| 1. |
- Linecker, Michael, et al.
(författare)
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Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity
- 2017
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Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 266:5, s. 779-786
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome. Background: ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome. Methods: ALPPS centers of the International ALPPS Registry having performed amp;gt;= 10 cases over a period of amp;gt;= 3 years were assessed for 90-day mortality and major interstage complications (amp;gt;= 3b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies. Results: Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P amp;lt; 0.001; OR: 1.62; 95% CI: 1.36-1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18-0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers. Conclusions: Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.
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| 2. |
- Alvarez, Rene, et al.
(författare)
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Anaerobic co-digestion of aquatic flora and quinoa with manures from Bolivian Altiplano
- 2008
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Ingår i: Waste Management: international journal of integrated waste management, science and technology. - : Elsevier BV. - 1879-2456. ; 28:10, s. 1933-1940
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Tidskriftsartikel (refereegranskat)abstract
- Quinoa stalk (Chenopodium quinoa Willd.) from agricultural crop residue, totora (Schoenoplectus tatora) and o-macrophytes (aquatic flora) from Lake Titicaca (on the Bolivian Altiplano) were studied in a wet anaerobic co-digestion process together with manure front llama, cow and sheep. Anaerobic semi-continuous experiments were performed in (10) 2-1 reactors at a temperature of 25 degrees C with 30 days of hydraulic retention time (HRT) and ail organic loading rate (OLR) of 1.8 kg VS m(-3) d(-1). Totora was found to be the best co-substrate. In mixture ratios of 1:1 (VS basis), it increased the biogas productivity by 130% for llama manure, 60% for cow manure, and 40% for sheep manure. It was possible to use up to 58% (VS basis) of totora in the substrate. Higher concentrations (including pure totora) could not be digested, as that caused acidification problems similar to those caused by other lignocellulosic materials. When quinoa and o-macrophytes were used as co-substrates, the increase in biogas productivity was slightly less. However, these co-substrates did not cause any operational problems. An additional advantage of quinoa and o-macrophytes was that they could be used in any proportion (even in pure form) without causing any destabilization problems in the anaerobic digestion process. (C) 2007 Elsevier Ltd. All rights reserved.
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| 3. |
- Alvarez, Rene
(författare)
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Anaerobic Digestion of Solid Residues on the Bolivian Altiplano
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anaerobic digestion and the production of biogas can provide an efficient means of meeting energy needs locally and reducing organic loading due to untreated waste material in water recipients. Furthermore, residues after anaerobic digestion may be used as a fertilizer to improve the soil in many parts of the world. Most natural organic waste can be used in anaerobic digestion. In developing countries, the primary substrate is cattle dung, but agricultural residues and aquatic flora may be added to co-digestion processes to produce more gas. Waste generated in urban areas (the organic fraction of municipal waste and industrial waste) are in principle also amenable to anaerobic digestion. However, these feedstocks have not been thoroughly explored in developing countries. Furthermore, harsh environmental conditions in some regions may limit the application of anaerobic digestion technology. The objective of the current work was to experimentally investigate anaerobic digestion of organic residues with specific emphasis on conditions particular to the Bolivian Altiplano. There are several potential barriers to the successful implementation of biogas production on the Altiplano. The aspects to which most attention was devoted here were the low mean temperature, the large daily temperature fluctuations and the character of the raw material typical for the region. Experiments conducted on semi-continuous anaerobic digestion from llama and cow manure showed that temperature, the hydraulic retention time (HRT), and the manure content in the feed were the significant factors, in this order, whereas the effect of pressure was not significant in the range studied. Llama manure appears to be the best raw material from the Altiplano, because of its high volatile solids content, high nutrient content and availability. In general, the methane yields obtained were lower than reported value at sea level, and this was attributed to the quality of the volatile solids (VS) in the manure, probably a consequence of the feed source of the livestock and the harsh environmental conditions at high altitude. The biogas productivity and methane yield (0.008 and 0.011 m3 biogas kg-1 dung, 0.03 and 0.01 m3 CH4 kg-1VS added, for cow and llama manure, respectively) obtained at 11oC, and a hydraulic residence time (HRT) of 50 days, could be increased up to 0.035-0.133 m3 biogas kg-1 mixture of substrate (0.09-0.15 m3 CH4 kg-1 VS added) by increasing the temperature and co-digestion with agricultural residues or aquatic flora. The anaerobic digestion of llama, cow and sheep manure in a semi-continuous process subject to a square-wave daily temperature fluctuation was also studied. The pH (7.2) in the effluent and the average methane content of the biogas (55-56%) were stable indicating a well-balanced biomethanation process. Furthermore, the mean biogas productivity was higher than that obtained at the average temperature. A semi-continuous co-digestion process treating solid slaughterhouse waste (rumen, stomach content and blood from cattle and swine), fruit &vegetable waste, together with manure (from cattle and swine) in a mesophilic process showed expected results, such as a reduction of volatile solid contents of between 50 and 65%, and methane yield of about 0.3 m3 CH4 kg-1 VS added, at organic loading rates up to 1.3 kg VS m-3d-1. These results show that anaerobic digestion offers a potential means of decreasing the environmental burden, and at the same time providing biogas for local energy needs. The domestic energy needs of the rural population of the Altiplano can be met if the animal dung is used for biogas production in small-scale biogas digesters. However, the harsh environment conditions demand systems or means of increasing the average temperature in the digesters.
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| 4. |
- Alvarez, Rene, et al.
(författare)
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Biogas production from llama and cow manure at high altitude
- 2006
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Ingår i: Biomass & Bioenergy. - : Elsevier BV. - 1873-2909 .- 0961-9534. ; 30:1, s. 66-75
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Tidskriftsartikel (refereegranskat)abstract
- Methane production from llama and cow manures from the Bolivian high plateau (The "Altiplano") was studied using a parallel reactor set-up consisting of 10 lab-scale biogasifiers. The effects of pressure (495 and 760 mmHg), temperature (11 and 35 degrees C), hydraulic retention time (20 and 50 days), and manure content in the slurry (10%, 20% and 50%) were evaluated with respect to productivity and methane yields based on two 2(4-1) fractional factorial designs with 8 treatments for each kind of manure. The reactors were operated semi-continuously with daily manure feeding for periods between 50 and 100 days. Temperature was the main factor effect found, and the hydraulic retention time and the manure content in feed were also found significant whereas the effect of pressure was not significant in the range studied. The methane yield obtained with cow manure at 11 degrees C was between 6.4 and 33.61 CH4 kg(-1) VS (volatile solids added) whereas at 35 degrees C the methane yield was between 49.6 and 131.31 CH4 kg(-1) VS. The methane yield from llama manure was somewhat lower than for cow manure (between 3.3 and 19.31 CH4 kg(-1) VS at 11 degrees C and between 35.6 and 84.11 CH4 kg(-1) VS at 35 degrees C, respectively). However, overall llama manure was found to be the best raw material of the two for biogas production, due to its high content of volatile solid-higher than has been previously reported for most manures-and also its high nitrogen and phosphorous content.
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| 5. |
- Alvarez, Rene, et al.
(författare)
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Low temperature anaerobic digestion of mixtures of llama, cow and sheep manure for improved methane production
- 2009
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Ingår i: Biomass & Bioenergy. - : Elsevier BV. - 1873-2909 .- 0961-9534. ; 33:3, s. 527-533
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Tidskriftsartikel (refereegranskat)abstract
- Biogas production in anaerobic digestion in farm-scale units is typically performed under mesophilic conditions when used for producing domestic fuel and stabilizing animal waste for the use of digested manure as a fertilizer. Previous studies on the digestion of llama and cow manure have shown the feasibility of producing biogas under altiplano conditions (low pressure and low temperature) and of llama manure as a promising feedstock. The present study concerns the utilization of various mixtures of feedstocks from the Bolivian altiplano under low temperature conditions (18-25 degrees C). Laboratory scale experiments were performed on the digestion of mixtures of llama, sheep and cow manure in a semi-continuous process using ten 2-L stainless steel digesters to determine the effects of organic loading rate (OLR) and the feed composition. The semi-continuous operation of mixture of llama-cow-sheep manure proved to be a reliable system, which could be operated with good stability. The results suggest that in a system digesting a mixture of llama-cow-sheep manure at low temperature (18-25 degrees C) the maximum OLR value is between 4 and 6 kg VS m(3) d(-1). The methane yields obtained in the mixture experiments were in the range 0.07-0.14 m(3) kg(-1) VS added, with a methane concentration in the gas of between 47 and 55%. (C) 2008 Elsevier Ltd. All rights reserved.
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| 6. |
- Alvarez, Rene, et al.
(författare)
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Semi-continuous co-digestion of solid slaughterhouse waste, manure, and fruit and vegetable waste
- 2008
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Ingår i: Renewable Energy. - : Elsevier BV. - 0960-1481. ; 33:4, s. 726-734
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Tidskriftsartikel (refereegranskat)abstract
- The potential of semi-continuous mesophilic anaerobic digestion (AD) for the treatment of solid slaughterhouse waste, fruit-vegetable wastes, and manure in a co-digestion process has been experimentally evaluated. A study was made at laboratory scale using four 2 L reactors working semi-continuously at 35 degrees C. The effect of the organic loading rate (OLR) was initially examined (using equal proportion of the three components on a volatile solids, VS, basis). Anaerobic co-digestion with OLRs in the range 0.3-1.3 kg VS m(-3) d(-1) resulted in methane yields of 0.3 m(3) kg(-1) VS added, with a methane content in the biogas of 54-56%. However, at a further increased loading, the biogas production decreased and there was a reduction in the methane yield indicating organic overload or insufficient buffering capacity in the digester. In the second part of the investigation, co-digestion was studied in a mixture experiment using 10 different feed compositions. The digestion of mixed substrates was in all cases better than that of the pure substrates, with the exception of the mixture of equal amounts of (VS/VS) solid cattle-swine slaughterhouse waste (SCSSW) with fruit and vegetable waste (FVW). For all other mixtures, the steady-state biogas production for the mixture was in the range 1.1-1.6 L d(-1), with a methane content of 50-57% after 60 days of operation. The methane yields were in the range 0.27-0.35 m(3) kg(-1) VS added and VS reductions of more than 50% and up to 67% were obtained.
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| 7. |
- Alvarez, Rene, et al.
(författare)
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The effect of temperature variation on biomethanation at high altitude.
- 2008
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Ingår i: Bioresource Technology. - : Elsevier BV. - 1873-2976 .- 0960-8524. ; 99, s. 7278-7284
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the current study was to examine effects of daily temperature variations on the performance of anaerobic digestion. Forced square-wave temperature variations (between 11 and 25, 15 and 28, and 19 and 32 degrees C) were imposed on a bench-scale digester using a mixture of llama-cow-sheep manure in a semi-continuous process. The volumetric biogas production rate, methane yield, and the volatile solid reductions were compared with the results obtained from anaerobic digestion (AD) at constant temperatures. The forced cyclic variations of temperature caused large cyclic variations in the rate of gas production and the methane content. As much as 94-97% of the daily biogas was obtained in the 12h half-cycle at high temperature. The values for volumetric biogas production rate and methane yield increased at higher temperatures. The average volumetric biogas production rate for cyclic operation between 11 and 25 degrees C was 0.22Ld(-1)L(-1) with a yield of 0.07m(3)CH(4)kg(-1) VS added (VSadd), whereas for operation between 15 and 29 degrees C the volumetric biogas production rate increased by 25% (to 0.27Ld(-1)L(-1) with a yield of 0.08m(3)CH(4)kg(-1) VSadd). In the highest temperature region a further increase of 7% in biogas production was found and the methane yield was 0.089m(3)CH(4)kg(-1) VSadd. The employed digester showed an immediate response when the temperature was elevated, which indicates a well-maintained metabolic capacity of the methanogenic bacteria during the period of low temperature. Overall, periodic temperature variations appear to give less decrease in process performance than a priori anticipated.
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| 8. |
- Bollati, Michela, et al.
(författare)
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Structure and functionality in flavivirus NS-proteins : perspectives for drug design
- 2010
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 87:2, s. 125-148
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Forskningsöversikt (refereegranskat)abstract
- Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads.
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| 9. |
- Bott, Lukas Thomas, et al.
(författare)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Konferensbidrag (refereegranskat)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 10. |
- Coelho, Teresa, et al.
(författare)
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Safety and efficacy of RNAi therapy for transthyretin amyloidosis
- 2013
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Ingår i: The New England journal of medicine. - 1533-4406. ; 369:9, s. 819-29
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).
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