J-modulated 19 F- and 1 H-detected dual-optimized inverted 1 JCC 1,n-ADEQUATE: A universal ADEQUATE experiment.

The recently reported 19 F-detected dual-optimized inverted 1 JCC 1,n-ADEQUATE experiment and the previously reported 1 H-detected version have been modified to incorporate J-modulation, making it feasible to acquire all 1,1- and 1,n-ADEQUATE correlations as well as 1 JCC and n JCC homonuclear scalar couplings in a single experiment. The experiments are demonstrated using N,N-dimethylamino-2,5,6-trifluoro-3,4-phthalonitrile and N,N-dimethylamino-3,4-phthalonitrile.

Model-Based Condition Monitoring of the Sensors and Actuators of an Electric and Automated Vehicle.

Constant monitoring of driving conditions and observation of the surrounding area are essential for achieving reliable, high-quality autonomous driving. This requires more reliable sensors and actuators, as there is always the potential that sensors and actuators will fail under real-world conditions. The sensitive condition-monitoring methods of sensors and actuators should be used to improve the reliability of the sensors and actuators. They should be able to detect and isolate the abnormal situations of faulty sensors and actuators. In this paper, a developed model-based method for condition monitoring of the sensors and actuators in an electric vehicle is presented that can determine whether a sensor has a fault and further reconfigure the sensor signal, as well as detect the abnormal behavior of the actuators with the reconfigured sensor signals. Through the simulation data obtained by the vehicle model in complex road conditions, it is proved that the method is effective for the state detection of sensors and actuators.

19 F-detected dual-optimized inverted 1 JCC 1,n-ADEQUATE.

Modification of the recently reported 19 F-detected 1,1-ADEQUATE experiment that incorporates dual-optimization to selectively invert a wide range of 1 JCC correlations in a 1,n-ADEQUATE experiment is reported. Parameters for the dual-optimization segment of the pulse sequence were modified to accommodate the increased size of 1 JCC homonuclear coupling constants of poly- and perfluorinated molecules relative to protonated molecules to allow broadband inversion of the 1 JCC correlations. The observation and utility of isotope shifts are reported for the first time for 1,1- and 1,n-ADEQUATE correlations.

Neoadjuvant Chemotherapy in Pancreatic Cancer: An Appraisal of the Current High-Level Evidence.

At the time of diagnosis, only about 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have resectable disease. PDAC treatment necessitates a multidisciplinary approach, and adjuvant chemotherapy after upfront resection is an established means of preventing recurrence. Neoadjuvant chemotherapy (NAT), originally introduced to downstage tumor size, is nowadays more frequently used for selection of patients with favorable tumor biology and to control potential micrometastases. While NAT is routinely applied in locally advanced (LA) PDAC, there is increasing evidence demonstrating benefits of NAT in borderline resectable (BR) PDAC. The concept of NAT has recently been tested in resectable PDAC, but to date NAT has been restricted to clinical trials, as the data are limited and no clear benefits have yet been shown in this patient group. This review summarizes the current evidence for NAT in resectable, BR, and LA PDAC, with a focus on high-level evidence and randomized controlled trials.

Generative Adversarial Network Performance in Low-Dimensional Settings.

A generative adversarial network (GAN) is an artifcial neural network with a distinctive training architecture, designed to create examples that faithfully reproduce a target distribution. GANs have recently had particular success in applications involving high-dimensional distributions in areas such as image processing. Little work has been reported for low dimensions, where properties of GANs may be better identifed and understood. We studied GAN performance in simulated low-dimensional settings, allowing us to transparently assess effects of target distribution complexity and training data sample size on GAN performance in a simple experiment. This experiment revealed two important forms of GAN error, tail underflling and bridge bias, where the latter is analogous to the tunneling observed in high-dimensional GANs.

Development of 19 F-detected 1,1-ADEQUATE for the characterization of polyfluorinated and perfluorinated compounds.

Polyfluorinated and perfluorinated compounds in the environment are a growing health concern. 19 F-detected variants of commonly employed heteronuclear shift correlation experiments such as heteronuclear single quantum correlation (HSQC) and heteronuclear multiple bond correlation (HMBC) are available; 19 F-detected experiments that employ carbon-carbon homonuclear coupling, in contrast, have never been reported. Herein, we report the measurement of the 1 JCC and n JCC coupling constants of a simple perfluorinated phthalonitrile and the first demonstration of a 19 F-detected 1,1-ADEQUATE experiment.

Modular Approach for Odometry Localization Method for Vehicles with Increased Maneuverability.

Localization and navigation not only serve to provide positioning and route guidance information for users, but also are important inputs for vehicle control. This paper investigates the possibility of using odometry to estimate the position and orientation of a vehicle with a wheel individual steering system in omnidirectional parking maneuvers. Vehicle models and sensors have been identified for this application. Several odometry versions are designed using a modular approach, which was developed in this paper to help users to design state estimators. Different odometry versions have been implemented and validated both in the simulation environment and in real driving tests. The evaluated results show that the versions using more models and using state variables in models provide both more accurate and more robust estimation.

13C-13C spin-coupling constants in crystalline 13C-labeled saccharides: conformational effects interrogated by solid-state 13C NMR spectroscopy.

Solid-state 13C NMR spectroscopy has been used in conjunction with selectively 13C-labeled mono- and disaccharides to measure 13C-13C spin-couplings (JCC) in crystalline samples. This experimental approach allows direct correlation of JCC values with specific molecular conformations since, in crystalline samples, molecular conformation is essentially static and can be determined by X-ray crystallography. JCC values measured in the solid-state in known molecular conformations can then be compared to corresponding JCC values calculated in the same conformations using density functional theory (DFT). The latter comparisons provide important validation of DFT-calculated J-couplings, which is not easily obtained by other approaches and is fundamental to obtaining reliable experiment-based conformational models from redundant J-couplings by MA'AT analysis. In this study, representative 1JCC, 2JCCC and 3JCOCC values were studied as either intra-residue couplings in the aldohexopyranosyl rings of monosaccharides or inter-residue (trans-glycoside) couplings in disaccharides. The results demonstrate that (a) accurate JCC values can be measured in crystalline saccharides that have been suitably labeled with 13C, and (b) DFT-calculated JCC values compare favorably with those determined by solid-state 13C NMR when molecular conformation is a constant in both determinations.

Dual-Bayes Localization Filter Extension for Safeguarding in the Case of Uncertain Direction Signals.

In order to run a localization filter for parking systems in real time, the directional information must be directly available when a distance measurement of the wheel speed sensor is detected. When the vehicle is launching, the wheel speed sensors may already detect distance measurement in the form of Delta-Wheel-Pulse-Counts (DWPCs) without having defined a rolling direction. This phenomenon is particularly problematic during parking maneuvers, where many small correction strokes are made. If a localization filter is used for positioning, the restrained DWPCs cannot process in real time. Without directional information in the form of a rolling direction signal, the filter has to ignore the DWPCs or artificially stop until a rolling direction signal is present. For this reason, methods for earlier estimation of the rolling direction based on the pattern of the incoming DWPCs and based on the force equilibrium have been presented. Since the new methods still have their weaknesses and a wrong estimation of the rolling direction can occur, an extension of a so-called Dual-Localization filter approach is presented. The Dual-Localization filter uses two localization filters and an intelligent initialization logic that ensures that both filters move in opposite directions at launching. The primary localization filter uses the estimated and the secondary one the opposite direction. As soon as a valid rolling direction signal is present, an initialization logic is used to decide which localization filter has previously moved in the true direction. The localization filter that has moved in the wrong direction is initialized with the states and covariances of the other localization filter. This extension allows for a fast and real-time capability to be achieved, and the accumulated velocity error can be dramatically reduced.

Pavement type and wear condition classification from tire cavity acoustic measurements with artificial neural networks.

Tire road noise is the major contributor to traffic noise, which leads to general annoyance, speech interference, and sleep disturbances. Standardized methods to measure tire road noise are expensive, sophisticated to use, and they cannot be applied comprehensively. This paper presents a method to automatically classify different types of pavement and the wear condition to identify noisy road surfaces. The methods are based on spectra of time series data of the tire cavity sound, acquired under normal vehicle operation. The classifier, an artificial neural network, correctly predicts three pavement types, whereas there are few bidirectional mis-classifications for two pavements, which have similar physical characteristics. The performance measures of the classifier to predict a new or worn out condition are over 94.6%. One could create a digital map with the output of the presented method. On the basis of these digital maps, road segments with a strong impact on tire road noise could be automatically identified. Furthermore, the method can estimate the road macro-texture, which has an impact on the tire road friction especially on wet conditions. Overall, this digital map would have a great benefit for civil engineering departments, road infrastructure operators, and for advanced driver assistance systems.

Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients.

OBJECTIVE: This study aims to determine the effectiveness of converting patients from high doses of full-opioid agonists to sublingual (SL) buprenorphine. DESIGN: An observational report of outcomes assessment. SETTING: An interventional pain management practice setting in the United States. SUBJECTS: Thirty-five chronic pain patients (age 24-66) were previously treated with high-dose opioid-agonist drugs and converted to SL buprenorphine. Patients' daily morphine equivalents ranged from 200 mg to 1,370 mg preconversion, with a mean daily dose of 550 mg. METHODS: A retrospective chart analysis examined numerical pain levels and quality of life scores before and 2 months after conversion to SL buprenorphine. RESULTS: After continuation of SL buprenorphine therapy for 2 months, the mean pain score decreased from 7.2 to 3.5 (P < 0.001), with 34 of the 35 patients examined reporting a decrease in pain. This pain score decrease was robust with regard to initial pain score and preconversion morphine equivalent dosage. Quality of life scores improved from 6.1 to 7.1 (P = 0.005). CONCLUSION: Average pain scores decreased from 7.2 to 3.5, and quality of life scores increased from 6.1 to 7.1 for 35 patients converted from high-dose full-opioid agonists to SL buprenorphine therapy for more than 60 days. Clinicians should consider buprenorphine SL conversion for all patients on high-dose opioids, particularly patients with severe pain (7-10) unrelieved by their current opioid regimen or patients for whom the clinician does not feel comfortable prescribing high-dose opioids.

Disease-specific knowledge and information preferences of young patients with congenital heart disease.

AIMS: Persons suffering from congenital heart defects require lifelong specialist medical care. Failure to attend cardiological follow-up examinations and risky health behaviour in the transition phase may cause severe medical complications. A good level of disease-specific knowledge enhances compliance. Therefore, the study's aim was to investigate: (a) the level of disease-specific knowledge, (b) information preferences, and (c) sources of information for children, adolescents, and young adults regarding their illness. METHODS AND RESULTS: In all, 596 patients, aged 10-30 years, participated in this cross-sectional survey study (response rate: 53%). All patients were already enrolled in the German National Register for Congenital Heart Defects. The main outcome measures included disease-specific knowledge, information preferences, and information sources regarding patients' individual cardiac condition. The patients demonstrated a major knowledge gap concerning their illness and how to live with it. For all three age groups, patients' information needs were unmet on nearly half of the topics of interest. Children's information needs were comparable to those of adolescents and adults concerning several important topics, for example, work/career, sports. Information preferences varied according to age and gender, rather than disease severity. The most important sources of information were physicians (71.0%), family and friends (58.2%), and the Internet (37.5%). CONCLUSION: The study revealed substantial knowledge gaps, indicating a need for structured multidisciplinary patient education interventions. These interventions should start as early as in childhood and help patients manage their condition and assume responsibility for their own health, so that the transition phase runs smoothly.

The effect of duration of antimicrobial treatment for bacteremia in critically ill patients on in-hospital mortality - Retrospective double center analysis.

PURPOSE: Excessive duration of antibiotic treatment is a major factor for inappropriate antibiotic consumption. Although in some instances shorter antibiotic courses are as efficient as longer ones, no specific recommendations as to the duration of antimicrobial treatment for bloodstream infections currently exist. In the present study, we investigated the effect of antibiotic treatment duration on in-hospital mortality using retrospective data from two cohorts that included patients with bacteremia at two Swiss tertiary Intensive Care Units (ICUs). MATERIALS AND METHODS: Overall 8227 consecutive patients requiring ICU admission were screened for bacteremia between 01/2012-12/2013 in Lausanne and between 07/2016-05/2017 in Bern. Patients with an infection known to require prolonged treatment or having single positive blood culture with common contaminant pathogens were excluded. The primary outcome of interest was the time from start of antimicrobial treatment to in-hospital death or hospital discharge, whichever comes first. The predictor of interest was adequate antimicrobial treatment duration, further divided into shorter (≤10 days) and longer (>10 days) durations. A time-dependent Cox model and a cloning approach were used to address immortality bias. The secondary outcomes were the median duration of antimicrobial treatment for patients with bacteremia overall and stratified by underlying infectious syndrome and pathogens in the case of secondary bacteremia. RESULTS: Out of the 707 patients with positive blood cultures, 382 were included into the primary analysis. Median duration of antibiotic therapy was 14 days (IQR, 7-20). Most bacteremia (84%) were monomicrobial; 18% of all episodes were primary bacteremia. Respiratory (28%), intra-abdominal (23%) and catheter infections (17%) were the most common sources of secondary bacteremia. Using methods to mitigate the risk of confounding associated with antibiotic treatment durations, shorter versus longer treatment groups showed no differences in in-hospital survival (time-dependent Cox-model: HR 1.5, 95% CI (0.8, 2.7), p = 0.20; Cloning approach: HR 1.0, 95% CI (0.7,1.5) p = 0.83). Sensitivity analyses showed that the interpretation did not change when using a 7 days cut-off. CONCLUSIONS: In this restrospective study, we found no evidence for a survival benefit of longer (>10 days) versus shorter treatment course in ICU patients with bacteremia. TRIAL REGISTRATION: The study was retrospectively registered on clinicatrials.gov (NCT05236283), 11 February 2022. The respective cantonal ethics commission (KEK Bern # 2021-02302) has approved the study.

Therapeutic Drug Monitoring in Children and Adolescents: Findings on Fluoxetine from the TDM-VIGIL Trial.

Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial ("TDM-VIGIL"), a transdiagnostic sample of children and adolescents (n = 138; mean age, 15; range, 7-18 years; 24.6% males) was treated with fluoxetine (10-40 mg/day). Analyses of both the last timepoint and all timepoints (n = 292 observations), utilizing (multiple) linear regressions, linear mixed-effect models, and cumulative link (mixed) models, were used to test the associations between dose, serum concentration, outcome, and potential predictors. The receiver operating curve and first to third interquartile methods, respectively, were used to examine concentration cutoff and reference values for responders. A strong positive relationship was found between dose and serum concentration of fluoxetine and its metabolite. Higher body weight was associated with lower serum concentrations, and female sex was associated with lower therapeutic response. The preliminary reference ranges for the active moiety (fluoxetine+norfluoxetine) were 208-328 ng/mL (transdiagnostically) and 201.5-306 ng/mL (depression). Most patients showed marked (45.6%) or minimal (43.5%) improvements and reported no adverse effects (64.9%). This study demonstrated a clear linear dose-serum level relationship for fluoxetine in youth, with the identified reference range being within that established for adults.

Stability of thyroid hormones during continuous infusion.

We investigated the stability of thyroid hormones during a mode of continuous drug infusion via polypropylene tubing using the same conditions that would be applied to treating patients in a hospital setting. The diluted thyroid hormones were prepared using aseptic technique, stored at 2-8°C (36-46°F) and tested within 24 h of preparation for stability and percent recovery from within plastic tubing. Experiments were done in duplicate with triplicate sets of readings for each assay point. Only T(4) prepared with 5% dextrose water (D5W) containing 1 mg/mL albumin remained constant, stable, predictable and accurate over time under various conditions. Other methods of preparation lost drug by adhering to the plastic containers and tubing by as much as 40% of starting concentration. T(3) recovery in the presence of 1 mg/mL of albumin was 107±2% (mean±standard error of the mean) of anticipated drug concentrations. We conclude from this series of experiments that to maintain an accurate and stable dosing of patients receiving intravenous thyroid hormones, 1 mg/mL of albumin must be added to the infusate to prevent lost on the plastic intravenous tubing.

Age and sex specific incidence for depression from early childhood to adolescence: A 13-year longitudinal analysis of German health insurance data.

BACKGROUND: Epidemiological studies indicate a disproportionate increase of depression incidence among adolescent girls, compared with boys. Since results regarding the age of onset of this sex difference are heterogeneous, this study aimed to investigate this difference on a large and representative sample. A second investigation sought to clarify whether there is a relevant sex difference in prepubertal onset of depression regarding the further course. METHODS: Health insurance data of 6-18-year-old Barmer insured patients, representing a 7.9% sample of the German population born in 1999 (N = 61.199), were analyzed. The incidence of depression episodes (ICD-10 F32.x) was evaluated. Subsequently, the absolute and relative risk of a depression diagnosis (F32.x/F33.x) in early/late adolescence was analyzed based on the diagnosis of depression in primary school age in unstratified and stratified univariate analyses performed in SAS. RESULTS: From 13 years of age, we found a significantly higher incidence of depressive disorders in girls than in boys. More than a fifth of the children with a depression diagnoses in primary school age had a depression relapse in early or late adolescence (early: 23.2%; 95% CI 19.6-26.9/late: 22.9%; 95% CI 19.3-26.5). Boys with depression in primary school age have a significantly higher relative risk for a depression relapse in late adolescence than girls (boys RR 4.2, 95% CI 3.3-5.2, girls RR: 2.1, 95% CI 1.7-2.7). LIMITATIONS: The analysis is based on administrative data. Low sensitivity for depression in primary care setting and low service utilization leads to an underestimation of the incidence. CONCLUSIONS: During puberty the risk for a first depressive episode increases more steeply in girls than in boys. Childhood depression has a high risk of relapse for both sexes, but is much more pronounced for boys.

The adaptation and evaluation of a CBT-based manual for the inpatient treatment of youth depression: a pilot study.

BACKGROUND: Although there is good evidence to support the effectiveness of cognitive behavioral therapy (CBT) for the outpatient treatment of adolescent major depressive disorder (MDD), evidence-based manuals for the inpatient setting are lacking. This pilot study sought to (i) adapt an existing CBT manual (treatment of adolescent depression; TADS) to an inpatient setting (TADS-in), (ii) test its effectiveness at symptom reduction and remission of MDD in a pre-post design, and (iii) assess the strengths and limitations of the manual via a focus-group with clinicians. METHODS: Twenty nine adolescents aged 12-17 years with a primary ICD-10 diagnosis of MDD being treated as inpatients at a psychiatric clinic were included. Embedded in the regular inpatient treatment course (8 weeks), patients received 12 sessions of the TADS-in manual. Quantitative assessment of symptom reduction and remission of MDD was conducted using a non-controlled pre-post design. The quantitative results were supplemented by a focus group with participating psychotherapists. RESULTS: Of the 29 patients included in the study at the beginning, 19 (65.5%) remained in the study at week 8. Symptoms of depression were statistically significantly lower at the end of treatment than at baseline according to self- (d = 1.38; mean change = 19.88; 95% CI = 12.48-27.28) and other reports (d = 0.64, mean change = 0.35; 95% CI = 0.08-0.62). Clinicians ratings of improvement (CGI-I) suggested that at the end of treatment, 15.8% were very much improved, 68.4% much improved, and 15.8% were minimally improved. According to diagnostic interviews with patients conducted at the end of treatment, 73.3% were in remission. The qualitative analysis showed that on the whole, the TADS-in manual is suitable for the inpatient setting. However, clinicians believed the effectiveness of TADS-in was limited by patient comorbidity and the fact that the inpatients were unable to practice incorporating techniques learnt into everyday life. CONCLUSIONS: This study is the first to adapt the TADS manual to the inpatient setting. The sample of depressed adolescents showed reduced symptomology following treatment, although these findings require replicating in a randomized controlled trial before effects can be attributed to the TADS-in manual specifically. This pilot study informs further development of the manual as well as representing an important first step in the evaluation of the inpatient treatment of adolescent depression.The study was retrospectively registered (DRKS00017308) and received no external funding.

Systematic review of the role of sedation in diagnostic spinal interventional techniques.

BACKGROUND: There is ongoing controversy regarding the validity of controlled diagnostic blocks due to variability in sensitivity, specificity, and accuracy. Consequently, identification of false-positive rates, false-negative rates, and placebo responses is crucial. The reasons described for false-positive responses to diagnostic anesthetic blocks are many; however, sedation and psychological factors have been implied as causes. Further, there is no consensus with regards to sedation prior to controlled diagnostic blocks and their influence on the accuracy and validity of a diagnosis. STUDY DESIGN: A systematic review of the literature evaluating the influence of sedation on diagnostic spinal interventional techniques. OBJECTIVES: To systematically assess the quality of clinical studies evaluating the diagnostic accuracy of controlled diagnostic blocks in the diagnosis of chronic spinal pain. METHODS: A comprehensive evaluation of the literature relating to sedation in diagnostic interventional techniques was performed. The methodologic quality assessment of the studies was carried out by utilizing Agency for Healthcare Research and Quality (AHRQ) methodologic quality criteria with scores of 50 or higher included in the assessment of the level of evidence. Level of evidence was based on the U.S. Preventive Services Task Force (USPSTF) criteria for the assessment of accuracy of diagnostic studies. LIMITATIONS: All 3 of the studies were produced by one group of authors. Thus paucity of the literature on the subject of facet joint pain and the lack of literature on the subjects of discogenic pain and sacroiliac joint pain are major limitations. RESULTS: Three studies were identified which met inclusion and methodologic assessment quality criteria. Sedation can be a confounding factor in a small population of patients specifically if fentanyl is employed and non-stringent criteria are followed. Based on the 3 randomized double-blind trials with stringent criteria utilizing 80% pain relief and the ability to perform prior painful movements without any significant pain following the diagnostic injection in evaluation of facet joint pain, the indicated evidence is Level II-1. CONCLUSION: This systematic review provides no significant evidence of the influence of sedation either with midazolam or fentanyl in the evaluation of cervical and lumbar facet joint pain with controlled cervical and lumbar facet joint nerve blocks with an indicated evidence of Level II-1, with application of stringent criteria of at least 80% pain relief and the ability to perform previously painful movements after the diagnostic blocks.

Spinal cord stimulation for patients with failed back surgery syndrome: a systematic review.

BACKGROUND: Failed back surgery syndrome is common in the United States. Management of post lumbar surgery syndrome with multiple modalities includes interventional techniques, resulting in moderate improvement, leaving a proportion of patients in intractable pain. The systematic reviews of long-term benefits and risks of spinal cord stimulation (SCS) for patients with failed back surgery syndrome showed limited to moderate evidence and cost effectiveness. However, with the exponential increase in surgery in the United States, spinal cord implants are also increasing. Thus, the discussion continues with claims of lack of evidence on one hand and escalating increases in utilization on the other hand. STUDY DESIGN: A systematic review of SCS in patients with failed back surgery syndrome. OBJECTIVES: This systematic review is undertaken to examine the evidence from randomized controlled trials (RCTs) and observational studies to evaluate the effectiveness of SCS in post lumbar surgery syndrome and to demonstrate clinical and cost effectiveness. METHODS: Review of the literature was performed according to the Cochrane Musculoskeletal Review Group Criteria as utilized for interventional techniques for randomized trials and the Agency for Healthcare Research and Quality (AHRQ) criteria for observational studies. The 5 levels of evidence were classified as Level I, II, or III with 3 subcategories in Level II based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature of the English language identified through searches of PubMed and EMBASE from 1966 to December 2008, and manual searches of bibliographies of known primary and review articles. OUTCOME MEASURES: The primary outcome measure was pain relief (short-term relief < or = one-year and long-term > one-year). Secondary outcome measures of improvement in functional status, psychological status, return to work, and reduction in opioid intake were utilized. RESULTS: The indicated evidence is Level II-1 or II-2 for long-term relief in managing patients with failed back surgery syndrome. LIMITATIONS: The limitations of this review included the paucity and heterogeneity of the literature. CONCLUSION: This systematic review evaluating the effectiveness of SCS in relieving chronic intractable pain of failed back surgery syndrome indicated the evidence to be Level II-1 or II-2 for clinical use on a long-term basis.

Interactions between FKBP5 variation and environmental stressors in adolescent Major Depression.

OBJECTIVE: Major Depression (MD) results from a complex interplay between environmental stressors and biological factors. Previous studies in adults have shown that adverse life events interact with genetic variation in FKBP5, a gene implicated in the stress-response system, to predict depressive symptoms and MD. This is the first study to investigate interactions between FKBP5 variants and a range of environmental stressors in adolescents with a clinical diagnosis of MD. METHOD: 148 male and female adolescents with MD and 143 typically developing (TD) controls (13-18 years) were included in the present study. For self-reported environmental stressors, subjective severity was assessed to allow a classification of these factors as mild, moderate and severe. Sociodemographic stressors were assessed via parental-report. RESULTS: With a heightened number of sociodemographic, moderate and total number of stressors, participants carrying at least one copy of the FKBP5 CATT haplotype or at least one minor allele of various FKBP5 SNPs had the highest risk for being in the MD group. No genetic main effects were found. Sociodemographic stressors as well as self-reported mild, moderate, and severe stressors were more common in depressed than in TD adolescents. CONCLUSION: This is the first study to show interactions between genetic variation in FKBP5 and environmental stressors in a sample of clinically depressed adolescents. The current study provides important starting-points for preventive efforts and highlights the need for a fine-grained analysis of different forms and severities of environmental stressors and their interplay with genetic variation for understanding the complex etiology of (youth) MD.