Self-management with alcohol over lifespan: psychological mechanisms, neurobiological underpinnings, and risk assessment.

Self-management includes all behavioural measures and cognitive activities aimed at coping with challenges arising throughout the lifespan. While virtually all of these challenges can be met without pharmacological means, alcohol consumption has long been instrumentalized as a supporting tool to help coping with problems arising selectively at adolescence, adulthood, and ageing. Here, we present, to our knowledge, the first systematic review of alcohol instrumentalization throughout lifespan. We searched MEDLINE, Google Scholar, PsycINFO and CINAHL (from Jan, 1990, to Dec, 2022) and analysed consumption patterns, goals and potential neurobiological mechanisms. Evidence shows a regular non-addictive use of alcohol to self-manage developmental issues during adolescence, adulthood, and ageing. Alcohol is selectively used to overcome problems arising from dysfunctional personality traits, which manifest in adolescence. A large range of psychiatric disorders gives rise to alcohol use for the self-management of distinct symptoms starting mainly in adulthood. We identify those neuropharmacological effects of alcohol that selectively serve self-management under specific conditions. Finally, we discuss the adverse effects and associated risks that arise from the use of alcohol for self-management. Even well-controlled alcohol use adversely impacts health. Based on these findings, we suggest the implementation of an entirely new view. Health policy action may actively embrace both sides of the phenomenon through a personalized informed use that allows for harm-controlled self-management with alcohol.

Preclinical patient-derived modeling of castration-resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease.

The use of mutation analysis of homologous recombination repair (HRR) genes to estimate PARP-inhibition response may miss a larger proportion of responding patients. Here, we provide preclinical models for castration-resistant prostate cancer (CRPC) that can be used to functionally predict HRR defects. In vitro, CRPC LNCaP sublines revealed an HRR defect and enhanced sensitivity to olaparib and cisplatin due to impaired RAD51 expression and recruitment. Ex vivo-induced castration-resistant tumor slice cultures or tumor slice cultures derived directly from CRPC patients showed increased olaparib- or cisplatin-associated enhancement of residual radiation-induced γH2AX/53BP1 foci. We established patient-derived tumor organoids (PDOs) from CRPC patients. These PDOs are morphologically similar to their primary tumors and genetically clustered with prostate cancer but not with normal prostate or other tumor entities. Using these PDOs, we functionally confirmed the enhanced sensitivity of CRPC patients to olaparib and cisplatin. Moreover, olaparib but not cisplatin significantly decreased the migration rate in CRPC cells. Collectively, we present robust patient-derived preclinical models for CRPC that recapitulate the features of their primary tumors and enable individualized drug screening, allowing translation of treatment sensitivities into tailored clinical therapy recommendations.

[Fall prevention in old people through occupational therapy home assessment, consultation and modification: a process outline]. / Sturzprävention bei älteren Menschen durch ergotherapeutische Wohnraumanalyse, -beratung und -anpassung: eine Prozessdarstellung.

Falls occur frequently in old people and are associated with relevant short-term and long-term trauma sequelae. Particularly in the light of demographic change, preventive measures such as falls prevention are increasingly gaining in importance. Occupational therapy home assessments enable the evaluation of external and behavioral risk factors for falls in the context of environmental prevention. Environmental prevention is an effective measure in preventing morbidity and mortality related to falls in old people and the increase in healthcare costs associated with falls. Occupational therapy home assessments effectively reduce fall risk and fall rate among older people at risk of falling and can be implemented in the context of existing regulatory frameworks. The aim of this overview is to illustrate the optimal process of home assessment and adaptation for patients at risk of falling by general practitioners, orthopedic surgeons and occupational therapists.

Assessment of fenestrated Anaconda stent graft design by numerical simulation: Results of a European prospective multicenter study.

OBJECTIVE: A crucial step in designing fenestrated stent grafts for treatment of complex aortic abdominal aneurysms is the accurate positioning of the fenestrations. The deployment of a fenestrated stent graft prototype in a patient-specific rigid aortic model can be used for design verification in vitro, but is time and human resources consuming. Numerical simulation (NS) of fenestrated stent graft deployment using the finite element analysis has recently been developed; the aim of this study was to compare the accuracy of fenestration positioning by NS and in vitro. METHODS: All consecutive cases of complex aortic abdominal aneurysm treated with the Fenestrated Anaconda (Terumo Aortic) in six European centers were included in a prospective, observational study. To compare fenestration positioning, the distance from the center of the fenestration to the proximal end of the stent graft (L) and the angular distance from the 0° position (C) were measured and compared between in vitro testing (L1, C1) and NS (L2, C2). The primary hypothesis was that ΔL (|L2 - L1|) and ΔC (|C2 - C1|) would be 2.5 or less mm in more than 80% of the cases. The duration of both processes was also compared. RESULTS: Between May 2018 and January 2019, 50 patients with complex aortic abdominal aneurysms received a fenestrated stent graft with a total of 176 fenestrations. The ΔL and ΔC was 2.5 mm or less for 173 (98%) and 174 (99%) fenestrations, respectively. The NS process duration was significantly shorter than the in vitro (2.1 days [range, 1.0-5.2 days] vs 20.6 days [range, 9-82 days]; P < .001). CONCLUSIONS: Positioning of fenestrations using NS is as accurate as in vitro and could significantly decrease delivery time of fenestrated stent grafts.

A Multicompany Survey Study for Helium Leak Container Closure Integrity Test.

All products labeled as sterile are required to be free of microbial contamination throughout their shelf life (obligatory critical quality attribute). Container closure integrity (CCI) needs to be addressed with a holistic life cycle strategy comprising adequate primary packaging components selection and the assessment of critical unit operations and critical process parameters (CPPs) according to quality by design (QbD) principles. The helium leak method is currently the most sensitive CCI test method and preferably used for the initial container closure system (CCS) qualification and characterization studies. Currently, two different measuring principles are used in the pharmaceutical industry, and no data is available in the public domain for typical method performance parameters such as accuracy, precision, intermediate-precision, and limit of quantification of the method. Furthermore, the performance of different types and sizes of artificial leaks as well as certified helium leak standards have not yet been characterized across different test laboratories. In this multicompany study, we shared 17 artificially prepared leak samples using the most common types of artificial leaks in relevant nominal size ranges that are commercially available or can be easily prepared in a laboratory. Each participating company generated results according to their in-house methods, applying their established test parameters as the aim of the study was not to create a standard for helium leak measurements, but to compare real-world performance between different laboratories. Consequently, this study is not an interlaboratory study using the same test method across laboratories.

Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis.

Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.

Assessment of Medication Adherence Using a Medical App Among Patients With Multiple Sclerosis Treated With Interferon Beta-1b: Pilot Digital Observational Study (PROmyBETAapp).

BACKGROUND: Accurate measurement of medication adherence using classical observational studies typically depends on patient self-reporting and is often costly and slow. In contrast, digital observational studies that collect data directly from the patient may pose minimal burden to patients while facilitating accurate, timely, and cost-efficient collection of real-world data. In Germany, ~80% of patients with multiple sclerosis (MS) treated with interferon beta 1b (Betaferon) use an electronic autoinjector (BETACONNECT), which automatically records every injection. Patients may also choose to use a medical app (myBETAapp) to document injection data and their well-being (using a "wellness tracker" feature). OBJECTIVE: The goal of this pilot study was to establish a digital study process that allows the collection of medication usage data and to assess medication usage among patients with MS treated with interferon beta-1b who use myBETAapp. METHODS: The PROmyBETAapp digital observational study was a mixed prospective and retrospective, noninterventional, cohort study conducted among users of myBETAapp in Germany (as of December 2017: registered accounts N=1334; actively used accounts N=522). Between September and December 2017, users received two invitations on their app asking them to participate. Interested patients were provided detailed information and completed an electronic consent process. Data from consenting patients' devices were collected retrospectively starting from the first day of usage if historical data were available in the database and collected prospectively following consent attainment. In total, 6 months of data on medication usage behavior were collected along with 3 months of wellness tracker data. Descriptive statistics were used to analyze persistence, compliance, and adherence to therapy. RESULTS: Of the 1334 registered accounts, 96 patients (7.2%) provided informed consent to participate in the study. Of these, one patient withdrew consent later. For another patient, injection data could not be recorded during the study period. Follow-up of the remaining 94 patients ended in May 2018. The mean age of participants was 46.6 years, and 50 (53%) were female. Over the 6-month study period, persistence with myBETAapp usage was 96% (90/94), mean compliance was 94% of injections completed, and adherence (persistence and ≥80% compliance) was 89% (84/94). There was no apparent difference between male and female participants and no trend across age groups. The wellness tracker was used by 21% of participants (20/94), with a mean of 3.1 entries per user. CONCLUSIONS: This study provides important information on medication usage among patients with MS treated with interferon beta-1b and on consenting behavior of patients in digital studies. In future studies, this approach may allow patients' feedback to be rapidly implemented in existing digital solutions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03134573; https://clinicaltrials.gov/ct2/show/NCT03134573.

Establishing Statistical Equivalence of Data from Different Sampling Approaches for Assessment of Bacterial Phenotypic Antimicrobial Resistance.

To assess phenotypic bacterial antimicrobial resistance (AMR) in different strata (e.g., host populations, environmental areas, manure, or sewage effluents) for epidemiological purposes, isolates of target bacteria can be obtained from a stratum using various sample types. Also, different sample processing methods can be applied. The MIC of each target antimicrobial drug for each isolate is measured. Statistical equivalence testing of the MIC data for the isolates allows evaluation of whether different sample types or sample processing methods yield equivalent estimates of the bacterial antimicrobial susceptibility in the stratum. We demonstrate this approach on the antimicrobial susceptibility estimates for (i) nontyphoidal Salmonella spp. from ground or trimmed meat versus cecal content samples of cattle in processing plants in 2013-2014 and (ii) nontyphoidal Salmonella spp. from urine, fecal, and blood human samples in 2015 (U.S. National Antimicrobial Resistance Monitoring System data). We found that the sample types for cattle yielded nonequivalent susceptibility estimates for several antimicrobial drug classes and thus may gauge distinct subpopulations of salmonellae. The quinolone and fluoroquinolone susceptibility estimates for nontyphoidal salmonellae from human blood are nonequivalent to those from urine or feces, conjecturally due to the fluoroquinolone (ciprofloxacin) use to treat infections caused by nontyphoidal salmonellae. We also demonstrate statistical equivalence testing for comparing sample processing methods for fecal samples (culturing one versus multiple aliquots per sample) to assess AMR in fecal Escherichia coli These methods yield equivalent results, except for tetracyclines. Importantly, statistical equivalence testing provides the MIC difference at which the data from two sample types or sample processing methods differ statistically. Data users (e.g., microbiologists and epidemiologists) may then interpret practical relevance of the difference.IMPORTANCE Bacterial antimicrobial resistance (AMR) needs to be assessed in different populations or strata for the purposes of surveillance and determination of the efficacy of interventions to halt AMR dissemination. To assess phenotypic antimicrobial susceptibility, isolates of target bacteria can be obtained from a stratum using different sample types or employing different sample processing methods in the laboratory. The MIC of each target antimicrobial drug for each of the isolates is measured, yielding the MIC distribution across the isolates from each sample type or sample processing method. We describe statistical equivalence testing for the MIC data for evaluating whether two sample types or sample processing methods yield equivalent estimates of the bacterial phenotypic antimicrobial susceptibility in the stratum. This includes estimating the MIC difference at which the data from the two approaches differ statistically. Data users (e.g., microbiologists, epidemiologists, and public health professionals) can then interpret whether that present difference is practically relevant.

Development of a short scale for assessing economic environmental aspects in patients with spinal diseases using Rasch analysis.

BACKGROUND: Economic environmental factors represent important barriers to participation and have deleterious effects on quality of life (QOL) in persons with spinal diseases (SpD). While economic factors are anchored in the International Classification of Functioning, Disability and Health, their influence on QOL and participation from patients' perspectives is an infrequent focus of research. The aim of the present research is to calibrate a culturally adapted Rasch-based questionnaire assessing economic QOL in patients with SpD. METHODS: The 11-items of the German economic-QOL-scale were answered by 325 patients with SpD on a four-point Likert-scale. Fit to the Rasch measurement model was investigated by testing for stochastic ordering of the items, unidimensionality, local independence, and differential item functioning (DIF). RESULTS: After adjusting for local dependency, fit to the Rasch model was achieved with a non-significant item-trait interaction (chi-squaredf = 20 = 34.8, p = 0.021). The person separation reliability equaled 0.88, the scale was free from age- or gender-related DIF, and unidimensionality could be verified. CONCLUSIONS: The Rasch-based German version of the economic-QOL-scale represents a suitable instrument to investigate the influences of economic factors on patients' QOL at a group and individual level. It can be easily applied in research and practice and may be administered quickly in combination with other instruments. The short test duration implies a low test burden for patients and a minimum of time expenditure by clinicians when evaluating the results.

Heart failure epidemiology 2000-2013: insights from the German Federal Health Monitoring System.

AIMS: Considerable differences in the long-term trends of heart failure (HF) exist between different countries. To extend the existing knowledge on HF epidemiology in Germany, we analysed trends of HF-related hospitalizations, hospital days and in-hospital deaths during a 14-year period (2000-2013). METHODS AND RESULTS: Data were derived from the official German Federal Health Monitoring System, which includes an annual and complete enumeration of inpatients at the time of discharge from the hospital. HF cases were identified by the primary diagnosis code for HF (I50). From 2000 to 2013, the absolute number of HF-related hospitalizations increased by 65.4% (239 694-396 380 cases) and by 28.4% after age-standardization (261-335 per 100 000 population). Accordingly, the absolute number of HF-related hospital days increased by 22.1% (3.4-4.2 million hospital days), despite a marked decrease by 25.9% in average length of stay (14.3-10.6 days). With approximately 35 000 in-hospital deaths (∼45 per 100 000 population), the annual number of HF-related in-hospital deaths remained consistently high, and in-hospital mortality rate in HF patients constituted 9.3% in 2013. Patients aged >65 years were disproportionately affected. In 2013, HF was the leading cause of disease-related hospitalizations and in-hospital deaths, representing 2.1% and 8.8% of all cases, respectively. CONCLUSION: In Germany, the burden of HF is growing further, and the risk of death in HF remains high. These trends can only be partly attributed to demographic developments suggesting an exigent need for increased awareness and enhanced efforts in the prevention and management of HF.

Predictors of High Profit and High Deficit Outliers under SwissDRG of a Tertiary Care Center.

PRINCIPLES: Case weights of Diagnosis Related Groups (DRGs) are determined by the average cost of cases from a previous billing period. However, a significant amount of cases are largely over- or underfunded. We therefore decided to analyze earning outliers of our hospital as to search for predictors enabling a better grouping under SwissDRG. METHODS: 28,893 inpatient cases without additional private insurance discharged from our hospital in 2012 were included in our analysis. Outliers were defined by the interquartile range method. Predictors for deficit and profit outliers were determined with logistic regressions. Predictors were shortlisted with the LASSO regularized logistic regression method and compared to results of Random forest analysis. 10 of these parameters were selected for quantile regression analysis as to quantify their impact on earnings. RESULTS: Psychiatric diagnosis and admission as an emergency case were significant predictors for higher deficit with negative regression coefficients for all analyzed quantiles (p<0.001). Admission from an external health care provider was a significant predictor for a higher deficit in all but the 90% quantile (p<0.001 for Q10, Q20, Q50, Q80 and p = 0.0017 for Q90). Burns predicted higher earnings for cases which were favorably remunerated (p<0.001 for the 90% quantile). Osteoporosis predicted a higher deficit in the most underfunded cases, but did not predict differences in earnings for balanced or profitable cases (Q10 and Q20: p<0.00, Q50: p = 0.10, Q80: p = 0.88 and Q90: p = 0.52). ICU stay, mechanical and patient clinical complexity level score (PCCL) predicted higher losses at the 10% quantile but also higher profits at the 90% quantile (p<0.001). CONCLUSION: We suggest considering psychiatric diagnosis, admission as an emergency case and admission from an external health care provider as DRG split criteria as they predict large, consistent and significant losses.

A mobile application to manage and minimise the risk of late effects caused by childhood cancer.

In their first 15 years of life, about 1 800 children are diagnosed with cancer each year in Germany. Their chances of survival, however, have improved significantly over the last 40 years. In Germany alone, over 30 000 survivors of childhood cancer are presently living. Therefore, the late effects caused by the therapy occur ever more frequently as chemotherapy and radiotherapy may leave traces even years later. In order to recognize and treat these late effects in survivors, structured and regular follow-up examinations are necessary from an early stage on. However, the compliance of former patients to participate in the recommended check-ups is not satisfying for multiple reasons. To enhance this compliance, an application for smartphones and tablets has been developed. The Aftercare App supplies a wide range of information regarding the aftercare and supports a reminder functionality to attend medical visits.

Eyes on the price: Human culture and its teaching.

Kline proposes an evolutionary framework for teaching as a major base of human culture, in which she outlines how different types of teaching may solve adaptive problems with a focus on human behavior. Here it is argued that the ability to teach and the different types of teaching behavior may not only solve adaptive problems, but also create them.

The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE.

BACKGROUND & AIMS: Recently, we developed the ART score (assessment for re-treatment with TACE) to guide the decision for a second transarterial chemoembolization (TACE-2) in patients with hepatocellular carcinoma (HCC). Patients with an ART score of 0-1.5 points gained benefit from a second TACE session, while patients with an ART score ≥2.5 points did not. Here, we investigated (1) the prognostic significance of the ART score prior to the third (TACE-3) and fourth TACE (TACE-4), and (2) the feasibility of an ART score guided re-treatment strategy by sequential assessment of the ART score in HCC patients treated with multiple TACE sessions. METHODS: 109 patients, diagnosed with intermediate stage HCC and treated with ≥3 TACE sessions between January 1999 and December 2009 at the Medical Universities of Vienna and Innsbruck, were included. The ART score prior to each TACE session was assessed in comparison to the TACE naïve liver. The prognostic performance of the ART score before TACE-3 and 4 was evaluated with and without stratification based on the ART score prior to the respective last intervention. RESULTS: The pre-TACE-3 ART score discriminated two groups with different prognosis and remained a valid predictor of OS independent of Child-Pugh score (5-7 points), CRP-levels and tumor characteristics. Even in patients with an initially beneficial ART score (0-1.5 points) before TACE-2, repeated ART score assessment before TACE-3 identified a subgroup of patients with dismal prognosis (median OS: 27.8 vs. 10.8 months, p<0.001). Similar results were observed when the ART score was applied before TACE-4. CONCLUSIONS: The sequential assessment of the ART score identifies patients with dismal prognosis prior to each TACE session.

Multidisciplinary Assessment to Personalize Length of Stay in Acute Decompensated Heart Failure (OPTIMA II ADHF).

BACKGROUND: Acute decompensated heart failure (ADHF) causes a substantial burden for health care systems. Data to rationally define the need for hospitalization or the appropriate length of stay (LOS) is limited. Our aim was to personalize length of stay in patients admitted to hospital for acute decompensated heart failure. METHODS: Consecutive patients with ADHF presenting to our emergency department were prospectively followed. We daily conducted a multidisciplinary risk assessment and compared proposed with actually observed triage decisions. RESULTS: At presentation, all patients required hospitalization. Median LOS was 11 days including 1 day after reaching medical stability. In 42.7% of patients, hospitalization was prolonged after medical stability mainly for nursing and organizational reasons. Within 30 days of enrollment, 7 (9.3%) patients were rehospitalized, 3 of them for persisting or relapsing heart failure. CONCLUSIONS: There appears to be potential to shorten inhospital stay in patients with ADHF mainly by providing post discharge ambulatory nursing care in order to improve resource utilization and to diminish "hospitalization-associated disability".

Recombinant antibody mixtures: production strategies and cost considerations.

Recombinant monoclonal antibodies have during the last two decades emerged as a very successful class of biological drugs for the treatment of a variety of different diseases used either as biological mono therapy or in combination with small molecule based drugs. Recombinant antibody mixtures offering targeting of more than one antigen is one of the new promising antibody technologies resulting in higher therapeutic effectiveness and/or broader reactivity. Such recombinant antibody mixtures can in principle be manufactured by different approaches but two main strategies is often applied, either individual manufacturing of the constituent antibodies or single batch manufacturing of the recombinant antibody mixture. Symphogen has developed an expression platform, Sympress™, allowing single batch manufacturing of recombinant antibody mixtures, while other companies are currently using a manufacturing strategy based on production of the individual constituent monoclonal antibodies. An overview and comparison of the different approaches with focus on the challenges in terms of cell banking strategy, manufacturing approach, and strategies for release and characterization will be reviewed in the present manuscript. Furthermore, the two manufacturing approaches are compared based on different parameters such as development timelines, preclinical developmental costs, and manufacturing cost of goods sold (COGS). We conclude that the single batch manufacturing approach expressing a mixture of full length IgG provides a robust and reproducible platform that can be used for cost effective manufacturing of recombinant antibody mixtures.

A combined cardiorenal assessment for the prediction of acute kidney injury in lower respiratory tract infections.

BACKGROUND: The accurate prediction of acute kidney injury (AKI) is an unmet clinical need. A combined assessment of cardiac stress and renal tubular damage might improve early AKI detection. METHODS: A total of 372 consecutive patients presenting to the Emergency Department with lower respiratory tract infections were enrolled. Plasma B-type natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured in a blinded fashion at presentation. The potential of these biomarkers to predict AKI was assessed as the primary endpoint. AKI was defined according to the AKI Network classification. RESULTS: Overall, 16 patients (4%) experienced early AKI. These patients were more likely to suffer from preexisting chronic cardiac disease or diabetes mellitus. At presentation, BNP (334 pg/mL [130-1119] vs 113 pg/mL [52-328], P <.01) and NGAL (269 ng/mL [119-398] vs 96 ng/mL [60-199], P <.01) levels were significantly higher in AKI patients. The predictive accuracy of presentation BNP and NGAL levels was comparable (BNP 0.74; 95% confidence interval [CI], 0.64-0.84 vs NGAL 0.74; 95% CI, 0.61-0.87). In a combined logistic model, a joint BNP/NGAL approach improved the predictive accuracy for early AKI over either biomarker alone (area under the receiver operating characteristic curve: 0.82; 95% CI, 0.74-0.89). The combined categorical cut point defined by BNP >267 pg/mL or NGAL >231 ng/mL correctly identified 15 of 16 early AKI patients (sensitivity 94%, specificity 61%). During multivariable regression analysis, the combined BNP/NGAL cutoff remained the independent predictor of early AKI (hazard ratio 10.82; 95% CI, 1.22-96.23; P = .03). CONCLUSION: A model combining the markers BNP and NGAL is a powerful predictor of early AKI in patients with lower respiratory tract infection.

Global parameter identification of stochastic reaction networks from single trajectories.

We consider the problem of inferring the unknown parameters of a stochastic biochemical network model from a single measured time-course of the concentration of some of the involved species. Such measurements are available, e.g., from live-cell fluorescence microscopy in image-based systems biology. In addition, fluctuation time-courses from, e.g., fluorescence correlation spectroscopy (FCS) provide additional information about the system dynamics that can be used to more robustly infer parameters than when considering only mean concentrations. Estimating model parameters from a single experimental trajectory enables single-cell measurements and quantification of cell-cell variability. We propose a novel combination of an adaptive Monte Carlo sampler, called Gaussian Adaptation (GaA), and efficient exact stochastic simulation algorithms (SSA) that allows parameter identification from single stochastic trajectories. We benchmark the proposed method on a linear and a non-linear reaction network at steady state and during transient phases. In addition, we demonstrate that the present method also provides an ellipsoidal volume estimate of the viable part of parameter space and is able to estimate the physical volume of the compartment in which the observed reactions take place.

[The day hospital in search of its identity]. / L'hôpital de jour à la recherche de son identité.

After more than fifty years of existence, the day hospital remains a little known tool. Submerged in the new psychiatric landscape, between part time therapeutic care centres, home hospital care and mutual support groups, this institution, which offers appropriate care, finds itself being questioned with regard to its place, its development and its future.