Collection Vessel Research Articles

Feasibility of Spray Drying Concentrated Acid Whey After Nanofiltration

Concentration of acid whey and crystallisation of lactose followed by spray drying in the production of acid whey powder are severely restricted by the presence of lactic acid (LA) and calcium (Ca). These compounds cause stickiness during spray drying. The present study examined the effects of removing LA and Ca by membrane processing to varying extents in order to improve the feasibility of the spray drying of an acid whey stream. Spray drying of unaltered acid whey achieved a powder recovery of ~ 18% in the collection vessel and ~ 31% in the cyclone. Removal of LA and Ca by 30 and 40%, respectively, by nanofiltration significantly increased the powder recovery to ~ 58% in the collection vessel. Powder particles decreased in size giving a D[4,3] of ~ 18 μm, with SEM images confirming the presence of well separated spherical powder particles. A solubility of > 75% was also achieved. However, removing Ca > 60% compromised the spray drying process. FTIR analysis suggested that water molecules in the hydration layer of lactose and the structural changes of both lactose and protein molecules at the molecular level appeared to play an important role in governing the extent of the drying feasibility. In addition, the formation of calcium lactate may restrict the diffusion of lactose molecules, once the appropriate stoichiometry was reached. Thus, manipulating LA and Ca concentrations in a particular acid whey stream can improve the spray drying process and production of a non-sticky acid whey powder.

Engineering Novel Lab Devices Using 3D Printing and Microcontrollers.

The application of 3D printing and microcontrollers allows users to rapidly engineer novel hardware solutions useful in a laboratory environment. 3D printing is transformative as it enables the rapid fabrication of adapters, housings, jigs, and small structural elements. Microcontrollers allow for the creation of simple, inexpensive machines that receive input from one or more sensors to trigger a mechanical or electrical output. Bringing these technologies together, we have developed custom solutions that improve capabilities and reduce costs, errors, and human intervention. In this article, we describe three devices: JetLid, TipWaster, and Remote Monitoring Device (REMIND). JetLid employs a microcontroller and presence sensor to trigger a high-speed fan that reliably de-lids microtiter plates on a high-throughput screening system. TipWaster uses a presence sensor to activate an active tip waste chute when tips are ejected from a pipetting head. REMIND is a wireless, networked lab monitoring device. In its current implementation, it monitors the liquid level of waste collection vessels or bulk liquid reagent containers. The modularity of this device makes adaptation to other sensors (temperature, humidity, light/darkness, movement, etc.) relatively simple. These three devices illustrate how 3D printing and microcontrollers have enabled the process of rapidly turning ideas into useful devices.

Technical note: A simple back-mounted harness for grazing dairy cows to facilitate the sulfur hexafluoride tracer gas technique

We describe here a cattle harness to attach a gas collection vessel to facilitate the sulfur hexafluoride (SF6) tracer gas technique. The harness consists of 2 major components: (1) a lightweight, robust body fabricated from an equine surcingle or lunge roller with padded thoracic trapezius pressure points, a bespoke shaping shaft for spine support, and adjustable buckles on both sides; and (2) an elastic flank-strap to prevent the harness from dislodging. The spine support consists of stainless steel laminated with carbon fiber. This support minimizes the contact area with the animal's skin, relieves the spine area of pressure, and creates free flow of ambient air below the platform, reducing sweat accumulation and hence preventing skin lesions. The harness weighs approximately 1.2 kg, allows for attachment of 2 gas collection vessels (animal and background sample), and is cost effective.

Characterization of Aerosol Particles Produced by a Skyscraper Demolition by Blasting

We present a study characterizing aerosol particles resulting from a skyscraper blasting. High PM10 mass concentrations with a maximum of 844.9 μg m-3 were present for a short time period of approximately 15minutes. They result in a day mean of 32.6μg m-3 compared to a 27.6μg m-3 background not exceeding the 50 μg m-3 EU maximum permissive value. The increase in particle number concentration was less pronounced with a maximum concentration of 6.9⋅104 cm-3 compared to the local background value of 1.8⋅104cm-3. The size-resolved number concentration shows a single mode of ultrafine particles at approximately 93nm. The spatial distribution of deposited dust was investigated with Bergerhoff glass collection vessels, showing a decrease with distance. In the deposited dust samples the concentrations of twelve metals was determined, non of them exceeded the regional background concentrations significantly. The chemical composition of individual particles emitted by the demolition was studied by Scanning Electron Microscopy. They were mainly concrete and steel particles, with 60% calcium carbonates, 19% calcium sulfates, 19% silicates and 2% steel. In energy-dispersive X-Ray Spectroscopy, no fibers like asbestos were observed. Using a broad spectrum of instruments and methods, we obtain comprehensive characterization of the particles emitted by the demolition.

An in-vitro urinary catheterization model that approximates clinical conditions for evaluation of innovations to prevent catheter-associated urinary tract infections

Catheter-associated urinary tract infections (CAUTI) account for approximately 25% of nosocomial infections globally, and often result in increased morbidity and healthcare costs. An additional concern is the presence of microbial biofilms which are major reservoirs of bacteria, especially antibiotic-resistant bacteria, in catheters. Since introduction of the use of closed drainage systems, innovations to combat CAUTI have not led to significant improvements in clinical outcomes. The lack of a robust laboratory platform to test new CAUTI preventive strategies may impede development of novel technologies. To establish an in-vitro catheterization model (IVCM) for testing of technological innovations to prevent CAUTI. The IVCM consists of a continuous supply of urine medium flowing into a receptacle (bladder) where the urine is drained through a urinary catheter connected to an effluent collection vessel (drainage bag). Test organism(s) can be introduced conveniently into the bladder via a rubber septa port. Development of bacteriuria and microbial biofilm on the catheter can be determined subsequently. With an initial inoculum of Escherichia coli [∼5×105colony-forming units (cfu)/mL] into the bladder, a 100% silicone catheter and a commercially available silver-hydrogel catheter showed heavy biofilm colonization (∼108cfu/cm and ∼107cfu/cm, respectively) with similar bacterial populations in the urine (bacteriuria) (∼108cfu/mL and ∼107cfu/mL, respectively) within three days. Interestingly, an antimicrobial peptide (CP11-6A)-coated catheter showed negligible biofilm colonization and no detectable bacteriuria. The IVCM is a useful preclinical approach to evaluate new strategies for the prevention of CAUTI.

Topical tacrolimus for the treatment of secondary lymphedema

Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema. This intervention markedly decreases swelling, T-cell infiltration and tissue fibrosis while significantly increasing formation of lymphatic collaterals with minimal systemic absorption. Animals treated with tacrolimus have markedly improved lymphatic function with increased collecting vessel contraction frequency and decreased dermal backflow. These results have profound implications for lymphedema treatment as topical tacrolimus is FDA-approved for other chronic skin conditions and has an established record of safety and tolerability.

Helium liquefaction using a two stage Gifford McMahon Cryocooler

This paper describes helium liquefaction using a commercial cryocooler with 1.5 W cooling power at 4.2 K, equipped with heat exchangers for pre-cooling the incoming gas. No external cooling of helium gas or Joule-Thomson stages have been utilized. In this typical liquefaction system, helium gas at room temperature is initially pre-cooled by the cooling power available at the first stage of the cryocooler. Thereafter, it is cooled by the special heat exchanger (with large surface area) mounted on the second stage of the cryocooler. The gas when passing over the cold surface areas, gets condensed into a liquid and this enters the collecting vessel which is also mounted on the second stage of the cryocooler. A pressure gauge is connected to the collection vessel through a long narrow stainless pipe to monitor the vapour pressure of the liquid. When the liquid touches the end of this stainless steel pipe, thermoacoustic oscillations are observed on the pressure gauge, which is used for monitoring helium liquefaction. This paper describes the experimental setup and studies of liquefaction of helium by the cryocooler.

T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions

T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged Tcell migration through afferent LVs invivo. Tcells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic Tcell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. Invitro, blockade of endothelial cell-expressed ICAM-1 reduced Tcell adhesion, crawling, and transmigration across lymphatic endothelium and decreased Tcell advancement from capillaries into lymphatic collectors in skin explants. Invivo, Tcell migration to draining lymph nodes was significantly reduced upon ICAM-1 or LFA-1 blockade. Our findings indicate that Tcell migration through LVs occurs in distinct steps and reveal a key role for ICAM-1/LFA-1 interactions in this process.

Efficiency Evaluation of Urine Collection Vessels with Impeded Urine Adulteration/Substance of Abuse (SOA) Rapid Detection Test Strips

Laboratory testing for drugs of abuse has become standard practice in many settings both forensic and clinical. Sending the specimen to any laboratory is waste of time and sometimes the rapid urine testing is a target. A limitation inherent in all urine drug testing is the possibility of sample adulteration or substitution. The aim of the current study is to prove the validity by deeply investigated procedures for urine collection vessels with impeded urine adulteration/substance of abuse (SOA) Test Strips (two types of investigated kits) and evaluation of their total turnaround time and efficacy for cannabinoids, opiates, benzodiazepines, tramadol and amphetamines in-comparison with immunoassay screening and GC-MS confirmatory procedures. Both Investigated Kits have the capability of detecting variable procedures of adulteration by a high efficiency degree. Therefore, SOA tests with rapid releasing results can improve patient management protocol with few percentage of pseudo-positivity/negativity results, unfortunately the operators immediate start the clinical action and realize the limitations of the test and wait for follow-up confirmation testing as appropriate before definitive medico-legal action.

Production of nanostructured molecular liquids by supercritical CO2 processing

Stable molecular clusters of ibuprofen and naproxen were prepared in dry ice, by supersonic jet expansion of their supercritical CO2 drug formulations into a liquid nitrogen cooled collection vessel, with up to 80% yield. Mixing the “dry ice” in water, resulted in the solubilization of the clusters and in the case of ibuprofen, we were able to create solutions, with concentrations of up to 6mg/ml, a 300-fold increase over previously reported values. Drop casting and ambient drying of these solutions on silicon substrate resulted in a stable, viscous liquid film, referred to as nanostructured molecular liquids. These liquids exhibited a highly aligned, fine (self-assembled) super lattice features. In vitro cancer cell viability studies of these formulations exhibited similar cytotoxicity to that of the original raw materials, thus retaining their original potency. Besides its scientific importance, this invention is expected to open up new drug delivery platforms.

Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell-rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs.

Accuracy of contrast-enhanced ultrasound compared with conventional ultrasound in acute pancreatitis: Diagnosis and complication monitoring.

Contrast-enhanced ultrasound (CEUS) has been used for diagnosing acute pancreatitis (AP), particularly severe acute pancreatitis (SAP). However, the diagnostic difference between CEUS and conventional ultrasonography (CUS) for AP and SAP has not been reported. The aim of the present study was to investigate the diagnostic accuracy of CUS and CEUS for AP. A total of 196 patients clinically diagnosed with AP were selected. All patients underwent CUS, CEUS and contrast-enhanced computed tomography (CECT) within 72 h. CECT was considered the gold standard. Pancreatic size, peripancreatic fluid collection (PPFC) and splenic vessel complications were the variables observed by CUS and CEUS. The differences in the variables among the three methods were analyzed using the χ2 test and statistical analysis software. Significant differences in pancreatic size, PPFC and splenic vessel complications in AP were observed between CEUS and CUS (P<0.05). χ2 test results indicated that CEUS significantly differed from CUS in terms of having a higher diagnostic accuracy for AP and SAP (P<0.05). The results indicate that CEUS is a reliable method for the diagnosis and monitoring of AP and SAP, and may be substituted for CECT.

VacuSIP, an Improved InEx Method for In Situ Measurement of Particulate and Dissolved Compounds Processed by Active Suspension Feeders.

Benthic suspension feeders play essential roles in the functioning of marine ecosystems. By filtering large volumes of water, removing plankton and detritus, and excreting particulate and dissolved compounds, they serve as important agents for benthic-pelagic coupling. Accurately measuring the compounds removed and excreted by suspension feeders (such as sponges, ascidians, polychaetes, bivalves) is crucial for the study of their physiology, metabolism, and feeding ecology, and is fundamental to determine the ecological relevance of the nutrient fluxes mediated by these organisms. However, the assessment of the rate by which suspension feeders process particulate and dissolved compounds in nature is restricted by the limitations of the currently available methodologies. Our goal was to develop a simple, reliable, and non-intrusive method that would allow clean and controlled water sampling from a specific point, such as the excurrent aperture of benthic suspension feeders, in situ. Our method allows simultaneous sampling of inhaled and exhaled water of the studied organism by using minute tubes installed on a custom-built manipulator device and carefully positioned inside the exhalant orifice of the sampled organism. Piercing a septum on the collecting vessel with a syringe needle attached to the distal end of each tube allows the external pressure to slowly force the sampled water into the vessel through the sampling tube. The slow and controlled sampling rate allows integrating the inherent patchiness in the water while ensuring contamination free sampling. We provide recommendations for the most suitable filtering devices, collection vessel, and storing procedures for the analyses of different particulate and dissolved compounds. The VacuSIP system offers a reliable method for the quantification of undisturbed suspension feeder metabolism in natural conditions that is cheap and easy to learn and apply to assess the physiology and functional role of filter feeders in different ecosystems.

Sigma Receptor Agonism by Afobazole Attenuates Lymphatic Pumping in Juvenile Rat Mesenteric Collecting Vessels

The mechanisms that govern tone and phasic contractions of collecting lymphatics are known to involve transient increases in intracellular free Ca2+ but are still poorly understood. The role of sigma (σ) receptors, chaperone proteins recently identified to modulate intracellular free Ca2+ has not been previously explored. We studied mesenteric collecting lymphatics isolated from 5–9 week old male Sprague Dawley rats, investigating whether: 1) sigma receptors, are expressed in lymphatic collecting vessels; and 2) Afobazole modulates tone and pumping. Lymphatics were mounted onto resistance‐matched glass micropipettes, in a 37°C albumin physiological salt solution (APSS) bath with 1–2 cm H2O luminal pressure. Concentrations of 50, 100 and 150 μM Afobazole were assessed. Video recordings were used to obtain contraction frequency (CF), end diastolic diameter (EDD), end systolic diameter (ESD), phasic contraction amplitude (AMP), tone, and ejection fraction (EF). Ca2+‐free APSS was used to obtain the maximal passive diameter (MaxD) used to normalize EDD, ESD and AMP. Expression of the sigma 1 (σ1) receptor in lymphatics was verified by q‐PCR and western blot. Afobazole (50–150 μM) decreased CF, AMP/MaxD, tone and EF, and increased ESD/MaxD compared to baseline. A 15‐min pre‐treatment with either BD 1047 dihydrobromide or BD 1063 dihydrochloride, both σ1 receptor antagonists, blocked the effects produced by 50 and 100 μM Afobazole. Similar pre‐treatment with SM‐21, a specific antagonist of the σ2 receptor, did not block the responses to Afobazole (50–100 μM). Lastly, using multi‐photon laser‐scanning microscopy, the σ1 receptor was detected in lymphatic collecting vessels, closely associated with the endothelium. This study shows, for the first time, that agonists of the σ1 receptor can negatively modulate juvenile mesenteric lymphatic vessel contractile function.Support or Funding InformationSupported by NIH grant L40HL097863

Enrichment of the Glycyrrhizic Acid from Licorice Roots (Glycyrrhiza glabra L.) by Isoelectric Focused Adsorptive Bubble Chromatography.

The main aim of this study was to enrich glycyrrhizic acid ammonium salt known as one of the main compounds of licorice roots (Glycyrrhiza glabra L.) by isoelectric focused adsorptive bubble separation technique with different foaming agents. In the experiments, four bubble separation parameters were used with β-lactoglobulin, albumin bovine, and starch (soluble) preferred as foaming agents and without additives. The enrichment of glycyrrhizic acid ammonium salt into the foam was influenced by different additive substances. The results showed that highest enrichment values were obtained from β-lactoglobulin as much as 368.3 times. The lowest enrichment values (5.9 times) were determined for the application without additive. After enrichment, each experiment of glycyrrhizic acid ammonium salt confirmed that these substances could be quantitatively enriched into the collection vessel with isoelectric focused adsorptive bubble separation technique. The transfer of glycyrrhizic acid ammonium salt into the foam from standard solution in the presence of additive was more efficient than aqueous licorice extract.

Effect of Tween-20 on Core Biomarkers Measured in Cerebrospinal Fluid from Patients with Alzheimer's Disease, Mild Cognitive Impairment, or Healthy Control Individuals.

There is substantial variation caused by preanalytical procedures in the measurement of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) reported in the literature. Determine whether the detergent Tween-20 improves diagnostic accuracy. CSF proteins (Aβ42, Aβ40, total tau, and phosphorylated tau) were measured by standard ELISA, in uncentrifuged CSF with or without 0.05% Tween-20 from patients with AD or amnestic mild cognitive impairment, and healthy elderly controls. In the main study, collection tubes containing Tween-20 (Sarstedt 15 mL) were filled with 5 mL CSF to ensure consistent detergent concentration across subsequent aliquots into Corning 2 mL tubes. These latter were also the primary collection vessel for samples without Tween-20. The effect of centrifugation, and extra tube transfer of samples with Tween-20 were also examined. 0.05% Tween-20 significantly increased mean measured CSF concentration of Aβ42 (30% ), Aβ40 (23% ), and total tau (4% ), but not phosphorylated tau. Generally, these increases were similar in all groups, although for Aβ42, the mean percentage increase with Tween-20 was slightly larger for AD. Areas under receiver-operator characteristic curves were similar whether Tween-20 was present or not. Centrifuged CSF without Tween-20 significantly reduced the measured concentration of Aβ42 versus non-centrifuged samples, a difference not seen when detergent was added. Similar CSF Aβ42 levels were found whether Tween-20 was added at collection in an extra tube or directly to the main collection tube. Addition of Tween-20 to CSF did not improve differentiation of patients from controls.

Adipose-derived stem cell transplantation for therapeutic lymphangiogenesis in a mouse secondary lymphedema model.

Secondary lymphedema is observed in common after postmalignancy treatment of the breast and the gynecologic organs but effective therapies are not established. Adipose-derived stem cells (ADSCs), which are pluripotent, regenerative in local injection, are tested for murine hindlimb secondary lymphedema by regenerative method. Mice were divided into four groups: no ADSCs, 1 × 10(6) ADSCs, 1 × 10(5) ADSCs and 1 × 10(4) ADSCs (each group, n = 20) in a stringent surgical resection and irradiation. Circumferential measurement, lymphatic flow assessment and quantification of lymphatic vessels were performed. The numbers of lymphatic vessels by LYVE-1 immunohistochemistry, and VEGF-C- or VEGFR3-expressing cells were significantly increased in transplanted groups (p < 0.05). ADSCs can restore the lymphatic vascular network in secondary lymphedema with increased collecting vessels.

Production of theophylline nanoparticles using rapid expansion of supercritical solutions with a solid cosolvent (RESS-SC) technique

We report on the production of theophylline nanoparticles by rapid expansion of supercritical solutions with a solid cosolvent (RESS-SC) using CO2 with l-menthol or vanillin. The effects of particle collection conditions such as collection temperatures and spray distances on the theophylline nanoparticles produced were investigated in order to elucidate crystal growth mechanism of the present RESS-SC process. A liquid phase appeared at a pre-expansion section in the case of using l-menthol, and this suggests that it is unsuitable for a solid cosolvent in the present conditions. In the case of using vanillin, nano-sized particles of around 85nm, which are about one-third as large as those produced by the conventional RESS technique, were obtained. Particle collection conditions have negligible effects on the particle sizes. This result suggests that crystal growth of theophylline particles crystallized in a collection vessel are blocked by crystallized vanillin particles those surrounds theophylline particles.

A new instrument to measure plot-scale runoff

Abstract. Accurate measurement of the amount and timing of surface runoff at multiple scales is needed to understand fundamental hydrological processes. At the plot scale (i.e., length scales on the order of 1–10 m) current methods for direct measurement of runoff either store the water in a collection vessel, which is not conducive to long-term monitoring studies, or utilize expensive installations such as large-scale tipping buckets or flume/weir systems. We developed an alternative low-cost, robust and reliable instrument to measure runoff that we call the "Upwelling Bernoulli Tube" (UBeTube). The UBeTube instrument is a pipe with a slot machined in its side that is installed vertically at the base of a runoff collection system. The flow rate through the slot is inferred by measuring the water height within the pipe. The geometry of the slot can be modified to suit the range of flow rates expected for a given site; we demonstrate a slot geometry that is capable of measuring flow rates across more than 3 orders of magnitude (up to 300 L min−1) while requiring only 30 cm of hydraulic head. System accuracy is dependent on both the geometry of the slot and the accuracy of the water level measurements. Using a pressure sensor with ±7 mm accuracy, the mean theoretical error for the demonstrated slot geometry was ~17% (ranging from errors of more than 50% at low flow rates to less than 2% at high flow rates), while the observed error during validation was 1–25%. A simple correction factor reduced this mean error to 0–14%, and further reductions in error could be achieved through the use of taller, narrower slot dimensions (which requires greater head gradients to drive flow) or through more accurate water level measurements. The UBeTube device has been successfully employed in a long-term rainfall-runoff study, demonstrating the ability of the instrument to measure surface runoff across a range of flows and conditions.

A first catch, non-DRE urine exosome gene signature to predict Gleason 7 prostate cancer on an initial prostate needle biopsy.

45 Background: There is a critical need to reduce initial prostate biopsies (PB) in the PSA ‘gray zone’ of 2-10 ng/mL. Non-invasive screening tools that add predictive value for identifying high-grade, Gleason score (GS) ≥7 should impact on the current diagnostic paradigm. We have developed standardized processes to isolate exosomal-RNA from first-catch urine specimens and sought to identify a gene signature that reliably differentiates GS7+ from GS6 and benign disease. Methods: First-catch non-DRE urine specimens were collected at six sites in standard collection vessels without preservative, stored at 2-8C (up to two weeks) and shipped on ice to a central laboratory (Exosome Diagnostics, St. Paul, MN). Upon receipt, samples were filtered (0.8um), and exosome isolation and RNA extraction performed. RT-qPCR RNA copy numbers of ERG and PCA3, normalized to SPDEF, were measured to generate a three-gene signature, defined to yield a score S between 0 and 30, where S&gt;10 predicts GS7+ vs. GS6 and benign lesions with optimal NPV, Sensitivity and Specificity. Results: Urine samples from 170 men (PSA 2-10 ng/mL, first biopsy,40 mL; median age 62 years, median PSA 5.1 ng/mL, 70% negative DRE, 77%, no family history, 82% Caucasian) of 453 total, with comparable demographics, were evaluated. With 46% and 21% prevalence of positive biopsy for any cancer or GS7+ disease, respectively, a dichotomous gene signature demonstrated good clinical performance in predicting biopsy result. For GS7+, the NPV and PPV were 98.6% and 34.7%, respectively. A continuous score alone had an AUC of 0.76 for discriminating GS7+ from GS6 and benign disease and the results were significantly better than the prostate cancer prevention trial risk calculator (PCPTRC), AUC 0.60. Conclusions: A novel, non-invasive urine exosome gene signature demonstrated independent, negative predictive value for the diagnosis of GS7+ from first biopsy patients with ‘gray zone’ serum PSA. Its use in the biopsy decision process could result in fewer prostate biopsies once validated on an expanded prospective cohort.