[Linking Interventional Cardiology clinical registry data with French hospital administrative data: Development and validation of deterministic record linkage]. / Appariement entre un registre régional de pratiques en cardiologie interventionnelle et la base médico-administrative d'hospitalisation française : développement et validation d'un algorithme d'appariement déterministe.

BACKGROUND: To recreate the in-hospital healthcare pathway for patients treated with coronary angiography or percutaneous coronary intervention, we linked the interventional cardiology registry (ACIRA) and the pseudonymized French hospital medical information system database (PMSI) in the Aquitaine region. The objective of this study was to develop and validate a deterministic merging algorithm between these exhaustive and complementary databases. METHODS: After a pre-treatment phase of the databases to standardize the 11 identified linking variables, a deterministic linking algorithm was developed on ACIRA hospital stays between December 2011 and December 2014 in nine interventional cardiology centers as well as the data from the consolidated PMSI databases of the Aquitaine region from 2011 to 2014. Merging was carried out through 12 successive steps, the first consisting in strict linking of the 11 variables. The performance of the algorithm was analyzed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Strategies complementary to the initial algorithm (change in the order of variables and base preprocessing) were tested. Comparative analysis of merged/unmerged patients explored potential causes of mismatch. RESULTS: The algorithm found 97.2% of the 31,621 ACIRA stays to have sensitivity of 99.9% (95% CI [99.9; 99.9]), specificity of 97.9% (95% CI [97.7; 98.1]), PPV of 99.9% (95% CI [99.9; 99.9]) and NPV of 96.9% (95% CI [96.7; 97.1]). Complementary strategies did not yield better results. The unmerged patients were older, and hospitalized mostly in 2012 in two interventional cardiology centers. CONCLUSION: This study underscored the feasibility and validity of an indirect deterministic pairing to routinely link a registry of practices using hospital data to pseudonymized medico-administrative databases. This method, which can be extrapolated to other health events leading to hospitalization, renders it possible to effectively reconstruct patients' hospital healthcare pathway.

Dual-energy computed tomography in calcium pyrophosphate deposition: initial clinical experience.

OBJECTIVE: To determine the dual-energy computed tomography (DECT) attenuation properties of meniscal calcifications in calcium pyrophosphate deposition (CPPD) in vivo, and assess whether DECT was able to discriminate meniscal CPP deposits from calcium hydroxyapatite (HA) in subchondral and trabecular bone. METHOD: Patients with clinical suspicion of crystal-related arthropathy (gout and/or CPPD) and knee DECT scans were retrospectively assigned to CPPD (n = 19) or control (n = 21) groups depending on the presence/absence of chondrocalcinosis on DECT. Two observers drew standardized regions of interest (ROI) in meniscal calcifications, non-calcified menisci, as well as subchondral and trabecular bone. Five DECT parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (ρe), and effective atomic number (Zeff). The four different knee structures were compared within/between patients and controls using linear mixed models, adjusting for confounders. RESULTS: Meniscal calcifications (n = 89) in CPPD patients had mean ± SD CT numbers at 80 and 140 kV of 257 ± 64 and 201 ± 48 HU, respectively; with a DEI of 0.023 ± 0.007, and ρe and Zeff of 140 ± 35 and 8.8 ± 0.3, respectively. Meniscal CPP deposits were readily distinguished from calcium HA in subchondral and trabecular bone (p ≤ 0.001), except at 80 kV separately (p = 0.74). Zeff and ρe both significantly differed between CPP deposits and calcium HA in subchondral and trabecular bone (p < 0.0001). CONCLUSION: This proof-of-concept study shows that DECT has the potential to discriminate meniscal CPP deposits from calcium HA in subchondral and trabecular bone in vivo, paving the way for the non-invasive biochemical signature assessment of intra- and juxta-articular calcium crystal deposits.

Screening of freshwater and seawater microalgae strains in fully controlled photobioreactors for biodiesel production.

Strain selection is one of the primary hurdles facing cost-effective microalgal biodiesel production. Indeed, the strain used affects both upstream and downstream biodiesel production processes. This study presents a screening procedure that considers the most significant criteria in microalgal biodiesel production including TAG production and wet extraction and recovery of TAGs. Fourteen freshwater and seawater strains were investigated. Large variation was observed between the strains in all the screening criteria. The overall screening procedure ultimately led to the identification of Parachlorella kessleri UTEX2229 and Nannochloropsis gaditana CCMP527 as the best freshwater and seawater strains, respectively. They featured the largest areal TAG productivity equal to 2.7×10(-3) and 2.3×10(-3)kgm(-2)d(-1), respectively. These two strains also displayed encouraging cell fragility in a high pressure bead milling process with 69% and 98% cell disruption at 1750bar making them remarkable strains for TAG extraction in wet environment.

Hydrothermal liquefaction of Nannochloropsis oceanica in different solvents.

Although the hydrothermal liquefaction is considered a promising technology for converting microalgae into liquid biofuels, there are still some disadvantages. This paper demonstrated that the bio-oil yield can be significantly improved by adding alcohols as co-solvents and carrying out the conversion at mild conditions (<250°C), but at the expense of a reduced bio-oil quality. By adding ethanol, the bio-oil yields obtained (up to ∼60%) were comparable to the yield obtained at severe operating conditions using only water as solvent (54±2% on average), but the quality of the bio-oil was lower. However, the main advantages of the process here described lie in the utilisation of wet microalgae (∼75% moisture) and alcohol concentrations which avoid both drying the microalgae and decreasing the amount of microalgae loaded in the reactor.

[Medication reconciliation at hospital admission: Results and identification of target patients]. / Conciliación de la medicación al ingreso: resultados e identificación de pacientes diana.

OBJECTIVE: To quantify and to classify the discrepancies between the admission treatment and the usual patient treatment. To determine the variables that predict those patients that will have more benefit from medication reconciliation. MATERIAL AND METHODS: A prospective medication reconciliation study was conducted in the Vascular Surgery Unit from March 2014 to December 2014. When the patients were admitted to the Vascular Surgery Unit, they were informed about the study and asked to prepare information about their chronic treatment. The pharmacist then checked their clinical records, outpatient prescriptions, and also interviewed the patient, obtaining the best pharmacotherapeutic history available. The discrepancies with the admission treatment were written into the patient electronic clinical records. Finally, the physician classified the discrepancies, and changed the treatment, if needed. The statistical analysis included a comparison between patients with and without a non-justified discrepancy (NJD). The statistically different characteristics were used to plot Receiver Operating Characteristic curves, in order to determine the sensitivity and the specificity of these variables to select patients with discrepancies. RESULTS: A total of 380 patients were included. There were 845 non-justified, 600 justified non-documented, and 439 justified documented discrepancies. At least one NJD was identified in 293 patients (77%), with 65 patients (17%) having only justified discrepancies, and 22 patients (6%) having no discrepancies. NJD were: different dose, route or schedule (51%), omission (39%), wrong drug (8%) and commission (2%). The variables associated with discrepancies were number of chronic medications drugs and provider of information. CONCLUSIONS: In most studies, omission is the most frequent error. In contrast, in our study the most frequent error is different dose, route, or schedule. The variable that allows selecting patients at higher risk of discrepancies is the number of chronic drugs. This risk is also increased if the patients are not the manager of their own medication.

A novel pre-treatment for the methane production from microalgae by using N-methylmorpholine-N-oxide (NMMO).

The aim of this work was to study the effect of the solvent N-methylmorpholine-N-oxide (NMMO) to pre-treat Nannochloropsis oculata before the anaerobic digestion process. The results indicated that the pre-treatment affects the characteristics of the cell wall, which consequently becomes more susceptible to the microorganisms attack during anaerobic digestion. The methane production was increased by 43% after the pre-treatment, from 238±6mLCH4/gVS until 339±4mLCH4/gVS. On the contrary, the methane production from Chlorella vulgaris decreased after the pre-treatment from 251±4mLCH4/gVS to 231±3mLCH4/gVS. The failure on the pre-treatment was attributed to the particular characteristics of the substrate in consequence of a previous drying step.

Late presentation to HIV testing is overestimated when based on the consensus definition.

OBJECTIVES: In 2011, a consensus was reached defining "late presenters" (LPs) as individuals presenting for care with a CD4 count < 350 cells/µL or with an AIDS-defining event, regardless of CD4 count. However, a transient low CD4 count is not uncommon in recent infections. The objective of this study was to investigate how measurements of late presentation change if the clinical stage at the time of diagnosis is taken into account. METHODS: Case surveillance data for newly diagnosed patients in Belgium in 1998-2012 were analysed, including CD4 count at diagnosis, the presence of AIDS-defining events, and recent infections (< 6 months) as reported by clinicians in the case of acute illness or a recent negative test. First, proportions of LPs were calculated according to the consensus definition. Secondly, LPs were reclassified as "nonlate" if infections were reported as recent. RESULTS: A total of 7949 HIV diagnoses were included in the study. Recent infections were increasingly reported over time, accounting for 8.2% of new infections in 1998 and 37.5% in 2012. The consideration of clinical stage significantly modified the proportion of LPs: 18.2% of men who have sex with men (MSM) diagnosed in 2012 would be classified as LPs instead of 30.9% using the consensus definition (P < 0.001). The proportion of patients misclassified as LPs increased significantly over time: 5% in MSM in 1998 vs. 41% in 2012. CONCLUSIONS: This study suggests that low CD4 counts in recent infections may lead to overestimation of late presentation when applying the consensus definition. The impact of transient CD4 count on late presentation estimates should be assessed and, if relevant, the introduction of clinical stage in the definition of late presentation should be considered.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

Occupational determinants of methicillin-resistant Staphylococcus aureus colonization among healthcare workers: a longitudinal study in a rehabilitation center.

BACKGROUND Staphylococcus aureus carriage among healthcare workers (HCWs) is a concern in hospital settings, where it may provide a reservoir for later infections in both patients and staff. Earlier studies have shown that the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in HCWs is highly variable, depending notably on location, hospital department type, MRSA prevalence among patients, and type of contacts with patients. However, MRSA incidence in HCWs and its occupational determinants have seldom been studied. METHODS A prospective, observational cohort study was conducted between May and October 2009 in a French rehabilitation center hospital. HCWs and patients were screened weekly for S. aureus nasal carriage. Methicillin-susceptible S. aureus and MRSA prevalence and incidence were estimated and factors associated with MRSA acquisition were identified using generalized estimating equation regression methods. RESULTS Among 343 HCWs included in the analysis, the average prevalence was 27% (95% CI, 24%-29%) for methicillin-susceptible S. aureus and 10% (8%-11%) for MRSA. We observed 129 MRSA colonization events. According to the multivariable analysis, high MRSA prevalence level among patients and HCW occupation were significantly associated with MRSA acquisition in HCWs, with assistant nurses being more at risk than nurses (odds ratio, 2.2; 95% CI, 1.4-3.6). CONCLUSIONS Our findings may help further our understanding of the transmission dynamics of MRSA carriage acquisition in HCWs, suggesting that it is notably driven by carriage among patients and by the type of contact with patients.

A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study.

OBJECTIVES: The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI). METHODS: An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/µL and HIV-1 RNA >30000 copies/mL (n=207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA <50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/µL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n=61) or to continue the PI-based ART (n=59). RESULTS: For the proportions of patients (intention-to-treat; missing=failure) with HIV-1 RNA <400 copies/mL (PI group, 66%; ABC/3TC/ZDV group, 71%) and <50 copies/mL (PI group, 63%; ABC/3TC/ZDV group, 62%) at 96 weeks, switching to ABC/3TC/ZDV was noninferior compared with continuing the PI regimen; the difference in failure rate (ABC/3TC/ZDV minus PI) was -4.4 percentage points [95% confidence interval (CI) -21.0 to +12.3 percentage points] and +0.4 percentage points (95% CI -16.9 to +17.7 percentage points), respectively. In the per protocol analysis, the difference in virological failure for HIV-1 RNA >400 copies/mL (0 of 39 patients in the PI group and two of 45 patients in the NRTI group) and for HIV-1 RNA >50 copies/mL (two of 39 and three of 45 patients, respectively) was +4.4 percentage points (95% CI -2.1 to +11.0 percentage points) and +1.5 percentage points (95% CI -8.6 to +11.7 percentage points), respectively, also showing noninferiority. Serum lipids significantly improved in the NRTI group, but not in the PI arm. CONCLUSIONS: A single-class NRTI regimen after successful induction with standard ART had similar antiviral efficacy compared to continuation of a PI-based regimen at 96 weeks after baseline, with improved serum lipids.

Development and validation of a screening procedure of microalgae for biodiesel production: application to the genus of marine microalgae Nannochloropsis.

Nannochloropsis has emerged as a promising alga for biodiesel production. However, the genus consists of 6 species and hundreds of strains making strain selection a challenge. Furthermore, oil productivity is instrumental to economic viability of any algal strain for industrial production, which is dependent on growth rate and oil content. In most cases, these two parameters have been studied independently. Thus, the goal of this study is to provide a combined method for evaluating strain performance in specially designed photobioreactors together with an in-depth lipidomic analyses. The nine strains of Nannochloropsis tested showed considerable variations in productivity and lipidomics highlighting the importance of strain selection. Finally, Nannochloropsis gaditana CCMP527 and Nannochloropsis salina CCMP537 emerged as the two most promising strains, with an oil content of 37 and 27 dry wt% after 11-day nitrogen starvation, respectively, resulting in TAG productivity of 13×10(-3) and 18×10(-3) kg m(-3) d(-1), respectively.

Mapping the 3D distribution of CdSe nanocrystals in highly oriented and nanostructured hybrid P3HT-CdSe films grown by directional epitaxial crystallization.

Highly oriented and nanostructured hybrid thin films made of regioregular poly(3-hexylthiophene) and colloidal CdSe nanocrystals are prepared by a zone melting method using epitaxial growth on 1,3,5-trichlorobenzene oriented crystals. The structure of the films has been analyzed by X-ray diffraction using synchrotron radiation, electron diffraction and 3D electron tomography to afford a multi-scale structural and morphological description of the highly structured hybrid films. A quantitative analysis of the reconstructed volumes based on electron tomography is used to establish a 3D map of the distribution of the CdSe nanocrystals in the bulk of the films. In particular, the influence of the P3HT-CdSe ratio on the 3D structure of the hybrid layers has been analyzed. In all cases, a bi-layer structure was observed. It is made of a first layer of pure oriented semi-crystalline P3HT grown epitaxially on the TCB substrate and a second P3HT layer containing CdSe nanocrystals uniformly distributed in the amorphous interlamellar zones of the polymer. The thickness of the P3HT layer containing CdSe nanoparticles increases gradually with increasing content of NCs in the films. A growth model is proposed to explain this original transversal organization of CdSe NCs in the oriented matrix of P3HT.

Investigation of fatty acids accumulation in Nannochloropsis oculata for biodiesel application.

Lipids production of the marine microalga species Nannochloropsis oculata was deeply investigated by studying under continuous light the effects of different nitrogen starvation strategies in photobioreactors of various thicknesses. Operating parameters like incident photons flux density (PFD), initial nitrogen (progressive starvation strategy) or biomass concentrations (sudden starvation strategy) were examined, with a detailed analysis of their effects on the quality and production kinetics of total (TL) and triglycerides (TG). In addition to the already known effect of nitrogen starvation to trigger reserve lipids accumulation (mainly TG), it was demonstrated the relevance of the light received per cell affecting TG content and productivities, as well as fatty acids (FA) profiles. With appropriate optimization, N. oculata was confirmed as an interesting candidate for biodiesel application, with high FA accumulation (up to around 50%DW with 43%DW in TG-FA), high productivity (maximum 3.6×10(-3)kg(TG-FA)m(-2)d(-1)) and a TG-FA profile close to palm oil.

Kinetic modeling of light limitation and sulfur deprivation effects in the induction of hydrogen production with Chlamydomonas reinhardtii. Part II: Definition of model-based protocols and experimental validation.

Photosynthetic hydrogen production under light by the green microalga Chlamydomonas reinhardtii was investigated in a torus-shaped PBR in sulfur-deprived conditions. Culture conditions, represented by the dry biomass concentration of the inoculum, sulfate concentration, and incident photon flux density (PFD), were optimized based on a previously published model (Fouchard et al., 2009. Biotechnol Bioeng 102:232-245). This allowed a strictly autotrophic production, whereas the sulfur-deprived protocol is usually applied in photoheterotrophic conditions. Experimental results combined with additional information from kinetic simulations emphasize effects of sulfur deprivation and light attenuation in the PBR in inducing anoxia and hydrogen production. A broad range of PFD was tested (up to 500 µmol photons m(-2) s(-1) ). Maximum hydrogen productivities were 1.0 ± 0.2 mL H2 /h/L (or 25 ± 5 mL H2 /m(2) h) and 3.1 mL ± 0.4 H2 /h L (or 77.5 ± 10 mL H2 /m(2) h), at 110 and 500 µmol photons m(-2) s(-1) , respectively. These values approached a maximum specific productivity of approximately 1.9 mL ± 0.4 H2 /h/g of biomass dry weight, clearly indicative of a limitation in cell capacity to produce hydrogen. The efficiency of the process and further optimizations are discussed.

Effect of prolonged hypoxia in autotrophic conditions in the hydrogen production by the green microalga Chlamydomonas reinhardtii in photobioreactor.

In the context of hydrogen production by the green alga Chlamydomonas reinhardtii, the control of light attenuation conditions is used to set-up anoxia under illuminated and autotrophic conditions, without affecting photosynthetic capacities of cells (as with sulphur deprivation or PSII inhibitors like DCMU). This paper presents a full description of the protocol where the incident photons flux density (PFD) is adapted during cultivation in order to obtain a sufficiently low illuminated fraction γ under 0.25 leading to anoxic hydrogen producing conditions during several days. The protocol is validated in a torus-shape photobioreactor (PBR) revealing after few days of anoxic conditions a peak of hydrogen production (1.44 ml H2/h/l of culture; [0.8-1.0] ml H2/h/g of dry weight biomass) concomitant with a decrease of biomass concentration, protein content and maximal photosynthetic yield. Effect of over-accumulating starch, as being known to increase hydrogen production by the PSII-independent pathway, is also investigated.

Systematic investigation of biomass and lipid productivity by microalgae in photobioreactors for biodiesel application.

We describe a methodology to investigate the potential of given microalgae species for biodiesel production by characterizing their productivity in terms of both biomass and lipids. A multi-step approach was used: determination of biological needs for macronutrients (nitrate, phosphate and sulphate), determination of maximum biomass productivity (the "light-limited" regime), scaling-up of biomass production in photobioreactors, including a theoretical framework to predict corresponding productivities, and investigation of how nitrate starvation protocol affects cell biochemical composition and triggers triacylglycerol (TAG) accumulation. The methodology was applied to two freshwater strains, Chlorella vulgaris and Neochloris oleoabundans, and one seawater diatom strain, Cylindrotheca closterium. The highest total lipid content was achieved with N. oleoabundans (25-37% of DW), while the highest TAG content was found in C. vulgaris (11-14% of DW). These two species showed similar TAG productivities.

Investigation of biomass and lipids production with Neochloris oleoabundans in photobioreactor.

The fresh water microalga Neochloris oleoabundans was investigated for its ability to accumulate lipids and especially triacylglycerols (TAG). A systematic study was conducted, from the determination of the growth medium to its characterization in an airlift photobioreactor. Without nutrient limitation, a maximal biomass areal productivity of 16.5 g m(-2) day(-1) was found. Effects of nitrogen starvation to induce lipids accumulation was next investigated. Due to initial N. oleoabundans total lipids high content (23% of dry weight), highest productivity was obtained without mineral limitation with a maximal total lipids productivity of 3.8 g m(-2) day(-1). Regarding TAG, an almost similar productivity was found whatever the protocol was: continuous production without mineral limitation (0.5 g m(-2) day(-1)) or batch production with either sudden or progressive nitrogen deprivation (0.7 g m(-2) day(-1)). The decrease in growth rate reduces the benefit of the important lipids and TAG accumulation as obtained in nitrogen starvation (37% and 18% of dry weight, respectively).

Bacterial colonization after tunneling in 402 perineural catheters: a prospective study.

BACKGROUND: Bacterial colonization of peripheral nerve catheters is frequent, although infection is relatively rare. With central venous catheters, the tunneling of the catheter into the subcutaneous tissue significantly decreases catheter colonization and catheter-related sepsis. We evaluated the incidence of bacterial colonization in adult patients with tunnelized perineural nerve catheters. METHODS: Peripheral nerve catheters placed under sterile conditions for postoperative analgesia were evaluated prospectively. After removal, they were analyzed for colonization. Quantitative culture was used as described by Brun-Buisson for intravascular catheters. The site of insertion was monitored daily for any signs of infection. RESULTS: Four-hundred-two patients were included in the study during a 2-yr period. The mean duration of peripheral nerve catheters was 48 h (47-50.4). Positive culture occurred in 25 catheters, indicating that the incidence of colonization was 6.22% (3.8-8.5). The microbiological analysis of the catheter tip cultures revealed coagulase-negative staphylococci in 72%. Twenty-two catheters of 25 catheters each had one microorganism, and for three catheters, two microorganisms were identified. No infection was found in any patient. CONCLUSION: The incidence of perineural catheter colonization is low with subcutaneous tunneling. Controlled randomized studies are warranted to determine whether this procedure decreases the risk for infection.

Kinetics modeling of alginate alkaline extraction from Laminaria digitata.

Alginates being depolymerized during their alkaline extraction, reducing extraction time could help producing higher rheological quality alginates. The purpose of the present work is to study fresh Laminaria digitata destructuration during alkaline extraction and its link to extraction kinetics. Both alginate extraction yield and mean diameter of algae particles were followed for different values of agitation level and initial size of algae pieces. Results highlighted the existence of a link between extraction yield and algal destructuration. Those elements and the specificity of L.digitata structure have been taken into account to propose a kinetics model based on a fluid-particle reaction with decreasing size particles. The model parameters have been adjusted thanks to acquisition data and its predictive capacity was assessed by validation data. Provided predictions appeared to be relevant and the model structure suitability was confirmed, as extraction yield kinetics specific shape was quite reliably described.