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A detailed understanding of the molecular and immunological changes that occur longitudinally across tumors exposed to immune checkpoint inhibitors is a significant knowledge gap in oncology. To address this unmet need, we created a statewide biospecimen collection and clinical informatics system to enable longitudinal tumor and immune profiling and to enhance translational research. The Texas Immuno-Oncology Biorepository (TIOB) consents patients to collect, process, store, and analyze serial biospecimens of tissue, blood, urine, and stool from a diverse population of over 100,000 cancer patients treated each year across the Baylor Scott & White Health system. Here we sought to demonstrate that these samples were fit for purpose with regard to downstream multi-omic assays. Plasma, urine, peripheral blood mononuclear cells, and stool samples from 11 enrolled patients were collected from various cancer types. RNA isolated from extracellular vesicles derived from plasma and urine was sufficient for transcriptomics. Peripheral blood mononuclear cells demonstrated excellent yield and viability. Ten of 11 stool samples produced RNA quality to enable microbiome characterization. Sample acquisition and processing methods are known to impact sample quality and performance. We demonstrate that consistent acquisition methodology, sample preparation, and sample storage employed by the TIOB can produce high-quality specimens, suited for employment in a wide array of multi-omic platforms, enabling comprehensive immune and molecular profiling., Competing Interests: Dr. Kelly has received institutional research support from Bristol Myers Squibb and Eli Lilly and has served on advisory boards for BMS, Merck, EMD Serono, Astra Zeneca, Daiichi Sankyo, Eisai, Astellas, Ipsen, Novartis, Takeda, Novocure, and Eli Lilly. The other authors have no conflicts to disclose., (Copyright © 2022 Baylor University Medical Center.)

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.

While biologging tags have answered a wealth of ecological questions, the drivers and consequences of movement and activity often remain difficult to ascertain, particularly marine vertebrates which are difficult to observe directly. Basking sharks, the second largest shark species in the world, aggregate in the summer in key foraging sites but despite advances in biologging technologies, little is known about their breeding ecology and sub-surface behaviour. Advances in camera technologies holds potential for filling in these knowledge gaps by providing environmental context and validating behaviours recorded with conventional telemetry. Six basking sharks were tagged at their feeding site in the Sea of Hebrides, Scotland, with towed cameras combined with time-depth recorders and satellite telemetry. Cameras recorded a cumulative 123 hours of video data over an average 64-hour deployment and confirmed the position of the sharks within the water column. Feeding events only occurred within a metre depth and made up ¾ of the time spent swimming near the surface. Sharks maintained similar tail beat frequencies regardless of whether feeding, swimming near the surface or the seabed, where they spent surprisingly up to 88% of daylight hours. This study reported the first complete breaching event and the first sub-surface putative courtship display, with nose-to-tail chasing, parallel swimming as well as the first observation of grouping behaviour near the seabed. Social groups of sharks are thought to be very short term and sporadic, and may play a role in finding breeding partners, particularly in solitary sharks which may use aggregations as an opportunity to breed. In situ observation of basking sharks at their seasonal aggregation site through animal borne cameras revealed unprecedented insight into the social and environmental context of basking shark behaviour which were previously limited to surface observations., Competing Interests: Since the funder, NatureScot, is not a commercial organisation, we do not have any commercial affiliations. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Basking sharks, the world's second largest fish, are endangered globally following two centuries of large-scale exploitation for their oily livers. In the northeast Atlantic, they seasonally gather in key sites, including the western Scottish Isles, where they feed on plankton, but their breeding grounds are currently completely unknown. Using high-resolution three-axis accelerometry and depth logging, we present the first direct records of breaching by basking sharks over 41 days. We show that basking sharks breach both during the night and day, starting at approximately 20 m depth and can breach multiple times in short succession. We also present early evidence of potential lateralisation in basking sharks. Given the energetic nature of breaching, it should have an important biological function, but this remains unclear.

Patients with cirrhosis and splenomegaly commonly develop cytopenias and require the transfusion of blood products. In this study, we evaluated spleen size as a clinical indicator for red blood cell transfusion effectiveness and hypothesized that transfusion would be less effective in patients with splenomegaly. Our retrospective cohort study compared 215 cirrhotic patients with splenomegaly and 114 cirrhotic patients without splenomegaly and measured their respective change in hemoglobin concentration after a unit of transfused red blood cells. The primary endpoint was the percent difference between the measured rise in hemoglobin after transfusion in these cohorts. Patient sex ( P  < 0.0035), body mass index ( P  < 0.0001), and the change in hemoglobin concentration after a leukocyte-reduced red blood transfusion ( P  < 0.0001) were found to be significantly related to spleen size. When compared to the nonsplenomegaly cohort, it was found that the splenomegaly cohort experienced 79.70% (95% CI 71.26%-89.14%) of the change in hemoglobin concentration after red blood cell transfusion when adjusted for patient sex and body mass index. In conclusion, in patients with cirrhosis, increased spleen size was correlated with a decreased responsiveness to red blood cell transfusion when adjusted for patient sex and body mass index., (Copyright © 2020 Baylor University Medical Center.)

Migratory movements in response to seasonal resources often influence population structure and dynamics. Yet in mobile marine predators, population genetic consequences of such repetitious behaviour remain inaccessible without comprehensive sampling strategies. Temporal genetic sampling of seasonally recurring aggregations of planktivorous basking sharks, Cetorhinus maximus, in the Northeast Atlantic (NEA) affords an opportunity to resolve individual re-encounters at key sites with population connectivity and patterns of relatedness. Genetic tagging (19 microsatellites) revealed 18% of re-sampled individuals in the NEA demonstrated inter/multi-annual site-specific re-encounters. High genetic connectivity and migration between aggregation sites indicate the Irish Sea as an important movement corridor, with a contemporary effective population estimate (N e ) of 382 (CI = 241-830). We contrast the prevailing view of high gene flow across oceanic regions with evidence of population structure within the NEA, with early-season sharks off southwest Ireland possibly representing genetically distinct migrants. Finally, we found basking sharks surfacing together in the NEA are on average more related than expected by chance, suggesting a genetic consequence of, or a potential mechanism maintaining, site-specific re-encounters. Long-term temporal genetic monitoring is paramount in determining future viability of cosmopolitan marine species, identifying genetic units for conservation management, and for understanding aggregation structure and dynamics.

The aim of this study was to promote nursing and practitioner satisfaction by improving communication and reducing rapid response team (RRT) activations and code blues hospitalwide by implementing the nursing cheat sheet, a list of key steps to be done before calling the primary provider. This prospective observational study took place over a year at a 636-bed teaching hospital in Central Texas. Education regarding the nursing cheat sheet was provided to nurses at monthly meetings, unit huddles, and interdisciplinary rounds. Units received monthly follow-up education and reminders, and the nursing cheat sheet was posted at nursing work areas. RRT activations and code blues were counted daily. After implementing the nursing cheat sheet, RRT activations were lower than the pre-intervention average and were outside the control band for July, August, and November. The number of code blues did not deviate from the control bands. The authors did not see a reduction in code blues after implementation of the nursing cheat sheet, but the average number of RRT activations decreased, indicating a significant difference in the number of RRT activations. It is not clear that this decrease was due to the intervention.

Animal migration is ubiquitous in nature with individuals within a population often exhibiting varying movement strategies. The basking shark (Cetorhinus maximus) is the world's second largest fish species, however, a comprehensive understanding of their long-term wider-ranging movements in the north-east Atlantic is currently lacking. Seventy satellite tags were deployed on basking sharks over four years (2012-2015) off the west coast of Scotland and the Isle of Man. Data from 28 satellite tags with attachment durations of over 165 days reveal post-summer ranging behaviours. Tagged sharks moved a median minimum straight-line distance of 3,633 km; achieving median displacement of 1,057 km from tagging locations. Tagged individuals exhibited one of three migration behaviours: remaining in waters of UK, Ireland and the Faroe Islands; migrating south to the Bay of Biscay or moving further south to waters off the Iberian Peninsula, and North Africa. Sharks used both continental shelf areas and oceanic habitats, primarily in the upper 50-200 m of the water column, spanning nine geo-political zones and the High Seas, demonstrating the need for multi-national cooperation in the management of this species across its range.

A method has been developed to display Doppler spectral waveforms in lower extremity vein grafts in conjunction with 3-D vessel geometry. Doppler spectral waveforms and cross-sectional images of the vein graft are collected with a custom 3-D ultrasound imaging system. Computer processing generates a display of the Doppler sample volumes registered in 3-D space with a surface reconstruction of the vein graft lumen. An interactive computer interface displays spectral waveforms at user-selected sites in the graft. Summary displays combining spectral waveforms, maximum velocity and cross-sectional area provide a pictorial record of the state of the vein graft along its full length. The method is demonstrated for two patient studies, each at two time points after graft revisions. The graphic display of both hemodynamics and geometry allows rapid assessment of vein graft changes over time.

Using ultrasound imaging, we investigated the roles of the potentially contractile veins and of the mantle (the powerful body wall that moves water over the gills, and also encloses the large veins and the hearts) in returning the blood of cuttlefish to its hearts. Ultrasound provided the first non-invasive observations of vascular function in an unanaesthetized, free-moving cephalopod. The large veins (anterior vena cava, lateral venae cavae and efferent branchial vessels) contracted in live, intact cuttlefish (Sepia officinalis L.). The anterior vena cava contracted at the same rate as the mantle, but it often expanded during mantle contraction. Furthermore, the anterior vena cava contracted peristaltically in vivo, suggesting that it actively aids venous return. The lateral venae cavae and efferent branchial vessels contracted at the same rate as the branchial and systemic hearts, but at a different rate from the mantle. A peristaltic wave appeared to travel along the lateral venae cavae to the branchial hearts, potentially aiding venous return. We found a muscular valve between the anterior and lateral venae cavae, which ensured that blood flowed only one way between these unsynchronized vessels. The mantle appears to have an unclear connection with cardiovascular function. We conclude that, when cuttlefish are at rest, the mantle does not compress any of the large veins that we imaged (including the anterior vena cava), and that peristaltic contractions of the large veins might be important in returning cephalopod blood to the hearts.

Objectives: To assess the ventricular rate response of rate-adaptive (VVIR) pacemakers in dogs using a multi-stage exercise test., Methods: The rate-responsiveness of VVIR pacemakers was assessed in seven dogs with complete atrioventricular (AV) block and implanted with various models of pulse generators (six motion sensors and one automatic dual-sensor rate-response pacemaker). Response activity was assessed with a multi-stage exercise test on a treadmill. Atrial and ventricular rate were analysed retrospectively at the end of the test and the AV ratio was calculated after each minute of exercise., Results: During exercise, the mean (sd) AV ratio recorded in all paced dogs was 1.7 (0.5) (expected physiological ratio 1.0), although a variety of individual performances was observed. A poor response (AV ratio 2.8 [0.2]) was obtained with the automatic dual-sensor pacemaker, suggesting that this type of rate-responsive device may not be indicated for implantation in dogs with complete AV block. The overall AV ratio for the six dogs implanted with motion sensors was 1.4 (0.2), showing a better performance of these pacemakers during exercise., Clinical Significance: This multi-stage exercise test represents an easy and repeatable method for assessing the accuracy of rate-responsive sensors and offers valuable information for the correct setting of VVIR pacemakers in dogs.

A retrospective study was undertaken to determine the prevalence of different diseases in cats referred for investigation of chronic nasal disease, to identify historical, clinical and diagnostic features which may assist in making a diagnosis, and to provide information pertaining to outcome in these cats. Diagnoses included neoplasia (30 cases), chronic rhinitis (27), foreign body (8), nasopharyngeal stenosis (5), Actinomyces infection (2), nasal polyps (2), stenotic nares (2), and rhinitis subsequent to trauma (1). The most common neoplasia was lymphosarcoma (21 cases), with a median survival of 98 days for cats treated with multiagent chemotherapy. Cats with neoplasia were older on average than the other cats, and were more likely to be dyspnoeic and have a haemorrhagic and/or unilateral nasal discharge than cats with chronic rhinitis. Cats with neoplasia were more likely to have radiographic evidence of nasal turbinate destruction, septal changes, or severe increases in soft tissue density than cats with chronic rhinitis. It was unusual for cats with diseases other than neoplasia to be euthanased as a result of their nasal disease.

This report details clinical, histopathological and immunohistochemical findings in 18 cats with chronic nasal disease diagnosed as nasal lymphoma. Eight of the cats were female and 10 were male, with a median age of 10.5 years (range 7-14 years). Three of the cats were Siamese, one was Burmese, and the rest were non-pedigree. The duration of clinical signs before referral ranged from 30 to 540 days (median 88.5 days). The most common clinical signs were nasal discharge, stertor and sneezing. Nasal radiographs were abnormal in 14/16 cases examined. Abnormal masses were detected endoscopically in 13/18 cases. Nine cats received multi-agent chemotherapy or radiation therapy, or both, with survival times ranging from 14 to >541 days. Biopsy material from these 18 cats was examined by light microscopy, and serial sections were subjected to immunohistochemical labelling for the T lymphocyte marker CD3 and the B lymphocyte marker CD79a. In 13 tissues, expression of class II molecules of the major histocompatibility complex and the myelomonocytic antigen MAC387 was also determined. Twelve of the tumours were classified as diffuse large B-cell lymphomas, four as lymphoblastic B-cell lymphomas, and one as a follicular B-cell lymphoma. The tumour cells within these lesions all expressed CD79a, and (where tested) most also expressed MHC class II. One tumour was an anaplastic large cell neoplasm, in which the neoplastic cells expressed MHC class II alone in the absence of either lymphoid marker. There was a variable infiltration of reactive small T lymphocytes into these tumours, and zones of necrosis within the tumour tissue were sometimes heavily infiltrated by MAC387+ phagocytic cells.

Polydipsia, defined as a water intake of over 100 ml/kg/day, is a common presenting medical complaint in dogs. Polydipsia can be secondary (eg, to central or nephrogenic diabetes insipidus) or primary in origin, where increased water intake cannot be explained as a response to obligatory water loss. Primary polydipsia is confirmed by ruling out other known causes of polydipsia and demonstrating that renal concentrating ability is intact. The causes and associations of primary polydipsia in dogs are poorly defined. This report describes three dogs presented with signs of gastrointestinal disease with concurrent polydipsia. Investigations (including water deprivation testing) showed normal renal urinary concentrating ability and indicated primary polydipsia. Treatment of the gastrointestinal signs resulted in resolution of the polydipsia in each case. This is the first description of a possible association between gastrointestinal disease and primary polydipsia in the dog, the pathophysiology of which remains obscure.

Objective: To examine the variation in surgical and adjuvant treatment of breast cancer of known histology and detected on screening in a large cohort of patients treated by the surgeons of a health region., Design: Part prospective, part retrospective observational study using the databases of a region's breast screening programme and of the cancer registry., Setting: The former South East Thames region., Subjects: 600 women aged 49-79 who presented during 1991-2 with invasive breast cancer up to 20 mm in diameter that had been detected on screening. These patients were treated by 35 surgeons., Main Outcome Measures: Mastectomy rate by surgeon and the use of adjuvant treatment (radiotherapy, tamoxifen, and chemotherapy) were compared with risk factors, tumour grade, resection margins, and axillary node status., Results: The mastectomy rate varied between nil and 80%, although the numbers at these extremes were small (0/13 v 8/10). Surgeons operating on more than 20 such cases had a lower mastectomy rate (15%) than surgeons treating fewer cases (23%), but this difference was confounded by variation in casemix. There were also wide variations in mastectomy rates and in axillary sampling rates that were independent of casemix or caseload. There was broad agreement on the use of adjuvant tamoxifen (94%), but few patients received chemotherapy (2.5%). 78 patients (19%) did not receive radiotherapy, including 51 out of 317 patients with unfavourable tumours, and 26 patients did not receive tamoxifen. Whether the patient received adjuvant treatment was more dependent on referral by the surgeon than the risk factors for local recurrence and was independent of caseload., Conclusion: Mastectomy rates for similar tumours vary widely by surgeon independently of casemix or caseload, but surgeons with a higher caseload tend to have a lower mastectomy rate. Omission of postoperative radiotherapy or tamoxifen after conservative treatment is not related to risk factors for local recurrence or caseload. Confidential feedback of treatment profiles to individual surgeons has been used, but when benefit has been established treatment should be guided by evidence based protocol.

Genomic mapping studies frequently employ retrovirus-mediated transfer of dominant selectable markers to specific target chromosomes. DNA probes containing sequences adjacent to inserted proviruses are valuable mapping tools in such studies. We have implemented a strategy for amplification of chromosomal sequences flanking the 5' LTR of MoMuLV-based vectors. Probes derived from these amplification products successfully differentiated murine versus human proviral localization in retrovirus-infected mouse-human chromosome 17q hybrid cells.

Subjects for this study were 13 hospitalized patients given the diagnosis of adjustment reaction to adolescence. The subjects were randomly divided into experimental and control groups. The experimental period consisted of 18 1-hour sessions. Subjects in the control group did not attend music therapy activities. Experimental subjects engaged in group discussions concerning moods and emotions in music, expression and identification of body language, story composition to recorded music, and drawing to music. Four types of pre and posttests were administered: agreement on mood or emotion expressed in music as measured by an adjective checklist; sociograms to measure group cohesion; the number of pronouns expressing group feelings ("we, our"); and scores of the Coopersmith Self-Esteem Inventory. Significant differences in favor of experimental subjects were found on the adjective checklist (p = .01) and the group versus personal pronouns (p less than .05). The group cohesion measure approached significance (p = .062).