Effects of a mastitis J5 bacterin vaccination on the productive performance of dairy cows: An observational study using propensity score matching techniques.

Inferring causal effects between variables when utilizing observational data is challenging due to confounding factors not controlled through a randomized experiment. Propensity score matching can decrease confounding in observational studies and offers insights about potential causal effects of prophylactic management interventions such as vaccinations. The objective of this study was to determine potential causality and impact of vaccination with an Escherichia coli J5 bacterin on the productive performance of dairy cows applying propensity score matching techniques to farm-recorded (e.g., observational) data. Traits of interest included 305-d milk yield (MY305), 305-d fat yield (FY305), 305-d protein yield (PY305), and somatic cell score (SCS). Records from 6,418 lactations generated by 5,121 animals were available for the analysis. Vaccination status of each animal was obtained from producer-recorded information. Confounding variables considered were herd-year-season groups (56 levels), parity (5 levels: 1, 2, 3, 4, and ≥5), and genetic quartile groups (4 levels: top 25% through bottom 25%) derived from genetic predictions for MY305, FY305, PY305, and SCS, as well as for the genetic susceptibility to mastitis. A logistic regression model was applied to estimate the propensity score (PS) for each cow. Subsequently, PS values were used to form pairs of animals (1 vaccinated with 1 unvaccinated control), depending on their PS similarities (difference in PS values of cows within a match required to be <20% of 1 standard deviation of the logit of PS). After the matching process, 2,091 pairs of animals (4,182 records) remained available to infer the causal effects of vaccinating dairy cows with the E. coli J5 bacterin. Causal effects estimation was performed using 2 approaches: simple matching and a bias-corrected matching. According to the PS methodology, causal effects of vaccinating dairy cows with a J5 bacterin on their productive performance were identified for MY305. The simple matched estimator suggested that vaccinated cows produced 163.89 kg more milk over an entire lactation when compared with nonvaccinated counterparts, whereas the bias-corrected estimator suggested that such increment in milk production was of 150.48 kg. Conversely, no causal effects of immunizing dairy cows with a J5 bacterin were identified for FY305, PY305, or SCS. In conclusion, the utilization of PS matching techniques applied to farm-recorded data was feasible and allowed us to identify that vaccination with an E. coli J5 bacterin relates to an overall milk production increment without compromising milk quality.

Predicting the periodic risk of anthrax in livestock in Victoria, Australia, using meteorological data.

Cases of anthrax in livestock are infrequently and irregularly reported in the state of Victoria, Australia; however, their impact on individual livestock, farming communities and the government agencies tasked with containing these outbreaks is high. This infrequency has been anecdotally associated with differences in annual and local weather patterns. In this study, we used historical anthrax cases and meteorological data from weather stations throughout Victoria to train a generalized linear mixed effects model to predict the daily odds of a case of anthrax occurring in each shire in the coming 30 days. Meteorological variables were transformed to deviations from the mean values for temperature or cumulative values for rainfall in the shire across all years. Shire was incorporated as a random effect to account for meteorological variation between shires. The model incorporated a post hoc weighting for the frequency of historic cases within each shire and the spatial contribution of each shire to the recently redefined Australian Anthrax Belt. Our model reveals that anthrax cases were associated with drier summer conditions (OR 0.96 (95% CI 0.95-0.97) and OR 0.98 (95% CI 0.97-0.99) for every mm increase in rainfall during September and December, respectively) and cooler than average spring (OR 0.20 (95% CI 0.11-0.52) for every °C increase in minimum daily temperature during November and warmer than average summer temperatures (OR 1.45 (95% CI 1.29-1.61) for every °C increase in maximum daily temperature during January. Cases were also preceded by a 40-day period of cooler, drier temperatures (OR 0.5 (95% CI 0.27-0.74) for every °C increase in maximum daily temperature and OR 0.96 (95% CI 0.95-0.97) for every mm increase in rainfall followed by a warmer than average minimum (or nightly) temperature 10 days immediately before the case (OR 1.46 (95% CI 1.35-1.58) for every °C increase in maximum daily temperature). These coefficients of this training model were then applied daily to meteorological data for each shire, and output of these models was presented as a choropleth and timeline plot in a Shiny web application. The application builds on previous spatial modelling and provides Victorian agencies with a tool to engage at-risk farmers and guide discussions towards anthrax control. This application can contribute to the wider rejuvenation of anthrax knowledge and control in Victoria and corroborates the anecdote that increased odds of disease can be linked to meteorological events.

Baseline characteristics and outcomes of children with cancer in the English-speaking Caribbean: A multinational retrospective cohort.

BACKGROUND: English-speaking Caribbean (ESC) childhood cancer outcomes are unknown. PROCEDURE: Through the SickKids-Caribbean Initiative (SCI), we established a multicenter childhood cancer database across seven centers in six ESC countries. Data managers entered patient demographics, disease, treatment, and outcome data. Data collection commenced in 2013, with retrospective collection to 2011 and subsequent prospective collection. RESULTS: A total of 367 children were diagnosed between 2011 and 2015 with a median age of 5.7 years (interquartile range 2.9-10.6 years). One hundred thirty (35.4%) patients were diagnosed with leukemia, 30 (8.2%) with lymphoma, and 149 (40.6%) with solid tumors. A relative paucity of children with brain tumors was seen (N = 58, 15.8%). Two-year event-free survival (EFS) for the cohort was 48.5% ± 3.2%; 2-year overall survival (OS) was 55.1% ± 3.1%. Children with acute lymphoblastic leukemia (ALL) and Wilms tumor (WT) experienced better 2-year EFS (62.1% ± 6.4% and 66.7% ± 10.1%), while dismal outcomes were seen in children with acute myeloid leukemia (AML; 22.7 ± 9.6%), rhabdomyosarcoma (21.0% ± 17.0%), and medulloblastoma (21.4% ± 17.8%). Of 108 deaths with known cause, 58 (53.7%) were attributed to disease and 50 (46.3%) to treatment complications. Death within 60 days of diagnosis was relatively common in acute leukemia [13/98 (13.3%) ALL, 8/26 (30.8%) AML]. Despite this, traditional prognosticators adversely impacted outcome in ALL, including higher age, higher white blood cell count, and T-cell lineage. CONCLUSIONS: ESC childhood cancer outcomes are significantly inferior to high-income country outcomes. Based on these data, interventions for improving supportive care and modifying treatment protocols are under way. Continued data collection will allow evaluation of interventions and ensure maximal outcome improvements.

Quantifying Lake Water Quality Evolution: Coupled Geochemistry, Hydrodynamics, and Aquatic Ecology in an Acidic Pit Lake.

Assessment of water quality evolution in the thousands of existing and future mine pit lakes worldwide requires new numerical tools that integrate geochemical, hydrological, and biological processes. A coupled model was used to test alternative hypothesized controls on water quality in a pit lake over ∼8 years. The evolution of pH, Al, and Fe were closely linked; field observations were reproduced with generic solubility equilibrium controls on Fe(III) and Al and a commonly reported acceleration of the abiotic Fe(II) oxidation rate by 2-3 orders of magnitude. Simulations indicated an ongoing acidity loading at the site, and the depletion of Al mineral buffering capacity after ∼5 years. Simulations also supported the existence of pH limitation on nitrification, and a limitation on phytoplankton growth other than the commonly postulated P and DIC limitations. Furthermore, the model reproduced the general patterns of salinity, pH, Al, and Fe during an uncontrolled river breach in 2011, however, incorporating sediment biogeochemical feedbacks is required to reproduce the observed postbreach internal alkalinity generation in the lake. The modeling approach is applicable to the study of hydrological, geochemical, and biological interactions for a range of lake and reservoir management challenges.

Needlestick injuries at a tertiary teaching hospital in Singapore.

This study investigated the incidence and risk to staff groups for sustaining needlestick injuries (NSIs) in the National University Hospital (NUH), Singapore. A retrospective cohort review of incident NSI cases was undertaken to determine the injury rate, causation, and epidemiological profile of such injuries. Analysis of the risk of sustaining recurrent NSI by occupation and location was done using the Cox proportional hazards model. There were 244 NSI cases in 5957 employees in NUH in 2014, giving an incidence rate of 4·1/100 healthcare workers (HCWs) per year. The incidence rate was highest for doctors at 21·3, and 2·7 for nurses; 40·6% of injuries occurred in wards, and 32·8% in operating theatres. There were 27 cases of repeated NSI cases. The estimated cost due to NSIs in NUH ranged from US$ 109 800 to US$ 563 152 in 2014. We conclude that creating a workplace environment where top priority is given to prevention of NSIs in HCWs, is essential to address the high incidence of reported NSIs. The data collected will be of value to inform the design of prevention programmes to reduce further the risk of NSIs in HCWs.

Intramammary immunization with ultraviolet-killed Escherichia coli shows partial protection against late gestation intramammary challenge with a homologous strain.

The objective of this study was to evaluate the efficacy of intramammary immunization with UV-killed Escherichia coli ECC-Z on prevention of intramammary colonization after a challenge with a dose of the homologous E. coli ECC-Z live bacteria. A total of 10 cows were included in a study to evaluate the efficacy of intramammary immunization. All 10 cows received an intramammary immunization of 100 cfu of UV-killed E. coli ECC-Z bacteria into one hind quarter at the time of dry off. Approximately 2wk before the anticipated calving date, both hind quarters of all cows were challenged with 100 cfu of live E. coli ECC-Z bacteria. Five of the cows were vaccinated parenterally with a commercial J5 bacterin, and 5 cows served as controls with no parenteral vaccination. The cows were then followed over time and infection risk, clinical scores, somatic cell count, and milk production were observed over time. The results of these 10 cows showed partial protection of intramammary immunization on the outcome of a subsequent homologous intramammary challenge. Immunization resulted in a lower probability of infection, a lower bacteria count, lower somatic cell counts and milk conductivity, a lower clinical mastitis score, and increased milk production compared with unimmunized control quarters. Once the analysis was corrected for immunization, parenteral J5 vaccination had no significant effect on any of the measured parameters. These results provide the first evidence that intramammary immunization may improve the outcome of an intramammary E. coli infection in late gestation and onset of mastitis immediately following parturition. Unlike systemic vaccination, which generally does not reduce the intramammary infection risk, the intramammary immunization did show a 5-times reduced odds of an established intramammary infection after challenge. Cytokine profiles indicated a local return of proinflammatory response after challenge as the data showed a more pronounced increase in in IFN-γ with a subsequent negative feedback due to a spike in the level of IL-10 in immunized quarters relative to nonimmunized quarters. Although these results are preliminary and obtained on only 10 cows, the results provide insight into the biological benefits of triggering mucosal immunity in the mammary gland.

Quantitative assessment of the distribution of dissolved Au, As and Sb in groundwater using the diffusive gradients in thin films technique.

The mobility of groundwater and its reactivity with subsurface lithologies makes it an ideal medium for investigating both the mineralogy of the extensive volume of the rocks and soils that it comes into contact with, including the distribution of potential commodities, and the presence of contaminants. Groundwater grab sampling is potentially an effective tool for evaluating metal and metalloid concentrations but can suffer from poor replication and high detection limits. This study evaluates the diffusive gradients in thin films (DGT) technique to detect signatures of Au mineralization in groundwater, as well as associated pathfinder and potential contaminant elements (As and Sb). The DGT technique was modified for Au by evaluating a "gel-less" configuration, with diffusion onto an activated carbon binding layer being controlled by the 0.13 mm thick filter membrane (0.45 µm porosity) only, in order to increase sensitivity in quiescent solutions. Laboratory-based measurements indicated that the diffusive boundary layer (DBL) was ∼ 0.40 mm in thickness in quiescent solutions. The modified DGT samplers were then deployed alongside ferrihydrite DGT devices (fitted with 0.8 mm diffusive gels) to simultaneously measure Au, As and Sb in groundwaters surrounding a known arsenopyrite-hosted Au ore body. DGT-measured Au concentrations ranged from 2.0 ng/L to 38.5 ng/L, and were within a factor of 5 of grab sample concentrations. DGT-measured concentrations of As and Sb were above the detection limits, while grab sample concentrations of As and Sb were often close to or below detection. The DGT technique demonstrated methodological improvement over grab sampling of groundwater for the investigated elements with respect to sensitivity, replication, and portability, although DGT requires further evaluation in a wider range of groundwater environments and conditions.

Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats.

INTRODUCTION/OBJECTIVES: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. ANIMALS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 µg/mL (0.45-1.17 µg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 µg/mL (1.91-2.48 µg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.

Development of the diffusive gradients in thin films technique for the measurement of labile gold in natural waters.

Gold is a precious metal that exists in most soils, sediments, and natural waters at extremely low concentrations (<1 µg/kg). The diffusive gradients in thin films (DGT) technique, used extensively for measuring trace metal concentrations in soils, sediments, and waters, has potential for geochemical exploration for gold, but has not been developed for this metal. This work investigates the possibility of measuring labile gold using DGT by introducing a new binding layer based on activated carbon. The performance of this new technique was assessed using gold(III) chloride in solution by: (1) determining the diffusion coefficient of gold(III) in hydrogels; (2) determining the uptake of gold(III) chloride by the new activated carbon binding layer; (3) determining an elution methodology for the binding layer and evaluating its efficiency; (4) assessing the capacity of the activated carbon binding layer to adsorb gold; (5) determining the effect of pH and ionic strength (as NaCl) on performance, and (6) assessing the selectivity of the new binding layer for gold. It was found that the diffusion coefficient of gold(III) increased as solution pH decreased. The diffusion coefficient also increased at high ionic strength (≥0.1 M NaCl). Accounting for these phenomena, the DGT technique behaved predictably under all tested conditions. The technique can potentially be used as a geochemical exploration tool for gold in soils and in aqueous environments, with method detection limits as low as 0.9 ng/L for a 7-day deployment.

Hepatopathy in Victorian dogs consuming pet meat contaminated with indospicine.

BACKGROUND: Indospicine is an arginine analogue and a natural toxin occurring only in Indigofera plant species, including Australian native species. It accumulates in the tissues of grazing animals, persisting for several months after ingestion. Dogs are particularly sensitive to indospicine toxicity and can suffer fatal liver disease after eating indospicine-contaminated pet meat. METHOD: A disease outbreak investigation was launched following notification to Agriculture Victoria of a cluster of 18 dogs displaying acute, severe, hepatopathy in the East Gippsland Shire in June 2021. RESULTS: Between June and September 2021, 24 pet dogs died, and 40 others experienced liver disease after eating commercially prepared pet meat found to contain indospicine. The investigation identified the toxin in serum and liver samples from affected dogs and at high levels in some samples of pet meat eaten by the dogs. Twenty-six horses that were moved from the Northern Territory and processed at a Pet Meat Processing facility (knackery) in eastern Victoria over a period of 14 days in late May-early June 2021 were identified as the likely source of the indospicine toxin in the pet meat. Pet meat produced by the knackery and on-sold by several retailers was determined to be the cause of the illness and death in the dogs. CONCLUSION: This is the first report of severe and frequently fatal hepatopathy in dogs in Victoria relating to consumption of pet meat contaminated with indospicine.

Routine antiseptic baths and MRSA decolonization: diverse approaches across Singapore's acute-care hospitals.

To determine the variation in practices on meticillin-resistant Staphylococcus aureus (MRSA) surveillance and management of MRSA-colonized patients amongst 17 acute healthcare facilities in Singapore, the Ministry of Health convened a sharing session with Infection Prevention and Control Leads. All hospitals practised close to universal MRSA entry swabbing in keeping with national policy. There were, however, major variations in the response to both positive and negative surveillance swabs across facilities including the role of routine antiseptic bathing and MRSA decolonization. Most undertaking decolonization considered its role to be in 'bioburden reduction' rather than longer-term clearance.

One size does not fit all: the effectiveness of messaging for hand hygiene compliance by profession in a tertiary hospital.

To determine the effectiveness of our messaging for hand hygiene compliance by profession, we conducted a hospital-wide survey followed by profession-specific focus group discussions to investigate impact, perceptions and areas for improvement. Results showed a good understanding that hand hygiene is a crucial part of the infection-prevention programme; however, the acceptance and impact of messages varied between professions and required tailoring. Motivation, use of influential role models and social cohesion should be considered when designing profession-specific messages to improve infection-prevention-related change uptake among healthcare professional groups.

High speed scintillation autoradiography.

Impregnation of nuclear track emulsion with liquid scintillator and exposure at -85 degrees C allows rapid autoradiographic labeling. With tritiated thymidine of high specific activity (40 to 60 curies per millimole), exposure time can be shortened to 20 to 60 minutes, allowing complete sample processing within 4 hours. In experiments requiring isotopes with low incorporation rates or low specific activity, exposure time can be shortened from months to several days.

Primary bioassay of human tumor stem cells.

A simple method has been developed to support human tumor stem cell colony growth in soft agar. The technique appears suitable for culture of a variety of neoplasms of differing histopathology. Tumor stem cell colonies arising from different types of cancer have differing growth characteristics and colony morphology. This bioassay should be suitable for clinical studies of effects of anticancer drugs or irradiation on human tumor stem cells.

Lymphocyte stimulation: selective destruction of cells during blastogenic response to transplantation antigens.

The blastogenic response of human lymphoid cells toward any individual's transplantation antigens can be deleted by the addition of tritiated thymidine of high specific activity during the incubation of the lymphoid cells in mixed leukocyte culture. After the immunocompetent clones which responded to histocompatibility antigens had been destroyed, the remaining population still retained its capacity to respond to unrelated antigens, including other transplantation antigens.

Classical swine fever in Victorian domestic pigs: evidence of disease freedom.

OBJECTIVE: Australia is currently regarded as free of classical swine fever (CSF), a highly contagious disease of pigs caused by a pestivirus. This study aimed to provide additional evidence that the Victorian domestic pig population is free of CSF. DESIGN: A structured representative sero-prevalence survey of Victorian domestic pigs at slaughter. METHOD: Three-hundred and ninety-one pigs from 23 holdings were sampled at the time of slaughter between March 2016 and October 2017. RESULTS: All samples were negative for CSF virus Ab on ELISA. Because of uncertainty in the sensitivity of the CSF Ab ELISA, estimates of the true prevalence of CSF were calculated using Bayesian methods. The median and upper bound of the 95% credible intervals for the true prevalence of CSF was zero when the diagnostic sensitivity of the CSF Ab ELISA was assumed to range from 0.75 to 0.95. CONCLUSION: These results provide evidence that the population of domestic pigs in Victoria in 2016-2017 was free of CSF.

Perceptions of anthrax in livestock from Victorian dairy farmers in the Goulburn-Murray region of Victoria, Australia.

To inform future anthrax surveillance and response activities and to revitalise the communication strategy for producers and their communities, seven dairy farmers in the Goulburn-Murray region of Victoria participated in a Design Thinking process to create a better method to share information about the annual probability of anthrax in their region. Design Thinking is a structured, user-centric design process that begins with intentionally un-structured interviews. Following each interview, transcripts are disassembled into common themes identified by clustering similar statements from these interviews. This short contribution presents these themes re-framed into eight core statements. These statements provide a framework for the remainder of the Design Thinking process but in isolation provide a reference for stake-holding agencies seeking to maximise farmer participation in surveillance programs for early anthrax detection, to encourage active farmer participation during a response and to minimise any anthrax-associated stigma by affected farmers post-response.

Immunoglobulin synthesis and total body tumor cell number in IgG multiple myeloma.

Studies of synthesis of IgG paraproteins were performed in 10 patients who had IgG myeloma in order to quantitate cellular immunosynthetic functions and derive estimates of the number of tumor cells present in such patients. Serial in vitro studies demonstrated constancy in the cellular rate of IgG paraprotein secretion for up to 8 months. Average molecular synthesis rates in different patients ranged from 12,500 to 85,000 molecules of IgG per minute per myeloma cell. Estimated total body tumor cell number ranged from 0.5 x 10(12) to 3.1 x 10(12) myeloma cells, and could be correlated with the degree of skeletal damage observed on roentgenograms (P = <0.01). Serial measurements of tumor cell number may prove useful in characterizing the growth rate and natural history of multiple myeloma. Myeloma is the first metastatic human malignancy in which quantitative measurements of the body's burden of malignant cells have been obtained.

Immunology of the lower respiratory tract. Functional properties of bronchoalveolar lymphocytes obtained from the normal canine lung.

While the alveolar macrophage has been studied extensively, little attention has been directed toward the immune functions of the bronchoalveolar lymphocyte. These cells, obtained by bronchopulmonary lavage of the normal canine lung, are derived from the air side of the alveolar-capillary membrane of the lower respiratory tract. The distribution of lymphocyte types within the bronchoalveolar cell population was determined and compared with that of leukocytes from blood and spleen.IgG synthesis in vitro was used as a measure of bone marrow-derived lymphocyte (B cell) function, and the blastogenic response of cell cultures to phytohemagglutinin was used as a measure of the presence or absence of thymus-dependent lymphocytes (T cells). De novo synthesis of IgG by bronchoalveolar cells was demonstrated consistently by two independent radio-immunoassays. Therefore, B cells are present in the air spaces of normal canine lungs. T cells were generally not detectable in aliquots of the same cell populations but could be recruited into alveolar spaces after local irritation. The distribution of lymphocyte types within the bronchoalveolar cell population is unique and distinctly different from that of blood and spleen. The spleen is rich in both T cells and B cells, blood is rich in T cells but poor in B cells, whereas the lung lacks T cells and contains substantial numbers of immunoglobulin-producing B cells. The findings indicate that bronchoalveolar lymphocytes do not reflect simply the lymphoid composition of peripheral blood.

Primary bioassay of human myeloma stem cells.

The ability to clone primary tumors in soft agar has proven useful in the study of the kinetics and biological properties of tumor stem cells. We report the development of an in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar. Colony growth has been observed from bone marrow aspirates from 75% of the 70 patients with multiple myeloma or related monoclonal disorders studied. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after 2-3 wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 10(5)-10(6) and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60-80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Colony growth was most easily achieved from the bone marrow cells of untreated patients or those in relapse. Only 50% of bone marrow samples from patients in remission were successfully cultured. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells was actively in transit through the cell cycle. Velocity sedimentation at 1 g showed myeloma stem cells sedimented in a broad band with a peak at 13 mm/h. Antibody to granulocyte colony-stimulating factor did not reduce the number or size of the colonies. Increased numbers of myeloma colonies were seen when the marrow was depleted of colony-stimulating factor elaborating adherent cells before plating. This bioassay should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B)-cell neoplasia. In addition, systematic and predictive studies of anticancer drug effects on myeloma stem cells should now be feasible.