DAC Stacking: A Deep Learning Ensemble to Classify Anxiety, Depression, and Their Comorbidity From Reddit Texts.

Depression is the most incapacitating disease worldwide, and it has an alarming comorbidity rate with anxiety. The use of social networks to expose personal difficulties has enabled works on the automatic identification of specific mental conditions, particularly depression. In spite of many solutions proposed for the automatic recognition of depression, fewer exist for anxiety and its comorbidity with depression. In this paper, we propose DAC Stacking, a solution that leverages stacking ensembles and Deep Learning (DL) to automatically identify depression, anxiety, and their comorbidity, using data extracted from Reddit. The stacking is composed of single-label binary classifiers, that either distinguish between specific disorders and control users (experts), or between pairs of target conditions (differentiating). A meta-learner explores these base classifiers as a context for reaching a multi-label decision. We assessed alternative ensemble topologies, exploring roles for base models, DL architectures, and word embeddings. All base classifiers and ensembles outperformed the baselines for depression and anxiety (f-measures near 0.79). The ensemble topology with the best performance (Hamming Loss of 0.29 and Exact Match Ratio of 0.46) combines base classifiers of three DL architectures, and includes expert and differentiating base models. The analysis of the influential classification features according to SHAP revealed the strengths of our solution and provided insights on the challenges for the automatic classification of the addressed mental conditions.

Thoracoscopy Approach in Prone Position for Esophagoplasty in Children.

Congenital esophageal stenosis (CES) is a very rare clinical condition found in 1 per 25,000 to 50,000 live births. There are three histological types of CES described: tracheobronchial remnants, fibromuscular stenosis (FMS), and membranous stenosis. The first-line treatment in most cases is the conservative treatment (dilatation with a Savary bougie or balloon), but in some CES types, dilatation may be ineffective or result in esophageal perforation with serious complications or lethal outcome. Resection of the stenotic segment and end-to-end esophageal anastomosis was formerly presented as the most common surgical treatment option for CES. However, esophagoplasty is a safe and feasible alternative for surgical treatment of esophageal stenosis in children. Our aim is to report two cases of FMS submitted to thoracoscopic esophagoplasty. Both cases started with dysphagia and refusal after transition to solid diet, at 6 months old, and the radiological examination showed stricture of the distal esophagus. Esophagoplasty was performed with the patients in prone position. The stenotic esophageal wall was incised longitudinally and transverse synthesis was performed. After surgery, the patients had prompt recovery, without recurrent stenosis, remaining asymptomatic, with good diet acceptance.

New Models for the Evaluation of Specialized Medicinal Products: Beyond Conventional Health Technology Assessment and Pricing.

New specialized therapeutics coming to market, such as advanced therapy medicinal products (ATMPs) and orphan drugs, differ from traditional therapies in terms of how they are manufactured and administered, as well as the potentially transformative benefits they may provide. The current health technology assessment (HTA) process that has been used for traditional therapies, such as small molecule drugs and antibodies, does not work adequately for specialized therapeutics, with a key issue being the generation of sufficient evidence to adequately capture the full long-term benefits. The objectives of this article are to discuss why the current HTA process is inadequate for evaluating these new therapies, how evidence should be continuously generated and presented to regulators and payers to support their use, and to propose new approaches to pricing models. This will enable payers to have an affordable, risk-mitigated means of funding new therapies in a timely manner, thus guaranteeing patient access to new, potentially life-saving therapies, while providing manufacturers with a return on their investment. Without new approaches or adaptation of existing frameworks, certain ATMPs may not reach patients in some or all countries or be at risk of withdrawal from the market.

Tell me your dreams and goals: Structuring communication exchanges to improve patient-centered care with chronic pain patients.

BACKGROUND: Communicating pain is a difficult endeavor due to the lack of observable pathology, the immeasurable nature of pain, and the presence of comorbid symptoms. While research has shown the value of cure-centered and care-centered communication, it is unclear how chronic pain patients would like to structure pain communication with their providers so that it produces pain disclosure and emotional support. Aim This study examines communication preferences of chronic pain patients including types of questions asked and information received to allow a holistic portrayal of the experience of living with chronic pain. DESIGN: The research used a quantitative survey that was disseminated via online chronic pain devoted support groups. PARTICIPANTS: 192 respondents took the survey, with women respondents outnumbering men at a 4:1 ratio. Respondents came from 38 states and represented eight countries. RESULTS: For providers to better understand patients' chronic pain, results indicate they would like providers to inquire about how pain impacts their daily activities, relationships, work responsibilities, and goals and dreams using open-ended questions. These low-stake questions can facilitate emotional disclosure, increase feelings of support, and allow for co-morbid linkages. CONCLUSION: These inquiries prioritize patients' own subjective knowledge, can deepen the communication exchange between provider and patient, and facilitate pain disclosure. The findings help to deliver patient-centered care, promote rapport, and foster trust between providers and their patients.

Reliability, validity, and the ability to detect change of the Psoriasis Symptom Scale (PSS) in patients with plaque psoriasis.

Introduction: The primary objective of the study was to evaluate the measurement properties of the patient-reported four-item Psoriasis Symptom Scale (PSS).Methods: Analysis of phase-III data on the efficacy of risankizumab to assess psychometric characteristics of the PSS in patients with moderate-to-severe psoriasis.Results: PSS items had a good range of symptom severity coverage. The PSS had good test-retest reliability (ICCs >0.90). Convergent and discriminant validity was indicated by moderate-to-strong correlations between the PSS and Dermatology Life Quality Index (DLQI), PSS pain item and EQ-5D pain/discomfort item at week 12 (0.63), and moderate negative correlation with EQ-Visual Analog Scale score at week 12 (-0.37). Known groups validity demonstrated as mean PSS total scores varied by Psoriasis Area and Severity Index (PASI) and Static Physician's Global Assessment (sPGA) defined groups (p < .0001). PSS total scores were responsive to changes in PASI score (p < .0001) and sPGA (p < .0001). PSS minimal, clinical, and meaningful change is estimated to be 1 to 2 points; a preliminary responder definition is a total change score of 3 to 4 points.Conclusions: The PSS is a short, valid unidimensional measure of psoriasis symptom severity, well suited for use in clinical trials.

A hierarchical classifier based on human blood plasma fluorescence for non-invasive colorectal cancer screening.

Colorectal cancer (CRC) a leading cause of death by cancer, and screening programs for its early identification are at the heart of the increasing survival rates. To motivate population participation, non-invasive, accurate, scalable and cost-effective diagnosis methods are required. Blood fluorescence spectroscopy provides rich information that can be used for cancer identification. The main challenges in analyzing blood fluorescence data for CRC classification are related to its high dimensionality and inherent variability, especially when analyzing a small number of samples. In this paper, we present a hierarchical classification method based on plasma fluorescence to identify not only CRC, but also adenomas and other non-malignant colorectal findings that may require further medical investigation. A feature selection algorithm is proposed to deal with the high dimensionality and select discriminant fluorescence wavelengths. These are used to train a binary support vector machine (SVM) in the first level to identify the CRC samples. The remaining samples are then presented to a one-class SVM trained on healthy subjects to detect deviant samples, and thus non-malignant findings. This hierarchical design, together with the one class-SVM, aims to reduce the effects of small samples and high variability. Using a dataset analyzed in previous studies comprised of 12,341 wavelengths, we achieved much superior results. Sensitivity and specificity are 0.87 and 0.95 for CRC detection, and 0.60 and 0.79 for non-malignant findings, respectively. Compared to related work, the proposed method presented a better accuracy, required fewer features, and provides a unified approach that expands CRC detection to non-malignant findings.

Dance Your Heart Out: A Community's Approach to Addressing Cardiovascular Health by Using a Logic Model.

Cardiovascular health has been identified as a prioritized community health need according to recent community health needs assessment data. While the Affordable Care Act mandates that nonprofit hospitals conduct a community health needs assessment, little guidance exists on how to address the identified needs. Logic models provide systematic structure and necessary direction in how communities can start to address their identified health needs. Completing logic models in a nonlinear fashion is encouraged to employ a strengths-based approach and verify the logic. This article provides an application of logic models as one strategy to generate a community-based program theory to improve cardiovascular health.

Microphase separation in solid lipid dosage forms as the cause of drug release instability.

Although lipid excipients are of increasing interest for development of taste-masked and modified release formulations, the drug release instability and the lack of mechanistic understanding in that regard still prevent their larger-scale application. In this work, we investigated the physical stability of a binary (tripalmitin/polysorbate 65) lipid coating formulation with a known stable polymorphism. The coating composition was characterized using DSC to construct the phase diagram of binary system and polarized light microscopy to display the microstructure organization. The water uptake and the erosion of slabs cast from the coating formulations were investigated post-production and after storage. Subsequently, N-acetylcysteine particles were coated with the selected formulations and the drug release stability was investigated. Additionally, microstructure characterization was performed via SEM and X-ray diffraction. The drug release instability was explained by polysorbate 65 and tripalmitin phase growth during storage, especially at 40°C, suggesting that polysorbate 65 can leak out of tripalmitin spherulitic structures, creating lipophilic and impermeable tripalmitin regions. The growth of polysorbate 65 phase leads to larger hydrophilic channels with reduced tortuosity. This work indicates that for obtaining stable drug release profiles from advanced lipid formulations, microphase separation should be prevented during storage.

Application of ICH Q9 Quality Risk Management Tools for Advanced Development of Hot Melt Coated Multiparticulate Systems.

This study aimed to apply quality risk management based on the The International Conference on Harmonisation guideline Q9 for the early development stage of hot melt coated multiparticulate systems for oral administration. N-acetylcysteine crystals were coated with a formulation composing tripalmitin and polysorbate 65. The critical quality attributes (CQAs) were initially prioritized using failure mode and effects analysis. The CQAs of the coated material were defined as particle size, taste-masking efficiency, and immediate release profile. The hot melt coated process was characterized via a flowchart, based on the identified potential critical process parameters (CPPs) and their impact on the CQAs. These CPPs were prioritized using a process failure mode, effects, and criticality analysis and their critical impact on the CQAs was experimentally confirmed using a statistical design of experiments. Spray rate, atomization air pressure, and air flow rate were identified as CPPs. Coating amount and content of polysorbate 65 in the coating formulation were identified as critical material attributes. A hazard and critical control points analysis was applied to define control strategies at the critical process points. A fault tree analysis evaluated causes for potential process failures. We successfully demonstrated that a standardized quality risk management approach optimizes the product development sustainability and supports the regulatory aspects.

Aadh2p: an Arxula adeninivorans alcohol dehydrogenase involved in the first step of the 1-butanol degradation pathway.

BACKGROUND: The non-conventional yeast Arxula adeninivorans uses 1-butanol as a carbon source and has recently attracted attention as a promising organism for 1-butanol production. Alcohol dehydrogenases (adhp) are important catalysts in 1-butanol metabolism, but only Aadh1p from Arxula has been characterized. This enzyme is involved in ethanol synthesis but has a low impact on 1-butanol degradation. RESULTS: In this study, we identified and characterized a second adhp from A. adeninivorans (Aadh2p). Compared to Saccharomyces cerevisiae ADHs' (ScAdh) protein sequences it originates from the same ancestral node as ScAdh6p, 7p and 4p. It is also localized in the cytoplasm and uses NAD(H) as cofactor. The enzyme has its highest activity with medium chain-length alcohols and maximum activity with 1-butanol with the catalytic efficiency of the purified enzyme being 42 and 43,000 times higher than with ethanol and acetaldehyde, respectively. Arxula adeninivorans strain G1212/YRC102-AADH2, which expresses the AADH2 gene under the control of the strong constitutive TEF1 promoter was constructed. It achieved an ADH activity of up to 8000 U/L and 500 U/g dry cell weight (dcw) which is in contrast to the control strain G1212/YRC102 which had an ADH activity of up to 1400 U/L and 200 U/g dcw. Gene expression analysis showed that AADH2 derepression or induction using non-fermentable carbon-sources such as ethanol, pyruvate, glycerol or 1-butanol did occur. Compared to G1212/YRC102 AADH2 knock-out strain had a slower growth rate and lower 1-butanol consumption if 1-butanol was used as sole carbon source and AADH2-transformants did not grow at all in the same conditions. However, addition of the branched-chain amino acids leucine, isoleucine and valine allowed the transformants to use 1-butanol as carbon source. The addition of these amino acids to the control strain and Δaadh2 mutant cultures had the effect of accelerating 1-butanol consumption. CONCLUSIONS: Our results confirm that Aadh2p plays a major role in A. adeninivorans 1-butanol metabolism. It is upregulated by up to 60-fold when the cells grow on 1-butanol, whereas only minor changes were found in the relative expression level for Aadh1p. Thus the constitutive overexpression of the AADH2 gene could be useful in the production of 1-butanol by A. adeninivorans, although it is likely that other ADHs will have to be knocked-out to prevent 1-butanol oxidation.

Improving the granule strength of roller-compacted ibuprofen sodium for hot-melt coating processing.

Solvent-free hot-melt coating processing is a novel and cost-efficient approach to manufacturing taste-masked multiparticulate systems. However, most API powders are fine and cohesive and not processable by hot-melt coating. The aim of this study was to produce dense and abrasion-resistant granules with high drug content (>80%) via roller compaction for hot-melt coating process optimization. The selected API was ibuprofen sodium dihydrate, a salt of ibuprofen with improved bioavailability and poor intrinsic compactibility. The formulation and roller compaction process were developed for the production of granules with 94%w/w of API and low friability (∼30%), using sorbitol and isomalt as excipients. The strong bonding mechanism relied on powder jamming prior to the rollers and was investigated via scanning electron microscopy, differential scanning calorimetry and small and wide angle X-ray scattering. It was shown that sorbitol crystals are solubilized during roller compaction and recrystallize as sorbitol hydrate, acting as strong solid bridges. The robustness of the roller compaction process and the re-compaction of fines were investigated. A statistical design of experiments was conducted to evaluate the hot-melt coating process for taste masking of ibuprofen sodium granules. Taste masking required coating ratios higher than 40%w/w of granule batch, emphasizing the need for high-drug-content and abrasion-resistant granules.

Advanced stable lipid-based formulations for a patient-centric product design.

Multiparticulate dosage forms are a recent strategy to meet the special needs of children, elderly people and patients suffering from dysphagia. Our study presents a novel and cost-efficient approach for the manufacturing of a taste-masked multiparticulate system with a stable immediate release profile by applying lipid-based excipients in a solvent-free hot melt coating process. The thermosensitive N-acetylcysteine (N-ac) was used as model drug and hot-melt coated with a mixture of tripalmitin and polysorbate 65. A predictive in vitro method for the evaluation of the taste masking efficiency was developed based on the deprotonation of the carboxyl group of N-ac and the decline of pH, responsible for the unpleasant sour taste of the compound. The method was confirmed using in vivo studies. Differential scanning calorimetry and X-ray scattering experiments revealed polymorphic transformation and its dependency on transformation time, temperature and emulsifier concentration. During the process, the coating was transformed almost completely into the stable ß-polymorph, leading to an unaltered dissolution profile during storage. A statistical design was conducted that revealed the critical process parameters affecting the taste masking efficiency and drug release. This study shows the successful application of solvent-free hot-melt coating in the development of a taste-masked and stable formulation.

Epidemiological analysis of polytrauma patients with kidney injuries in a university hospital / Análise epidemiológica de politraumatizados com lesões renais em um hospital universitário

Objective: To analyze the characteristics of trauma patients with renal lesions treated at a university hospital in Curitiba. Methods: We conducted a retrospective, cross-sectional study guided by review of medical records of trauma victims who underwent surgical treatment. The variables analyzed were age, gender, mechanism of injury, degree of kidney damage, conduct individualized according to the degree of renal injury, associated injuries, complications and deaths. We classified lesions according to the American Association of Trauma Surgery (TSAA). Results: We analyzed 794 records and found renal lesions in 33 patients, with mean age 29.8 years, most (87.8%) being male. Penetrating trauma accounted for 84.8% of cases. The most common renal injuries were grade II (33.3%), followed by grade I (18.1%), III, IV and V. Nephrectomy treated 45.4% of injuries, 73.3% being total nephrectomy, and 45.4% by nephrorraphy. In 9% treatment was non-surgical. Only 12.1% of patients had isolated renal lesions. Complications ensued in 15.1% and mortality was 6.06%. Conclusion: The surgical approach was preferred due to penetrating trauma mechanism. We achieved low rates of complications and deaths, and neither case could be directly related to kidney damage, and there were patients with multiple lesions. In this sample, we could not observe a direct relationship between kidney damage and complications, deaths or the type of conduct employed.

Objetivo: analisar as características de pacientes vítimas de trauma, com lesões renais atendidos em um hospital universitário de Curitiba. Métodos: estudo transversal retrospectivo guiado por revisão de prontuários de vítimas de trauma submetidos ao tratamento cirúrgico. As variáveis analisadas foram idade, sexo, mecanismo de trauma, grau das lesões renais, conduta individualizada de acordo com o grau da lesão renal, lesões associadas, complicações e óbitos. As lesões foram classificadas de acordo com a Associação Americana de Cirurgia do Trauma (AAST). Resultados: foram analisados 794 prontuários, a lesão renal foi encontrada em 33 pacientes, a média de idade foi 29,8 anos, a maioria dos pacientes era (87,8%) do sexo masculino. O trauma penetrante foi responsável por 84,8% dos casos. As lesões mais frequentes foram as de grau II (33,3%), seguidas pelas lesões de grau I (18,1%) e pelas lesões de grau III, IV e V. Foram tratadas com nefrectomia, 45,4% das lesões, 73,3% por nefrectomia total e 45,4%, por nefrorrafia. Em 9% o tratamento não foi cirúrgico. Apenas 12,1% dos pacientes apresentaram lesões renais isoladas. Complicações foram observadas em 15,1% e a taxa de óbito foi 6,06%. Conclusão: a abordagem cirúrgica foi a preferencial devido ao mecanismo de trauma penetrante. Obtivemos baixos índices de óbitos e complicações, sendo que nenhum dos casos pôde ser relacionado diretamente à lesão renal, e ocorreram em pacientes com múltiplas lesões. Nesta amostra, não foi possível provar relação direta entre lesão renal e complicações, óbitos ou com o tipo de conduta empregada.

Role of Lipid Blooming and Crystallite Size in the Performance of Highly Soluble Drug-Loaded Microcapsules.

Hot-melt coating is of growing interest, because it does not require solvents, resulting in reduced process times and costs. However, excipients for this technology are mainly triacylglycerides (TAGs) or their derivatives, which exhibit polymorphism, surface disruption, and complex crystallite networks, affecting the release profile of produced microcapsules. In this work, anhydrous citric acid crystals were coated with molten tristearin using conventional inlet air temperatures (microcapsules A) and temperatures above the melting point of α-form (microcapsules B). Additionally, microcapsules A were tempered to achieve polymorphic stability (microcapsules AB). The product yield and coating efficacy were above 90% and 97%, respectively, demonstrating the feasibility and efficacy of the process. Small angle X-ray scattering analysis confirmed that the tristearin shell of microcapsules B is in the ß-form with a larger average crystallite size than microcapsules A and AB. Scanning electron microscopy images revealed a nonbloomed surface of microcapsules B. We showed that blooming does not play a critical role in the drug release, but the apparent diffusion coefficient of drug is dramatically reduced by increasing TAGs crystallite size and resulting tortuosity. This work brings new insights on the micrometric properties of solid lipid dosage forms, being an important step to prevent the overuse of excipients with unknown toxicity.

The power of the context map: Designing realistic outcome evaluation strategies and other unanticipated benefits.

Developing a feasible evaluation plan is challenging when multiple activities, often sponsored by multiple agencies, work together toward a common goal. Often, resources are limited and not every agency's interest can be represented in the final evaluation plan. The article illustrates how the Antecedent Target Measurement (ATM) approach to logic modeling was adapted to meet this challenge. The key adaptation is the context map generated in the first step of the ATM approach. The context map makes visually explicit many of the underlying conditions contributing to a problem as possible. The article also shares how a prioritization matrix can assist the evaluator in filtering through the context map to prioritize the outcomes to be included in the final evaluation plan as well as creating realistic outcomes. This transparent prioritization process can be especially helpful in managing evaluation expectations of multiple agencies with competing interests. Additional strategic planning benefits of the context map include pinpointing redundancies caused by overlapping collaborative efforts, identifying gaps in coverage, and assisting the coordination of multiple stakeholders.

Solvent-free melting techniques for the preparation of lipid-based solid oral formulations.

Lipid excipients are applied for numerous purposes such as taste masking, controlled release, improvement of swallowability and moisture protection. Several melting techniques have evolved in the last decades. Common examples are melt coating, melt granulation and melt extrusion. The required equipment ranges from ordinary glass beakers for lab scale up to large machines such as fluid bed coaters, spray dryers or extruders. This allows for upscaling to pilot or production scale. Solvent free melt processing provides a cost-effective, time-saving and eco-friendly method for the food and pharmaceutical industries. This review intends to give a critical overview of the published literature on experiences, formulations and challenges and to show possibilities for future developments in this promising field. Moreover, it should serve as a guide for selecting the best excipients and manufacturing techniques for the development of a product with specific properties using solvent free melt processing.

Conducting Community Health Needs Assessments in rural communities: lessons learned.

The Affordable Care Act of 2010 requires all nonprofit hospitals in the United States to conduct a Community Health Needs Assessment (CHNA) at least every 3 years. With this law in its infancy, the best practice to conduct an assessment that complies with the law is unknown. Research designs vary across states and agencies, and little is known about the reliability or representativeness of results. The rural community group model (RCGM) is a newly developed model designed for conducting assessments in rural communities. Key components of the model are disseminating surveys, conducting key informant interviews, facilitating focus groups, and integrating secondary data of county-level health behaviors and outcomes. It has been used to conduct CHNAs on more than half the critical access hospitals in North Dakota (58%). Given this large sample size, which used the same methodology, this article provides an evaluation of the model focusing on lessons learned and challenges encountered in the conduct of CHNAs. Particular strategies for assessment planners are warding off group think, monitoring against bias creep in data collection, and integrating multiple data sources to inform decision making. The model is recommended for replication in rural settings to provide meaningful feedback that allows a hospital to match long-term planning with community needs.

Epidemiological analysis of polytrauma patients with kidney injuries in a university hospital.

OBJECTIVE: To analyze the characteristics of trauma patients with renal lesions treated at a university hospital in Curitiba. METHODS: We conducted a retrospective, cross-sectional study guided by review of medical records of trauma victims who underwent surgical treatment. The variables analyzed were age, gender, mechanism of injury, degree of kidney damage, conduct individualized according to the degree of renal injury, associated injuries, complications and deaths. We classified lesions according to the American Association of Trauma Surgery (TSAA). RESULTS: We analyzed 794 records and found renal lesions in 33 patients, with mean age 29.8 years, most (87.8%) being male. Penetrating trauma accounted for 84.8% of cases. The most common renal injuries were grade II (33.3%), followed by grade I (18.1%), III, IV and V. Nephrectomy treated 45.4% of injuries, 73.3% being total nephrectomy, and 45.4% by nephrorraphy. In 9% treatment was non-surgical. Only 12.1% of patients had isolated renal lesions. Complications ensued in 15.1% and mortality was 6.06%. CONCLUSION: The surgical approach was preferred due to penetrating trauma mechanism. We achieved low rates of complications and deaths, and neither case could be directly related to kidney damage, and there were patients with multiple lesions. In this sample, we could not observe a direct relationship between kidney damage and complications, deaths or the type of conduct employed.

Coexpression of Lactobacillus brevis ADH with GDH or G6PDH in Arxula adeninivorans for the synthesis of 1-(R)-phenylethanol.

The yeast Arxula adeninivorans was used for the overexpression of an ADH gene of Lactobacillus brevis coding for (R)-specific alcohol dehydrogenase (LbADH) to synthesise enantiomerically pure 1-(R)-phenylethanol. Glucose dehydrogenase gene from Bacillus megaterium (BmGDH) or glucose 6-phosphate dehydrogenase of Bacillus pumilus (BpG6PDH) were coexpressed in Arxula to regenerate the cofactor NADPH by oxidising glucose or glucose 6-phosphate. The yeast strain expressing LbADH and BpG6PDH produced 5200 U l(-1) ADH and 370 U l(-1) G6PDH activity, whereas the strain expressing LbADH and BmGDH produced 2700 U l(-1) ADH and 170 U l(-1) GDH activity. However, the crude extract of both strains reduced 40 mM acetophenone to pure 1-(R)-phenylethanol with an enantiomeric excess (ee) of >99 % in 60 min without detectable by-products. An increase in yield was achieved using immobilised crude extracts (IEs), Triton X-100 permeabilised cells (PCs) and permeabilised immobilised cells (PICs) with PICs being most stable with GDH regeneration over 52 cycles. Even though the activity and synthesis rate of 1-(R)-phenylethanol with the BpG6PDH and LbADH coexpressing strain was higher, the BmGDH-LbADH strain was more stable over successive reaction cycles. This, combined with its higher total turnover number (TTN) of 391 mol product per mole NADP(+), makes it the preferred strain for continuous reaction systems. The initial non-optimised semi-continuous reaction produced 9.74 g l(-1) day(-1) or 406 g kg(-1) dry cell weight (dcw) day(-1) isolated 1-(R)-phenylethanol with an ee of 100 % and a TTN of 206 mol product per mole NADP(+). In conclusion, A. adeninivorans is a promising host for LbADH and BpG6PDH or BmGDH production and offers a simple method for the production of enantiomerically pure alcohols.

Does the 2013 GOLD classification improve the ability to predict lung function decline, exacerbations and mortality: a post-hoc analysis of the 4-year UPLIFT trial.

BACKGROUND: The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk). Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping. The previous system was solely based on airflow obstruction. Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations. The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline. METHODS: Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates. A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage. Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history. Lung function decline was analysed in a repeated measures model. RESULTS: Mortality increased from A to D, but there was no difference between B and C. For the previous GOLD stages 2-4, survival curves were clearly separated. Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D. Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D. With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations. Distinguishing between the sub-stages of high-risk led to substantial improvements. CONCLUSIONS: The new classification system is a modest step towards a phenotype approach. It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline. TRIAL REGISTRATION: ClinicalTrials.gov NCT00144339 (September 2, 2005).