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Study Objectives: Alerts for vital sign abnormalities seek to identify meaningful patient instability while limiting alarm fatigue. Optimal vital sign alarm settings for postoperative patients remain unknown, as is whether alerts lead to effective clinical responses reducing vital sign disturbances. We conducted a 2-phase pilot study to identify thresholds and delays and test the hypothesis that alerts from continuous monitoring reduce the duration of vital sign abnormalities., Design: Two-phase pilot., Patients: 250 adults having major non-cardiac surgery., Setting: Surgical wards., Intervention: All patients had routine vital sign monitoring by nurses at 4-h intervals. We initially continuously recorded clinician-blinded saturation, heart rate, and respiratory rate in 100 patients. In the second phase, we randomized 150 patients to blinded versus unblinded continuous vital sign monitoring. In unblinded patients, nurses were verbally alerted to abnormal vital signs., Measurements: In the first phase, we modeled expected alarm counts using 6082 h of continuous oxygen saturation, heart rate, and respiratory rate data. Thresholds and delays targeting ∼3 alarms per patient per day were selected for phase two. Primary analysis assessed the effect of unblinded monitoring across a 5-component primary composite of cumulative durations of vital sign abnormalities. Secondary outcomes included fraction of alerts deemed meaningful by nurses and number of clinical interventions., Results: In phase one, we identified alarm settings that yielded an average of 2.3 alerts per patient per day. In phase two, the average relative effect ratio of geometric duration means for vital signs exceeding thresholds was 0.75 [95 % CI: 0.51, 1.1], P = 0.17. Sixty alarms (82 %) were deemed useful in unblinded patients, leading to 60 % more interventions in unblinded patients., Conclusions: We were able to select continuous saturation, heart rate, and respiratory rate thresholds that generated about 2 alerts per patient per day, nearly all of which were considered useful by nurses. Unblinded monitoring and nursing alerts led to interventions (mostly increasing oxygen delivery) that non-significantly reduced vital sign abnormalities by 25 %., Clinicaltrials: gov registration: NCT05280574., Competing Interests: Declaration of competing interest The CEO of the Cleveland Clinic is a Director for GE HealthCare. R Coffeng and JW Beard are employees of GE HealthCare. None of the other authors has a personal financial interest in this research., (Copyright © 2024. Published by Elsevier Inc.)

Point of care (PoC) nucleic acid amplification tests (NAATs) are a cornerstone of public health, providing the earliest and most accurate diagnostic method for many communicable diseases in the same location where the patient receives treatment. Communicable diseases, such as human immunodeficiency virus (HIV), disproportionately impact low-resource communities where NAATs are often unobtainable due to the resource-intensive enzymes that drive the tests. Enzyme-free nucleic acid detection methods, such as hybridization chain reaction (HCR), use DNA secondary structures for self-driven amplification schemes, producing large DNA nanostructures, capable of single-molecule detection in cellulo . These thermodynamically driven DNA-based tests have struggled to penetrate the PoC diagnostic field due to their inadequate limits of detection or complex workflows. Here, we present a proof-of-concept NAAT that combines HCR-based amplification of a target nucleic acid sequence with paper-based nucleic acid filtration and enrichment capable of detecting sub-pM levels of synthetic DNA. We reconstruct the favorable hybridization conditions of an in cellulo reaction in vitro by incubating HCR in an evaporating, microvolume environment containing poly(ethylene glycol) as a crowding agent. We demonstrate that the kinetics and thermodynamics of DNA-DNA and DNA-RNA hybridization is enhanced by the dynamic evaporating environment and inclusion of crowding agents, bringing HCR closer to meeting PoC NAAT needs.

Background: Patient monitoring devices are critical for alerting of potential cardiac arrhythmias during hospitalization; however, there are concerns of alarm fatigue due to high false alarm rates., Objective: The purpose of this study was to evaluate the sensitivity and false alarm rate of hospital-based continuous electrocardiographic (ECG) monitoring technologies., Methods: Six commonly used multiparameter bedside monitoring systems available in the United States were evaluated: B125M (GE HealthCare), ePM10 and iPM12 (Mindray), Efficia and IntelliVue (Philips), and Life Scope (Nihon Kohden). Sensitivity was tested using ECG recordings containing 57 true ventricular tachycardia (VT) events. False-positive rate testing used 205 patient-hours of ECG recordings containing no cardiac arrhythmias. Signals from ECG recordings were fed to devices simultaneously; high-severity arrhythmia alarms were tracked. Sensitivity to true VT events and false-positive rates were determined. Differences were assessed using Fisher exact tests (sensitivity) and Z -tests (false-positive rates)., Results: B125M raised 56 total alarms for 57 annotated VT events and had the highest sensitivity (98%; P <.05), followed by iPM12 (84%), Life Scope (81%), Efficia (79%), ePM10 (77%), and IntelliVue (75%). B125M raised 20 false alarms, which was significantly lower ( P <.0001) than iPM12 (284), Life Scope (292), IntelliVue (304), ePM10 (324), and Efficia (493). The most common false alarm was VT, followed by nonsustained VT., Conclusion: We found significant performance differences among multiparameter bedside ECG monitoring systems using previously collected recordings. B125M had the highest sensitivity in detecting true VT events and lowest false alarm rate. These results can assist in minimizing alarm fatigue and optimizing patient safety by careful selection of in-hospital continuous monitoring technology., (© 2024 Heart Rhythm Society.)

Accurate ECG interpretation is vital, but variations in skills exist among healthcare professionals. This study aims to identify factors contributing to ECG interpretation proficiency. Survey data and ECG interpretation test scores from participants in the EDUCATE Trial were analyzed to identify predictors of performance for 30 sequential 12-lead ECGs. Nonmodifiable factors (being a physician, clinical experience, patient care impact) and modifiable factors (weekly interpretation volume, training hours, expert supervision frequency) were analyzed. Bivariate and multivariate analyses were used to generate a Comprehensive Model (incorporating all factors) and Actionable Model (incorporating modifiable factors only). Among 1206 participants analyzed, there were 72 (6.0%) primary care physicians, 146 (12.1%) cardiology fellows-in-training, 353 (29.3%) resident physicians, 182 (15.1%) medical students, 84 (7.0%) advanced practice providers, 120 (9.9%) nurses, and 249 (20.7%) allied health professionals. Among them, 571 (47.3%) were physicians and 453 (37.6%) were nonphysicians. The average test score was 56.4% ± 17.2%. Bivariate analysis demonstrated significant associations between test scores and >10 weekly ECG interpretations, being a physician, >5 training hours, patient care impact, and expert supervision but not clinical experience. In the Comprehensive Model, independent associations were found with weekly interpretation volume (9.9 score increase; 95% CI, 7.9-11.8; P < 0.001), being a physician (9.0 score increase; 95% CI, 7.2-10.8; P < 0.001), and training hours (5.7 score increase; 95% CI, 3.7-7.6; P < 0.001). In the Actionable Model, scores were independently associated with weekly interpretation volume (12.0 score increase; 95% CI, 10.0-14.0; P < 0.001) and training hours (4.7 score increase; 95% CI, 2.6-6.7; P < 0.001). The Comprehensive and Actionable Models explained 18.7% and 12.3% of the variance in test scores, respectively. Predictors of ECG interpretation proficiency include nonmodifiable factors like physician status and modifiable factors such as training hours and weekly ECG interpretation volume., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Author (Anthony Kashou, MD) is the founder and CEO of The EKG Guy and has received research funding from GE HealthCare (Milwaukee, WI)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The interpretation of electrocardiograms (ECGs) involves a dynamic interplay between computerized ECG interpretation (CEI) software and human overread. However, the impact of computer ECG interpretation on the performance of healthcare professionals remains largely unexplored. The aim of this study was to evaluate the interpretation proficiency of various medical professional groups, with and without access to the CEI report. Healthcare professionals from diverse disciplines, training levels, and countries sequentially interpreted 60 standard 12-lead ECGs, demonstrating both urgent and nonurgent findings. The interpretation process consisted of 2 phases. In the first phase, participants interpreted 30 ECGs with clinical statements. In the second phase, the same 30 ECGs and clinical statements were randomized and accompanied by a CEI report. Diagnostic performance was evaluated based on interpretation accuracy, time per ECG (in seconds [s]), and self-reported confidence (rated 0 [not confident], 1 [somewhat confident], or 2 [confident]). A total of 892 participants from various medical professional groups participated in the study. This cohort included 44 (4.9%) primary care physicians, 123 (13.8%) cardiology fellows-in-training, 259 (29.0%) resident physicians, 137 (15.4%) medical students, 56 (6.3%) advanced practice providers, 82 (9.2%) nurses, and 191 (21.4%) allied health professionals. The inclusion of the CEI was associated with a significant improvement in interpretation accuracy by 15.1% (95% confidence interval, 14.3-16.0; P < 0.001), decrease in interpretation time by 52 s (-56 to -48; P < 0.001), and increase in confidence by 0.06 (0.03-0.09; P = 0.003). Improvement in interpretation accuracy was seen across all professional subgroups, including primary care physicians by 12.9% (9.4-16.3; P = 0.003), cardiology fellows-in-training by 10.9% (9.1-12.7; P < 0.001), resident physicians by 14.4% (13.0-15.8; P < 0.001), medical students by 19.9% (16.8-23.0; P < 0.001), advanced practice providers by 17.1% (13.3-21.0; P < 0.001), nurses by 16.2% (13.4-18.9; P < 0.001), allied health professionals by 15% (13.4-16.6; P < 0.001), physicians by 13.2% (12.2-14.3; P < 0.001), and nonphysicians by 15.6% (14.3-17.0; P < 0.001).CEI integration improves ECG interpretation accuracy, efficiency, and confidence among healthcare professionals., Competing Interests: Declaration of Competing Interest A.H.K. is the founder and CEO of The EKG Guy, and has received research funding from GE HealthCare (Milwaukee, WI)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The electrocardiogram (ECG) is a crucial diagnostic tool in medicine with concerns about its interpretation proficiency across various medical disciplines. Our study aimed to explore potential causes of these issues and identify areas requiring improvement. A survey was conducted among medical professionals to understand their experiences with ECG interpretation and education. A total of 2515 participants from diverse medical backgrounds were surveyed. A total of 1989 (79%) participants reported ECG interpretation as part of their practice. However, 45% expressed discomfort with independent interpretation. A significant 73% received less than 5 hours of ECG-specific education, with 45% reporting no education at all. Also, 87% reported limited or no expert supervision. Nearly all medical professionals (2461, 98%) expressed a desire for more ECG education. These findings were consistent across all groups and did not vary between primary care physicians, cardiology FIT, resident physicians, medical students, APPs, nurses, physicians, and nonphysicians. This study reveals substantial deficiencies in ECG interpretation training, supervision, and confidence among medical professionals, despite a strong interest in increased ECG education., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Author (Anthony Kashou, MD) is the founder and CEO of The EKG Guy, and has received research funding from GE HealthCare (Milwaukee, WI)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aimed to determine the potential cost-savings for implementing continuous vital sign monitoring in a hospital's medical-surgical units., Methods: A cost-savings analysis was designed to calculate potential cost-savings for an average-sized U.S. community hospital (153 total beds) over a 1-year time horizon. Analysis parameters were extracted from national databases and previous studies that compared outcomes for patients receiving continuous vital sign monitoring (SpO 2 , HR, and RR) or standard of care (intermittent vital sign measurements) in medical-surgical units based on a targeted literature review. Clinical parameters and associated costs served as analysis inputs. The analysis outputs were costs and potential cost-savings using a 50% and 100% adoption rate of continuous monitoring technologies across the medical-surgical unit., Results: Potential annual cost-savings for in-hospital medical-surgical stays were estimated at $3,414,709 (2022 USD) and $6,829,418 for a 50% and 100% adoption rate, respectively. The cost-savings for an adoption rate of 100% equated to a ∼14% reduction in the overall annual cost of medical-surgical unit stays for an average-sized hospital. The largest contribution to potential cost-savings came from patients that avoided serious adverse events that require transfer to the intensive care unit; this resulted in annual cost-savings from reduced average length of stay between $1,756,613 and $3,513,226 (50% and 100% adoption rate, respectively). Additional cost-savings can be attained from reductions in in-hospital cardiac arrest-associated hospitalizations and decreased rapid response team activation., Conclusions: Our findings demonstrate that there is the potential for cost-savings of over $6.8 million dollars per year in an average-sized US community hospital by improving patient outcomes through implementation of continuous monitoring technologies in medical-surgical units. Continuous vital sign monitoring technologies that increase patient mobility and facilitate recovery may further contribute to cost-savings and should be considered for economic analyses. Future research is needed to explore these health-related outcomes.

Paper-based analytical devices, or μPADs, have proven to be valuable bioanalytical tools for a broad range of applications. New methods for μPAD fabrication are needed, however, to facilitate their mass production at a competitive cost. To address this need, we report the use of a boronic acid-containing siloxane polymer (BorSilOx) for patterning hydrophobic barriers for μPADs. This material functions by covalently binding to hydroxyl groups in the paper substrate. It is compatible with inkjet printing or roll-to-roll (stamping) processes, as demonstrated here using three different deposition methods. BorSilOx is able to render a broad range of cellulosic materials (from paper towels to wood) hydrophobic, with contact angle measurements demonstrating superhydrophobicity in many cases. We further demonstrate the utility of the polymer in μPADs via assays for pH and glucose.

Introduction: Complete and accurate documentation of opioids administered by patient-controlled analgesia (PCA) pumps is critical for ensuring a high-quality medication record and an accurate conversion of the intravenous (IV) regimen to oral therapy. Incomplete charting of PCA usage through a manual process may be associated with fragmented documentation of delivered therapy affecting the completeness of the medical record and the IV to oral dose conversion. This study is the first to evaluate the association between auto-documentation of opioid administration provided by PCA smart pump-electronic health record (EHR) interoperability and the completion of PCA opioid administration charting tasks., Methods: This retrospective cohort study was conducted at Lancaster General Hospital, Lancaster, Pennsylvania. Patients were assigned to pre-auto-documentation (n = 55) or post-auto-documentation groups (n = 58) based on whether they received PCA therapy prior to or after PCA-EHR interoperability was implemented. Charting of PCA therapy included documentation of the number of patient attempts, number of doses given, and total volume infused for both pre- and post-auto-documentation groups. In addition, total dose delivered was documented for the post-auto-documentation group. The overall chart-field completion rate was evaluated as the primary outcome. Individual chart completion percentages were assessed by stratified groups as secondary outcomes., Results: PCA smart pump-EHR interoperability with auto-documentation was associated with an increase in overall chart-field completion rate from 69.9 to 97.0% (p < 0.001). Auto-documentation was also associated with an increase in fully completed charts from 38 to 91% (139.3% increase, p < 0.001) and reductions of incomplete records in each stratified group (p < 0.001)., Conclusions: PCA smart pump-EHR interoperability with auto-documentation is associated with significant improvements in the completion of opioid administration chart-fields. Improved documentation of PCA administered opioids may have implications for the safety of opioid administration. Additional studies will be needed to assess the potential clinical impact of these results., Funding: ICU Medical, Inc.

Background: Smart pump-electronic health record (EHR) interoperability has been demonstrated to reduce adverse events and increase documentation and billing accuracy. However, relatively little is known about the impact of interoperability on infusion therapy billing claims and hospital finances., Objective: Our objective was to evaluate the association between smart pump-EHR interoperability with auto-documentation and current procedural terminology (CPT ® )-coded infusion-therapy billing claims submissions., Methods: At Penn Medicine Lancaster General Health (Lancaster, PA, USA), infusion-therapy billing data were collected for 158,379 patient days (a visit to the emergency department [ED] or 24 h admission to a non-ED unit) and divided into two groups: 78,241 pre- and 80,138 post-auto-documentation. The count and types of submitted CPT-coded claims were analyzed for ED/non-ED groups, inpatient/outpatient status and non-ED unit where the infusion was administered. Dollar amounts for CPT codes were calculated using Medicare Addendum B 2017. Patient day and CPT code counts were converted to annualized values to facilitate analysis., Results: Patient days did not increase significantly from pre- to post-auto-documentation, whereas annualized submitted CPT-coded claims increased significantly by 14.5% (p < 0.001). The corresponding billing claim dollar value increased by $US1,147,652 (13.5%). ED patient days increased by 2.0% (p = 0.44), whereas submitted CPT-coded claims increased significantly by 4.0% (p < 0.001) and $US478,980 (7.4%). Non-ED patient days increased by 2.8% (p = 0.2), whereas CPT-coded claims increased significantly by 31.7% (p < 0.001) and $US668,672 (34.0%). The total number of submitted CPT-coded claims increased by 13.4% for inpatients and 12.3% for outpatients., Conclusion: Our findings suggest that auto-documentation of infusion-therapy services may have a positive impact on hospital financial performance, which could help drive adoption of this technology.

Child maltreatment is a very complex medical and social problem. Many children have died as a result of child maltreatment; others are depressed, engaging in risky behaviors and substance abuse and running away from home. The purpose of this article is to provide an overview of child maltreatment in the United States. Characteristics and contributing factors of maltreatment are described, and health and behavior problems associated with maltreated adolescents will be reviewed. Additionally the role of the school nurse will be discussed. It is imperative that school nurses are aware of the significance of the problem and the effects that child maltreatment has on children as they mature into early adulthood.

Studies were made on the oncogenic response of 3086 young chicks to i.v. inoculation of MC29 avian leukosis virus from blood plasma of previous-passage birds or the supernatant fluid of cultures of chick embryo cells infected with strain MC29. Among the large variety of neoplasms of other tissues previously described, there occurred a high incidence of primary growths of the liver. Pathomorphology of the growths frequently differed greatly in both different hosts and the same bird, but some uniformity of the types of neoplasms was evident in many animals. Despite much variation in histopathology, the large proportion of growths could be grouped in several distinctive categories. Examinations by light and electron microscopy provided evidence of derivation of the tumors by alteration of hepatocytes originating principally in the portal regions as indicated by forms transitional from the parenchymal cells to the cells of the different types of growths. Neoplastic aspects of the growths were evident by infiltration and invasion of adjacent tissues, penetration of blood vessels, transplantability to other avian hosts (described in another report), and metastasis to distant organs including the lung, kidney, and spleen. There was no evidence of tumors arising from the biliary system, and growths of cells resembling the biliary type could be traced to altered hepatocytes. None of the findings suggested conversion of biliary-type cells to hepatocytes. Continued growth resulted in anaplastic and metaplastic changes in cell morphology and structural organization and in the formation of cartilage, osteoid, and sarcoma-like spindle-cell tumors of probable epithelial origin. Development of the growths wasnot associated with cirrhosis, and necrosis was limited to infrequent disseminated, essentially unicellular changes or necrobiosis of small groups of cells. The marked variations in the type of virus-induced growths demonstrated the remarkable capacity of cells morphologically inidistinguishable from the hepatocytes for the most diverse alterations in cell structure and tissue organization. This neoplastic response of hepatocytes to the MC29 strain constitutes the only demonstration thus far of the specific hepatocarcinogenic activity of an avian tumor virus.

Activity of RNA-dependent DNA polymerase (RDDP) from avian myeloblastosis virus (AMV), either in purified form or in virus lysates, was increased by phosphorylation. Stability of RDDP in lysates buffered with phosphate was much greater (no loss of activity in 48 hours at 4 degrees) than that in lysates buffered with Tris-Cl (76% loss). Activity lost in the Tris-buffered extracts was completely restored by phosphorylation. The findings suggested that AMV RDDP activity is influenced by the degree of phosphorylation of the enzyme or enzyme-associated proteins and that this chemical modification is mediated by protein phosphokinase and phosphoprotein phosphatase present in crude extracts of purified AMV. Application of these results provided the basis of procedures whereby RDDP can be recovered in significantly higher yield and purity than formerly.

A hepatomatous growth derived from primary liver tumors induced in chickens by i.v. inoculation with MC29 leukosis virus has been established and maintained in the avian host. Hepatoma tissue transplanted into the abdominal cavity in a total of 278 chicks in 35 experiments yielded tumors in 222 animals (80%). The i.m. implantation in 69 birds in 7 experiments resulted in growth in 67 chicks (97%). Tumor tissue introduced inadvertently into the s.c. tissue likewise grew very rapidly. Histological and cytological features of the transplants in all sites showed preservation of the morphological characteristics of the original primary liver tumors through repeated passages. The properties of this first transplantable hepatoma derived from virus-induced primary liver tumors are compared with those of other transplantable hepatomas.

Four virus-infected avian cell lines have been established in culture. Two of these lines, infected with BAI strain A virus, liberate only small quantities of virus in the culture fluid. The cells retain the ability to induce myeloblastic leukemia when inoculated i.v. into 1- to 2-day-old chicks, but do so less efficiently than freshly obtained myeloblasts. These cells do not appear to be transplantable, since the disease produced is characterized by the presence of myeloblasts that liberate large quantities of virus. The other two cell lines, infected with the MC29 strain of avian leukosis virus, liberate normal levels of infectious virus in the culture fluid. When these cells are inoculated into the wing web of 1- to 2-day-old chicks, tumors develop at the site of inoculation which are detectable as early as 4 to 7 days after challenge. Chromosome studies demonstrate that the four cell lines have karyotypes typical of Gallus domesticus. The myeloblastic cell lines (D.U. 11157 and D.U. 1765) show a reduction in the number of microchromosomes. These cell lines have been carried in continuous culture for various lengths of time, can be frozen, are easily recovered in viable form, and appear to be capable of indefinite growth.

Previous reports described the induction of avian renal neoplasms by leukosis virus strains BAI A [avian myeloblastosis virus (AMV)] and MC29, and illustrated morphological characteristics of the tumors. Continued studies in this work confirm evidence of the origin of the tumors from embryonal cells residual in the posthatched chick. The work further emphasizes differences in histopathology of the neoplasms caused by the two viruses and reveals differences in the histopathogenesis of the respective growths. Embryonal rests may consist of two types of cells, those of epithelial characteristics and a second element of differentiation between nephroblastema (mesenchyme) and epithelium and designated here as nephromesoblastoma. Infection by AMV induces tumors of epithelial characteristics and, in addition, derivatives of nephromesoblastoma consisting of cartilage, bone, areas of keratinization, and sarcoma. Keratinized structures in the nephroblastoma originate from nephromesoblastoma. In contrast, MC29 virus induces only epithelial growths representing principally aberrant and malformed glomerular and tubular structures with occasional cartilage derived from epithelial cells. MC29 tumors are completely lacking in nephromesoblastoma tissue and contain no bone, sarcoma, or keratinized formations. In MC29 tumors, occasional cartilage was derived from epithelium. Tumors caused by AMV exhibit the complex structure of nephroblastoma with all of the features of the growth in humans (Wilms' tumor). The neoplasms induced by both AMV and MC29 exhibit marked aberration, distortion, and malformation in the differentiation of the cells growing out from the embryonal rests representing rare manifestations of cell genetic influence inherent in the primordial growth of nephroblastema. The results thus illustrate fundamental differences in cellular composition and capacity to respond to etiologically different leukosis viruses.

From lots of 20 to 30 g of avian myeloblastosis virus RNA-dependent DNA polymerase was obtained in preparations of purity greater than 95% by using a two-step column chromatographic procedure employing DEAE (DE 52) and carboxymethylcellulose (CM 52.). Yields of RNA-dependent DNA polymerase varied from approximately 20,000 to 35,000 U/g of virus. Specific activity of the enzyme was about 35,000 to 60,000 U/mg of protein. Free of detectable RNase activity, the product exhibited a molecular weight of about 160,000, an isoelectric point of 6.5, and approximately 2 mol of fatty acid per mol of enzyme.

A protein kinase associated with purified virions of avian myeloblastosis BAI strain A was partially purified by ion-exchange chromatography and gel filtration. The transfer of phosphate catalyzed by this enzyme required a divalent metal ion and ATP as phosphate donor. GTP could not be substituted for ATP, and the reaction was unaffected by either cyclic AMP or beef-heart protein-kinase inhibitor. Of the virus and nonvirus proteins tested as phosphate acceptors, only acidic proteins were phosphorylated. In particular, purified preparations of reverse transcriptase from avian myeloblastosis virus did not accept phosphate. The enzyme is a basic protein (pI = 9.3), and, on the basis of molecular sieving through Sephadex G-200 and velocity sedimentation on glycerol gradient, the protein kinase has a molecular weight of 45,000.

The papillomas induced in domestic rabbits with virus procured from cottontails undergo progressive changes in the direction of malignancy when they grow vigorously. From the beginning they exhibit the traits whereby tumors are characterized, and they have malignant potentialities. In seven animals of a group of ten carrying papillomas for more than 200 days, cancer has developed, and in an eighth a tumor of problematic malignancy has arisen. One of the remaining two rabbits died early in the cancer period, and the papillomas of the other eventually retrogressed. Ten cottontails with induced growths of much longer duration have not developed cancer. The malignant tumors have all been acanthomatous in type, and have arisen directly from the papillomas by graded, continuous alterations. These have often gone further after malignancy has been attained, and have eventuated in great anaplasia. Metastasis has been frequent, and transplantation to another host has proved successful. Individual growths have occurred expressive of each stage of the transformation to cancer, as if through a stabilization at this stage; yet despite the variety thus afforded, the tumors must all be looked upon as the consequence of alterations in cells of a single sort, namely epidermal cells affected by the virus, and the alterations themselves have taken a single direction. In the morphology of many of the cancers the influence of the virus is still manifest. The better the papilloma grew, the more likely was cancer to occur, and the greater was the tendency to multiple tumors. In the most favorable rabbits malignant changes took place at numerous locations in the papillomatous tissue, and were imminent at many others. Intercurrent factors had much to do with determining frank carcinosis; and when the tendency to it was not marked their influence sometimes seemed crucial. Analogous instances of a graded alteration from papilloma to cancer are frequent in human pathology. The virus that gives rise to the rabbit papillomas must be looked upon as the primary cause of the cancers developing therefrom. Whether it is their proximate cause has yet to be determined.

The serum of a rabbit with large cancers resulting from the transplantation of a squamous cell carcinoma that had arisen from a virusinduced papilloma, possessed the power to neutralize the virus, and so too in less degree did that of an animal of the same transplantation series in which a small nodule had developed. The sera of rabbits carrying tar papillomas or the Brown-Pearce carcinoma proved wholly devoid of effect on the virus. The implantation of Brown-Pearce tumor material mixed with virus did not lead to an enduring establishment of the latter in the resulting growths, nor to any immediate changes in their morphological character. The significance of the facts is discussed.