Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models.

3 D human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in pre-clinical investigative dermatology and regulatory toxicology. Here, we investigated the utility of electrical impedance spectroscopy (EIS) for non-invasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for seven consecutive days did not impact epidermal morphology and readouts showed comparable trends to HEEs measured only once. We determined two frequency ranges in the resulting impedance spectra: a lower frequency range termed EISdiff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9 engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to pro-inflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine-associated decrease in EISdiff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a non-invasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects and repair.

Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models.

3 D human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in pre-clinical investigative dermatology and regulatory toxicology. Here, we investigated the utility of electrical impedance spectroscopy (EIS) for non-invasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for seven consecutive days did not impact epidermal morphology and readouts showed comparable trends to HEEs measured only once. We determined two frequency ranges in the resulting impedance spectra: a lower frequency range termed EISdiff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9 engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to pro-inflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine-associated decrease in EISdiff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a non-invasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects and repair.

Contralateral hearing loss in children with a unilateral enlarged vestibular aqueduct.

OBJECTIVE: To evaluate the long-term ipsi- and contralateral hearing of patients with a unilateral enlarged vestibular aqueduct (EVA). STUDY DESIGN: Multicenter retrospective cohort study. SETTING: Three tertiary otology and audiology referral centers. PATIENTS AND DIAGNOSTIC INTERVENTIONS: A total of 34 children with a unilateral enlarged vestibular aqueduct as identified on CT and/or MR imaging were evaluated with pure tone and speech perception audiometry. MEAN OUTCOME MEASURES: Radiologic measurements of the vestibular aqueduct, ipsi- and contralateral hearing loss, ipsi- and contralateral hearing loss progression over time and DNA test results. RESULTS: All patients in this cohort with unilateral EVA presented with hearing loss. Hearing loss was progressive in 38% of the ipsilateral ears. In 29% of the children, hearing loss was also found in the contralateral ear without EVA. In 90%, the contralateral hearing was stable, with a mean follow up of 4.2 years. We found a significant correlation between the severity of the hearing loss and the size of the EVA. A genetic diagnosis associated with EVA and/or SNHL was found in only 7%. CONCLUSION: About a third of the children with unilateral EVA are at risk of developing hearing loss in the contralateral ear. This indicates that at least in some patients with a unilateral EVA, a bilateral pathogenic process underlies the hearing loss, in contrary to what the imaging results suggest. These findings are important for counseling of EVA patients and their parents and have implications for follow up.

Efficacy of digital cognitive behavioural therapy for symptoms of generalised anxiety disorder: a study protocol for a randomised controlled trial.

BACKGROUND: Generalised anxiety disorder (GAD) is a chronic and disabling condition with considerable personal and economic impact. Cognitive behavioural therapy (CBT) is a recommended psychological therapy for GAD; however, there are substantial barriers to accessing treatment. Digital CBT, in particular smartphone-delivered CBT, has the potential to improve accessibility and increase dissemination of CBT. Despite the emerging evidence of smartphone-based psychological interventions for reducing anxiety, effect size scores are typically smaller than in-person interventions, and there is a lack of research assessing the efficacy of smartphone-delivered digital interventions specifically for GAD. METHODS: In the DeLTA trial (DigitaL Therapy for Anxiety), we plan to conduct a parallel-group superiority randomised controlled trial examining the efficacy of a novel smartphone-based digital CBT intervention for GAD compared to a waitlist control. We aim to recruit 242 adults (aged 18 years or above) with moderate-to-severe symptoms of GAD. This trial will be conducted entirely online and will involve assessments at baseline (week 0; immediately preceding randomisation), mid-intervention (week 3), post-intervention (week 6; primary end point) and follow-up (week 10). The primary objective is to evaluate the efficacy of the intervention on GAD symptom severity compared to a waitlist control at post-intervention. Secondary objectives are to examine between-group effects on GAD at follow-up, and to examine the following secondary outcomes at both post-intervention and follow-up: 1) worry; 2) depressive symptoms; 3) wellbeing; 4) quality of life; and 5) sleep difficulty. DISCUSSION: This trial will report findings on the initial efficacy of a novel digital CBT intervention for GAD. Results have the potential to contribute towards the evidence base for digital CBT for GAD and increase the dissemination of CBT. TRIAL REGISTRATION: ISRCTN, ISRCTN12765810. Registered on 11 January 2019.

Endogenous testosterone levels are predictive of symptom reduction with exposure therapy in social anxiety disorder.

The Hypothalamus-Pituitary-Gonadal (HPG)-axis, and testosterone in particular, play an important role in social motivational behavior. Socially avoidant behavior, characteristic of social anxiety disorder (SAD), has been linked to low endogenous testosterone levels, and can be alleviated by testosterone administration in SAD. Although these beneficial effects of testosterone may translate to exposure therapy, it remains unknown whether testosterone increases prior to exposure improve therapy outcomes. In this proof-of-principle study, we tested whether pre-exposure (reactive and baseline) endogenous testosterone levels were predictive of exposure outcome in SAD. Seventy-three participants (52 females) with a principal SAD diagnosis performed four speech exposures: three during one standardized exposure therapy session and one at post-assessment one week later. Subjective fear levels were assessed before and after each speech exposure and social anxiety symptoms were assessed at pre- and post-treatment. Pre-treatment testosterone levels were assessed before (baseline) and in response to a pre-exposure instruction session (reactive). Pre-treatment testosterone levels were not related to fear levels during exposure therapy, but predicted pre- to post-treatment reductions in social anxiety symptom severity. Specifically, low baseline and high reactive pre-treatment testosterone levels were associated with larger reductions in social anxiety symptom severity. These findings support the role of HPG-axis in social fear reduction. Specifically, our finding that high reactive testosterone as well as low baseline testosterone predicted exposure outcome in SAD, suggests that good reactivity of the HPG-axis is a promising marker for the symptom-reducing effects of exposure therapy.

Imaging trapped quantum gases by off-axis holography.

We present a dispersive imaging method for trapped quantum gases based on digital off-axis holography. Both phase delay and intensity of the probe field are determined from the same image. Due to the heterodyne gain inherent to the holographic method, it is possible to retrieve the phase delay induced by the atoms at probe beam doses two orders of magnitude lower than phase-contrast imaging methods. Using the full field of the probe beam, we numerically correct for image defocusing.

Influence of season and pituitary pars intermedia dysfunction on hair cortisol concentration in horses.

Hair cortisol has been demonstrated to reflect hypothalamic-pituitary-adrenal axis activity (including Cushing's disease and stress) in several species. We hypothesized that hair cortisol concentrations are increased in horses with pituitary pars intermedia dysfunction (PPID) compared with healthy adult horses and that this difference is magnified in the fall, when circulating adrenocorticotropin (ACTH) is generally the highest. Cortisol from hair collected using clippers with a #40 blade from the neck was compared between PPID horses and control horses over several months in the fall (August-December) and 1 mo in spring (May). Cortisol from hair at several sampling sites (neck, jugular furrow, sternum, and submandibular) were compared between PPID (n = 6) and control (n = 8) horses in May. Relationships between hair cortisol and ACTH were assessed in the fall. Hair cortisol when measured by weight was higher in PPID vs control horses in October and November (P ≤ 0.01) but not December (P = 0.15), May (P > 0.7), or August-September (P = 0.18). When normalized for hair length, hair cortisol was higher in PPID vs control horses in November (P = 0.0006), but not October or December (P ≥ 0.06). Hair cortisol concentrations did not differ between PPID and control horses from any collection site in May (P > 0.7). There were no consistent relationships between ACTH and hair cortisol concentrations in October, November, or December (P ≥ 0.05). These findings suggest that PPID horses have increased hair cortisol accumulation in the fall compared with control horses. Additional work is needed to clarify whether assessing cortisol per weight or per hair length is most relevant in the horse.

Combined OCT distance and FBG force sensing cannulation needle for retinal vein cannulation: in vivo animal validation.

PURPOSE: Retinal vein cannulation is an experimental procedure during which a clot-dissolving drug is injected into an obstructed retinal vein. However, due to the fragility and minute size of retinal veins, such procedure is considered too risky to perform manually. With the aid of surgical robots, key limiting factors such as: unwanted eye rotations, hand tremor and instrument immobilization can be tackled. However, local instrument anatomy distance and force estimation remain unresolved issues. A reliable, real-time local interaction estimation between instrument tip and the retina could be a solution. This paper reports on the development of a combined force and distance sensing cannulation needle, and its experimental validation during in vivo animal trials. METHODS: Two prototypes are reported, relying on force and distance measurements based on FBG and OCT A-scan fibres, respectively. Both instruments provide an 80 [Formula: see text] needle tip and have outer shaft diameters of 0.6 and 2.3 mm, respectively. RESULTS: Both prototypes were characterized and experimentally validated ex vivo. Then, paired with a previously developed surgical robot, in vivo experimental validation was performed. The first prototype successfully demonstrated the feasibility of using a combined force and distance sensing instrument in an in vivo setting. CONCLUSION: The results demonstrate the feasibility of deploying a combined sensing instrument in an in vivo setting. The performed study provides a foundation for further work on real-time local modelling of the surgical scene. This paper provides initial insights; however, additional processing remains necessary.

Changes in thyroid function of nestling tree swallows (Tachycineta bicolor) in relation to polycyclic aromatic compounds and other environmental stressors in the Athabasca Oil Sands Region.

In the Canadian Athabasca Oil Sands Region (AOSR), nestling tree swallows (Tachycineta bicolor) raised near mining-related activities accumulated greater concentrations of polycyclic aromatic compounds (PACs) that contributed to their poorer condition, growth, and reproductive success. Here, we report changes in thyroid function of the same 14 day old (do) nestlings (N ≤ 68) at these mining-related sites (OS1, OS2) compared to reference nestlings (REF1), and in relation to multiple environmental stressors that influence avian thyroid function. Thyroid function was compromised for OS1 nestlings but generally comparable between OS2 and REF1 chicks. In 2012, circulating total triiodothyronine (TT3) and thyroxine (TT4) were similar among all nestlings. The OS1 chicks had more active thyroid glands based on histological endpoints. Hepatic T4 outer-ring deiodinase (T4-ORD) activity was suppressed in OS1 and OS2 chicks. Despite inter-annual differences, OS1 chicks continued experiencing compromised thyroid function with significantly higher circulating TT4 and more active thyroid glands in 2013. The OS2 chicks had less active thyroid glands, which conceivably contributed to their suppressed growth (previously reported) relative to the heavier OS1 nestlings with more active thyroid glands. Thyroid gland activity was more influenced by the chicks' accumulation of (muscle), than exposure (feces) to naphthalene, C2-naphthalenes, and C1-fluorenes. Of four major volatile organic contaminants, sulfur dioxide (SO2) primarily influenced thyroid gland activity and structure, supporting previous findings with captive birds. When collectively considering environmental-thyroidal stressors, chicks had a greater thyroidal response when they experienced colder temperatures, accumulated more C2-naphthalenes, and consumed aquatic-emerging insects with higher PAC burdens than terrestrial insects (carbon (δ13C)). We hypothesize that the more active thyroid glands and higher circulating TT4 of the OS1 chicks supported their growth and survival despite having the highest PAC burdens, whereas the lack of thyroid response in the OS2 chicks combined with high PAC burdens, contributed to their smaller size, poorer condition and poorer survival.

A qualitative study of the feasibility and acceptability of a smoking cessation program for people living with HIV and emotional dysregulation.

Despite high rates of co-occurring tobacco use and anxiety among persons living with HIV, evidence-based interventions for these individuals are limited. An existing cognitive-behavioral treatment protocol for smoking cessation and anxiety (Norton, P. J., & Barrera, T. L. (2012). Transdiagnostic versus diagnosis-specific CBT for anxiety disorders: A preliminary randomized controlled noninferiority trial. Depression and Anxiety, 29(10), 874-882. https://doi.org/10.1002/da.21974) was modified to address transdiagnostic constructs, such as anxiety sensitivity, distress tolerance, and depressive symptomatology (Labbe, A. K., Wilner, J. G., Kosiba, J. D., Gonzalez, A., Smits, J. A., Zvolensky, M. J., … O'Cleirigh, C. (2017). Demonstration of an Integrated Treatment for Smoking Cessation and Anxiety Symptoms in People with HIV: A Clinical Case Study. Cognitive and Behavioral Practice, 24(2), 200-214. https://doi.org/10.1016/j.cbpra.2016.03.009). This study examines the feasibility and acceptability of the intervention as determined from qualitative data from structured exit interviews from 10 participants who completed treatment. Results demonstrated that participants were very motivated to quit smoking and enrolled in the program for health-related reasons and to be able to quit. Participants found nearly all the treatment components to be useful for reaching their smoking cessation goal and in managing emotional dysregulation. Last, all participants stated that they would strongly recommend the treatment program. This qualitative study provides initial evidence for the feasibility and acceptability of a modified smoking cessation treatment protocol for HIV+ individuals with anxiety and emotional dysregulation. Future research will focus on evaluating the efficacy of the protocol in a full-scale randomized controlled trial, as well as working to collect qualitative data from participants who discontinue treatment to better understand reasons for treatment attrition.

Observation of a Space-Time Crystal in a Superfluid Quantum Gas.

Time crystals are a phase of matter, for which the discrete time symmetry of the driving Hamiltonian is spontaneously broken. The breaking of discrete time symmetry has been observed in several experiments in driven spin systems. Here, we show the observation of a space-time crystal using ultracold atoms, where the periodic structure in both space and time is directly visible in the experimental images. The underlying physics in our superfluid can be described ab initio and allows for a clear identification of the mechanism that causes the spontaneous symmetry breaking. Our results pave the way for the usage of space-time crystals for the discovery of novel nonequilibrium phases of matter.

Reproductive and developmental changes in tree swallows (Tachycineta bicolor) are influenced by multiple stressors, including polycyclic aromatic compounds, in the Athabasca Oil Sands.

Mining in the Athabasca Oil Sands Region (AOSR) has contributed extensively to increased exposure of wildlife to naturally occurring polycyclic aromatic compounds (PACs), yet little is known about the toxicity of PACs to wildlife in this region. We identified reproductive and developmental changes in tree swallows (Tachycineta bicolor) breeding in close proximity to mining-related activities in the AOSR, and determined these changes in relation to the birds' exposure and accumulation of 41 PACs (parent-, alkylated-PAHs), dibenzothiophenes (DBTs; previously published), diet (carbon (δ13C), nitrogen (δ15N)), volatile organic compounds, and weather variables. Tree swallow pairs (N = 43) were compared among mining-related (OS1, OS2) and reference (REF1, REF2) sites. At OS2, clutch initiation was slightly advanced (2012) but reproductive success (65%) was much lower than at the other sites (≥ 79%). Fledgling production by each pair was influenced by the timing of clutch initiation (years combined); in a highly inclement brood rearing period (2013), additional influences included the nestlings' exposure to ΣDBTs, accumulation of C1-naphthalene, the trophic position of the prey in their diet (δ15N), and record-breaking rainfall. Nestlings at OS2 were significantly lighter at day (d) 9 and d14, and in poorer body condition (d9). Nestling body mass was influenced by multiple stressors that varied by site: mass of younger nestlings (d9) was related to dietary source (δ13C; e.g., wetlands, terrestrial fields), exposure and/or accumulation of C1-phenanthrenes, C2-fluorenes, Σalkyl-PAHs and ΣDBTs, while for older nestlings (d14), body mass was related to sex, hatch date and/or rainfall during brood rearing. The swallows' exposure and accumulation of parent-PACs, alkyl-PACs and DBTs, the timing of hatching, their diet and exposure to highly inclement rains, contributed to their reproductive and developmental changes.

Solution nuclear magnetic resonance spectroscopy on a nanostructured diamond chip.

Sensors using nitrogen-vacancy centers in diamond are a promising tool for small-volume nuclear magnetic resonance (NMR) spectroscopy, but the limited sensitivity remains a challenge. Here we show nearly two orders of magnitude improvement in concentration sensitivity over previous nitrogen-vacancy and picoliter NMR studies. We demonstrate NMR spectroscopy of picoliter-volume solutions using a nanostructured diamond chip with dense, high-aspect-ratio nanogratings, enhancing the surface area by 15 times. The nanograting sidewalls are doped with nitrogen-vacancies located a few nanometers from the diamond surface to detect the NMR spectrum of roughly 1 pl of fluid lying within adjacent nanograting grooves. We perform 1H and 19F nuclear magnetic resonance spectroscopy at room temperature in magnetic fields below 50 mT. Using a solution of CsF in glycerol, we determine that 4 ± 2 × 1012 19F spins in a 1 pl volume can be detected with a signal-to-noise ratio of 3 in 1 s of integration.Nitrogen vacancy (NV) centres in diamond can be used for NMR spectroscopy, but increased sensitivity is needed to avoid long measurement times. Kehayias et al. present a nanostructured diamond grating with a high density of NV centres, enabling NMR spectroscopy of picoliter-volume solutions.

Introduction of the lung allocation score in Germany.

The aim of this study was to assess performance of the new lung allocation system in Germany based on lung allocation score (LAS). Retrospective analysis of waitlist (WL) outflow, lung transplantation (LTx) activity and 3-month outcomes comparing 1-year pre- and post-LAS introduction on December 10, 2011 was performed. Following LAS introduction, WL registrations remained constant, while WL mortality fell by 23% (p = 0.04). Reductions in WL mortality occurred in patients with cystic fibrosis (CF; -52%), emphysema (chronic obstructive pulmonary disease [COPD]; -49%) and pulmonary hypertension (PH; -67%), but not idiopathic pulmonary fibrosis (IPF; +48%). LTx activity increased by 9% (p = 0.146). Compared to pre-LAS, more patients with IPF (32% vs. 29%) and CF (20% vs. 18%) underwent transplantation and comparatively fewer with COPD (30% vs. 39%). Median LAS among transplant recipients was highest in PH (53) and IPF (49) and lowest in COPD (34). Transplantation under invasive respiratory support increased to 13% (in CF 28%, +85%, p = 0.017). Three-month survival remained unchanged (pre: 96.1% and post: 94.9%, p = 0.94). Following LAS implementation in Germany, reductions in waiting list size and WL mortality were observed. Composition of transplant recipients changed, with fewer COPD and more IPF recipients. Transplantation under invasive respiratory support increased. Reductions in WL mortality were most pronounced among CF and PH patients.

Stable nitrogen isotopes of nestling tree swallows indicate exposure to different types of oil sands reclamation.

Tree swallows (Tachycineta bicolor) inhabiting reclaimed wetlands on the oil sands in northern Alberta are potentially exposed to elevated levels of oil sands constituents such as polycyclic aromatic compounds (PAC) through diet. While increased detoxification enzyme activity as measured using 7-ethoxyresorufin O-deethylase in nestlings is a generally accepted indicator of exposure to oil sands constituents, there is no apparent method to detect dietary exposure specific to oil sands processed material (OSPM). In this study, stable C and N isotopes were analyzed from muscle and feathers of nestling tree swallows (15 d old) to distinguish dietary exposure of birds near reference and OSPM wetlands. High δ¹5N and low δ¹³C values in the nestling tissues differentiated those from the OSPM wetlands and reference sites. Lower δ¹5N values of nestlings compared to the δ¹5N values of larval chironomids from an earlier study suggested that the majority of the diet of the nestlings was derived from non-OSPM sources, despite residence near and on the OSPM wetlands. Our finding of limited utilization of OSPM resources by tree swallows indicates either low abundance or diversity of dietary items emerging from OSPM wetlands, or sensory avoidance of prey from those wetlands. Minimal consumption of OSPM-derived dietary sources may be attributed to published findings of limited adverse effects on tree swallow reproduction, or growth and development for these same nestlings. This study demonstrated that stable isotope analysis, particularly for N isotopes, may serve as a useful tool to trace dietary exposure to OSPM constituents as part of avian ecotoxicology assessments of reclaimed wetlands on the oil sands.

Food web structure in oil sands reclaimed wetlands.

Boreal wetlands play an important role in global carbon balance. However, their ecosystem function is threatened by direct anthropogenic disturbance and climate change. Oil sands surface mining in the boreal regions of Western Canada denudes tracts of land of organic materials, leaves large areas in need of reclamation, and generates considerable quantities of extraction process-affected materials. Knowledge and validation of reclamation techniques that lead to self-sustaining wetlands has lagged behind development of protocols for reclaiming terrestrial systems. It is important to know whether wetlands reclaimed with oil sands process materials can be restored to levels equivalent to their original ecosystem function. We approached this question by assessing carbon flows and food web structure in naturally formed and oil sands-affected wetlands constructed in 1970-2004 in the postmining landscape. We evaluated whether a prescribed reclamation strategy, involving organic matter amendment, accelerated reclaimed wetland development, leading to wetlands that were more similar to their natural marsh counterparts than wetlands that were not supplemented with organic matter. We measured compartment standing stocks for bacterioplankton, microbial biofilm, macrophytes, detritus, and zoobenthos; concentrations of dissolved organic carbon and residual naphthenic acids; and microbial production, gas fluxes, and aquatic-terrestrial exports (i.e., aquatic insect emergence). The total biomass of several biotic compartments differed significantly between oil sands and reference wetlands. Submerged macrophyte biomass, macroinvertebrate trophic diversity, and predator biomass and richness were lower in oil sands-affected wetlands than in reference wetlands. There was insufficient evidence to conclude that wetland age and wetland amendment with peat-mineral mix mitigate effects of oil sands waste materials on the fully aquatic biota. Although high variability was observed within most compartments, our data show that 20-year-old wetlands containing oil sands material have not yet reached the same level of function as their reference counterparts.

Pathology of enteric infections induced by the acanthocephalan Profilicollis chasmagnathi in Olrog's gull, Larus atlanticus, from Argentina.

Acanthocephalans can be pathogenic helminths of marine birds. Every year during the breeding season, there is variable mortality among prefledged chicks from the largest known Olrog's gull (Larus atlanticus) colony. Mortality has been associated with infection by the acanthocephalan Profilicollis chasmagnathi. Our aim was to study the role of chicks' size as a risk factor for intensity of infection and severe pathology, and to expand upon previous pathological findings reported in acanthocephalan-infected chicks. Size of the chick was associated with intensity of infection and number of intestinal perforations, which increased by 6.9% and 4.1%, respectively, for each millimetre increment in chick size. Infection was associated with inflammatory enteritis and granulomatous peritonitis. Complete intestinal perforations were observed in 85% and 97.3% of the studied chicks in 2005 and 2006, respectively, and they were observed very early during the post-hatching period. Our results show: (1) the presence of advanced pathology associated with acanthocephalan infections in chicks, beginning very early in the post-hatching period; and (2) significant increases in the intensity of infection and the associated pathology as a function of size of chicks, in dead chicks during this period.

Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation.

Static cold storage (CS) is the most widely used organ preservation method for deceased donor kidney grafts but there is increasing evidence that hypothermic machine perfusion (MP) may result in better outcome after transplantation. We performed an economic evaluation of MP versus CS alongside a multicenter RCT investigating short- and long-term cost-effectiveness. Three hundred thirty-six consecutive kidney pairs were included, one of which was assigned to MP and one to CS. The economic evaluation combined the short-term results based on the empirical data from the study with a Markov model with a 10-year time horizon. Direct medical costs of hospital stay, dialysis treatment, and complications were included. Data regarding long-term survival, quality of life, and long-term costs were derived from literature. The short-term evaluation showed that MP reduced the risk of delayed graft function and graft failure at lower costs than CS. The Markov model revealed cost savings of $86,750 per life-year gained in favor of MP. The corresponding incremental cost-utility ratio was minus $496,223 per quality-adjusted life-year (QALY) gained. We conclude that life-years and QALYs can be gained while reducing costs at the same time, when kidneys are preserved by MP instead of CS.