vertebral case of hypervitaminosis A in a cat.

PubMed

Franch, J; Pastor, J; Franch, B; Durall, I; Manzanares, M C

2000-03-01

We describe a clinical case of hypervitaminosis A in a cat. The main lesions were bony fusions of both the hip and stifle joints, without spinal involvement. A post-mortem study using back-scattered scanning electron microscopy (BEI-SEM) revealed that exostoses had formed around the joints without articular surface involvement. The more recently formed areas of bony proliferation were composed mainly of chondroid tissue surrounded by different degrees of woven bone. As the bony reaction occurred, remodelling of the trabeculae was observed which lead to progressive substitution of chondroid tissue by woven bone surrounded by apposition of lamellar bone. No traces of calcified cartilage were observed in any of the bone sections evaluated. Copyright 2000 European Society of Feline Medicine.

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans.

PubMed

Blanchette, Cassandra R; Thackeray, Andrea; Perrat, Paola N; Hekimi, Siegfried; Bénard, Claire Y

2017-01-01

The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development.

Meeting the Challenge of Installing Canes During New Ship Construction on LPD 28

DTIC Science & Technology

2015-03-01

components making up the SWAN are enclosed in Raytheon-designed hardware systems that meet Military Specification MIL-S-901D Grade B shock...Connected Connected Connected, NRE Connected, Engr Control Sys (ECS), Integrated to segreg; tte NREto Condition Assmt Sys (I CAS) SWAN develop HM&E...Hull Mecllanical & Electrical (HM&E) - COA Connected NA Connected Connected, NRE Connected, Damage Control Action Management Dependent to segreg; tte

Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion.

PubMed

Malode, Vilas N; Paradkar, Anant; Devarajan, Padma V

2015-08-01

We present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit(®) RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit(®) RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 min but inadequate total floating time (TFT) of 3h. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12h with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24h and t90% of 10.12h. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40°C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of heat-moisture exchanger and closed-circuit technique on airway climate during desflurane anesthesia.

PubMed

Lu, Chih-Cherng; Ho, Shung-Tai; Liaw, Wen-Jinn; Chen, Ruei-Ming; Chen, Ta-Liang; Lin, Chung-Yuan

2008-01-01

We assessed whether closed-circuit anesthesia (CCA) could provide a more favorable airway climate than semi-closed anesthesia (SCA), and we also determined the beneficial effect of heat moisture exchangers (HMEs) on the preservation of airway climate during desflurane anesthesia. Forty patients scheduled for colorectal surgery (n = 10 for each group) were randomized to receive a fresh gas flow of 250 or 3000 ml.min(-1) with or without HMEs. Anesthesia was maintained by adjusting the inspired concentration of 6% desflurane. Absolute moisture and temperature of inspired gases were measured as the baseline value first at 5 min after tracheal intubation, and then at 10, 20, 45, 60, 90, and 120 min after the induction of anesthesia. At 120 min, the inspiratory humidity and temperature were higher in CCA than in SCA. The HME led to major improvements of the humidity (from 22.1 to 35.7 mg H(2)O.l(-1)) and temperature (from 23.6 degrees C to 31.5 degrees C) of anesthetic gases in the CCA group. CCA was much more advantageous than SCA for maintaining the patient's airway climate during the 2-h study. The beneficial effect of HME on the airway climate should be emphasized, especially in patients undergoing general anesthesia.

Bioavailability enhancement of atovaquone using hot melt extrusion technology.

PubMed

Kate, Laxman; Gokarna, Vinod; Borhade, Vivek; Prabhu, Priyanka; Deshpande, Vinita; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

2016-04-30

Emerging parasite resistance and poor oral bioavailability of anti-malarials are the two cardinal issues which hinder the clinical success of malaria chemotherapy. Atovaquone-Proguanil is a WHO approved fixed dose combination used to tackle the problem of emerging resistance. However, Atovaquone is a highly lipophilic drug having poor aqueous solubility (less than 0.2 μg/ml) thus reducing its oral bioavailability. The aim of the present investigation was to explore hot melt extrusion (HME) as a solvent-free technique to enhance solubility and oral bioavailability of Atovaquone and to develop an oral dosage form for Atovaquone-Proguanil combination. Solid dispersion of Atovaquone was successfully developed using HME. The solid dispersion was characterized for DSC, FTIR, XRD, SEM, and flow properties. It was filled in size 2 hard gelatin capsules. The formulation showed better release as compared to Malarone® tablets, and 3.2-fold and 4.6-fold higher bioavailability as compared to Malarone® tablets and Atovaquone respectively. The enhanced bioavailability also resulted in 100% anti-malarial activity in murine infection model at 1/8(th) therapeutic dose. Thus the developed methodology shows promising potential to solve the problems associated with Atovaquone therapy, namely its high cost and poor oral bioavailability, resulting in increased therapeutic efficacy of Atovaquone. Copyright © 2016 Elsevier B.V. All rights reserved.

3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

PubMed

Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

2018-01-30

It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

Standardization of Hull, Mechanical, and Electrical Equipment (H,M&E) inventory

DTIC Science & Technology

1987-09-01

Miami University, 1974 M.B.A., George Washington University, 1985 Submitted in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE...Motors, Pumps, and Controllers) within the Weapon System 84 Interview with Messrs. George Blackmore, and William Bunge, Equipment Specialist, SPCC, May 18... George Blackmore, and William Bunge, SPCC, May 18, 1987. 52 V. S identical equipment. The reduction in the equipment range increased the volume for

False aneurysm of the popliteal artery complicated by a deep venous thrombosis revealing an exostosis in a 20-year-old young woman.

PubMed

Bakkali, Tarik; Hormatallah, Mohamed; Bounssir, Ayoub; Aghtoutane, Nabil; Taous, Hamza; Idrissi, Redouane; Sefiani, Yasser; Lekhel, Brahim; Mesnaoui, Abbes; Bensaid, Younes

2018-05-19

Exostoses or osteochondromas are benign osseous tumors that develop on the bone surface and can be sporadic or hereditary. Their evolution is generally benign but they may be complicated in some patients by conflicts with the surrounding nervous or vascular structures, in particular arteries. We report a case of false aneurysm of the popliteal artery secondary to an isolated exostosis of the left femur in a 20-year-old young woman. A delay in the diagnosis allowed the development of the false aneurysm which was at the origin of a major venous compression. The surgical treatment consisted in aneurysmectomy and reconstruction by end to end anastomosis associated to the resection of the osseous tumor, and the deep venous thrombosis was treated medically. Copyright © 2018. Published by Elsevier Inc.

Psychiatric comorbidity in treatment-seeking substance use disorder patients with and without attention deficit hyperactivity disorder: results of the IASP study

PubMed Central

van Emmerik-van Oortmerssen, Katelijne; van de Glind, Geurt; Koeter, Maarten W. J.; Allsop, Steve; Auriacombe, Marc; Barta, Csaba; Bu, Eli Torild H.; Burren, Yuliya; Carpentier, Pieter-Jan; Carruthers, Susan; Casas, Miguel; Demetrovics, Zsolt; Dom, Geert; Faraone, Stephen V.; Fatseas, Melina; Franck, Johan; Johnson, Brian; Kapitány-Fövény, Máté; Kaye, Sharlene; Konstenius, Maija; Levin, Frances R.; Moggi, Franz; Møller, Merete; Ramos-Quiroga, J. Antoni; Schillinger, Arild; Skutle, Arvid; Verspreet, Sofie; van den Brink, Wim; Schoevers, Robert A.

2014-01-01

Aims To determine comorbidity patterns in treatment-seeking substance use disorder (SUD) patients with and without adult attention deficit hyperactivity disorder (ADHD), with an emphasis on subgroups defined by ADHD subtype, taking into account differences related to gender and primary substance of abuse. Design Data were obtained from the cross-sectional International ADHD in Substance use disorder Prevalence (IASP) study. Setting Forty-seven centres of SUD treatment in 10 countries. Participants A total of 1205 treatment-seeking SUD patients. Measurements Structured diagnostic assessments were used for all disorders: presence of ADHD was assessed with the Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID), the presence of antisocial personality disorder (ASPD), major depression (MD) and (hypo)manic episode (HME) was assessed with the Mini International Neuropsychiatric Interview-Plus (MINI Plus), and the presence of borderline personality disorder (BPD) was assessed with the Structured Clinical Interview for DSM-IV Axis II (SCID II). Findings The prevalence of DSM-IV adult ADHD in this SUD sample was 13.9%. ASPD [odds ratio (OR) = 2.8, 95% confidence interval (CI) = 1.8–4.2], BPD (OR = 7.0, 95% CI = 3.1–15.6 for alcohol; OR = 3.4, 95% CI = 1.8–6.4 for drugs), MD in patients with alcohol as primary substance of abuse (OR = 4.1, 95% CI = 2.1–7.8) and HME (OR = 4.3, 95% CI = 2.1–8.7) were all more prevalent in ADHD+ compared with ADHD− patients (P < 0.001). These results also indicate increased levels of BPD and MD for alcohol compared with drugs as primary substance of abuse. Comorbidity patterns differed between ADHD subtypes with increased MD in the inattentive and combined subtype (P < 0.01), increased HME and ASPD in the hyperactive/impulsive (P < 0.01) and combined subtypes (P < 0.001) and increased BPD in all subtypes (P < 0.001) compared with SUD patients without ADHD. Seventy-five per cent of ADHD patients had at least one additional comorbid disorder compared with 37% of SUD patients without ADHD. Conclusions Treatment-seeking substance use disorder patients with attention deficit hyperactivity disorder are at a very high risk for additional externalizing disorders. PMID:24118292

Out-of-Pocket and Informal Payment Before and After the Health Transformation Plan in Iran: Evidence from Hospitals Located in Kurdistan, Iran

PubMed Central

Piroozi, Bakhtiar; Rashidian, Arash; Moradi, Ghobad; Takian, Amirhossein; Ghasri, Hooman; Ghadimi, Tayyeb

2017-01-01

Background: One of the objectives of the health transformation plan (HTP) in Iran is to reduce out-of-pocket (OOP) payments for inpatient services and eradicate informal payments. The HTP has three phases: the first phase (launched in May 5, 2014) is focused on reducing OOP payments for inpatient services; the second phase (launched in May 22, 2014) is focused on primary healthcare (PHC) and the third phase utilizes an updated relative value units for health services (launched in September 29, 2014) and is focused on the elimination of informal payments. This aim of this study was to determine the OOP payments and the frequency of informal cash payments to physicians for inpatient services before and after the HTP in Kurdistan province, Iran. Methods: This quasi-experimental study used multistage sampling method to select and evaluate 265 patients ischarged from hospitals in Kurdistan province. The study covered 3 phases (before the HTP, after the first, and third phases of the HTP). Part of the data was collected using a hospital information system form and the rest were collected using a questionnaire. Data were analyzed using Fisher exact test, logistic regression, and independent samples t test. Results: The mean OOP payments before the HTP and after the first and third phases, respectively, were US$59.4, US$17.6, and US$14.3 in hospital affiliated to the Ministry of Health and Medical Education (MoHME), US$39.6, US$33.7, and US$13.7 in hospitals affiliated to Social Security Organization (SSO), and US$153.3, US$188.7, and US$66.4 in private hospitals. In hospitals affiliated to SSO and MoHME there was a significant difference between the mean OOP payments before the HTP and after the third phase (P<.05). The percentage of informal payments to physicians in hospitals affiliated to MoHME, SSO, and private sector, respectively, were 4.5%, 8.1%, and 12.5% before the HTP, and 0.0%, 7.1%, and 10.0% after the first phase. Contrary to the time before the HTP, no informal payment was reported after the third phase. Conclusion: It seems that the implementation of the HTP has reduced the OOP payments for inpatient services and eradicated informal payments to physician in Kurdistan province. PMID:28949473

BRCA1-IRIS Overexpression Promotes Formation of Aggressive Breast Cancers

PubMed Central

Shimizu, Yoshiko; Luk, Hugh; Horio, David; Miron, Penelope; Griswold, Michael; Iglehart, Dirk; Hernandez, Brenda; Killeen, Jeffrey; ElShamy, Wael M.

2012-01-01

Introduction Women with HER2+ or triple negative/basal-like (TN/BL) breast cancers succumb to their cancer rapidly due, in part to acquired Herceptin resistance and lack of TN/BL-targeted therapies. BRCA1-IRIS is a recently discovered, 1399 residue, BRCA1 locus alternative product, which while sharing 1365 residues with the full-length product of this tumor suppressor gene, BRCA1/p220, it has oncoprotein-like properties. Here, we examine whether BRCA1-IRIS is a valuable treatment target for HER2+ and/or TN/BL tumors. Methodology/Principal Findings Immunohistochemical staining of large cohort of human breast tumor samples using new monoclonal anti-BRCA1-IRIS antibody, followed by correlation of BRCA1-IRIS expression with that of AKT1, AKT2, p-AKT, survivin and BRCA1/p220, tumor status and age at diagnosis. Generation of subcutaneous tumors in SCID mice using human mammary epithelial (HME) cells overexpressing TERT/LT/BRCA1-IRIS, followed by comparing AKT, survivin, and BRCA1/p220 expression, tumor status and aggressiveness in these tumors to that in tumors developed using TERT/LT/RasV12-overexpressing HME cells. Induction of primary and invasive rat mammary tumors using the carcinogen N-methyl-N-nitrosourea (NMU), followed by analysis of rat BRCA1-IRIS and ERα mRNA levels in these tumors. High BRCA1-IRIS expression was detected in the majority of human breast tumors analyzed, which was positively correlated with that of AKT1-, AKT2-, p-AKT-, survivin, but negatively with BRCA1/p220 expression. BRCA1-IRIS-positivity induced high-grade, early onset and metastatic HER2+ or TN/BL tumors. TERT/LT/BRCA1-IRIS overexpressing HME cells formed invasive subcutaneous tumors that express high AKT1, AKT2, p-AKT and vimentin, but no CK19, p63 or BRCA1/p220. NMU-induced primary and invasive rat breast cancers expressed high levels of rat BRCA1-IRIS mRNA but low levels of rat ERα mRNA. Conclusion/Significance BRCA1-IRIS overexpression triggers aggressive breast tumor formation, especially in patients with HER2+ or TN/BL subtypes. We propose that BRCA1-IRIS inhibition may be pursued as a novel therapeutic option to treat these aggressive breast tumor subtypes. PMID:22511931

Estimation of Model's Marginal likelihood Using Adaptive Sparse Grid Surrogates in Bayesian Model Averaging

NASA Astrophysics Data System (ADS)

Zeng, X.

2015-12-01

A large number of model executions are required to obtain alternative conceptual models' predictions and their posterior probabilities in Bayesian model averaging (BMA). The posterior model probability is estimated through models' marginal likelihood and prior probability. The heavy computation burden hinders the implementation of BMA prediction, especially for the elaborated marginal likelihood estimator. For overcoming the computation burden of BMA, an adaptive sparse grid (SG) stochastic collocation method is used to build surrogates for alternative conceptual models through the numerical experiment of a synthetical groundwater model. BMA predictions depend on model posterior weights (or marginal likelihoods), and this study also evaluated four marginal likelihood estimators, including arithmetic mean estimator (AME), harmonic mean estimator (HME), stabilized harmonic mean estimator (SHME), and thermodynamic integration estimator (TIE). The results demonstrate that TIE is accurate in estimating conceptual models' marginal likelihoods. The BMA-TIE has better predictive performance than other BMA predictions. TIE has high stability for estimating conceptual model's marginal likelihood. The repeated estimated conceptual model's marginal likelihoods by TIE have significant less variability than that estimated by other estimators. In addition, the SG surrogates are efficient to facilitate BMA predictions, especially for BMA-TIE. The number of model executions needed for building surrogates is 4.13%, 6.89%, 3.44%, and 0.43% of the required model executions of BMA-AME, BMA-HME, BMA-SHME, and BMA-TIE, respectively.

Formulation Optimization of Hot Melt Extruded Abuse Deterrent Pellet Dosage Form Utilizing Design of Experiments (DOE)

PubMed Central

Maddineni, Sindhuri; Battu, Sunil Kumar; Morott, Joe; Majumdar, Soumyajit; Repka, Michael A.

2014-01-01

The objective of the present study was to develop techniques for an abuse-deterrent (AD) platform utilizing hot melt extrusion (HME) process. Formulation optimization was accomplished by utilizing Box-Behnken design of experiments to determine the effect of the three formulation factors: PolyOx™ WSR301, Benecel™ K15M, and Carbopol 71G; each of which was studied at three levels on TR attributes of the produced melt extruded pellets. A response surface methodology was utilized to identify the optimized formulation. Lidocaine Hydrochloride was used as a model drug, and suitable formulation ingredients were employed as carrier matrices and processing aids. All of the formulations were evaluated for the TR attributes such as particle size post-milling, gelling, percentage of drug extraction in water and alcohol. All of the DOE formulations demonstrated sufficient hardness and elasticity, and could not be reduced into fine particles (<150µm), which is a desirable feature to prevent snorting. In addition, all of the formulations exhibited good gelling tendency in water with minimal extraction of drug in the aqueous medium. Moreover, Benecel™ K15M in combination with PolyOx™ WSR301 could be utilized to produce pellets with TR potential. HME has been demonstrated to be a viable technique with a potential to develop novel abuse-deterrent formulations. PMID:24433429

Impact of polymer type on bioperformance and physical stability of hot melt extruded formulations of a poorly water soluble drug.

PubMed

Mitra, Amitava; Li, Li; Marsac, Patrick; Marks, Brian; Liu, Zhen; Brown, Chad

2016-05-30

Amorphous solid dispersion formulations have been widely used to enhance bioavailability of poorly soluble drugs. In these formulations, polymer is included to physically stabilize the amorphous drug by dispersing it in the polymeric carrier and thus forming a solid solution. The polymer can also maintain supersaturation and promote speciation during dissolution, thus enabling better absorption as compared to crystalline drug substance. In this paper, we report the use of hot melt extrusion (HME) to develop amorphous formulations of a poorly soluble compound (FaSSIF solubility=1μg/mL). The poor solubility of the compound and high dose (300mg) necessitated the use of amorphous formulation to achieve adequate bioperformance. The effect of using three different polymers (HPMCAS-HF, HPMCAS-LF and copovidone), on the dissolution, physical stability, and bioperformance of the formulations was demonstrated. In this particular case, HPMCAS-HF containing HME provided the highest bioavailability and also had better physical stability as compared to extrudates using HPMCAS-LF and copovidone. The data demonstrated that the polymer type can have significant impact on the formulation bioperformance and physical stability. Thus a thorough understanding of the polymer choice is imperative when designing an amorphous solid dispersion formulation, such that the formulation provides robust bioperformance and has adequate shelf life. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmaceutical 3D printing: Design and qualification of a single step print and fill capsule.

PubMed

Smith, Derrick M; Kapoor, Yash; Klinzing, Gerard R; Procopio, Adam T

2018-06-10

Fused deposition modeling (FDM) 3D printing (3DP) has a potential to change how we envision manufacturing in the pharmaceutical industry. A more common utilization for FDM 3DP is to build upon existing hot melt extrusion (HME) technology where the drug is dispersed in the polymer matrix. However, reliable manufacturing of drug-containing filaments remains a challenge along with the limitation of active ingredients which can sustain the processing risks involved in the HME process. To circumvent this obstacle, a single step FDM 3DP process was developed to manufacture thin-walled drug-free capsules which can be filled with dry or liquid drug product formulations. Drug release from these systems is governed by the combined dissolution of the FDM capsule 'shell' and the dosage form encapsulated in these shells. To prepare the shells, the 3D printer files (extension '.gcode') were modified by creating discrete zones, so-called 'zoning process', with individual print parameters. Capsules printed without the zoning process resulted in macroscopic print defects and holes. X-ray computed tomography, finite element analysis and mechanical testing were used to guide the zoning process and printing parameters in order to manufacture consistent and robust capsule shell geometries. Additionally, dose consistencies of drug containing liquid formulations were investigated in this work. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of an analytical method for crystalline content determination in amorphous solid dispersions produced by hot-melt extrusion using transmission Raman spectroscopy: A feasibility study.

PubMed

Netchacovitch, L; Dumont, E; Cailletaud, J; Thiry, J; De Bleye, C; Sacré, P-Y; Boiret, M; Evrard, B; Hubert, Ph; Ziemons, E

2017-09-15

The development of a quantitative method determining the crystalline percentage in an amorphous solid dispersion is of great interest in the pharmaceutical field. Indeed, the crystalline Active Pharmaceutical Ingredient transformation into its amorphous state is increasingly used as it enhances the solubility and bioavailability of Biopharmaceutical Classification System class II drugs. One way to produce amorphous solid dispersions is the Hot-Melt Extrusion (HME) process. This study reported the development and the comparison of the analytical performances of two techniques, based on backscattering and transmission Raman spectroscopy, determining the crystalline remaining content in amorphous solid dispersions produced by HME. Principal Component Analysis (PCA) and Partial Least Squares (PLS) regression were performed on preprocessed data and tended towards the same conclusions: for the backscattering Raman results, the use of the DuoScan™ mode improved the PCA and PLS results, due to a larger analyzed sampling volume. For the transmission Raman results, the determination of low crystalline percentages was possible and the best regression model was obtained using this technique. Indeed, the latter acquired spectra through the whole sample volume, in contrast with the previous surface analyses performed using the backscattering mode. This study consequently highlighted the importance of the analyzed sampling volume. Copyright © 2017 Elsevier B.V. All rights reserved.

A flexible-dose dispenser for immediate and extended release 3D printed tablets.

PubMed

Pietrzak, Katarzyna; Isreb, Abdullah; Alhnan, Mohamed A

2015-10-01

The advances in personalised medicine increased the demand for a fast, accurate and reliable production method of tablets that can be digitally controlled by healthcare staff. A flexible dose tablet system is presented in this study that proved to be suitable for immediate and extended release tablets with a realistic drug loading and an easy-to-swallow tablet design. The method bridges the affordable and digitally controlled Fused Deposition Modelling (FDM) 3D printing with a standard pharmaceutical manufacturing process, Hot Melt Extrusion (HME). The reported method was compatible with three methacrylic polymers (Eudragit RL, RS and E) as well as a cellulose-based one (hydroxypropyl cellulose, HPC SSL). The use of a HME based pharmaceutical filament preserved the linear relationship between the mass and printed volume and was utilized to digitally control the dose via an input from computer software with dose accuracy in the range of 91-95%. Higher resolution printing quality doubled the printing time, but showed a little effect on in vitro release pattern of theophylline and weight accuracy. Physical characterization studies indicated that the majority of the model drug (theophylline) in the 3D printed tablet exists in a crystal form. Owing to the small size, ease of use and the highly adjustable nature of FDM 3D printers, the method holds promise for future individualised treatment. Copyright © 2015. Published by Elsevier B.V.

A comparative study of the effect of spray drying and hot-melt extrusion on the properties of amorphous solid dispersions containing felodipine.

PubMed

Mahmah, Osama; Tabbakh, Rami; Kelly, Adrian; Paradkar, Anant

2014-02-01

To compare the properties of solid dispersions of felodipine for oral bioavailability enhancement using two different polymers, polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt extrusion (HME) and spray drying. Felodipine solid dispersions were prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed characterization was performed using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and in-vitro dissolution testing. Dissolution profiles were evaluated in the presence of sodium dodecyl sulphate. Stability of different solid dispersions was studied under accelerated conditions (40°C/75% RH) over 8 weeks. Spray-dried formulations were found to release felodipine faster than melt extruded formulations for both polymer matrices. Solid dispersions containing HMPCAS exhibited higher drug release rates and better wettability than those produced with a PVP matrix. No significant differences in stability were observed except with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried formulations. Solid dispersions of felodipine produced by spray drying exhibited more rapid drug release than corresponding melt extruded formulations, although in some cases improved stability was observed for melt extruded formulations. © 2013 Royal Pharmaceutical Society.

Primary Neoplasms of Bones in Mice: Retrospective Study and Review of Literature

PubMed Central

Kavirayani, A. M.; Sundberg, J. P.; Foreman, O.

2011-01-01

To compare and summarize the mechanisms, frequencies of occurrence, and classification schemes of spontaneous, experimental, and genetically engineered, mouse skeletal neoplasms, the literature was reviewed and archived case material at The Jackson Laboratory examined. The frequency of occurrence of spontaneous bone neoplasms was less than 1% for most strains, with the exceptions of osteomas in CF-1 (5.5% and 10% in two studies) and OF-1 outbred strains (35%), and osteosarcomas in NOD/ShiLtJ (11.5%) and NOD derived (7.1%) mice. The frequency was 100% for osteochondromas induced by conditional inactivation of exostoses (multiple) 1 (Ext1) in chondrocytes, osteosarcomas induced by tibial intramedullary inoculation of Moloney’s murine sarcoma virus, and osteosarcomas induced by conditional inactivation of Trp53-with or without inactivation of Rb1-in osteoblast precursors. Spontaneous osteogenic neoplasms were more frequent than spontaneous cartilaginous and vascular types. Malignant neoplasms were more frequent than benign ones. The age of occurrence for spontaneous neoplasms ranged from 37 to 720 (Mean 316.35) days for benign, and 35 to 990 (Mean 299.28) days for malignant neoplasms. In genetically engineered mice, the average age of occurrence ranged from 28 to 70 days for benign, and from 35 to 690 days for malignant neoplasms. Histologically, non-osteogenic neoplasms were similar across strains and mutant stocks; osteogenic neoplasms exhibited greater diversity. This comparison and summarization of mouse bone neoplasms provides valuable information for the selection of strains to create, compare, and validate models of bone neoplasms. PMID:21343597

Variation of methods in small-scale safety and thermal testing of improvised explosives

DOE PAGES

Sandstrom, Mary M.; Brown, Geoffrey W.; Preston, Daniel N.; ...

2014-09-29

Here, one of the first steps in establishing safe handling procedures for explosives is small-scale safety and thermal (SSST) testing. To better understand the response of homemade or improvised explosives (HMEs) to SSST testing, 16 HME materials were compared to 3 standard military explosives in a proficiency-type round robin study among five laboratories, two U.S. Department of Defense and three U.S. Department of Energy, sponsored by the Department of Homeland Security, Science & Technology Directorate, Explosives Division.

Identification of Stem Cells in a Novel Human Mammary Epithelial Culture (HMEC) System that Reproducibly Demonstrates Ductal Organotypic Architecture in 3 Weeks

DTIC Science & Technology

2006-10-01

diagnostic for the inherited cancer- prone disease xeroderma pigmentosum , where it is usually performed in lymphocytes or skin fibroblasts. Our novel HME...Waugh AP, Hawk JL: Immune function, mutant frequency, and cancer risk in the DNA repair defective genodermatoses xeroderma pigmentosum , Cockayne’s...internal neoplasia: evidence from xeroderma pigmentosum . Carcinogenesis 1984, 5:511-514. 38. Forlenza MJ, Latimer JJ, Baum A: The effects of stress on

Identification of Stem Cells in a Novel Human Mammary Epithelial Culture (HMEC) System that Reproducibly Demonstrates Ductal Organotypic Architecture in 3 Weeks

DTIC Science & Technology

2005-10-01

diagnostic for the inherited cancer- prone disease xeroderma pigmentosum , where it is usually performed in lymphocytes or skin fibroblasts. Our novel HME...Waugh AP, Hawk JL: Immune function, mutant frequency, and cancer risk in the DNA repair defective genodermatoses xeroderma pigmentosum , Cockayne’s...internal neoplasia: evidence from xeroderma pigmentosum . Carcinogenesis 1984, 5:511-514. 38. Forlenza MJ, Latimer JJ, Baum A: The effects of stress on

Communication Interface for a System of Distributed Processes.

DTIC Science & Technology

1981-03-03

Tnterprocess Communication Service Apnlied in a nistrihuted Data Rase System" (submitte to VCI, Miinchen 10/Rl) and "The Trans- port Service of an...1980 4) B6’-hme, K.: An Tnternrocess Communication Service Applied in a Distribut.1 Data Pase System. Submitted to FCI, tliinchen, Oct. 3091l 5) ribme...K(. The "ransport Service of an Tnterprocess Commiunication Systell. Snbmitte to 7th Data Cor’nunicatinrin rooi1 !’exico City, Oct. 1091 ’"’h~e oi1

Airway humidification with a heat and moisture exchanger in mechanically ventilated neonates : a preliminary evaluation.

PubMed

Fassassi, Mikaïla; Michel, Fabrice; Thomachot, Laurent; Nicaise, Claire; Vialet, Renaud; Jammes, Yves; Lagier, Pierre; Martin, Claude

2007-02-01

We set out to evaluate the efficacy of passive inspiratory gas conditioning in mechanically ventilated neonates and compared it with that of a heated humidifier (HH). Prospective, randomized, controlled study. Neonatal and pediatric intensive care unit. Fourteen mechanically ventilated neonates nursed in incubators. The HH was set to deliver a temperature of 37 degrees C and an absolute humidity of 40 mgH(2)O/l at the incubator entrance. Inspired temperature (T degrees ) and absolute humidity (AH) were measured by the psychometric method, transpulmonary pressure (Tpres) by means of a differential pressure transducer. Measurements were performed at 5, 10, and 15 min. The values of T degrees were significantly higher using the HH (34.6+/-1.6 degrees C) than the heat and moisture exchanger (HME) (33.8+/2.3, p<0.001). The values of AH were significantly higher using the HH (36.6+/-2.5 mgH(2)O/l) than the HME (32.4+/-2.8 mgH(2)O/l, p<0.001). No significant changes were observed in transpulmonary pressure. A significant positive correlation was observed between incubator temperature and the temperature delivered by the HH (R(2)=0.61, p<0.001). The use of HMEs in neonates made it possible to achieve an absolute humidity of 28 mgH(2)O/l or more and a temperature of 30 degrees C or more. Higher values are obtained using a HH.

In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions.

PubMed

Grymonpré, W; Verstraete, G; Van Bockstal, P J; Van Renterghem, J; Rombouts, P; De Beer, T; Remon, J P; Vervaet, C

2017-01-30

As the number of applications for polymers in pharmaceutical development is increasing, there is need for fundamental understanding on how such compounds behave during tableting. This research is focussed on the tableting behaviour of amorphous polymers, their solid dispersions and the impact of hot-melt extrusion on the compaction properties of these materials. Soluplus, Kollidon VA 64 and Eudragit EPO were selected as amorphous polymers since these are widely studied carriers for solid dispersions, while Celecoxib was chosen as BCS class II model drug. Neat polymers and physical mixtures (up to 35% drug load) were processed by hot-melt extrusion (HME), milled and sieved to obtain powders with comparable particle sizes as the neat polymer. A novel approach was used for in-line analysis of the compaction properties on a rotary tablet press (Modul P, GEA) using complementary sensors and software (CDAAS, GEA). By combining 'in-die' and 'out-of-die' techniques, it was possible to investigate in a comprehensive way the impact of HME on the tableting behaviour of amorphous polymers and their formulations. The formation of stable glassy solutions altered the formulations towards more fragmentary behaviour under compression which was beneficial for the tabletability. Principal component analysis (PCA) was applied to summarize the behaviour during compaction of the formulations, enabling the selection of Soluplus and Kollidon VA 64 as the most favourable polymers for compaction of glassy solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

Water Uptake Performance of Hygroscopic Heat and Moisture Exchangers after 24-Hour Tracheostoma Application.

PubMed

van den Boer, Cindy; Vas Nunes, Jonathan H; Muller, Sara H; van der Noort, Vincent; van den Brekel, Michiel W M; Hilgers, Frans J M

2014-06-01

After total laryngectomy, patients suffer from pulmonary complaints due to the shortcut of the upper airways that results in decreased warming and humidification of inspired air. Laryngectomized patients are advised to use a heat and moisture exchanger (HME) to optimize the inspired air. According to manufacturers' guidelines, these medical devices should be replaced every 24 hours. The aim of this study is to determine whether HMEs still function after 24-hour tracheostoma application. Assessment of residual water uptake capacity of used HMEs by measuring the difference between wet and dry core weight. Tertiary comprehensive cancer center. Three hygroscopic HME types were tested after use by laryngectomized patients in long-term follow-up. Water uptake of 41 used devices (including 10 prematurely replaced devices) was compared with that of control (unused) devices of the same type and with a control device with a relatively low performance. After 24 hours, the mean water uptake of the 3 device types had decreased compared with that of the control devices. For only one type was this difference significant. None of the used HMEs had a water uptake lower than that of the low-performing control device. The water uptake capacity of hygroscopic HEMs is clinically acceptable although no longer optimal after 24-hour tracheostoma application. From a functional point of view, the guideline for daily device replacement is therefore justified. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Development of a floating drug delivery system with superior buoyancy in gastric fluid using hot-melt extrusion coupled with pressurized CO₂.

PubMed

Almutairy, B K; Alshetaili, A S; Ashour, E A; Patil, H; Tiwari, R V; Alshehri, S M; Repka, M A

2016-03-01

The present study aimed to develop a continuous single-step manufacturing platform to prepare a porous, low-density, and floating multi-particulate system (mini-tablet, 4 mm size). This process involves injecting inert, non-toxic pressurized CO₂gas (P-CO₂) in zone 4 of a 16-mm hot-melt extruder (HME) to continuously generate pores throughout the carrier matrix. Unlike conventional methods for preparing floating drug delivery systems, additional chemical excipients and additives are not needed in this approach to create minute openings on the surface of the matrices. The buoyancy efficiency of the prepared floating system (injection of P-CO₂) in terms of lag time (0 s) significantly improved (P < 0.05), compared to the formulation prepared by adding the excipient sodium bicarbonate (lag time 120 s). The main advantages of this novel manufacturing technique include: (i) no additional chemical excipients need to be incorporated in the formulation, (ii) few manufacturing steps are required, (iii) high buoyancy efficiency is attained, and (iv) the extrudate is free of toxic solvent residues. Floating mini-tablets containing acetaminophen (APAP) as a model drug within the matrix-forming carrier (Eudragit® RL PO) have been successfully processed via this combined technique (P-CO₂/HME). Desired controlled release profile of APAP from the polymer Eudragit® RL PO is attained in the optimized formulation, which remains buoyant on the surface of gastric fluids prior to gastric emptying time (average each 4 h).

Conjugation of Hot-Melt Extrusion with High-Pressure Homogenization: a Novel Method of Continuously Preparing Nanocrystal Solid Dispersions.

PubMed

Ye, Xingyou; Patil, Hemlata; Feng, Xin; Tiwari, Roshan V; Lu, Jiannan; Gryczke, Andreas; Kolter, Karl; Langley, Nigel; Majumdar, Soumyajit; Neupane, Dipesh; Mishra, Sanjay R; Repka, Michael A

2016-02-01

Over the past few decades, nanocrystal formulations have evolved as promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods of preparing nanocrystal formulations, such as spray drying and freeze drying, have some drawbacks including high cost, time and energy inefficiency, traces of residual solvent, and difficulties in continuous operation. Therefore, new techniques for the production of nanocrystal formulations are necessary. The main objective of this study was to introduce a new technique for the production of nanocrystal solid dispersions (NCSDs) by combining high-pressure homogenization (HPH) and hot-melt extrusion (HME). Efavirenz (EFZ), a Biopharmaceutics Classification System class II drug, which is used for the treatment of human immunodeficiency virus (HIV) type I, was selected as the model drug for this study. A nanosuspension (NS) was first prepared by HPH using sodium lauryl sulfate (SLS) and Kollidon® 30 as a stabilizer system. The NS was then mixed with Soluplus® in the extruder barrel, and the water was removed by evaporation. The decreased particle size and crystalline state of EFZ were confirmed by scanning electron microscopy, zeta particle size analysis, and differential scanning calorimetry. The increased dissolution rate was also determined. EFZ NCSD was found to be highly stable after storage for 6 months. In summary, the conjugation of HPH with HME technology was demonstrated to be a promising novel method for the production of NCSDs.

Preparation and characterization of azithromycin--Aerosil 200 solid dispersions with enhanced physical stability.

PubMed

Li, Xuechao; Peng, Huanhuan; Tian, Bin; Gou, Jingxin; Yao, Qing; Tao, Xiaoguang; He, Haibing; Zhang, Yu; Tang, Xing; Cai, Cuifang

2015-01-01

The main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). For solid dispersions prepared with both methods, no crystalline of AZI was detected (except for AZI: Aerosil 200=75:25) by DSC or PXRD, indicating the amorphous state of AZI in solid dispersions. The FT-IR results demonstrated the loss of crystallization water and the formation of hydrogen bonds between Aerosil 200 and AZI during the preparation of solid dispersions. After 4 weeks storage under accelerated condition, the degree of crystallinity of AZI increased in solid dispersions prepared by BM, whereas for solid dispersions containing AZI, Aerosil 200 and glyceryl behenate (GB) prepared by HME, no crystalline of AZI was identified. This high stability can be attributed to the hydrophobic properties of GB and the presence of hydrogen bonds. Based on the above results, it is inferred the protection of hydrogen bonds between AZI and Aerosil 200 formed during preparation process effectively inhibited the recrystallization of AZI and improved the physical stability of amorphous AZI in the presence of Aerosil 200. Copyright © 2015 Elsevier B.V. All rights reserved.

Cost-Benefit Analysis of a Bridge to Integrate the Management of Technical Information for Producing Technical Manuals and Training Courses

DTIC Science & Technology

2010-11-01

Philadelphia, and all Computer-Based Training (CBT) courses delivered by Navy eLearning (NeL), a part of the Naval Education and Training Command (NETC...concentrated exclu- sively on the benefit side—whether the Bridge would save money in producing future technical manuals and training courses. It...of $78.1 million in 10-year costs: a savings of $86.8 million in producing future HM&E manuals and NeL-delivered courses less $8.7 million in

Navy Construction Contract Regulations versus the Board of Contract Appeals.

DTIC Science & Technology

1987-12-01

This is unfortunate because the amount of useful knowledge in the cases is vast, but the access to it is time- comsuming . The selection of the cases is...AlE) was out of town. This figure cannot be used blindly. Other factors such as Government behavior , contractor behavior , or nature of the submittal...job. To complicate matters, t "h C (-,n t r a c:i n:; I:Dict.r may not be aware of th_ contractor’ h.me _.f... overhead behavior . The alternative Is

Coordination polymers of 5-substituted isophthalic acid

DOE PAGES

McCormick, Laura J.; Morris, Samuel A.; Slawin, Alexandra M. Z.; ...

2015-12-10

In this work, the synthesis and characterisation of five coordination polymers - Ni 2(mip) 2 (H 2O) 8 ·2H 2O (1), Zn 6(mip) 5(OH) 2(H 2O) 4 ·7.4H 2O (2), Zn 6(mip) 5(OH) 2(H 2O) 2 ·4H 2O (3), Mn(HMeOip) 2 (4), and Mn 3(tbip) 2(Htbip) 2(EtOH) 2 (5) - are reported. Preliminary nitric oxide release data on compounds 2 and 3 are also given.

Hacker within! Ehrlichia chaffeensis Effector Driven Phagocyte Reprogramming Strategy

PubMed Central

Lina, Taslima T.; Farris, Tierra; Luo, Tian; Mitra, Shubhajit; Zhu, Bing; McBride, Jere W.

2016-01-01

Ehrlichia chaffeensis is a small, gram negative, obligately intracellular bacterium that preferentially infects mononuclear phagocytes. It is the etiologic agent of human monocytotropic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms that underlie Ehrlichia host cellular reprogramming strategies that enable intracellular survival. PMID:27303657

Epidemiology of Congenital Upper Limb Anomalies in a Midwest United States Population: An Assessment Using the OMT Classification

PubMed Central

Goldfarb, Charles A.; Wall, Lindley B.; Bohn, Deborah C.; Moen, Patrick; Van Heest, Ann E.

2014-01-01

Purpose To examine the relative presentation frequency of children with upper limb congenital anomalies at 3 Midwestern referral centers using the Oberg, Manske, and Tonkin (OMT) classification and to assess the utility of this new classification system. Methods 641 individuals with 653 congenital upper extremity anomalies were identified at 3 hospitals in 2 large metropolitan areas during a 1-year interval. Patients were identified prospectively and the specific upper extremity anomaly and any associated syndromes were confirmed using medical records and radiographs. We applied the OMT classification that categorizes anomalies using a dysmorphology outline as malformations, dysplasias, deformations, and syndromes, and assessed its utility and ease of use. Results There were 480 extremities (74%) with a limb malformation including 184 involving the entire limb. Arthrogryposis was the most common of these (53 extremities). Anomalies affecting only the hand plate accounted for 62% (296) of the malformations. Of these, radial polydactyly (15%) was the most common specific anomaly, followed by symbrachydactyly (13%) and cleft hand (11%). Dysplasias were noted in 86 extremities; 55 of these were multiple hereditary exostoses. There were 87 extremities with deformations and 58 of these were trigger digits. A total of 98 children had a syndrome or association. Constriction ring sequence was most common. The OMT was straightforward to use and most anomalies could be easily assigned. There were a few conditions, such as Madelung deformity and symbrachydactyly, that would benefit from clarification on how to best classify them. Conclusions Malformations were the most common congenital anomalies in the 653 upper extremities evaluated over a 1-year period at 3 institutions. We were able to classify all individuals using the OMT classification system. PMID:25534840

Epidemiology of congenital upper limb anomalies in a midwest United States population: an assessment using the Oberg, Manske, and Tonkin classification.

PubMed

Goldfarb, Charles A; Wall, Lindley B; Bohn, Deborah C; Moen, Patrick; Van Heest, Ann E

2015-01-01

To examine the relative presentation frequency of children with upper limb congenital anomalies at 3 Midwestern referral centers using the Oberg, Manske, and Tonkin (OMT) classification and to assess the utility of this new classification system. 641 individuals with 653 congenital upper extremity anomalies were identified at 3 hospitals in 2 large metropolitan areas during a 1-year interval. Patients were identified prospectively and the specific upper extremity anomaly and any associated syndromes were confirmed using medical records and radiographs. We applied the OMT classification that categorizes anomalies using a dysmorphology outline as malformations, dysplasias, deformations, and syndromes, and assessed its utility and ease of use. There were 480 extremities (74%) with a limb malformation including 184 involving the entire limb. Arthrogryposis was the most common of these (53 extremities). Anomalies affecting only the hand plate accounted for 62% (296) of the malformations. Of these, radial polydactyly (15%) was the most common specific anomaly, followed by symbrachydactyly (13%) and cleft hand (11%). Dysplasias were noted in 86 extremities; 55 of these were multiple hereditary exostoses. There were 87 extremities with deformations and 58 of these were trigger digits. A total of 109 children had a syndrome or association. Constriction ring sequence was most common. The OMT was straightforward to use and most anomalies could be easily assigned. There were a few conditions, such as Madelung deformity and symbrachydactyly, that would benefit from clarification on how to best classify them. Malformations were the most common congenital anomalies in the 653 upper extremities evaluated over a 1-year period at 3 institutions. We were able to classify all individuals using the OMT classification system. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Autosomal dominant transmission of a Goldenhar-like syndrome: Description of a family and report of a sporadic case with a de novo 4p16;8q24.11 translocation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graganm H.N. Jr.; Hixon, H.; Bacino, C.A.

1994-09-01

We report vertical transmission of a Goldenhar-like syndrome, including a father and 5 offspring, with male-to-male transmission and variable features that include hearing loss, ear anomalies (microtia, ear tags/pits), branchial cysts, ocular/periocular dermoids, micrognathia and seizures. We also report an individual with an apparently balanced de novo reciprocal translocation with breakpoints at 4p16 and 8q24.11. This individual has unilateral microtia, an epibulbar dermoid cyst, facial asymmetry with a small chin, and seizures. In addition to these features resembling those seen in the family above, she has multiple exostoses, supraventricular tachycardia, hypoglycemia and mild developmental delays. Based on the overlap inmore » physical findings between this family and the individual with the de novo reciprocal translocation, linkage studies on the family were intiated. Preliminary results exclude linkage to HOX 7 at 4p16.1 but not to 8q. The brancho-oto-renal syndrome has previously been localized to 8q11-8q13, but linkage to this region appears unlikely. Although most cases of Goldenhar syndrome appear to be sporadic, there are a few reports of autosomal dominant inheritance (MIM No. 164210). One such family showed vertical transmission of dermoids, ear anomalies, hearing loss, micrognathia and vertebral anomalies, but no branchial cysts. Another family showed sensorineural deafness, preauricular pits, and branchial fistulae, and other families reveal ear anomalies, branchial fistulas, and hearing loss. These latter families appear to lack ocular/periocular dermoids, and appear to be affected by a different disorder (MIM No. 125100). Further clinical delineation of such families, combined with genetic linkage analysis, should help to sort out this heterogeneity.« less

The Effects of Screw Configuration and Polymeric Carriers on Hot-Melt Extruded Taste-Masked Formulations Incorporated into Orally Disintegrating Tablets

PubMed Central

Morott, Joseph T.; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P.; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A.

2015-01-01

The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. PMID:25410968

Peer Learning in Instrumental Practicing

PubMed Central

Nielsen, Siw G.; Johansen, Guro G.; Jørgensen, Harald

2018-01-01

In higher music education (HME), the notion of “private teaching, private learning” has a long tradition, where the learning part rests on the student's individual practicing between instrumental lessons. However, recent research suggests that collaborative learning among peers is beneficial in several aspects, such as sense of belonging, motivation and self-efficacy. This is consistent with the concept of vicarious learning. In this study, we conducted a survey among bachelor music students in church music, performance or music education programs enrolled in a music academy (N = 96), where parts of the questionnaire addressed peer learning and peer's influence on the students's instrumental practicing, and the degree of satisfaction with their practicing. These issues were seen in relation to gender, musical genre and study program. Overall, the students reported engaging in peer learning related to their instrumental practicing, to various degrees. This involved discussing practicing matters with peers, and practicing together with peers. However, student's reports of their views on peer learning, show that they perceive it more beneficial than the amount of time reported doing it would indicate. No significant gender differences were found, but students within improvised music/jazz engaged the most in peer learning, and church music students the least. Neither the degree of engaging in peer learning nor reported influence from peers correlated significantly with the degree of satisfaction. We discuss whether a general dissatisfaction is caused by being in a competitive learning environment combined with a privatized culture for learning. Finally, we suggest that collaborative forums for instrumental practicing within HME institutions can function as constructive and supportive arenas to enhance students learning and inner motivation. PMID:29599738

Hot-melt extrusion of sugar-starch-pellets.

PubMed

Yeung, Chi-Wah; Rein, Hubert

2015-09-30

Sugar-starch-pellets (syn. sugar spheres) are usually manufactured through fluidized bed granulation or wet extrusion techniques. This paper introduces hot-melt extrusion (HME) as an alternative method to manufacture sugar-starch-pellets. A twin-screw extruder coupled with a Leistritz Micro Pelletizer (LMP) cutting machine was utilized for the extrusion of different types (normal-, waxy-, and high-amlyose) of corn starch, blended with varying amounts of sucrose. Pellets were characterized for their physicochemical properties including crystallinity, particle size distribution, tensile strength, and swelling expansion. Furthermore, the influence of sugar content and humidity on the product was investigated. Both sucrose and water lowered the Tg of the starch system allowing a convenient extrusion process. Mechanical strength and swelling behavior could be associated with varying amylose and amylopectin. X-ray powder diffractometric (XRPD) peaks of increasing sucrose contents appeared above 30%. This signified the oversaturation of the extruded starch matrix system with sucrose. Otherwise, had the dissolved sucrose been embedded into the molten starch matrix, no crystalline peak could have been recognized. The replacement of starch with sucrose reduced the starch pellets' swelling effect, which resulted in less sectional expansion (SEI) and changed the surface appearance. Further, a nearly equal tensile strength could be detected for sugar spheres with more than 40% sucrose. This observation stands in good relation with the analyzed values of the commercial pellets. Both techniques (fluidized bed and HME) allowed a high yield of spherical pellets (less friability) for further layering processes. Thermal influence on the sugar-starch system is still an obstacle to be controlled. Copyright © 2015 Elsevier B.V. All rights reserved.

Rat Palatability Study for Taste Assessment of Caffeine Citrate Formulation Prepared via Hot-Melt Extrusion Technology

PubMed Central

Tiwari, Roshan V.; Polk, Ashley N.; Patil, Hemlata; Ye, Xingyou; Pimparade, Manjeet B.; Repka, Michael A.

2017-01-01

Developing a pediatric oral formulation with an age-appropriate dosage form and taste masking of naturally bitter active pharmaceutical ingredients (APIs) are key challenges for formulation scientists. Several techniques are used for taste masking of bitter APIs to improve formulation palatability; however, not all the techniques are applicable to pediatric dosage forms because of the limitations on the kind and concentration of the excipients that can be used. Hot-melt extrusion (HME) technology is used successfully for taste masking of bitter APIs, and overcomes some of the limitations of the existing taste masking techniques. Likewise, analytical taste assessment is an important quality control parameter evaluated by several in vivo and in vitro methods, such as the human taste panel, electrophysiological methods, electronic sensor, and animal preference tests to aid in selecting a taste-masked formulation. However, the most appropriate in-vivo method to assess the taste-masking efficacy of pediatric formulations remains unknown, because it is not known to what extent the human taste panel/electronic tongue can predict the palatability in the pediatric patients. The purpose of this study was to develop taste-masked caffeine citrate extrudates via HME, and to demonstrate the wide applicability of a single bottle-test rat model to record and compare the volume consumed of the taste-masked solutions to that of the pure API. Thus, this rat model can be considered as a low-cost alternative taste-assessment method to the most commonly used expensive human taste panel/electronic tongue method for pediatric formulations. PMID:26573158

Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices.

PubMed

Genina, Natalja; Holländer, Jenny; Jukarainen, Harri; Mäkilä, Ermei; Salonen, Jarno; Sandler, Niklas

2016-07-30

The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcutaneous rods (SR). The goal was to select an EVA grade with optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug in this study. Out of the twelve tested grades of the EVA five were printable. One of them showed superior print quality and was further investigated by printing drug-loaded filaments, containing 5% and 15% indomethacin. The feedstock filaments were fabricated by hot-melt extrusion (HME) below the melting point of the drug substance and the IUS and SR were successfully printed at the temperature above the melting point of the drug. As a result, the drug substance in the printed prototypes showed to be at least partly amorphous, while the drug in the corresponding HME filaments was crystalline. This difference affected the drug release profiles from the filaments and printed prototype products: faster release from the prototypes over 30days in the in vitro tests. To conclude, this study indicates that certain grades of EVA were applicable feedstock material for 3D printing to produce drug-loaded implantable prototypes. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation and evaluation of enteric coated tablets of hot melt extruded lansoprazole

PubMed Central

Alsulays, Bader B.; Kulkarni, Vijay; Alshehri, Sultan M.; Almutairy, Bjad K.; Ashour, Eman A.; Morott, Joseph T.; Alshetaili, Abdullah S.; Park, Jun-Bom; Tiwari, Roshan V.; Repka, Michael A.

2017-01-01

The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L 100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L 100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for 6 months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods. PMID:27486807

[Constitutional narrowing of the cervical spinal canal. Radiological and clinical findings].

PubMed

Ritter, G; Rittmeyer, K; Hopf, H C

1975-02-21

A constitutional narrowing of the cervical spinal canal was seen in 31 patients with neurological disorders. The ratio of the inner diameter of the spinal canal to the diameter of the vertebral body was smaller than 1 (normal greater than 1). Clinical signs were observed from 45 years upwards where reactivedegenerative changes cause additional narrowing. The majority of patients were male, predominantly heavy manual labourers. There is often a trauma preceding. On myelography multilocular deformations of the spinal subarachnoid space and nerve roots are seen. On the mechanical narrowing of the spinal canal a vascular factor supervenes, caused by exostoses, intervertebral disc protrusions, and fibrosing processes. Clinically a chronic progressive spinal transection syndrome (cervical myelopathy) dominates besides a multilocular root involvement. Posterior column sensibility is predominantly lost. Pain in the extemities and the cervical column is an early symptom. Non-specific CSF changes occur frequently. In case of root involvement the electromyogram is pathological. The prognosis is bad. Operation can only remove reactive processes but not the constitutional anomaly.

Sonar Based Navigation of an Autonomous Underwater Vehicle

DTIC Science & Technology

1994-06-01

3.1.4 Obstacles that are not on the map are marked, known initial position. 35 Eommd Trejecay of AUV 25 Elied -Solid ine Actual :Dashed line 20, 15 I...actual trajectory. Efifets of Camn*= in do Pai~on of AUV. 20 15- 5- 0 S 10 15 20 25 30 35 Figure 3.16 The effects of currents in the trajectory of the...vehicle. 38 E~med T~MjMMa~ ofAUV 20Eadalmd 3affid one Actual :Dashed hMe 15- 0- 0 5 10 15 20 25 30 35 X (irn faet) Figure 3.17 Position estimation

Out-of-Pocket and Informal Payment Before and After the Health Transformation Plan in Iran: Evidence from Hospitals Located in Kurdistan, Iran.

PubMed

Piroozi, Bakhtiar; Rashidian, Arash; Moradi, Ghobad; Takian, Amirhossein; Ghasri, Hooman; Ghadimi, Tayyeb

2017-02-11

One of the objectives of the health transformation plan (HTP) in Iran is to reduce out-of-pocket (OOP) payments for inpatient services and eradicate informal payments. The HTP has three phases: the first phase (launched in May 5, 2014) is focused on reducing OOP payments for inpatient services; the second phase (launched in May 22, 2014) is focused on primary healthcare (PHC) and the third phase utilizes an updated relative value units for health services (launched in September 29, 2014) and is focused on the elimination of informal payments. This aim of this study was to determine the OOP payments and the frequency of informal cash payments to physicians for inpatient services before and after the HTP in Kurdistan province, Iran. This quasi-experimental study used multistage sampling method to select and evaluate 265 patients discharged from hospitals in Kurdistan province. The study covered 3 phases (before the HTP, after the first, and third phases of the HTP). Part of the data was collected using a hospital information system form and the rest were collected using a questionnaire. Data were analyzed using Fisher exact test, logistic regression, and independent samples t test. The mean OOP payments before the HTP and after the first and third phases, respectively, were US$59.4, US$17.6, and US$14.3 in hospital affiliated to the Ministry of Health and Medical Education (MoHME), US$39.6, US$33.7, and US$13.7 in hospitals affiliated to Social Security Organization (SSO), and US$153.3, US$188.7, and US$66.4 in private hospitals. In hospitals affiliated to SSO and MoHME there was a significant difference between the mean OOP payments before the HTP and after the third phase (P<.05). The percentage of informal payments to physicians in hospitals affiliated to MoHME, SSO, and private sector, respectively, were 4.5%, 8.1%, and 12.5% before the HTP, and 0.0%, 7.1%, and 10.0% after the first phase. Contrary to the time before the HTP, no informal payment was reported after the third phase. It seems that the implementation of the HTP has reduced the OOP payments for inpatient services and eradicated informal payments to physician in Kurdistan province. © 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cost-effectiveness of heat and moisture exchangers compared to usual care for pulmonary rehabilitation after total laryngectomy in Poland.

PubMed

Retèl, Valesca P; van den Boer, Cindy; Steuten, Lotte M G; Okła, Sławomir; Hilgers, Frans J; van den Brekel, Michiel W

2015-09-01

The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmonary rehabilitation of laryngectomy patients are well evidenced. However, cost-effectiveness in terms of costs per additional quality-adjusted life years (QALYs) has not yet been investigated. Therefore, a model-based cost-effectiveness analysis of using HMEs versus usual care (UC) (including stoma covers, suction system and/or external humidifier) for patients after laryngectomy was performed. Primary outcomes were costs, QALYs and incremental cost-effectiveness ratio (ICER). Secondary outcomes were pulmonary infections, and sleeping problems. The analysis was performed from a health care perspective of Poland, using a time horizon of 10 years and cycle length of 1 year. Transition probabilities were derived from various sources, amongst others a Polish randomized clinical trial. Quality of life data was derived from an Italian study on similar patients. Data on frequencies and mortality-related tracheobronchitis and/or pneumonia were derived from a Europe-wide survey amongst head and neck cancer experts. Substantial differences in quality-adjusted survival between the use of HMEs (3.63 QALYs) versus UC (2.95 QALYs) were observed. Total health care costs/patient were 39,553 PLN (9465 Euro) for the HME strategy and 4889 PLN (1168 Euro) for the UC strategy. HME use resulted in fewer pulmonary infections, and less sleeping problems. We could conclude that given the Polish threshold of 99,000 PLN/QALY, using HMEs is cost-effective compared to UC, resulting in 51,326 PLN/QALY (12,264 Euro/QALY) gained for patients after total laryngectomy. For the hospital period alone (2 weeks), HMEs were cost-saving: less costly and more effective.

Hot-melt extrusion as a continuous manufacturing process to form ternary cyclodextrin inclusion complexes.

PubMed

Thiry, Justine; Krier, Fabrice; Ratwatte, Shenelka; Thomassin, Jean-Michel; Jerome, Christine; Evrard, Brigitte

2017-01-01

The aim of this study was to evaluate hot-melt extrusion (HME) as a continuous process to form cyclodextrin (CD) inclusion complexes in order to increase the solubility and dissolution rate of itraconazole (ITZ), a class II model drug molecule of the Biopharmaceutics Classification System. Different CD derivatives were tested in a 1:1 (CD:ITZ) molar ratio to obtain CD ternary inclusion complexes in the presence of a polymer, namely Soluplus ® (SOL). The CD used in this series of experiments were β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD) with degrees of substitution of 0.63 and 0.87, randomly methylated β-cyclodextrin (Rameb ® ), sulfobutylether-β-cyclodextrin (Captisol ® ) and methyl-β-cyclodextrin (Crysmeb ® ). Rheology testing and mini extrusion using a conical twin screw mini extruder were performed to test the processability of the different CD mixtures since CD are not thermoplastic. This allowed Captisol ® and Crysmeb ® to be discarded from the study due to their high impact on the viscosity of the SOL/ITZ mixture. The remaining CD were processed by HME in an 18mm twin screw extruder. Saturation concentration measurements confirmed the enhancement of solubility of ITZ for the four CD formulations. Biphasic dissolution tests indicated that all four formulations had faster release profiles compared to the SOL/ITZ solid dispersion. Formulations of HPβCD 0.63 and Rameb ® even reached 95% of ITZ released in both phases after 1h. The formulations were characterized using thermal differential scanning calorimetry and attenuated total reflectance infra-red analysis. These analyses confirmed that the increased release profile was due to the formation of ternary inclusion complexes. Copyright © 2016 Elsevier B.V. All rights reserved.

An in-vitro-in-vivo taste assessment of bitter drug: comparative electronic tongues study.

PubMed

Maniruzzaman, Mohammed; Douroumis, Dennis

2015-01-01

The efficiency of the Astree e-tongue and Taste Sensing system TS5000Z for the evaluation of the taste masking effect of hot melt extruded formulations was investigated in this study. Hot melt extrusion (HME) processing was optimized using Randcastle single screw extruder (USA) to manufacture extrudates with desirable characteristics. Cationic model drug propranolol HCl (PRP) was processed with the anionic polymers - Eudragit L100 (L100) and Eudragit L100-55 (Acryl-EZE). Solid state of the drug in polymer matrices was evaluated by scanning electron microscopy (SEM), differential scanning calorimetry, particle size analysis, Fourier transform infrared (FTIR) and Nuclear magnetic resonance (NMR) analysis. In-vitro taste masking efficiency of the two polymers was performed by using two different e-tongues (Astree e-tongue and TS5000Z). The results obtained from both e-tongues were further compared and contrast to find out the sensor outputs in all formulations. Solid state analysis of the extruded formulations revealed the presence of amorphous PRP. Both e-tongues were able to detect the taste masking variations of the extrudates and were in good agreement with the in-vivo results obtained from a panel of six healthy human volunteers (R(2)  > 0.84). However, each e-tongue sensor demonstrated different sensitivity, suggesting a careful consideration of the experimental findings during melt extrusion, is necessary for the development of taste-masked formulations. Furthermore, FTIR spectroscopy and NMR studies revealed possible drug polymer intermolecular interactions as the mechanism of successful taste masking. HME can effectively be used to manufacture taste-masked extruded formulations, while both e-tongues demonstrated satisfactory taste analysis for the development of taste-masked formulations. © 2014 Royal Pharmaceutical Society.

PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion.

PubMed

Li, Yongcheng; Lu, Ming; Wu, Chuanbin

2017-11-10

The purpose of this study was to explore poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) as a novel release-modifier to tailor the drug release from ethylcellulose (EC)-based mini-matrices prepared via hot melt extrusion (HME). Quetiapine fumarate (QF) was selected as model drug. QF/EC/PVP VA64 mini-matrices were extruded with 30% drug loading. The physical state of QF in extruded mini-matrices was characterized using differential scanning calorimetry, X-ray powder diffraction, and confocal Raman microscopy. The release-controlled ability of PVP VA64 was investigated and compared with that of xanthan gum, crospovidone, and low-substituted hydroxypropylcellulose. The influences of PVP VA64 content and processing temperature on QF release behavior and mechanism were also studied. The results indicated QF dispersed as the crystalline state in all mini-matrices. The release of QF from EC was very slow as only 4% QF was released in 24 h. PVP VA64 exhibited the best ability to enhance the drug release as compared with other three release-modifiers. The drug release increased to 50-100% in 24 h with the addition of 20-40% PVP VA64. Increasing processing temperature slightly slowed down the drug release by decreasing free volume and pore size. The release kinetics showed good fit with the Ritger-Peppas model. The values of release exponent (n) increased as PVP VA64 is added (0.14 for pure EC, 0.41 for 20% PVP VA64, and 0.61 for 40% PVP VA64), revealing that the addition of PVP VA64 enhanced the erosion mechanism. This work presented a new polymer blend system of EC with PVP VA64 for sustained-release prepared via HME.

Study the influence of formulation process parameters on solubility and dissolution enhancement of efavirenz solid solutions prepared by hot-melt extrusion: a QbD methodology.

PubMed

Pawar, Jaywant; Suryawanshi, Dilipkumar; Moravkar, Kailas; Aware, Rahul; Shetty, Vasant; Maniruzzaman, Mohammed; Amin, Purnima

2018-02-09

The current study investigates the dissolution rate performance of amorphous solid solutions of a poorly water-soluble drug, efavirenz (EFV), in amorphous Soluplus® (SOL) and Kollidon® VA 64 (KVA64) polymeric systems. For the purpose of the study, various formulations with varying drug loadings of 30, 50, and 70% w/w were developed via hot-melt extrusion processing and adopting a Box-Behnken design of experiment (DoE) approach. The polymers were selected based on the Hansen solubility parameter calculation and the prediction of the possible drug-polymer miscibility. In DoE experiments, a Box-Behnken factorial design was conducted to evaluate the effect of independent variables such as Soluplus® ratio (A 1 ), HME screw speed (A 2 ), and processing temperature (A 3 ), and Kollidon®VA64 ratio (B 1 ), screw speed (B 2 ), and processing temperature (B 3 ) on responses such as solubility (X 1 and Y 1 ) and dissolution rate (X 2 and Y 2 ) for both ASS [EFV:SOL] and BSS [EFV:KVA64] systems. DSC and XRD data confirmed that bulk crystalline EFV transformed to amorphous form during the HME processing. Advanced chemical analyses conducted via 2D COSY NMR, FTIR chemical imaging, AFM analysis, and FTIR showed that EFV was homogenously dispersed in the respective polymer matrices. The maximum solubility and dissolution rate was observed in formulations containing 30% EFV with both SOL and KVA64 alone. This could be attributed to the maximum drug-polymer miscibility in the optimized formulations. The actual and predicted values of both responses were found precise and close to each other.

Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters.

PubMed

Li, Shu; Tian, Yiwei; Jones, David S; Andrews, Gavin P

2016-02-01

The aim of this article was to construct a T-ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature-composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)-Eudragit(®) EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10 wt% FD-EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperature-composition (T-ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid-solid curve in a F-H T-ϕ phase diagram. If extruded between the spinodal and liquid-solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F-H T-ϕ phase diagrams are valuable not only in the understanding drug-polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.

K(Ca)3.1 channels facilitate K+ secretion or Na+ absorption depending on apical or basolateral P2Y receptor stimulation.

PubMed

Palmer, Melissa L; Peitzman, Elizabeth R; Maniak, Peter J; Sieck, Gary C; Prakash, Y S; O'Grady, Scott M

2011-07-15

Human mammary epithelial (HME) cells express several P2Y receptor subtypes located in both apical and basolateral membranes. Apical UTP or ATP-γ-S stimulation of monolayers mounted in Ussing chambers evoked a rapid, but transient decrease in short circuit current (I(sc)), consistent with activation of an apical K+ conductance. In contrast, basolateral P2Y receptor stimulation activated basolateral K+ channels and increased transepithelial Na+ absorption. Chelating intracellular Ca2+ using the membrane-permeable compound BAPTA-AM, abolished the effects of purinoceptor activation on I(sc). Apical pretreatment with charybdotoxin also blocked the I(sc) decrease by >90% and similar magnitudes of inhibition were observed with clotrimazole and TRAM-34. In contrast, iberiotoxin and apamin did not block the effects of apical P2Y receptor stimulation. Silencing the expression of K(Ca)3.1 produced ∼70% inhibition of mRNA expression and a similar reduction in the effects of apical purinoceptor agonists on I(sc). In addition, silencing P2Y2 receptors reduced the level of P2Y2 mRNA by 75% and blocked the effects of ATP-γ-S by 65%. These results suggest that P2Y2 receptors mediate the effects of purinoceptor agonists on K+ secretion by regulating the activity of K(Ca)3.1 channels expressed in the apical membrane of HME cells. The results also indicate that release of ATP or UTP across the apical or basolateral membrane elicits qualitatively different effects on ion transport that may ultimately determine the [Na+]/[K+] composition of fluid within the mammary ductal network.

Hypervitaminosis A-induced hepatic fibrosis in a cat.

PubMed

Guerra, Juliana M; Daniel, Alexandre G T; Aloia, Thiago P A; de Siqueira, Adriana; Fukushima, André R; Simões, Denise M N; Reche-Júior, Archivaldo; Cogliati, Bruno

2014-03-01

The excessive intake of vitamin A in the form of vitamin concentrate, supplement or vitamin-rich liver can result in hypervitaminosis A in man and animals. Although osteopathologies resulting from chronic vitamin A intoxication in cats are well characterized, no information is available concerning feline hypervitaminosis A-induced liver disease. We report the first case of hepatic stellate cell lipidosis and hepatic fibrosis in a domestic cat that had been fed a diet based on raw beef liver. Radiographic examination revealed exostoses and ankylosis between vertebrae C1 and T7, compatible with deforming cervical spondylosis. Necropsy showed a slightly enlarged and light yellow to bronze liver. Microscopic and ultrastructural analyses of liver tissues revealed diffuse and severe liver fibrosis associated with hepatic stellate cell hyperplasia and hypertrophy. These cells showed immunopositive staining for α-smooth muscle actin and desmin markers. The necropsy findings of chronic liver disease coupled with osteopathology supported the diagnosis of hypervitaminosis A. As in human hepatology, if there is dietary evidence to support increased intake of vitamin A, then hypervitaminosis A should be considered in the differential diagnosis of chronic liver disease in cats.

Are specialized endotracheal tubes and heat-and-moisture exchangers cost-effective in preventing ventilator associated pneumonia?

PubMed

Gentile, Michael A; Siobal, Mark S

2010-02-01

Ventilator-associated pneumonia (VAP) is a common and serious complication of mechanical ventilation via an artificial airway. As with all nosocomial infections, VAP increases costs, morbidity, and mortality in the intensive care unit (ICU). VAP prevention is a multifaceted priority of the intensive care team, and can include the use of specialized artificial airways and heat-and-moisture exchangers (HME). Substantial evidence supports the use of endotracheal tubes (ETTs) that allow subglottic suctioning; silver-coated and antiseptic-impregnated ETTs; ETTs with thin-walled polyurethane cuffs; and HMEs, but these devices also can have adverse effects. Controversy still exists regarding the evidence, cost-effectiveness, and disadvantages and risks of these devices.

On the Specification of Upward-Propagating Tides for ICON Science Investigations

NASA Astrophysics Data System (ADS)

Forbes, Jeffrey M.; Zhang, Xiaoli; Hagan, Maura E.; England, Scott L.; Liu, Guiping; Gasperini, Federico

2017-10-01

The National Center for Atmospheric Research (NCAR) Thermosphere Ionosphere Electrodynamics General Circulation Model (TIEGCM) will provide a physics-based context for the interpretation of ICON measurements. To optimize the realism of the model simulations, ICON wind and temperature measurements near the ˜97 km lower boundary of the TIEGCM will be used to specify the upward-propagating tidal spectrum at this altitude. This will be done by fitting a set of basis functions called Hough Mode Extensions (HMEs) to 27-day mean tidal winds and temperatures between 90 and 105 km altitude and between 12 °S and 42 °N latitude on a day-by-day basis. The current paper assesses the veracity of the HME fitting methodology given the restricted latitude sampling and the UT-longitude sampling afforded by the MIGHTI instrument viewing from the ICON satellite, which will be in a circular 27° inclination orbit. These issues are investigated using the output from a reanalysis-driven global circulation model, which contains realistic variability of the important tidal components, as a mock data set. ICON sampling of the model reveals that the 27-day mean diurnal and semidiurnal tidal components replicate well the 27-day mean tidal components obtained from full synoptic sampling of the model, but the terdiurnal tidal components are not faithfully reproduced. It is also demonstrated that reconstructed tidal components based on HME fitting to the model tides between 12 °S and 42 °N latitude provide good approximations to the major tidal components expected to be encountered during the ICON mission. This is because the constraints provided by fitting both winds and temperatures over the 90-105 km height range are adequate to offset the restricted sampling in latitude. The boundary conditions provided by the methodology described herein will greatly enhance the ability of the TIEGCM to provide a physical framework for interpreting atmosphere-ionosphere coupling in ICON observations due to atmospheric tides.

Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet

PubMed Central

Shen, Youqing; Huang, Guoyuan; McCormick, Bryan P.; Song, Tao

2017-01-01

The aim of the present study was to compare the effects of high-intensity interval training (HI) to mild-intensity endurance training (ME), combined with a high-fat diet (HFD) or control diet (CD) on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11), CD and ME (CME, n = 8), CD and HI (CHI, n = 8), HFD and sedentary (HS, n = 10), HFD and ME (HME, n = 8), and HFD and HI (HHI, n = 8). All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P < 0.01, η2 > 0.06), as well as higher corticosterone levels (P < 0.01, η2 = 0.09) compared with the CD groups. Exercise training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P < 0.01, η2 = 0.123). Furthermore, body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P < 0.05) were lower with HI training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P < 0.01). Corticosterone level was inversely correlated with QUICKI (r = −0.38, P < 0.01). Altogether, these results indicate that HFD may elicit an exacerbated basal serum corticosterone level and thus producing a metabolic imbalance. Compared with ME training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders. PMID:28727846

A New Method of Constructing a Drug-Polymer Temperature-Composition Phase Diagram Using Hot-Melt Extrusion.

PubMed

Tian, Yiwei; Jones, David S; Donnelly, Conor; Brannigan, Timothy; Li, Shu; Andrews, Gavin P

2018-04-02

Current experimental methodologies used to determine the thermodynamic solubility of an API within a polymer typically involves establishing the dissolution/melting end point of the crystalline API within a physical mixture or through the use of the glass transition temperature measurement of a demixed amorphous solid dispersion. The measurable "equilibrium" points for solubility are normally well above the glass transition temperature of the system, meaning extrapolation is required to predict the drug solubility at pharmaceutically relevant temperatures. In this manuscript, we argue that the presence of highly viscous polymers in these systems results in experimental data that exhibits an under or overestimated value relative to the true thermodynamic solubility. In previous work, we demonstrated the effects of experimental conditions and their impact on measured and predicted thermodynamic solubility points. In light of current understanding, we have developed a new method to limit error associated with viscosity effects for application in small-scale hot-melt extrusion (HME). In this study, HME was used to generate an intermediate (multiphase) system containing crystalline drug, amorphous drug/polymer-rich regions as well as drug that was molecularly dispersed in polymer. An extended annealing method was used together with high-speed differential scanning calorimetry to accurately determine the upper and lower boundaries of the thermodynamic solubility of a model drug-polymer system (felodipine and Soluplus). Compared to our previously published data, the current results confirmed our hypothesis that the prediction of the liquid-solid curve using dynamic determination of dissolution/melting end point of the crystalline API physical mixture presents an underestimation relative to the thermodynamic solubility point. With this proposed method, we were able to experimentally measure the upper and lower boundaries of the liquid-solid curve for the model system. The relationship between inverse temperature and drug-polymer solubility parameter (χ) remained linear at lower drug loadings. Significantly higher solubility and miscibility between the felodipine-Soluplus system were derived from the new χ values.

Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet.

PubMed

Shen, Youqing; Huang, Guoyuan; McCormick, Bryan P; Song, Tao; Xu, Xiangfeng

2017-01-01

The aim of the present study was to compare the effects of high-intensity interval training (HI) to mild-intensity endurance training (ME), combined with a high-fat diet (HFD) or control diet (CD) on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11), CD and ME (CME, n = 8), CD and HI (CHI, n = 8), HFD and sedentary (HS, n = 10), HFD and ME (HME, n = 8), and HFD and HI (HHI, n = 8). All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P < 0.01, η2 > 0.06), as well as higher corticosterone levels (P < 0.01, η2 = 0.09) compared with the CD groups. Exercise training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P < 0.01, η2 = 0.123). Furthermore, body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P < 0.05) were lower with HI training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P < 0.01). Corticosterone level was inversely correlated with QUICKI (r = -0.38, P < 0.01). Altogether, these results indicate that HFD may elicit an exacerbated basal serum corticosterone level and thus producing a metabolic imbalance. Compared with ME training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders.

Theodoricus Gravius (fl. 1600-1661): some biographical notes on a German chymist and scribe working in seventeenth-century England.

PubMed

Poole, William

2009-11-01

This article establishes the career of Theodoricus Gravius (fl. 1600-1661), a German refugee who worked in Great Linford as a laboratory assistant and scribe to the cleric and practitioner of astrological medicine, Richard Napier (1559-1634). Gravius was the first transmitter to England of the texts of the mystic Jacob Böhme, and although he settled in England, he undertook subsequent foreign visits to attempt the recovery of his property and to learn more about chymical matters. He also visited the Oxonian George Hakewill (1578-1649), and is responsible for scribing one of the manuscripts of the revisions to Hakewill's celebrated Apologie or Declaration Concerning the Power and Providence of God (1635).

Dissecting the Molecular Mechanism of RhoC GTPase Expression in the Normal and Malignant Breast

DTIC Science & Technology

2011-09-01

and cancer. Nature reviews 2, 133-142. Valastyan, S., Reinhardt, F ., Benaich, N., Calogrias, D., Szasz, A.M., Wang, Z.C., Brock, J.E., Richardson...prostate cancer progression. Cancer cell 17, 443-454.   R ho C F IS H Normal SUM149 SUM190A Figure 1 75 75 75 0 0 0 0 200 R ea ds (R P K M ) R...RhoC A B C D Figure 3 0 5 10 15 20 25 HME MCF7 SUM149 MDA-MB-231 Fo ld E nr ic hm en t o f p 65 B in di ng p65 (-2834) p65 (-2259) p65 (-6) A B

Development of an Ointment Formulation Using Hot-Melt Extrusion Technology.

PubMed

Bhagurkar, Ajinkya M; Angamuthu, Muralikrishnan; Patil, Hemlata; Tiwari, Roshan V; Maurya, Abhijeet; Hashemnejad, Seyed Meysam; Kundu, Santanu; Murthy, S Narasimha; Repka, Michael A

2016-02-01

Ointments are generally prepared either by fusion or by levigation methods. The current study proposes the use of hot-melt extrusion (HME) processing for the preparation of a polyethylene glycol base ointment. Lidocaine was used as a model drug. A modified screw design was used in this process, and parameters such as feeding rate, barrel temperature, and screw speed were optimized to obtain a uniform product. The product characteristics were compared with an ointment of similar composition prepared by conventional fusion method. The rheological properties, drug release profile, and texture characteristics of the hot-melt extruded product were similar to the conventionally prepared product. This study demonstrates a novel application of the hot-melt extrusion process in the manufacturing of topical semi-solids.

A novel TRPS1 mutation in a Moroccan family with Tricho-rhino-phalangeal syndrome type III: case report.

PubMed

Smaili, W; Elalaoui, S Chafai; Meier, S; Zerkaoui, M; Sefiani, A; Heinimann, K

2017-05-03

Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, pear-shaped nose and cone shaped epiphyses. This condition is caused by haploinsufficiency of the TRPS1 gene. Previous genotype-phenotype studies have correlated exon 6 missense mutations with TRPS type III, a severe form of type I with pronounced, facial characteristics, short stature and brachydactyly and differing from type II by the absence of exostoses and mental retardation. We report the first case of a Moroccan family, a father and his three children, in which the diagnosis of type III TRPS was suspected based on severe clinical and radiological features. Molecular analysis of the TRPS1 gene revealed a novel missense mutation in exon 6, (p.Ala932Ser), located in the GATA-type DNA-binding zinc finger domain. Our observations in this kindred support the previous genotype-phenotype results suggesting that patients with more pronounced facial characteristics and more severe shortening of hands and feet are more likely to have mutation in exon 6 of TRPS1.

High bioavailability iron maize (Zea mays L.) developed through molecular breeding provides more absorbable iron in vitro (Caco-2 model) and in vivo (Gallus gallus).

PubMed

Tako, Elad; Hoekenga, Owen A; Kochian, Leon V; Glahn, Raymond P

2013-01-04

Iron (Fe) deficiency is the most common micronutrient deficiency worldwide. Iron biofortification is a preventative strategy that alleviates Fe deficiency by improving the amount of absorbable Fe in crops. In the present study, we used an in vitro digestion/Caco 2 cell culture model as the guiding tool for breeding and development of two maize (Zea mays L.) lines with contrasting Fe bioavailability (ie. Low and High). Our objective was to confirm and validate the in vitro results and approach. Also, to compare the capacities of our two maize hybrid varieties to deliver Fe for hemoglobin (Hb) synthesis and to improve the Fe status of Fe deficient broiler chickens. We compared the Fe-bioavailability between these two maize varieties with the presence or absence of added Fe in the maize based-diets. Diets were made with 75% (w/w) maize of either low or high Fe-bioavailability maize, with or without Fe (ferric citrate). Chicks (Gallus gallus) were fed the diets for 6 wk. Hb, liver ferritin and Fe related transporter/enzyme gene-expression were measured. Hemoglobin maintenance efficiency (HME) and total body Hb Fe values were used to estimate Fe bioavailability from the diets. DMT-1, DcytB and ferroportin expressions were higher (P<0.05) in the "Low Fe" group than in the "High Fe" group (no added Fe), indicating lower Fe status and adaptation to less Fe-bioavailability. At times, Hb concentrations (d 21,28,35), HME (d 21), Hb-Fe (as from d 14) and liver ferritin were higher in the "High Fe" than in the "Low Fe" groups (P<0.05), indicating greater Fe absorption from the diet and improved Fe status. We conclude that the High Fe-bioavailability maize contains more bioavailable Fe than the Low Fe-bioavailability maize, presumably due to a more favorable matrix for absorption. Maize shows promise for Fe biofortification; therefore, human trials should be conducted to determine the efficacy of consuming the high bioavailable Fe maize to reduce Fe deficiency.

Heated humidification versus heat and moisture exchangers for ventilated adults and children.

PubMed

Kelly, Margaret; Gillies, Donna; Todd, David A; Lockwood, Catherine

2010-04-14

Humidification by artificial means must be provided when the upper airway is bypassed during mechanical ventilation. Heated humidification (HH) and heat and moisture exchangers (HME) are the most commonly used types of artificial humidification in this situation. To determine whether HHs or HMEs are more effective in preventing mortality and other complications in people who are mechanically ventilated. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4) and MEDLINE, EMBASE and CINAHL (January, 2010) to identify relevant randomized controlled trials (RCTs). We included RCTs comparing heat and moisture exchangers (HMEs) to heated humidifiers (HHs) in mechanically ventilated adults and children. We included randomized crossover studies. We assessed the quality of each study and extracted the relevant data. Where appropriate, results from relevant studies were meta-analysed for individual outcomes. We included 33 trials with 2833 participants, 25 studies were parallel group design (n = 2710) and eight crossover design (n = 123). Only three included studies reported data for infants or children. There was no overall effect on artificial airway occlusion, mortality, pneumonia, or respiratory complications; however, the PaCO(2) and minute ventilation were increased when HMEs were compared to HHs and body temperature was lower. The cost of HMEs was lower in all studies that reported this outcome. There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia and that blockages of artificial airways may be increased with the use of HMEs in certain subgroups of patients. There is little evidence of an overall difference between HMEs and HHs. However, hydrophobic HMEs may reduce the risk of pneumonia and the use of an HME may increase artificial airway occlusion in certain subgroups of patients. Therefore, HMEs may not be suitable for patients with limited respiratory reserve or prone to airway blockage. Further research is needed relating to hydrophobic versus hygroscopic HMEs and the use of HMEs in the paediatric and neonatal populations. As the design of HMEs evolves, evaluation of new generation HMEs will also need to be undertaken.

3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems.

PubMed

Goyanes, Alvaro; Det-Amornrat, Usanee; Wang, Jie; Basit, Abdul W; Gaisford, Simon

2016-07-28

Acne is a multifactorial inflammatory skin disease with high prevalence. In this work, the potential of 3D printing to produce flexible personalised-shape anti-acne drug (salicylic acid) loaded devices was demonstrated by two different 3D printing (3DP) technologies: Fused Deposition Modelling (FDM) and stereolithography (SLA). 3D scanning technology was used to obtain a 3D model of a nose adapted to the morphology of an individual. In FDM 3DP, commercially produced Flex EcoPLA™ (FPLA) and polycaprolactone (PCL) filaments were loaded with salicylic acid by hot melt extrusion (HME) (theoretical drug loading - 2% w/w) and used as feedstock material for 3D printing. Drug loading in the FPLA-salicylic acid and PCL-salicylic acid 3D printed patches was 0.4% w/w and 1.2% w/w respectively, indicating significant thermal degradation of drug during HME and 3D printing. Diffusion testing in Franz cells using a synthetic membrane revealed that the drug loaded printed samples released <187μg/cm(2) within 3h. FPLA-salicylic acid filament was successfully printed as a nose-shape mask by FDM 3DP, but the PCL-salicylic acid filament was not. In the SLA printing process, the drug was dissolved in different mixtures of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) (PEG) that were solidified by the action of a laser beam. SLA printing led to 3D printed devices (nose-shape) with higher resolution and higher drug loading (1.9% w/w) than FDM, with no drug degradation. The results of drug diffusion tests revealed that drug diffusion was faster than with the FDM devices, 229 and 291μg/cm(2) within 3h for the two formulations evaluated. In this study, SLA printing was the more appropriate 3D printing technology to manufacture anti-acne devices with salicylic acid. The combination of 3D scanning and 3D printing has the potential to offer solutions to produce personalised drug loaded devices, adapted in shape and size to individual patients. Copyright © 2016 Elsevier B.V. All rights reserved.

The palaeoclimatic significance of Eurasian Giant Salamanders (Cryptobranchidae: Zaissanurus, Andrias) - indications for elevated humidity in Central Asia during global warm periods (Eocene, late Oligocene warming, Miocene Climate Optimum)

NASA Astrophysics Data System (ADS)

Vasilyan, Davit; Böhme, Madelaine; Winklhofer, Michael

2010-05-01

Cryptobranchids represent a group of large sized (up to 1.8 m) tailed amphibians known since the Middle Jurassic (Gao & Shubin 2003). Two species are living today in eastern Eurasia: Andrias davidianus (China) and A. japonicus (Japan). Cenozoic Eurasian fossil giant salamanders are known with two genera and two or three species from over 30 localities, ranging from the Late Eocene to the Early Pliocene (Böhme & Ilg 2003). The Late Eocene species Zaissanurus beliajevae is restricted to the Central Asian Zaissan Basin (SE-Kazakhstan, 50°N, 85°E), whereas the Late Oligocene to Early Pliocene species Andrias scheuchzeri is distributed from Central Europe to the Zaissan Basin. In the latter basin the species occur during two periods; the latest Oligocene and the late Early to early Middle Miocene (Chkhikvadse 1982). Andrias scheuchzeri is osteological indistinguishable from both recent species, indicating a similar ecology (Westfahl 1958). To investigate the palaeoclimatic significance of giant salamanders we analyzed the climate within the present-day distribution area and at selected fossil localities with independent palaeoclimate record. Our results indicate that fossil and recent Andrias species occur in humid areas where the mean annual precipitation reach over 900 mm (900 - 1.300 mm). As a working hypothesis (assuming a similar ecology of Andrias and Zaissanurus) we interpret occurrences of both fossil Eurasian giant salamanders as indicative for humid palaeoclimatic conditions. Based on this assumption the Late Eocene, the latest Oligocene (late Oligocene warming) and the late Early to early Middle Miocene (Miocene Climatic Optimum) of Central Asia (Zaissan Basin) are periods of elevated humidity, suggesting a direct (positive) relationship between global climate and Central Asian humidity evolution. Böhme M., Ilg A. 2003: fosFARbase, www.wahre-staerke.com/ Chkhikvadze V.M. 1982. On the finding of fossil Cryptobranchidae in the USSR and Mongolia. Vertebrata Hungarica, 21: 63-67. Gao K.-Q., Shubin N.H. 2003. Earliest known crown-group Salamanders. Nature, 422: 424-428. Westphal F. 1958. Die Tertiären und rezenten Eurasiatischen Riesensalamander. Palaeontolographica Abt. A, 110: 20-92.

Characterisation and expression of microRNAs in developing wings of the neotropical butterfly Heliconius melpomene

PubMed Central

2011-01-01

Background Heliconius butterflies are an excellent system for studies of adaptive convergent and divergent phenotypic traits. Wing colour patterns are used as signals to both predators and potential mates and are inherited in a Mendelian manner. The underlying genetic mechanisms of pattern formation have been studied for many years and shed light on broad issues, such as the repeatability of evolution. In Heliconius melpomene, the yellow hindwing bar is controlled by the HmYb locus. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that have key roles in many biological processes, including development. miRNAs could act as regulators of genes involved in wing development, patterning and pigmentation. For this reason we characterised miRNAs in developing butterfly wings and examined differences in their expression between colour pattern races. Results We sequenced small RNA libraries from two colour pattern races and detected 142 Heliconius miRNAs with homology to others found in miRBase. Several highly abundant miRNAs were differentially represented in the libraries between colour pattern races. These candidates were tested further using Northern blots, showing that differences in expression were primarily due to developmental stage rather than colour pattern. Assembly of sequenced reads to the HmYb region identified hme-miR-193 and hme-miR-2788; located 2380 bp apart in an intergenic region. These two miRNAs are expressed in wings and show an upregulation between 24 and 72 hours post-pupation, indicating a potential role in butterfly wing development. A search for miRNAs in all available H. melpomene BAC sequences (~ 2.5 Mb) did not reveal any other miRNAs and no novel miRNAs were predicted. Conclusions Here we describe the first butterfly miRNAs and characterise their expression in developing wings. Some show differences in expression across developing pupal stages and may have important functions in butterfly wing development. Two miRNAs were located in the HmYb region and were expressed in developing pupal wings. Future work will examine the expression of these miRNAs in different colour pattern races and identify miRNA targets among wing patterning genes. PMID:21266089

Characterisation and expression of microRNAs in developing wings of the neotropical butterfly Heliconius melpomene.

PubMed

Surridge, Alison K; Lopez-Gomollon, Sara; Moxon, Simon; Maroja, Luana S; Rathjen, Tina; Nadeau, Nicola J; Dalmay, Tamas; Jiggins, Chris D

2011-01-26

Heliconius butterflies are an excellent system for studies of adaptive convergent and divergent phenotypic traits. Wing colour patterns are used as signals to both predators and potential mates and are inherited in a Mendelian manner. The underlying genetic mechanisms of pattern formation have been studied for many years and shed light on broad issues, such as the repeatability of evolution. In Heliconius melpomene, the yellow hindwing bar is controlled by the HmYb locus. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that have key roles in many biological processes, including development. miRNAs could act as regulators of genes involved in wing development, patterning and pigmentation. For this reason we characterised miRNAs in developing butterfly wings and examined differences in their expression between colour pattern races. We sequenced small RNA libraries from two colour pattern races and detected 142 Heliconius miRNAs with homology to others found in miRBase. Several highly abundant miRNAs were differentially represented in the libraries between colour pattern races. These candidates were tested further using Northern blots, showing that differences in expression were primarily due to developmental stage rather than colour pattern. Assembly of sequenced reads to the HmYb region identified hme-miR-193 and hme-miR-2788; located 2380 bp apart in an intergenic region. These two miRNAs are expressed in wings and show an upregulation between 24 and 72 hours post-pupation, indicating a potential role in butterfly wing development. A search for miRNAs in all available H. melpomene BAC sequences (~2.5 Mb) did not reveal any other miRNAs and no novel miRNAs were predicted. Here we describe the first butterfly miRNAs and characterise their expression in developing wings. Some show differences in expression across developing pupal stages and may have important functions in butterfly wing development. Two miRNAs were located in the HmYb region and were expressed in developing pupal wings. Future work will examine the expression of these miRNAs in different colour pattern races and identify miRNA targets among wing patterning genes.

High bioavailablilty iron maize (Zea mays L.) developed through molecular breeding provides more absorbable iron in vitro (Caco-2 model) and in vivo (Gallus gallus)

PubMed Central

2013-01-01

Background Iron (Fe) deficiency is the most common micronutrient deficiency worldwide. Iron biofortification is a preventative strategy that alleviates Fe deficiency by improving the amount of absorbable Fe in crops. In the present study, we used an in vitro digestion/Caco 2 cell culture model as the guiding tool for breeding and development of two maize (Zea mays L.) lines with contrasting Fe bioavailability (ie. Low and High). Our objective was to confirm and validate the in vitro results and approach. Also, to compare the capacities of our two maize hybrid varieties to deliver Fe for hemoglobin (Hb) synthesis and to improve the Fe status of Fe deficient broiler chickens. Methods We compared the Fe-bioavailability between these two maize varieties with the presence or absence of added Fe in the maize based-diets. Diets were made with 75% (w/w) maize of either low or high Fe-bioavailability maize, with or without Fe (ferric citrate). Chicks (Gallus gallus) were fed the diets for 6 wk. Hb, liver ferritin and Fe related transporter/enzyme gene-expression were measured. Hemoglobin maintenance efficiency (HME) and total body Hb Fe values were used to estimate Fe bioavailability from the diets. Results DMT-1, DcytB and ferroportin expressions were higher (P < 0.05) in the "Low Fe" group than in the "High Fe" group (no added Fe), indicating lower Fe status and adaptation to less Fe-bioavailability. At times, Hb concentrations (d 21,28,35), HME (d 21), Hb-Fe (as from d 14) and liver ferritin were higher in the "High Fe" than in the "Low Fe" groups (P < 0.05), indicating greater Fe absorption from the diet and improved Fe status. Conclusions We conclude that the High Fe-bioavailability maize contains more bioavailable Fe than the Low Fe-bioavailability maize, presumably due to a more favorable matrix for absorption. Maize shows promise for Fe biofortification; therefore, human trials should be conducted to determine the efficacy of consuming the high bioavailable Fe maize to reduce Fe deficiency. PMID:23286295

Increased dissolution rates of tranilast solid dispersions extruded with inorganic excipients.

PubMed

Maniruzzaman, Mohammed; Ross, Steven A; Islam, Muhammad Tariqul; Scoutaris, Nikolaos; Nair, Arun; Douroumis, Dennis

2017-06-01

The purpose of this study was to evaluate the performance of Neusilin® (NEU) a synthetic magnesium aluminometasilicate as an inorganic drug carrier co-processed with the hydrophilic surfactants Labrasol and Labrafil to develop Tranilast (TLT)-based solid dispersions using continuous melt extrusion (HME) processing. Twin-screw extrusion was optimized to develop various TLT/excipient/surfactant formulations followed by continuous capsule filling in the absence of any downstream equipment. Physicochemical characterization showed the existence of TLT in partially crystalline state in the porous network of inorganic NEU for all extruded formulations. Furthermore, in-line NIR studies revealed a possible intermolecular H-bonding formation between the drug and the carrier resulting in the increase of TLT dissolution rates. The capsules containing TLT-extruded solid dispersions showed enhanced dissolution rates and compared with the marketed Rizaben ® product.

AFOSR (Air Force Office of Scientific Research) Technical Report Summaries, July-September 1983.

DTIC Science & Technology

1983-09-01

I ~ ~ ~ fllffbff flfl fffIN hl h9hhhhhhhI 0mhhhhF/8h5/2hME lffffffffffffl 2.2l PHOTOGRAPH THIS SHEET 0) LEVEL INVENTORY z 0 I DOCUMENT IDENTIFICATION... MCQ . LILU C) -0 L. Z- m (C. *..iV 0 :--M L - -0 41 - w M - = C c m < 0 L L.. "t Wco t- . C - W -Z L C3C 0) M- co- - - < 0l..(AJ (D ) -- U n 0. aL...U10- .. v C 0 .1U -L L-UW.O- -0 < -- 44-00in 0 / 10 14 ( - (A 0 0- 0 ixa .410 > C 0 .L UC 41 vJC Cw MIX -- -M DIM U C4 1-L C - 0 - C)U1 )Q) XC 1000 xa o

Integrated analysis reveals that STAT3 is central to the crosstalk between HER/ErbB receptor signaling pathways in human mammary epithelial cells

DOE PAGES

Gong, Chunhong; Zhang, Yi; Shankaran, Harish; ...

2014-10-02

Human epidermal growth factor receptors (HER, also known as ErbB) drive cellular proliferation, pro-survival and stress responses by activating several downstream kinases, in particular ERK, p38, JNK (SAPK), the PI3K/AKT, as well as various transcriptional regulators such as STAT3. When co-expressed, first three members of HER family (HER1-3) can form homo- and hetero-dimers. Based on the considerable evidence which suggest that every receptor dimer activates intracellular signaling pathways differentially, we hypothesized that the HER dimerization pattern is a better predictor of downstream signaling than the total receptor activation levels. We validated our hypothesis using a combination of model-based analysis tomore » quantify the HER dimerization patterns and multi-factorial experiments where HER dimerization patterns and signaling crosstalk were rationally perturbed. We have measured the activation of HER1-3 receptors and of the sentinel signaling proteins ERK, AKT, p38, JNK, STAT3 as a function of time in a panel of human mammary epithelial (HME) cells expressing different levels of HER1-3 stimulated with various ligand combinations. Our analysis using multiple ways of clustering the activation data has confirmed that the HER receptor dimer is a better predictor of the signaling through p38, ERK and AKT pathways than the total HER receptor expression and activation levels. Targeted inhibition studies to identify the causal effects allowed us to obtain a consensus regulatory interaction model, which revealed that STAT3 occupies a central role in the crosstalk between the studied pathways.« less

One-step continuous extrusion process for the manufacturing of solid dispersions.

PubMed

Maniruzzaman, M; Nair, A; Scoutaris, N; Bradley, Michael S A; Snowden, M J; Douroumis, D

2015-12-30

The purpose of this study was to evaluate the performance of synthetic magnesium aluminometasilicate (MAS) as a novel inorganic carrier in hot melt extrusion (HME) processing of indomethacin (IND) for the development of solid dispersions. A continuous extrusion process at various IND/excipient blend ratios (20%, 30% and 40%) was performed using a twin-screw extruder. Physicochemical characterization carried out by SEM, DSC, and XRPD demonstrated the presence of IND in amorphous nature within the porous network of the inorganic material for all extruded formulations. Further, AFM and FTIR studies revealed a single-phase amorphous system and intermolecular H-bonding formation. The IND/MAS extrudates showed enhanced INM dissolution rates within 100% been released within 1h. Stability studies under accelerated conditions (40°C, RH 75%) showed that MAS retained the physical stability of the amorphous solid dispersions even at high drug loadings for 12 months. Copyright © 2015 Elsevier B.V. All rights reserved.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs.

PubMed

Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R

2015-01-01

Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs

PubMed Central

Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R.

2015-01-01

Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older. PMID:26153689

Pathology and the posture of the La Chapelle-aux-Saints Neandertal.

PubMed

Trinkaus, E

1985-05-01

The depiction of the Neandertals as incompletely erect was based primarily on Boule's (1911, 1912a, 1913) analysis of the La Chapelle-aux-Saints 1 partial skeleton. The inaccurate aspects of Boule's postural reconstruction were corrected during the 1950s. However, it has come to be believed, following Straus and Cave (1957), that Boule's errors of reconstruction were due to the diseased condition of the La Chapelle-aux-Saints 1 remains, rather than to Boule's misinterpretation of morphology. The abnormalities on the La Chapelle-aux-Saints 1 postcranium include: lower cervical, upper thoracic, and lower thoracic intervertebral degenerative joint disease (DJD), a distal fracture of a mid-thoracic rib, extensive DJD of the left hip, DJD of the right fifth proximal interphalangeal articulation, bilateral humeral head eburnation, and minor exostosis formation on the right humerus, ulna, and radius. These were associated with extensive alveolar inflammation including apical abscesses and antemortem tooth loss, some temporomandibular DJD, bilateral auditory exostoses, and minimal occipital condyle DJD. None of these abnormalities significantly affected Boule's Neandertal postural reconstruction, and a review of his analysis indicates that early twentieth century interpretations of skeletal morphology (primarily of the cranium, cervical vertebrae, lumbar and sacral vertebrae, proximal femora and tibiae, posterior tarsals, and hallucial tarsometatarsal joint), combined with Boule's evolutionary preconceptions, were responsible for his mistaken view of Neandertal posture.

Serologic Evidence of Human Monocytic and Granulocytic Ehrlichiosis in Israel

PubMed Central

Keysary, Avi; Amram, Lili; Keren, Gershon; Sthoeger, Zev; Potasman, Israel; Jacob, Amir; Strenger, Carmella; Dawson, Jacqueline E.

1999-01-01

We conducted a retrospective serosurvey of 1,000 persons in Israel who had fever of undetermined cause to look for Ehrlichia chaffeensis antibodies. Four of five cases with antibodies reactive to E. chaffeensis were diagnosed in the summer, when ticks are more active. All patients had influenzalike symptoms with high fever. None of the cases was fatal. Three serum samples were also seroreactive for antibodies to E. canis, and one was also reactive to the human granulocytic ehrlichiosis (HGE) agent. The titer to the HGE agent in this patient was higher than the serum titer to E. chaffeensis, and the Western blot analysis also indicated that the HGE agent was the primary cause of infection. We present the first serologic evidence that the agents of human monocytic ehrlichiosis (HME) and HGE are present in Israel. Therefore, human ehrlichiosis should be included in the differential diagnoses for persons in Israel who have been exposed to ticks and have influenzalike symptoms. PMID:10603210

[Microorganisms of the order Rickettsiales in taiga tick (Ixodes persulcatus Sch.) from the Pre-Ural region].

PubMed

Nefedova, V V; Korenberg, E I; Kovalevskiĭ, Iu V; Gorelova, N B; Vorob'eva, N N

2008-01-01

The PCR and sequence analysis revealed DNA Ehrlichia muris, Anaplasma phagocytophilum, and Rickettsia spp. in the I. persulcatus ticks and blood samples from a patients with acute febrile illness occurring after a tick bite, registered in the seasonal peak of the tick activity of one of the highly endemic areas of Russia (Perm region). These data confirmed the validity a diagnosis of HME and HGA, which were made earlier on the basis of the clinical-serologic survey. In 10.0% of the tested taiga ticks were detected DNA of two and more agents in various combinations i.e. E. muris and Rickettsia spp, A. phagocytophilum and Rickettsia spp., and E. muris, A. phagocytophilum and Rickettsia spp. DNA of a R. helvetica was detected in I. persulcatus tick and blood tick-bitten patient with febrile episodes. Probably that R. helvetica can be etiological agent in some part of cases with the serologically unconfirmed diagnoses of acute feverish diseases developing after tick bite.

dbHiMo: a web-based epigenomics platform for histone-modifying enzymes.

PubMed

Choi, Jaeyoung; Kim, Ki-Tae; Huh, Aram; Kwon, Seomun; Hong, Changyoung; Asiegbu, Fred O; Jeon, Junhyun; Lee, Yong-Hwan

2015-01-01

Over the past two decades, epigenetics has evolved into a key concept for understanding regulation of gene expression. Among many epigenetic mechanisms, covalent modifications such as acetylation and methylation of lysine residues on core histones emerged as a major mechanism in epigenetic regulation. Here, we present the database for histone-modifying enzymes (dbHiMo; http://hme.riceblast.snu.ac.kr/) aimed at facilitating functional and comparative analysis of histone-modifying enzymes (HMEs). HMEs were identified by applying a search pipeline built upon profile hidden Markov model (HMM) to proteomes. The database incorporates 11,576 HMEs identified from 603 proteomes including 483 fungal, 32 plants and 51 metazoan species. The dbHiMo provides users with web-based personalized data browsing and analysis tools, supporting comparative and evolutionary genomics. With comprehensive data entries and associated web-based tools, our database will be a valuable resource for future epigenetics/epigenomics studies. © The Author(s) 2015. Published by Oxford University Press.

Laboratory evaluation of 10 heat and moisture exchangers using simulated aeromedical evacuation conditions.

PubMed

Suliman, Huda S; Fecura, Stephen E; Baskin, Jonathan; Kalns, John E

2011-06-01

Heat and moisture exchangers (HMEs) are used for airway humidification in mechanically ventilated patients and have been evaluated only under hospital conditions. U.S. Air Force aeromedical evacuation transports are performed under rugged conditions further complicated by the cold and dry environment in military aircrafts, and HMEs are used to provide airway humidification for patients. This study evaluated 10 commercial HMEs using a test system that simulated aeromedical evacuation conditions. Although the American National Standards Institute recommends inspired air to be at an absolute humidity value of > or = 30 mg/L for mechanically ventilated patients, the highest absolute humidity by any HME was approximately 20 mg/L. Although none of the HMEs were able to maintain a temperature high enough to achieve the humidity standard of the American National Standards Institute, the clinical significance of this standard may be less important than the relative humidity maintained in the respired air, especially on evacuation flights of short duration.

Bovine calves as ideal bio-indicators for fluoridated drinking water and endemic osteo-dental fluorosis.

PubMed

Choubisa, S L

2014-07-01

Relative susceptibility to fluoride (F) toxicosis in the form of osteo-dental fluorosis was observed in an observational survey of 2,747 mature and 887 immature domestic animals of diverse species living in areas with naturally fluoridated (>1.5 ppm F) drinking water. These animals included buffaloes (Bubalus bubalis), cattle (Bos taurus), camels (Camelus dromedarius), donkeys (Equus asinus), horses (Equus caballus), goats (Capra hircus), and sheep (Ovis aries). Of these mature and immature animals, 899 (32.7 %) and 322 (36.3 %) showed evidence of dental fluorosis with varying grades, respectively. Their incisor teeth were stained with light to deep brownish color. On clinical examination, 31.2 % mature and 10.7 % immature animals revealed periosteal exostoses, intermittent lameness, and stiffness of tendons in the legs as signs of skeletal fluorosis. The maximum susceptibility to fluoride toxicosis was found in bovines (buffaloes and cattle) followed by equines (donkeys and horses), flocks (goats and sheep), and camelids (camels). The bovine calves were found to be more sensitive and highly susceptible to F toxicosis and revealed the maximum prevalence (92.2 %) of dental fluorosis. This indicates that bovine calves are less tolerant and give early sign of F poisoning (dental fluorosis) and therefore, they can be considered as bio-indicators for fluoridated water as well as for endemicity of osteo-dental fluorosis. Causes for variation in susceptibility to F toxicosis (fluorosis) in various species of domestic animal are also discussed.

A Reusable Design for Precision Lunar Landing Systems

NASA Technical Reports Server (NTRS)

Fuhrman, Linda; Brand, Timothy; Fill, Tom; Norris, Lee; Paschall, Steve

2005-01-01

The top-level architecture to accomplish NASA's Vision for Space Exploration is to use Lunar missions and systems not just as an end in themselves, but also as testbeds for the more ambitious goals of Human Mars Exploration (HME). This approach means that Lunar missions and systems are most likely going to be targeted for (Lunar) polar missions, and also for long-duration (months) surface stays. This overacting theme creates basic top-level requirements for any next-generation lander system: 1) Long duration stays: a) Multiple landers in close proximity; b) Pinpoint landings for "surface rendezvous"; c) Autonomous landing of pre-positioned assets; and d) Autonomous Hazard Detection and Avoidance. 2) Polar and deep-crater landings (dark); 3) Common/extensible systems for Moon and Mars, crew and cargo. These requirements pose challenging technology and capability needs. Compare and contrast: 4) Apollo: a) 1 km landing accuracy; b) Lunar near-side (well imaged and direct-to-Earth com. possible); c) Lunar equatorial (landing trajectories offer best navigation support from Earth); d) Limited lighting conditions; e) Significant ground-in-the-loop operations; 5) Lunar Access: a) 10-100m landing precision; b) "Anywhere" access includes polar (potentially poor nav. support from Earth) and far side (poor gravity and imaging; no direct-to-Earth com); c) "Anytime" access includes any lighting condition (including dark); d) Full autonomous landing capability; e) Extensible design for tele-operation or operator-in-the-loop; and f) Minimal ground support to reduce operations costs. The Lunar Access program objectives, therefore, are to: a) Develop a baseline Lunar Precision Landing System (PLS) design to enable pinpoint "anywhere, anytime" landings; b) landing precision 10m-100m; c) Any LAT, LON; and d) Any lighting condition; This paper will characterize basic features of the next generation Lunar landing system, including trajectory types, sensor suite options and a reference system architecture.

A Qualitative Assessment of the Evidence Utilization for Health Policy-Making on the Basis of SUPPORT Tools in a Developing Country

PubMed Central

Hasan Imani-Nasab, Mohammad; Seyedin, Hesam; Yazdizadeh, Bahareh; Majdzadeh, Reza

2017-01-01

Background: SUPPORT tools consist of 18 articles addressing the health policy-makers so that they can learn how to make evidence-informed health policies. These tools have been particularly recommended for developing countries. The present study tries to explain the process of evidence utilization for developing policy documents in the Iranian Ministry of Health and Medical Education (MoHME) and to compare the findings with those of SUPPORT tools. Methods: A qualitative research was conducted, using the framework analysis approach. Participants consisted of senior managers and technicians in MoHME. Purposeful sampling was done, with a maximum variety, for the selection of research participants: individuals having at least 5 years of experience in preparing evidence-based policy documents. Face-to-face interviews were conducted for data collection. As a guideline for the interviews, ‘the Utilization of Evidence in Policy-Making Organizations’ procedure was used. The data were analyzed through the analysis of the framework method using MAXQDA 10 software. Results: The participants acquired the research evidence in a topic-based form, and they were less likely to search on the basis of the evidence pyramid. To assess the quality of evidence, they did not use standard critical tools; to adapt the evidence and interventions with the local setting, they did not use the ideas and experiences of all stakeholders, and in preparing the evidence-based policy documents, they did not take into consideration the window of opportunity, did not refrain from using highly technical terms, did not write user-friendly summaries, and did not present alternative policy options. In order to develop health policies, however, they used the following innovations: attention to the financial burden of policy issues on the agenda, sensitivity analysis of the preferred policy option on the basis of technical, sociopolitical, and economic feasibility, advocacy from other scholars, using the multi-criteria decision-making models for the prioritization of policy options, implementation of policy based on the degree of readiness of policy-implementing units, and the classification of policy documents on the basis of different conditions of policy-making (urgent, short-term, and long-term). Conclusion: Findings showed that the process of evidence utilization in IR-MoH enjoys some innovations for the support of health policy development. The present study provides IR-MoH with considerable opportunities for the improvement of evidence-informed health policy-making. Moreover, the SUPPORT process and tools are recommended to be used in developing countries. PMID:28812845

Thricho-rhino-phalangeal syndrome and severe osteoporosis: a rare association or a feature? An effective therapeutic approach with biphosphonates.

PubMed

Macchiaiolo, M; Mennini, M; Digilio, M C; Buonuomo, P S; Lepri, F R; Gnazzo, M; Grandin, A; Angioni, A; Bartuli, A

2014-03-01

Trichorhinophalangeal syndrome (TRPS) is a rare, autosomal dominant malformation syndrome characterized by hair, craniofacial and skeletal abnormalities, skin laxity, deformation of phalanges and anomalies of pelvis, femurs, and tibias. Three subtypes have been described: TRPS I, caused by mutations in TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. We present the case of a 7-year-old boy, affected by TRPS with a severe osteoporosis and several spontaneous bone fractures, an association described only once in the literature, successfully treated with biphosphonates. Bone mineral density (BMD) at dual-energy X-ray Absorptiometry (DXA) was of 0.331 g/cm(2) at lumbar spine with. He had four spontaneous femoral fractures in a year, and for this reason he was been operated for positioning intramedullary osteosynthesis and orthopedic supports. Due to the severity of the clinical and radiological pattern it was established, after approval of the Ethical Committee, to begin off-label therapy with infusions of neridronate at a dose of 2 mg/kg IV every 3 months. The treatment was, in this patient, effective both in terms of clinical (absence of new fractures) and mineralomethric (+45% BMD ath the lumbar level). We therefore suggest that treatment with biphosponates can be taken in account as a possible therapeutic option in case of bone fragility in patients with TRPSI. © 2013 Wiley Periodicals, Inc.

Excess thermodynamics of mixtures involving xenon and light linear alkanes by computer simulation.

PubMed

Carvalho, A J Palace; Ramalho, J P Prates; Martins, Luís F G

2007-06-14

Excess molar enthalpies and excess molar volumes as a function of composition for liquid mixtures of xenon + ethane (at 161.40 K), xenon + propane (at 161.40 K) and xenon + n-butane (at 182.34 K) have been obtained by Monte Carlo computer simulations and compared with available experimental data. Simulation conditions were chosen to closely match those of the corresponding experimental results. The TraPPE-UA force field was selected among other force fields to model all the alkanes studied, whereas the one-center Lennard-Jones potential from Bohn et al. was used for xenon. The calculated H(m)(E) and V(m)(E) for all systems are negative, increasing in magnitude as the alkane chain length increases. The results for these systems were compared with experimental data and with other theoretical calculations using the SAFT approach. An excellent agreement between simulation and experimental results was found for xenon + ethane system, whereas for the remaining two systems, some deviations that become progressively more significant as the alkane chain length increases were observed.

Improving Injectable Medicines Prescription in Outpatient Services: A Path Towards Rational Use of Medicines in Iran

PubMed Central

Bairami, Firoozeh; Soleymani, Fatemeh; Rashidian, Arash

2016-01-01

Injection is one of the most common medical procedures in the health sector. Annually up to 16 billion injections are prescribed in low- and middle-income countries (LMICs), many of them are not necessary for the patients, increase the healthcare costs and may result in side effects. Currently over 40% of outpatient prescriptions in Iran contain at least one injectable medicine. To address the issue, a working group was established (August 2014 to April 2015) to provide a comprehensive policy brief to be used by national decision-makers. This report is the extract of methods that were followed and the main policy options for improving injectable medicines prescribing in outpatient services. Thirty-three potential policy options were developed focusing on different stakeholders. The panel reached consensus on seven policy options, noting effectiveness, cost, durability, and feasibility of each policy. The recommended policy options are targeted at patients and public (2 policies), insurers (2), physicians (1), pharmacies (1), and the Ministry of Health and Medical Education (MoHME) (1). PMID:27239881

Department of Homeland Security (DHS) Proficiency Testing on Small-Scale Safety and Thermal Testing of Improvised Explosives

NASA Astrophysics Data System (ADS)

Reynolds, John; Sandstrom, Mary; Brown, Geoffrey; Warner, Kirstin; Phillips, Jason; Shelley, Timothy; Reyes, Jose; Hsu, Peter

2013-06-01

One of the first steps in establishing safe handling procedures for explosives is small-scale safety and thermal (SSST) testing. To better understand the response of improvised materials or HMEs to SSST testing, 18 HME materials were compared to 3 standard military explosives in a proficiency-type round robin study among five laboratories--2 DoD and 3 DOE--sponsored by DHS. The testing matrix has been designed to address problems encountered with improvised materials--powder mixtures, liquid suspensions, partially wetted solids, immiscible liquids, and reactive materials. Over 30 issues have been identified that indicate standard test methods may require modification when applied to HMEs to derive accurate sensitivity assessments needed for development safe handling and storage practices. This presentation will discuss experimental difficulties encountered when testing these problematic samples, show inter-laboratory testing results, show some statistical interpretation of the results, and highlight some of the testing issues. Some of the work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-617519 (721812).

DHS small-scale safety and thermal testing of improvised explosives-comparison of testing performance

NASA Astrophysics Data System (ADS)

Reynolds, J. G.; Sandstrom, M. M.; Brown, G. W.; Warner, K. F.; Phillips, J. J.; Shelley, T. J.; Reyes, J. A.; Hsu, P. C.

2014-05-01

One of the first steps in establishing safe handling procedures for explosives is small-scale safety and thermal (SSST) testing. To better understand the response of improvised materials or homemade explosives (HMEs) to SSST testing, 16 HME materials were compared to three standard military explosives in a proficiency-type round robin study among five laboratories-two DoD and three DOE-sponsored by DHS. The testing matrix has been designed to address problems encountered with improvised materials-powder mixtures, liquid suspensions, partially wetted solids, immiscible liquids, and reactive materials. More than 30 issues have been identified that indicate standard test methods may require modification when applied to HMEs to derive accurate sensitivity assessments needed for developing safe handling and storage practices. This paper presents a generalized comparison of the results among the testing participants, comparison of friction results from BAM (German Bundesanstalt für Materi-alprüfung) and ABL (Allegany Ballistics Laboratory) designed testing equipment, and an overview of the statistical results from the RDX (1,3,5-Trinitroperhydro-1,3,5-triazine) standard tested throughout the proficiency test.

Acute injury and chronic disability resulting from surfboard riding.

PubMed

Taylor, D McD; Bennett, D; Carter, M; Garewal, D; Finch, C F

2004-12-01

We undertook a cross-sectional survey of surfers at eight Victorian beaches between February and May 2003 and analysed acute injury and chronic disability sustained while surfing during the preceding 12 months. Significant injuries were defined as requiring medical attention or time off surfing/work. 646 surfers were enrolled (90.2% male, median age 27 years, median years of surfing 10). 145 surfers sustained 168 significant acute injuries in the preceding 12 months (0.26 injuries/surfer/year, 95% CI 0.22-0.30). Most were caused by striking a surfboard or another surfer (45.2%, 95% CI 37.6-53.1), "wiping out" (36.3%, 95% CI 29.1-44.1) or striking the seabed (17.9%, 95% CI 12.6-24.7). Injuries included lacerations (46.4%, 95% CI 38.8-54.3), sprains (28.6%, 95% CI 22.0-36.1), dislocations (10.7%, 95% CI 6.7-16.6) and fractures (8.9%, 95% CI 5.3-14.6). Body parts most frequently injured were the lower limb (45.8%, 95% CI 38.2-53.7) and the head/face (26.2%, 95% CI 19.9-33.6). Surfing injuries that were treated in Victorian emergency departments over a six year period revealed a similar pattern, although there was a greater proportion of head/face injuries (42.0%, 95% CI 36.0-48.1, p = 0.001). 20 surfers reported long-term effects from acute injuries, mainly unstable/stiff/painful joints. 136 surfers reported chronic health problems not related to acute injury including chronic/recurrent otitis externa and exostoses, muscle and joint pain/stiffness and pterygium. Significant injury while surfing is not uncommon. Although head injury accounts for a considerable proportion, very few surfers wear protective headgear. Greater use of protective headgear should be considered.

[Femoral artery pseudoaneurysms encountered in orthopedics and traumatology].

PubMed

Raherinantenaina, F; Rajaonanahary, T M A; Rakoto Ratsimba, H N

2015-12-01

Most published articles regarding orthopedic- and trauma-related femoral artery pseudoaneurysms (FAPs) are case reports in English. Reported cases are often associated with a literature review but actually provide little robust data. We wanted to summarize the current knowledge on diagnostic and therapeutic features of these FAPs. A new case of superficial FAP is described followed by a review of the literature. A bibliographic search was performed online (PubMed, ScinceDirect) from 1964 to 2015 using the descriptors "traumatic femoral pseudoaneurysm, orthopedic surgery, osteochondroma". A total of 64 cases of FAPs was analyzed. There were 50 men with an average age of 40.72±26.45 years old. The most common clinical presentation was painful swelling (34%). Arteriography was the commonest radiological investigation used (63%). The main etiologies were orthopedic injuries (47%), surgery of the upper thigh (30%) and femoral osteochondromas (23%). Arterial injuries included superficial femoral (47%) and profunda femoris artery (50%). The treatment was open surgery (56%) or endovascular repair (36%). Deep femoral artery and its branches were embolized (47%) or ligated (38%). Endovascular stenting was performed in 30% of posttraumatic FAPs. All FAPs relating to osteochondromas were repaired surgically. Postoperative courses were uneventful in 95% of patients. Endovascular embolization is preferred in management of postsurgical FAPs which have usually involved the deep femoral artery. Endovascular stenting graft may be proposed for posttraumatic FAPs, for which the superficial femoral trunk is the most often involved vessel. Surgical repair should be performed when endovascular stenting graft is not feasible. Surgical repair is mandatory for all FAPs secondary to traumatic exostoses. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Predicting melt rheology for hot-melt extrusion by means of a simple Tg-measurement.

PubMed

Bochmann, Esther S; Üstüner, Elgin E; Gryczke, Andreas; Wagner, Karl G

2017-10-01

The feasibility of predicting melt rheology by using the glass transition temperature (T g ) of a desired amorphous solid dispersion (ASD) for hot-melt extrusion (HME) and other melt based processes is presented. Three groups of three different active pharmaceutical ingredients (APIs) or plasticizer/copovidone mixtures, with identical glass transition in rheological testing, were used. Their rheological behavior as a function of temperature and frequency were analyzed by means of small amplitude oscillatory shear (SAOS) on an oscillatory rheometer. The zero-shear viscosity (η 0 ) identified at 150°C was compared to T g , measured by differential scanning calorimetry (DSC) and SAOS. A strong correlation between η 0 and T g was identified, independent of the API or plasticizer used to achieve T g of the mixture. To evaluate and rate the discrepancy in η 0 of the different mixtures at same T g , hot-melt extrusion trials were conducted to measure torque and mean residence time. In this paper, carbamazepine, dipyridamole, indomethacin, ibuprofen, polyethylene glycol (PEG 1500) in vinylpyrrolidone-vinyl acetate copolymer (copovidone) as matrix polymer were used. Copyright © 2017. Published by Elsevier B.V.

Injection molding as a one-step process for the direct production of pharmaceutical dosage forms from primary powders.

PubMed

Eggenreich, K; Windhab, S; Schrank, S; Treffer, D; Juster, H; Steinbichler, G; Laske, S; Koscher, G; Roblegg, E; Khinast, J G

2016-05-30

The objective of the present study was to develop a one-step process for the production of tablets directly from primary powder by means of injection molding (IM), to create solid-dispersion based tablets. Fenofibrate was used as the model API, a polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft co-polymer served as a matrix system. Formulations were injection-molded into tablets using state-of-the-art IM equipment. The resulting tablets were physico-chemically characterized and the drug release kinetics and mechanism were determined. Comparison tablets were produced, either directly from powder or from pre-processed pellets prepared via hot melt extrusion (HME). The content of the model drug in the formulations was 10% (w/w), 20% (w/w) and 30% (w/w), respectively. After 120min, both powder-based and pellet-based injection-molded tablets exhibited a drug release of 60% independent of the processing route. Content uniformity analysis demonstrated that the model drug was homogeneously distributed. Moreover, analysis of single dose uniformity also revealed geometric drug homogeneity between tablets of one shot. Copyright © 2016 Elsevier B.V. All rights reserved.

3D Printed "Starmix" Drug Loaded Dosage Forms for Paediatric Applications.

PubMed

Scoutaris, Nicolaos; Ross, Steven A; Douroumis, Dennis

2018-01-16

Three- dimensional (3D) printing has received significant attention as a manufacturing process for pharmaceutical dosage forms. In this study, we used Fusion Deposition Modelling (FDM) in order to print "candy - like" formulations by imitating Starmix® sweets to prepare paediatric medicines with enhanced palatability. Hot melt extrusion processing (HME) was coupled with FDM to prepare extruded filaments of indomethacin (IND), hypromellose acetate succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently feed them in the 3D printer. The shapes of the Starmix® objects were printed in the form of a heart, ring, bottle, ring, bear and lion. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug - excipient interactions and the content uniformity. Physicochemical analysis showed the presence of molecularly dispersed IND in the printed tablets. In vivo taste masking evaluation demonstrated excellent masking of the drug bitterness. The printed forms were evaluated for drug dissolution and showed immediate IND release independently of the printed shape, within 60 min. 3D printing was used successfully to process drug loaded filaments for the development of paediatric printed tablets in the form of Starmix® designs.

A Qualitative Assessment of the Evidence Utilization for Health Policy-Making on the Basis of SUPPORT Tools in a Developing Country.

PubMed

Hasan Imani-Nasab, Mohammad; Seyedin, Hesam; Yazdizadeh, Bahareh; Majdzadeh, Reza

2017-01-08

SUPPORT tools consist of 18 articles addressing the health policy-makers so that they can learn how to make evidence-informed health policies. These tools have been particularly recommended for developing countries. The present study tries to explain the process of evidence utilization for developing policy documents in the Iranian Ministry of Health and Medical Education (MoHME) and to compare the findings with those of SUPPORT tools. A qualitative research was conducted, using the framework analysis approach. Participants consisted of senior managers and technicians in MoHME. Purposeful sampling was done, with a maximum variety, for the selection of research participants: individuals having at least 5 years of experience in preparing evidence-based policy documents. Face-to-face interviews were conducted for data collection. As a guideline for the interviews, 'the Utilization of Evidence in Policy-Making Organizations' procedure was used. The data were analyzed through the analysis of the framework method using MAXQDA 10 software. The participants acquired the research evidence in a topic-based form, and they were less likely to search on the basis of the evidence pyramid. To assess the quality of evidence, they did not use standard critical tools; to adapt the evidence and interventions with the local setting, they did not use the ideas and experiences of all stakeholders, and in preparing the evidence-based policy documents, they did not take into consideration the window of opportunity, did not refrain from using highly technical terms, did not write user-friendly summaries, and did not present alternative policy options. In order to develop health policies, however, they used the following innovations: attention to the financial burden of policy issues on the agenda, sensitivity analysis of the preferred policy option on the basis of technical, sociopolitical, and economic feasibility, advocacy from other scholars, using the multi-criteria decision-making models for the prioritization of policy options, implementation of policy based on the degree of readiness of policy-implementing units, and the classification of policy documents on the basis of different conditions of policy-making (urgent, short-term, and long-term). Findings showed that the process of evidence utilization in IR-MoH enjoys some innovations for the support of health policy development. The present study provides IR-MoH with considerable opportunities for the improvement of evidence-informed health policy-making. Moreover, the SUPPORT process and tools are recommended to be used in developing countries. © 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Active versus passive humidification for self-ventilating tracheostomy and laryngectomy patients: a systematic review of the literature.

PubMed

Wong, C Y Y; Shakir, A A; Farboud, A; Whittet, H B

2016-12-01

To determine whether active or passive humidification methods are more effective in preventing pulmonary complications in self-ventilating neck breather patients. Systematic Review adhering to PRISMA guidance (checklist sourced from www.equator-network.org/). Review of current published relevant literature at a tertiary department of Otolaryngology and Head & Neck Surgery. We included all separate studies and comparison studies of active and passive humidification techniques in adult and paediatric neck breather patients. The primary outcome is the reduction in pulmonary complications. Secondary outcomes include patient compliance; carer and user satisfaction. Seven studies were included in this review: two RCTs (133 patients), one randomised controlled cross-over trial (29 patients), three randomised prospective studies (171 patients), and one retrospective study (73 patients). Only one study was conducted on paediatric neck breathers. The overall quality of the studies was low. Five studies were at a high risk of bias. Of the remaining two studies, one study had a low risk of bias and the other had an unclear risk. Despite limited subject evidence, results show that passive methods of humidification (mainly HME) is the preferred choice of humidification in the spontaneously breathing neck breather patients group mainly due to the reduction in pulmonary complaints, and better patient compliance. © 2015 John Wiley & Sons Ltd.

Heated wire humidification circuit attenuates the decrease of core temperature during general anesthesia in patients undergoing arthroscopic hip surgery.

PubMed

Park, Sooyong; Yoon, Seok-Hwa; Youn, Ann Misun; Song, Seung Hyun; Hwang, Ja Gyung

2017-12-01

Intraoperative hypothermia is common in patients undergoing general anesthesia during arthroscopic hip surgery. In the present study, we assessed the effect of heating and humidifying the airway with a heated wire humidification circuit (HHC) to attenuate the decrease of core temperature and prevent hypothermia in patients undergoing arthroscopic hip surgery under general anesthesia. Fifty-six patients scheduled for arthroscopic hip surgery were randomly assigned to either a control group using a breathing circuit connected with a heat and moisture exchanger (HME) (n = 28) or an HHC group using a heated wire humidification circuit (n = 28). The decrease in core temperature was measured from anesthetic induction and every 15 minutes thereafter using an esophageal stethoscope. Decrease in core temperature from anesthetic induction to 120 minutes after induction was lower in the HHC group (-0.60 ± 0.27℃) compared to the control group (-0.86 ± 0.29℃) (P = 0.001). However, there was no statistically significant difference in the incidence of intraoperative hypothermia or the incidence of shivering in the postanesthetic care unit. The use of HHC may be considered as a method to attenuate intraoperative decrease in core temperature during arthroscopic hip surgery performed under general anesthesia and exceeding 2 hours in duration.

Mosquito (Diptera: Culicidae) grouping based on larval habitat characteristics in high mountain ecosystems of Antioquia, Colombia.

PubMed

Rosero-García, Doris; Rúa-Uribe, Guillermo; Correa, Margarita M; Conn, Jan E; Uribe-Soto, Sandra

2018-06-01

Information about mosquito ecology in the high mountain ecosystems of the Neotropical region is sparse. In general, few genera and species have been reported in these ecosystems and there is no information available on habitats and the mosquitoes occupying them. In the present study, specimens collected from NW Colombia in HME were grouped using larval habitat data via an Operational Taxonomic Unit (OTU) determination. A total of 719 mosquitoes was analyzed belonging to 44 OTUs. The analysis considered habitat features and clustered the specimens into six groups from A-F. Five of these included species from different genera, suggesting common habitat requirements. Group E with four genera, seven subgenera, and six species occupied the highest areas (above 3,000 m), whereas three groups (B, D, F) were detected at lower altitudes (1,960-2,002 m). Bromeliads were the most common larval habitat, with 47% (335/719) of the specimens; five genera, six subgenera, and eight species were identified and classified into 66% (29/44) of the OTUs. This work showed some similarities to the habitat requirements and provides a grouping system that constitutes an important baseline for the classification of mosquito fauna from high mountain ecosystems according to altitude and larval habitat. © 2018 The Society for Vector Ecology.

Rheological Characterization of Molten Polymer-Drug Dispersions as a Predictive Tool for Pharmaceutical Hot-Melt Extrusion Processability.

PubMed

Van Renterghem, Jeroen; Vervaet, Chris; De Beer, Thomas

2017-11-01

The aim of this study was to investigate (i) the influence of drug solid-state (crystalline or dissolved in the polymer matrix) on the melt viscosity and (ii) the influence of the drug concentration, temperature and shear rate on polymer crystallization using rheological tests. Poly (ethylene oxide) (PEO) (100.000 g/mol) and physical mixtures (PM) containing 10-20-30-40% (w/w) ketoprofen or 10% (w/w) theophylline in PEO were rheologically characterized. Rheological tests were performed (frequency and temperature sweeps in oscillatory shear as well as shear-induced crystallization experiments) to obtain a thorough understanding of the flow behaviour and crystallization of PEO-drug dispersions. Theophylline did not dissolve in PEO as the complex viscosity (η*) of the drug-polymer mixture increased as compared to that of neat PEO. In contrast, ketoprofen dissolved in PEO and acted as a plasticizer, decreasing η*. Acting as a nucleating agent, theophylline induced the crystallization of PEO upon cooling from the melt. On the other hand, ketoprofen inhibited crystallization upon cooling. Moreover, higher concentrations of ketoprofen in the drug-polymer mixture increasingly inhibited polymer crystallization. However, shear-induced crystallization was observed for all tested mixtures containing ketoprofen. The obtained rheological results are relevant for understanding and predicting HME processability (e.g., barrel temperature selection) and downstream processing such as injection moulding (e.g., mold temperature selection).

Influence of pressurized carbon dioxide on ketoprofen-incorporated hot-melt extruded low molecular weight hydroxypropylcellulose.

PubMed

A Ashour, Eman; Kulkarni, Vijay; Almutairy, Bjad; Park, Jun-Bom; Shah, Sejal P; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Vivian; Durig, Thomas; Martin, Scott T; Repka, Michael A

2016-01-01

The aim of the current research project was to investigate the effect of pressurized carbon dioxide (P-CO 2 ) on the physico-mechanical properties of ketoprofen (KTP)-incorporated hydroxypropylcellulose (HPC) (Klucel™ ELF, EF, and LF) produced using hot-melt extrusion (HME) techniques and to assess the plasticization effect of P-CO 2 on the various polymers tested. The physico-mechanical properties of extrudates with and without injection of P-CO 2 were examined and compared with extrudates with the addition of 5% liquid plasticizer of propylene glycol (PG). The extrudates were milled and compressed into tablets. Tablet characteristics of the extrudates with and without injection of P-CO 2 were evaluated. P-CO 2 acted as a plasticizer for tested polymers, which allowed for the reduction in extrusion processing temperature. The microscopic morphology of the extrudates was changed to a foam-like structure due to the expansion of the CO 2 at the extrusion die. The foamy extrudates demonstrated enhanced KTP release compared with the extrudates processed without P-CO 2 due to the increase of porosity and surface area of those extrudates. Furthermore, the hardness of the tablets prepared by foamy extrudates was increased and the percent friability was decreased. Thus, the good binding properties and compressibility of the extrudates were positively influenced by utilizing P-CO 2 processing.

Influence of Pressurized Carbon Dioxide on Ketoprofen-Incorporated Hot-Melt Extruded Low Molecular Weight Hydroxypropylcellulose

PubMed Central

Ashour, Eman A.; Kulkarni, Vijay; Almutairy, Bjad; Park, Jun-Bom; Shah, Sejal; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Martin, Scott T.; Repka, Michael A.

2017-01-01

Objectives The aim of the current research project was to investigate the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of Ketoprofen (KTP)-incorporated hydroxypropylcellulose (HPC) (Klucel™ ELF, EF and LF) produced using hot melt extrusion (HME) techniques and to assess the plasticization effect of P-CO2 on the various polymers tested. Methods The physico-mechanical properties of extrudates with and without injection of P-CO2 were examined and compared to extrudates with the addition of 5% liquid plasticizer of propylene glycol (PG). The extrudates were milled and compressed into tablets. Tablet characteristics of the extrudates with and without injection of P-CO2 were evaluated. Results & conclusion P-CO2 acted as a plasticizer for tested polymers, which allowed for the reduction in extrusion processing temperature. The microscopic morphology of the extrudates were changed to a foam-like structure due to expansion of the CO2 at the extrusion die. The foamy extrudates demonstrated enhanced KTP release compared to the extrudates processed without P-CO2 due to the increase of porosity and surface area of those extrudates. Furthermore, the hardness of the tablets prepared by foamy extrudates was increased and the percent friability was decreased. Thus, the good binding properties and compressibility of the extrudates were positively influenced by utilizing P-CO2 processing. PMID:25997363

Evaluation of board performance in Iran's universities of medical sciences.

PubMed

Sajadi, Haniye Sadat; Maleki, Mohammadreza; Ravaghi, Hamid; Farzan, Homayoun; Aminlou, Hasan; Hadi, Mohammad

2014-10-01

The critical role that the board plays in governance of universities clarifies the necessity of evaluating its performance. This study was aimed to evaluate the performance of the boards of medical universities and provide solutions to enhance its performance. The first phase of present study was a qualitative research in which data were collected through face-to-face semi-structured interviews. Data were analyzed by thematic approach. The second phase was a mixed qualitative and quantitative study, with quantitative part in cross-sectional format and qualitative part in content analysis format. In the quantitative part, data were collected through Ministry of Health and Medical Education (MoHME). In the qualitative part, the content of 2,148 resolutions that were selected by using stratified sampling method were analyzed. Participants believed that the boards had no acceptable performance for a long time.RESULTS also indicated the increasing number of meetings and resolutions of the boards in these 21 years. The boards' resolutions were mostly operational in domain and administrative in nature. The share of specific resolutions was more than the general ones. Given the current pace of change and development and the need to timely respond them, it is recommended to accelerate the slow pace of improvement process of the boards. It appears that more delegation and strengthening the position of the boards are the effective strategies to speed up this process.

[Humidification assessment of four heat and moisture exchanger filters according to ISO 9360: 2000 standard].

PubMed

Lannoy, D; Décaudin, B; Resibois, J-P; Barrier, F; Wierre, L; Horrent, S; Batt, C; Moulront, S; Odou, P

2008-02-01

This work consisted of the assessment of humidification parameters and flow resistance for different heat and moisture exchanger filters (HMEF) used in intensive care unit. Four electrostatic HMEF were assessed: Hygrobac S (Tyco); Humidvent compact S (Teleflex); Hygrovent S/HME (Medisize-Dräger); Clear-Therm+HMEF (Intersurgical). Humidification parameters (loss of water weight, average absolute moisture [AAM], absolute variation of moisture) have been evaluated on a bench-test in conformity with the ISO 9360: 2000 standard, for 24h with the following ventilatory settings: tidal volume at 500 ml, respiratory rate at 15 c/min, and inspiration/expiration ratio at 1:1. The flow resistance of HMEFs assessed using the pressure drop method was measured before and after 24h of humidification for three increasing air flows of 30, 60, and 90 l/min. All the HMEFs allowed satisfactory level of humidification exceeding 30 mgH(2)O/l. The less powerful remained the Clear-Therm. Concerning HMEFs flow resistance, results showed a pressure drop slightly more important for the Hygrobac S filter as compared with other filters. This test showed differences between the HMEFs for both humidification and resistance parameters. When compared to the new version of the standards, HMEFs demonstrated their reliability. However, evolution of humidification and flow resistance characteristics over 24h showed a structural degradation of HMEFs, limiting their use over a longer period.

Hydridomethyl iridium complex

DOEpatents

Bergman, Robert G.; Buchanan, J. Michael; Stryker, Jeffrey M.; Wax, Michael J.

1989-01-01

A process for functionalizing methane comprising: (a) reacting methane with a hydridoalkyl metal complex of the formula: CpIr[P(R.sub.1).sub.3 ]H(R.sub.2) wherein Cp represents a cyclopentadienyl or alkylcyclopentadienyl radical having from 1 to 5 carbon atoms; Ir represents an iridium atom; P represents a phosphorus atom; R.sub.1 represents an alkyl group; R.sub.2 represents an alkyl group having at least two carbon atoms; and H represents a hydrogen atom, in the presence of a liquid alkane R.sub.3 H having at least three carbon atoms to form a hydridomethyl complex of the formula: CpIr[P(R.sub.1).sub.3 ]HMe where Me represents a methyl radical. (b) reacting said hydridomethyl complex with an organic halogenating agent such as a tetrahalomethane or a haloform of the formulas: CX'X"X'"X"" or CHX'X"X'"; wherein X', X", X"', and X"" represent halogens selected from bromine, iodine and chlorine, to halomethyl complex of step (a) having the formula: CpIr[P(R.sub.1).sub.3 ]MeX: (c) reacting said halomethyl complex with a mercuric halide of the formula HgX.sub.2 to form a methyl mercuric halide of the formula HgMeX; and (d) reacting said methyl mercuric halide with a molecular halogen of the formula X.sub.2 to form methyl halide.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterization.

PubMed

Li, Shu; Yu, Tao; Tian, Yiwei; McCoy, Colin P; Jones, David S; Andrews, Gavin P

2016-09-06

Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.

Heated wire humidification circuit attenuates the decrease of core temperature during general anesthesia in patients undergoing arthroscopic hip surgery

PubMed Central

Park, Sooyong; Song, Seung Hyun; Hwang, Ja Gyung

2017-01-01

Background Intraoperative hypothermia is common in patients undergoing general anesthesia during arthroscopic hip surgery. In the present study, we assessed the effect of heating and humidifying the airway with a heated wire humidification circuit (HHC) to attenuate the decrease of core temperature and prevent hypothermia in patients undergoing arthroscopic hip surgery under general anesthesia. Methods Fifty-six patients scheduled for arthroscopic hip surgery were randomly assigned to either a control group using a breathing circuit connected with a heat and moisture exchanger (HME) (n = 28) or an HHC group using a heated wire humidification circuit (n = 28). The decrease in core temperature was measured from anesthetic induction and every 15 minutes thereafter using an esophageal stethoscope. Results Decrease in core temperature from anesthetic induction to 120 minutes after induction was lower in the HHC group (–0.60 ± 0.27℃) compared to the control group (–0.86 ± 0.29℃) (P = 0.001). However, there was no statistically significant difference in the incidence of intraoperative hypothermia or the incidence of shivering in the postanesthetic care unit. Conclusions The use of HHC may be considered as a method to attenuate intraoperative decrease in core temperature during arthroscopic hip surgery performed under general anesthesia and exceeding 2 hours in duration. PMID:29225745

A New Physical Meaning of Sommerfeld Fine Structure Constant

NASA Astrophysics Data System (ADS)

Sohrab, Siavash

2015-04-01

Identifying physical space or Casimir vacuum as a compressible tachyon fluid, Planck compressible ether, leads to stochastic definitions of Planck h = mk <λk > c and Boltzmann k = mk <νk > c constants, finite photon mass mk = (hk/c3)1/2 , amu = mk c2 = (hkc)1/2 , and modified Avogadro-Loschmidt number No = 1/(hkc)1/2 = 6.03766 x1023 mole-1 . Thus, Lorentz-FitzGerald contractions now result from compressibility of physical space and become causal (Pauli) in accordance with Poincaré-Lorentz dynamic theory of relativity as opposed to Einstein kinematic theory of relativity. At thermodynamic equilibrium he = me <λe > ve = hk = mk <λk > c = h, Compton wavelength can be expressed as λc = h/me c = (ve /c)h <λe > /(me <λe > ve) = αλe . Hence, Sommerfeld fine structure constant α is identified as the ratio of electron to photon speeds α = e2/(2ɛo hc) = ve/c = 1/137.036. The mean thermal speed of electron at equilibrium with photon gas is ve = 2.187640x106 m/s and its de Broglie wavelength is λe = 3.3250x10-10 m. Also, electron kinetic energy for oscillations in two directions < x + > and < x- > or ɛe = hνe = me ve2= kTe results in electron temperature Te = 3.15690x105 K.

Direct Analysis in Real Time Mass Spectrometry of Potential By-Products from Homemade Nitrate Ester Explosive Synthesis

PubMed Central

Sisco, Edward; Forbes, Thomas P.

2016-01-01

This work demonstrates the coupling of direct analysis in real time (DART) ionization with time-of-flight mass spectrometry (MS) in an off-axis configuration for the trace detection and analysis of potential partially nitrated and dimerized by-products of homemade nitrate ester explosive synthesis. Five compounds relating to the synthesis of nitroglycerin (NG) and pentaerythritol tetranitrate (PETN) were examined. Deprotonated ions and adducts with molecular oxygen, nitrite, and nitrate were observed in the mass spectral responses of these compounds. A global optimum temperature of 350 °C for the by-products investigated here, enabled single nanogram to sub nanogram trace detection. Matrix effects were examined through a series of mixtures containing one or more compounds (sugar alcohol precursors, by-products, and/or explosives) across a range of mass loadings. The explosives MS responses experienced competitive ionization in the presence of all by-products. The magnitude of this influence corresponded to both the degree of by-product nitration and the relative mass loading of the by-product to the explosive. This work provides a characterization of potential by-products from homemade nitrate ester synthesis, including matrix effects and potential challenges that might arise from the trace detection of homemade explosives (HMEs) containing impurities. Detection and understanding of HME impurities and complex mixtures may provide valuable information for the screening and sourcing of homemade nitrate ester explosives. PMID:26838397

Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

PubMed Central

Amin, Purnima

2014-01-01

Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72) and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72) and Cmax higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension. PMID:25143935

Effect of Compression on the Molecular Arrangement of Itraconazole-Soluplus Solid Dispersions: Induction of Liquid Crystals or Exacerbation of Phase Separation?

PubMed

Singh, Abhishek; Bharati, Avanish; Frederiks, Pauline; Verkinderen, Olivier; Goderis, Bart; Cardinaels, Ruth; Moldenaers, Paula; Van Humbeeck, Jan; Van den Mooter, Guy

2016-06-06

Predensification and compression are unit operations imperative to the manufacture of tablets and capsules. Such stress-inducing steps can cause destabilization of solid dispersions which can alter their molecular arrangement and ultimately affect dissolution rate and bioavailability. In this study, itraconazole-Soluplus solid dispersions with 50% (w/w) drug loading prepared by hot-melt extrusion (HME) were investigated. Compression was performed at both pharmaceutically relevant and extreme compression pressures and dwell times. The starting materials, powder, and compressed solid dispersions were analyzed using modulated differential scanning calorimetry (MDSC), X-ray diffraction (XRD), small- and wide-angle X-ray scattering (SWAXS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and broadband dielectric spectroscopy (BDS). MDSC analysis revealed that compression promotes phase separation of solid dispersions as indicated by an increase in glass transition width, occurrence of a peak in the nonreversing heat flow signal, and an increase in the net heat of fusion indicating crystallinity in the systems. SWAXS analysis ruled out the presence of mesophases. BDS measurements elucidated an increase in the Soluplus-rich regions of the solid dispersion upon compression. FTIR indicated changes in the spatiotemporal architecture of the solid dispersions mediated via disruption in hydrogen bonding and ultimately altered dynamics. These changes can have significant consequences on the final stability and performance of the solid dispersions.

Burden of major diarrheagenic protozoan parasitic co-infection among amoebic dysentery cases from North East India: a case report.

PubMed

Nath, Joyobrato; Hussain, Gulzar; Singha, Baby; Paul, Jaishree; Ghosh, Sankar Kumar

2015-09-01

Intestinal diarrheagenic polyparasitic infections are among the major public health concerns in developing countries. Here we examined stool specimens by microscopy, DNA dot blot and polymerase chain reaction (PCR) to evaluate the co-infection of four principal protozoans among amoebic dysentery cases from Northeast Indian population. The multiplex PCR confirmed Entamoeba histolytica (8.1%), Entamoeba dispar (4.8%) and mixed infection of both the parasites (3.4%) in 68 of 356 stool specimens that were positive in microscopy and/or HMe probe based DNA dot blot screening. The prevailing parasite that co-exists with E. histolytica was Giardia duodenalis (34.1%), followed by Enterocytozoon bieneusi (22.0%), Cryptosporidium parvum (14.6%) and Cyclospora cayetanensis (7.3%, P = 0.017). Symptomatic participants (odds ratio (OR) = 4.07; 95% confidence interval (CI) = 1.06, 15.68; P = 0.041), monsoon season (OR = 7.47; 95% CI = 1.40, 39.84; P = 0.046) and participants with family history of parasitic infection (OR = 4.50; 95% CI = 1.16, 17.51; P = 0.030) have significant association with overall co-infection rate. According to molecular consensus, comprehensive microscopy yielded 3.4% (12/356) false-negative and 7.6% (27/356) false-positive outcome, suggesting an improved broad-spectrum PCR-based diagnostic is required to scale down the poor sensitivity and specificity as well as implementation of integrated control strategy.

Evaluation of board performance in Iran’s universities of medical sciences

PubMed Central

Sajadi, Haniye Sadat; Maleki, Mohammadreza; Ravaghi, Hamid; Farzan, Homayoun; Aminlou, Hasan; Hadi, Mohammad

2014-01-01

Background: The critical role that the board plays in governance of universities clarifies the necessity of evaluating its performance. This study was aimed to evaluate the performance of the boards of medical universities and provide solutions to enhance its performance. Methods: The first phase of present study was a qualitative research in which data were collected through face-to-face semi-structured interviews. Data were analyzed by thematic approach. The second phase was a mixed qualitative and quantitative study, with quantitative part in cross-sectional format and qualitative part in content analysis format. In the quantitative part, data were collected through Ministry of Health and Medical Education (MoHME). In the qualitative part, the content of 2,148 resolutions that were selected by using stratified sampling method were analyzed. Results: Participants believed that the boards had no acceptable performance for a long time.Results also indicated the increasing number of meetings and resolutions of the boards in these 21 years. The boards’ resolutions were mostly operational in domain and administrative in nature. The share of specific resolutions was more than the general ones. Conclusion: Given the current pace of change and development and the need to timely respond them, it is recommended to accelerate the slow pace of improvement process of the boards. It appears that more delegation and strengthening the position of the boards are the effective strategies to speed up this process. PMID:25337597

Comparing two heat and moisture exchangers, one hydrophobic and one hygroscopic, on humidifying efficacy and the rate of nosocomial pneumonia.

PubMed

Thomachot, L; Viviand, X; Arnaud, S; Boisson, C; Martin, C D

1998-11-01

Many heat and moisture exchangers with filter (HMEF) have been developed. In-house data from companies provide some information about their performances; unfortunately, to our knowledge, no comparative evaluation in clinical conditions has been undertaken of these newer products. The aim of this study was to compare the efficiency of two HMEFs, one hydrophobic and one hygroscopic, on humidifying capacity and the rate of bronchial colonization and ventilator-associated pneumonia in ICU patients. Prospective, randomized study. ICU of a university hospital. All patients who required mechanical ventilation for > or = 24 h during the study period. On admission to the ICU, patients were randomly assigned to one of two groups. In one group, the patients were ventilated with a hygroscopic device (Humid-Vent Filter Light HMEF; Gibeck; Upplands Vaesby, Sweden). The condensation surface was made of paper (Microwell) impregnated with CaCl2. The filter membrane was made of polypropylene. In the other group, the patients were ventilated with a hydrophobic device (Pall BB100 HMEF). The condensation surface was made of a hydrophobic resin with a hydrophylic layer. The filter membrane was made of ceramic fibers. In both groups, HMEFs were changed daily. Both groups of patients were similar for the tested characteristics, including parameters of mechanical ventilation. Sixty-six patients were ventilated for 11.7+/-11 days with the Humid-Vent Filter Light HMEF and 70 patients for 12.2+/-12 days with the Pall BB 100. Patients ventilated with the Humid-Vent Filter Light underwent 6.0+/-3.0 tracheal aspirations and 1.7+/-2.0 instillations per day, and those with the Pall BB 100, 6.0+/-3.0 and 1.6+/-2.0 per day, respectively (not significant [NS]). Abundance of tracheal secretions, presence of blood, and viscosity, evaluated by semiquantitative scales, were similar in both groups. No difference in the rate of atelectasis was observed between the two groups (7.5% and 7.1%, NS). One episode of tracheal tube occlusion was observed with the Humid-Vent Filter Light HMEF, and one with the other HMEF (NS). One patient in each group (NS) was switched to an active heated humidifier because of very tenacious bronchial secretions despite repeated instillations. Tracheal colonization was observed at a rate of 67% with the Humid-Vent Filter Light and 58% with the Pall BB 100 (NS). A small, but NS difference was observed in the rate of ventilator-associated pneumonia: Humid-Vent Filter Light, 32% (27.1 per 1000 ventilator days); and Pall BB 100, 37% (30.4 per 1000 ventilator days). Bacteria responsible for tracheal colonization and pneumonia were similar in both groups. Three patients in each group died from their nosocomial pneumonia. Despite differences in their components, the two HMEFs tested achieved similar performances in terms of humidification and heating of inspired gases. Only one episode of endotracheal tube occlusion was detected and very few patients (one in each group) had to be switched to an active heated humidifier. No difference was observed either in the rate of tracheal colonization or of ventilator-associated pneumonia. These data show that the hygroscopic HME (Humid-Vent Filter Light) and the hydrophobic HME (Pall BB 100) are suited for use in ICU patients.

Thermodynamic behavior of the binaries 1-butylpyridinium tetrafluoroborate with water and alkanols: their interpretation using 1H NMR spectroscopy and quantum-chemistry calculations.

PubMed

Vreekamp, Remko; Castellano, Desire; Palomar, José; Ortega, Juan; Espiau, Fernando; Fernández, Luís; Penco, Eduvigis

2011-07-14

Here we present experimental data of different properties for a set of binary mixtures composed of water or alkanols (methanol to butanol) with an ionic liquid (IL), butylpyridinium tetrafluoroborate [bpy][BF(4)]. Solubility data (x(IL),T) are presented for each of the mixtures, including water, which is found to have a small interval of compositions in IL, x(IL), with immiscibility. In each case, the upper critical solubility temperature (UCST) is determined and a correlation was observed between the UCST and the nature of the compounds in the mixtures. Miscibility curves establish the composition and temperature intervals where thermodynamic properties of the mixtures, such as enthalpies H(m)(E) and volumes V(m)(E), can be determined. Hence, at 298.15 and 318.15 K these can only be found with the first four alkanols. All mixing properties are correlated with a suitable equation ξ (x(IL),T,Y(m)(E) = 0. An analysis on the influence of the temperature in the properties is shown, likewise a comparison between the results obtained here and those of analogous mixtures, discussing the position of the -CH(3) group in the pyridinic ring. The (1)H NMR spectra are determined to analyze the molecular interactions present, especially those due to hydrogen bonds. Additional information about the molecular interactions and their influence on the mixing properties is obtained by quantum chemistry calculations. © 2011 American Chemical Society

CopM is a novel copper-binding protein involved in copper resistance in Synechocystis sp. PCC 6803.

PubMed

Giner-Lamia, Joaquín; López-Maury, Luis; Florencio, Francisco J

2015-02-01

Copper resistance system in the cyanobacterium Synechocystis sp. PCC 6803 comprises two operons, copMRS and copBAC, which are expressed in response to copper in the media. copBAC codes for a heavy-metal efflux-resistance nodulation and division (HME-RND) system, while copMRS codes for a protein of unknown function, CopM, and a two-component system CopRS, which controls the expression of these two operons. Here, we report that CopM is a periplasmic protein able to bind Cu(I) with high affinity (KD ~3 × 10(-16) ). Mutants lacking copM showed a sensitive copper phenotype similar to mutants affected in copB, but lower than mutants of the two-component system CopRS, suggesting that CopBAC and CopM constitute two independent resistance mechanisms. Moreover, constitutive expression of copM is able to partially suppress the copper sensitivity of the copR mutant strain, pointing out that CopM per se is able to confer copper resistance. Furthermore, constitutive expression of copM was able to reduce total cellular copper content of the copR mutant to the levels determined in the wild-type (WT) strain. Finally, CopM was localized not only in the periplasm but also in the extracellular space, suggesting that CopM can also prevent copper accumulation probably by direct copper binding outside the cell. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Montreal's experience with Cyranose heat and moisture exchanger use in 15 laryngectomized patients.

PubMed

Dupuis, Paule; Guertin, Louis; Rainville, Marie-Stéphane; Prud'homme, Dominique-Louise; Lavigne, François

2007-08-01

Evaluate the effects of the improvement of filtration, heating and humidification of inspired air with Cyranose heat and moisture exchanger (HME) on voice quality, breathing, and secretion handling in laryngectomized patients. Prospective study. Fifteen laryngectomized patients, mean age 68, ages ranging from 50 to 91 years. Information was given to patients through video and brochures. Patients were selected if they had minimal understanding, permanent decanulization, no tumour progression or bronchopulmonary infections, and received no recent radiation therapy treatment. They were given the prosthesis and a starter kit. They were then evaluated by a speech pathologist with a structured questionnaire after one week, one month, and three months. The outcomes measured were comfort, breathing, secretions, and ease of use of the prosthesis as well as its effect on voice. Impressions of patients on humidification, filtration, and heating of inspired air were also recorded. At conclusion of trial, 75% of patients wore the prosthesis on a daily basis and they all found it easy to use. All patients who completed the trial found breathing and handling of secretions easier as they thought humidification and filtration of air had improved. Quality of voice improved for 50% while remaining unchanged for 37%. The positive effect of the prosthesis progressed throughout the trial. Seven patients dropped out of the trial, mainly because of adhesive-related issues. Laryngectomized patients from the Montreal area could benefit from Cyranose artificial nose following an adaptation period during our cold winter.

FORESEE: Fully Outsourced secuRe gEnome Study basEd on homomorphic Encryption

PubMed Central

2015-01-01

Background The increasing availability of genome data motivates massive research studies in personalized treatment and precision medicine. Public cloud services provide a flexible way to mitigate the storage and computation burden in conducting genome-wide association studies (GWAS). However, data privacy has been widely concerned when sharing the sensitive information in a cloud environment. Methods We presented a novel framework (FORESEE: Fully Outsourced secuRe gEnome Study basEd on homomorphic Encryption) to fully outsource GWAS (i.e., chi-square statistic computation) using homomorphic encryption. The proposed framework enables secure divisions over encrypted data. We introduced two division protocols (i.e., secure errorless division and secure approximation division) with a trade-off between complexity and accuracy in computing chi-square statistics. Results The proposed framework was evaluated for the task of chi-square statistic computation with two case-control datasets from the 2015 iDASH genome privacy protection challenge. Experimental results show that the performance of FORESEE can be significantly improved through algorithmic optimization and parallel computation. Remarkably, the secure approximation division provides significant performance gain, but without missing any significance SNPs in the chi-square association test using the aforementioned datasets. Conclusions Unlike many existing HME based studies, in which final results need to be computed by the data owner due to the lack of the secure division operation, the proposed FORESEE framework support complete outsourcing to the cloud and output the final encrypted chi-square statistics. PMID:26733391

Direct analysis in real time mass spectrometry of potential by-products from homemade nitrate ester explosive synthesis.

PubMed

Sisco, Edward; Forbes, Thomas P

2016-04-01

This work demonstrates the coupling of direct analysis in real time (DART) ionization with time-of-flight mass spectrometry (MS) in an off-axis configuration for the trace detection and analysis of potential partially nitrated and dimerized by-products of homemade nitrate ester explosive synthesis. Five compounds relating to the synthesis of nitroglycerin (NG) and pentaerythritol tetranitrate (PETN) were examined. Deprotonated ions and adducts with molecular oxygen, nitrite, and nitrate were observed in the mass spectral responses of these compounds. A global optimum temperature of 350 °C for the by-products investigated here enabled single nanogram to sub nanogram trace detection. Matrix effects were examined through a series of mixtures containing one or more compounds (sugar alcohol precursors, by-products, and/or explosives) across a range of mass loadings. The explosives MS responses experienced competitive ionization in the presence of all by-products. The magnitude of this influence corresponded to both the degree of by-product nitration and the relative mass loading of the by-product to the explosive. This work provides a characterization of potential by-products from homemade nitrate ester synthesis, including matrix effects and potential challenges that might arise from the trace detection of homemade explosives (HMEs) containing impurities. Detection and understanding of HME impurities and complex mixtures may provide valuable information for the screening and sourcing of homemade nitrate ester explosives. Published by Elsevier B.V.

Bioactive Potential of 3D-Printed Oleo-Gum-Resin Disks: B. papyrifera, C. myrrha, and S. benzoin Loading Nanooxides—TiO2, P25, Cu2O, and MoO3

PubMed Central

Tebcherani, Sergio Mazurek; Kubaski, Evaldo Toniolo; de Almeida Vieira, Rogério

2017-01-01

This experimental study investigates the bioactive potential of filaments produced via hot melt extrusion (HME) and intended for fused deposition modeling (FDM) 3D printing purposes. The oleo-gum-resins from benzoin, myrrha, and olibanum in pure state and also charged with 10% of metal oxide nanoparticles, TiO2, P25, Cu2O, and MoO3, were characterized by ultraviolet-visible (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray microanalysis (EDXMA), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Disks were 3D-printed into model geometries (10 × 5 mm) and the disk-diffusion methodology was used for the evaluation of antimicrobial and antifungal activity of materials in study against the clinical isolates: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. Due to their intrinsic properties, disks containing resins in pure state mostly prevent surface-associated growth; meanwhile, disks loaded with 10% oxides prevent planktonic growth of microorganisms in the susceptibility assay. The microscopy analysis showed that part of nanoparticles was encapsulated by the biopolymeric matrix of resins, in most cases remaining disorderly dispersed over the surface of resins. Thermal analysis shows that plant resins have peculiar characteristics, with a thermal behavior similar to commercial available semicrystalline polymers, although their structure consists of a mix of organic compounds. PMID:28811751

Preparation and characterization of fusion processed solid dispersions containing a viscous thermally labile polymeric carrier.

PubMed

Hughey, Justin R; Keen, Justin M; Miller, Dave A; Brough, Chris; McGinity, James W

2012-11-15

The primary aim of the present study was to investigate the ability of hydroxypropyl and methoxyl substituted cellulose ethers to stabilize supersaturated concentrations of itraconazole (ITZ), a poorly water-soluble weak base, after an acid-to-neutral pH transition. A secondary aim of the study was to evaluate the effect of fusion processes on polymer stability and molecular weight. Polymer screening studies showed that stabilization of ITZ supersaturation was related to the molecular weight of the polymer and levels of hydroxypropyl and methoxyl substitution. METHOCEL E50LV (E50LV), which is characterized as having a high melt viscosity, was selected for solid dispersion formulation studies. Hot-melt extrusion processing of E50LV based compositions resulted in high torque loads, low material throughput and polymer degradation. KinetiSol Dispersing, a novel fusion based processing technique, was evaluated as a method to prepare the solid dispersions with reduced levels of polymer degradation. An experimental design revealed that polymer molecular weight was sensitive to shearing forces and high temperatures. However, optimal processing conditions resulted in significantly reduced E50LV degradation relative to HME processing. The technique was effectively utilized to prepare homogenous solid solutions of E50LV and ITZ, characterized as having a single glass transition temperature over a wide range of drug loadings. All prepared compositions provided for a high degree of ITZ supersaturation stabilization. Copyright © 2012 Elsevier B.V. All rights reserved.

Bottom-up and Top-down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates.

PubMed

Chen, Jiali; Chen, Yuqi; Huang, Wencong; Wang, Hanning; Du, Yang; Xiong, Subin

2018-05-05

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and/or SDS were prepared by hot melt extrusion (HME), and characterized by PLM, DSC and FT-IR. Results indicated that Soluplus inhibited FLDP crystallization and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS(1:2:0.15∼0.3 and 1:3:0.2∼0.4) extrudates. Internal SDS (5%-10%) decreased Tgs of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the non-sink condition of 0.05%SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the non-sink condition. Copyright © 2018. Published by Elsevier Inc.

Humidification during invasive and noninvasive mechanical ventilation: 2012.

PubMed

Restrepo, Ruben D; Walsh, Brian K

2012-05-01

We searched the MEDLINE, CINAHL, and Cochrane Library databases for articles published between January 1990 and December 2011. The update of this clinical practice guideline is based on 184 clinical trials and systematic reviews, and 10 articles investigating humidification during invasive and noninvasive mechanical ventilation. The following recommendations are made following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scoring system: 1. Humidification is recommended on every patient receiving invasive mechanical ventilation. 2. Active humidification is suggested for noninvasive mechanical ventilation, as it may improve adherence and comfort. 3. When providing active humidification to patients who are invasively ventilated, it is suggested that the device provide a humidity level between 33 mg H(2)O/L and 44 mg H(2)O/L and gas temperature between 34°C and 41°C at the circuit Y-piece, with a relative humidity of 100%. 4. When providing passive humidification to patients undergoing invasive mechanical ventilation, it is suggested that the HME provide a minimum of 30 mg H(2)O/L. 5. Passive humidification is not recommended for noninvasive mechanical ventilation. 6. When providing humidification to patients with low tidal volumes, such as when lung-protective ventilation strategies are used, HMEs are not recommended because they contribute additional dead space, which can increase the ventilation requirement and P(aCO(2)). 7. It is suggested that HMEs are not used as a prevention strategy for ventilator-associated pneumonia.

Matrix-assisted cocrystallization (MAC) simultaneous production and formulation of pharmaceutical cocrystals by hot-melt extrusion.

PubMed

Boksa, Kevin; Otte, Andrew; Pinal, Rodolfo

2014-09-01

A novel method for the simultaneous production and formulation of pharmaceutical cocrystals, matrix-assisted cocrystallization (MAC), is presented. Hot-melt extrusion (HME) is used to create cocrystals by coprocessing the drug and coformer in the presence of a matrix material. Carbamazepine (CBZ), nicotinamide (NCT), and Soluplus were used as a model drug, coformer, and matrix, respectively. The MAC product containing 80:20 (w/w) cocrystal:matrix was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. A partial least squares (PLS) regression model was developed for quantifying the efficiency of cocrystal formation. The MAC product was estimated to be 78% (w/w) cocrystal (theoretical 80%), with approximately 0.3% mixture of free (unreacted) CBZ and NCT, and 21.6% Soluplus (theoretical 20%) with the PLS model. A physical mixture (PM) of a reference cocrystal (RCC), prepared by precipitation from solution, and Soluplus resulted in faster dissolution relative to the pure RCC. However, the MAC product with the exact same composition resulted in considerably faster dissolution and higher maximum concentration (∼five-fold) than those of the PM. The MAC product consists of high-quality cocrystals embedded in a matrix. The processing aspect of MAC plays a major role on the faster dissolution observed. The MAC approach offers a scalable process, suitable for the continuous manufacturing and formulation of pharmaceutical cocrystals. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Design and validation of inert homemade explosive simulants for X-ray-based inspection systems

NASA Astrophysics Data System (ADS)

Faust, Anthony A.; Nacson, Sabatino; Koffler, Bruce; Bourbeau, Éric; Gagne, Louis; Laing, Robin; Anderson, C. J.

2014-05-01

Transport Canada (TC), the Canadian Armed Forces, and other public security agencies have an interest in the assessment of the potential utility of advanced explosives detection technologies to aid in the detection and interdiction of commercial grade, military grade, and homemade or improvised explosives (HME or IE). The availability of suitable, non-hazardous, non-toxic, explosive simulants is of concern when assessing the potential utility of such detection systems. Lack of simulants limits the training opportunities, and ultimately the detection probability, of security personnel using these systems. While simulants for commercial and military grade explosives are available for a wide variety of detection technologies, the design and production of materials to simulate improvised explosives has not kept pace with this emerging threat. Funded by TC and the Canadian Safety and Security Program, Defence Research and Development Canada (DRDC), Visiontec Systems, and Optosecurity engaged in an effort to develop inert, non-toxic Xray interrogation simulants for IE materials such as ammonium nitrate, potassium chlorate, and triacetone triperoxide. These simulants were designed to mimic key X-ray interrogation-relevant material properties of real improvised explosives, principally their bulk density and effective atomic number. Different forms of the simulants were produced and tested, simulating the different explosive threat formulations that could be encountered by front line security workers. These simulants comply with safety and stability requirements, and as best as possible match form and homogeneity. This paper outlines the research program, simulant design, and validation.

CopM is a novel copper-binding protein involved in copper resistance in Synechocystis sp. PCC 6803

PubMed Central

Giner-Lamia, Joaquín; López-Maury, Luis; Florencio, Francisco J

2015-01-01

Copper resistance system in the cyanobacterium Synechocystis sp. PCC 6803 comprises two operons, copMRS and copBAC, which are expressed in response to copper in the media. copBAC codes for a heavy-metal efflux–resistance nodulation and division (HME-RND) system, while copMRS codes for a protein of unknown function, CopM, and a two-component system CopRS, which controls the expression of these two operons. Here, we report that CopM is a periplasmic protein able to bind Cu(I) with high affinity (KD ∼3 × 10−16). Mutants lacking copM showed a sensitive copper phenotype similar to mutants affected in copB, but lower than mutants of the two-component system CopRS, suggesting that CopBAC and CopM constitute two independent resistance mechanisms. Moreover, constitutive expression of copM is able to partially suppress the copper sensitivity of the copR mutant strain, pointing out that CopM per se is able to confer copper resistance. Furthermore, constitutive expression of copM was able to reduce total cellular copper content of the copR mutant to the levels determined in the wild-type (WT) strain. Finally, CopM was localized not only in the periplasm but also in the extracellular space, suggesting that CopM can also prevent copper accumulation probably by direct copper binding outside the cell. PMID:25545960

Bioactive Potential of 3D-Printed Oleo-Gum-Resin Disks: B. papyrifera, C. myrrha, and S. benzoin Loading Nanooxides-TiO2, P25, Cu2O, and MoO3.

PubMed

Horst, Diogo José; Tebcherani, Sergio Mazurek; Kubaski, Evaldo Toniolo; de Almeida Vieira, Rogério

2017-01-01

This experimental study investigates the bioactive potential of filaments produced via hot melt extrusion (HME) and intended for fused deposition modeling (FDM) 3D printing purposes. The oleo-gum-resins from benzoin, myrrha, and olibanum in pure state and also charged with 10% of metal oxide nanoparticles, TiO 2 , P25, Cu 2 O, and MoO 3 , were characterized by ultraviolet-visible (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray microanalysis (EDXMA), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Disks were 3D-printed into model geometries (10 × 5 mm) and the disk-diffusion methodology was used for the evaluation of antimicrobial and antifungal activity of materials in study against the clinical isolates: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli , and Candida albicans . Due to their intrinsic properties, disks containing resins in pure state mostly prevent surface-associated growth; meanwhile, disks loaded with 10% oxides prevent planktonic growth of microorganisms in the susceptibility assay. The microscopy analysis showed that part of nanoparticles was encapsulated by the biopolymeric matrix of resins, in most cases remaining disorderly dispersed over the surface of resins. Thermal analysis shows that plant resins have peculiar characteristics, with a thermal behavior similar to commercial available semicrystalline polymers, although their structure consists of a mix of organic compounds.

Pyrazolates advance cerium chemistry: a CeIII/CeIV redox equilibrium with benzoquinone.

PubMed

Werner, Daniel; Deacon, Glen B; Junk, Peter C; Anwander, Reiner

2017-05-16

Two stable cerium(iv) 3,5-dialkylpyrazolate complexes are presented, namely dimeric [Ce(Me 2 pz) 4 ] 2 (Me 2 pz = 3,5-dimethylpyrazolate) and monomeric Ce(tBu 2 pz) 4 (tBu 2 pz = 3,5-di-tert-butylpyrazolate) along with their trivalent counterparts [Ce(Me 2 pz) 3 ] and [Ce(tBu 2 pz) 3 ] 2 . All complexes were obtained from protonolysis reactions employing the silylamide precursors Ce[N(SiHMe 2 ) 2 ] 4 and Ce[N(SiMe 3 ) 2 ] 3 . Treatment of homoleptic Ce IV and Ce III Me 2 pz complexes with 1,4-hydroquinone (H 2 hq) or 1,4-benzoquinone (bq), respectively, ultimately gave the same trimetallic Ce III species via a cerium redox equilibrium. The Ce III complex Ce 3 (Me 2 pz) 5 (pchd) 2 (L) (pchd = 1,4-bis(3,5-dimethylpyrazol-1-yl)cyclohex-2,5-diene-1,4-diolato; L = Me 2 pzH or (thf) 2 ) results from a di-1,4-pyrazolyl attack on pre-coordinated bq. The reduction of bq by [Ce(Me 2 pz) 3 (thf)] 2 , and re-oxidation by the resulting Ce IV species was supported by UV-vis spectroscopic investigations. Comparisons with the redox-innocent complexes [Ln(Me 2 pz) 3 (thf)] 2 (Ln = La and Pr) revealed far less selective reactions with bq, giving hexametallic and octametallic rare-earth metal side products containing 2-Me 2 pz substituted hq ligands.

Metal Nanoparticles Covered with a Metal-Organic Framework: From One-Pot Synthetic Methods to Synergistic Energy Storage and Conversion Functions.

PubMed

Kobayashi, Hirokazu; Mitsuka, Yuko; Kitagawa, Hiroshi

2016-08-01

Hybrid materials composed of metal nanoparticles and metal-organic frameworks (MOFs) have attracted much attention in many applications, such as enhanced gas storage and catalytic, magnetic, and optical properties, because of the synergetic effects between the metal nanoparticles and MOFs. In this Forum Article, we describe our recent progress on novel synthetic methods to produce metal nanoparticles covered with a MOF (metal@MOF). We first present Pd@copper(II) 1,3,5-benzenetricarboxylate (HKUST-1) as a novel hydrogen-storage material. The HKUST-1 coating on Pd nanocrystals results in a remarkably enhanced hydrogen-storage capacity and speed in the Pd nanocrystals, originating from charge transfer from Pd nanocrystals to HKUST-1. Another material, Pd-Au@Zn(MeIM)2 (ZIF-8, where HMeIM = 2-methylimidazole), exhibits much different catalytic activity for alcohol oxidation compared with Pd-Au nanoparticles, indicating a design guideline for the development of composite catalysts with high selectivity. A composite material composed of Cu nanoparticles and Cr3F(H2O)2O{C6H3(CO2)3}2 (MIL-100-Cr) demonstrates higher catalytic activity for CO2 reduction into methanol than Cu/γ-Al2O3. We also present novel one-pot synthetic methods to produce composite materials including Pd/ZIF-8 and Ni@Ni2(dhtp) (MOF-74, where H4dhtp = 2,5-dihydroxyterephthalic acid).

FORESEE: Fully Outsourced secuRe gEnome Study basEd on homomorphic Encryption.

PubMed

Zhang, Yuchen; Dai, Wenrui; Jiang, Xiaoqian; Xiong, Hongkai; Wang, Shuang

2015-01-01

The increasing availability of genome data motivates massive research studies in personalized treatment and precision medicine. Public cloud services provide a flexible way to mitigate the storage and computation burden in conducting genome-wide association studies (GWAS). However, data privacy has been widely concerned when sharing the sensitive information in a cloud environment. We presented a novel framework (FORESEE: Fully Outsourced secuRe gEnome Study basEd on homomorphic Encryption) to fully outsource GWAS (i.e., chi-square statistic computation) using homomorphic encryption. The proposed framework enables secure divisions over encrypted data. We introduced two division protocols (i.e., secure errorless division and secure approximation division) with a trade-off between complexity and accuracy in computing chi-square statistics. The proposed framework was evaluated for the task of chi-square statistic computation with two case-control datasets from the 2015 iDASH genome privacy protection challenge. Experimental results show that the performance of FORESEE can be significantly improved through algorithmic optimization and parallel computation. Remarkably, the secure approximation division provides significant performance gain, but without missing any significance SNPs in the chi-square association test using the aforementioned datasets. Unlike many existing HME based studies, in which final results need to be computed by the data owner due to the lack of the secure division operation, the proposed FORESEE framework support complete outsourcing to the cloud and output the final encrypted chi-square statistics.

[The assessment of suicidal risk in the concept of the presuicidal syndrome, and the possibilities it provides for suicide prevention and therapy--review].

PubMed

Polewka, Andrzej; Chrostek Maj, Jan; Warchoł, Katarzyna; Groszek, Barbara

2005-01-01

To present Erwin Ringel's theory of the presuicidal syndrome as an instrument for the assessment of suicidal risk. The literature regarding the presuicidal syndrome was reviewed. As it is evident from the research and works by Ringel, and also from the works by other classics of suicidological literature, such as Farberow, Poldinger, Schneidmann, Beck, and B6hme, the discovery of the presuicidal syndrome has opened up new vistas for the therapy of suicidal tendencies. The knowledge of the nature of the presuicidal syndrome indicates that a specific "anti-suicide" therapy has to be applied. The principal aims of such a therapy include the removal of the patient's feeling of alienation by the creation of a good doctor-patient relationship, the creation of the conditions enabling the patient to vent his/her aggression verbally, the removal of the presuicidal narrowing of the patient's consciousness by the reinforcement of the effective, positive behaviour, and the stimulation of the patient's imagination towards the formulation of new aims in life. The concept of the presuicidal syndrome, although somewhat forgotten, still can enhance the understanding of the psychopathology of suicide, contribute to the effective identification of individuals endangered by the occurrence of suicidal tendencies, and contribute to the increase in the effectiveness of the therapy required. Finally, the present authors suggest that the presuicidal syndrome, as a special multifactor psychopathological phenomenon, should be recognized as a diagnostic unit, thus filling in the present gap in the classifications of mental illnesses.

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets.

PubMed

Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A

2016-11-20

This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Tracheostomy cannulas and voice prosthesis

PubMed Central

Kramp, Burkhard; Dommerich, Steffen

2011-01-01

Cannulas and voice prostheses are mechanical aids for patients who had to undergo tracheotomy or laryngectomy for different reasons. For better understanding of the function of those artificial devices, first the indications and particularities of the previous surgical intervention are described in the context of this review. Despite the established procedure of percutaneous dilatation tracheotomy e.g. in intensive care units, the application of epithelised tracheostomas has its own position, especially when airway obstruction is persistent (e.g. caused by traumata, inflammations, or tumors) and a longer artificial ventilation or special care of the patient are required. In order to keep the airways open after tracheotomy, tracheostomy cannulas of different materials with different functions are available. For each patient the most appropriate type of cannula must be found. Voice prostheses are meanwhile the device of choice for rapid and efficient voice rehabilitation after laryngectomy. Individual sizes and materials allow adaptation of the voice prostheses to the individual anatomical situation of the patients. The combined application of voice prostheses with HME (Head and Moisture Exchanger) allows a good vocal as well as pulmonary rehabilitation. Precondition for efficient voice prosthesis is the observation of certain surgical principles during laryngectomy. The duration of the prosthesis mainly depends on material properties and biofilms, mostly consisting of funguses and bacteries. The quality of voice with valve prosthesis is clearly superior to esophagus prosthesis or electro-laryngeal voice. Whenever possible, tracheostoma valves for free-hand speech should be applied. Physicians taking care of patients with speech prostheses after laryngectomy should know exactly what to do in case the device fails or gets lost. PMID:22073098

Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus® processed by hot melt extrusion.

PubMed

Albadarin, Ahmad B; Potter, Catherine B; Davis, Mark T; Iqbal, Javed; Korde, Sachin; Pagire, Sudhir; Paradkar, Anant; Walker, Gavin

2017-10-30

The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus ® polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was selected as the model drug. The ASDs were characterized by Powder X-Ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Solid State Nuclear Magnetic Resonance (ssNMR) and dissolution studies. The data showed that the ASDs were physically and chemically stable at 20°C and 50% RH over 12 months. PXRD results indicated that the ITZ in the ASDs was in the amorphous state and no recrystallization occurred. DSC scans confirmed that each formulation exhibited a single intermediate glass transition (T g ), around 96.4°C, indicating that ITZ was completely miscible in the polymeric blends of HPMCP and Soluplus ® at up to 30% (w/w) drug loading and that the two polymers were miscible with each other in the presence of ITZ. The FTIR analysis indicated the formation of strong hydrogen bonding between ITZ, HPMCP and Soluplus ® . The dissolution end-point of the ASDs was determined to be approximately 10 times greater than that of the crystalline ITZ. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

PubMed

Gioumouxouzis, Christos I; Chatzitaki, Aikaterini-Theodora; Karavasili, Christina; Katsamenis, Orestis L; Tzetzis, Dimitrios; Mystiridou, Emmanouela; Bouropoulos, Nikolaos; Fatouros, Dimitrios G

2018-06-14

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

Site specific solubility improvement using solid dispersions of HPMC-AS/HPC SSL--mixtures.

PubMed

Zecevic, Damir Elmar; Meier, Robin; Daniels, Rolf; Wagner, Karl-Gerhard

2014-07-01

Many upcoming drug candidates are pH-dependent poorly soluble weak bases in the pH range of the gastrointestinal tract. This often leads to a high in vivo variability and bioavailability issues. Aiming to overcome these limitations, the design of solid dispersions for site specific dissolution improvement or maintenance of a potent supersaturation over the entire gastro-intestinal pH-range, is proposed to assure a reliable drug therapy. Solid dispersions containing different ratios of Dipyridamole (DPD) or Griseofulvin (GRI) and the enteric polymer hydroxypropylmethylcellulose-acetate succinate (HPMC-AS) and the water soluble low-viscosity hydroxypropylcellulose (HPC-SSL) were prepared by hot melt extrusion (HME). The solid dispersions were evaluated for their solid state, dissolution characteristics applying a three pH-step dissolution method following an acidic to neutral pH transition and stability. The use of HPMC-AS in binary mixtures with DPD and GRI facilitated increased solubility and supersaturation at pH-controlled release of the preserved amorphous state of the dispersed drug, which even inverted the pH-dependent solubility profile of the weakly basic model drug (Dipyridamole). I.e. a potent site specific delivery system was created. With ternary solid dispersions of API, HPMC-AS and HPC-SSL, tailored release profiles with superior supersaturation over the applied pH-range could be obtained. At the same time, binary and ternary mixtures showed favorable stability properties at a temperature difference between glass transition temperature and the applied storage temperature of down to 16°C. Copyright © 2014 Elsevier B.V. All rights reserved.

A central review of histopathology reports after breast cancer neoadjuvant chemotherapy in the neo-tango trial

PubMed Central

Provenzano, E; Vallier, A-L; Champ, R; Walland, K; Bowden, S; Grier, A; Fenwick, N; Abraham, J; Iddawela, M; Caldas, C; Hiller, L; Dunn, J; Earl, H M

2013-01-01

Background: Neo-tAnGo, a National Cancer Research Network (NCRN) multicentre randomised neoadjuvant chemotherapy trial in early breast cancer, enroled 831 patients in the United Kingdom. We report a central review of post-chemotherapy histopathology reports on the surgical specimens, to assess the presence and degree of response. Methods: A central independent two-reader review (EP and HME) of histopathology reports from post-treatment surgical specimens was performed. The quality and completeness of pathology reporting across all centres was assessed. The reviews included pathological response to chemotherapy (pathological complete response (pCR); minimal residual disease (MRD); and lesser degrees of response), laterality, the number of axillary metastases and axillary nodes, and the type of surgery. A consensus was reached after discussion. Results: In all, 825 surgical reports from 816 patients were available for review. Out of 4125 data items there were 347 discrepant results (8.4% of classifications), which involved 281 patients. These involved grading of breast response (169 but only 9 involving pCR vs MRD); laterality (6); presence of axillary metastasis (35); lymph node counts (108); and type of axillary surgery (29). Excluding cases with pCR, only 45% of reports included any comment regarding response in the breast and 30% in the axillary lymph nodes. Conclusion: We found considerable variability in the completeness of reporting of surgical specimens within this national neoadjuvant breast cancer trial. This highlights the need for consensus guidelines among trial groups on histopathology reporting, and the participation of histopathologists throughout the development and analysis of neoadjuvant trials. PMID:23299526

Global approach for the validation of an in-line Raman spectroscopic method to determine the API content in real-time during a hot-melt extrusion process.

PubMed

Netchacovitch, L; Thiry, J; De Bleye, C; Dumont, E; Cailletaud, J; Sacré, P-Y; Evrard, B; Hubert, Ph; Ziemons, E

2017-08-15

Since the Food and Drug Administration (FDA) published a guidance based on the Process Analytical Technology (PAT) approach, real-time analyses during manufacturing processes are in real expansion. In this study, in-line Raman spectroscopic analyses were performed during a Hot-Melt Extrusion (HME) process to determine the Active Pharmaceutical Ingredient (API) content in real-time. The method was validated based on a univariate and a multivariate approach and the analytical performances of the obtained models were compared. Moreover, on one hand, in-line data were correlated with the real API concentration present in the sample quantified by a previously validated off-line confocal Raman microspectroscopic method. On the other hand, in-line data were also treated in function of the concentration based on the weighing of the components in the prepared mixture. The importance of developing quantitative methods based on the use of a reference method was thus highlighted. The method was validated according to the total error approach fixing the acceptance limits at ±15% and the α risk at ±5%. This method reaches the requirements of the European Pharmacopeia norms for the uniformity of content of single-dose preparations. The validation proves that future results will be in the acceptance limits with a previously defined probability. Finally, the in-line validated method was compared with the off-line one to demonstrate its ability to be used in routine analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

Tracheostomy cannulas and voice prosthesis.

PubMed

Kramp, Burkhard; Dommerich, Steffen

2009-01-01

Cannulas and voice prostheses are mechanical aids for patients who had to undergo tracheotomy or laryngectomy for different reasons. For better understanding of the function of those artificial devices, first the indications and particularities of the previous surgical intervention are described in the context of this review. Despite the established procedure of percutaneous dilatation tracheotomy e.g. in intensive care units, the application of epithelised tracheostomas has its own position, especially when airway obstruction is persistent (e.g. caused by traumata, inflammations, or tumors) and a longer artificial ventilation or special care of the patient are required. In order to keep the airways open after tracheotomy, tracheostomy cannulas of different materials with different functions are available. For each patient the most appropriate type of cannula must be found. Voice prostheses are meanwhile the device of choice for rapid and efficient voice rehabilitation after laryngectomy. Individual sizes and materials allow adaptation of the voice prostheses to the individual anatomical situation of the patients. The combined application of voice prostheses with HME (Head and Moisture Exchanger) allows a good vocal as well as pulmonary rehabilitation. Precondition for efficient voice prosthesis is the observation of certain surgical principles during laryngectomy. The duration of the prosthesis mainly depends on material properties and biofilms, mostly consisting of funguses and bacteries. The quality of voice with valve prosthesis is clearly superior to esophagus prosthesis or electro-laryngeal voice. Whenever possible, tracheostoma valves for free-hand speech should be applied. Physicians taking care of patients with speech prostheses after laryngectomy should know exactly what to do in case the device fails or gets lost.

Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice1

PubMed Central

Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

2014-01-01

Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1f/f;Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2 weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous by EXT mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss, osteoarthritis and HME. PMID:23958822

Integrated Data Collection Analysis (IDCA) Program - RDX Type II Class 5 Standard, Data Set 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandstrom, Mary M.; Brown, Geoffrey W.; Preston, Daniel N.

This document describes the results of the first reference sample material—RDX Type II Class 5—examined in the proficiency study for small-scale safety and thermal (SSST) testing of explosive materials for the Integrated Data Collection Analysis (IDCA) Program. The IDCA program is conducting proficiency testing on homemade explosives (HMEs). The reference sample materials are being studied to establish the accuracy of traditional explosives safety testing for each performing laboratory. These results will be used for comparison to results from testing HMEs. This effort, funded by the Department of Homeland Security (DHS), ultimately will put the issues of safe handling of thesemore » materials in perspective with standard military explosives. The results of the study will add SSST testing results for a broad suite of different HMEs to the literature, potentially suggest new guidelines and methods for HME testing, and possibly establish what are the needed accuracies in SSST testing to develop safe handling practices. Described here are the results for impact, friction, electrostatic discharge, and scanning calorimetry analysis of a reference sample of RDX Type II Class 5. The results from each participating testing laboratory are compared using identical test material and preparation methods wherever possible. Note, however, the test procedures differ among the laboratories. These results are then compared to historical data from various sources. The performers involved are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Air Force Research Laboratory/ RXQL (AFRL), Indian Head Division, Naval Surface Warfare Center, (IHD-NSWC), and Sandia National Laboratories (SNL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to understand how to compare results when test protocols are not identical.« less

Processing thermally labile drugs by hot-melt extrusion: The lesson with gliclazide.

PubMed

Huang, Siyuan; O'Donnell, Kevin P; Delpon de Vaux, Sophie M; O'Brien, John; Stutzman, John; Williams, Robert O

2017-10-01

The formation of molecularly dispersed amorphous solid dispersions by the hot-melt extrusion technique relies on the thermal and mechanical energy inputs, which can cause chemical degradation of drugs and polymeric carriers. Additionally, drug degradation may be exacerbated as drugs convert from a more stable crystalline form to a higher energy amorphous form. Therefore, it is imperative to study how drug degrades and evaluate methods to minimize drug degradation during the extrusion process. In this work, gliclazide was used as a model thermally labile drug for the degradation kinetics and process optimization studies. Preformulation studies were conducted using thermal analyses, and liquid chromatography-mass spectroscopy to identify drug degradation pathways and to determine initial extrusion conditions. Formulations containing 10% drug and 90% AFFINISOL™ HPMC HME 100LV were then extruded using a twin screw extruder, and the extrudates were characterized using X-ray powder diffraction, modulated dynamic scanning calorimetry, and potency testing to evaluate physicochemical properties. The energies of activation for both amorphous gliclazide, crystalline gliclazide, and gliclazide solution were calculated using the Arrhenius equation to further guide the extrusion optimization process. Preformulation studies identify two hydrolysis degradation pathways of gliclazide at elevated temperatures. The activation energy study indicates a significantly higher degradation rate for the amorphous gliclazide compared to the crystalline form. After optimization of the hot-melt extrusion process, including improved screw designs, machine setup, and processing conditions, gliclazide amorphous solid dispersion with ∼95% drug recovery was achieved. The ability to process thermally labile drugs and polymers using hot-melt extrusion will significantly expand the possible applications of this manufacturing process. Copyright © 2017 Elsevier B.V. All rights reserved.

The Synthesis, Characterization and Dehydrogenation of Sigma-Complexes of BN-Cyclohexanes

DOE PAGES

Kumar, Amit; Ishibashi, Jacob S. A.; Hooper, Thomas N.; ...

2015-11-25

The coordination chemistry of the 1,2-BN-cyclohexanes 2,2-R 2-1,2-B,N-C 4H 10 (R 2=HH, MeH, Me 2) with Ir and Rh metal fragments has been studied. This led to the solution (NMR spectroscopy) and solid-state (X-ray diffraction) characterization of [Ir(PCy 3) 2(H) 2(η 2η 2-H 2BNR 2C 4H 8)][BAr F 4] (NR 2=NH 2, NMeH) and [Rh( iPr 2PCH 2CH 2CH 2P iPr 2)(η 2η 2-H 2BNR 2C 4H 8)][BAr F 4] (NR 2=NH 2, NMeH, NMe 2). For NR 2=NH 2 subsequent metal-promoted, dehydrocoupling shows the eventual formation of the cyclic tricyclic borazine [BNC 4H 8] 3, via amino-borane and, tentativelymore » characterized using DFT/GIAO chemical shift calculations, cycloborazane intermediates. For NR 2=NMeH the final product is the cyclic amino-borane HBNMeC 4H 8. The mechanism of dehydrogenation of 2,2-H,Me-1,2-B,N-C 4H 10 using the {Rh( iPr 2PCH 2CH 2CH 2P iPr 2)} + catalyst has been probed. Catalytic experiments indicate the rapid formation of a dimeric species, [Rh 2( iPr 2PCH 2CH 2CH 2P iPr 2) 2H 5][BAr F 4]. Using the initial rate method starting from this dimer, a first-order relationship to [amine-borane], but half-order to [Rh] is established, which is suggested to be due to a rapid dimer–monomer equilibrium operating.« less

High speed radiometric measurements of IED detonation fireballs

NASA Astrophysics Data System (ADS)

Spidell, Matthew T.; Gordon, J. Motos; Pitz, Jeremey; Gross, Kevin C.; Perram, Glen P.

2010-04-01

Continuum emission is predominant in fireball spectral phenomena and in some demonstrated cases, fine detail in the temporal evolution of infrared spectral emissions can be used to estimate size and chemical composition of the device. Recent work indicates that a few narrow radiometric bands may reveal forensic information needed for the explosive discrimination and classification problem, representing an essential step in moving from "laboratory" measurements to a rugged, fieldable system. To explore phenomena not observable in previous experiments, a high speed (10μs resolution) radiometer with four channels spanning the infrared spectrum observed the detonation of nine home made explosive (HME) devices in the < 100lb class. Radiometric measurements indicate that the detonation fireball is well approximated as a single temperature blackbody at early time (0 < t <~ 3ms). The effective radius obtained from absolute intensity indicates fireball growth at supersonic velocity during this time. Peak fireball temperatures during this initial detonation range between 3000.3500K. The initial temperature decay with time (t <~ 10ms) can be described by a simple phenomenological model based on radiative cooling. After this rapid decay, temperature exhibits a small, steady increase with time (10 <~ t <~ 50ms) and peaking somewhere between 1000.1500K-likely the result of post-detonation combustion-before subsequent cooling back to ambient conditions . Radius derived from radiometric measurements can be described well (R2 > 0.98) using blast model functional forms, suggesting that energy release could be estimated from single-pixel radiometric detectors. Comparison of radiometer-derived fireball size with FLIR infrared imagery indicate the Planckian intensity size estimates are about a factor of two smaller than the physical extent of the fireball.

Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells.

PubMed

Lyall, Marcus J; Cartier, Jessy; Thomson, John P; Cameron, Kate; Meseguer-Ripolles, Jose; O'Duibhir, Eoghan; Szkolnicka, Dagmara; Villarin, Baltasar Lucendo; Wang, Yu; Blanco, Giovanny Rodriguez; Dunn, Warwick B; Meehan, Richard R; Hay, David C; Drake, Amanda J

2018-07-05

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in developed countries. An in vitro NAFLD model would permit mechanistic studies and enable high-throughput therapeutic screening. While hepatic cancer-derived cell lines are a convenient, renewable resource, their genomic, epigenomic and functional alterations mean their utility in NAFLD modelling is unclear. Additionally, the epigenetic mark 5-hydroxymethylcytosine (5hmC), a cell lineage identifier, is rapidly lost during cell culture, alongside expression of the Ten-eleven-translocation ( TET ) methylcytosine dioxygenase enzymes, restricting meaningful epigenetic analysis. Hepatocyte-like cells (HLCs) derived from human embryonic stem cells can provide a non-neoplastic, renewable model for liver research. Here, we have developed a model of NAFLD using HLCs exposed to lactate, pyruvate and octanoic acid (LPO) that bear all the hallmarks, including 5hmC profiles, of liver functionality. We exposed HLCs to LPO for 48 h to induce lipid accumulation. We characterized the transcriptome using RNA-seq, the metabolome using ultra-performance liquid chromatography-mass spectrometry and the epigenome using 5-hydroxymethylation DNA immunoprecipitation (hmeDIP) sequencing. LPO exposure induced an NAFLD phenotype in HLCs with transcriptional and metabolomic dysregulation consistent with those present in human NAFLD. HLCs maintain expression of the TET enzymes and have a liver-like epigenome. LPO exposure-induced 5hmC enrichment at lipid synthesis and transport genes. HLCs treated with LPO recapitulate the transcriptional and metabolic dysregulation seen in NAFLD and additionally retain TET expression and 5hmC. This in vitro model of NAFLD will be useful for future mechanistic and therapeutic studies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Authors.

Investigation of Y6Mn23 and YMn12 intermetallic alloys under high hydrogen pressure

NASA Astrophysics Data System (ADS)

Filipek, S. M.; Sato, R.; Kuriyama, N.; Tanaka, H.; Takeichi, N.

2010-03-01

Among three intermetallic compounds existing in Y-Mn system the YMn2 and Y6Mn23 can easily form interstitial hydrides while for YMn12 existence of hydride has never been reported. At moderate hydrogen pressure YMn2 and Y6Mn23 transform into YMn2H4.5 and Y6Mn23H25 respectively. At high hydrogen pressure the YMn2 (C15 or C14 parent structure) forms a unique YMn2H6 (s.g. Fm3m) complex hydride of fluorite structure in which one Mn atom Mn(1) and Y randomly occupy the 8c sites while second manganese (Mn2) in position 4a forms complex anion with 6 hydrogen atoms located in positions 24e. Formation of YMn2H6 independently of the structure of parent phase (C14 or C15) as well as occupation of the same site (8c) by Y and Mn(1) atoms suggested that also Y6Mn23 and YMn12 could transform into YMn2H6 - type hydride in which suitable number of Y atoms will be substituted by Mn(1) in the 8c positions. This assumption was confirmed by exposing R6Mn23 and RMn12 to 1 GPa of hydrogen pressure at 1000C. Formation of (RxMn2-x)MnH6 (where x = 18/29 or 3/13 for R6Mn23 and RMn12 hydrides respectively) was confirmed by XRD. Hydrogen concentration in both R6Mn23 and RMn12 based hydrides reached H/Me = 2 thus value two times higher than in R6Mn23H25.

The impact of health sector evolution plan on hospitalization and cesarean section rates in Iran: an interrupted time series analysis.

PubMed

Karami Matin, Behzad; Hajizadeh, Mohammad; Najafi, Farid; Homaie Rad, Enayatollah; Piroozi, Bakhtiar; Rezaei, Satar

2018-02-01

To investigate the effect of the health sector evolution plan (HSEP) on hospitalization and cesarean section (C-section) rates in Kermanshah province in the western region of Iran. Interrupted time series analysis. Hospital care system in Kermanshah province. Fifteen hospitals affiliated to Ministry of Health and Medical Education (MoHME) in Kermanshah province. Health sector evolution plan. Hospitalization rate and C-section rate. We observed a statistically significant increase in the hospitalization rate (12.9 hospitalizations per 10 000 population, P < 0.001) in the first month after the implementation of the HSEP. Compared with the monthly trend in hospitalization rate before the intervention, we found a significant increase of 0.70 hospitalizations per 10 000 population (P < 0.001) in monthly trend in hospitalization rate after the HSEP. Although the proportion of C-section from total deliveries decreased by 11% (P = 0.044) in the first month after the implementation of the HSEP, the proportion of C-section from total deliveries increased at the rate of 0.0017% (P = 0.001) per month during post-intervention period. We found an increase in the hospitalization rate after the intervention of HSEP. Although the C-section rate in the first month after the HSEP decreased, we observed an increasing trend in C-section rate over the study period; this implies that the HSEP did not promote vaginal delivery in Iran, which is outlined as one of the objectives of the intervention. © The Author(s) 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Mucilaginibacter antarcticus sp. nov., isolated from tundra soil.

PubMed

Zheng, Ruichen; Zhao, Yiming; Wang, Liqiu; Chang, Xulu; Zhang, Yumin; Da, Xuyang; Peng, Fang

2016-12-01

The novel, pale yellow bacterial strain, designated S14-88T, was isolated from a tundra soil near Antarctic Peninsula, South Shetland Islands, and its taxonomic position was investigated by a genotypic and phenotypic analysis. Cells were facultatively anaerobic, Gram-stain-negative, non-motile and rod-shaped. Growth occurred at 4-28 °C (optimum at 15 °C), at pH 7.0-8.0 (optimum at 7.0) and with 0-0.6 % (w/v) NaCl (optimum, no NaCl). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S14-88T formed a lineage within the genus Mucilaginibacter. The 16S rRNA gene sequence similarity between strain S14-88T and the type strains of related species ranged from 92.2 to 96.5 %, and the 16S rRNA gene sequence of S14-88T showed highest similarity of 96.5 % to Mucilaginibacter soyangensis HME6664T. The major cellular fatty acids of strain S14-88T were iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The major respiratory quinone was menaquinone MK-7, and the main polar lipid was phosphatidylethanolamine. The DNA G+C content of strain S14-88T was 42.3 mol%. On the basis of the evidence presented in this study, strain S14-88T is considered to represent a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter antarcticus sp. nov. is proposed. The type strain is S14-88T (=CCTCC AB 2015321T=KCTC 52232T).

Tailored on demand anti-coagulant dosing: an in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms.

PubMed

Arafat, Basel; Qinna, Nidal; Cieszynska, Milena; Forbes, Robert T; Alhnan, Mohamed A

2018-04-16

Coumarin therapy has been associated with high levels of inter- and intra-individual variation in the required dose to reach a therapeutic anticoagulation outcome. Therefore, a dynamic system that is able to achieve accurate delivery of a warfarin dose is of significant importance. Here we assess, the ability of 3D printing to fabricate and deliver tailored individualised precision dosing using an in-vitro model. Sodium warfarin loaded filaments were compounded using hot melt extrusion (HME) and further fabricated via fused deposition modelling (FDM) 3D printing to produce capsular-ovoid-shaped dosage forms loaded at 200 and 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague-Dawley rats. In vitro, warfarin release was faster at pH 1.2 in comparison to pH 2. A novel UV imaging approach indicated that the erosion of the methacrylate matrix was at a rate of 16.4 and 15.2 µm/min for horizontal and vertical planes respectively. In vivo, 3D printed forms were as proportionately effective as their comparative solution form in doubling plasma exposure following a doubling of warfarin dose (184% versus 192% respectively). The 3D printed ovoids showed a lower C max of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer T max (6 and 3.7 versus 4 and 1.5 h) in comparison to liquid formulation. This work demonstrates for the first time in vivo, the potential of FDM 3D printing to produce a tailored specific dosage form and to accurately titrate coumarin dose response to an individual patient. Copyright © 2018. Published by Elsevier B.V.

Humidification performance of humidifying devices for tracheostomized patients with spontaneous breathing: a bench study.

PubMed

Chikata, Yusuke; Oto, Jun; Onodera, Mutsuo; Nishimura, Masaji

2013-09-01

Heat and moisture exchangers (HMEs) are commonly used for humidifying respiratory gases administered to mechanically ventilated patients. While they are also applied to tracheostomized patients with spontaneous breathing, their performance in this role has not yet been clarified. We carried out a bench study to investigate the effects of spontaneous breathing parameters and oxygen flow on the humidification performance of 11 HMEs. We evaluated the humidification provided by 11 HMEs for tracheostomized patients, and also by a system delivering high-flow CPAP, and an oxygen mask with nebulizer heater. Spontaneous breathing was simulated with a mechanical ventilator, lung model, and servo-controlled heated humidifier at tidal volumes of 300, 500, and 700 mL, and breathing frequencies of 10 and 20 breaths/min. Expired gas was warmed to 37°C. The high-flow CPAP system was set to deliver 15, 30, and 45 L/min. With the 8 HMEs that were equipped with ports to deliver oxygen, and with the high-flow CPAP system, measurements were taken when delivering 0 and 3 L/min of dry oxygen. After stabilization we measured the absolute humidity (AH) of inspired gas with a hygrometer. AH differed among HMEs applied to tracheostomized patients with spontaneous breathing. For all the HMEs, as tidal volume increased, AH decreased. At 20 breaths/min, AH was higher than at 10 breaths/min. For all the HMEs, when oxygen was delivered, AH decreased to below 30 mg/L. With an oxygen mask and high-flow CPAP, at all settings, AH exceeded 30 mg/L. None of the HMEs provided adequate humidification when supplemental oxygen was added. In the ICU, caution is required when applying HME to tracheostomized patients with spontaneous breathing, especially when supplemental oxygen is required.

Humidification performance of 48 passive airway humidifiers: comparison with manufacturer data.

PubMed

Lellouche, François; Taillé, Solenne; Lefrançois, Frédéric; Deye, Nicolas; Maggiore, Salvatore Maurizio; Jouvet, Philippe; Ricard, Jean-Damien; Fumagalli, Bruno; Brochard, Laurent

2009-02-01

Heat and moisture exchangers (HMEs) are increasingly used in the ICU for gas conditioning during mechanical ventilation. Independent assessments of the humidification performance of HMEs are scarce. The aim of the present study was thus to assess the humidification performance of a large number of adult HMEs. We assessed 48 devices using a bench test apparatus that simulated real-life physiologic ventilation conditions. Thirty-two devices were described by the manufacturers as HMEs, and 16 were described as antibacterial filters. The test apparatus provided expiratory gases with an absolute humidity (AH) of 35 mg H(2)O/L. The AH of inspired gases was measured after steady state using the psychrometric method. We performed three hygrometric measurements for each device, measured their resistance, and compared our results with the manufacturer data. Of the 32 HMEs tested, only 37.5% performed well (>or= 30 mg H(2)O/L), while 25% performed poorly (< 25 mg H(2)O/L). The mean difference (+/- SD) between our measurements and the manufacturer data was 3.0 +/- 2.7 mg H(2)O/L for devices described as HMEs (maximum, 8.9 mg H(2)O/L) [p = 0.0001], while the mean difference for 36% of the HMEs was > 4 mg H(2)O/L. The mean difference for the antibacterial filters was 0.2 +/- 1.4 mg H(2)O/L. The mean resistance of all the tested devices was 2.17 +/- 0.70 cm H(2)O/L/s. Several HMEs performed poorly and should not be used as HMEs. The values determined by independent assessments may be lower than the manufacturer data. Describing a device as an HME does not guarantee that it provides adequate humidification. The performance of HMEs must be verified by independent assessment.

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of change of matrix crystallinity and polymorphism on ovalbumin release from lipid-based implants.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-05-30

The objectives of this study were to prepare lipid-based implants by hot melt extrusion (HME) for the prolonged release of ovalbumin (OVA), and to relate protein release to crystallinity and polymorphic changes of the lipid matrix. Two lipids, glycerol tristearate and hydrogenated palm oil, with different composition and degree of crystallinity were studied. Solid OVA was dispersed within the lipid matrixes, which preserved its stability during extrusion. This was partially attributed to a protective effect of the lipidic matrix. The incorporation of OVA decreased the mechanical strength of the implants prepared with the more crystalline matrix, glycerol tristearate, whereas it remained comparable for the hydrogenated palm oil because of stronger physical and non-covalent interactions between the protein and this lipid. This was also the reason for the faster release of OVA from the glycerol tristearate matrix when compared to the hydrogenated palm oil (8 vs. 28 weeks). Curing induced and increased crystallinity, and changes in the release rate, especially for the more crystalline matrix. In this case, both an increase and a decrease in release, were observed depending on the tempering condition. Curing at higher temperatures induced a melt-mediated crystallization and solid state transformation of the glycerol tristearate matrix and led to rearrangements of the inner structure with the formation of larger pores, which accelerated the release. In contrast, changes in the hydrogenated palm oil under the same curing conditions were less noticeable leading to a more robust formulation, because of less polymorphic changes over time. This study helps to understand the effect of lipid matrix composition and crystallinity degree on the performance of protein-loaded implants, and to establish criteria for the selection of a lipid carrier depending on the release profile desired. Copyright © 2018. Published by Elsevier B.V.

Human impacts of droughts, floods and other extremes in South Moravia

NASA Astrophysics Data System (ADS)

Dolák, Lukáš; Brázdil, Rudolf; Řezníčková, Ladislava; Valášek, Hubert; Chromá, Kateřina

2015-04-01

Chronicles and taxation records related to tax relief for farmers whose livelihoods were affected by droughts, floods and other hydrometeorological extremes (HMEs) in South Moravia (the Czech Republic) in the 17th-20th centuries are used to study the impacts of HMEs on the socio-economic situation of the farmers. The first flood event was reported in 1652 on the River Morava and extraordinary dry years were documented since 1718 - in this year the River Dyje totally dried up. Moreover, downpours, hailstorms, windstorms, late frosts and blizzards caused a great damage during the period studied as well and in many cases had a negative effect to human society. The impacts of HMEs are here classified into three categories: agricultural production, material property and the socio-economic situation of individual farmers. Direct impacts took the form of losses to property, supplies and farming equipment, and further of bad field and fruit yields, depletion of livestock, damage to fields and meadows, lack of water for daily use, watermills and transport and increased threat of wildfires. Simple lack of income, debt, impoverishment, reduction in livestock and deterioration in field fertility were among the longer-term effects. Impacts are discussed with respect to approaches to mitigation of the negative effects of HMEs and to problems associated with obtaining support and in terms of a hierarchy of consequent impacts. A great number of records related to HMEs, preserved in the Moravian Land Archives in Brno and other district South Moravian archives, represents a rich source of data allowing re-discovering of historical natural disasters. The paper embodies a methodological approach that is intended for the analysis of HME impacts in South Moravia from the 17th to the 20th centuries.

A new age model for the early-middle Miocene in the North Alpine Foreland Basin

NASA Astrophysics Data System (ADS)

Reichenbacher, Bettina; Krijgsman, Wout; Pippèrr, Martina; Sant, Karin; Kirscher, Uwe

2016-04-01

The establishment of high-resolution age models for sedimentary successions is crucial for numerous research questions in the geosciences and related disciplines. Such models provide an absolute chronology that permits precise dating of depositional episodes and related processes such as mountain uplift or climate change. Recently, our work in the Miocene sediments of the North Alpine Foreland Basin (NAFB) has revealed a significantly younger age (16.6 Myr) for sediments that were thought to have been deposited 18 Myr ago. This implies that a fundamentally revised new age model is needed for the entire suite of lower-middle Miocene sedimentary rocks in the NAFB (20 to 15-Myr). Our new data also indicate that previously published reconstructions of early-middle Miocene palaeogeography, sedimentation dynamics, mountain uplift and climate change in the NAFB all require a critical review and revision. Further, the time-span addressed is of special interest, since it encompasses the onset of a global warming phase. However, it appears that a fundamentally revised new age model for the entire suite of lower-middle Miocene sedimentary rocks in the NAFB can only be achieved based on a 500 m deep drilling in the NAFB for which we currently seek collaboration partners to develop a grant application to the International Continental Deep Drilling Program (ICDP). Reference: Reichenbacher, B., W. Krijgsman, Y. Lataster, M. Pippèrr, C. G. C. Van Baak, L. Chang, D. Kälin, J. Jost, G. Doppler, D. Jung, J. Prieto, H. Abdul Aziz, M. Böhme, J. Garnish, U. Kirscher, and V. Bachtadse. 2013. A new magnetostratigraphic framework for the Lower Miocene (Burdigalian/Ottnangian, Karpatian) in the North Alpine Foreland Basin. Swiss Journal of Geosciences 106:309-334.

Cycloheptatrienyl zirconium sandwich complexes with lewis basic phospholyl ligands (phosphatrozircenes): synthesis, structure, bonding and coordination chemistry.

PubMed

Glöckner, Andreas; Bannenberg, Thomas; Büschel, Susanne; Daniliuc, Constantin G; Jones, Peter G; Tamm, Matthias

2011-05-23

The transmetalation reaction between [(η(7) -C(7) H(7) )ZrCl(tmeda)] (1; tmeda=N,N,N',N'-tetramethylethylenediamine) and various phospholide anions leads to a new class of mixed sandwich complexes: [(η(7)-C(7)H(7))Zr(η(5)-C(4)PMe(4))] (2), [(η(7)-C(7)H(7))Zr(η(5)-C(4)PH(2)Me(2))] (3) and [(η(7)-C(7)H(7))Zr(η(5)-C(4)PPhHMe(2))] (4). The presence of Lewis basic phosphorus atoms and Lewis acidic zirconium atoms allows ambiphilic behaviour to be observed, and X-ray diffraction analysis reveals dimeric arrangements for 2 and 3 with long intermolecular Zr-P bonds, whereas 4 remains monomeric in the solid state. DFT calculations indicate that the metal-phosphorus interaction is weak, and accordingly, complexes 2-4 act as monodentate ligands upon reaction with [W(CO)(5)(thf)]. The resulting complexes [W(CO)(5)(L)] 5-7 (L=2-4) were studied by IR spectroscopy and compared with the [W(CO)(5) ] complex 9, containing the phosphane-functionalised trozircene [(η(7)-C(7)H(7))Zr(η(5)-C(5)H(4)PPh(2))] (8). They all show a close resemblance to simple phosphanes, such as PMe(3) , although molecular orbital analysis of 2 reveals that the free electron pair in the phosphatrozircenes is not the HOMO. Four equivalents of 2 can replace 1,4-cyclooctadiene (COD) in [Ni(cod)(2)] to form the homoleptic, distorted tetrahedral complex [Ni{2}(4)] (10). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flavobacterium hibisci sp. nov., isolated from the rhizosphere of Hibiscus syriacus L.

PubMed

Moya, Gabriela; Yan, Zheng-Fei; Trinh, Huan; Won, Kyung-Hwa; Yang, Jung-Eun; Kook, Moo-Chang; Yi, Tae-Hoo

2017-04-01

A Gram-stain-negative, smooth, bright-yellow-pigmented, rod-shaped bacterial strain, slightly motile by gliding, catalase- and oxidase-positive and aerobic, but growing weakly under anaerobic conditions, was isolated from the rhizosphere of the flower mugunghwa (Hibiscus syriacus L.) located in Kyung Hee University, Yongin, Gyeonggi, South Korea. The strain named THG-HG1.4T grew at 15-35 °C, pH 6.5-9.0 and in the presence of 0-2.5 % (w/v) NaCl. The phylogenetic analysis based on 16S rRNA gene sequence showed that strain THG-HG1.4T was most closely related to Flavobacterium gyeonganense HME7524T (98.83 %) and Flavobacterium arsenitoxidans S2-3HT (97.28 %). The DNA G+C content of strain THG-HG1.4T was 41.2 mol%. In DNA-DNA hybridization, the DNA-DNA relatedness between strain THG-HG1.4T and its closest phylogenetic neighbour was below 64.1 %. The predominant isoprenoid quinone detected in strain THG-HG1.4T was menaquinone-6 (MK-6). The major polar lipids were found to be phosphatidylethanolamine, three unidentified lipids, two unidentified glycolipids and an unidentified aminolipid. The major fatty acids were identified as iso-C15 : 0, iso-C15 : 0 3-OH, C16 : 0, iso-C17 : 0 3-OH and summed feature 3. Thus, based on the report of the phenotypic, genotypic and phylogenetic characterization of strain THG-HG1.4T, it has been concluded that the novel isolate represents a novel species of the genus Flavobacterium.Flavobacterium hibisci sp. nov. is proposed, with THG-HG1.4T (=KACC 18852T=CCTCC AB 2016178T) as the type strain.

Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy.

PubMed

Okwuosa, Tochukwu C; Pereira, Beatriz C; Arafat, Basel; Cieszynska, Milena; Isreb, Abdullah; Alhnan, Mohamed A

2017-02-01

Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing. The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers. Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient's needs.

Gratkorn - A new late Middle Miocene vertebrate fauna from Styria (Late Sarmatian, Austria)

NASA Astrophysics Data System (ADS)

Gross, M.; Böhme, M.; Prieto, J.

2009-04-01

Integrated stratigraphic approaches provide precise correlations of global standard stages with regional Paratethys stages. Nevertheless, higher resolution stratigraphic matching of terrestrial deposits remains challenging due to the lack of a practical continental biostratigraphy. The mostly used tool for biostratigraphic correlation of non-marine deposits in the Old World is still the concept of Neogene Mammal-zones (MN-zones). However, at higher biostratigraphic resolution (<1 million years) this concept looses its practicability and has to be replaced by a taxon-range-zonation. To solve this problem a higher number of independently dated small-mammal localities are needed. This is especially crucial for the late Middle to earliest Late Miocene, for which vertebrate faunas in the (Central-)Paratethyan area rare. Recently, a new vertebrate fauna was discovered at the locality Gratkorn (clay pit St. Stefan) just beyond the northwestern margin of the Styrian Basin (Gratkorn Basin; 10 km NW Graz; 15°20'55"E/47°08'15"N). The fauna originates from a c. 0.5 m thick hydromorphic paleosol, underlain by fluvial sands and gravels and topped by c. 15 m thick limnic pelites (Gross, 2008). Sedimentological data as well as the gastropod (Harzhauser et al., 2008) and vertebrate faunas point to a highly structured, more or less vegetated alluvial fan/braided river landscape. Active and abandoned fluvial channels, moist floodplain-soils and ephemeral ponds but also nearby dryer open areas and limestone screes of the up-lifting Palaeozoic basement offered a wide range of habitats. The occurrence of xero- and thermophile terrestrial gastropods and ectothermic vertebrates correspond well with the late Middle/early Late Miocene dry-spell in Central Europe (Böhme et al., 2008). Furthermore, an overall semiarid climate is supported by the development of a calcrete horizon c. 0.6 m below the fossiliferous horizon. The vertebrate remains are irregularly distributed throughout the paleosol. Although articulated skeletons are missing, skeletal elements belonging to the same individual were found frequently close to each other. Many bones are broken and display imprints of gnawing structures. These taphonomic features point to a longer surface exposure before burial without considerable transportation. Trampling and the activity of scavengers (crunching, displacement of cadavers) are probable. Locally small- and medium-sized mammal remains (jaws and postcranial elements) of e.g., hamsters, flying squirrels, gymnures and shrews are concentrated, perhaps demonstrating feeding places of carnivores or more probably of birds of prey. Nonetheless, from geologic point of view, this paleosol represents an event horizon, which accumulated rapidly maybe within tens or hundreds of years. The vertebrate fauna comprises of scattered fishes (e.g. cyprinids, gobiids, ?channids), amphibians (e.g. salamandrids, ranids, discoglossids, bufonids, pelobatids,), reptiles (scincids, lacertids, gekkonids, anguids, varanids, colubrids, testudinids, emydids), birds (coliiformes), rodents and lagomorphs (cricetids, glirids, eomyids, sciurids, castorids), insectivores and chiropterans (erinaceids, soricids, talpids), and large mammals (suids, tragulids, moschids, cervids, ?palaeomerycids, equids, chalicotheriids, rhinos, proboscidians, carnivors). Litho- and biostratigraphy (terrestrial gastropods) as well as magnetostratigraphic data and the sequence stratigraphic and geodynamic frame indicate an age of 12-12.2 Ma (early Late Sarmatian s.str., chron 5An.1n) for the locality. Therefore, Gratkorn is one of richest and most complete fauna of the late Middle Miocene of Central Europe and will be confidentially one of the key faunas for a high-resolution continental biostratigraphy and the comprehension of the faunal succession and interchanges near the Middle/Late Miocene transition. Acknowledgements This is a preliminary overview of the Gratkorn vertebrate fauna. Several taxa are still under investigation. We are especially grateful to Gudrun Daxner-Höck, Ursula Göhlich (both Natural History Museum Vienna) and Getrud Rössner (University of Munich) for their comments to the rodents, ruminants, proboscidians and bird remains. References Böhme, M., Ilg, A., Winklhofer, M. 2008. Late Miocene "washhouse" climate in Europe.- Earth and Planetary Science Letters, 275: 393-401. Gross, M., 2008. A limnic ostracod fauna from the surroundings of the Central Paratethys (Late Middle Miocene/Early Late Miocene; Styrian Basin; Austria).- Palaeogeography, Palaeoclimatology, Palaeoecology, 264/3-4: 263-276. Harzhauser, M., Gross, M. & Binder, H., 2008. Biostratigraphy of Middle Miocene (Sarmatian) wetland systems in an Eastern Alpine intramontane basin (Gratkorn Basin, Austria): the terrestrial gastropod approach.- Geologica Carpathica, 59/1: 45-58.

Leprosy in Medieval Denmark--osteological and epidemiological analyses.

PubMed

Boldsen, Jesper L

2009-12-01

A total of 3033 skeletons from 11 medieval Danish cemeteries and 99 skeletons from the North Scandinavian medieval site of Westerhus were examined for seven lesions indicative of leprosy. The seven lesions are: rounding to the edge of the nasal aperture, degeneration of spina nasalis anterior, degeneration of the alveolar process of the pre-maxilla, porosity or perforation of the palatine process of maxilla, sub-periostal exostoses on the fibula, general swelling of the shaft of the fibula, and degeneration of the 5th metatarsal bone. The dichotomous scores of these lesions were used to estimate sensitivity and specificity of the lesion scores in relation to leprosy and to estimate sample point prevalence of leprosy at death among adults. In turn the estimates of sensitivity and specificity were used to calculate an individual comprehensive statistic, lamda, indicating leprosy status. Among adults the lamda statistic did not associate with age at death, but this cannot be taken as a sign of lack of selective mortality for leprosy but a combination of the opposing effects of long waiting time before developing leprosy related lesions and short survival with these lesions. In urban communities sufferers of leprosy were institutionalized when the leprosarium was established (in Odense around 1275); in rural communities this did not happen but the pattern of burial does indicate an internal segregation of sufferers. In the early Middle Ages (AD 1150-1350) the point prevalence at death among adults of leprosy was higher in rural (25-40 percent) than in urban (10-20 percent) communities, and villages close to town showed lower frequencies of leprosy than villages situated further away from these centers. Leprosy declined in the late Middle Ages, first in towns and cities, later in rural communities. In Odense and Malmö it appears that leprosy was effectively eliminated by 1350 whereas there were still sufferers of leprosy at Øm Kloster around 1550. Leprosy appears to have been less common in North Scandinavia than in South Scandinavia, and there are some indications that leprosy was much more common in the Sámi population than in the North population of North Scandinavia. It is suggested that the rapid and early decline of leprosy in the towns was caused by the breaking of chains of infection by institutionalizing the most affected sufferers from leprosy. In rural communities it is suggested that the later decline of leprosy was brought about by a natural vaccination with the active substance in the Calmette vaccine, Mycobacterium bovis.

Health Sector Evolution Plan in Iran; Equity and Sustainability Concerns.

PubMed

Moradi-Lakeh, Maziar; Vosoogh-Moghaddam, Abbas

2015-08-31

In 2014, a series of reforms, called as the Health Sector Evolution Plan (HSEP), was launched in the health system of Iran in a stepwise process. HSEP was mainly based on the fifth 5-year health development national strategies (2011-2016). It included different interventions to: increase population coverage of basic health insurance, increase quality of care in the Ministry of Health and Medical Education (MoHME) affiliated hospitals, reduce out-of-pocket (OOP) payments for inpatient services, increase quality of primary healthcare, launch updated relative value units (RVUs) of clinical services, and update tariffs to more realistic values. The reforms resulted in extensive social reaction and different professional feedback. The official monitoring program shows general public satisfaction. However, there are some concerns for sustainability of the programs and equity of financing. Securing financial sources and fairness of the financial contribution to the new programs are the main concerns of policy-makers. Healthcare providers' concerns (as powerful and influential stakeholders) potentially threat the sustainability and efficiency of HSEP. Previous experiences on extending health insurance coverage show that they can lead to a regressive healthcare financing and threat financial equity. To secure financial sources and to increase fairness, the contributions of people to new interventions should be progressive by their income and wealth. A specific progressive tax would be the best source, however, since it is not immediately feasible, a stepwise increase in the progressivity of financing must be followed. Technical concerns of healthcare providers (such as nonplausible RVUs for specific procedures or nonefficient insurance-provider processes) should be addressed through proper revision(s) while nontechnical concerns (which are derived from conflicting interests) must be responded through clarification and providing transparent information. The requirements of HSEP and especially the key element of progressive tax should be considered properly in the coming sixth national development plan (2016-2021). © 2015 by Kerman University of Medical Sciences.

Isolation, characterization and cloning of a cDNA encoding a new antifungal defensin from Phaseolus vulgaris L. seeds.

PubMed

Games, Patrícia D; Dos Santos, Izabela S; Mello, Erica O; Diz, Mariângela S S; Carvalho, André O; de Souza-Filho, Gonçalo A; Da Cunha, Maura; Vasconcelos, Ilka M; Ferreira, Beatriz Dos S; Gomes, Valdirene M

2008-12-01

The PvD1 defensin was purified from Phaseolus vulgaris (cv. Pérola) seeds, basically as described by Terras et al. [Terras FRG, Schoofs HME, De Bolle MFC, Van Leuven F, Ress SB, Vanderleyden J, Cammue BPA, Broekaer TWF. Analysis of two novel classes of plant antifungal proteins from radish (Raphanus sativus L.) seeds. J Biol Chem 1992;267(22):15301-9], with some modifications. A DEAE-Sepharose, equilibrated with 20mM Tris-HCl, pH 8.0, was initially utilized for the separation of peptides after ammonium sulfate fractionation. The basic fraction (the non-retained peak) obtained showed the presence of one unique band in SDS-Tricine gel electrophoresis with a molecular mass of approximately 6kDa. The purification of this peptide was confirmed after a reverse-phase chromatography in a C2/C18 column by HPLC, where once again only one peak was observed and denominated H1. H1 was submitted to N-terminal sequencing and the comparative analysis in databanks revealed high similarity with sequences of different defensins isolated from other plants species. The N-terminal sequence of the mature defensin isolated was used to produce a degenerated primer. This primer allowed the amplification of the defensin cDNA by RT-PCR from mRNA of P. vulgaris seeds. The sequence analysis of the cloned cDNA, named PVD1, demonstrated 314bp encoding a polypeptide of 47 amino acids. The deduced peptide presented high similarity with plant defensins of Vigna unguiculata (93%), Cicer arietinum (95%) and Pachyrhizus erosus (87%). PvD1 inhibited the growth of the yeasts, Candida albicans, Candida parapsilosis, Candida tropicalis, Candida guilliermondii, Kluyveromyces marxiannus and Saccharomyces cerevisiae. PvD1 also presented an inhibitory activity against the growth of phytopathogenic fungi including Fusarium oxysporum, Fusarium solani, Fusarium lateritium and Rizoctonia solani.

Integrated Data Collection Analysis (IDCA) Program - AN and Bullseye Smokeless Powder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandstrom, Mary M.; Brown, Geoffrey W.; Preston, Daniel N.

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of ammonium nitrate (AN) mixed with Bullseye® smokeless powder (Gunpowder). The participants found the AN/Gunpowder to: 1) have a range of sensitivity to impact, comparable to or less than RDX, 2) be fairly insensitive to friction as measured by BAM and ABL, 3) have a range for ESD, from insensitive to more sensitive than PETN, and 4) have thermal sensitivity aboutmore » the same as PETN and Gunpowder. This effort, funded by the Department of Homeland Security (DHS), is putting the issues of safe handling of these materials in perspective with standard military explosives. The study is adding SSST testing results for a broad suite of different HMEs to the literature. Ultimately the study has the potential to suggest new guidelines and methods and possibly establish the SSST testing accuracies needed when developing safe handling practices for HMEs. Each participating testing laboratory uses identical test materials and preparation methods. Note, however, the test procedures differ among the laboratories. The testing performers involved are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Indian Head Division, Naval Surface Warfare Center, (NSWC IHD), Sandia National Laboratories (SNL), and Air Force Research Laboratory (AFRL/RXQL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to compare results when these testing variables cannot be made consistent. Keywords: Small-scale safety testing, proficiency test, impact-, friction-, spark discharge-, thermal testing, round-robin test, safety testing protocols, HME, RDX, potassium perchlorate, potassium chlorate, sodium chlorate, sugar, dodecane, PETN, carbon, ammonium nitrate, Gunpowder, Bullseye® smokeless powder.« less

Creating Drug Solubilization Compartments via Phase Separation in Multicomponent Buccal Patches Prepared by Direct Hot Melt Extrusion-Injection Molding.

PubMed

Alhijjaj, Muqdad; Bouman, Jacob; Wellner, Nikolaus; Belton, Peter; Qi, Sheng

2015-12-07

Creating in situ phase separation in solid dispersion based formulations to allow enhanced functionality of the dosage form, such as improving dissolution of poorly soluble model drug as well as being mucoadhesive, can significantly maximize the in vitro and in vivo performance of the dosage form. This formulation strategy can benefit a wide range of solid dosage forms for oral and alternative routes of delivery. This study using buccal patches as an example created separated phases in situ of the buccal patches by selecting the excipients with different miscibility with each other and the model drug. The quaternary dispersion based buccal patches containing PEG, PEO, Tween 80, and felodipine were prepared by direct hot melt extrusion-injection molding (HME-IM). The partial miscibility between Tween 80 and semicrystalline PEG-PEO led to the phase separation after extrusion. The Tween phases acted as drug solubilization compartments, and the PEG-PEO phase had the primary function of providing mucoadhesion and carrier controlled dissolution. As felodipine was preferably solubilized in the amorphous regions of PEG-PEO, the high crystallinity of PEG-PEO resulted in an overall low drug solubilizing capacity. Tween 80 was added to improve the solubilization capacity of the system as the model drug showed good solubility in Tween. Increasing the drug loading led to the supersaturation of drug in Tween compartments and crystalline drug dispersed in PEG-PEO phases. The spatial distribution of these phase-separated compartments was mapped using X-ray micro-CT, which revealed that the domain size and heterogeneity of the phase separation increased with increasing the drug loading. The outcome of this study provides new insights into the applicability of in situ formed phase separation as a formulation strategy for the delivery of poorly soluble drugs and demonstrated the basic principle of excipient selection for such technology.

Influence of ambient temperature and minute ventilation on passive and active heat and moisture exchangers.

PubMed

Lellouche, François; Qader, Siham; Taillé, Solenne; Lyazidi, Aissam; Brochard, Laurent

2014-05-01

During invasive mechanical ventilation, inspired gases must be humidified. We previously showed that high ambient temperature greatly impaired the hygrometric performance of heated wire-heated humidifiers. The aim of this bench and clinical study was to assess the humidification performance of passive and active heat and moisture exchangers (HMEs) and the impact of ambient temperature and ventilator settings. We first tested on the bench a device with passive and active humidification properties (Humid-Heat, Teleflex), and 2 passive hydrophobic/hygroscopic HMEs (Hygrobac and Hygrobac S, Tyco Healthcare). The devices were tested at 3 different ambient temperatures (from 22 to 30 °C), and at 2 minute ventilation settings (10 and 20 L/min). Inspired gas hygrometry was measured at the Y-piece with the psychrometric method. In addition to the bench study, we measured the hygrometry of inspired gases in 2 different clinical studies. In 15 mechanically ventilated patients, we evaluated Humid-Heat at different settings. Additionally, we evaluated Humid-Heat and compared it with Hygrobac in a crossover study in 10 patients. On the bench, with the Hygrobac and Hygrobac S the inspired absolute humidity was ∼ 30 mg H2O/L, and with the Humid-Heat, slightly < 35 mg H2O/L. Ambient temperature and minute ventilation did not have a clinically important difference on the performance of the tested devices. During the clinical evaluation, Humid-Heat provided inspired humidity in a range from 28.5 to 42.0 mg H2O/L, depending on settings, and was only weakly influenced by the patient's body temperature. In this study both passive and active HMEs had stable humidification performance with negligible influence of ambient temperature and minute ventilation. This contrasts with previous findings with heated wire-heated humidifiers. Although there are no clear data demonstrating that higher humidification impacts outcomes, it is worth noting that humidity was significantly higher with the active HME.

Health Sector Evolution Plan in Iran; Equity and Sustainability Concerns

PubMed Central

Moradi-Lakeh, Maziar; Vosoogh-Moghaddam, Abbas

2015-01-01

In 2014, a series of reforms, called as the Health Sector Evolution Plan (HSEP), was launched in the health system of Iran in a stepwise process. HSEP was mainly based on the fifth 5-year health development national strategies (2011-2016). It included different interventions to: increase population coverage of basic health insurance, increase quality of care in the Ministry of Health and Medical Education (MoHME) affiliated hospitals, reduce out-of-pocket (OOP) payments for inpatient services, increase quality of primary healthcare, launch updated relative value units (RVUs) of clinical services, and update tariffs to more realistic values. The reforms resulted in extensive social reaction and different professional feedback. The official monitoring program shows general public satisfaction. However, there are some concerns for sustainability of the programs and equity of financing. Securing financial sources and fairness of the financial contribution to the new programs are the main concerns of policy-makers. Healthcare providers’ concerns (as powerful and influential stakeholders) potentially threat the sustainability and efficiency of HSEP. Previous experiences on extending health insurance coverage show that they can lead to a regressive healthcare financing and threat financial equity. To secure financial sources and to increase fairness, the contributions of people to new interventions should be progressive by their income and wealth. A specific progressive tax would be the best source, however, since it is not immediately feasible, a stepwise increase in the progressivity of financing must be followed. Technical concerns of healthcare providers (such as nonplausible RVUs for specific procedures or nonefficient insurance-provider processes) should be addressed through proper revision(s) while nontechnical concerns (which are derived from conflicting interests) must be responded through clarification and providing transparent information. The requirements of HSEP and especially the key element of progressive tax should be considered properly in the coming sixth national development plan (2016-2021). PMID:26673172

In vitro and in vivo evaluation of a new active heat moisture exchanger

PubMed Central

Chiumello, Davide; Pelosi, Paolo; Park, Gilbert; Candiani, Andrea; Bottino, Nicola; Storelli, Ezio; Severgnini, Paolo; D'Onofrio, Dunia; Gattinoni, Luciano; Chiaranda, Massimo

2004-01-01

Introduction In order to improve the efficiency of heat moisture exchangers (HMEs), new hybrid humidifiers (active HMEs) that add water and heat to HMEs have been developed. In this study we evaluated the efficiency, both in vitro and in vivo, of a new active HME (the Performer; StarMed, Mirandola, Italy) as compared with that of existing HMEs (Hygroster and Hygrobac; Mallinckrodt, Mirandola, Italy). Methods We tested the efficiency by measuring the temperature and absolute humidity (AH) in vitro using a test lung ventilated at three levels of minute ventilation (5, 10 and 15 l/min) and at two tidal volumes (0.5 and 1 l), and in vivo in 42 patients with acute lung injury (arterial oxygen tension/fractional inspired oxygen ratio 283 ± 72 mmHg). We also evaluated the efficiency in vivo after 12 hours. Results In vitro, passive Performer and Hygrobac had higher airway temperature and AH (29.2 ± 0.7°C and 29.2 ± 0.5°C, [P < 0.05]; AH: 28.9 ± 1.6 mgH2O/l and 28.1 ± 0.8 mgH2O/l, [P < 0.05]) than did Hygroster (airway temperature: 28.1 ± 0.3°C [P < 0.05]; AH: 27 ± 1.2 mgH2O/l [P < 0.05]). Both devices suffered a loss of efficiency at the highest minute ventilation and tidal volume, and at the lowest minute ventilation. Active Performer had higher airway temperature and AH (31.9 ± 0.3°C and 34.3 ± 0.6 mgH2O/l; [P < 0.05]) than did Hygrobac and Hygroster, and was not influenced by minute ventilation or tidal volume. In vivo, the efficiency of passive Performer was similar to that of Hygrobac but better than Hygroster, whereas Active Performer was better than both. The active Performer exhibited good efficiency when used for up to 12 hours in vivo. Conclusion This study showed that active Performer may provide adequate conditioning of inspired gases, both as a passive and as an active device. PMID:15469569

In vitro and in vivo evaluation of a new active heat moisture exchanger.

PubMed

Chiumello, Davide; Pelosi, Paolo; Park, Gilbert; Candiani, Andrea; Bottino, Nicola; Storelli, Ezio; Severgnini, Paolo; D'Onofrio, Dunia; Gattinoni, Luciano; Chiaranda, Massimo

2004-10-01

In order to improve the efficiency of heat moisture exchangers (HMEs), new hybrid humidifiers (active HMEs) that add water and heat to HMEs have been developed. In this study we evaluated the efficiency, both in vitro and in vivo, of a new active HME (the Performer; StarMed, Mirandola, Italy) as compared with that of existing HMEs (Hygroster and Hygrobac; Mallinckrodt, Mirandola, Italy). We tested the efficiency by measuring the temperature and absolute humidity (AH) in vitro using a test lung ventilated at three levels of minute ventilation (5, 10 and 15 l/min) and at two tidal volumes (0.5 and 1 l), and in vivo in 42 patients with acute lung injury (arterial oxygen tension/fractional inspired oxygen ratio 283 +/- 72 mmHg). We also evaluated the efficiency in vivo after 12 hours. In vitro, passive Performer and Hygrobac had higher airway temperature and AH (29.2 +/- 0.7 degrees C and 29.2 +/- 0.5 degrees C, [P < 0.05]; AH: 28.9 +/- 1.6 mgH2O/l and 28.1 +/- 0.8 mgH2O/l, [P < 0.05]) than did Hygroster (airway temperature: 28.1 +/- 0.3 degrees C [P < 0.05]; AH: 27 +/- 1.2 mgH2O/l [P < 0.05]). Both devices suffered a loss of efficiency at the highest minute ventilation and tidal volume, and at the lowest minute ventilation. Active Performer had higher airway temperature and AH (31.9 +/- 0.3 degrees C and 34.3 +/- 0.6 mgH2O/l; [P < 0.05]) than did Hygrobac and Hygroster, and was not influenced by minute ventilation or tidal volume. In vivo, the efficiency of passive Performer was similar to that of Hygrobac but better than Hygroster, whereas Active Performer was better than both. The active Performer exhibited good efficiency when used for up to 12 hours in vivo. This study showed that active Performer may provide adequate conditioning of inspired gases, both as a passive and as an active device.

Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Subeihi, Ala' A.A., E-mail: ala.alsubeihi@wur.nl; BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority; Spenkelink, Bert

2012-05-01

This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were compared with those of a previously developed PBK model for methyleugenol (ME) in male rat. The results obtained reveal that formation of 1′-hydroxymethyleugenol glucuronide (1′HMEG), a major metabolic pathway in male rat liver, appears to represent a minor metabolic pathway in human liver whereas in human liver a significantly higher formation of 1′-oxomethyleugenolmore » (1′OME) compared with male rat liver is observed. Furthermore, formation of 1′-sulfooxymethyleugenol (1′HMES), which readily undergoes desulfonation to a reactive carbonium ion (CA) that can form DNA or protein adducts (DA), is predicted to be the same in the liver of both human and male rat at oral doses of 0.0034 and 300 mg/kg bw. Altogether despite a significant difference in especially the metabolic pathways of the proximate carcinogenic metabolite 1′-hydroxymethyleugenol (1′HME) between human and male rat, the influence of species differences on the ultimate overall bioactivation of methyleugenol (ME) to 1′-sulfooxymethyleugenol (1′HMES) appears to be negligible. Moreover, the PBK model predicted the formation of 1′-sulfooxymethyleugenol (1′HMES) in the liver of human and rat to be linear from doses as high as the benchmark dose (BMD{sub 10}) down to as low as the virtual safe dose (VSD). This study shows that kinetic data do not provide a reason to argue against linear extrapolation from the rat tumor data to the human situation. -- Highlights: ► A PBK model is made for bioactivation and detoxification of methyleugenol in human. ► Comparison to the PBK model in male rat revealed species differences. ► PBK results support linear extrapolation from high to low dose and from rat to human.« less

Assessment of different polymers and drug loads for fused deposition modeling of drug loaded implants.

PubMed

Kempin, Wiebke; Franz, Christian; Koster, Lynn-Christine; Schneider, Felix; Bogdahn, Malte; Weitschies, Werner; Seidlitz, Anne

2017-06-01

The 3D printing technique of fused deposition modeling® (FDM) has lately come into focus as a potential fabrication technique for pharmaceutical dosage forms and medical devices that allows the preparation of delivery systems with nearly any shape. This is particular promising for implants administered at application sites with a high anatomical variability where an individual shape adaption appears reasonable. In this work different polymers (Eudragit®RS, polycaprolactone (PCL), poly(l-lactide) (PLLA) and ethyl cellulose (EC)) were evaluated with respect to their suitability for FDM of drug loaded implants and their drug release behaviour was evaluated. The fluorescent dye quinine was used as a model drug to visualize drug distribution in filaments and implants. Quinine loaded filaments were produced by solvent casting and subsequent hot melt extrusion (HME) and model implants were printed as hollow cylinders using a standard FDM printer. Parameters were found at which model implants (hollow cylinders, outer diameter 4-5mm, height 3mm) could be produced from all tested polymers. The drug release which was examined by incubation of the printed implants in phosphate buffered saline solution (PBS) pH 7.4 was highly dependent on the used polymer. The fastest relative drug release of approximately 76% in 51days was observed for PCL and the lowest for Eudragit®RS and EC with less than 5% of quinine release in 78 and 100days, respectively. For PCL further filaments were prepared with different quinine loads ranging from 2.5% to 25% and thermal analysis proved the presence of a solid dispersion of quinine in the polymer for all tested concentrations. Increasing the drug load also increased the overall percentage of drug released to the medium since nearly the same absolute amount of quinine remained trapped in PCL at the end of drug release studies. This knowledge is valuable for future developments of printed implants with a desired drug release profile that might be controlled by the choice of the polymer and the drug load. Copyright © 2017 Elsevier B.V. All rights reserved.

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1.

PubMed

Xu, Dan; Chen, Xiaofeng; He, Quanyong; Luo, Chengqun

2016-01-01

MicroRNAs (miRs) are a class of small noncoding RNAs that negatively regulate the gene expression by directly binding to the 3' untranslated region of their target mRNA, thus resulting in mRNA degradation or translational repression. miR-9 has recently been demonstrated to play a role in the development and progression of malignant melanoma (MM), but the regulatory mechanism of miR-9 in the malignant phenotypes of MM still remains largely unknown. In this study, a total of 73 pairs of MM tissues and adjacent normal tissues were collected. Real-time reverse transcription polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of miR-9. MTT assay, wound healing assay, and transwell assay were conducted to determine the cell proliferation, migration, and invasion. Luciferase reporter assay was used to determine the targeting relationship between miR-9 and NRP1. Our data demonstrated that miR-9 expression was significantly downregulated in MM tissues compared with that in adjacent normal tissues. The decreased miR-9 level was significantly associated with the tumor stage and metastasis of MM. We also found that the expression level of miR-9 was decreased in MM cell lines (G361, B16, A375, and HME1) compared with normal skin HACAT cells. Ectopic expression of miR-9 led to a significant decrease in the ability of proliferation, migration, and invasion in A375 cells. NRP1 was further identified as a direct target gene of miR-9, and the protein expression of NRP1 was negatively regulated by miR-9 in A375 cells. Furthermore, overexpression of NRP1 reversed the suppressive effects of miR-9 on the malignant phenotypes of A375 cells. In vivo study revealed that miR-9 overexpression decreased the tumor growth, while overexpression of NRP1 increased MM growth. In summary, our findings suggest that the miR-9/NRP1 axis may serve as a potential target for the treatment of MM.

A new device for 100 per cent humidification of inspired air

PubMed Central

Larsson, Anders; Gustafsson, Ann; Svanborg, Lennart

2000-01-01

Introduction: Devices for active humidification of the inspired air in mechanically ventilated patients cause water condensation in the ventilator tubing, which may become contaminated or interfere with the function of the ventilator. The present study describes and tests the performance of a new humidifier, which is designed to eliminate water condensation. Objectives: To test the performance of the new humidifier at different ventilator settings in a lung model, and to compare this new humidifier with a conventional active humidifier in ventilator-treated critically ill patients. Materials and methods: The humidifier (Humid-Heat; Louis Gibeck AB, Upplands Väsby, Sweden) consists of a supply unit with a microprocessor and a water pump, and a humidification device, which is placed between the Y-piece and the endotracheal tube. The humidification device is based on a hygroscopic heat-moisture exchanger (HME), which absorbs the expired heat and moisture and releases it into the inspired gas. External heat and water are then added to the patient side of the HME, so the inspired gas should reach 100% humidity at 37°C (44 mg H2O/l air). The external water is delivered to the humidification device via a pump onto a wick and then evaporated into the inspired air by an electrical heater. The microprocessor controls the water pump and the heater by an algorithm using the minute ventilation (which is fed into the microprocessor) and the airway temperature measured by a sensor mounted in the flex-tube on the patient side of the humidification device. The performance characteristics were tested in a lung model ventilated with a constant flow (inspiratory:expiratory ratio 1:2, rate 12–20 breaths/min and a minute ventilation of 3–25 l/min) or with a decelerating flow (inspiratory:expiratory ratio 1:2, rate 12–15 breaths/min and a minute ventilation of 4.7–16.4 l/min). The device was also tested prospectively and in a randomized order compared with a conventional active humidifier (Fisher & Paykel MR730, Auckland, New Zealand) in eight mechanically ventilated, endotracheally intubated patients in the intensive care unit. The test period with each device was 24 h. The amount of fluid consumed and the amount of water in the water traps were measured. The number of times that the water traps were emptied, changes of machine filters, the suctions and quality of secretions, nebulizations, and the amount of saline instillations and endotracheal tube obstruction were recorded. In order to evaluate increased expiratory resistance due to the device, the airway pressure was measured at the end of a prolonged end-expiratory pause at 1 h of use and at the end of the test, and was compared with the corresponding pressure before the experiment. The body temperature of the patient was measured before and after the test of each device. Results: Both with constant flow and decelerating flow, the Humid-Heat gave an absolute humidity of 41–44 mgH2O/l at 37°C, with the lower level at the highest ventilation. In the patients, both Humid-Heat and the conventional active humidifier (MR730) maintained temperatures, indicating that they provided the intended heat and moisture to the inspired air. With both devices, the body temperature was maintained during the test period. There was no difference in the amount of secretions, the quality of the secretions and the frequency of suctions, saline instillations or nebulizations between the test periods with the two devices. There was no endotracheal tube obstruction, and after 1 h of use and at the end of the test no increased airway resistance was found with either device. When the MR730 was used, however, the water traps needed to be emptied six to 14 (mean eight) times (total amount of fluid in the traps was 100–300 ml) and the machine filters were changed two to six (mean four) times due to an excessive amount of condensed water with flow obstruction. No condensation of water was found in the tubing with the Humid-Heat. The water consumption was 23–65 ml/h (mean 30 ml/h) with the MR730 and 4–8 ml/h (mean 6 ml/h) with the Humid-Heat (P < 0.0008). The same relations were found when the water consumption was corrected for differences in minute ventilation. Discussion: The new humidifier, the Humid-Heat, gave an absolute humidity of 41–44 mg/l at 37°C in the bench tests. The tests in ventilated patients showed that the device was well tolerated and that condensation in the tubing was eliminated. There was no need to empty water traps. The test period was too short to evaluate whether the new device had any other advantages or disadvantages compared with conventional humidifiers. PMID:11056746

New global electron density observations from GPS-RO in the D- and E-Region ionosphere

NASA Astrophysics Data System (ADS)

Wu, Dong L.

2018-06-01

A novel retrieval technique is developed for electron density (Ne) in the D- and E-region (80-120 km) using the high-quality 50-Hz GPS radio occultation (GPS-RO) phase measurements. The new algorithm assumes a slow, linear variation in the F-region background when the GPS-RO passes through the D- and E-region, and extracts the Ne profiles at 80-130 km from the phase advance signal caused by Ne. Unlike the conventional Abel function, the new approach produces a sharp Ne weighting function in the lower ionosphere, and the Ne retrievals are in good agreement with the IRI (International Reference Ionosphere) model in terms of monthly maps, zonal means and diurnal variations. The daytime GPS-RO Ne profiles can be well characterized by the α-Chapman function of three parameters (NmE, hmE and H), showing that the bottom of E-region is deepening and sharpening towards the summer pole. At high latitudes the monthly GPS-RO Ne maps at 80-120 km reveal clear enhancement in the auroral zones, more prominent at night, as a result of energetic electron precipitation (EEP) from the outer radiation belt. The D-/E-region auroral Ne is strongly correlated with Kp on a daily basis. The new Ne data allow further comprehensive analyses of the sporadic E (Es) phenomena in connection with the background Ne in the E-region. The layered (2-10 km) and fluctuated (<2 km) Es components, namely Ne_Layer than Ne_Pert, are extracted with respect to the background Ne_Region on a profile-by-profile basis. The Ne_Layer component has a strong but highly-refined peak at ∼105 km, with an amplitude smaller than Ne_Region approximately by an order of magnitude. The Ne_Pert component, which was studied extensively in the past, is ∼2 orders of magnitude weaker than Ne_Layer. Both Ne_Layer and Ne_Pert are subject to significant diurnal and semidiurnal variations, showing downward progression with local time in amplitude. The 11-year solar cycle dominates the Ne interannual variations, showing larger Ne_Region and Ne_Layer but smaller Ne_Pert amplitudes in the solar maximum years. Enhanced Ne profiles are often observed in the polar winter, showing good correlation with solar proton events (SPEs) and geomagnetic activity. The new methodology offers great potential for retrieving low Ne in the D-region, where radio propagation and communication blackouts can occur due to enhanced ionization. For space weather applications it is recommended for GPS-RO operations to raise the top of high-rate data acquisition to ∼140 km in the future.

Statistical Power in Evaluations That Investigate Effects on Multiple Outcomes: A Guide for Researchers

ERIC Educational Resources Information Center

Porter, Kristin E.

2018-01-01

Researchers are often interested in testing the effectiveness of an intervention on multiple outcomes, for multiple subgroups, at multiple points in time, or across multiple treatment groups. The resulting multiplicity of statistical hypothesis tests can lead to spurious findings of effects. Multiple testing procedures (MTPs) are statistical…

The Research of Multiple Attenuation Based on Feedback Iteration and Independent Component Analysis

NASA Astrophysics Data System (ADS)

Xu, X.; Tong, S.; Wang, L.

2017-12-01

How to solve the problem of multiple suppression is a difficult problem in seismic data processing. The traditional technology for multiple attenuation is based on the principle of the minimum output energy of the seismic signal, this criterion is based on the second order statistics, and it can't achieve the multiple attenuation when the primaries and multiples are non-orthogonal. In order to solve the above problems, we combine the feedback iteration method based on the wave equation and the improved independent component analysis (ICA) based on high order statistics to suppress the multiple waves. We first use iterative feedback method to predict the free surface multiples of each order. Then, in order to predict multiples from real multiple in amplitude and phase, we design an expanded pseudo multi-channel matching filtering method to get a more accurate matching multiple result. Finally, we present the improved fast ICA algorithm which is based on the maximum non-Gauss criterion of output signal to the matching multiples and get better separation results of the primaries and the multiples. The advantage of our method is that we don't need any priori information to the prediction of the multiples, and can have a better separation result. The method has been applied to several synthetic data generated by finite-difference model technique and the Sigsbee2B model multiple data, the primaries and multiples are non-orthogonal in these models. The experiments show that after three to four iterations, we can get the perfect multiple results. Using our matching method and Fast ICA adaptive multiple subtraction, we can not only effectively preserve the effective wave energy in seismic records, but also can effectively suppress the free surface multiples, especially the multiples related to the middle and deep areas.

Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

PubMed

Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

2016-06-01

It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. © The Author(s) 2016.

Combined adaptive multiple subtraction based on optimized event tracing and extended wiener filtering

NASA Astrophysics Data System (ADS)

Tan, Jun; Song, Peng; Li, Jinshan; Wang, Lei; Zhong, Mengxuan; Zhang, Xiaobo

2017-06-01

The surface-related multiple elimination (SRME) method is based on feedback formulation and has become one of the most preferred multiple suppression methods used. However, some differences are apparent between the predicted multiples and those in the source seismic records, which may result in conventional adaptive multiple subtraction methods being barely able to effectively suppress multiples in actual production. This paper introduces a combined adaptive multiple attenuation method based on the optimized event tracing technique and extended Wiener filtering. The method firstly uses multiple records predicted by SRME to generate a multiple velocity spectrum, then separates the original record to an approximate primary record and an approximate multiple record by applying the optimized event tracing method and short-time window FK filtering method. After applying the extended Wiener filtering method, residual multiples in the approximate primary record can then be eliminated and the damaged primary can be restored from the approximate multiple record. This method combines the advantages of multiple elimination based on the optimized event tracing method and the extended Wiener filtering technique. It is an ideal method for suppressing typical hyperbolic and other types of multiples, with the advantage of minimizing damage of the primary. Synthetic and field data tests show that this method produces better multiple elimination results than the traditional multi-channel Wiener filter method and is more suitable for multiple elimination in complicated geological areas.

Common pitfalls in statistical analysis: The perils of multiple testing

PubMed Central

Ranganathan, Priya; Pramesh, C. S.; Buyse, Marc

2016-01-01

Multiple testing refers to situations where a dataset is subjected to statistical testing multiple times - either at multiple time-points or through multiple subgroups or for multiple end-points. This amplifies the probability of a false-positive finding. In this article, we look at the consequences of multiple testing and explore various methods to deal with this issue. PMID:27141478

Estimating Statistical Power When Making Adjustments for Multiple Tests

ERIC Educational Resources Information Center

Porter, Kristin E.

2016-01-01

In recent years, there has been increasing focus on the issue of multiple hypotheses testing in education evaluation studies. In these studies, researchers are typically interested in testing the effectiveness of an intervention on multiple outcomes, for multiple subgroups, at multiple points in time or across multiple treatment groups. When…

Preparing for Multiple Births

MedlinePlus

... problem. What Should I Eat if I'm Pregnant With Multiples? If you're pregnant with multiples, ... Much Weight Should I Gain if I'm Pregnant With Multiples? Mothers carrying multiples are expected to ...

Fourth Annual International Acquisitions Workshop: Access to Multiple Media Worldwide

NASA Technical Reports Server (NTRS)

1994-01-01

Topics discussed during the workshop include: (1) Multinational-Multiple media collections and activities spanning many countries; (2) Multiple media in North American trade and commerce; (3) African spotlight; (4) Europe-Multiple media in national libraries and services; (5) Scandinavian spotlight; (6) Internet update; (7) Multiple media in US federal agencies; (8) Open-source multiple media in US federal agencies; and (9) Multiple media at US federal technical agencies-NIST and NOAA.

Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

PubMed

Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

2016-07-01

Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. © The Author(s) 2016.

Statistical Power in Evaluations That Investigate Effects on Multiple Outcomes: A Guide for Researchers

ERIC Educational Resources Information Center

Porter, Kristin E.

2016-01-01

In education research and in many other fields, researchers are often interested in testing the effectiveness of an intervention on multiple outcomes, for multiple subgroups, at multiple points in time, or across multiple treatment groups. The resulting multiplicity of statistical hypothesis tests can lead to spurious findings of effects. Multiple…

The Multiple Control of Verbal Behavior

PubMed Central

Michael, Jack; Palmer, David C; Sundberg, Mark L

2011-01-01

Amid the novel terms and original analyses in Skinner's Verbal Behavior, the importance of his discussion of multiple control is easily missed, but multiple control of verbal responses is the rule rather than the exception. In this paper we summarize and illustrate Skinner's analysis of multiple control and introduce the terms convergent multiple control and divergent multiple control. We point out some implications for applied work and discuss examples of the role of multiple control in humor, poetry, problem solving, and recall. Joint control and conditional discrimination are discussed as special cases of multiple control. We suggest that multiple control is a useful analytic tool for interpreting virtually all complex behavior, and we consider the concepts of derived relations and naming as cases in point. PMID:22532752

Multiplicity: An Explorative Interview Study on Personal Experiences of People with Multiple Selves.

PubMed

Ribáry, Gergő; Lajtai, László; Demetrovics, Zsolt; Maraz, Aniko

2017-01-01

Background and aims: Personality psychology research relies on the notion that humans have a single self that is the result of the individual's thoughts, feelings, and behaviors that can be reliably described (i.e., through traits). People who identify themselves as "multiple" have a system of multiple or alternative, selves, that share the same physical body. This is the first study to explore the phenomenon of multiplicity by assessing the experiences of people who identify themselves as "multiple." Methods: First, an Internet forum search was performed using the terms "multiplicity" and "multiple system." Based on that search, people who identified themselves as multiple were contacted. Interviews were conducted by a consultant psychiatrist, which produced six case vignettes. Results: Multiplicity is discussed on Twitter, Tumblr, Google+ and several other personal websites, blogs, and forums maintained by multiples. According to the study's estimates, there are 200-300 individuals who participate in these forums and believe they are multiple. Based on the six interviews, it appears that multiples have several selves who are relatively independent of each other and constitute the personality's system. Each "resident person" or self, has their own unique behavioral pattern, which is triggered by different situations. However, multiples are a heterogeneous group in terms of their system organization, memory functions, and control over switching between selves. Conclusions: Multiplicity can be placed along a continuum between identity disturbance and dissociative identity disorder (DID), although most systems function relatively well in everyday life. Further research is needed to explore this phenomenon, especially in terms of the extent to which multiplicity can be regarded as a healthy way of coping.

A Multiple-Sequence Variant of the Multiple-Baseline Design: A Strategy for Analysis of Sequence Effects and Treatment Comparison.

ERIC Educational Resources Information Center

Noell, George H.; Gresham, Frank M.

2001-01-01

Describes design logic and potential uses of a variant of the multiple-baseline design. The multiple-baseline multiple-sequence (MBL-MS) consists of multiple-baseline designs that are interlaced with one another and include all possible sequences of treatments. The MBL-MS design appears to be primarily useful for comparison of treatments taking…

Should "Multiple Imputations" Be Treated as "Multiple Indicators"?

ERIC Educational Resources Information Center

Mislevy, Robert J.

1993-01-01

Multiple imputations for latent variables are constructed so that analyses treating them as true variables have the correct expectations for population characteristics. Analyzing multiple imputations in accordance with their construction yields correct estimates of population characteristics, whereas analyzing them as multiple indicators generally…

Dean's Great Discovery: Multiplication, Division and Fractions

ERIC Educational Resources Information Center

Vale, Colleen; Davies, Anne

2007-01-01

Multiplication, division and fractions are "hotspots" for students in the middle years with many students experiencing difficulty with these concepts. Arrays effectively model multiplication and help children develop multiplicative thinking and learn multiplication facts. In this article the authors show how an open-ended array problem…

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

PubMed

Lin, John C; Spinella, Philip C; Fitzgerald, Julie C; Tucci, Marisa; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

2017-01-01

To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Secondary analysis of a prospective, cross-sectional, point prevalence study. International, multicenter PICUs. Pediatric patients with severe sepsis identified on five separate days over a 1-year period. None. Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

Semantic Structures of One-Step Word Problems Involving Multiplication or Division.

ERIC Educational Resources Information Center

Schmidt, Siegbert; Weiser, Werner

1995-01-01

Proposes a four-category classification of semantic structures of one-step word problems involving multiplication and division: forming the n-th multiple of measures, combinatorial multiplication, composition of operators, and multiplication by formula. This classification is compatible with semantic structures of addition and subtraction word…

Multiple Contact Dates and SARS Incubation Periods

PubMed Central

2004-01-01

Many severe acute respiratory syndrome (SARS) patients have multiple possible incubation periods due to multiple contact dates. Multiple contact dates cannot be used in standard statistical analytic techniques, however. I present a simple spreadsheet-based method that uses multiple contact dates to calculate the possible incubation periods of SARS. PMID:15030684

Multiple Testing in the Context of Gene Discovery in Sickle Cell Disease Using Genome-Wide Association Studies.

PubMed

Kuo, Kevin H M

2017-01-01

The issue of multiple testing, also termed multiplicity, is ubiquitous in studies where multiple hypotheses are tested simultaneously. Genome-wide association study (GWAS), a type of genetic association study that has gained popularity in the past decade, is most susceptible to the issue of multiple testing. Different methodologies have been employed to address the issue of multiple testing in GWAS. The purpose of the review is to examine the methodologies employed in dealing with multiple testing in the context of gene discovery using GWAS in sickle cell disease complications.

Quantum theory of multiple-input-multiple-output Markovian feedback with diffusive measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chia, A.; Wiseman, H. M.

2011-07-15

Feedback control engineers have been interested in multiple-input-multiple-output (MIMO) extensions of single-input-single-output (SISO) results of various kinds due to its rich mathematical structure and practical applications. An outstanding problem in quantum feedback control is the extension of the SISO theory of Markovian feedback by Wiseman and Milburn [Phys. Rev. Lett. 70, 548 (1993)] to multiple inputs and multiple outputs. Here we generalize the SISO homodyne-mediated feedback theory to allow for multiple inputs, multiple outputs, and arbitrary diffusive quantum measurements. We thus obtain a MIMO framework which resembles the SISO theory and whose additional mathematical structure is highlighted by the extensivemore » use of vector-operator algebra.« less

Least squares reverse time migration of controlled order multiples

NASA Astrophysics Data System (ADS)

Liu, Y.

2016-12-01

Imaging using the reverse time migration of multiples generates inherent crosstalk artifacts due to the interference among different order multiples. Traditionally, least-square fitting has been used to address this issue by seeking the best objective function to measure the amplitude differences between the predicted and observed data. We have developed an alternative objective function by decomposing multiples into different orders to minimize the difference between Born modeling predicted multiples and specific-order multiples from observational data in order to attenuate the crosstalk. This method is denoted as the least-squares reverse time migration of controlled order multiples (LSRTM-CM). Our numerical examples demonstrated that the LSRTM-CM can significantly improve image quality compared with reverse time migration of multiples and least-square reverse time migration of multiples. Acknowledgments This research was funded by the National Nature Science Foundation of China (Grant Nos. 41430321 and 41374138).

Multiple testing and power calculations in genetic association studies.

PubMed

So, Hon-Cheong; Sham, Pak C

2011-01-01

Modern genetic association studies typically involve multiple single-nucleotide polymorphisms (SNPs) and/or multiple genes. With the development of high-throughput genotyping technologies and the reduction in genotyping cost, investigators can now assay up to a million SNPs for direct or indirect association with disease phenotypes. In addition, some studies involve multiple disease or related phenotypes and use multiple methods of statistical analysis. The combination of multiple genetic loci, multiple phenotypes, and multiple methods of evaluating associations between genotype and phenotype means that modern genetic studies often involve the testing of an enormous number of hypotheses. When multiple hypothesis tests are performed in a study, there is a risk of inflation of the type I error rate (i.e., the chance of falsely claiming an association when there is none). Several methods for multiple-testing correction are in popular use, and they all have strengths and weaknesses. Because no single method is universally adopted or always appropriate, it is important to understand the principles, strengths, and weaknesses of the methods so that they can be applied appropriately in practice. In this article, we review the three principle methods for multiple-testing correction and provide guidance for calculating statistical power.

Seismic multiple attenuation in the northern continent-ocean transition zone of the South China Sea

NASA Astrophysics Data System (ADS)

Chen, N.; Li, C. F.

2017-12-01

In seismic exploration, especially in marine oil and gas exploration, presence of multiple reflections lowers signal-to-noise ratio of seismic data and makes it difficult to analyze seismic velocity. In northern continent-ocean transition zone of the South China Sea (SCS), low-velocity Cenozoic strata cover sets of high-velocity carbonate strata directly, and over 1000 m thick of sediments were deposited on the igneous basement in the northwest SCS. These sedimentary boundaries generate quite strong impedance interfaces and strong internal multiples. Diffractions as a result of variation of seabed topography, coupled with the vibration, free surface multiples and refraction multiples, cause a variety of strong energy disturbances and missing of frequency component. In this study, we process four recently acquired multichannel reflection seismic profiles from the northern continent-ocean transition zone of the SCS with a new combination of demultiple techniques. There is a variety of strong multiples in the raw data, and the seabed multiple occurs between 9 to 11 seconds in two-way travel time (TWTT), and we apply Surface-related Multiple Elimination (SRME) to attenuate the free surface multiples. After SRME, we use high-resolution Radon transform (RAMUR) to attenuate deep multiples concentrating below 10 seconds in TWTT. Normal moveout correction (NMO) is necessary to flatten true reflections and turn multiples into a parabola before RAMUR, and we can attenuate the deep multiples in theτ-p domain. The seabed topography varies greatly in the continent-ocean transition zone, so the diffractions are well developed. However, SRME and RAMUR are not effective in attenuating diffractions and internal multiples. We select diffracted multiple attenuation (DIMAT) after many trials and detailed analysis. The diffractions are extracted in decomposed frequency bands. The internal multiples below 11 seconds in TWTT and high-amplitude noises are successfully suppressed while keeping the primary events. This combination of SRME, RAMUR and DIMAT in sequence demonstrates to be quite effective in attenuating these types of multiples on the continent-ocean transition zone. Keywords: Continent-ocean transition zone, seismic exploration, data processing, multiple attenuation

Exciton multiplication from first principles.

PubMed

Jaeger, Heather M; Hyeon-Deuk, Kim; Prezhdo, Oleg V

2013-06-18

Third-generation photovolatics require demanding cost and power conversion efficiency standards, which may be achieved through efficient exciton multiplication. Therefore, generating more than one electron-hole pair from the absorption of a single photon has vast ramifications on solar power conversion technology. Unlike their bulk counterparts, irradiated semiconductor quantum dots exhibit efficient exciton multiplication, due to confinement-enhanced Coulomb interactions and slower nonradiative losses. The exact characterization of the complicated photoexcited processes within quantum-dot photovoltaics is a work in progress. In this Account, we focus on the photophysics of nanocrystals and investigate three constituent processes of exciton multiplication, including photoexcitation, phonon-induced dephasing, and impact ionization. We quantify the role of each process in exciton multiplication through ab initio computation and analysis of many-electron wave functions. The probability of observing a multiple exciton in a photoexcited state is proportional to the magnitude of electron correlation, where correlated electrons can be simultaneously promoted across the band gap. Energies of multiple excitons are determined directly from the excited state wave functions, defining the threshold for multiple exciton generation. This threshold is strongly perturbed in the presence of surface defects, dopants, and ionization. Within a few femtoseconds following photoexcitation, the quantum state loses coherence through interactions with the vibrating atomic lattice. The phase relationship between single excitons and multiple excitons dissipates first, followed by multiple exciton fission. Single excitons are coupled to multiple excitons through Coulomb and electron-phonon interactions, and as a consequence, single excitons convert to multiple excitons and vice versa. Here, exciton multiplication depends on the initial energy and coupling magnitude and competes with electron-phonon energy relaxation. Multiple excitons are generated through impact ionization within picoseconds. The basis of exciton multiplication in quantum dots is the collective result of photoexcitation, dephasing, and nonadiabatic evolution. Each process is characterized by a distinct time-scale, and the overall multiple exciton generation dynamics is complete by about 10 ps. Without relying on semiempirical parameters, we computed quantum mechanical probabilities of multiple excitons for small model systems. Because exciton correlations and coherences are microscopic, quantum properties, results for small model systems can be extrapolated to larger, realistic quantum dots.

ESSC-ESF Position Paper-Science-Driven Scenario for Space Exploration: Report from the European Space Sciences Committee (ESSC)

NASA Astrophysics Data System (ADS)

Worms, Jean-Claude; Lammer, Helmut; Barucci, Antonella; Beebe, Reta; Bibring, Jean-Pierre; Blamont, Jacques; Blanc, Michel; Bonnet, Roger; Brucato, John R.; Chassefière, Eric; Coradini, Angioletta; Crawford, Ian; Ehrenfreund, Pascale; Falcke, Heino; Gerzer, Rupert; Grady, Monica; Grande, Manuel; Haerendel, Gerhard; Horneck, Gerda; Koch, Bernhard; Lobanov, Andreï; Lopez-Moreno, José J.; Marco, Robert; Norsk, Peter; Rothery, Dave; Swings, Jean-Pierre; Tropea, Cam; Ulamec, Stephan; Westall, Frances; Zarnecki, John

2009-02-01

In 2005 the then ESA Directorate for Human Spaceflight, Microgravity and Exploration (D-HME) commissioned a study from the European Science Foundation's (ESF) European Space Sciences Committee (ESSC) to examine the science aspects of the Aurora Programme in preparation for the December 2005 Ministerial Conference of ESA Member States, held in Berlin. A first interim report was presented to ESA at the second stakeholders meeting on 30 and 31 May 2005. A second draft report was made available at the time of the final science stakeholders meeting on 16 September 2005 in order for ESA to use its recommendations to prepare the Executive proposal to the Ministerial Conference. The final ESSC report on that activity came a few months after the Ministerial Conference (June 2006) and attempted to capture some elements of the new situation after Berlin, and in the context of the reduction in NASA's budget that was taking place at that time; e.g., the postponement sine die of the Mars Sample Return mission. At the time of this study, ESSC made it clear to ESA that the timeline imposed prior to the Berlin Conference had not allowed for a proper consultation of the relevant science community and that this should be corrected in the near future. In response to that recommendation, ESSC was asked again in the summer of 2006 to initiate a broad consultation to define a science-driven scenario for the Aurora Programme. This exercise ran between October 2006 and May 2007. ESA provided the funding for staff support, publication costs, and costs related to meetings of a Steering Group, two meetings of a larger ad hoc group (7 and 8 December 2006 and 8 February 2007), and a final scientific workshop on 15 and 16 May 2007 in Athens. As a result of these meetings a draft report was produced and examined by the Ad Hoc Group. Following their endorsement of the report and its approval by the plenary meeting of the ESSC, the draft report was externally refereed, as is now normal practice with all ESSC-ESF reports, and amended accordingly. The Ad Hoc Group defined overarching scientific goals for Europe's exploration programme, dubbed "Emergence and co-evolution of life with its planetary environments," focusing on those targets that can ultimately be reached by humans, i.e., Mars, the Moon, and Near Earth Objects. Mars was further recognized as the focus of that programme, with Mars sample return as the recognized primary goal; furthermore the report clearly states that Europe should position itself as a major actor in defining and leading Mars sample return missions. The report is reproduced in this article. On 26 November 2008 the Ministers of ESA Member States decided to give a high strategic priority to the robotic exploration programme of Mars by funding the enhanced ExoMars mission component, in line therefore with the recommendations from this ESSC-ESF report.

[Evaluation of arguments in research reports].

PubMed

Botes, A

1999-06-01

Some authors on research methodology are of opinion that research reports are based on the logic of reasoning and that such reports communicate with the reader by presenting logical, coherent arguments (Böhme, 1975:206; Mouton, 1996:69). This view implies that researchers draw specific conclusions and that such conclusions are justified by way of reasoning (Doppelt, 1998:105; Giere, 1984:26; Harre, 1965:11; Leherer & Wagner, 1983 & Pitt, 1988:7). The structure of a research report thus consists mainly of conclusions and reasons for such conclusions (Booth, Colomb & Williams, 1995:97). From this it appears that justification by means of reasoning is a standard procedure in research and research reports. Despite the fact that the logic of research is based on reasoning, that the justification of research findings by way of reasoning appears to be standard procedure and that the structure of a research report comprises arguments, the evaluation or assessment of research, as described in most textbooks on research methodology (Burns & Grove, 1993:647; Creswell, 1994:193; LoBiondo-Wood & Haber, 1994:441/481) does not focus on the arguments of research. The evaluation criteria for research reports which are set in these textbooks are related to the way in which the research process is carried out and focus on the measures for internal, external, theoretical, measurement and inferential validity. This means that criteria for the evaluation of research are comprehensive and they should be very specific in respect of each type of research (for example quantitative or qualitative). When the evaluation of research reports is focused on arguments and logic, there could probably be one set of universal standards against which all types of human science research reports can be assessed. Such a universal set of standards could possibly simplify the evaluation of research reports in the human sciences since they can be used to assess all the critical aspects of research reports. As arguments from the basic structure of research reports and are probably also important in the evaluation of research reports in the human sciences, the following questions which I want to answer, are relevant to this paper namely: What are the standards which the reasoning in research reports in the human sciences should meet? How can research reports in the human sciences be assessed or evaluated according to these standards? In answering the first question, the logical demands that are made on reasoning in research are investigated. From these demands the acceptability of the statements, relevance and support of the premises to the conclusion are set as standards for reasoning in research. In answering the second question, a research article is used to demonstrate how the macro- and micro-arguments of research reports can be assessed or evaluated according to these standards. With evaluation it is indicated that the aspects of internal, external, theoretical, measurement and inferential validity can be evaluated according to these standards.

ESSC-ESF position paper--science-driven scenario for space exploration: report from the European Space Sciences Committee (ESSC).

PubMed

Worms, Jean-Claude; Lammer, Helmut; Barucci, Antonella; Beebe, Reta; Bibring, Jean-Pierre; Blamont, Jacques; Blanc, Michel; Bonnet, Roger; Brucato, John R; Chassefière, Eric; Coradini, Angioletta; Crawford, Ian; Ehrenfreund, Pascale; Falcke, Heino; Gerzer, Rupert; Grady, Monica; Grande, Manuel; Haerendel, Gerhard; Horneck, Gerda; Koch, Bernhard; Lobanov, Andreï; Lopez-Moreno, José J; Marco, Roberto; Norsk, Peter; Rothery, Dave; Swings, Jean-Pierre; Tropea, Cam; Ulamec, Stephan; Westall, Frances; Zarnecki, John

2009-01-01

In 2005 the then ESA Directorate for Human Spaceflight, Microgravity and Exploration (D-HME) commissioned a study from the European Science Foundation's (ESF) European Space Sciences Committee (ESSC) to examine the science aspects of the Aurora Programme in preparation for the December 2005 Ministerial Conference of ESA Member States, held in Berlin. A first interim report was presented to ESA at the second stakeholders meeting on 30 and 31 May 2005. A second draft report was made available at the time of the final science stakeholders meeting on 16 September 2005 in order for ESA to use its recommendations to prepare the Executive proposal to the Ministerial Conference. The final ESSC report on that activity came a few months after the Ministerial Conference (June 2006) and attempted to capture some elements of the new situation after Berlin, and in the context of the reduction in NASA's budget that was taking place at that time; e.g., the postponement sine die of the Mars Sample Return mission. At the time of this study, ESSC made it clear to ESA that the timeline imposed prior to the Berlin Conference had not allowed for a proper consultation of the relevant science community and that this should be corrected in the near future. In response to that recommendation, ESSC was asked again in the summer of 2006 to initiate a broad consultation to define a science-driven scenario for the Aurora Programme. This exercise ran between October 2006 and May 2007. ESA provided the funding for staff support, publication costs, and costs related to meetings of a Steering Group, two meetings of a larger ad hoc group (7 and 8 December 2006 and 8 February 2007), and a final scientific workshop on 15 and 16 May 2007 in Athens. As a result of these meetings a draft report was produced and examined by the Ad Hoc Group. Following their endorsement of the report and its approval by the plenary meeting of the ESSC, the draft report was externally refereed, as is now normal practice with all ESSC-ESF reports, and amended accordingly. The Ad Hoc Group defined overarching scientific goals for Europe's exploration programme, dubbed "Emergence and co-evolution of life with its planetary environments," focusing on those targets that can ultimately be reached by humans, i.e., Mars, the Moon, and Near Earth Objects. Mars was further recognized as the focus of that programme, with Mars sample return as the recognized primary goal; furthermore the report clearly states that Europe should position itself as a major actor in defining and leading Mars sample return missions. The report is reproduced in this article. On 26 November 2008 the Ministers of ESA Member States decided to give a high strategic priority to the robotic exploration programme of Mars by funding the enhanced ExoMars mission component, in line therefore with the recommendations from this ESSC-ESF report.

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

PubMed

Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

2004-01-01

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external sphincterotomy followed by condom catheter drainage is recommended. However, if external urethral sphincterotomy fails to reduce residual urine and detrusor pressure, urinary diversion or bladder reconstruction may be necessary.

Multiplicity: An Explorative Interview Study on Personal Experiences of People with Multiple Selves

PubMed Central

Ribáry, Gergő; Lajtai, László; Demetrovics, Zsolt; Maraz, Aniko

2017-01-01

Background and aims: Personality psychology research relies on the notion that humans have a single self that is the result of the individual's thoughts, feelings, and behaviors that can be reliably described (i.e., through traits). People who identify themselves as “multiple” have a system of multiple or alternative, selves, that share the same physical body. This is the first study to explore the phenomenon of multiplicity by assessing the experiences of people who identify themselves as “multiple.” Methods: First, an Internet forum search was performed using the terms “multiplicity” and “multiple system.” Based on that search, people who identified themselves as multiple were contacted. Interviews were conducted by a consultant psychiatrist, which produced six case vignettes. Results: Multiplicity is discussed on Twitter, Tumblr, Google+ and several other personal websites, blogs, and forums maintained by multiples. According to the study's estimates, there are 200–300 individuals who participate in these forums and believe they are multiple. Based on the six interviews, it appears that multiples have several selves who are relatively independent of each other and constitute the personality's system. Each “resident person” or self, has their own unique behavioral pattern, which is triggered by different situations. However, multiples are a heterogeneous group in terms of their system organization, memory functions, and control over switching between selves. Conclusions: Multiplicity can be placed along a continuum between identity disturbance and dissociative identity disorder (DID), although most systems function relatively well in everyday life. Further research is needed to explore this phenomenon, especially in terms of the extent to which multiplicity can be regarded as a healthy way of coping. PMID:28659840

An introduction to multiplicity issues in clinical trials: the what, why, when and how.

PubMed

Li, Guowei; Taljaard, Monica; Van den Heuvel, Edwin R; Levine, Mitchell Ah; Cook, Deborah J; Wells, George A; Devereaux, Philip J; Thabane, Lehana

2017-04-01

In clinical trials it is not uncommon to face a multiple testing problem which can have an impact on both type I and type II error rates, leading to inappropriate interpretation of trial results. Multiplicity issues may need to be considered at the design, analysis and interpretation stages of a trial. The proportion of trial reports not adequately correcting for multiple testing remains substantial. The purpose of this article is to provide an introduction to multiple testing issues in clinical trials, and to reduce confusion around the need for multiplicity adjustments. We use a tutorial, question-and-answer approach to address the key issues of why, when and how to consider multiplicity adjustments in trials. We summarize the relevant circumstances under which multiplicity adjustments ought to be considered, as well as options for carrying out multiplicity adjustments in terms of trial design factors including Population, Intervention/Comparison, Outcome, Time frame and Analysis (PICOTA). Results are presented in an easy-to-use table and flow diagrams. Confusion about multiplicity issues can be reduced or avoided by considering the potential impact of multiplicity on type I and II errors and, if necessary pre-specifying statistical approaches to either avoid or adjust for multiplicity in the trial protocol or analysis plan. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Immunoglobulin A multiple myeloma with cutaneous involvement in a dog.

PubMed

Mayer, Monique N; Kerr, Moira E; Grier, Candace K; Macdonald, Valerie S

2008-07-01

An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed.

Immunoglobulin A multiple myeloma with cutaneous involvement in a dog

PubMed Central

Mayer, Monique N.; Kerr, Moira E.; Grier, Candace K.; MacDonald, Valerie S.

2008-01-01

An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed. PMID:18827847

An omnibus test for family-based association studies with multiple SNPs and multiple phenotypes.

PubMed

Lasky-Su, Jessica; Murphy, Amy; McQueen, Matthew B; Weiss, Scott; Lange, Christoph

2010-06-01

We propose an omnibus family-based association test (MFBAT) that can be applied to multiple markers and multiple phenotypes and that has only one degree of freedom. The proposed test statistic extends current FBAT methodology to incorporate multiple markers as well as multiple phenotypes. Using simulation studies, power estimates for the proposed methodology are compared with the standard methodologies. On the basis of these simulations, we find that MFBAT substantially outperforms other methods, including haplotypic approaches and doing multiple tests with single single-nucleotide polymorphisms (SNPs) and single phenotypes. The practical relevance of the approach is illustrated by an application to asthma in which SNP/phenotype combinations are identified and reach overall significance that would not have been identified using other approaches. This methodology is directly applicable to cases in which there are multiple SNPs, such as candidate gene studies, cases in which there are multiple phenotypes, such as expression data, and cases in which there are multiple phenotypes and genotypes, such as genome-wide association studies that incorporate expression profiles as phenotypes. This program is available in the PBAT analysis package.

Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-κB and STAT3.

PubMed

Ma, Jing; Gong, Wei; Liu, Su; Li, Qian; Guo, Mengzheng; Wang, Jinhan; Wang, Suying; Chen, Naiyao; Wang, Yafei; Liu, Qiang; Zhao, Hui

2018-01-01

The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma. Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine kinase, while its effects on multiple myeloma have not been well described. Here, we show that microRNA-21 is an oncogenic marker closely linked with progression of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-κB and signal transducer and activator of transcription 3 signaling pathways. Taken together, our results suggest that ibrutinib is a promising potential treatment for multiple myeloma. Further investigation of mechanisms of ibrutinib function in multiple myeloma will be necessary to evaluate its use as a novel multiple myeloma treatment.

Multiple attenuation to reflection seismic data using Radon filter and Wave Equation Multiple Rejection (WEMR) method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erlangga, Mokhammad Puput

Separation between signal and noise, incoherent or coherent, is important in seismic data processing. Although we have processed the seismic data, the coherent noise is still mixing with the primary signal. Multiple reflections are a kind of coherent noise. In this research, we processed seismic data to attenuate multiple reflections in the both synthetic and real seismic data of Mentawai. There are several methods to attenuate multiple reflection, one of them is Radon filter method that discriminates between primary reflection and multiple reflection in the τ-p domain based on move out difference between primary reflection and multiple reflection. However, inmore » case where the move out difference is too small, the Radon filter method is not enough to attenuate the multiple reflections. The Radon filter also produces the artifacts on the gathers data. Except the Radon filter method, we also use the Wave Equation Multiple Elimination (WEMR) method to attenuate the long period multiple reflection. The WEMR method can attenuate the long period multiple reflection based on wave equation inversion. Refer to the inversion of wave equation and the magnitude of the seismic wave amplitude that observed on the free surface, we get the water bottom reflectivity which is used to eliminate the multiple reflections. The WEMR method does not depend on the move out difference to attenuate the long period multiple reflection. Therefore, the WEMR method can be applied to the seismic data which has small move out difference as the Mentawai seismic data. The small move out difference on the Mentawai seismic data is caused by the restrictiveness of far offset, which is only 705 meter. We compared the real free multiple stacking data after processing with Radon filter and WEMR process. The conclusion is the WEMR method can more attenuate the long period multiple reflection than the Radon filter method on the real (Mentawai) seismic data.« less

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1.

PubMed

Abreu, Pedro; Pedrosa, Rui; Sá, Maria José; Cerqueira, João; Sousa, Lívia; Da Silva, Ana Martins; Pinheiro, Joaquim; De Sá, João; Batista, Sónia; Simões, Rita Moiron; Pereira, Daniela Jardim; Vilela, Pedro; Vale, José

2018-05-30

Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.

How agricultural multiple ecosystem services respond to socioeconomic factors in Mengyin County, China.

PubMed

Chen, Yajuan; Yu, Zhenrong; Li, Xuedong; Li, Pengyao

2018-07-15

Provisioning services have always been the main focus of agriculture, and which have led to a decline in biodiversity and have damaged a number of other services. Agriculture should contribute to current and future food security while producing multiple ecosystem services (ES). Restoration outcomes of multiple ES were affected by different socioeconomic drivers, thus a better understanding of how multiple ES respond to socioeconomic drivers can help to restore multiple ES. This paper used rural people's perceptions of ES to quantify and map ecosystem service obtainment and demand in the Mengyin County, China. An integrative index of multiple ecosystem services (IMES) was used to effectively aggregate the values of multiple ES. The threat categorization framework is designed to communicate the degree to which the adequate and sustainable provision of multiple ES is threatened, in order to prioritize conservation actions. The results revealed that 6 townships in the Mengyin County exhibited an excessive obtainment situation (demand is less than obtainment) of multiple ES; an insufficient obtainment situation (demand is greater than obtainment) of multiple ES was mainly situated in the northern part of Mengyin County. Overall, the current state of multiple ES across Mengyin County is classified as "Endangered" classification according to application of threat categorization framework. It is necessary to restructure and manage socioeconomic factors for multiple ES. At national level, the macro decision-making (controlling population density) and the mechanisms (attracting high-quality human resources into the rural) will play an important role in promoting multiple ES management, and it is necessary to provide 3 or more years of tailored educational resources for rural residents to advance multiple ES in agricultural landscape. Development of agricultural PES programs in China that enable farmers to profit from production ES is a sustainable strategy for increasing multiple ecosystem services. Copyright © 2018 Elsevier B.V. All rights reserved.

The Testing Methods and Gender Differences in Multiple-Choice Assessment

NASA Astrophysics Data System (ADS)

Ng, Annie W. Y.; Chan, Alan H. S.

2009-10-01

This paper provides a comprehensive review of the multiple-choice assessment in the past two decades for facilitating people to conduct effective testing in various subject areas. It was revealed that a variety of multiple-choice test methods viz. conventional multiple-choice, liberal multiple-choice, elimination testing, confidence marking, probability testing, and order-of-preference scheme are available for use in assessing subjects' knowledge and decision ability. However, the best multiple-choice test method for use has not yet been identified. The review also indicated that the existence of gender differences in multiple-choice task performance might be due to the test area, instruction/scoring condition, and item difficulty.

Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape.

PubMed

Benda, Norbert; Brandt, Andreas

2018-01-01

Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

FAST TRACK PAPER: A construct of internal multiples from surface data only: the concept of virtual seismic events

NASA Astrophysics Data System (ADS)

Ikelle, Luc T.

2006-02-01

We here describe one way of constructing internal multiples from surface seismic data only. The key feature of our construct of internal multiples is the introduction of the concept of virtual seismic events. Virtual events here are events, which are not directly recorded in standard seismic data acquisition, but their existence allows us to construct internal multiples with scattering points at the sea surface; the standard construct of internal multiples does not include any scattering points at the sea surface. The mathematical and computational operations invoked in our construction of virtual events and internal multiples are similar to those encountered in the construction of free-surface multiples based on the Kirchhoff or Born scattering theory. For instance, our construct operates on one temporal frequency at a time, just like free-surface demultiple algorithms; other internal multiple constructs tend to require all frequencies for the computation of an internal multiple at a given frequency. It does not require any knowledge of the subsurface nor an explicit knowledge of specific interfaces that are responsible for the generation of internal multiples in seismic data. However, our construct requires that the data be divided into two, three or four windows to avoid generating primaries. This segmentation of the data also allows us to select a range of periods of internal multiples that one wishes to construct because, in the context of the attenuation of internal multiples, it is important to avoid generating short-period internal multiples that may constructively average to form primaries at the seismic scale.

Multiplicity Counting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geist, William H.

2015-12-01

This set of slides begins by giving background and a review of neutron counting; three attributes of a verification item are discussed: 240Pu eff mass; α, the ratio of (α,n) neutrons to spontaneous fission neutrons; and leakage multiplication. It then takes up neutron detector systems – theory & concepts (coincidence counting, moderation, die-away time); detector systems – some important details (deadtime, corrections); introduction to multiplicity counting; multiplicity electronics and example distributions; singles, doubles, and triples from measured multiplicity distributions; and the point model: multiplicity mathematics.

Polynuclear aromatic hydrocarbons for fullerene synthesis in flames

DOEpatents

Alford, J. Michael; Diener, Michael D.

2006-12-19

This invention provides improved methods for combustion synthesis of carbon nanomaterials, including fullerenes, employing multiple-ring aromatic hydrocarbon fuels selected for high carbon conversion to extractable fullerenes. The multiple-ring aromatic hydrocarbon fuels include those that contain polynuclear aromatic hydrocarbons. More specifically, multiple-ring aromatic hydrocarbon fuels contain a substantial amount of indene, methylnapthalenes or mixtures thereof. Coal tar and petroleum distillate fractions provide low cost hydrocarbon fuels containing polynuclear aromatic hydrocarbons, including without limitation, indene, methylnapthalenes or mixtures thereof.

Upper Extremity Function in Multiple Sclerosis Patients With Advanced Disability Treated With Ocrevus

ClinicalTrials.gov

2018-06-18

Multiple Sclerosis; Pathologic Processes; Demyelinating Diseases; Demyelinating Autoimmune Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Primary Progressive Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis

The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis.

PubMed

Cottrell, D A; Kremenchutzky, M; Rice, G P; Koopman, W J; Hader, W; Baskerville, J; Ebers, G C

1999-04-01

We report a natural history study of 216 patients with primary progressive (PP)- multiple sclerosis defined by at least 1 year of exacerbation-free progression at onset. This represents 19.8% of a largely population-based patient cohort having a mean longitudinal follow-up of 23 years. This subgroup of PP-multiple sclerosis patients had a mean age of onset of 38.5 years, with females predominating by a ratio of 1.3:1.0. The rate of deterioration from disease onset was substantially more rapid than for relapsing-remitting multiple sclerosis, with a median time to disability status score (DSS) 6 and DSS 8 of 8 and 18 years, respectively. Forty-nine percent of patients were followed through to death. Examination of the early disease course revealed two groups with adverse prognostic profiles. Firstly, a shorter time to reach DSS 3 from onset of PP-multiple sclerosis significantly adversely influenced time to DSS 8. Second, involvement of three or more neurological systems at onset resulted in a median time to DSS 10 of 13.5 years in contrast to PP-multiple sclerosis patients with one system involved at onset where median time to death from multiple sclerosis was 33.2 years. However, age, gender and type of neurological system involved at onset appeared to have little influence on prognosis. Life expectancy, cause of mortality and familial history profile were similar in PP-multiple sclerosis and non-PP-multiple sclerosis (all other multiple sclerosis patients from the total population). From clinical onset, rate of progression was faster in the PP-multiple sclerosis group than in the secondary progressive (SP)-multiple sclerosis group. When the rates of progression from onset of the progressive phase to DSS 6, 8 and 10 were compared, SP-multiple sclerosis had a more rapid progressive phase. A substantial minority (28%) of the PP-multiple sclerosis cohort had a distinct relapse even decades after onset of progressive deterioration. These studies establish natural history outcomes for the subgroup of multiple sclerosis patients with primary progressive disease.

The Challenge of Multiple Perspectives: Multiple Solution Tasks for Students Incorporating Diverse Tools and Representation Systems

ERIC Educational Resources Information Center

Kordaki, Maria

2015-01-01

This study focuses on the role of multiple solution tasks (MST) incorporating multiple learning tools and representation systems (MTRS) in encouraging each student to develop multiple perspectives on the learning concepts under study and creativity of thought. Specifically, two types of MST were used, namely tasks that allowed and demanded…

Using Simultaneous Prompting Procedure to Promote Recall of Multiplication Facts by Middle School Students with Cognitive Impairment

ERIC Educational Resources Information Center

Rao, Shaila; Mallow, Lynette

2009-01-01

This study examined effectiveness of simultaneous prompting system in teaching students with cognitive impairment to automate recall of multiplication facts. A multiple probes design with multiple sets of math facts and replicated across multiple subjects was used to assess effectiveness of simultaneous prompting on recall of basic multiplication…

Teaching Multiplication of Numbers from 1 to 10 to STKIP Surya Students Using Matematika GASING

ERIC Educational Resources Information Center

Kusuma, Josephine; Sulistiawati

2014-01-01

Multiplication of numbers from 1 to 10 is very important as it provides the basis for learning multiplication of other larger numbers as well as other related mathematical operations. How do students learn multiplication? Usually students just memorize the results of multiplication. This is often performed without a complete comprehension of the…

Summary from Working Group on Multiple Beams and Funneling

NASA Technical Reports Server (NTRS)

Wangler, T. P.

1985-01-01

The working group on Multiple Beams and Funneling discussed various topics related to multiple beams and funneling, including (1) design considerations for multiple-beam accelerators; (2) scaling of current, emittance, and brightness for multiple-beam systems; (3) funneling lines using either discrete components or a radiofrequency quadrupole (RFQ) funneling structure; and (4) alternatives to funneling.

Multiple Correlation versus Multiple Regression.

ERIC Educational Resources Information Center

Huberty, Carl J.

2003-01-01

Describes differences between multiple correlation analysis (MCA) and multiple regression analysis (MRA), showing how these approaches involve different research questions and study designs, different inferential approaches, different analysis strategies, and different reported information. (SLD)

A Bayesian Poisson-lognormal Model for Count Data for Multiple-Trait Multiple-Environment Genomic-Enabled Prediction

PubMed Central

Montesinos-López, Osval A.; Montesinos-López, Abelardo; Crossa, José; Toledo, Fernando H.; Montesinos-López, José C.; Singh, Pawan; Juliana, Philomin; Salinas-Ruiz, Josafhat

2017-01-01

When a plant scientist wishes to make genomic-enabled predictions of multiple traits measured in multiple individuals in multiple environments, the most common strategy for performing the analysis is to use a single trait at a time taking into account genotype × environment interaction (G × E), because there is a lack of comprehensive models that simultaneously take into account the correlated counting traits and G × E. For this reason, in this study we propose a multiple-trait and multiple-environment model for count data. The proposed model was developed under the Bayesian paradigm for which we developed a Markov Chain Monte Carlo (MCMC) with noninformative priors. This allows obtaining all required full conditional distributions of the parameters leading to an exact Gibbs sampler for the posterior distribution. Our model was tested with simulated data and a real data set. Results show that the proposed multi-trait, multi-environment model is an attractive alternative for modeling multiple count traits measured in multiple environments. PMID:28364037

Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma

ClinicalTrials.gov

2018-02-27

Extramedullary Plasmacytoma; Isolated Plasmacytoma of Bone; Light Chain Deposition Disease; Primary Systemic Amyloidosis; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

PubMed

Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

2017-04-01

Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Skin contamination dosimeter

DOEpatents

Hamby, David M [Corvallis, OR; Farsoni, Abdollah T [Corvallis, OR; Cazalas, Edward [Corvallis, OR

2011-06-21

A technique and device provides absolute skin dosimetry in real time at multiple tissue depths simultaneously. The device uses a phoswich detector which has multiple scintillators embedded at different depths within a non-scintillating material. A digital pulse processor connected to the phoswich detector measures a differential distribution (dN/dH) of count rate N as function of pulse height H for signals from each of the multiple scintillators. A digital processor computes in real time from the differential count-rate distribution for each of multiple scintillators an estimate of an ionizing radiation dose delivered to each of multiple depths of skin tissue corresponding to the multiple scintillators embedded at multiple corresponding depths within the non-scintillating material.

Improving Multiple Fault Diagnosability using Possible Conflicts

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Biswas, Gautam; Koutsoukos, Xenofon; Pulido, Belarmino

2012-01-01

Multiple fault diagnosis is a difficult problem for dynamic systems. Due to fault masking, compensation, and relative time of fault occurrence, multiple faults can manifest in many different ways as observable fault signature sequences. This decreases diagnosability of multiple faults, and therefore leads to a loss in effectiveness of the fault isolation step. We develop a qualitative, event-based, multiple fault isolation framework, and derive several notions of multiple fault diagnosability. We show that using Possible Conflicts, a model decomposition technique that decouples faults from residuals, we can significantly improve the diagnosability of multiple faults compared to an approach using a single global model. We demonstrate these concepts and provide results using a multi-tank system as a case study.

Effective seat-to-head transmissibility in whole-body vibration: Effects of posture and arm position

NASA Astrophysics Data System (ADS)

Rahmatalla, Salam; DeShaw, Jonathan

2011-12-01

Seat-to-head transmissibility is a biomechanical measure that has been widely used for many decades to evaluate seat dynamics and human response to vibration. Traditionally, transmissibility has been used to correlate single-input or multiple-input with single-output motion; it has not been effectively used for multiple-input and multiple-output scenarios due to the complexity of dealing with the coupled motions caused by the cross-axis effect. This work presents a novel approach to use transmissibility effectively for single- and multiple-input and multiple-output whole-body vibrations. In this regard, the full transmissibility matrix is transformed into a single graph, such as those for single-input and single-output motions. Singular value decomposition and maximum distortion energy theory were used to achieve the latter goal. Seat-to-head transmissibility matrices for single-input/multiple-output in the fore-aft direction, single-input/multiple-output in the vertical direction, and multiple-input/multiple-output directions are investigated in this work. A total of ten subjects participated in this study. Discrete frequencies of 0.5-16 Hz were used for the fore-aft direction using supported and unsupported back postures. Random ride files from a dozer machine were used for the vertical and multiple-axis scenarios considering two arm postures: using the armrests or grasping the steering wheel. For single-input/multiple-output, the results showed that the proposed method was very effective in showing the frequencies where the transmissibility is mostly sensitive for the two sitting postures and two arm positions. For multiple-input/multiple-output, the results showed that the proposed effective transmissibility indicated higher values for the armrest-supported posture than for the steering-wheel-supported posture.

Managing Multiple Health Problems: Living with Multiple Health Problems

MedlinePlus

... treatments affect people with multiple health problems. Guiding Principles on Caring for Older Adults with Multiple Health ... interactions and other side effects. Each of the principles above is intended to help improve the health ...

Treatment of Cognitive Impairment in Multiple Sclerosis

PubMed Central

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

Multiple emulsions: an overview.

PubMed

Khan, Azhar Yaqoob; Talegaonkar, Sushama; Iqbal, Zeenat; Ahmed, Farhan Jalees; Khar, Roop Krishan

2006-10-01

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.

Relative efficiency of joint-model and full-conditional-specification multiple imputation when conditional models are compatible: The general location model.

PubMed

Seaman, Shaun R; Hughes, Rachael A

2018-06-01

Estimating the parameters of a regression model of interest is complicated by missing data on the variables in that model. Multiple imputation is commonly used to handle these missing data. Joint model multiple imputation and full-conditional specification multiple imputation are known to yield imputed data with the same asymptotic distribution when the conditional models of full-conditional specification are compatible with that joint model. We show that this asymptotic equivalence of imputation distributions does not imply that joint model multiple imputation and full-conditional specification multiple imputation will also yield asymptotically equally efficient inference about the parameters of the model of interest, nor that they will be equally robust to misspecification of the joint model. When the conditional models used by full-conditional specification multiple imputation are linear, logistic and multinomial regressions, these are compatible with a restricted general location joint model. We show that multiple imputation using the restricted general location joint model can be substantially more asymptotically efficient than full-conditional specification multiple imputation, but this typically requires very strong associations between variables. When associations are weaker, the efficiency gain is small. Moreover, full-conditional specification multiple imputation is shown to be potentially much more robust than joint model multiple imputation using the restricted general location model to mispecification of that model when there is substantial missingness in the outcome variable.

Detection of Multiple Stationary Humans Using UWB MIMO Radar.

PubMed

Liang, Fulai; Qi, Fugui; An, Qiang; Lv, Hao; Chen, Fuming; Li, Zhao; Wang, Jianqi

2016-11-16

Remarkable progress has been achieved in the detection of single stationary human. However, restricted by the mutual interference of multiple humans (e.g., strong sidelobes of the torsos and the shadow effect), detection and localization of the multiple stationary humans remains a huge challenge. In this paper, ultra-wideband (UWB) multiple-input and multiple-output (MIMO) radar is exploited to improve the detection performance of multiple stationary humans for its multiple sight angles and high-resolution two-dimensional imaging capacity. A signal model of the vital sign considering both bi-static angles and attitude angle of the human body is firstly developed, and then a novel detection method is proposed to detect and localize multiple stationary humans. In this method, preprocessing is firstly implemented to improve the signal-to-noise ratio (SNR) of the vital signs, and then a vital-sign-enhanced imaging algorithm is presented to suppress the environmental clutters and mutual affection of multiple humans. Finally, an automatic detection algorithm including constant false alarm rate (CFAR), morphological filtering and clustering is implemented to improve the detection performance of weak human targets affected by heavy clutters and shadow effect. The simulation and experimental results show that the proposed method can get a high-quality image of multiple humans and we can use it to discriminate and localize multiple adjacent human targets behind brick walls.

Detection of Multiple Stationary Humans Using UWB MIMO Radar

PubMed Central

Liang, Fulai; Qi, Fugui; An, Qiang; Lv, Hao; Chen, Fuming; Li, Zhao; Wang, Jianqi

2016-01-01

Remarkable progress has been achieved in the detection of single stationary human. However, restricted by the mutual interference of multiple humans (e.g., strong sidelobes of the torsos and the shadow effect), detection and localization of the multiple stationary humans remains a huge challenge. In this paper, ultra-wideband (UWB) multiple-input and multiple-output (MIMO) radar is exploited to improve the detection performance of multiple stationary humans for its multiple sight angles and high-resolution two-dimensional imaging capacity. A signal model of the vital sign considering both bi-static angles and attitude angle of the human body is firstly developed, and then a novel detection method is proposed to detect and localize multiple stationary humans. In this method, preprocessing is firstly implemented to improve the signal-to-noise ratio (SNR) of the vital signs, and then a vital-sign-enhanced imaging algorithm is presented to suppress the environmental clutters and mutual affection of multiple humans. Finally, an automatic detection algorithm including constant false alarm rate (CFAR), morphological filtering and clustering is implemented to improve the detection performance of weak human targets affected by heavy clutters and shadow effect. The simulation and experimental results show that the proposed method can get a high-quality image of multiple humans and we can use it to discriminate and localize multiple adjacent human targets behind brick walls. PMID:27854356

Generating clock signals for a cycle accurate, cycle reproducible FPGA based hardware accelerator

DOEpatents

Asaad, Sameth W.; Kapur, Mohit

2016-01-05

A method, system and computer program product are disclosed for generating clock signals for a cycle accurate FPGA based hardware accelerator used to simulate operations of a device-under-test (DUT). In one embodiment, the DUT includes multiple device clocks generating multiple device clock signals at multiple frequencies and at a defined frequency ratio; and the FPG hardware accelerator includes multiple accelerator clocks generating multiple accelerator clock signals to operate the FPGA hardware accelerator to simulate the operations of the DUT. In one embodiment, operations of the DUT are mapped to the FPGA hardware accelerator, and the accelerator clock signals are generated at multiple frequencies and at the defined frequency ratio of the frequencies of the multiple device clocks, to maintain cycle accuracy between the DUT and the FPGA hardware accelerator. In an embodiment, the FPGA hardware accelerator may be used to control the frequencies of the multiple device clocks.

Accounting for multiple births in randomised trials: a systematic review.

PubMed

Yelland, Lisa Nicole; Sullivan, Thomas Richard; Makrides, Maria

2015-03-01

Multiple births are an important subgroup to consider in trials aimed at reducing preterm birth or its consequences. Including multiples results in a unique mixture of independent and clustered data, which has implications for the design, analysis and reporting of the trial. We aimed to determine how multiple births were taken into account in the design and analysis of recent trials involving preterm infants, and whether key information relevant to multiple births was reported. We conducted a systematic review of multicentre randomised trials involving preterm infants published between 2008 and 2013. Information relevant to multiple births was extracted. Of the 56 trials included in the review, 6 (11%) excluded multiples and 24 (43%) failed to indicate whether multiples were included. Among the 26 trials that reported multiples were included, only one (4%) accounted for clustering in the sample size calculations and eight (31%) took the clustering into account in the analysis of the primary outcome. Of the 20 trials that randomised infants, 12 (60%) failed to report how infants from the same birth were randomised. Information on multiple births is often poorly reported in trials involving preterm infants, and clustering due to multiple births is rarely taken into account. Since ignoring clustering could result in inappropriate recommendations for clinical practice, clustering should be taken into account in the design and analysis of future neonatal and perinatal trials including infants from a multiple birth. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Multiple switching modes and multiple level states in memristive devices

NASA Astrophysics Data System (ADS)

Miao, Feng; Yang, J. Joshua; Borghetti, Julien; Strachan, John Paul; Zhang, M.-X.; Goldfarb, Ilan; Medeiros-Ribeiro, Gilberto; Williams, R. Stanley

2011-03-01

As one of the most promising technologies for next generation non-volatile memory, metal oxide based memristive devices have demonstrated great advantages on scalability, operating speed and power consumption. Here we report the observation of multiple switching modes and multiple level states in different memristive systems. The multiple switching modes can be obtained by limiting the current during electroforming, and related transport behaviors, including ionic and electronic motions, are characterized. Such observation can be rationalized by a model of two effective switching layers adjacent to the bottom and top electrodes. Multiple level states, corresponding to different composition of the conducting channel, will also be discussed in the context of multiple-level storage for high density, non-volatile memory applications.

Li-ion battery thermal runaway suppression system using microchannel coolers and refrigerant injections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bandhauer, Todd M.; Farmer, Joseph C.

A battery management system with thermally integrated fire suppression includes a multiplicity of individual battery cells in a housing; a multiplicity of cooling passages in the housing within or between the multiplicity of individual battery cells; a multiplicity of sensors operably connected to the individual battery cells, the sensors adapted to detect a thermal runaway event related to one or more of the multiplicity of individual battery cells; and a management system adapted to inject coolant into at least one of the multiplicity of cooling passages upon the detection of the thermal runaway event by the any one of themore » multiplicity of sensors, so that the thermal runaway event is rapidly quenched.« less

Data matching for free-surface multiple attenuation by multidimensional deconvolution

NASA Astrophysics Data System (ADS)

van der Neut, Joost; Frijlink, Martijn; van Borselen, Roald

2012-09-01

A common strategy for surface-related multiple elimination of seismic data is to predict multiples by a convolutional model and subtract these adaptively from the input gathers. Problems can be posed by interfering multiples and primaries. Removing multiples by multidimensional deconvolution (MDD) (inversion) does not suffer from these problems. However, this approach requires data to be consistent, which is often not the case, especially not at interpolated near-offsets. A novel method is proposed to improve data consistency prior to inversion. This is done by backpropagating first-order multiples with a time-gated reference primary event and matching these with early primaries in the input gather. After data matching, multiple elimination by MDD can be applied with a deterministic inversion scheme.

A Bayesian Poisson-lognormal Model for Count Data for Multiple-Trait Multiple-Environment Genomic-Enabled Prediction.

PubMed

Montesinos-López, Osval A; Montesinos-López, Abelardo; Crossa, José; Toledo, Fernando H; Montesinos-López, José C; Singh, Pawan; Juliana, Philomin; Salinas-Ruiz, Josafhat

2017-05-05

When a plant scientist wishes to make genomic-enabled predictions of multiple traits measured in multiple individuals in multiple environments, the most common strategy for performing the analysis is to use a single trait at a time taking into account genotype × environment interaction (G × E), because there is a lack of comprehensive models that simultaneously take into account the correlated counting traits and G × E. For this reason, in this study we propose a multiple-trait and multiple-environment model for count data. The proposed model was developed under the Bayesian paradigm for which we developed a Markov Chain Monte Carlo (MCMC) with noninformative priors. This allows obtaining all required full conditional distributions of the parameters leading to an exact Gibbs sampler for the posterior distribution. Our model was tested with simulated data and a real data set. Results show that the proposed multi-trait, multi-environment model is an attractive alternative for modeling multiple count traits measured in multiple environments. Copyright © 2017 Montesinos-López et al.

The influence of talker and foreign-accent variability on spoken word identification.

PubMed

Bent, Tessa; Holt, Rachael Frush

2013-03-01

In spoken word identification and memory tasks, stimulus variability from numerous sources impairs performance. In the current study, the influence of foreign-accent variability on spoken word identification was evaluated in two experiments. Experiment 1 used a between-subjects design to test word identification in noise in single-talker and two multiple-talker conditions: multiple talkers with the same accent and multiple talkers with different accents. Identification performance was highest in the single-talker condition, but there was no difference between the single-accent and multiple-accent conditions. Experiment 2 further explored word recognition for multiple talkers in single-accent versus multiple-accent conditions using a mixed design. A detriment to word recognition was observed in the multiple-accent condition compared to the single-accent condition, but the effect differed across the language backgrounds tested. These results demonstrate that the processing of foreign-accent variation may influence word recognition in ways similar to other sources of variability (e.g., speaking rate or style) in that the inclusion of multiple foreign accents can result in a small but significant performance decrement beyond the multiple-talker effect.

A Comparison of Raw-to-Scale Conversion Consistency between Single- and Multiple-Linking Using a Nonequivalent Groups Anchor Test Design. Research Report. ETS RR-14-13

ERIC Educational Resources Information Center

Liu, Jinghua; Guo, Hongwen; Dorans, Neil J.

2014-01-01

Maintaining score interchangeability and scale consistency is crucial for any testing programs that administer multiple forms across years. The use of a multiple linking design, which involves equating a new form to multiple old forms and averaging the conversions, has been proposed to control scale drift. However, the use of multiple linking…

Multiple-hypothesis multiple-model line tracking

NASA Astrophysics Data System (ADS)

Pace, Donald W.; Owen, Mark W.; Cox, Henry

2000-07-01

Passive sonar signal processing generally includes tracking of narrowband and/or broadband signature components observed on a Lofargram or on a Bearing-Time-Record (BTR) display. Fielded line tracking approaches to date have been recursive and single-hypthesis-oriented Kalman- or alpha-beta filters, with no mechanism for considering tracking alternatives beyond the most recent scan of measurements. While adaptivity is often built into the filter to handle changing track dynamics, these approaches are still extensions of single target tracking solutions to multiple target tracking environment. This paper describes an application of multiple-hypothesis, multiple target tracking technology to the sonar line tracking problem. A Multiple Hypothesis Line Tracker (MHLT) is developed which retains the recursive minimum-mean-square-error tracking behavior of a Kalman Filter in a maximum-a-posteriori delayed-decision multiple hypothesis context. Multiple line track filter states are developed and maintained using the interacting multiple model (IMM) state representation. Further, the data association and assignment problem is enhanced by considering line attribute information (line bandwidth and SNR) in addition to beam/bearing and frequency fit. MHLT results on real sonar data are presented to demonstrate the benefits of the multiple hypothesis approach. The utility of the system in cluttered environments and particularly in crossing line situations is shown.

Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis.

PubMed

Fröhlich, Kilian; Winder, Klemens; Linker, Ralf A; Engelhorn, Tobias; Dörfler, Arnd; Lee, De-Hyung; Hilz, Max J; Schwab, Stefan; Seifert, Frank

2018-06-01

Background It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients. Methods We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test. Results From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia. Conclusions Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.

Recent trends in the incidence of multiple births and its consequences on perinatal problems in Korea.

PubMed

Choi, Sun Hee; Park, Young Sil; Shim, Kye Shik; Choi, Yong Sung; Chang, Ji Young; Hahn, Won Ho; Bae, Chong-Woo

2010-08-01

The aim of this study was to survey multiple birth data and to analyze the recent trends of multiple births and its consequences on perinatal problems in Korea from 1991 to 2008. Data were obtained from the Korean Statistical Information Service. The total number of multiple births showed increasing trends. The multiple birth rate was maintained within less than 10.0 for the decade from 1981 to 1990. However, it increased gradually to reach 27.5 in 2008. The maternal age for multiple births was higher than for total live births. The mean birth weight of the total live births was 3.23 kg; for the multiple births it was 2.40 kg in 2008. The incidence of low birth weight infants (LBWI) among total live births was 3.8% in 2000 and 4.9% in 2008. For multiple births it was 49.2% and 53.0% during the same years. The incidence of preterm births among total live births was 3.8% in 2000 and 5.5% in 2008; for the multiple births it was 38.3% and 51.5% during the same years. The incidence of multiple births and its consequences on perinatal problems (preterm, LBWI, and advanced-maternal age) have been increased steadily over the last two decades in Korea.

Interfacial film stabilized W/O/W nano multiple emulsions loaded with green tea and lotus extracts: systematic characterization of physicochemical properties and shelf-storage stability.

PubMed

Mahmood, Tariq; Akhtar, Naveed; Manickam, Sivakumar

2014-05-12

Multiple emulsions have excellent encapsulating potential and this investigation has been aimed to encapsulate two different plant extracts as functional cosmetic agents in the W/O/W multiple emulsions and the resultant system's long term stability has been determined in the presence of a thickener, hydroxypropyl methylcellulose (HPMC). Multiple W/O/W emulsions have been generated using cetyl dimethicone copolyol as lipophilic emulsifier and a blend of polyoxyethylene (20) cetyl ether and cetomacrogol 1000® as hydrophilic emulsifiers. The generated multiple emulsions have been characterized with conductivity, pH, microscopic analysis, phase separation and rheology for a period of 30 days. Moreover, long term shelf-storage stability has been tested to understand the shelf-life by keeping the generated multiple emulsion formulations at 25 ± 10°C and at 40 ± 10% relative humidity for a period of 12 months. It has been observed that the hydrophilic emulsifiers and HPMC have considerably improved the stability of multiple emulsions for the followed period of 12 months at different storage conditions. These multiple emulsions have shown improved entrapment efficiencies concluded on the release rate of conductometric tracer entrapped in the inner aqueous phase of the multiple emulsions. Multiple emulsions have been found to be stable for a longer period of time with promising characteristics. Hence, stable multiple emulsions loaded with green tea and lotus extracts could be explored for their cosmetic benefits.

Describing and understanding behavioral responses to multiple stressors and multiple stimuli.

PubMed

Hale, Robin; Piggott, Jeremy J; Swearer, Stephen E

2017-01-01

Understanding the effects of environmental change on natural ecosystems is a major challenge, particularly when multiple stressors interact to produce unexpected "ecological surprises" in the form of complex, nonadditive effects that can amplify or reduce their individual effects. Animals often respond behaviorally to environmental change, and multiple stressors can have both population-level and community-level effects. However, the individual, not combined, effects of stressors on animal behavior are commonly studied. There is a need to understand how animals respond to the more complex combinations of stressors that occur in nature, which requires a systematic and rigorous approach to quantify the various potential behavioral responses to the independent and interactive effects of stressors. We illustrate a robust, systematic approach for understanding behavioral responses to multiple stressors based on integrating schemes used to quantitatively classify interactions in multiple-stressor research and to qualitatively view interactions between multiple stimuli in behavioral experiments. We introduce and unify the two frameworks, highlighting their conceptual and methodological similarities, and use four case studies to demonstrate how this unification could improve our interpretation of interactions in behavioral experiments and guide efforts to manage the effects of multiple stressors. Our unified approach: (1) provides behavioral ecologists with a more rigorous and systematic way to quantify how animals respond to interactions between multiple stimuli, an important theoretical advance, (2) helps us better understand how animals behave when they encounter multiple, potentially interacting stressors, and (3) contributes more generally to the understanding of "ecological surprises" in multiple stressors research.

21 CFR 866.5660 - Multiple autoantibodies immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5660 Multiple autoantibodies immunological test system. (a) Identification. A multiple autoantibodies... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system...

Multiplicities of secondary hadrons produced in vp and overlinevp charged current interactions

NASA Astrophysics Data System (ADS)

Grässler, H.; Lanske, D.; Schulte, R.; Jones, G. T.; Middleton, R. P.; O'Neale, S. W.; Böckmann, K.; Gebel, W.; Geich-Gimbel, C.; Nellen, B.; Grant, A.; Klein, H.; Morrison, D. R. O.; Schmid, P.; Wachsmuth, H.; Chima, J. S.; Mobayyen, M. M.; Talebzadeh, M.; Villalobos-Baillie, O.; Aderholz, M.; Deck, L.; Schmitz, N.; Settles, R.; Wernhard, K. L.; Wittek, W.; Corrigan, G.; Myatt, G.; Radojicić, D.; Saitta, B.; Wells, J.; Aachen-Birmingham-Bonn-CERN-Imperial College-München (MPI)-Oxford Collaboration

1983-08-01

In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in νp and overlinevp interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e +e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and a larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above ˜ 7 GeV and local charge compensation within an event.

Abnormal pain perception in patients with Multiple System Atrophy.

PubMed

Ory-Magne, F; Pellaprat, J; Harroch, E; Galitzsky, M; Rousseau, V; Pavy-Le Traon, A; Rascol, O; Gerdelat, A; Brefel-Courbon, C

2018-03-01

Patients with Parkinson's disease or Multiple System Atrophy frequently experience painful sensations. The few studies investigating pain mechanisms in Multiple System Atrophy patients have reported contradictory results. In our study, we compared pain thresholds in Multiple System Atrophy and Parkinson's disease patients and healthy controls and evaluated the effect of l-DOPA on pain thresholds. We assessed subjective and objective pain thresholds (using a thermotest and RIII reflex), and pain tolerance in OFF and ON conditions, clinical pain, motor and psychological evaluation. Pain was reported in 78.6% of Multiple System Atrophy patients and in 37.5% of Parkinson's disease patients. In the OFF condition, subjective and objective pain thresholds were significantly lower in Multiple System Atrophy patients than in healthy controls (43.8 °C ± 1.3 vs 45.7 °C ± 0.8; p = 0.0005 and 7.4 mA ± 3.8 vs 13.7 mA ± 2.8; p = 0.002, respectively). They were also significantly reduced in Multiple System Atrophy compared to Parkinson's disease patients. No significant difference was found in pain tolerance for the 3 groups and in the effect of l-DOPA on pain thresholds in Multiple System Atrophy and Parkinson's disease patients. In the ON condition, pain tolerance tended to be reduced in Multiple System Atrophy versus Parkinson's disease patients (p = 0.05). Multiple System Atrophy patients had an increase in pain perception compared to Parkinson's disease patients and healthy controls. The l-DOPA effect was similar for pain thresholds in Multiple System Atrophy and Parkinson's disease patients, but tended to worsen pain tolerance in Multiple System Atrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of electrofishing gear type on spatial and temporal variability in fish community sampling

USGS Publications Warehouse

Meador, M.R.; McIntyre, J.P.

2003-01-01

Fish community data collected from 24 major river basins between 1993 and 1998 as part of the U.S. Geological Survey's National Water-Quality Assessment Program were analyzed to assess multiple-reach (three consecutive reaches) and multiple-year (three consecutive years) variability in samples collected at a site. Variability was assessed using the coefficient of variation (CV; SD/mean) of species richness, the Jaccard index (JI), and the percent similarity index (PSI). Data were categorized by three electrofishing sample collection methods: backpack, towed barge, and boat. Overall, multiple-reach CV values were significantly lower than those for multiple years, whereas multiple-reach JI and PSI values were significantly greater than those for multiple years. Multiple-reach and multiple-year CV values did not vary significantly among electrofishing methods, although JI and PSI values were significantly greatest for backpack electrofishing across multiple reaches and multiple years. The absolute difference between mean species richness for multiple-reach samples and mean species richness for multiple-year samples was 0.8 species (9.5% of total species richness) for backpack samples, 1.7 species (10.1%) for towed-barge samples, and 4.5 species (24.4%) for boat-collected samples. Review of boat-collected fish samples indicated that representatives of four taxonomic families - Catostomidae, Centrarchidae, Cyprinidae, and Ictaluridae - were collected at all sites. Of these, catostomids exhibited greater interannual variability than centrarchids, cyprinids, or ictalurids. Caution should be exercised when combining boat-collected fish community data from different years because of relatively high interannual variability, which is primarily due to certain relatively mobile species. Such variability may obscure longer-term trends.

Influence of the Supramolecular Micro-Assembly of Multiple Emulsions on their Biopharmaceutical Features and In vivo Therapeutic Response.

PubMed

Cilurzo, Felisa; Cristiano, Maria Chiara; Di Marzio, Luisa; Cosco, Donato; Carafa, Maria; Ventura, Cinzia Anna; Fresta, Massimo; Paolino, Donatella

2015-01-01

The ability of some surfactants to self-assemble in a water/oil bi-phase environment thus forming supramolecular structure leading to the formation of w/o/w multiple emulsions was investigated. The w/o/w multiple emulsions obtained by self-assembling (one-step preparation method) were compared with those prepared following the traditional two-step procedure. Methyl-nicotinate was used as a hydrophilic model drug. The formation of the multiple emulsion structure was evidenced by optical microscopy, which showed a mean size of the inner oil droplets of 6 μm and 10 μm for one-step and two-step multiple emulsions, respectively. The in vitrobiopharmaceutical features of the various w/o/w multiple emulsion formulations were evaluated by means of viscosimetry studies, drug release and in vitro percutaneous permeation experiments through human stratum corneum and viable epidermis membranes. The self-assembled multiple emulsions allowed a more gradual percutaneous permeation (a zero-order permeation rate) than the two-step ones. The in vivotopical carrier properties of the two different multiple emulsions were evaluated on healthy human volunteers by using the spectrophotometry of reflectance, an in vivonon invasive method. These multiple emulsion systems were also compared with conventional emulsion formulations. Our findings demonstrated that the multiple emulsions obtained by self-assembling were able to provide a more sustained drug delivery into the skin and hence a longer therapeutic action than two-step multiple emulsions and conventional emulsion formulations. Finally, our findings showed that the supramolecular micro-assembly of multiple emulsions was able to influence not only the biopharmaceutical characteristics but also the potential in vivotherapeutic response.

Sit less and move more: perspectives of adults with multiple sclerosis.

PubMed

Aminian, Saeideh; Ezeugwu, Victor E; Motl, Robert W; Manns, Patricia J

2017-12-20

Multiple sclerosis is a chronic neurological disease with the highest prevalence in Canada. Replacing sedentary behavior with light activities may be a feasible approach to manage multiple sclerosis symptoms. This study explored the perspectives of adults with multiple sclerosis about sedentary behavior, physical activity and ways to change behavior. Fifteen adults with multiple sclerosis (age 43 ± 13 years; mean ± standard deviation), recruited through the multiple sclerosis Clinic at the University of Alberta, Edmonton, Canada, participated in semi-structured interviews. Interview audios were transcribed verbatim and coded. NVivo software was used to facilitate the inductive process of thematic analysis. Balancing competing priorities between sitting and moving was the primary theme. Participants were aware of the benefits of physical activity to their overall health, and in the management of fatigue and muscle stiffness. Due to fatigue, they often chose sitting to get their energy back. Further, some barriers included perceived fear of losing balance or embarrassment while walking. Activity monitoring, accountability, educational and individualized programs were suggested strategies to motivate more movement. Adults with multiple sclerosis were open to the idea of replacing sitting with light activities. Motivational and educational programs are required to help them to change sedentary behavior to moving more. IMPLICATIONS FOR REHABILITATION One of the most challenging and common difficulties of multiple sclerosis is walking impairment that worsens because of multiple sclerosis progression, and is a common goal in the rehabilitation of people with multiple sclerosis. The deterioration in walking abilities is related to lower levels of physical activity and more sedentary behavior, such that adults with multiple sclerosis spend 8 to 10.5 h per day sitting. Replacing prolonged sedentary behavior with light physical activities, and incorporating education, encouragement, and self-monitoring strategies are feasible approaches to manage the symptoms of multiple sclerosis.

Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades.

PubMed

Kyle, Robert A; Therneau, Terry M; Rajkumar, S Vincent; Larson, Dirk R; Plevak, Matthew F; Melton, L Joseph

2004-12-01

Previous studies have indicated that the incidence and mortality rates for multiple myeloma have increased in the United States. The authors reported on the incidence of multiple myeloma in Olmsted County, Minnesota, between 1991 and 2001 and on trends in multiple myeloma incidence over the last 56 years. Using the files of the Mayo Clinic and the Olmsted Medical Center (Rochester, MN), the authors identified all residents of Olmsted County who had multiple myeloma, suspected myeloma, or a related disorder. Reports of all laboratory determinations, in addition to autopsy findings and death certificates, were obtained. The criteria for the diagnosis of multiple myeloma have not changed during the last 6 decades. All but 1 of the 47 residents with multiple myeloma first diagnosed between 1991 and 2001 were recognized antemortem. Fifty-five percent had a previous monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma before multiple myeloma was diagnosed. From 1991 to 2001, the overall annual incidence rate, age-adjusted to the 2000 U.S. population, was 4.3 per 100,000 (95% confidence interval, 3.0-5.5 per 100,000). Poisson regression analysis showed no statistically significant trend in Olmsted County incidence rates over 56 years. In similar fashion, the authors adjusted multiple myeloma incidence rates from nine other studies worldwide for which adequate data were available and documented similar findings in each case, except for one study that included patients with smoldering multiple myeloma. The overall incidence of multiple myeloma in Olmsted County, Minnesota, has not changed in almost 6 decades. The apparent increase in incidence elsewhere is unexplained but probably is attributable to improvements in diagnostic techniques, particularly in older patients. (c) 2004 American Cancer Society

q-Gaussian distributions and multiplicative stochastic processes for analysis of multiple financial time series

NASA Astrophysics Data System (ADS)

Sato, Aki-Hiro

2010-12-01

This study considers q-Gaussian distributions and stochastic differential equations with both multiplicative and additive noises. In the M-dimensional case a q-Gaussian distribution can be theoretically derived as a stationary probability distribution of the multiplicative stochastic differential equation with both mutually independent multiplicative and additive noises. By using the proposed stochastic differential equation a method to evaluate a default probability under a given risk buffer is proposed.

Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC).

PubMed

Birmann, Brenda M; Andreotti, Gabriella; De Roos, Anneclaire J; Camp, Nicola J; Chiu, Brian C H; Spinelli, John J; Becker, Nikolaus; Benhaim-Luzon, Véronique; Bhatti, Parveen; Boffetta, Paolo; Brennan, Paul; Brown, Elizabeth E; Cocco, Pierluigi; Costas, Laura; Cozen, Wendy; de Sanjosé, Silvia; Foretová, Lenka; Giles, Graham G; Maynadié, Marc; Moysich, Kirsten; Nieters, Alexandra; Staines, Anthony; Tricot, Guido; Weisenburger, Dennis; Zhang, Yawei; Baris, Dalsu; Purdue, Mark P

2017-06-01

Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m 2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; P = 0.007]. We observed significant heterogeneity by study design ( P = 0.04), noting the BMI-multiple myeloma association only for population-based studies ( P trend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m 2 ; OR, 1.2; 95% CI, 1.1-1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI ( P interaction <0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25-<30 kg/m 2 ) or obese (30+ kg/m 2 ) in both younger and usual adulthood (vs. individuals consistently <25 kg/m 2 ), but not for those overweight or obese at only one time period. Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood. Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Tehran Survey of Potential Risk Factors for Multiple Births.

PubMed

Omani Samani, Reza; Almasi-Hashiani, Amir; Vesali, Samira; Shokri, Fatemeh; Cheraghi, Rezvaneh; Torkestani, Farahnaz; Sepidarkish, Mahdi

2017-10-01

The multiple pregnancy incidence is increasing worldwide. This increased incidence is concerning to the health care system. This study aims to determine the frequency of multiple pregnancy and identify factors that affect this frequency in Tehran, Iran. This cross-sectional study included 5170 mothers in labor between July 6-21, 2015 from 103 hospitals with Obstetrics and Gynecology Wards. The questionnaire used in this study consisted of five parts: demographic characteristics; information related to pregnancy; information related to the infant; information regarding the multiple pregnancy; and information associated with infertility. We recruited 103 trained midwives to collect data related to the questionnaire from eligible participants through an interview and medical records review. Frequencies and odds ratios (OR) for the association between multiple pregnancy and the selected characteristics (maternal age, economic status, history of multiple pregnancy in first-degree relatives, and reproductive history) were computed by multiple logistic regression. Stata software, version 13 (Stata Corp, College Station, TX, USA) was used for all statistical analyses. Multiple pregnancy had a prevalence of 1.48% [95% confidence interval (CI): 1.19-1.85]. After controlling for confounding variables, we observed a significant association between frequency of multiple pregnancy and mother's age (OR=1.04, 95% CI: 1.001-1.09, P=0.044), assisted reproductive technique (ART, OR=6.11, 95% CI: 1.7- 21.97, P=0.006), and history of multiple pregnancy in the mother's family (OR=5.49, 95% CI: 3.55-9.93, P=0.001). The frequency of multiple pregnancy approximated results reported in previous studies in Iran. Based on the results, we observed significantly greater frequency of multiple pregnancy in older women, those with a history of ART, and a history of multiple pregnancy in the mother's family compared to the other variables. Copyright© by Royan Institute. All rights reserved.

Measurement of charm and beauty production at central rapidity versus charged-particle multiplicity in proton-proton collisions at $$ \\sqrt{s}=7 $$ TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adam, J.

Prompt D meson and non-prompt J/ψ yields are studied as a function of the multiplicity of charged particles produced in inelastic proton-proton collisions at a centre-of-mass energy ofmore » $$ \\sqrt{s}=7 $$ TeV. The results are reported as a ratio between yields in a given multiplicity interval normalised to the multiplicity-integrated ones (relative yields). They are shown as a function of the multiplicity of charged particles normalised to the average value for inelastic collisions (relative charged-particle multiplicity). D 0, D + and D *+ mesons are measured in five p T intervals from 1 GeV/c to 20 GeV/c and for |y| < 0.5 via their hadronic decays. The D-meson relative yield is found to increase with increasing charged-particle multiplicity. For events with multiplicity six times higher than the average multiplicity of inelastic collisions, a yield enhancement of a factor about 15 relative to the multiplicity-integrated yield in inelastic collisions is observed. The yield enhancement is independent of transverse momentum within the uncertainties of the measurement. The D 0-meson relative yield is also measured as a function of the relative multiplicity at forward pseudo-rapidity. The non-prompt J/ψ, i.e. the B hadron, contribution to the inclusive J/ψ production is measured in the di-electron decay channel at central rapidity. It is evaluated for p T > 1.3 GeV/c and |y| < 0.9, and extrapolated to p T > 0. The fraction of non-prompt J/ψ in the inclusive J/ψ yields shows no dependence on the charged-particle multiplicity at central rapidity. Charm and beauty hadron relative yields exhibit a similar increase with increasing charged-particle multiplicity. Finally, the measurements are compared to PYTHIA 8, EPOS 3 and percolation calculations.« less

Measurement of charm and beauty production at central rapidity versus charged-particle multiplicity in proton-proton collisions at $$ \\sqrt{s}=7 $$ TeV

DOE PAGES

Adam, J.

2015-09-22

Prompt D meson and non-prompt J/ψ yields are studied as a function of the multiplicity of charged particles produced in inelastic proton-proton collisions at a centre-of-mass energy ofmore » $$ \\sqrt{s}=7 $$ TeV. The results are reported as a ratio between yields in a given multiplicity interval normalised to the multiplicity-integrated ones (relative yields). They are shown as a function of the multiplicity of charged particles normalised to the average value for inelastic collisions (relative charged-particle multiplicity). D 0, D + and D *+ mesons are measured in five p T intervals from 1 GeV/c to 20 GeV/c and for |y| < 0.5 via their hadronic decays. The D-meson relative yield is found to increase with increasing charged-particle multiplicity. For events with multiplicity six times higher than the average multiplicity of inelastic collisions, a yield enhancement of a factor about 15 relative to the multiplicity-integrated yield in inelastic collisions is observed. The yield enhancement is independent of transverse momentum within the uncertainties of the measurement. The D 0-meson relative yield is also measured as a function of the relative multiplicity at forward pseudo-rapidity. The non-prompt J/ψ, i.e. the B hadron, contribution to the inclusive J/ψ production is measured in the di-electron decay channel at central rapidity. It is evaluated for p T > 1.3 GeV/c and |y| < 0.9, and extrapolated to p T > 0. The fraction of non-prompt J/ψ in the inclusive J/ψ yields shows no dependence on the charged-particle multiplicity at central rapidity. Charm and beauty hadron relative yields exhibit a similar increase with increasing charged-particle multiplicity. Finally, the measurements are compared to PYTHIA 8, EPOS 3 and percolation calculations.« less

Seismic reflection imaging, accounting for primary and multiple reflections

NASA Astrophysics Data System (ADS)

Wapenaar, Kees; van der Neut, Joost; Thorbecke, Jan; Broggini, Filippo; Slob, Evert; Snieder, Roel

2015-04-01

Imaging of seismic reflection data is usually based on the assumption that the seismic response consists of primary reflections only. Multiple reflections, i.e. waves that have reflected more than once, are treated as primaries and are imaged at wrong positions. There are two classes of multiple reflections, which we will call surface-related multiples and internal multiples. Surface-related multiples are those multiples that contain at least one reflection at the earth's surface, whereas internal multiples consist of waves that have reflected only at subsurface interfaces. Surface-related multiples are the strongest, but also relatively easy to deal with because the reflecting boundary (the earth's surface) is known. Internal multiples constitute a much more difficult problem for seismic imaging, because the positions and properties of the reflecting interfaces are not known. We are developing reflection imaging methodology which deals with internal multiples. Starting with the Marchenko equation for 1D inverse scattering problems, we derived 3D Marchenko-type equations, which relate reflection data at the surface to Green's functions between virtual sources anywhere in the subsurface and receivers at the surface. Based on these equations, we derived an iterative scheme by which these Green's functions can be retrieved from the reflection data at the surface. This iterative scheme requires an estimate of the direct wave of the Green's functions in a background medium. Note that this is precisely the same information that is also required by standard reflection imaging schemes. However, unlike in standard imaging, our iterative Marchenko scheme retrieves the multiple reflections of the Green's functions from the reflection data at the surface. For this, no knowledge of the positions and properties of the reflecting interfaces is required. Once the full Green's functions are retrieved, reflection imaging can be carried out by which the primaries and multiples are mapped to their correct positions, with correct reflection amplitudes. In the presentation we will illustrate this new methodology with numerical examples and discuss its potential and limitations.

Functional Multiple-Set Canonical Correlation Analysis

ERIC Educational Resources Information Center

Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

2012-01-01

We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

29 CFR 1926.761 - Training.

Code of Federal Regulations, 2010 CFR

2010-07-01

... following activities. (1) Multiple lift rigging procedure. The employer shall ensure that each employee who performs multiple lift rigging has been provided training in the following areas: (i) The nature of the hazards associated with multiple lifts; and (ii) The proper procedures and equipment to perform multiple...

29 CFR 1926.761 - Training.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following activities. (1) Multiple lift rigging procedure. The employer shall ensure that each employee who performs multiple lift rigging has been provided training in the following areas: (i) The nature of the hazards associated with multiple lifts; and (ii) The proper procedures and equipment to perform multiple...

Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

PubMed

Giovannoni, Gavin

2018-06-01

The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

Feedback enhances the positive effects and reduces the negative effects of multiple-choice testing.

PubMed

Butler, Andrew C; Roediger, Henry L

2008-04-01

Multiple-choice tests are used frequently in higher education without much consideration of the impact this form of assessment has on learning. Multiple-choice testing enhances retention of the material tested (the testing effect); however, unlike other tests, multiple-choice can also be detrimental because it exposes students to misinformation in the form of lures. The selection of lures can lead students to acquire false knowledge (Roediger & Marsh, 2005). The present research investigated whether feedback could be used to boost the positive effects and reduce the negative effects of multiple-choice testing. Subjects studied passages and then received a multiple-choice test with immediate feedback, delayed feedback, or no feedback. In comparison with the no-feedback condition, both immediate and delayed feedback increased the proportion of correct responses and reduced the proportion of intrusions (i.e., lure responses from the initial multiple-choice test) on a delayed cued recall test. Educators should provide feedback when using multiple-choice tests.

Multiplicities of charged hadrons in 280 GeV/c muon-proton scattering

NASA Astrophysics Data System (ADS)

Arneodo, M.; Arvidson, A.; Aubert, J. J.; Badelek, B.; Beaufays, J.; Becks, K. H.; Bee, C. P.; Benchouk, C.; Berghoff, G.; Bird, I.; Blum, D.; Böhm, E.; De Bouard, X.; Brasse, F. W.; Braun, H.; Broll, C.; Brown, S.; Brück, H.; Calen, H.; Callebaut, D.; Chima, J. S.; Ciborowski, J.; Clifft, R.; Coignet, G.; Combley, F.; Coughlan, J.; D'Agostini, G.; Dahlgren, S.; Dengler, F.; Derado, I.; Dreyer, T.; Drees, J.; Düren, M.; Eckardt, V.; Edwards, A.; Edwards, M.; Ernst, T.; Eszes, G.; Favier, J.; Ferrero, M. I.; Figiel, J.; Flauger, W.; Foster, J.; Gabathuler, E.; Gajewski, J.; Gamet, R.; Gayler, J.; Geddes, N.; Giubellino, P.; Grafström, P.; Grard, F.; Hass, J.; Hagberg, E.; Hasert, F. J.; Hayman, P.; Heusse, P.; Hoppe, C.; Jaffré, M.; Jacholkowska, A.; Janata, F.; Jancso, G.; Johnson, A. S.; Kabuss, E. M.; Kellner, G.; Kesteman, J.; Korbel, V.; Krüger, J.; Kullander, S.; Landgraf, U.; Lanske, D.; Loken, J.; Long, K.; Maire, M.; Manz, A.; Mohr, W.; Montanet, F.; Montgomery, H. E.; Nagy, E.; Nassalski, J.; Norton, P. R.; Oakham, F. G.; Osborne, A. M.; Pascaud, C.; Pawlik, B.; Payre, P.; Peroni, C.; Pessard, H.; Pettingale, J.; Pietrzyk, B.; Pönsgen, B.; Pötsch, M.; Renton, P.; Ribarics, P.; Rith, K.; Rondio, E.; Scheer, M.; Schlagböhmer, A.; Schiemann, H.; Schmitz, N.; Schneegans, M.; Schröder, T.; Schouten, M.; Schultze, K.; Sholz, M.; Sloan, T.; Stier, H. E.; Stockhausen, W.; Studt, M.; Taylor, G. N.; Thénard, J. M.; Thompson, J. C.; De La Torre, A.; Toth, J.; Urban, L.; Urban, L.; Wahlen, H.; Wallucks, W.; Whalley, M.; Wheeler, S.; Williams, W. S. C.; Wimpenny, S. J.; Windmolders, R.; Wolf, G.; European Muon Collaboration

Properties of the hadron multiplicity distributions in 280 GeV/ c μ +p interactions have been investigated. The c.m. energy dependence in the range from 4 to 20 GeV of the total charged multiplicities are presented. No variation faster than logarithmic is seen in the energy range of this experiment. Comparison with νp and overlineνp data at lower energy has been made and shows good agreement between μ +p and overlineνp total charged multiplicities. It has been found that the average forward multiplicity (charged hadrons with xF > 0) exceeds the average backward multiplicity (charged hadrons with xF < 0) in the whole energy range and presents a different energy variation. The average forward multiplicity has been compared to e +e - data and shows a similar dependence on energy. Little correlation was observed between the forward and backward multiplicities indicating that the current and target regions fragment almost independently.

Attenuation of multiples in image space

NASA Astrophysics Data System (ADS)

Alvarez, Gabriel F.

In complex subsurface areas, attenuation of 3D specular and diffracted multiples in data space is difficult and inaccurate. In those areas, image space is an attractive alternative. There are several reasons: (1) migration increases the signal-to-noise ratio of the data; (2) primaries are mapped to coherent events in Subsurface Offset Domain Common Image Gathers (SODCIGs) or Angle Domain Common Image Gathers (ADCIGs); (3) image space is regular and smaller; (4) attenuating the multiples in data space leaves holes in the frequency-Wavenumber space that generate artifacts after migration. I develop a new equation for the residual moveout of specular multiples in ADCIGs and use it for the kernel of an apex-shifted Radon transform to focus and separate the primaries from specular and diffracted multiples. Because of small amplitude, phase and kinematic errors in the multiple estimate, we need adaptive matching and subtraction to estimate the primaries. I pose this problem as an iterative least-squares inversion that simultaneously matches the estimates of primaries and multiples to the data. Standard methods match only the estimate of the multiples. I demonstrate with real and synthetic data that the method produces primaries and multiples with little cross-talk. In 3D, the multiples exhibit residual moveout in SODCIGs in in-line and cross-line offsets. They map away from zero subsurface offsets when migrated with the faster velocity of the primaries. In ADCIGs the residual moveout of the primaries as a function of the aperture angle, for a given azimuth, is flat for those angles that illuminate the reflector. The multiples have residual moveout towards increasing depth for increasing aperture angles at all azimuths. As a function of azimuth, the primaries have better azimuth resolution than the multiples at larger aperture angles. I show, with a real 3D dataset, that even below salt, where illumination is poor, the multiples are well attenuated in ADCIGs with the new Radon transform in planes of azimuth-stacked ADCIGs. The angle stacks of the estimated primaries show little residual multiple energy.

Protein function prediction--the power of multiplicity.

PubMed

Rentzsch, Robert; Orengo, Christine A

2009-04-01

Advances in experimental and computational methods have quietly ushered in a new era in protein function annotation. This 'age of multiplicity' is marked by the notion that only the use of multiple tools, multiple evidence and considering the multiple aspects of function can give us the broad picture that 21st century biology will need to link and alter micro- and macroscopic phenotypes. It might also help us to undo past mistakes by removing errors from our databases and prevent us from producing more. On the downside, multiplicity is often confusing. We therefore systematically review methods and resources for automated protein function prediction, looking at individual (biochemical) and contextual (network) functions, respectively.

Multiplicity distributions of shower particles and target fragments in 84 Kr 36-emulsion interactions at 1 GeV per nucleon

NASA Astrophysics Data System (ADS)

Singh, M. K.; Soma, A. K.; Pathak, Ramji; Singh, V.

2014-03-01

This article focuses on multiplicity distributions of shower particles and target fragments for interaction of 84 Kr 36 with NIKFI BR-2 nuclear emulsion target at kinetic energy of 1 GeV per nucleon. Experimental multiplicity distributions of shower particles, grey particles, black particles and heavily ionization particles are well described by multi-component Erlang distribution of multi-source thermal model. We have observed a linear correlation in multiplicities for the above mentioned particles or fragments. Further experimental studies have shown a saturation phenomenon in shower particle multiplicity with the increase of target fragment multiplicity.

Users manual for program ADMIT: Admittance and pressure transfer function developed for use on a PC computer

NASA Technical Reports Server (NTRS)

Armstrong, Wilbur C.

1992-01-01

The piping in a liquid rocket can assume complex configurations due to multiple tanks, multiple engines, and structures that must be piped around. The capability to handle some of these complex configurations have been incorporated into the ADMIT code. The capability to modify the input on line has been implemented. The configurations allowed include multiple tanks, multiple engines, the splitting of a pipe into unequal segments going to different (or the same) engines. This program will handle the following type elements: straight pipes, bends, inline accumulators, tuned stub accumulators, Helmholtz resonators, parallel resonators, pumps, split pipes, multiple tanks, and multiple engines.

Medicolegal issues in multiple pregnancy.

PubMed

Gersell, Deborah J

2007-02-01

Any discussion of multiple pregnancy figures prominently in the consideration of the medicolegal aspects of placental pathology. Multiple gestations are common and becoming more so with assisted reproductive techniques, and multiples are associated with a disproportionate share of complications that may result in disputes over quality of care. Higher rates of intrauterine growth retardation, prematurity, stillbirth, morbidity, mortality, cerebral palsy, anomalous development, and malformation as compared with singletons are well documented in multiple pregnancy and should be anticipated. Monochorionic placentation and complications of vascular anastomosis are important factors contributing to poor outcome. Other factors, although occurring in all gestations, are relevant because they are more common in multiple gestations.

The positive and negative consequences of multiple-choice testing.

PubMed

Roediger, Henry L; Marsh, Elizabeth J

2005-09-01

Multiple-choice tests are commonly used in educational settings but with unknown effects on students' knowledge. The authors examined the consequences of taking a multiple-choice test on a later general knowledge test in which students were warned not to guess. A large positive testing effect was obtained: Prior testing of facts aided final cued-recall performance. However, prior testing also had negative consequences. Prior reading of a greater number of multiple-choice lures decreased the positive testing effect and increased production of multiple-choice lures as incorrect answers on the final test. Multiple-choice testing may inadvertently lead to the creation of false knowledge.

Coexistence of multiple sclerosis and ankylosing spondylitis: Report of four cases from Russia and review of the literature.

PubMed

Fominykh, Vera; Shevtsova, Tatyana; Arzumanian, Narine; Brylev, Lev

2017-10-01

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system. There are many cases of multiple sclerosis - like syndrome and demyelinating disorders in systemic lupus erythematosus, Sjogren disease, Behcet disease and other autoimmune conditions. Coexistence of ankylosing spondylitis and multiple sclerosis usually is rare but in this article we report 4 Russian patients with concomitant multiple sclerosis and ankylosing spondylitis diseases. None of these patients received anti-tumor necrosis factor alpha therapy prior to diagnosis of multiple sclerosis. Pathogenesis, diagnostic and treatment challenges are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Users manual for program SSFREQ intermediate mode stability curves: Developed for use on a PC computer

NASA Technical Reports Server (NTRS)

Armstrong, Wilbur C.

1992-01-01

The piping in a liquid rocket can assume complex configurations due to multiple tanks, multiple engines, and structures that must be piped around. The capability to handle some of these complex configurations have been incorporated into the SSFREQ code. The capability to modify the input on line has been implemented. The configurations allowed include multiple tanks, multiple engines, the splitting of a pipe into equal segments going to different (or the same) engines. This program will handle the following type elements: straight pipes, bends, inline accumulators, tuned stub accumulators, Helmholtz resonators, parallel resonators, pumps, split pipes, multiple tanks, and multiple engines.

Multiple Paths to Mathematics Practice in Al-Kashi's Key to Arithmetic

NASA Astrophysics Data System (ADS)

Taani, Osama

2014-01-01

In this paper, I discuss one of the most distinguishing features of Jamshid al-Kashi's pedagogy from his Key to Arithmetic, a well-known Arabic mathematics textbook from the fifteenth century. This feature is the multiple paths that he includes to find a desired result. In the first section light is shed on al-Kashi's life and his contributions to mathematics and astronomy. Section 2 starts with a brief discussion of the contents and pedagogy of the Key to Arithmetic. Al-Kashi's multiple approaches are discussed through four different examples of his versatility in presenting a topic from multiple perspectives. These examples are multiple definitions, multiple algorithms, multiple formulas, and multiple methods for solving word problems. Section 3 is devoted to some benefits that can be gained by implementing al-Kashi's multiple paths approach in modern curricula. For this discussion, examples from two teaching modules taken from the Key to Arithmetic and implemented in Pre-Calculus and mathematics courses for preservice teachers are discussed. Also, the conclusions are supported by some aspects of these modules. This paper is an attempt to help mathematics educators explore more benefits from reading from original sources.

Allelic imbalance of multiple sclerosis susceptibility genes IKZF3 and IQGAP1 in human peripheral blood.

PubMed

Keshari, Pankaj K; Harbo, Hanne F; Myhr, Kjell-Morten; Aarseth, Jan H; Bos, Steffan D; Berge, Tone

2016-04-14

Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown. Consistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively. Using multiple sclerosis patients and healthy controls heterozygous for rs907091 and rs11609, we showed that the multiple sclerosis risk alleles at IKZF3 and IQGAP1 are expressed at higher levels as compared to the protective allele. Furthermore, individuals homozygous for the multiple sclerosis risk allele at IQGAP1 had a significantly higher total expression of IQGAP1 compared to individuals homozygous for the protective allele. Our data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. We suggest that such cis-acting mechanisms may contribute to the multiple sclerosis association of single nucleotide polymorphisms at IKZF3 and IQGAP1.

Facilitating Multiple Intelligences through Multimodal Learning Analytics

ERIC Educational Resources Information Center

Perveen, Ayesha

2018-01-01

This paper develops a theoretical framework for employing learning analytics in online education to trace multiple learning variations of online students by considering their potential of being multiple intelligences based on Howard Gardner's 1983 theory of multiple intelligences. The study first emphasizes the need to facilitate students as…

Pathways of Learning: Teaching Students and Parents about Multiple Intelligences.

ERIC Educational Resources Information Center

Lazear, David

This book is concerned with reinventing the learning process from a multiple intelligences perspective and urges explicitly teaching students about multiple intelligences to further their metacognitive understanding. The multiple-intelligence-based curriculum is intended to interface with the regular academic curriculum. An introductory chapter…

In Australia: Multiple Intelligences in Multiple Settings.

ERIC Educational Resources Information Center

Vialle, Wilma

1997-01-01

In Australia, Gardner's multiple-intelligences theory has strongly influenced primary, preschool, and special education. A survey of 30 schools revealed that teachers use two basic approaches: teaching to, and teaching through, multiple intelligences. The first approach might develop children's music skills via playing an instrument. The second…

Multiplicative Thinking: Much More than Knowing Multiplication Facts and Procedures

ERIC Educational Resources Information Center

Hurst, Chris; Hurrell, Derek

2016-01-01

Multiplicative thinking is accepted as a "big idea" of mathematics that underpins important mathematical concepts such as fraction understanding, proportional reasoning, and algebraic thinking. It is characterised by understandings such as the multiplicative relationship between places in the number system, basic and extended number…