Using Multimodal Data to Improve Precision of Inpatient Event Timelines.

Textual data often describe events in time but frequently contain little information about their specific timing, whereas complementary structured data streams may have precise timestamps but may omit important contextual information. We investigate the problem in healthcare, where we produce clinician annotations of discharge summaries, with access to either unimodal (text) or multimodal (text and tabular) data, (i) to determine event interval timings and (ii) to train multimodal language models to locate those events in time. We find our annotation procedures, dashboard tools, and annotations result in high-quality timestamps. Specifically, the multimodal approach produces more precise timestamping, with uncertainties of the lower bound, upper bounds, and duration reduced by 42% (95% CI 34-51%), 36% (95% CI 28-44%), and 13% (95% CI 10-17%), respectively. In the classification version of our task, we find that, trained on our annotations, our multimodal BERT model outperforms unimodal BERT model and Llama-2 encoder-decoder models with improvements in F1 scores for upper (10% and 61%, respectively) and lower bounds (8% and 56%, respectively). The code for the annotation tool and the BERT model is available (link).

A Visual and Narrative Timeline Review of Spinal Cord Stimulation Technology and US Food and Drug Administration Milestones.

OBJECTIVES: The aim of this study was to present key technologic and regulatory milestones in spinal cord stimulation (SCS) for managing chronic pain on a narrative timeline with visual representation, relying on original sources to the extent possible. MATERIALS AND METHODS: We identified technical advances in SCS that facilitated and enhanced treatment on the basis of scientific publications and approvals from the United States (US) Food and Drug Administration (FDA). We presented milestones limited to first use in key indications and in the context of new technology validation. We focused primarily on pain management, but other indications (eg, motor disorder in multiple sclerosis) were included when they affected technology development. RESULTS: We developed a comprehensive visual and narrative timeline of SCS technology and US FDA milestones. Since its conception in the 1960s, the science and technology of SCS neuromodulation have continuously evolved. Advances span lead design (from paddle-type to percutaneous, and increased electrode contacts) and stimulator technology (from wireless power to internally powered and rechargeable, with miniaturized components, and programmable multichannel devices), with expanding stimulation program flexibility (such as burst and kilohertz stimulation frequencies), as well as usage features (such as remote programming and magnetic resonance imaging conditional compatibility). CONCLUSIONS: This timeline represents the evolution of SCS technology alongside expanding FDA-approved indications for use.

Relationship between alcohol intake based on daily smartphone-reported consumption and PEth concentrations in healthy volunteers.

AIMS: To investigate the association between alcohol consumption registered daily with a digital smartphone-based diary and concentration of phosphatidylethanol (PEth) 16:0/18:1 in a population without a known alcohol use disorder (AUD), and evaluate whether prospective registration of alcohol consumption is better than retrospective registration and if the association between alcohol intake and PEth was affected by sex or body mass index (BMI). METHODS: A total of 41 women and 21 men without AUD-diagnosis registered their alcohol consumption prospectively with a digital diary for 14 days, and retrospectively with the Timeline Followback method in the same time interval. PEth was measured before and after the registration period. RESULTS: The correlation between alcohol consumption and PEth varied from 0.65 to 0.87. It did not depend significantly on the reporting method, and was not influenced by sex or BMI. Based on the regression coefficient, a reduction of alcohol consumption by two alcohol units (26 g of pure ethanol) per day would lead to a reduction of the PEth concentration of about 0.1 µmol/l, and vice versa. CONCLUSIONS: There was a good correlation between PEth concentration and alcohol consumption, both when alcohol consumption was reported prospectively and retrospectively. The preferred cut-off for PEth should be adjusted to the level of alcohol consumption considered harmful and a purposeful trade-off between sensitivity and specificity. In order to identify persons with a daily alcohol consumption of more than two or three units of alcohol with a sensitivity of 80% or 90%, we suggest a cut-off of around 0.1 µmol/l.

Dependency of mitochondrial quantity on blastocyst timeline obscures its actual effect to pregnancy outcomes.

Objectives: To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy. Methods: A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints. Results: Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman's ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints. Conclusions: Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.

Clinical and genetic factors affecting diagnostic timeline of amyotrophic lateral sclerosis: a 15-year retrospective study.

OBJECTIVES: Amyotrophic Lateral Sclerosis (ALS) diagnosis can take 10-16 months from symptom onset, leading to delays in treatment and patient counselling. We studied the impact of clinical and genetic risk factors on the diagnostic timeline of ALS. METHODS: Baseline characteristics, family history, gene testing, onset location, time from symptom onset to diagnosis, and time from first doctor visit to suspected ALS was collected. We used multiple regression to assess the interaction of these factors on ALS diagnostic timeline. We analysed a subgroup of patients with genetic testing and compared positive or negative tests, sporadic or familial and ALS-related genes to time for diagnosis. RESULTS: Four hundred and forty-eight patients diagnosed with ALS at the University of Massachusetts Chan Medical Center between January 2007 and December 2021 were analysed. The median time to ALS diagnosis was 12 months and remained unchanged from 2007 to 2021 (p = 0.20). Diagnosis was delayed in patients with sporadic compared with familial ALS (mean months [standard deviation], 16.5[13.5] and 11.2[8.5], p < 0.001); cognitive onset (41[21.26]) had longer time to diagnosis than bulbar (11.9[8.2]), limb (15.9[13.2]), respiratory (19.7[13.9]) and ALS with multiple onset locations (20.77[15.71], p < 0.001). One hundred and thirty-four patients had gene testing and 32 tested positive (23.8%). Gene testing (p = 0.23), a positive genetic test (p = 0.16), different ALS genes (p = 0.25) and sporadic (p = 0.92) or familial (p = 0.85) ALS testing positive for ALS genes did not influence time to diagnosis. DISCUSSION: Time for ALS diagnosis remained unchanged from 2007 to 2021, bulbar-onset and familial ALS made for faster diagnosis.

Identification of Alcohol Use Prior to Major Cancer Surgery: Timeline Follow Back Interview Compared to Four Other Markers.

BACKGROUND: The postoperative complication rate is 30-64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. METHODS: Diagnostic test sub-study of a randomized controlled trial (STOP-OP trial), based on a cohort of 94 patients scheduled for major bladder cancer surgery. Identification of risky alcohol use using Timeline Follow Back interviews (TLFB) were compared to the AUDIT-C questionnaire and three biomarkers: carbohydrate-deficient transferrin in plasma (P-CDT), phosphatidyl-ethanol in blood (B-PEth), and ethyl glucuronide in urine (U-EtG). RESULTS: The correlation between TLFB and AUDIT-C was strong (ρ = 0.75), while it was moderate between TLFB and the biomarkers (ρ = 0.55-0.65). Overall, sensitivity ranged from 56 to 82% and specificity from 38 to 100%. B-PEth showed the lowest sensitivity at 56%, but the highest specificity of 100%. All tests had high positive predictive values (79-100%), but low negative predictive values (42-55%). CONCLUSIONS: Despite high positive predictive values, negative predictive values were weak compared to TLFB. For now, TLFB interviews seem preferable for preoperative identification of risky alcohol use.

A common framework to situate digital and physical traces in time.

In this article, three main approaches to situate forensic traces in time were revisited under the prism of the Sydney Declaration and adapted to be applicable to a large range of physical and digital traces. The first approach is based on time tags which are time-based characteristics produced as the result of an activity at a specific time. They can either be directly related to time (i.e., time stamps) or indirectly (i.e., time indicators). While relatively straightforward, time tags require scientific knowledge to be correctly interpreted and to account for the risks of desynchronisation, anomalies and manipulation. The second approach is based on time dynamics and aim at measuring changes that occur as a function of time, such as caesium pulsation (i.e., on which international atomic time is based) or body cooling after death (i.e., from which time since death can be inferred). However, time dynamics phenomena are generally also influenced by other case-specific factors (e.g., environmental factors), and thus more difficult to reliably implement in practice. Finally, the third approach relies on relative sequences, using information unrelated to time, such as relative positions or dynamics of traces at the scene. As each approach has its potential and limitations, a combination of traces from different (both material and digital) sources and approaches is recommended to answer time questions in practice (When? How long? In which succession?) and enhance the reliability of the dating endeavours. It is strongly recommended to consider the principles of the Sydney Declaration when implementing or developing dating methods, as they point at potential issues that are often forgotten in forensic research and practice, such as uncertainties linked to the concept of trace, scene investigation, the asymmetry of time, the importance of context and the multiplicity of purposes. Future research should focus on improving the reliability of these dating approaches by combining and systematising their usage in investigative practice, as well as in broader intelligence processes.

Critical complex network structures in animal gastrointestinal tract microbiomes.

BACKGROUND: Living things from microbes to their hosts (plants, animals and humans) interact with each other, and their relationships may be described with complex network models. The present study focuses on the critical network structures, specifically the core/periphery nodes and backbones (paths of high-salience skeletons) in animal gastrointestinal microbiomes (AGMs) networks. The core/periphery network (CPN) mirrors nearly ubiquitous nestedness in ecological communities, particularly dividing the network as densely interconnected core-species and periphery-species that only sparsely linked to the core. Complementarily, the high-salience skeleton network (HSN) mirrors the pervasive asymmetrical species interactions (strictly microbial species correlations), particularly forming heterogenous pathways in AGM networks with both "backbones" and "rural roads" (regular or weak links). While the cores and backbones can act as critical functional structures, the periphery nodes and weak links may stabilize network functionalities through redundancy. RESULTS: Here, we build and analyze 36 pairs of CPN/HSN for the AGMs based on 4903 gastrointestinal-microbiome samples containing 473,359 microbial species collected from 318 animal species covering all vertebrate and four major invertebrate classes. The network analyses were performed at host species, order, class, phylum, kingdom scales and diet types with selected and comparative taxon pairs. Besides diet types, the influence of host phylogeny, measured with phylogenetic (evolutionary) timeline or "age", were integrated into the analyses. For example, it was found that the evolutionary trends of three primary microbial phyla (Bacteroidetes/Firmicutes/Proteobacteria) and their pairwise abundance-ratios in animals do not mirror the patterns in modern humans phylogenetically, although they are consistent in terms of diet types. CONCLUSIONS: Overall, the critical network structures of AGMs are qualitatively and structurally similar to those of the human gut microbiomes. Nevertheless, it appears that the critical composition (the three phyla of Bacteroidetes, Firmicutes, and Proteobacteria) in human gut microbiomes has broken the evolutionary trend from animals to humans, possibly attributable to the Anthropocene epoch and reflecting the far-reaching influences of agriculture and industrial revolution on the human gut microbiomes. The influences may have led to the deviations between modern humans and our hunter-gather ancestors and animals.

Kinetic coevolutionary models predict the temporal emergence of HIV-1 resistance mutations under drug selection pressure.

Drug resistance in HIV type 1 (HIV-1) is a pervasive problem that affects the lives of millions of people worldwide. Although records of drug-resistant mutations (DRMs) have been extensively tabulated within public repositories, our understanding of the evolutionary kinetics of DRMs and how they evolve together remains limited. Epistasis, the interaction between a DRM and other residues in HIV-1 protein sequences, is key to the temporal evolution of drug resistance. We use a Potts sequence-covariation statistical-energy model of HIV-1 protein fitness under drug selection pressure, which captures epistatic interactions between all positions, combined with kinetic Monte-Carlo simulations of sequence evolutionary trajectories, to explore the acquisition of DRMs as they arise in an ensemble of drug-naive patient protein sequences. We follow the time course of 52 DRMs in the enzymes protease, RT, and integrase, the primary targets of antiretroviral therapy. The rates at which DRMs emerge are highly correlated with their observed acquisition rates reported in the literature when drug pressure is applied. This result highlights the central role of epistasis in determining the kinetics governing DRM emergence. Whereas rapidly acquired DRMs begin to accumulate as soon as drug pressure is applied, slowly acquired DRMs are contingent on accessory mutations that appear only after prolonged drug pressure. We provide a foundation for using computational methods to determine the temporal evolution of drug resistance using Potts statistical potentials, which can be used to gain mechanistic insights into drug resistance pathways in HIV-1 and other infectious agents.

Inhibition and working memory capacity modulate the mental space-time association.

This research aimed to investigate whether the mental space-time association of temporal concepts could be modulated by the availability of cognitive resources (in terms of working memory and inhibitory control capacities) and to explore whether access to this association could be an automatic process. To achieve this, two experiments were carried out. In Experiment 1, participants had to classify words with future and past meanings. The working memory load (high vs. low) was manipulated and the participants were grouped into quartiles according to their visuospatial working memory capacity (WMC). Temporal concepts were displayed subliminally (immediate masking) and supraliminally (delayed masking). The ANOVA showed a performance pattern consistent with the left-past right-future conceptual scheme, regardless of both the type of masking and the working memory load, except in high WMC participants, in which, interestingly, the space-time association effect was absent. In Experiment 2, participants were asked to respond to the colour of the font of the temporal words, and their attentional control capacity was assessed. The results indicated a timeline effect that was irrespective of the WM load and the type of perceptual processing, but not of the WM capacity or the inhibitory abilities. These findings partially endorse the automatic and implicit access to the mental space-time association and suggest the involvement of the availability of cognitive resources. Individual WMC differences appear to modulate the automatic nature of the effect rather than the processing conditions themselves.

100 Years of the American Public Health Association's Public Health Education and Health Promotion Section: Celebrating the Past, Forging the Future.

The American Public Health Association's Public Health Education and Health Promotion (APHA PHEHP) Section celebrates its 100th anniversary by reflecting on its humble beginnings and early contributions to the field of health education. This article highlights the often-unsung history of our field and its fledgling beginnings, which is important to scholars and students alike. First codified as the Health Education and Publicity Section in the early 1920s, we trace the history and challenges of using new modes of publicity such as motion pictures and innovative exhibits to help curb the spread of infectious diseases (e.g., tuberculosis, venereal disease). Evart G. Routzahn, credited as the Section's father, worked tirelessly to increase the Section's visibility (renamed the Health Education Section in 1927 and the Public Health Education and Health Promotion Section in 1990) and in advancing the professionalization of health education during a time when there were no formal professional preparation programs in health education. Over the years, the Section has played significant roles in strengthening the practice of health education and communication; advancing APHA's overall leadership, infrastructure, and governance; and contributing to the unified voice and advocacy for the health education profession and health equity. We conclude by describing contemporary initiatives that reflect the continued spirit and vibrancy of the Section in setting the stage for the next 100 years.

Postoperative inpatient surgical complications following head and neck microvascular free tissue transfer.

BACKGROUND: Complications following head and neck microvascular free tissue transfer (MFTT) are common. Less is known about when they occur. METHOD: Retrospective study of patients with primary or recurrent head and neck cancer undergoing MFTT reconstruction at a tertiary care institution. MFTT reconstructions with inpatient postoperative complications were included. The Kruskal-Wallis test was used to compare median postoperative day (POD) onset of complication by flap type. RESULTS: Of 1090 patients undergoing MFTT reconstruction, 126 (11.6%) patients experienced inpatient complications including fibula (n = 35), anterolateral thigh (n = 60), or radial forearm (n = 31) MFTTs. POD onset was shortest for surgical site hematoma (median = 1 [IQR 1-5]), and longest for donor site infection (median = 11.5 [IQR 8-15]). There was no significant difference between flap types and POD onset of complications (p > 0.05). CONCLUSION: Hematoma formation and flap failure occur earliest during hospitalization, while dehiscence, infection, and fistula occur later. There is no difference in complication timing between flap types.

When will we have a clone? An industry perspective on the typical CLD timeline.

Cell line development (CLD) represents a complex but highly critical process during the development of a biological drug. To shed light on this crucial workflow, a team of BioPhorum members (authors) has developed and executed surveys focused on the activities and effort involved in a typical CLD campaign. An average of 27 members from different companies that participate in the BioPhorum CLD working group answered surveys covering three distinguishable stages of a standard CLD process: (1) Pre-transfection, including vector design and construction; (2) Transfection, spanning the initial introduction of vector into cells and subsequent selection and analysis of the pools; and (3) Single Cell Cloning and Lead Clone Selection, comprising methods of isolating single cells and confirming clonal origin, subsequent expansion and screening processes, and methods for identifying and banking lead clones. The surveys were very extensive, including a total of 341 questions split between antibody and complex molecule CLD processes. In this survey review, the authors interpret and highlight responses for antibody development and, where relevant, contrast complex molecule development challenges to provide a comprehensive industry perspective on the typical time and effort required to develop a CHO production cell line.

The late origins of the timeline, or: three paradoxes explained.

We are all used to drawing straight lines to represent time, and above them, we plot historical events or physical or economic data. What to us is a self-evident convention, is however of an astonishingly recent date: it emerged only in the second half of the eighteenth century. To us, this late date seems paradoxical and cries out for an explanation. How else did earlier periods measure change, if not as a function of time? it will be argued that since Antiquity, time was taken to measure change, and change to occur in space. 'Our' idea of representing time as an independent dimension would have seemed aberrant. But then, a second issue arises. Did not medieval natural philosophers employ timelines, Oresme's diagram of the mean speed theorem being the most famous case? However, as will be shown, our interpretation of his diagram is probably wrong. This insight, in turn, takes care of a third paradox, namely Galileo's initial inability to represent the law of free fall correctly. This article will document that the timeline first emerged in the late sixteenth century in works on chronology, made its first appearance in physics in Galileo's diagrams, and had its general breakthrough in the eighteenth century.

Vertical Mental Timeline Is Not Influenced by VisuoSpatial Processing.

The results examining the direction (bottom-to-top vs. top-to-bottom) of the mental vertical timeline are not conclusive. The visuospatial processing of temporal stimuli along vertical space could influence this time representation. This study aimed to investigate whether and how the visuospatial processing stage modulated the vertical timeline in an online temporal categorization task. In three studies, Italian university students (N = 150) responded more quickly to words expressing the past with a down arrow key, and more quickly to words expressing the future with an up arrow key, irrespective of whether the words were located in the top, middle, or bottom space (Experiment 1), or were presented downward (from top to bottom; Experiment 2A) or upward (from bottom to top Experiment 2B). These results suggest that the representation of time was not influenced by the visuospatial processing. The daily experience with verticality (e.g., to reach the attic, the lift goes up) could explain the bottom-to-top direction of the mental timeline.

Can mindfulness facilitate posttraumatic growth in breast cancer patients? The mediating role of illness perceptions and positive emotions.

The current observational study aimed to examine the relationship between mindfulness and posttraumatic growth (PTG) among patients with breast cancer. Additionally, it explores the mediating role of illness perceptions and positive emotions. A total of 697 women with breast cancer were recruited from four clinical sites as part of the Bounce project in Finland, Portugal, Italy, and Israel. The study measures were mindfulness (MAAS), illness perceptions (IPQ), positive affect (PANAS), and post-traumatic growth (PTGI) at three time points: near the time of diagnosis, 6 months, and 12 months post-diagnosis. A higher level of mindfulness was associated with perceptions of the illness as less chronic. Specifically, the perception of a limited timeline of breast cancer was associated with positive emotions, thus leading to enhanced PTG. Emphasis should be placed on promoting mindfulness, elaborating on illness perceptions, and maintaining positive affect as part of clinical interventions for PTG among breast cancer patients.

Evolution of lumbar degenerative spondylolisthesis with key radiographic features.

Spondylolisthesis is a common finding in middle-aged and older adults with back pain. The pathophysiology of degenerative spondylolisthesis is a subject of controversy regarding not only its etiology but also the mechanisms of its progression. It is theorized that degeneration of the facets and discs can lead to segmental instability, leading to displacement over time. Kirkaldy-Willis divided degenerative spondylolisthesis into three phases: dysfunction, instability, and finally, restabilization. There is a paucity of literature on the unification of the radiological hallmarks seen in spondylolisthesis within these phases. The radiographic features include (1) facet morphology/arthropathy, (2) facet effusion, (3) facet vacuum, (4) synovial cyst, (5) interspinous ligament bursitis, and (6) vacuum disc as markers of dysfunction, instability, and/or restabilization. We discuss these features, which can be seen on X-ray, CT, and MRI, with the intention of establishing a timeline upon which they present clinically. Spondylolisthesis is initiated as either degeneration of the intervertebral disc or facet joints. Early degeneration can be seen as facet vacuum without considerable arthropathy. As the vertebral segment becomes increasingly dynamic, fluid accumulates within the facet joint space. Further degeneration will lead to the advancement of facet arthropathy, degenerative disc disease, and posterior ligamentous complex pathology. Facet effusion can eventually be replaced with a vacuum in severe facet osteoarthritis. Intervertebral disc vacuum continues to accumulate with further cleft formation and degeneration. Ultimately, autofusion of the vertebra at the facets and endplates can be observed. With this review, we hope to increase awareness of these radiographical markers and their timeline, thus placing them within the framework of the currently accepted model of degenerative spondylolisthesis, to help guide future research and to help refine management guidelines.

Infections After Liver Transplant -Timeline, Management and Prevention.

Liver transplantation (LT) is the standard treatment for end- stage liver disease. Patient and graft survival have improved significantly in the last three decades owing to improvement in surgical technique, better perioperative management and better immunosuppressive regimens. However, LT recipients are at increased risk of infections, particularly in the first year after transplantation. The risk of infection is directly proportional to immunosuppressive regimen and graft function. In this review, we will briefly discuss the timeline of infections after liver transplant, preventive strategies and management of infectious complications.

Longitudinal NGAL and cystatin C plasma profiles present a high level of heterogeneity in a mixed ICU population.

BACKGROUND: NGAL and Cystatin C (CysC) as biomarkers for the early detection of AKI are subject to both pathophysiological, as well as patient related heterogeneity. The aim of this study was to investigate the timeline of plasma levels of NGAL and CysC during the first seven days of ICU admission in a mixed ICU population and to relate these to AKI severity during ICU stay. Via these means we aimed to bring clarity to the previously reported heterogeneity of these renal biomarkers. METHODS: Prospective Observation Cohort. Consecutive patients admitted to adult ICU at an academic hospital in the Netherlands between 18-02-2014 and 31-03-2014 were included. Urine output, serum creatinine, plasma NGAL and CysC were recorded during the first seven days of ICU admission. Biomarker expression was analyzed based on KDIGO score and time of AKI diagnosis. RESULTS: 335 patients were included, 110 met KDIGO criteria for AKI. NGAL and CysC plasma levels were higher in AKI patients compared to non-AKI, high variability in individual values resulted in 56% of AKI patients having a false negative, and 32% of non-AKI patients having a false positive. Individual biomarker levels were variable, and no pattern based on KDIGO score was observed. CONCLUSIONS: Plasma NGAL and CysC as biomarkers for the early AKI detection may be subject to pathophysiological, and patient related heterogeneity. Further understanding of individual biomarker profiles may help in their application amongst mixed ICU populations. TRIAL REGISTRATION: The need for informed consent was waived by the Institutional Ethical Review Board of the University Medical Center Groningen (METc 2013 - 174) by Prof. dr. W.A. Kamps on May 17th 2013.