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International building certification systems, such as the WELL and Leadership in Energy and Environmental Design (LEED) standards, play a pivotal role in the design of healthy and sustainable buildings. While LEED adopts a holistic approach to designing healthy and sustainable buildings, the WELL standard has a strong emphasis on human health, comfort, and well-being. Although prior research has revealed inconsistent results for occupant satisfaction in office buildings with WELL certification compared to buildings without WELL certification, or are certified using another certification system (e.g., LEED), most of these comparisons tend to lack methodological rigor. This study used a statistical procedure to match and compare 1634 occupant surveys from LEED-certified buildings to 1634 surveys from WELL-certified buildings. Six important architectural and experiential parameters were matched, masking their influence on the outcome. Overall building and workspace satisfaction was high in both WELL-certified buildings (94% and 87%) and LEED-certified (73% and 71%). We found that there is a 39% higher probability of finding occupants who are more satisfied in WELL-certified buildings compared to LEED-certified buildings, indicating occupant satisfaction is higher in buildings with WELL certification. Although we were unable to pinpoint the reason for higher occupant satisfaction in WELL-certified buildings, the results consistently showed that perceived indoor environmental quality was enhanced across all parameters except for the amount of space.

Genome-wide association studies (GWAS) in long-lived human populations have led to identification of variants associated with Alzheimer's disease and cardiovascular disease, the latter being the most common cause of mortality in people worldwide. In contrast, naturally occurring cancer represents the leading cause of death in pet dogs, and specific breeds like the Golden Retriever (GR) carry up to a 65% cancer-related death rate. We hypothesized that GWAS of long-lived GRs might lead to the identification of genetic variants capable of modifying longevity within this cancer-predisposed breed. A GWAS was performed comparing GR dogs ≥ 14 years to dogs dying prior to age 12 which revealed a significant association to ERBB4, the only member of the epidermal growth factor receptor family capable of serving as both a tumor suppressor gene and an oncogene. No coding variants were identified, however, distinct haplotypes in the 5'UTR were associated with reduced lifespan in two separate populations of GR dogs. When all GR dogs were analyzed together (n = 304), the presence of haplotype 3 was associated with shorter survival (11.8 years vs. 12.8 years, p = 0.024). GRs homozygous for haplotype 3 had the shortest survival, and GRs homozygous for haplotype 1 had the longest survival (11.6 years vs. 13.5 years, p = 0.0008). Sub-analyses revealed that the difference in lifespan for GRs carrying at least 1 copy of haplotype 3 was specific to female dogs (p = 0.009), whereas survival remained significantly different in both male and female GRs homozygous for haplotype 1 or haplotype 3 (p = 0.026 and p = 0.009, respectively). Taken together, these findings implicate a potential role for ERBB4 in GR longevity and provide evidence that within-breed canine lifespan studies could serve as a mechanism to identify favorable or disease-modifying variants important to the axis of aging and cancer.

BackgroundNatural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product.MethodsStarting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach.ResultsCalculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment.ConclusionsOverall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

BackgroundHypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors.ResultsThirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV.Conclusions[18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

INTRODUCTION: The primary objective of this retrospective study was to document the normal variation of clinical mobility of the mandibular symphysis in cats and possible associations with bodyweight, age, sex, sexual status, breed and skull morphology. Secondarily, the radiographic appearance of the mandibular symphysis and possible associations with the analyzed data were evaluated. MATERIALS AND METHODS: Two hundred and sixteen cats of 15 different breeds that underwent maxillofacial, oral and dental procedures from April 2015 to December 2021 were included. Clinical mobility was evaluated under general anesthesia using a 0 to 3 scale in lateromedial (LM) and dorsoventral (DV) directions. The symphysis was radiographically classified on the occlusal radiographic view of the rostral mandibles as fused or open, and with parallel or divergent margins. RESULTS: Bodyweight ranged from 2.2 to 12.5 kg (median 4.0 kg), age from 4 months to 17 years and 4 months (median 6 years and 4 months). At the first evaluation DV symphyseal mobility was 0 in 177 cases (82%), 1 in 32 cases (14.8%) and 2 in 7 cases (3.2%), LM mobility was 0 in 61 cases (28.3%), 1 in 110 cases (50.9%) and 2 in 45 cases (20.8%). 81.1% of the radiographs were included in the statistical analysis. Three symphyses (1.6%) were classified as fused and 190 (98.4%) as open, 129 (68.8%) having divergent margins and 61 (31.6%) parallel. One hundred and forty-eight cases (76.7%) did not show the presence of odontoclastic replacement resorption on the canine teeth (TR subgroup 1), 23 (11.9%) showed stage ≤3 lesions (TR subgroup 2) and 22 (11.4%) stage 4 lesions (TR subgroup 3). Logistic regression models exploring factors that affected DV and LM mobility were statistically significant (p

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques. We interrogated the identified polymorphism/mutation in canine Ly49 and assessed the potential impact on structure using computational modeling of three-dimensional protein structure and protein-protein docking of canine Ly49 with MHC class I (MHC-I). Bulk and single-cell RNA-sequencing analysis was performed to detect gene expression of Ly49/KLRA1 in resting and activated NK cells. Tertiary protein structure demonstrated significant structural similarity to the known murine system. Molecular docking of canine Ly49 with MHC-I was favorable, converging at a single low-energy conformation. RNA sequencing revealed expression of Ly49/KLRA1 in both resting and activated NK cells and demonstrated almost exclusive expression of the gene in the NK cluster at the single-cell level. Despite prior reports of a mutated, nonfunctional canine Ly49, our data support that the protein product is predicted to bind to MHC-I in a comparable conformation to the murine system and is expressed in canine NK cells with upregulation following activation. Taken together, these data suggest that Ly49 is capable of recognizing MHC-I and therefore regulating NK cell function in dogs.

Elevated air movement produced by fans can offset air-conditioning energy requirements by allowing temperature setpoints to be raised without compromising thermal comfort. These advantages are even greater in hot and humid climates that inherently have large and sustained indoor cooling requirements. Few studies have assessed the in-situ benefits of fans in actual buildings. We installed ceiling and desk fans into a Zero Energy office building (675 m2) in Singapore. Across an 11-week period, 35 occupants alternated between two conditions (no fan vs. fan): 24 °C setpoint with fans off, and 26.5 °C setpoint with fans on. When the temperature setpoint was raised and elevated air movement was provided, a 32% energy reduction was obtained. The energy savings accrued without any negative impacts occurring on thermal satisfaction. Overcooling caused by thermal preference to slightly warmer and warmer conditions was substantially reduced from 33 to 9%. No changes in perceived air-staleness or self-reported alertness and ability to concentrate occurred either, indicating parity across the no fan and fan conditions. Although occupants primarily relied on ceiling fans at the 26.5 °C setpoint, they were by default on at the beginning of each day, giving less incentive to use the desk fans. Our study took place in a high-performance Zero Energy building, whereby thermal dissatisfaction was already low (7%). Therefore, notable changes did not occur, but significant improvements to thermal comfort could still occur in buildings that are unable to maintain high levels of thermal satisfaction.

Published radiotherapy results for spinal nephroblastomas in dogs are limited. In this retrospective longitudinal study (1/2007-1/2022), five dogs with a median age of 2.8 years received post-operative 3D conformal, conventional fractionated radiotherapy (CFRT) with 2-4 fields (parallel-opposed with or without two hinge-angle fields), for an incompletely resected nephroblastoma. Clinical findings prior to surgery included one or more of the following: pelvic limb paresis (5), faecal incontinence (2), flaccid tail (1), non-ambulatory (2) and deep pain loss (1). All masses were located between T11 and L3 and surgically removed via hemilaminectomy. Dogs received 45-50 Gray (Gy) in 18-20 fractions, and no dogs received chemotherapy post-radiation. At analysis, all dogs were deceased, with none lost to follow-up. The median overall survival (OS) from first treatment to death of any cause was 3.4 years (1234 days; 95% CI 68 days-upper limit not reached; range: 68-3607 days). The median planning target volume was 51.3 cc, with a median PTV dose of 51.4 Gy and median D98 = 48.3 Gy. Late complications or recurrence was difficult to fully determine in this small dataset; however, some degree of ataxia persisted throughout life in all dogs. This study provides preliminary evidence that post-operative radiotherapy may result in prolonged survival times dogs with spinal nephroblastomas.

BackgroundMany dog owners alter their dog's nutritional regimen after a diagnosis of cancer. There are limited data as to specific changes made and reasons behind these changes.Hypothesis/objectivesTo collect updated and detailed data on changes made by owners to their dog's diet and supplements after a cancer diagnosis.AnimalsResponses were collected from a survey of dog owners who brought their dogs to the UC Davis Veterinary Medical Teaching Hospital's Oncology Service for the first time after a cancer diagnosis. Dogs with recurrence or presenting for a second type of cancer were excluded.MethodsEligible owners were surveyed between December 2020 and March 2022. The survey contained 62 questions regarding diet, supplement use, and treats, and how these were altered after a cancer diagnosis. Responses were matched to medical record data.ResultsOne hundred twenty-eight surveys were retained for analysis, including 120 respondents that completed the survey. In response to a cancer diagnosis, 54.8% (95% CI; 45.7%-63.8%) of owners altered diets or supplements or both. The most common informational resource for dog diets was veterinarians (53.9%). Usage of home-prepared foods significantly increased after a cancer diagnosis (P = .03). There was no significant difference in commercial diet usage before or after a diagnosis (P = .25). Joint support products were the most common supplements given both before (37.4%) and after (35.0%) diagnosis.Conclusions and clinical importanceMany dog owners alter their dog's nutritional intake after a cancer diagnosis. These owners should be provided information relating to commonly observed alterations, including home-prepared foods and supplements.

IntroductionWe previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the information to best inform treatment decisions, here we reanalyze the data and present the results in a more patient-centered format. We also provide information on patient-defined clinically relevant benefits to facilitate evaluation of available studies and guide future trial design.MethodsThe original trial enrolled participants with a limb amputation and phantom pain who were randomized to receive a 6-day continuous peripheral nerve block(s) of either ropivacaine (n=71) or saline (n=73) in a double-masked fashion. Here we calculate the percentage of each treatment group that experienced a clinically relevant improvement as defined by previous studies as well as present what the participants of our study defined as small, medium, and large analgesic improvements using the 7-point ordinal Patient Global Impression of Change scale.ResultsAmong patients who were given a 6-day ropivacaine infusion, 57% experienced at least a 2-point improvement on the 11-point numeric rating scale in their average and worst phantom pain 4 weeks postbaseline as compared with 26% (p

Daylighting standards provide an assessment method that can be used to evaluate the quality of window views. As part of this evaluation process, designers must achieve five environmental information criteria (location, time, weather, nature, and people) to obtain an excellent view. To the best of our knowledge, these criteria have not yet been verified and their scientific validity remains conjectural. In a two-stage experiment, a total of 451 persons evaluated six window view images. Using machine learning models, we found that the five criteria could provide accurate predictions for window view preferences. When one view was largely preferred over the other, the accuracy of decision tree models ranged from 83% to 90%. For smaller differences in preference, the accuracy was 67%. As ratings given to the five criteria increased, so did evaluations for psychological restoration and positive affect. Although causation was not established, the role of most environmental information criteria was important for predicting window view preferences, with nature generally outweighed the others. We recommend the use of the environmental information criteria in practice, but suggest some alterations to these standards to emphasize the importance of nature within window view design. Instead of only supporting high-quality views, nature should be promoted across all thresholds dictating view quality.

PurposeWe evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors.MethodsSixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMRmax) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. TMRmax was compared with radiotracer trapping rate (k 3), influx rate (K i), and distribution volume (V T).ResultsTumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. TMRmax was strongly correlated with the irreversible parameters (k 3 and K i) for [18F]FMISO at > 90 min and with the reversible parameter (V T) for [18F]FAZA at > 120 min.ConclusionsOur results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation between TMRmax over the 90-150 min and 120-150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement (TMRmax) is a good alternative to quantify tumor hypoxia.Supplementary informationThe online version contains supplementary material available at 10.1007/s13139-022-00780-4.

Using fans alone or in coordination with HVAC systems to cool people offers several significant enhancements compared to conventional HVAC systems, including improved thermal comfort, indoor air quality, air distribution, energy savings, and initial cost savings.Despite the numerous benefits of fans and fan-integrated systems, comprehensive resources are unavailable to guide engineers and architects in designing and implementing such systems. The purpose of this guideline is to address this gap and provide practitioners with valuable materials and answers to common questions.What are the available fan options?Various fan types are available in the market, such as ceiling fans, desk fans, and pedestal fans. This guideline provides a comprehensive overview of the criteria for fan type selection. These criteria cover blade characteristics, fan size, airflow patterns, fan performance metrics, motors and drives, power and efficiency, and control strategies. Ceiling fans are generally preferred for their higher efficiency, control and effectiveness, but cost, flickering and fixed location are limitations. This guideline can assist users in selecting suitable fan types based on individual building characteristics and specific application needs.How to integrate fans with my existing AC system?Adequate fan choice mainly depends on design intents, space characteristics, and HVAC operation strategies. This guidebook discusses which HVAC systems can be integrated with fans. With well-defined design intent, the guidebook provides a step-by-step process for determining the number and size of fans and their layout, ensuring proper fan installation, and integrating the fans with the control of the HVAC system.How do we implement and operate fans-integrated systems?Designing a successful fans-integrated system involves more than adding fans to a building. This guidebook assists building designers and operators by helping them adjust appropriate settings in chillers, air handling units, environmental conditions, and operation strategies. This optimization maximizes energy savings while ensuring occupants' comfort within the building. Additionally, the guidelines explore HVAC systems design that can enhance air distribution effectiveness and minimize construction costs. Most importantly, the guidelines outline a transformation strategy for transitioning from conventional air conditioning to a fan-integrated system with minimal disruption to occupants. This comprehensive approach ensures a smooth and efficient integration of fans into the existing air-conditioning infrastructure.Which design tools and case studies are available?This guidebook recommends using the and the CBE Thermal Comfort Tool CBE Ceiling Fan Design Tool. These tools enable users to define the comfort zone with elevated air speed and determine the optimal arrangement of ceiling fans based on room conditions specified by the users. In addition, the guidebook highlights relevant codes and standards related to environmental conditions, fan testing procedures, fire safety, and seismic requirements (subject to variations in different countries' regulations). Furthermore, we presented several case studies of buildings successfully implementing the fan-integrated HVAC system.We released two versions of our guidebook online: the Practitioner Summary and the Full Guide. These resources support selecting, designing, constructing, operating, and implementing fans and fans integrated HVAC systems. The Practitioner Summary offers a concise overview (~15 pages) of key considerations for building practitioners, providing brief descriptions of the fan-integrated system. In contrast, the Full Guidebook provides a more comprehensive exploration (~70 pages) of the fan and fan integrated system, including real building references, catering to users from diverse backgrounds. So we expect that many readers, after studying the Practitioner Summary, will move to sections of the Full Guidebook that are relevant to their work. Fans and fans-integrated HVAC systems will result in more sustainable and healthy buildings.

INTRODUCTION: The primary objective of this retrospective study was to document the normal variation of clinical mobility of the mandibular symphysis in dogs, and evaluate possible associations with breed, bodyweight, age, sex, and skull morphology. Secondarily, the radiographic appearance of the mandibular symphysis and possible associations with the analyzed data were also evaluated. METHODS: Medical records of dogs that underwent anesthetic procedures for maxillofacial, oral and dental evaluation from April 2015 to December 2021 were included. RESULTS: 567 dogs of 95 different breeds were included, with a total of 695 evaluations. Body weight ranged from 0.8 kg to 79 kg (median 14.4 kg) and age from 3 months to 16 years and 4 months (median 6 years and 9 months). Clinical mobility was evaluated under general anesthesia using a 0 to 3 scale, in lateromedial (LM) and dorsoventral (DV) directions. The symphysis was radiographically classified as being fused or open. The open symphyses were further radiographically divided in having parallel or divergent margins. At the time of the first evaluation DV mobility was 0 in 551 cases (97.2%) and 1 in 16 cases (2.8%). LM mobility was 0 in 401 cases (70.7%), 1 in 148 cases (26.1%) and 2 in 18 cases (3.2%). There was not a significant change in mobility over time for cases examined more than once (P= 0.76). All cases had an intraoral radiographic examination. 83.8% of the radiographs were included in the statistical analysis. Two symphyses (0.4%) were classified as fused and 473 (99.6%) as open, 355 (74.7%) having divergent margins and 118 (24.8%) parallel margins. Logistic regression models exploring factors that affected DV and LM mobility were statistically significant (P < 0.0001; P < 0.0001), with an increase in LM mobility predicting an increase in DV mobility, and vice versa. An increase in age and in bodyweight was associated with a decrease in mobility. There was no statistical difference in clinical mobility across specific breeds or sexes. Increased probability of a divergent symphysis and increased DV mobility was found to be associated with a brachycephalic conformation. The increase in LM mobility was comparatively higher in small brachycephalic breeds compared with larger brachycephalic breed. DISCUSSION: The majority of the cases showed little to no mobility of the mandibular symphysis and radiographically bony fusion can be rarely seen.

OBJECTIVE: To train and validate the use of a novel artificial intelligence-based thermal imaging system as a screening tool to rule out malignancy in cutaneous and subcutaneous masses in dogs. ANIMALS: Training study: 147 client-owned dogs with 233 masses. Validation Study: 299 client-owned dogs with 525 masses. Cytology was non-diagnostic in 94 masses, resulting in 431 masses from 248 dogs with diagnostic samples. PROCEDURES: The prospective studies were conducted between June 2020 and July 2022. During the scan, each mass and its adjacent healthy tissue was heated by a high-power Light-Emitting Diode. The tissue temperature was recorded by the device and consequently analyzed using a supervised machine learning algorithm to determine whether the mass required further investigation. The first study was performed to collect data to train the algorithm. The second study validated the algorithm, as the real-time device predictions were compared to the cytology and/or biopsy results. RESULTS: The results for the validation study were that the device correctly classified 45 out of 53 malignant masses and 253 out of 378 benign masses (sensitivity = 85% and specificity = 67%). The negative predictive value of the system (i.e., percent of benign masses identified as benign) was 97%. CLINICAL RELEVANCE: The results demonstrate that this novel system could be used as a decision-support tool at the point of care, enabling clinicians to differentiate between benign lesions and those requiring further diagnostics.

For dogs with oral tumors, cervical lymph node (LN) metastasis alters treatment and prognosis. It is therefore prudent to make an accurate determination of the clinical presence (cN+ neck) or absence (cN0 neck) of metastasis prior to treatment. Currently, surgical LN extirpation with histopathology is the gold standard for a diagnosis of metastasis. Yet, recommendations to perform elective neck dissection (END) for staging are rare due to morbidity. Sentinel lymph node (SLN) mapping with indirect computed tomography lymphangiography (ICTL) followed by targeted biopsy (SLNB) is an alternative option to END. In this prospective study, SLN mapping followed by bilateral END of all mandibular LNs (MLNs) and medial retropharyngeal LNs (MRLNs) was performed in 39 dogs with spontaneously occurring oral neoplasia. A SLN was identified by ICTL in 38 (97%) dogs. Lymphatic drainage patterns were variable although most often the SLN was identified as a single ipsilateral MLN. In the 13 dogs (33%) with histopathologically confirmed LN metastasis, ICTL correctly identified the draining lymphocentrum in all (100%). Metastasis was confined to the SLN in 11 dogs (85%); 2 dogs (15%) had metastasis beyond the SLN ipsilaterally. Contrast enhanced CT features had good accuracy in predicting metastasis, with short axis measurements less than 10.5 mm most predictive. ICTL imaging features alone were unable to predict metastasis. Cytologic or histopathologic SLN sampling is recommended prior to treatment to inform clinical decision-making. This is the largest study to show potential clinical utility of minimally invasive ICTL for cervical LN evaluation in canine oral tumors.

IntroductionEarly diagnosis of cancer enhances treatment planning and improves prognosis. Many masses presenting to veterinary clinics are difficult to diagnose without using invasive, time-consuming, and costly tests. Our objective was to perform a preliminary proof-of-concept for the HT Vista device, a novel artificial intelligence-based thermal imaging system, developed and designed to differentiate benign from malignant, cutaneous and subcutaneous masses in dogs.MethodsForty-five dogs with a total of 69 masses were recruited. Each mass was clipped and heated by the HT Vista device. The heat emitted by the mass and its adjacent healthy tissue was automatically recorded using a built-in thermal camera. The thermal data from both areas were subsequently analyzed using an Artificial Intelligence algorithm. Cytology and/or biopsy results were later compared to the results obtained from the HT Vista system and used to train the algorithm. Validation was done using a "Leave One Out" cross-validation to determine the algorithm's performance.ResultsThe accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the system were 90%, 93%, 88%, 83%, and 95%, respectively for all masses.ConclusionWe propose that this novel system, with further development, could be used to provide a decision-support tool enabling clinicians to differentiate between benign lesions and those requiring additional diagnostics. Our study also provides a proof-of-concept for ongoing prospective trials for cancer diagnosis using advanced thermodynamics and machine learning procedures in companion dogs.

BackgroundCats placed on anticoagulant medication require frequent monitoring. The veterinary viscoelastic coagulation monitor (VCM-Vet) could provide a convenient and cost-effective monitoring, enabling therapeutic decision making.Hypothesis/objectivesEnoxaparin will lead to changes in VCM-Vet variables and these will correlate with antiXa activity.AnimalsTwenty-one healthy cats.MethodsCats were randomized to receive either enoxaparin (1 mg/kg) subcutaneously or 0.9% NaCl (equal volume) and crossed over with a 7-day washout period. The investigators were blinded to group allocation until data analysis. Jugular blood samples were drawn at time 0, and 2, 4, and 8 hours after injection for VCM-Vet analysis within 2 min of collection. Citrated plasma was frozen at -80°C for antiXa activity analysis. A Generalized Linear Model was completed to assess changes between baseline measurements and all time points.ResultsSignificant differences between the enoxaparin-treated cats and controls at for T0h and T2h were found and presented as mean ± SD for clotting time (enoxaparin, 593.4 ± 78.0 s; control, 448.5 ± 50.3 s, P

Daylight can reduce electric lighting in buildings. This is facilitated by sensors that relay real-time illuminance data to a light controller. When daylight provides greater than required or desired levels of illuminance, control actions enable electric lights to reduce their output and save energy. Occupant behaviours can block desk sensors and this reduces the amount of energy saved. However, no method exists that can be used to continuously monitor sensors to ensure they operate as intended (e.g. remain unblocked). We carried out a study in an open-plan office building in Singapore, consisting of 39 workstations each fitted with desk illuminance sensors independently controlling a dedicated ceiling light. Power over Ethernet was used to collect individual data signals for both illuminance and power from each workstation. Data were collected across a one month period, sampling signals at every 2-minute interval. A linear support vector machine model accurately classified 99% of the data points using our sensor blocking algorithm. From 447,455 data points analysed, 12% of dataset showed that sensors were blocked and this had an estimated energy penalty of 24%. We do not recommend installing illuminance sensors at the desk. Our study highlights the usefulness of Power over Ethernet for closed-loop daylight harvesting. The data collected can be used to monitor the health of the sensors’ performance to help minimise energy use.

PurposeAlthough recombinant human interleukin-15 (rhIL-15) has generated much excitement as an immunotherapeutic agent for cancer, activity in human clinical trials has been modest to date, in part due to the risks of toxicity with significant dose escalation. Since pulmonary metastases are a major site of distant failure in human and dog cancers, we sought to investigate inhaled rhIL-15 in dogs with naturally occurring lung metastases from osteosarcoma (OSA) or melanoma. We hypothesized a favorable benefit/risk profile given the concentrated delivery to the lungs with decreased systemic exposure.Experimental designWe performed a phase I trial of inhaled rhIL-15 in dogs with gross pulmonary metastases using a traditional 3+3 cohort design. A starting dose of 10 µg twice daily × 14 days was used based on human, non-human primate, and murine studies. Safety, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) were the primary objectives, while response rates, progression-free and overall survival (OS), and pharmacokinetic and immune correlative analyses were secondary.ResultsFrom October 2018 to December 2020, we enrolled 21 dogs with 18 dogs reaching the 28-day response assessment to be evaluable. At dose level 5 (70 μg), we observed two DLTs, thereby establishing 50 µg twice daily × 14 days as the MTD and recommended phase 2 dose. Among 18 evaluable dogs, we observed one complete response >1 year, one partial response with resolution of multiple target lesions, and five stable disease for an overall clinical benefit rate of 39%. Plasma rhIL-15 quantitation revealed detectable and sustained rhIL-15 concentrations between 1-hour and 6 hour postnebulization. Decreased pretreatment lymphocyte counts were significantly associated with clinical benefit. Cytotoxicity assays of banked peripheral blood mononuclear cells revealed significant increases in peak cytotoxicity against canine melanoma and OSA targets that correlated with OS.ConclusionsIn this first-in-dog clinical trial of inhaled rhIL-15 in dogs with advanced metastatic disease, we observed promising clinical activity when administered as a monotherapy for only 14 days. These data have significant clinical and biological implications for both dogs and humans with refractory lung metastases and support exploration of combinatorial therapies using inhaled rhIL-15.

PurposeThe purpose of this work is to evaluate the Hyperscint-RP100 scintillation dosimetry research platform (Hyperscint-RP100, Medscint Inc., Quebec, QC, Canada) designed for clinical quality assurance (QA) for use in in vivo dosimetry measurements.MethodsThe pre-clinical evaluation of the scintillator was performed using a Varian TrueBeam linear accelerator. Dependency on field size, depth, dose, dose rate, and temperature were evaluated in a water tank and compared to calibration data from commissioning and annual QA. Angularity was evaluated with a 3D printed phantom. The clinical evaluation was first performed in two cadaver dogs, and then in three companion animal dogs receiving radiation therapy for nasal tumors. A treatment planning CT scan was performed for cadavers and clinical patients. Prior to treatment, the probe was inserted into the radiation field. Radiation was then delivered and measured with the scintillator. For cadavers, the treatment was repeated after making an intentional shift in patient position to simulate a treatment error.ResultsIn the preclinical measurements the dose differed from annual measurements as follows: field size -0.77 to 0.43%, depth dose -0.36 to 1.14%, dose -0.54 to 2.93%, dose rate 0.3 to 3.6%, and angularity -1.18 to 0.01%. Temperature dependency required a correction factor of 0.11%/°C. In the two cadavers, the dose differed by -1.17 to 0.91%. The device correctly detected the treatment error when the heads were intentionally laterally shifted. In three canine clinical patients treated in multiple fractions, the detected dose ranged from 98.33 to 103.15%.ConclusionResults of this new device are promising although more work is necessary to fully validate it for clinical dosimetry.

Sex steroids regulate bone metabolism directly and indirectly through receptors on bone. Estrogen receptors (ER-∝, ER-β), progesterone receptor (PR), and androgen receptor (AR), have been previously identified on human osteosarcoma (OSA) cells, and are considered to influence tumor growth, but their expression and role in canine OSA is unknown. The aim of this study was to characterize sex hormone receptor expression levels in naturally occurring OSA tissue and in three canine OSA cell lines. The expression of ER-α, ER-β, PR, and AR was investigated using RT-PCR. PR expression levels were also quantified in OSA cells cultured under hypoxic conditions or in the presence of estradiol. The effects of progesterone on cell proliferation were quantified. Results demonstrated varying expression levels of these receptors in five OSA subtypes. OSA cell lines demonstrated high gene expression levels of PR and low gene expression levels of ER-α and ER-β and no gene expression of AR. PR expression was increased in OSA cells cultured under hypoxic conditions in a HIF-∝ independent manner. Interestingly, one cell line expressed very high levels of PR, expression of which decreased in response to estradiol. In addition, progesterone decreased OSA cell proliferation in this particular cell line. Further investigation of the role of sex steroids, particularly PR and its ligands, in regulation of canine OSA is recommended.

Client-owned cats who underwent a post-mortem examination (n = 3,108) at a veterinary medical teaching hospital between 1989 and 2019 were studied to determine longevity and factors affecting mortality. Demographic factors, environmental factors, age, and causes of death were assessed. Sexes included 5.66% intact females, 39.86% spayed females, 6.95% intact males and 47.49% neutered males. 84.2% were mixed breed cats. Age at death was known for 2,974 cases with a median of 9.07 years. Cancer was the most common pathophysiologic cause of death (35.81%) and was identified in 41.3% of cats. When categorized by organ system, mortality was most attributed to multiorgan/systemic (21.72%). Renal histologic abnormalities were noted in 62.84% of cats but was considered the primary cause of death in only 13.06% of cats. Intact female and male cats had significantly shorter lifespans than their spayed or neutered counterparts. FeLV positive status was associated with decreased longevity (P

Research on cancer in dogs and cats, among other diseases, finds an important source of information in registry data collected from hospitals. These sources have proved to be decisive in establishing incidences and identifying temporal patterns and risk factors. However, the attendance of patients is not random, so the correct delimitation of the hospital catchment area (CA) as well as the identification of the factors influencing its shape is relevant to prevent possible biases in posterior inferences. Despite this, there is a lack of data-driven approaches in veterinary epidemiology to establish CA. Therefore, our aim here was to apply a Bayesian method to estimate the CA of a hospital. We obtained cancer (n = 27,390) and visit (n = 232,014) registries of dogs and cats attending the Veterinary Medical Teaching Hospital of the University of California, Davis from 2000 to 2019 with 2,707 census tracts (CTs) of 40 neighboring counties. We ran hierarchical Bayesian models with different likelihood distributions to define CA for cancer cases and visits based on the exceedance probabilities for CT random effects, adjusting for species and period (2000-2004, 2005-2009, 2010-2014, and 2015-2019). The identified CAs of cancer cases and visits represented 75.4 and 83.1% of the records, respectively, including only 34.6 and 39.3% of the CT in the study area. The models detected variation by species (higher number of records in dogs) and period. We also found that distance to hospital and average household income were important predictors of the inclusion of a CT in the CA. Our results show that the application of this methodology is useful for obtaining data-driven CA and evaluating the factors that influence and predict data collection. Therefore, this could be useful to improve the accuracy of analysis and inferences based on registry data.

In dogs with non-resectable hepatic neoplasia, treatment options are limited. The objectives of this study were to describe the use of a novel drug-eluting embolic microsphere containing paclitaxel for use during transarterial chemoembolization (TACE), to compare results of liver-specific owner questionnaires and tumor volume pre- and post-TACE, and to measure systemic paclitaxel concentration post-TACE. Client-owned dogs with non-resectable hepatic neoplasia were prospectively enrolled. All owners completed questionnaires validated for the assessment of subjective outcomes in dogs with cancer before the TACE procedure and approximately 4 weeks after the TACE procedure. A CT scan was performed before TACE and 1 month after TACE; results were compared. Blood samples were obtained at specified time points post-TACE to determine systemic paclitaxel concentrations. Seven dogs (median weight: 8.9 kg; range, 4.3-31 kg) were enrolled. TACE was successfully performed in all dogs, and no intra-procedural complications were encountered. Questionnaire scores improved significantly post-TACE. Among the 6 dogs for which full data were available, median pre-TACE tumor volume was 390 cc (range 152-1,484; interquartile range 231-1,139) and median post-TACE tumor volume was 203 cc (range 98-889; interquartile range 151-369), which was significantly (P = .028) lower. All 6 dogs had a reduction in volume at the post-TACE measurement. Mean percent change in tumor volume was -45.6% (95%CI -58.6 to -32.6%). The mean plasma paclitaxel concentration in canine blood peaked at 4 days post-TACE procedure and was 25.7 ng/mL (range = 3.09-110 ng/mL) Median survival time was 629 days (95%CI 18 to upper limit not reached). The use of a novel paclitaxel-eluting microsphere in this cohort of dogs successfully decreased tumor volume significantly after TACE and improved clinical signs. Future investigation into the use of TACE and other similar therapies is warranted due to the promising outcomes noted in this cohort.

The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.

Urothelial carcinoma (UC), the most common urologic cancer in dogs, is often diagnosed late because the clinical signs are shared by other non-malignant lower urinary tract disorders (LUTD). The urine-based BRAFV595E test for UC is highly effective only in certain breeds; hence additional non-invasive biomarkers of UC are needed. Here, urine from dogs with UC (n = 27), urolithiasis (n = 8), or urolithiasis with urinary tract infection (UTI) (n = 8) were subjected to untargeted metabolomics analyses, using GC-TOF-MS for primary metabolites, QTOF-MS for complex lipids, and HILIC-QTOF MS for secondary and charged metabolites. After adjusting for age and sex, we identified 1123 known metabolites that were differentially expressed between UC and LUTD. Twenty-seven metabolites were significant (1.5 ≤ log2FC ≤ −1.5, adjusted p-value < 0.05); however, 10 of these could be attributed to treatment-related changes. Of the remaining 17, 6 (hippuric acid, N-Acetylphenylalanine, sarcosine, octanoylcarnitine, N-alpha-methylhistamine, glycerol-3-galactoside) discriminated between UC and LUTD (area under the ROC curve > 0.85). Of the 6 metabolites, only hippuric acid and N-alpha-methylhistamine were discriminatory in both male (n = 20) and female (n = 23) dogs, while sarcosine was an effective discriminator in several breeds, but only in females. Further investigation of these metabolites is warranted for potential use as non-invasive diagnostic biomarkers of dogs with UC that present with LUTD-related clinical signs.

This article discusses ratings of visual discomfort from glare across different buildings located in Singapore. These data were used to determine if range effects influence the vertical illuminance values for the same ratings of visual discomfort when the category rating procedure is used. The effect occurs when maxima and minima vertical illuminance (i.e. the range) vary across buildings. Our analyses showed that with a higher vertical illuminance range in a building, the mean vertical illuminance value for the same criterion of visual discomfort also increased. The results suggest that the effect caused by different ranges of measured vertical illuminance present across the buildings biased the ratings of visual discomfort. Although these effects may be unavoidable in some buildings that have vastly different levels of light, the data suggest that the overall range of vertical illuminance must be carefully evaluated when predicting visual discomfort. Matching these conditions may enable vertical illuminance to provide more reliable evaluations of discomfort due to glare.

ObjectiveTo measure and compare viscoelastic coagulation in 2 canine blood donor populations using a novel, point-of-care device (VCM Vet Analyzer, VCM).DesignCohort study.SettingAcademic and commercial veterinary blood banks.AnimalsNon-Greyhounds from community-based blood donor program and Greyhounds from a blood bank colony.InterventionBlood was collected from all dogs via direct venipuncture for a complete hemogram, biochemistry, and point-of-care viscoelastic coagulation.Measurement and main resultsAll biochemical measurements for all dogs in Group NG (n = 38, non-Greyhounds) and Group G (n = 53, Greyhounds) were within local reference intervals. Hematology data showed significant statistical differences between groups in hemoglobin, RBC, platelet, and WBC concentrations. Group G demonstrated lower maximum clot firmness (MCF) with 17 VCM units (26 VCM units in Group NG), increased lysis with 30 VCM units at 30 minutes (LI30) and 27 VCM units at 45 minutes (LI45) (86 VCM units LI30 and 85 VCM units LI45 in Group NG), and decreased amplitude of 13 VCM units 10 minutes (A10) after clot time (CT) and 6 VCM units 20 minutes after CT (A20) (18 VCM units [A10] and 22 VCM units [A20] in Group NG).ConclusionThis study found differences between healthy Greyhound and non-Greyhound blood donors in measures of clot strength and fibrinolysis as measured by the VCM. Whereas Greyhound have unique hematologic and hemostatic profiles, these measured viscoelastic differences are important to note prior to and following surgical intervention to aid in clinical decision-making if bleeding complications develop.

Studies often aim to determine which indoor environmental quality parameters best predict the overall workspace assessment. However, this method overlooks important differences distinguishing satisfied and dissatisfied occupant groups. We used a new analytical approach on 36671 post-occupancy evaluation responses to overcome this problem and better understand workspace satisfaction in office buildings. Principal components analysis reduced satisfaction votes with 15 different IEQ items into two principal components related to: 1) privacy and amount of space, and 2) cleanliness and maintenance. We grouped the data by occupants that were either satisfied or dissatisfied with their workspace. Principal component 1 explained half of the variability in the dataset and reliably distinguished occupants satisfied with their workspace from those that were dissatisfied. We used support vector machine to classify the satisfied and dissatisfied groups based on principal components 1 and 2. Classification of occupant satisfaction with the overall workspace was highly accurate (approximately 90%) and based predominantly on the component related to privacy and amount of space. Further analyses showed that occupants satisfied with their overall workspace were generally satisfied with all other IEQ items. There was greater independence between workspace attributes for those dissatisfied with their overall workspace. Issues of privacy and available space were an overwhelming determinant of occupant dissatisfaction irrespective of the success of other workspace attributes. These findings suggest that efforts to improve occupant satisfaction with workspaces should leverage designs that ensure privacy and provide sufficient space to support occupants in their work.

Muscle-invasive urothelial carcinoma (MIUC) is the most common type of bladder malignancy in humans, but also in dogs that represent a naturally occurring model for this disease. Dogs are immunocompetent animals that share risk factors, pathophysiological features, clinical signs and response to chemotherapeutics with human cancer patients. This review summarizes the fundamental pathways for canine MIUC initiation, progression, and metastasis, emerging therapeutic targets and mechanisms of drug resistance, and proposes new opportunities for potential prognostic and diagnostic biomarkers and therapeutics. Identifying similarities and differences between cancer signaling in dogs and humans is of utmost importance for the efficient translation of in vitro research to successful clinical trials for both species.

Histone demethylases are overexpressed or display altered activity in numerous human cancers leading to alterations in cell cycle dynamics, DNA repair kinetics, and therapeutic resistance. Consequently, therapeutic targeting of histone demethylases has become an active and promising area of research in human oncology. However, the role of histone demethylases and the potential efficacy of demethylase inhibition in canine cancers remains largely unknown. In the present work, we addressed this knowledge gap by exploring the therapeutic potential of histone demethylase inhibitors (HDIs) in canine oral melanoma. Using canine melanoma cell lines, we determined that broad spectrum HDIs result in decreased cell survival and prolonged DNA damage repair kinetics. We then showed that JARID1B, a histone H3 demethylase implicated in proliferation-dormancy regulation and drug sensitivity in human cancers, is highly expressed in canine tumour tissues. HDIs targeting JARID1B, and related JARID1 family members, significantly reduced survival fractions in canine melanoma cell lines, but did not appear to modulate DNA damage repair kinetics like broad spectrum HDI treatments. Importantly, we found that the anti-proliferative effects of JARID1-targeted HDIs are preserved in cell lines resistant to platinum-based chemotherapeutics, suggesting that HDIs may serve as a viable therapeutic strategy when faced with oral melanomas that progress despite the use of conventional therapies.

A 10-year-old female spayed mixed breed dog was evaluated for diarrhea and vomiting. Diagnostic imaging demonstrated the presence of an intracardiac mass. A modified Seldinger technique was used to access the right jugular vein, and an endomyocardial biopsy forceps was introduced through a sheath to obtain several biopsies. Histopathology and immunohistochemistry demonstrated a paraganglioma. The dog underwent 1 fraction of radiotherapy and l-asparaginase chemotherapy and was discharged. The dog developed a pulmonary thromboembolism 2 days after radiotherapy and chemotherapy, and the owner elected humane euthanasia. Although long-term assessment of treatment response was unable to be performed, this novel diagnostic option could be considered for similar cases due to success in obtaining a histopathologic diagnosis, which is essential in developing a disease-specific treatment plan. This report also describes the use of radiotherapy for primary treatment of an intracardiac neoplasm, which can be a consideration in the future.

Rationale and objectivesTo establish a proof-of-principle for combined assessment of pulmonary ventilation and perfusion using single-energy computed tomography (CT) and image processing/analysis (denoted as single-energy CT ventilation/perfusion imaging).Materials and methodsBreath-hold CT scans were acquired at end-expiration and end-inspiration before injection of iodinated contrast agents, and repeated at end-inspiration after contrast injection for 17 canines (8 normal and 9 diseased lung subjects). Ventilation images were calculated with deformable image registration to map the end-expiratory and end-inspiratory CT images and quantitative analysis for regional volume changes as surrogates for ventilation. Perfusion images were calculated by subtracting the end-inspiratory precontrast CT from the deformably registered end-inspiratory postcontrast CT, yielding a map of regional Hounsfield unit enhancement as a surrogate for perfusion. Ventilation-perfusion matching, spatial heterogeneity, and gravitationally directed gradients were compared between two groups using a Wilcoxon rank-sum test.ResultsThe normal group had significantly higher Dice similarity coefficients for spatial overlap of segmented functional volumes between ventilation and perfusion (median 0.40 vs. 0.33, p = 0.05), suggesting stronger ventilation-perfusion matching. The normal group also had greater Spearman's correlation coefficients based on 16 regions of interest (median 0.58 vs. 0.40, p = 0.09). The coefficients of variation were comparable (median, ventilation 0.71 vs. 0.91, p = 0.60; perfusion 0.63 vs. 0.75, p = 0.27). The linear regression slopes of gravitationally directed gradient were also comparable for ventilation (median, ventilation -0.26 vs. -0.18, p = 0.19; perfusion -0.17 vs. -0.06, p = 0.11).ConclusionThese findings provide proof-of-principle for single-energy CT ventilation/perfusion imaging.

Thermochromic windows have been widely studied as a technology that can potentially offer increases in energy conservation and provide a desirable luminous environment inside buildings. However, there has been little attention placed on how the tinted states of thermochromic glazing influence occupant behaviour and visual perception. An experiment under controlled conditions was designed to test the influence of different thermochromic tint states on human response. By using a controllable artificial window, five typical luminous conditions were set up, including clear (no tint) and two different levels of blue and bronze tint states, respectively, which produced different room colour temperatures. Thirty-one subjects were recruited who completed three visual tasks, including a visual acuity and a colour naming tasks using the coloured Landolt ring chart and a sustained attention test using the d2 test. Subjective assessments were also collected using questionnaires. Statistical analyses showed the across the thermochromic window conditions, no significant differences in performance were found for the visual acuity and d2 tests. However, there was a significant effect for the colour naming task from the Landolt ring test. Under blue tint conditions, subjects reported higher alertness and produced fewer errors. More natural and acceptable lighting conditions were found under the bronze-tinted conditions. Therefore, when developing innovative thermochromic windows applied in buildings, it is also important to cater for the visual requirements of the occupants in the space, not only energy efficiency goals.

Phantom limb pain is thought to be sustained by reentrant neural pathways, which provoke dysfunctional reorganization in the somatosensory cortex. We hypothesized that disrupting reentrant pathways with a 6-day-long continuous peripheral nerve block reduces phantom pain 4 weeks after treatment. We enrolled patients who had an upper- or lower-limb amputation and established phantom pain. Each was randomized to receive a 6-day perineural infusion of either ropivacaine or normal saline. The primary outcome was the average phantom pain severity as measured with a Numeric Rating Scale (0-10) at 4 weeks, after which an optional crossover treatment was offered within the following 0 to 12 weeks. Pretreatment pain scores were similar in both groups, with a median (interquartile range) of 5.0 (4.0, 7.0) for each. After 4 weeks, average phantom limb pain intensity was a mean (SD) of 3.0 (2.9) in patients given local anesthetic vs 4.5 (2.6) in those given placebo (difference [95% confidence interval] 1.3 [0.4, 2.2], P = 0.003). Patients given local anesthetic had improved global impression of change and less pain-induced physical and emotional dysfunction, but did not differ on depression scores. For subjects who received only the first infusion (no self-selected crossover), the median decrease in phantom limb pain at 6 months for treated subjects was 3.0 (0, 5.0) vs 1.5 (0, 5.0) for the placebo group; there seemed to be little residual benefit at 12 months. We conclude that a 6-day continuous peripheral nerve block reduces phantom limb pain as well as physical and emotional dysfunction for at least 1 month.

Published radiotherapy results for suspected heart-based tumours in dogs are limited. In this retrospective longitudinal study (3/2014-2019), eight dogs with either clinical signs attributable to a heart-base mass (6), or asymptomatic with a progressively larger mass on echocardiogram (2), received conventional fractionated radiotherapy (CFRT) or stereotactic body radiotherapy (SBRT). Clinical findings in symptomatic cases included one or more of the following: retching/coughing (4), exercise intolerance (2), collapse (1), pericardial effusion (2), rare ventricular premature contractions (2), abdominal effusion (1), or respiratory distress due to chylothorax (1). CFRT cases received 50 Gray (Gy) in 20 fractions and SBRT cases received 30 Gy in 5 or 24 Gy in three fractions. Two dogs received chemotherapy post-radiation. At analysis, 7/8 dogs were deceased and one was alive 684 days post-treatment. The estimated median overall survival (MOS) from first treatment was 785 days (95% CI 114-868 days, [range 114-1492 days]). Five dogs received CFRT (MOS 817 days; (95% CI 155 days-not reached [range 155-1492 days])). Three dogs received SBRT with one alive at analysis (MOS 414 days, (95% CI, 114 days-not reached [range 114-414 days])). No statistically significant difference was found between survival for CFRT and SBRT. Of the symptomatic patients, 5/6 showed improvement. Mass size reduced in 4/5 cases receiving follow-up ultrasounds. Possible complications included asymptomatic radiation pneumonitis (4), atrial tachycardia/premature beats (4) and pericardial effusion with heart failure coincident with tumour progression (1). This study provides preliminary evidence that radiotherapy may impact clinically relevant or progressively enlarging heart-base masses.

ObjectiveTo compare the efficacy of fresh frozen plasma (FFP) with cryopoor plasma (CPP) to treat vitamin K-dependent factor deficiency in a canine in vitro setting.DesignIn vitro laboratory study.SettingUniversity veterinary medical teaching hospital.AnimalsSeven units of FFP and 6 units of CPP from unique canine donors from the university veterinary blood bank.InterventionsCanine FFP was adsorbed by oral barium sulfate suspension to mimic vitamin K-dependent coagulopathy. A sequential mixing study was completed by adding FPP or CPP to the adsorbed plasma. Measurements of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and factor activities of factors II, VII, and IX (FII, FVII, and FIX) were compared between the 2 treatment groups.Measurements and main resultsWhen comparing the sequential addition of CPP or FPP to adsorbed plasma, the following had no statistical significance: PT (P = 0.94), aPTT (P = 0.66), FII (P = 0.05), and FIX (P = 0.90). There was a dose-dependent decrease with PT and aPTT and a dose-dependent increase with FII and FIX. In contrast, after the addition of either CPP or FFP, there was a significant difference between the treatment groups for the concentration of fibrinogen (P = 0.005) and activity of FVII (P = 0.044), with FFP resulting in a greater concentration of fibrinogen and CPP resulting in a greater concentration of FVII. Measurements of factor X (FX) were initially included in the study but were later excluded because FX appeared to be continually adsorbed even after the addition of CPP or FFP.ConclusionsCPP partially corrected the coagulation times and concentration of vitamin K-dependent coagulation factors to the same degree as FFP. CPP, generally less expensive than FFP, may provide an alternative treatment option for vitamin K-dependent coagulopathies, although in vivo testing is needed.

Metastatic osteosarcoma has a bleak prognosis in both humans and dogs, and there have been minimal therapeutic advances in recent decades to improve outcomes. Naturally occurring osteosarcoma in dogs is shown to be a highly suitable model for human osteosarcoma, and limited data suggest the similarities between species extend into immune responses to cancer. Studies show that immune infiltrates in canine osteosarcoma resemble those of human osteosarcoma, and the analysis of tumor immune constituents as predictors of therapeutic response is a promising direction for future research. Additionally, clinical studies in dogs have piloted the use of NK transfer to treat osteosarcoma and can serve as valuable precursors to clinical trials in humans. Cytotoxic lymphocytes in dogs and humans with osteosarcoma have increased activation and exhaustion markers within tumors compared with blood. Accordingly, NK and T cells have complex interactions among cancer cells and other immune cells, which can lead to changes in pathways that work both for and against the tumor. Studies focused on NK and T cell interactions within the tumor microenvironment can open the door to targeted therapies, such as checkpoint inhibitors. Specifically, PD-1/PD-L1 checkpoint expression is conserved across tumors in both species, but further characterization of PD-L1 in canine osteosarcoma is needed to assess its prognostic significance compared with humans. Ultimately, a comparative understanding of T and NK cells in the osteosarcoma tumor microenvironment in both dogs and humans can be a platform for translational studies that improve outcomes in both dogs and humans with this frequently aggressive disease.