TEMPus VoLA: The timed Epstein multi-pressure vessel at low accelerations.

The field of planetary system formation relies extensively on our understanding of the aerodynamic interaction between gas and dust in protoplanetary disks. Of particular importance are the mechanisms triggering fluid instabilities and clumping of dust particles into aggregates, and their subsequent inclusion into planetesimals. We introduce the timed Epstein multi-pressure vessel at low accelerations, which is an experimental apparatus for the study of particle dynamics and rarefied gas under micro-gravity conditions. This facility contains three experiments dedicated to studying aerodynamic processes: (i) the development of pressure gradients due to collective particle-gas interaction, (ii) the drag coefficients of dust aggregates with variable particle-gas velocity, and (iii) the effect of dust on the profile of a shear flow and resultant onset of turbulence. The approach is innovative with respect to previous experiments because we access an untouched parameter space in terms of dust particle packing fraction, and Knudsen, Stokes, and Reynolds numbers. The mechanisms investigated are also relevant for our understanding of the emission of dust from active surfaces, such as cometary nuclei, and new experimental data will help interpreting previous datasets (Rosetta) and prepare future spacecraft observations (Comet Interceptor). We report on the performance of the experiments, which has been tested over the course of multiple flight campaigns. The project is now ready to benefit from additional flight campaigns, to cover a wide parameter space. The outcome will be a comprehensive framework to test models and numerical recipes for studying collective dust particle aerodynamics under space-like conditions.

Altered DNA methylation at age-associated CpG sites in children with growth disorders: impact on age estimation?

Age estimation based on DNA methylation (DNAm) can be applied to children, adolescents and adults, but many CG dinucleotides (CpGs) exhibit different kinetics of age-associated DNAm across these age ranges. Furthermore, it is still unclear how growth disorders impact epigenetic age predictions, and this may be particularly relevant for a forensic application. In this study, we analyzed buccal mucosa samples from 95 healthy children and 104 children with different growth disorders. DNAm was analysed by pyrosequencing for 22 CpGs in the genes PDE4C, ELOVL2, RPA2, EDARADD and DDO. The relationship between DNAm and age in healthy children was tested by Spearman's rank correlation. Differences in DNAm between the groups "healthy children" and the (sub-)groups of children with growth disorders were tested by ANCOVA. Models for age estimation were trained (1) based on the data from 11 CpGs with a close correlation between DNAm and age (R ≥ 0.75) and (2) on five CpGs that also did not present significant differences in DNAm between healthy and diseased children. Statistical analysis revealed significant differences between the healthy group and the group with growth disorders (11 CpGs), the subgroup with a short stature (12 CpGs) and the non-short stature subgroup (three CpGs). The results are in line with the assumption of an epigenetic regulation of height-influencing genes. Age predictors trained on 11 CpGs with high correlations between DNAm and age revealed higher mean absolute errors (MAEs) in the group of growth disorders (mean MAE 2.21 years versus MAE 1.79 in the healthy group) as well as in the short stature (sub-)groups; furthermore, there was a clear tendency for overestimation of ages in all growth disorder groups (mean age deviations: total growth disorder group 1.85 years, short stature group 1.99 years). Age estimates on samples from children with growth disorders were more precise when using a model containing only the five CpGs that did not present significant differences in DNAm between healthy and diseased children (mean age deviations: total growth disorder group 1.45 years, short stature group 1.66 years). The results suggest that CpGs in genes involved in processes relevant for growth and development should be avoided in age prediction models for children since they may be sensitive for alterations in the DNAm pattern in cases of growth disorders.

Evidence for differences in DNA methylation between Germans and Japanese.

As a contribution to the discussion about the possible effects of ethnicity/ancestry on age estimation based on DNA methylation (DNAm) patterns, we directly compared age-associated DNAm in German and Japanese donors in one laboratory under identical conditions. DNAm was analyzed by pyrosequencing for 22 CpG sites (CpGs) in the genes PDE4C, RPA2, ELOVL2, DDO, and EDARADD in buccal mucosa samples from German and Japanese donors (N = 368 and N = 89, respectively).Twenty of these CpGs revealed a very high correlation with age and were subsequently tested for differences between German and Japanese donors aged between 10 and 65 years (N = 287 and N = 83, respectively). ANCOVA was performed by testing the Japanese samples against age- and sex-matched German subsamples (N = 83 each; extracted 500 times from the German total sample). The median p values suggest a strong evidence for significant differences (p < 0.05) at least for two CpGs (EDARADD, CpG 2, and PDE4C, CpG 2) and no differences for 11 CpGs (p > 0.3).Age prediction models based on DNAm data from all 20 CpGs from German training data did not reveal relevant differences between the Japanese test samples and German subsamples. Obviously, the high number of included "robust CpGs" prevented relevant effects of differences in DNAm at two CpGs.Nevertheless, the presented data demonstrates the need for further research regarding the impact of confounding factors on DNAm in the context of ethnicity/ancestry to ensure a high quality of age estimation. One approach may be the search for "robust" CpG markers-which requires the targeted investigation of different populations, at best by collaborative research with coordinated research strategies.

The CoPhyLab comet-simulation chamber.

The Comet Physics Laboratory (CoPhyLab) is an international research program to study the physical properties of cometary analog materials under simulated space conditions. The project is dedicated to studying, with the help of multiple instruments and the different expertise and background from the different partners, the physics of comets, including the processes inside cometary nuclei, the activity leading to the ejection of dust and gas, and the sub-surface and surface evolution of cometary nuclei when exposed to solar illumination. CoPhyLab will provide essential information on the formation and evolution of comets and insights into the origins of primitive Solar System bodies. To this end, we constructed a new laboratory that hosts several small-scale experiments and a large-scale comet-simulation chamber (L-Chamber). This chamber has been designed and constructed to host ice-dust samples with a diameter of up to 250 mm and a variable height between 100 and 300 mm. The cometary-analog samples will be kept at temperatures below 120 K and pressures around 10-6 mbar to ensure cometary-like conditions. In total, 14 different scientific instruments are attached to the L-Chamber to study the temporal evolution of the physical properties of the sample under different insolation conditions. Due to the implementation of a scale inside the L-Chamber that can measure weight changes of the samples with high precision, the cooling system is mechanically decoupled from the sample holder and cooling of the samples occurs by radiation only. The constructed chamber allows us to conduct uninterrupted experiments at low temperatures and pressures up to several weeks.

Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial.

BACKGROUND: In EMBRACA, talazoparib prolonged progression-free survival versus chemotherapy (hazard ratio [HR] 0.542 [95% confidence interval (CI) 0.413-0.711]; P < 0.0001) and improved patient-reported outcomes (PRO) in germline BRCA1/2 (gBRCA1/2)-mutated advanced breast cancer (ABC). We report final overall survival (OS). PATIENTS AND METHODS: This randomized phase III trial enrolled patients with gBRCA1/2-mutated HER2-negative ABC. Patients received talazoparib or physician's choice of chemotherapy. OS was analyzed using stratified HR and log-rank test and prespecified rank-preserving structural failure time model to account for subsequent treatments. RESULTS: A total of 431 patients were entered in a randomized study (287 talazoparib/144 chemotherapy) with 412 patients treated (286 talazoparib/126 chemotherapy). By 30 September 2019, 216 deaths (75.3%) occurred for talazoparib and 108 (75.0%) chemotherapy; median follow-up was 44.9 and 36.8 months, respectively. HR for OS with talazoparib versus chemotherapy was 0.848 (95% CI 0.670-1.073; P = 0.17); median (95% CI) 19.3 months (16.6-22.5 months) versus 19.5 months (17.4-22.4 months). Kaplan-Meier survival percentages (95% CI) for talazoparib versus chemotherapy: month 12, 71% (66% to 76%)/74% (66% to 81%); month 24, 42% (36% to 47%)/38% (30% to 47%); month 36, 27% (22% to 33%)/21% (14% to 29%). Most patients received subsequent treatments: for talazoparib and chemotherapy, 46.3%/41.7% received platinum and 4.5%/32.6% received a poly(ADP-ribose) polymerase (PARP) inhibitor, respectively. Adjusting for subsequent PARP and/or platinum use, HR for OS was 0.756 (95% bootstrap CI 0.503-1.029). Grade 3-4 adverse events occurred in 69.6% (talazoparib) and 64.3% (chemotherapy) patients, consistent with previous reports. Extended follow-up showed significant overall improvement and delay in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms favoring talazoparib versus chemotherapy (P < 0.01 for all), consistent with initial analyses. CONCLUSIONS: In gBRCA1/2-mutated HER2-negative ABC, talazoparib did not significantly improve OS over chemotherapy; subsequent treatments may have impacted analysis. Safety was consistent with previous observations. PRO continued to favor talazoparib.

Scattering of light by a large, densely packed agglomerate of small silica spheres.

We model the measured phase function and degree of linear polarization of a macroscopic agglomerate made of micrometer-scale silica spheres using the methodology of multiple scattering. In the laboratory work, the agglomerate is produced ballistically, characterized by scanning electron microscopy, and measured with the $ {\text{PROGRA}^{2}} $PROGRA2 instrument to obtain the light scattering properties. The model phase function and degree of polarization are in satisfactory agreement with the experimental data. To our best knowledge, this is the first time the degree of linear polarization has been modeled well for a large, densely packed agglomerate composed of small particles with known sizes and shapes. The study emphasizes the relevance of the degree of linear polarization and gives insights into the effects of particle aggregation on the scattering characteristics.

Influence of software parameters on measurements in automatized image-based analysis of fat tissue histology.

The understanding of fat tissue plays an eminent role in plastic surgery as well as in metabolic research. Histopathological analysis of tissue samples provides insight in free fat graft survival and culture experiments help to better understand fat tissue derived stem cells (ASCs). To facilitate such experiments, modern image-based histology could provide an automatized approach to a large amount of data to gain not only qualitative but also quantitative data. This study was designed to critically evaluate image-based analysis of fat tissue samples in cell culture or in tissue probes and to identify critical parameters to avoid bias in further studies. In the first part of the study, ASCs were harvested and differentiated into adipocytes in cell culture. Histology was performed with the fluorescent dye BODIPY and the obtained digital images were analyzed using Image J software. In the second part of the study, digitalized histology of a previous in vivo study was subjected to automatized fat vacuole quantification using Image J. Both approaches were critically reviewed, and different software parameter settings were tested. Results showed that automatized digital image analysis allows the quantification of fat tissue probes with enough precision giving significant results. But the testing of different software parameters revealed a significant influence of parameters themselves on calculated results. Therefore, we recommend the use of image-based analysis to quantify fat tissue probes to improve the comparability of studies. But we also emphasize to calibrate software using internal controls in every single experimental approach.

Core outcome sets for prevention and treatment of postpartum haemorrhage: an international Delphi consensus study.

OBJECTIVE: To develop core outcome sets (COS) for studies evaluating interventions for (1) prevention and (2) treatment of postpartum haemorrhage (PPH), and recommendations on how to report the COS. DESIGN: A two-round Delphi survey and face-to-face meeting. POPULATION: Healthcare professionals and women's representatives. METHODS: Outcomes were identified from systematic reviews of PPH studies and stakeholder consultation. Participants scored each outcome in the Delphi on a Likert scale between 1 (not important) and 9 (critically important). Results were discussed at the face-to-face meeting to agree the final COS. Consensus at the meeting was defined as ≥ 70% of participants scoring the outcome as critically important (7-9). Lectures, discussion and voting were used to agree how to report COS outcomes. MAIN OUTCOME MEASURES: Outcomes from systematic reviews and consultations. RESULTS: Both Delphi rounds were completed by 152/205 (74%) participants for prevention and 143/197 (73%) for treatment. For prevention of PPH, nine core outcomes were selected: blood loss, shock, maternal death, use of additional uterotonics, blood transfusion, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. For treatment of PPH, 12 core outcomes were selected: blood loss, shock, coagulopathy, hysterectomy, organ dysfunction, maternal death, blood transfusion, use of additional haemostatic intervention, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. Recommendations were developed on how to report these outcomes where possible. CONCLUSIONS: These COS will help standardise outcome reporting in PPH trials. TWEETABLE ABSTRACT: Core outcome sets for PPH: nine core outcomes for PPH prevention and 12 core outcomes for PPH treatment.

Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial.

Background: In the EMBRACA phase III trial, talazoparib (1 mg daily, orally) demonstrated a statistically significant improvement in PFS versus physician's choice of chemotherapy (PCT; capecitabine, eribulin, gemcitabine, or vinorelbine) in patients with HER2-negative advanced breast cancer carrying a germline BRCA1/2 mutation; we evaluated patient-reported outcomes (PROs). Patients and methods: Patients were randomized 2 : 1 to receive talazoparib or PCT. PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks), and at the end of treatment, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) and its breast cancer module, QLQ-BR23. Prespecified exploratory analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis carried out in the global health status/quality of life (GHS/QoL), and all functional and symptom scales from the EORTC QLQ-C30 and -BR23 questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and a Cox proportional hazards model. Results: Baseline scores were similar between arms. Statistically significant estimated overall improvement from baseline in GHS/QoL was seen for talazoparib compared with statistically significant deterioration for PCT {3.0 [95% confidence interval (CI) 1.2, 4.8] versus -5.4 [95% CI -8.8, -2.0]; between arms, P < 0.0001}. A statistically significant greater delay was observed in TTD in GHS/QoL, favoring talazoparib over PCT [hazard ratio, 0.38 (95% CI 0.26, 0.55; median, 24.3 versus 6.3 months, respectively; P < 0.0001)]. A statistically significant overall change and a statistically significant delay in TTD, all favoring talazoparib, were also observed in multiple functions and symptoms. Conclusion: Patients who received talazoparib had significant overall improvements and significant delay in TTD in multiple cancer-related and breast cancer-specific symptoms, functions, and GHS/QoL. ClinicalTrials.gov: NCT01945775.

Blood plasma traits associated with genetic merit for feed utilization in Holstein cows.

The objective of this study was to evaluate the potential of selection for feed utilization on associated blood plasma metabolite and hormone traits. Dry matter intake (DMI) was recorded in 970 Holsteins from 11 commercial farms in Pennsylvania and used to derive dry matter efficiency (DME; fat-corrected milk yield/DMI), crude protein efficiency (CPE; protein yield/crude protein intake), and residual feed intake (RFI, defined as actual feed intake minus expected feed intake for maintenance and milk production, based on calculation of DMI adjusted for yield, body weight, and body condition score). Estimated breeding values for the 4 feed utilization traits (DMI, DME, CPE, and RFI), yield traits, body traits, and days open were standardized according to their respective genetic standard deviations. Up to 631 blood samples from 393 cows from 0 to 60 d in milk (DIM) were evaluated for blood plasma concentrations of glucose, nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), creatinine, urea, growth hormone (GH), 3,5,3'-triiodothyronine (T3), and other parameters. Blood plasma traits were regressed on DIM, lactation number, herd, and standardized genetic merit. Cows with higher genetic merit for yield had significantly higher concentrations of GH, NEFA (milk and protein yield), and BHB (fat yield) from 31 to 60 DIM, but lower concentrations of glucose from 0 to 30 DIM, and T3 (milk yield, 0-60 DIM). The high GH-low glucose-low T3 concentration pattern was further accentuated for cows with genetic merit for enhanced feed efficiency (higher DME and lower RFI). Cows with a genetic tendency to be thin (low body condition score) also had elevated GH concentrations, but lower blood glucose, creatinine, and T3 concentrations. Those characteristics associated with enhanced feed efficiency (higher GH and lower glucose and T3 concentrations) were unfavorably associated with fertility, as indicated by elevated days open. Elevated NEFA and BHB concentrations were also associated with extended days open. Consideration of metabolic profiles when evaluating feed efficiency might be a method of maintaining high levels of health and reproductive fitness when selecting for feed efficiency.

Development of a home-based auditory training to improve speech recognition on the telephone for patients with cochlear implants: A randomised trial.

OBJECTIVES: Speech recognition on the telephone poses a challenge for patients with cochlear implants (CIs) due to a reduced bandwidth of transmission. This trial evaluates a home-based auditory training with telephone-specific filtered speech material to improve sentence recognition. DESIGN: Randomised controlled parallel double-blind. SETTING: One tertiary referral centre. PARTICIPANTS: A total of 20 postlingually deafened patients with CIs. MAIN OUTCOME MEASURES: Primary outcome measure was sentence recognition assessed by a modified version of the Oldenburg Sentence Test filtered to the telephone bandwidth of 0.3-3.4 kHz. Additionally, pure tone thresholds, recognition of monosyllables and subjective hearing benefit were acquired at two separate visits before and after a home-based training period of 10-14 weeks. For training, patients received a CD with speech material, either unmodified for the unfiltered training group or filtered to the telephone bandwidth in the filtered group. RESULTS: Patients in the unfiltered training group achieved an average sentence recognition score of 70.0%±13.6% (mean±SD) before and 73.6%±16.5% after training. Patients in the filtered training group achieved 70.7%±13.8% and 78.9%±7.0%, a statistically significant difference (P=.034, t10 =2.292; two-way RM ANOVA/Bonferroni). An increase in the recognition of monosyllabic words was noted in both groups. The subjective benefit was positive for filtered and negative for unfiltered training. CONCLUSIONS: Auditory training with specifically filtered speech material provided an improvement in sentence recognition on the telephone compared to training with unfiltered material.

[Flexible Guidance of Ultra-Short Laser Pulses in Ophthalmic Therapy Systems]. / Flexible Führung ultrakurzer Laserpulse in ophthalmologischen Therapiesystemen.

In the last 20 years, the role of ultrashort pulsed lasers in ophthalmology has become increasingly important. However, it is still impossible to guide ultra-short laser pulses with standard glass fibres. The highly energetic femtosecond pulses would destroy the fibre material, and non-linear dispersion effects would significantly change beam parameters. In contrast, photonic crystal fibres mainly guide the laser pulses in air, so that absorption and dispersive pulse broadening have essentially no effect. This article compares classical beam guidance with mirrors, lenses and prisms with photonic crystal fibres and describes the underlying concepts and the current state of technology. A classical mirror arm possesses more variable optical properties, while the HCF (Hollow-Core Photonic Crystal Fibre) must be matched in terms of the laser energy and the laser spectrum. In contrast, the HCF has more advantages in respect of handling, system integration and costs. For applications based on photodisruptive laser-tissue interaction, the relatively low damage threshold of photonic crystal fibres compared to classic beam guiding systems is unacceptable. If, however, pulsed laser radiation has a sufficiently low peak intensity, e.g. as used for plasma-induced ablation, photonic crystal fibres can definitely be considered as an alternative solution to classic beam guidance.

Strongyloidiasis in Latin American immigrants: a pilot study.

The United States of America (USA) has the largest international population of any nation in the world. Immigrants from Latin American countries, where intestinal parasites are endemic, comprise more than half of this population. This study aims to determine the prevalence of strongyloidiasis, a potentially deadly parasitic infection, in foreign-born individuals. We conducted a cross-sectional study in Washington, DC, to determine the seroprevalence of Strongyloides stercoralis infection using an NIE-ELISA IgG antibody assay. Multi-parallel quantitative real-time polymerase chain reaction (qPCR) was performed in stool samples of NIE-ELISA-positive patients to investigate possible polyparasitism. The NIE-ELISA assay detected an S. stercoralis prevalence of 4.2% in a group of 119 volunteers. Combining NIE-ELISA and qPCR detected a parasite prevalence of 5.0%. Our results underscore the relevance of systematic testing for gastrointestinal parasites in individuals from endemic regions. It also makes a case for a survey in the USA to identify immigrants' risk for strongyloidiasis and other gastrointestinal parasitic infections.

Agomelatine and Transient Elevation of Creatine Phosphokinase.

Agomelatine is an antidepressant drug with moderate agonistic action at the melatonine receptor MT1 and weak effect at MT2. According to clinical studies, agomelatine ameliorates depressive symptoms and improves sleep quality. Side effects such as elevated liver enzymes are well-known. Therefore, routine laboratory monitoring of liver function is recommended periodically throughout treatment because of a rare risk of more serious liver reactions. 2 patients with creatine phosphokinase elevation during treatment with agomelatine are presented. We recommend a check of the creatine phosphokinase level during the initial treatment phase in patients receiving agomelatine for the first time.

Flux and composition of interstellar dust at Saturn from Cassini's Cosmic Dust Analyzer.

Interstellar dust (ISD) is the condensed phase of the interstellar medium. In situ data from the Cosmic Dust Analyzer on board the Cassini spacecraft reveal that the Saturnian system is passed by ISD grains from our immediate interstellar neighborhood, the local interstellar cloud. We determine the mass distribution of 36 interstellar grains, their elemental composition, and a lower limit for the ISD flux at Saturn. Mass spectra and grain dynamics suggest the presence of magnesium-rich grains of silicate and oxide composition, partly with iron inclusions. Major rock-forming elements (magnesium, silicon, iron, and calcium) are present in cosmic abundances, with only small grain-to-grain variations, but sulfur and carbon are depleted. The ISD grains in the solar neighborhood appear to be homogenized, likely by repeated processing in the interstellar medium.

Physical Characterization and Innate Immunogenicity of Aggregated Intravenous Immunoglobulin (IGIV) in an In Vitro Cell-Based Model.

PURPOSE: To investigate in vitro the innate immune response to accelerated stress-induced aggregates of intravenous immunoglobulin (IGIV) using a well-defined human cell-line model, and to correlate the innate response to physical properties of the aggregates. METHODS: IGIV aggregates were prepared by applying various accelerated stress methods, and particle size, count and structure were characterized. Immune cell activation as tracked by inflammatory cytokines released in response to aggregates was evaluated in vitro using peripheral blood mononuclear cells (PBMC), primary monocytes and immortalized human monocyte-like cell lines. RESULTS: IGIV aggregates produced by mechanical stress induced higher cytokine release by PBMC and primary monocytes than aggregates formed by other stresses. Results with the monocytic cell line THP-1 paralleled trends in PBMC and primary monocytes. Effects were dose-dependent, enhanced by complement opsonization, and partially inhibited by blocking toll-like receptors (TLR2 and TLR4) and to a lesser extent by blocking Fc gamma receptors (FcγRs). CONCLUSIONS: Stress-induced IGIV aggregates stimulate a dose-dependent cytokine response in human monocytes and THP-1 cells, mediated in part by TLRs, FcγRs and complement opsonization. THP-1 cells resemble primary monocytes in many respects with regard to tracking the innate response to IgG aggregates. Accordingly, the measurement of inflammatory cytokines released by THP-1 cells provides a readily accessible assay system to screen for the potential innate immunogenicity of IgG aggregates. The results also highlight the role of aggregate structure in interacting with the different receptors mediating innate immunity.

Effects of cortisol administration on craving in heroin addicts.

Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P = 0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P = 0.0019; after heroin administration: P = 0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction.