Comparison of contrast-enhanced videofluoroscopy to unenhanced dynamic MRI in minor patients following surgical correction of velopharyngeal dysfunction.

OBJECTIVES: To compare dynamic magnetic resonance imaging (MRI) with videofluoroscopy (VFS) regarding image quality and assessment of gap size between soft palate (SP) and posterior pharyngeal wall (PPW) in children and adolescents following surgical correction of velopharyngeal dysfunction (VPD). METHODS: Twenty-one patients undergoing unenhanced 3-T MRI and contrast-enhanced VFS were included in this IRB-approved prospective study. The MRI scan protocol comprised refocused gradient-echo sequences in transverse and sagittal planes during speech, with TE 1.97 ms, TR 3.95 ms, flip angle 8°, matrix size 128 × 128, and 5-mm slice thickness. Radial k-space sampling and sliding window reconstruction were used to achieve an image acquisition rate of 28 frames per second (fps). VFS with 30 fps was similarly performed in both planes. Closure of the velopharyngeal port during phonation was evaluated by two experienced radiologists. RESULTS: Eleven (52.4%) patients displayed a complete closure, whereas ten (47.6%) patients showed a post-operative gap during speech. VFS and MRI equally identified the cases with persistent or recurrent VPD. Differences in SP-PPW distance between VFS (3.9 ± 1.6 mm) and MRI (4.1 ± 1.5 mm) were not statistically significant (p = 0.5). The subjective overall image quality of MRI was rated inferior (p < 0.001) compared with VFS, with almost perfect inter-rater agreement (κ = 0.90). The presence of susceptibility artifacts did not limit anatomical measurements. CONCLUSION: Dynamic MRI is equally reliable as VFS to assess persistent or recurrent inadequate velum closure in patients following surgical treatment of VPD. KEY POINTS: • Unenhanced 3-T dynamic MRI and contrast-enhanced videofluoroscopy are equally useful for the identification of patients with incomplete velopharyngeal closure during speech. • MRI using refocused gradient-echo acquisition with radial k-space sampling and sliding window reconstruction generates diagnostic images with 28 frames per second. • MRI can offer a radiation-free alternative to currently established videofluoroscopy for young patients.

Reducing achievement gaps in undergraduate general chemistry could lift underrepresented students into a "hyperpersistent zone".

Students from underrepresented groups start college with the same level of interest in STEM majors as their peers, but leave STEM at higher rates. We tested the hypothesis that low grades in general chemistry contribute to this "weeding," using records from 25,768 students. In the first course of a general chemistry series, grade gaps based on binary gender, race/ethnicity, socioeconomic status, and family education background ranged from 0.12 to 0.54 on a four-point scale. Gaps persisted when the analysis controlled for academic preparation, indicating that students from underrepresented groups underperformed relative to their capability. Underrepresented students were less likely than well-represented peers to persist in chemistry if they performed below a C-, but more likely to persist if they got a C or better. This "hyperpersistent zone" suggests that reducing achievement gaps could have a disproportionately large impact on efforts to achieve equity in STEM majors and professions.

Are cost advantages from a modern Indian hospital transferable to the United States?

BACKGROUND: Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals' cost advantages to US peers remains unclear. METHODS: Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH's cost savings. RESULTS: After removing non-transferable sources of efficiency, NH's residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH's high annual CABG volume facilitates such supervised work "downshifting." The study is subject to limitations inherent in case studies, does not account for the younger age of NH's patients, or capture savings attributable to NH's negligible frequency of re-admission or post-acute care facility placement. CONCLUSIONS: Most transferable bases for a modern Indian hospital's cost advantage would require more flexible American states' hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.

Genetic investigation of equine recurrent uveitis in Appaloosa horses.

Equine recurrent uveitis (ERU) is characterized by intraocular inflammation that often leads to blindness in horses. Appaloosas are more likely than any other breed to develop insidious ERU, distinguished by low-grade chronic intraocular inflammation, suggesting a genetic predisposition. Appaloosas are known for their white coat spotting patterns caused by the leopard complex spotting allele (LP) and the modifier PATN1. A marker linked to LP on ECA1 and markers near MHC on ECA20 were previously associated with increased ERU risk. This study aims to further investigate these loci and identify additional genetic risk factors. A GWAS was performed using the Illumina Equine SNP70 BeadChip in 91 horses. Additive mixed model approaches were used to correct for relatedness. Although they do not reach a strict Bonferroni genome-wide significance threshold, two SNPs on ECA1 and one SNP each on ECA12 and ECA29 were among the highest ranking SNPs and thus warranted further analysis (P = 1.20 × 10-5 , P = 5.91 × 10-6 , P = 4.91 × 10-5 , P = 6.46 × 10-5 ). In a second cohort (n = 98), only an association with the LP allele on ECA1 was replicated (P = 5.33 × 10-5 ). Modeling disease risk with LP, age and additional depigmentation factors (PATN1 genotype and extent of roaning) supports an additive role for LP and suggests an additive role for PATN1. Genotyping for LP and PATN1 may help predict ERU risk (AUC = 0.83). The functional role of LP and PATN1 in ERU development requires further investigation. Testing samples across breeds with leopard complex spotting patterns and a denser set of markers is warranted to further refine the genetic components of ERU.

[Muscular injuries in the inguinal region including apophyseal injuries]. / Muskelverletzungen der Leistenregion einschließlich apophysärer Verletzungen.

BACKGROUND: Muscular and apophyseal injuries in the inguinal region are a common cause of groin pain in athletes. PURPOSE: Frequently occurring muscular and apophyseal injuries in the groin region are described. MATERIAL AND METHODS: Fundamental studies and expert recommendations are discussed. Examination protocols for routine clinical practice are presented. RESULTS: The exact diagnosis and classification of muscular or apophyseal injuries in the inguinal region are the basic prerequisites for the initiation of a targeted treatment and thus crucial for the return to sport time. These injuries are occurring with increasing frequency in both professional and recreational sports. CONCLUSION: In addition to the clinical examination and the history of the course of the injury, MRI plays an important role in the evaluation of muscular and apophyseal injuries in the inguinal region.

Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project.

The Functional Annotation of Animal Genomes (FAANG) project aims to identify genomic regulatory elements in both sexes across multiple stages of development in domesticated animals. This study represents the first stage of the FAANG project for the horse, Equus caballus. A biobank of 80 tissue samples, two cell lines and six body fluids was created from two adult Thoroughbred mares. Ante-mortem assessments included full physical examinations, lameness, ophthalmologic and neurologic evaluations. Complete blood counts and serum biochemistries were also performed. At necropsy, in addition to tissue samples, aliquots of serum, ethylenediaminetetraacetic acid (EDTA) plasma, heparinized plasma, cerebrospinal fluid, synovial fluid, urine and microbiome samples from all regions of the gastrointestinal and urogenital tracts were collected. Epidermal keratinocytes and dermal fibroblasts were cultured from skin samples. All tissues were grossly and histologically evaluated by a board-certified veterinary pathologist. The results of the clinical and pathological evaluations identified subclinical eosinophilic and lymphocytic infiltration throughout the length of the gastrointestinal tract as well as a mild clinical lameness in both animals. Each sample was cryo-preserved in multiple ways, and nuclei were extracted from selected tissues. These samples represent the first published systemically healthy equine-specific biobank with extensive clinical phenotyping ante- and post-mortem. The tissues in the biobank are intended for community-wide use in the functional annotation of the equine genome. The use of the biobank will improve the quality of the reference annotation and allow all equine researchers to elucidate unknown genomic and epigenomic causes of disease.

Expression of cutaneous immunity markers during infant skin maturation.

BACKGROUND/OBJECTIVES: Infant skin undergoes a maturation process during the early years of life. Little is known about the skin's innate immunity. We investigated the dynamics of innate immunity markers collected from the surface of infant skin during the first 36 months of life. METHODS: A total of 117 healthy infants aged 3-36 months participated in the study. We extracted human beta defensin-1 and interleukin 1 alpha and its receptor antagonist using transdermal analysis patches from the skin surface of the posterior lower leg area. The extracts were analyzed using a spot enzyme-linked immunosorbent assay. RESULTS: Skin surface human beta defensin-1 levels were higher early in life and decreased with infant age. The ratio of interleukin 1 alpha receptor antagonist to interleukin 1 alpha did not change significantly with age but showed a distinct difference between sexes, with female infants having higher values than male infants. CONCLUSION: As is the case with skin structure and functional properties, cutaneous innate immunity also appears to undergo a maturation period during infancy, with innate immunity slowly declining as adaptive immunity takes over. Sex differences in immune markers may explain sex-dependent susceptibilities to infection.

[Insertional Achilles tendinopathy : Differentiated diagnostics and therapy]. / Ansatznahe Erkrankungen der Achillessehne : Differenzierte Diagnostik und Therapie.

Achilles tendinopathy at the calcaneal insertion is classified into insertional tendinopathy, retrocalcaneal and superficial bursitis. The aim of this study was to present the current evidence on conservative and surgical treatment of insertional tendinopathy of the Achilles tendon. Conservative first-line therapy includes reduction of activity levels, administration of non-steroidal anti-inflammatory drugs (NSAID), adaptation of footwear, heel wedges and orthoses or immobilization. In addition, further conservative therapy options are also available. Eccentric stretching exercises should be integral components of physiotherapy and can achieve a 40% reduction in pain. Extracorporeal shock wave therapy has been shown to reduce pain by 60% with a patient satisfaction of 80%. Due to the limited evidence, injections with platelet-rich plasma (PRP), dextrose (prolotherapy) or polidocanol (sclerotherapy) cannot currently be recommended. Operative therapy is indicated after 6 months of unsuccessful conservative therapy. Open debridement allows all pathologies to be addressed, including osseous abnormalities and intratendinous necrosis. The success rate of over 70% is contrasted by complication rates of up to 40%. The Achilles tendon should be reattached, if detached by >50%. No valid data are available for the transfer of the tendon of the flexor hallucis longus (FHL) muscle but it is frequently applied in cases of more than 50% debridement of the diameter of the Achilles tendon. Lengthening of the gastrocnemius muscle cannot be recommended because insufficient data are available. Tendoscopy is a promising treatment option for isolated retrocalcaneal bursitis and has shown similar success rates to open debridement with significantly lower complication rates.

Centennial-scale reductions in nitrogen availability in temperate forests of the United States.

Forests cover 30% of the terrestrial Earth surface and are a major component of the global carbon (C) cycle. Humans have doubled the amount of global reactive nitrogen (N), increasing deposition of N onto forests worldwide. However, other global changes-especially climate change and elevated atmospheric carbon dioxide concentrations-are increasing demand for N, the element limiting primary productivity in temperate forests, which could be reducing N availability. To determine the long-term, integrated effects of global changes on forest N cycling, we measured stable N isotopes in wood, a proxy for N supply relative to demand, on large spatial and temporal scales across the continental U.S.A. Here, we show that forest N availability has generally declined across much of the U.S. since at least 1850 C.E. with cool, wet forests demonstrating the greatest declines. Across sites, recent trajectories of N availability were independent of recent atmospheric N deposition rates, implying a minor role for modern N deposition on the trajectory of N status of North American forests. Our results demonstrate that current trends of global changes are likely to be consistent with forest oligotrophication into the foreseeable future, further constraining forest C fixation and potentially storage.

Further development of an in vitro model for studying the penetration of chemicals through compromised skin.

A new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired.

Hard water softening effect of a baby cleanser.

BACKGROUND: Hard water is associated with atopic dermatitis (eczema). We wanted to determine if a baby cleanser and its individual components altered free ionized calcium (Ca2+) in a simulated hard water baby bath. For these studies, an in vitro determination of free Ca2+ in a simulated hard water baby bath, and an in vivo exploratory study of free Ca2+ absorption into skin from hard water were performed. METHODS: Free Ca2+ was measured with an ion-sensitive electrode in vitro in hard water (100-500 ppm, Ca2+) before and after addition of the cleanser and/or its components. In an exploratory study, absorption of Ca2+ into skin from hard water was determined in three female participants (aged 21-29 years). RESULTS: At an in-use dilution of 1%, the test cleanser reduced free Ca2+ from ~500 ppm to <200 ppm; a 10% in-use dilution bound virtually all free Ca2+. The anionic surfactant component contributed the most to this effect. In the exploratory in vivo study, we measured a reduction of ~15% in free Ca2+ from simulated hard water over 10 minutes. CONCLUSION: Baby cleansers can bind free Ca2+ and reduce the effective water hardness of bath water. Reducing the amount of free Ca2+ in the water will reduce the availability of the ion for binding to the skin. Altering or reducing free Ca2+ concentrations in bath water may be an important parameter in creating the ideal baby bath.

Minimally invasive screw fixation of fractures in the thoracic spine: CT-controlled pre-surgical guidewire implantation in routine clinical practice.

AIM: To evaluate the feasibility and accuracy of minimally invasive, transpedicular screw placement in cervicothoracic fractures with the help of computed tomography (CT)-controlled guidewires. MATERIALS AND METHODS: Two hundred and ninety-three guidewires were inserted in 35 patients (42.9±21.2 years) under CT fluoroscopy (286 thoracic, seven cervical). There were 28 traumatic cases, three pathological fractures, three fractures due to infectious infiltrations, and one osteoporotic fracture. In 151 pedicles, screw placement was performed in the CT room. CT images were reviewed regarding accuracy and cortical violations using the popular 2 mm increment deviation classification of Gertzbein and Robbins. RESULTS: Guidewire implantation resulted in only 28 cortical contacts. Minor encroachments of the pedicle wall by inserted screws occurred in 39.1% (59 of 151) and in 23.8% if taking unavoidable encroachments into account (30 of 59). Pedicular isthmus width correlated to cortical guidewire contacts (r=-0.449; p=0.077) and pedicle violations (all graded "A") by the inserted screws (r=-0.581; p=0.049). Total procedural duration was 138.6±44.2 minutes, representing 14.5±11.6 minutes for each pedicle, while showing a significant correlation against higher vertebral levels (r=-0.849; p=0.0002) and the occurrence of pedicle violations (r=-0.641; p=0.027). CONCLUSIONS: The treatment of vertebral fractures with a guidewire-based pedicle screw insertion technique under CT imaging results in very high accuracy and a low complication rate.

Developmental Changes in Skin Barrier and Structure during the First 5 Years of Life.

The structure of the stratum corneum (SC) and the corresponding skin barrier develops from before birth up to about 4 years of age. Large subject-to-subject variability within an age group requires a large population to observe trends in skin barrier properties over time. Barrier function, quantified by transepidermal water loss (TEWL) and SC thickness, was measured on the upper inner arm and dorsal forearm in subjects aged 3 months to 4 years (n = 171) and a subset of mothers (n = 44). The rate of skin surface area expansion as a function of age peaked before birth (∼90 cm2/week) and declined to a steady plateau (∼10 cm2/week) by 1 year of age. SC thickness increased and TEWL decreased, but did not reach adult values until 3-4 years of age. A better understanding of how skin hydration changes after birth suggests that barrier function may be related mechanistically to skin surface area expansion.

Basophils Trigger Fibroblast Activation in Cardiac Allograft Fibrosis Development.

Fibrosis is a major component of chronic cardiac allograft rejection. Although several cell types are able to produce collagen, resident (donor-derived) fibroblasts are mainly responsible for excessive production of extracellular matrix proteins. It is currently unclear which cells regulate production of connective tissue elements in allograft fibrosis and how basophils, as potential producers of profibrotic cytokines, are involved this process. We studied this question in a fully MHC-mismatched model of heart transplantation with transient depletion of CD4(+) T cells to largely prevent acute rejection. The model is characterized by myocardial infiltration of leukocytes and development of interstitial fibrosis and allograft vasculopathy. Using depletion of basophils, IL-4-deficient recipients and IL-4 receptor-deficient grafts, we showed that basophils and IL-4 play crucial roles in activation of fibroblasts and development of fibrotic organ remodeling. In the absence of CD4(+) T cells, basophils are the predominant source of IL-4 in the graft and contribute to expansion of myofibroblasts, interstitial deposition of collagen and development of allograft vasculopathy. Our results indicated that basophils trigger the production of various connective tissue elements by myofibroblasts. Basophil-derived IL-4 may be an attractive target for treatment of chronic allograft rejection.

T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis.

The transcription factor T-bet is highly expressed by Th cells isolated from the inflamed intestine of Crohn's disease patients, and has been regarded a critical driver of murine T cell-induced colitis. However, we show here that T-bet expression by Th cells is not required for the manifestation of T-cell-induced colitis in the presence of segmented filamentous bacteria and Helicobacter hepaticus. T-bet expression by Th cells controls their survival and localization, their repertoire of chemokine and chemokine receptor expression, the accumulation of monocytes and macrophages in the inflamed colon, and their differentiation to the M1 type, i.e., type 1 inflammation. Nevertheless, T-bet-deficient Th cells efficiently induce colitis, as reflected by weight loss, diarrhea, and colon histopathology. T-bet-deficient Th cells differentiate into Th1/17 cells, able to express IFN-γ and IL-17A upon restimulation. While neutralization of IL-17A exacerbated colitis induced by wild-type or T-bet-deficient Th cells, neutralization of IFN-γ completely abolished colitis.

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

Recovery of arctic tundra from thermal erosion disturbance is constrained by nutrient accumulation: a modeling analysis.

Abstract. We calibrated the Multiple Element Limitation (MEL) model to Alaskan arctic tundra to simulate recovery of thermal erosion features (TEFs) caused by permafrost thaw and mass wasting. TEFs could significantly alter regional carbon (C) and nutrient budgets because permafrost soils contain large stocks of soil organic matter (SOM) and TEFs are expected to become more frequent as the climate warms. We simulated recovery following TEF stabilization and did not address initial, short-term losses of C and nutrients during TEF formation. To capture the variability among and within TEFs, we modeled a range of post-stabilization conditions by varying the initial size of SOM stocks and nutrient supply rates. Simulations indicate that nitrogen (N) losses after the TEF stabilizes are small, but phosphorus (P) losses continue. Vegetation biomass recovered 90% of its undisturbed C, N, and P stocks in 100 years using nutrients mineralized from SOM. Because of low litter inputs but continued decomposition, younger SOM continued to be lost for 10 years after the TEF began to recover, but recovered to about 84% of its undisturbed amount in 100 years. The older recalcitrant SOM in mineral soil continued to be lost throughout the 100-year simulation. Simulations suggest that biomass recovery depended on the amount of SOM remaining after disturbance. Recovery was initially limited by the photosynthetic capacity of vegetation but became co-limited by N and P once a plant canopy developed. Biomass and SOM recovery was enhanced by increasing nutrient supplies, but the magnitude, source, and controls on these supplies are poorly understood. Faster mineralization of nutrients from SOM (e.g., by warming) enhanced vegetation recovery but delayed recovery of SOM. Taken together, these results suggest that although vegetation and surface SOM on TEFs recovered quickly (25 and 100 years, respectively), the recovery of deep, mineral soil SOM took centuries and represented a major ecosystem C loss.

Geometrical and topological analysis of in vivo confocal microscopy images reveals dynamic maturation of epidermal structures during the first years of life.

Reflectance confocal microscopy is successfully used in infant skin research. Infant skin structure, function, and composition are undergoing a maturation process. We aimed to uncover how the epidermal architecture and cellular topology change with time. Images were collected from three age groups of healthy infants between one and four years of age and adults. Cell centers were manually identified on the images at the stratum granulosum (SG) and stratum spinosum (SS) levels. Voronoi diagrams were used to calculate geometrical and topological parameters. Infant cell density is higher than that of adults and decreases with age. Projected cell area, cell perimeter, and average distance to the nearest neighbors increase with age but do so distinctly between the two layers. Structural entropy is different between the two strata, but remains constant with time. For all ages and layers, the distribution of the number of nearest neighbors is typical of a cooperator network architecture. The topological analysis provides evidence of the maturation process in infant skin. The differences between infant and adult are more pronounced in the SG than SS, while cell cooperation is evident in all cases of healthy skin examined.

Topically applied ceramide accumulates in skin glyphs.

Ceramides (CERs), structural components of the stratum corneum (SC), impart essential barrier properties to this thin outer layer of the epidermis. Variations in CER species within this layer have been linked to several skin diseases. A recent proliferation of CER-containing topical skin-care products warrants the elucidation of CER penetration profiles in both healthy and diseased skin. In the current study, the spatial distributions of CER concentration profiles, following topical application of two species of CER, were tracked using infrared imaging. Suspensions of single-chain perdeuterated sphingosine and phytosphingosine CER in oleic acid were applied, in separate experiments, to the surface of healthy intact ex vivo human skin using Franz diffusion cells. Following either a 24- or 48-hour incubation period at 34°C, infrared images were acquired from microtomed skin sections. Both CER species accumulated in glyph regions of the skin and penetrated into the SC, to a limited extent, only in these regions. The concentration profiles observed herein were independent of the CER species and incubation time utilized in the study. As a result, a very heterogeneous, sparse, spatial distribution of CERs in the SC was revealed. In contrast, oleic acid was found to be fairly homogeneously distributed throughout the SC and viable epidermis, albeit at lower concentrations in the latter. A more uniform, lateral distribution of CERs in the SC would likely be important for barrier efficacy or enhancement.

Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study.

BACKGROUND: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. METHODS: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. RESULTS: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25-0.94). CONCLUSIONS: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.