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Background and aims Hepatitis C virus (HCV) infection is highly prevalent among homeless individuals, but the scope of HCV-associated liver fibrosis in this population is poorly understood. Methods Using the FIB-4 Index, we describe the prevalence and correlates of advanced fibrosis among a retrospective cohort of all homeless-experienced adults with HCV seen at Boston Health Care for the Homeless Program (BHCHP) over a one-year period. Results Of 832 BHCHP patients with HCV, 15.8% had advanced fibrosis. In multivariable regression analysis, alcohol use disorder (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.65-3.81) and having unknown or poorly characterized housing circumstances (aOR 2.88, 95% CI 1.02-8.14, relative to housed patients) were independently associated with advanced fibrosis. Conclusions The prevalence of advanced fibrosis in this cohort of homeless adults with HCV appears similar to national estimates among housed individuals, but their psychosocial complexity is greater, especially among those who are older.

Background In the establishment of ST elevation myocardial infarction (STEMI) systems of care, transfer times between primary care units (PCU) and the cardiac catheterization lab (CCL) are pillars to therapeutic success. Objective: To analyze the relationship between PCU-CCL distance with transport time and main clinical outcomes in STEMI patients (p) treated with pharmaco-invasive therapy (PIT) and referred for rescue PCI after failed fibrinolysis. Methods Between January 2010 and December 2018, of the 2241 patients who received tenecteplase in PCU inserted in a large city STEMI network, 801 (35.7%) evolved without reperfusion criteria after 90 minutes (persistence of chest pain, less than 50% reduction on ST elevation or hemodynamic instability), being urgently transferred to the CCL. The PCU were divided according to the distance to the tertiary center in Group 1: between 5 and 9km (N=208p), Group 2: between 16 and 18km (N=315p) and Group 3: between 22 and 30km=266p). Considering an alpha of 0.05, sample size n=801 and an effect size of 0.11, a power of 0.80 was obtained. Results The groups were comparable for baseline features (Table 1). Group 2 (intermediate distances) had the highest median transport time (G1 260 interquartile 145–437 min vs G2 355 interquartile 206–573 min vs G3 241 interquartile 125–418 min; p Table 1. Group's baseline features G1: Short distances G2: Intermediate distances G3: Long distances p value (5–9 km) N=208 (16–18 km) N=315 (22–30 km) N=266 Age (median) 57.5 (51–64) 57 (49–66) 59 (52–67) 0.27 Female 29.7% 28.3% 35.1% 0.19 Hypertension 67.3% 60.9% 64.4% 0.31 Diabetes 37.0% 32.1% 37.8% 0.30 Renal failure 10.3% 9.7% 6.3% 0.21 Anterior STEMI 56.1% 58.4% 62.4% 0.36 Pain-to-needle time (median min) 197.5 (137–330) 195 (120–295) 195 (125–345) 0.38 Conclusion In STEMI patients with failed fibrinolysis treated with pharmaco-invasive therapy, the PCU-CCL distance was not related to transfer time or to outcomes of in-hospital death and cardiogenic shock. The longer transport time of hospitals located at intermediate distance can possibly reflect local logistical difficulties and are not due to hub-spoke distance. Continuous improvement in structuring and coordination of public STEMI networks is aimed.

Background Risk stratification using scores is a valuable tool in cardiogenic shock after ST elevation myocardial infarction (STEMI). During pharmacoinvasive therapy (PIT) their use is unexplored in the literature. Objective: To validate the IABP-SHOCK II (Intra-aortic Balloon Pump in Cardiogenic Shock) score in patients treated with PIT and to analyze the influence of ischemia time on the different risk strata. Methods and results Of 2,143 STEMI patients seen between May 2010 and April 2017, 212 (9.9%) developed cardiogenic shock. Thirty-one patients (14.6%) with incomplete data were excluded from the analysis and the validation cohort included the remaining 181. Mortality rates were similar between the analyzed and excluded patients (42.5% and 45.1% respectively, p=0.77). The 30-day mortality using the IABP-SHOCK II score was 26.6% for low-risk (n=94), 53.2% for moderate-risk (n=62), and 76% for high-risk (n=25) (p 30-day mortality in scored strata Conclusion In patients with cardiogenic shock after STEMI treated with PIT, risk stratification using the IABP-SHOCK II score was adequate. There was no influence of pain-to-needle and fibrinolytic-catheterization times on the ability to the score model stratification.

When considering silicon heterojunction technology (HJT) for mass production the most frequently expressed reservations are related to the performance and cost constraints the standard TCO on the cell front side namely thin indium tin oxide (ITO) constitutes. We address these concerns with our HJT 2.0 concept in which the front electrode is made of a bi-layer of ITO that is supplemented by a silicon nitride (SiN) layer. This cell concept was developed to yield an increase in efficiency of typically 0.2% absolute due to improved cell current and a cost saving in the range of 30-40% with respect to cost of ownership (CoO).

The status of the development of triple-junction (amorphous silicon/microcrystalline/microcrystalline silicon) test cells fabricated with up-scalable PECVD processes is given. A first draft of novel rather flat scattering superstrates with an optimized high bandgap amorphous silicon top cell including a carbon-free buffer at the p/i interface is presented. The careful optimization of the interfaces (including sub-oxide doped layers and buffers) and of the bulk crystallinity of the middle and bottom microcrystalline sub-cells allowed to reach a stabilized efficiency of 13.5 % (after 1000 h light-soaking, internal measurement). Sub-cells individual developments are discussed and their specific integration into the full triple-junction device with its optimization for AM1.5G illumination relying on a partly LED supported solar simulator characterization is presented.

Thin film tandem solar cells based on amorphous and microcrystalline silicon (MicromorphTM in superstrate configuration) benefit from strongly light-scattering nano-textured substrates. A development methodology for the evaluation of the performance of the Micromorph test cells deposited on such substrates with very different surface shapes is presented and illustrated. It is shown that growth related defects and non-conformal coverage of the silicon layers restrict the choice of surface shapes for this photovoltaic application. General guidelines are given in this study for the preferred selection of the surface geometry for MicromorphTM test cells. The results indicate that the application of advanced surface shapes for higher conversion efficiencies requires improved silicon deposition process compared to current industrial state-of-the-art.

Homeless individuals face an elevated risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Identifying the prevalence and risk factors for MRSA nasal colonization may reduce infection risk. A cross-sectional study was conducted at a health clinic for homeless persons in Boston, MA, USA (n=194). In-person interviews and nasal swab specimens were collected. MRSA isolates were genotyped using pulse-field gel electrophoresis (PFGE) and assessed for antibiotic susceptibility. The prevalence of MRSA nasal colonization was 8.3 %. Seventy-five percent of isolates reflected clonal similarity to USA300. USA100 (18.8 %) and USA500 (6.3 %) were also recovered. Resistance to erythromycin (81.3 %), levofloxacin (31.3 %) and clindamycin (23.1 %) was identified. Recent inpatient status, endocarditis, haemodialysis, heavy drinking, not showering daily and transience were positively associated with MRSA nasal colonization. Carriage of community-acquired MRSA strains predominated in this population, although nosocomial strains co-circulate. Attention to behavioural and hygiene-related risk factors, not typically included in MRSA prevention efforts, may reduce risk.

Background In the face of an increasingly fatal opioid crisis, Boston Health Care for the Homeless Program (BHCHP) opened the Supportive Place for Observation and Treatment (SPOT), a unique low-threshold harm reduction program for monitoring people who have injected drugs and are at imminent risk of overdose. This study examines the impact of the opening of the SPOT program on measures of injection drug-related public order in the neighborhood surrounding the facility. Methods Data was collected at 10 weeks prior and 12 weeks post SPOT implementation on: number of over-sedated individuals in public, publicly discarded syringes, publicly discarded injection-related litter, and instances of active injection drug use or exchange of drugs. Changes were evaluated using Poisson log-linear regression models. Potential confounders such as weather and police presence were measured and controlled for. Results The average number of over-sedated individuals observed in public significantly decreased by 28% (4.3 [95% Confidence Interval (CI) 2.7–6.9] v 3.1 [CI 1.4–6.8]) after SPOT opened. The opening of SPOT did not have a significant effect on the other measures of public order. The daily average number of publicly discarded syringes (28.5 [CI 24.5–33.1] v 28.4 [CI 22.0–36.5]), pieces of publicly discarded injection-related litter (376.3 [CI 358.6–394.8] v 375.0 [CI 345.8–406.6]), and observed instances of active use or exchange of drugs (0.2 [CI 0.1–0.9] v 0.1 [CI 0.0–0.1]) were not statistically significantly different after the opening of SPOT. Conclusions The opening of SPOT was associated with a significant decrease in observed over-sedated individuals. Other measures of injection-drug related public order did not improve or worsen with the opening of SPOT, however, they have been shown to improve with the implementation of a supervised injection facility.

Micronization of minocycline hydrochloride dissolved in ethanol and with supercritical carbon dioxide as antisolvent was successfully performed using a supercritical antisolvent (SAS) apparatus. Amorphous particles of minocycline ranging from 0.1 to 1 μm (depending on the operating conditions) were obtained. The mean particle size and the particle size distribution were determined by dynamic light scattering. Images were obtained by Scanning Electron Microscopy (SEM) to confirm the morphology and the size of the powders before and after the material is processed. The quality of the micronized minocycline was analyzed by HPLC and was compared with that obtained before micronization. Experiments were carried out in order to study the effects of the pressure (75–130 bar), temperature (35–50 °C) and concentration of the liquid solution (1–20 mg mL−1) on the mean particle size and particle size distribution of the final product obtained. The effect of the antisolvent flow/liquid solution flow (AS/L) ratio was also analyzed. Experiments were performed with (AS/L) ratios equal to 5, 15 and 50 on a mass basis. The experimental results clearly indicate that SAS micronization of minocycline hydrochloride with ethanol as solvent and SC-CO2 as antisolvent, above approximately 80 bar (the only region where it occurs), takes place in a homogeneous supercritical phase formed in the precipitator and particle formation results from gas-phase nucleation. This conclusion is consistent with results mentioned in the literature for similar systems.

A comparative study is reported of the three main types of continuous reactors, continuous feed stirred tank reactor (CFSTR), packed bed reactor (PBR) and fluidised bed reactor (FBR), for the conversion at 50°C of a 30% (w/w) corn syrup 40 DE using glucoamylase (exo-1,4-D-glucosidase, EC 3.2.1.3) immobilised on carbonyl derivatives of titanium(IV)-activated porous silica by a method developed previously.1–3 The hydrolysis of starch in these reactors is described by a simple kinetic model4 which involves the intrinsic kinetic constants as well as mass transfer and dispersion effects, and allows the computation of enzyme activity values under continuous operation. FBR appears to be more effective for the hydrolysis of starch. This reactor also confers a better operational stability (t1/2=775h) on the immobilised enzyme than the other immobilised glucoamylase reactors (PBR, t1/2=629h; CFSTR, t1/2=239h).

Evaluation of ultrafiltration performance for the purpose of isolation of clavulanic acid from fermentation broths was carried out using two tubular ceramic membranes with molecular weight cut-offs (MWCO) of 15 and 150 kDa and two flat sheet organic membranes with MWCO of 20 and 5 kDa in order to establish the sequence of operations needed to achieve a good phase separation when the permeates are subjected to solvent extraction. Ultrafiltration fluxes are higher for the 150 kDa membrane, but the quality of its permeate is not good enough for acceptable phase separation: so, for solid—liquid separation a further purification of its permeates using the 20 kDa membrane is required. The purification of the permeates of the membrane of 20 kDa using a membrane of 5 kDa was also investigated. This last operation did not brought any improvement to the process. Ultrafiltration experiments using either the membranes of 15 kDa or of 20 kDa directly for the solid liquid separation showed that a good performance is obtained for both membranes. High fluxes and high yields of antibiotic were obtained as well as a good phase separation when their permeates were subjected to solvent extraction.

The ultrafiltration of fermentation broths of demethylchlortetracycline (DMCT) produced at an industrial scale at CIPAN SA, has been carried out, using two ultrafiltration systems of different module geometries: a tubular module (B1 from Paterson Candy International Ltd.) and a plate-and-frame module (LabStak M20 from Danish Separation Systems). A PVDF and a fluoro polymer ultrafiltration membranes both with a MWCO of 100 KD were used. Although the highest permeate fluxes were obtained with plate-and-frame geometry, serious problems arose in cleaning the whole system, due to accumulation of solids inside the module as the broths under study are not homogeneous and contain oil–mycelium aggregates of macroscopic dimensions that cover a wide range of particle size (from less than 100 μm to about 2 mm). The results obtained for the ultrafiltration operation are also compared with those obtained for the industrial filtration using rotary vacuum filters. The same yields are achieved for about the same dilution, but ultrafiltration has the advantage of not requiring filter aid and flocculants as the conventional filtration process does. The filtrate quality is also another advantage of the membrane process, as the permeates are completely free of suspended solids. A rejection to demethylchlortetracycline related products (namely the undesirable isomer epi -DMCT) by the two membranes under study higher than that to DMCT is observed as well.

Benzylpenicillin filtered broths purified by ultrafiltration and fermented broths clarified by ultrafiltration and afterwards concentrated by reverse osmosis were used directly for enzymatic conversion of benzylpenicillin to 6-aminopenicillanic acid and phenylacetic acid by immobilised penicillin G acylase or amidase. It was concluded that, when the ultrafiltration operation retained 100% of protein, the concentrates from reverse osmosis could be successfully directly fed to the enzymatic reactor, giving high enzymatic conversion yield of benzylpenicillin to 6-aminopenicillanic acid.

Concentration of benzylpenicillin filtered broths purified by ultrafiltration and fermented broths clarified by ultrafiltration was carried out by reverse osmosis. This study was done using a reverse osmosis laboratory/pilot installation from Paterson Candy International Ltd. whose module has a tubular configuration and a membrane with a molecular weight cut-off of 100 Dalton (ZF99) made of a polyamide film with a rejection of 99% of NaCl. It was concluded that reverse osmosis is an adequate technique to concentrate benzylpenicillin ultrafiltered broths, leading to low losses of benzylpenicillin in the permeate and high benzylpenicillin recovery for high volumetric concentration factors.

The comparative efficiencies of two special biocatalytic reactors designed to handle gel-like immobilized biocatalysts, the hollow tubes and the hollow zones reactors, have been assessed for the performance of the hydrolysis of benzylpenicillin to 6-aminopenicillanic acid and phenyl acetic acid by an immobilized penicillin amidase preparation.

Experiments of ultrafiltration with diafiltration were performed on fermented broths of benzylpenicillin and clavulanic acid produced at pilot scale at CIPAN, SA to achieve solid/liquid separation, antibiotic recovery and soluble protein retention. This study was done using a laboratorial/pilot scale ultrafiltration facility from Paterson Candy International Ltd. whose modules have a tubular configuration. PVDF membranes with a molecular weight cut-off of 100 000 (FP10) and 200 000 (FP200) were assessed. Comparison between solvent extraction of benzylpenicillin and clavulanic acid from filtered broth and ultrafiltered broth was also done. It was concluded that ultrafiltration with diafiltration of fermented broths of antibiotics using the FP10 membrane is a valid alternative to the use of rotary vacuum filters, flocculants and filter aid, deserving a further study to establish the best operating conditions. An economic appraisal also seems to be of paramount importance.

This article is concerned with the development of a model to maximize the overall yield of isolation of antibiotics recovered from fermented broths by the so-called direct precipitation method. In this process, as in most antibiotics isolation processes, a second filtration of the semiexhaust mycellium from the first filtration, after slurrying it in water at the suitable pH, is required. The maximization of the overall yield of isolation implies the use of an optimal amount of water, measured as a volume to fermented broth mass ratio, which can be calculated by using the model derived here. The model also allows for the calculation of the partial and overall yields of the isolation process, and its validity is demonstrated by its ability to describe reasonably well the isolation data of two different tetracycline-fermented broths produced according to two different technologies. The application of the model requires only the knowledge of easily obtainable fermented broth parameters and is illustrated for two different types of tetracycline-fermented broths. Although the model had been derived for the optimization of the overall yield of isolation of antibiotics recovered by direct precipitation, it can easily be adapted to be used for the optimization of the overall yield of isolation of antibiotics recovered by other isolation processes. © 1993 John Wiley & Sons, Inc.

Purification of benzylpenicillin filtered broths obtained from fermented broths produced at CIPAN, SA Pilot Plant Fermentation was carried out by ultrafiltration with diafiltration. This study was done using an ultrafiltration laboratory/pilot installation from Paterson Candy International Ltd. whose module has a tubular configuration. Membranes with molecular weight cut-offs of 8000 (polysulfone), 20 000 (polysulfone) and 100 000 (PVDF) were assessed. Comparison between solvent extraction of benzylpenicillin from ultrafiltered broths and from filtered broths using flocculants was also done. Ultrafiltration with diafiltration of benzylpenicillin filtered broths was used successfully to remove proteins, colored substances and other impurities giving high benzylpenicillin recovery in the permeate, as an alternative to the use of flocculants and anti-emulsion agents to obtain good phases separation in benzylpenicillin solvent extraction.

This paper describes the purification of Penicillin G Amidase (EC 3.5.1.11) using quaternary ammonium salts with the aim of increasing the activity of immobilised enzymes prepared from the purified solutions. Two different quaternary ammonium salts were tested with different solutions of the enzyme. It was concluded that the quaternary ammonium salts used selectively precipitated the non-enzymatic protein leaving in solution practically all the enzyme resulting in a high yield of purification. Optimal conditions for purification using the two types of quaternary ammonium salts were determined. Immobilisation studies were performed from various purified enzyme solutions, using different amounts of a quaternary ammonium salt. The immobilised enzymes so obtained showed a much higher activity than the immobilised enzyme obtained from non-purified enzyme solutions.

Dispersion and mass-transfer characteristics and fluidization parameters influencing the performance of a small pilot-plant immobilized enzyme reactor are evaluated. The suitability of a dispersed plug-flow model to predict the conversions obtained in the enzymatic reaction (starch → glucose) catalyzed by amyloglucosidase immobilized to solid and porous carriers is assessed. The performance of a fluidized-bed reactor is compared on the basis of a normalized residence time with that of a fixed bed and found to be superior.

A new process to couple amyloglucosidase (AG) to inorganic supports is described. The technique consists in activating the support with a transition metal salt according to the metal-link method and subsequent amination and linkage of the alkylamine derivative using glutaraldehyde. The various parameters susceptible of influencing the properties of the immobilized enzyme (IME) preparation are investigated. The best result are obtained when 100 mg of 1000-A controlled porous glass (CPG) are treated with 45 mg of TiCl4 and the activated carrier aminated using a 10-g/L solution of hexamethylenediamine (HMDA) in carbon tetrachloride (10 Ml/100 mg). Preparation obtained according to the process here described show operational stabilities much superior to those of AG immobilized on the same support by the traditional metal-link method or its variations. The mechanism involved in the preparation of the amino derivative of CPG is proposed.

This paper is concerned with the development of a model to plan a strategy for an enzymatic batch process whereby the enzyme is subjected to deactivation as described by the exponential (first-order) decay model. The particular system used was the enzymatic hydrolysis of penicillin to 6-aminopenicillanic acid, but the model can be utilised with other batch systems, provided that decay of the immobilised enzyme preparation is described by the exponential decay model. The model developed is eminently practical and simple, and several examples of its application are given. Experimental data obtained in a small pilot plant batch recirculated reactor could, on average, be well fitted by this model.

This paper deals with the modelling of the hydrolysis of benzylpenicillin to 6-aminopenicillanic acid (6-APA) and phenyl acetic acid (PAA) in a small pilot plant batch recirculated reactor by an immobilised penicillin amidase preparation. By using the following linearised form for an integrated Michaelis-Menten equation Et/V0X=α+β| In (1-X)/X| where α and β are reaction kinetic parameters, good correlations are obtained of α and β with linear velocity across the reactor, substrate concentration and temperature of operation. A process to determine α and β from initial velocity measurements is outlined. The applicability of the above equation to published data is also analysed.

Glucoamylase (EC 3.2.1.3.) was immobilized on controlled pore silica by a new covalent method of enzyme immobilization on inorganic supports. A 30 wt.%

Controlled pore glass was activated by transition metal salts, FeCl 2 , FeCl 3 , VCl 3 and ZrCl 4 , and derivatized by the method of Cabral et al. 1 Glucoamylase (exo-1,4-α- d -glucosidase, EC 3.2.3.1) was coupled to the aldehyde derivative, the resulting initial activities being 61.7, 71.8, 57.6 and 63.2 U g −1 of matrix, respectively. The immobilized glucoamylase preparations in which the carrier was activated with zirconium (IV) chloride displayed a very stable behaviour, with a half-life of 1709 h, in contrast with the preparations activated with iron(II) chloride ( t 1 2 = 43 7 h , iron(III) chloride ( t 1 2 = 518 h ) and vanadium(III) chloride ( t 1 2 = 893 h ). Several biocatalysts, fungal α-amylase (EC 3.2.1.1), bacterial α-amylase (EC 3.2.1.1), β- d -fructofuranosidase (invertase, EC 3.2.1.26), papain (EC 3.4.22.2) and yeast cells of Saccharomyces cerevisiae with β- d -fructofuranosidase activity were immobilized on aldehyde derivatives of titanium(IV)-activated porous silica (Spherosil), half-lives of 140, 157, 980, 236 and 413 h being obtained, respectively.

This article is concerned with the development of a model to plan a strategy for an enzymatic batch process where enzyme is subjected to deactivation described by the inverted linear decay model. The particular system studied is the enzymatic hydrolysis of penicillin to 6-amino penicillanic acid (6 APA), but the model can be utilized with other batch systems as long as the decay of the immobilized enzyme (IME) preparation is described by the inverted linear decay model. The model developed is eminently practical and simple and several example of its application are shown. Experimental data obtained in a small pilot plant batch recirculated reactor on the average are well fitted by this model. For IME systems whose decay is best described by the first-order decay model, it is not possible to use the same approach.

Description d'un modele base sur les resultats experimentaux de l'hydrolyse de l'amidon soluble et des maltodextrines. Comparaison des performances de l'enzyme dans des reacteurs a lit fixe et a lit fluidise

Penicillin acylase (EC 3.5.1.11) was immobilized by covalent binding on a silica gel carrier activated by silanization. High immobilization yields, operational stability, enzyme loading and support reutilization capacity were obtained. The effects of several variables on the activation of the support and on the immobilization method were studied. Other supports and immobilization methods were assessed for the immobilization of penicillin acylase and compared with the basic process used. Activity versus temperature, pH, buffer molarity and penicillin concentration profiles were determined and compared for the free, crosslinked and covalently-bound silica carrier penicillin acylase preparations. The hydrolysis performance of the latter preparation was assessed in a batch basket reactor and the time course of the hydrolysis reaction modelled by a two parameter model equation. The operational stabilities of penicillin acylase coupled covalently to the silica gel support and immobilized by a crosslinking procedure using glutaraldehyde were also compared.