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STRUCTURED Summary Background Registered nurses perform numerous functions critical to the success of antimicrobial stewardship but only 63% of pre-registration nursing programmes include any teaching about stewardship. Updated nursing standards highlight nurses require antimicrobial stewardship knowledge and skills. Aim To explore the delivery of key antimicrobial stewardship competencies within updated pre-registration nursing programmes. Method A cross-sectional survey design. Data were collected between March and June 2021. Findings Lecturers from 35 UK universities responsible for teaching antimicrobial stewardship participated. The provision of antimicrobial stewardship teaching and learning was inconsistent across programmes with competencies in infection prevention and control, patient centred care, and interprofessional collaborative practice taking precedent over those pertaining to the use, management, and monitoring of antimicrobials. On-line learning and teaching surrounding hand hygiene, personal protective equipment, and immunisation theory was reported to have increased during the pandemic. Only a small number of respondents reported that students shared taught learning with other healthcare professional groups. Conclusion There is a need to ensure consistency in antimicrobial stewardship across programmes, and greater knowledge pertaining to the use, management and monitoring of antimicrobials should be included. Programmes need to adopt teaching strategies and methods that allow nurses to develop interprofessional skill in order to practice collaboratively.

Acute coronary syndrome is a rare complication of vasculitis. We present a case of fulminant medium-vessel vasculitis, most likely PAN, complicated by STEMI and stroke, that was successfully treated with percutaneous revascularization, high-quality stroke care, and immunosuppression. This case highlights the importance of prompt diagnosis and treatment of vasculitis and the recognition of coronary and cerebral ischemia as potentially serious complications.

Curriculum that informs students about social work practice with Native Peoples must be culturally relevant and responsive. However, the voices of Native Peoples are often excluded from identification of needs and relevant practice models for services. A unique partnership between the Native People from several tribes and a rural southwestern social work program led to an innovative project of curriculum development for social work practice with Native Peoples. The curriculum content evolved directly from the experiences of Native tribal members in the region. A retreat format initiated the process with subsequent quarterly meetings that provided a venue for course development with specific attention to the development of Native faculty as authors and teachers. The impact of this process is discussed through the voices of Council members, students, and Native instructors. This paper offers guidance to social work programs who are interested in expanding their understanding of Native curriculum development.

Introduction: A study of 42,000 cardiology consults within the Veterans Health Administration (VHA) in 2016 found that patients who received electronic consultation (e-consults) had similar healthcare costs at 6 months compared to those who received face-to-face (F2F) consults. However, results may have been confounded if patients with less costly conditions received e-consults. Our aim was to compare costs between those receiving F2F vs. e-consults for a similar indication. Hypothesis: Electronic rather than F2F consultation for atrial fibrillation (AF) management will be associated with lower total healthcare costs. Methods: We conducted a retrospective cohort study of a national sample of VHA patients who received cardiology consultation in 2016. We used a natural language processing script to identify consults for AF management. Primary outcomes were total healthcare costs at 3 and 6 months. Secondary outcomes included inpatient and outpatient costs. We compared costs between groups using a generalized linear model with a gamma distribution and log link. We adjusted for community wage and Charlson comorbidity indices, distance to nearest facility, age, and gender. Standard errors were clustered at the facility level. Results: We sampled 176 F2F and 136 e-consults from 43 facilities. Mean total 6-month costs were $12,928 (95% confidence interval [CI]: 1,377; 40,644) and $8,286 (95% CI: 959; 31,320) among e-consult and F2F groups, respectively. The e-consult group had 12.3% higher 3-month (p Conclusions: Use of e-consults for AF management is associated with reduced inpatient costs at 3 months, but higher total costs, which were largely driven by outpatient costs. Improving our understanding of healthcare utilization after initial consultation, or in differences in reasons for consultation within AF management may help explain these differences.

Accurate evaluation of salt diffusion coefficients from transport rate data in ion exchange membranes requires accounting for frame of reference and non-ideal thermodynamic effects. Due to a lack of models and experimental data quantifying membrane ion activity coefficients, it has been impossible to evaluate the impact of non-ideal thermodynamic effects on observed salt diffusion coefficients. Here, a framework is presented that includes both frame of reference (i.e., convection) and non-ideal thermodynamic effects in calculating salt diffusion coefficients in ion exchange membranes. Effective concentration averaged NaCl diffusion coefficients were determined as a function of upstream NaCl concentration in commercial ion exchange membranes from NaCl permeability and sorption measurements via the solution-diffusion model. Frame of reference effects were evaluated using a version of Fick's law that accounts for convection. The factors necessary to account for non-ideal thermodynamic effects were developed using Manning's counter-ion condensation theory. At low upstream NaCl concentrations, frame of reference and non-ideal thermodynamic effects on diffusion coefficients were negligible. However, at higher upstream NaCl concentrations (e.g., >0.1 M), both effects contribute measurably to NaCl diffusion coefficients. Correcting for frame of reference effects increased apparent NaCl diffusion coefficients. However, correcting for thermodynamic non-idealities of the ions sorbed into the membranes reduced apparent NaCl diffusion coefficients. Fortuitously, for the materials considered in this study, frame of reference and non-ideal thermodynamic effects nearly cancel each other.

Background Up to one-third of children will have a mental health condition. However, only 20% of these children receive mental health care and half of mental health referrals from primary care providers result in children being connected to care. Highlighting the need to improve pediatric resident training in the management of mental health issues, the AAP published a policy statement calling for enhanced mental health curriculums in pediatric residencies. Methods We developed a novel 6-month longitudinal mental health curriculum based on several existing models used to train practicing pediatricians. All pediatric residents were invited to participate; this project was IRB-exempt. The curriculum included a child psychiatrist-led, half-day orientation focused on assessment, diagnosis and management of major depressive disorder (MDD), generalized anxiety disorder (GAD), attention deficit hyperactivity disorder (ADHD) and acute behavioral events through a case-based, interactive format, as well as monthly group-based discussions of resident patients. Residents were paired with a psychiatrist consultant for as needed, real-time consultation throughout the projects duration. Residents were surveyed pre- and post-orientation for perceived comfort in the diagnosis and treatment of pediatric mental health conditions. Results Nineteen percent of (14/74) residents participated. Post-orientation, residents reported clinically meaningful increased comfort in all survey domains. Statistically significant (p Conclusions Developing and implementing a longitudinal mental health curriculum in conjunction with child psychiatrists is both feasible and results in overall improvement in residents comfort level with common mental health diagnoses.

The objective of this study was to use estrous behavior alone to determine the appropriate time for beginning an oxytocin treatment protocol for estrus suppression. We hypothesized that administration of oxytocin beginning 8 days after the onset of estrus will prolong the luteal phase in mares. Twenty-three light breed mares (aged 4-20 years) were exposed to a stallion and observed for signs of sexual receptivity. Mares not displaying signs received 250 μg of cloprostenol intramuscularly (IM) and were teased again 3-4 days later. On the day that estrous behavior was observed (Day 0), mares were randomly divided into two groups: oxytocin (n = 11): oxytocin (60 IU, IM) was administered once daily from Day 8-17; control (n = 12): did not receive treatment. Blood was collected from all mares every 4 days throughout Day 17, and every 7 days thereafter until Day 45. Serum progesterone concentrations1.0 ng/mL were indicative of a functioning corpus luteum. Interestrus interval was defined as the period between Day 0 and the day when progesterone next reached1.0 ng/mL. The average interestrus interval was higher for treated mares compared with control mares (32.4 ± 4.2 vs. 21.8 ± 1.5 days, respectively, P = .01). In the oxytocin group, the interestrus interval was longer than 31 days in 6 of 11 (54.5%) mares and up to 45 days in 5 of 11 mares (45.5%). We conclude that luteal maintenance beyond 30 days was attained by once-daily oxytocin administration beginning 8 days following behavioral estrus in a majority of mares.

Study Design Cross-sectional. Objectives To determine the accuracy of athlete single leg test on the Biodex balance system (BBS) and Y-balance test in distinguishing individuals with chronic ankle instability (CAI) from healthy controls. Background Lateral ankle sprains are common orthopaedic injuries that often result in chronic ankle instability characterised by many residual symptoms. Single leg standing test and Y-balance are commonly used to assess postural control in individuals with CAI. However, the accuracy of these tests for distinguishing individuals with CAI from healthy controls are unknown. Methods and Measures Eighteen individuals with unilateral CAI (age=22.4±2.8 years; IdFAI=21.3±8.3), 15 individuals with unilateral injury who are copers (age=22.4±3.2 years; IdFAI=7.3±2.5), and 18 healthy controls (age=22.2±3.0 years; IdFAI=2.9±3.1) participated. Everyone completed two 20 s trials of athlete single leg testing without visual feedback at Levels 4, 8 ,12, and static levels on the BBS. Each level corresponded to the degree of tilt of the platform surface with a lower number corresponding to lesser stability. Overall stability index (OSI) and sway area was calculated for each level. Maximum reach values of three trials for 3 directions (Anterior, postero-medial and postero-lateral) were recorded and used to calculate the composite score for the Y-balance test. Accuracy was quantified using area under curve from ROC curve analysis. Results Comparing CAI and controls, the accuracy ranged from 0.213 for Y-balance composite score (indicating failure to accurately distinguish CAI from Controls) to 0.62 for sway area at Level 8 (indicating poor accuracy). Comparing CAI and Copers, the accuracy ranged from 0.389 for OSI at Level 12 (indicating failure to accurately distinguish CAI from Copers) to 0.60 for sway area at Level 8 (indicating poor accuracy). Conclusion Athlete single leg testing on BBS and Y-balance test seem to have poor diagnostic accuracy in distinguishing individuals with CAI from healthy controls.

Study Design Cross-sectional. Objectives To investigate the relationship between subjective measures of function and quality of life, and objective measures of balance in individuals with Chronic Ankle Instability (CAI). Background CAI results due to an inadequately healed ankle sprain, and may impact the individual’s balance and quality of life. However, it is unknown how they are related. Methods and Measures Participants: 1) CAI group (n=18; age 22.4±2.8 years) had a history of at least 1 significant ankle sprain with feelings of instability and/or recurrent sprain, 2) Copers (n=15; age 22.4±3.2 years) also sustained 1 significant ankle sprain, but are able to return to their pre-injury levels without residual symptoms and 3) Control (n=18; 22.2±3.0 years), who never had ankle injury. Static balance was tested using single leg standing on the Biodex Balance System platform set to levels of varying stability. Dynamic balance was tested using Y-balance system. Foot and Ankle Ability Measure (FAAM) and the Foot and Ankle Outcome Score (FAOS) surveys were administered. Results For CAI group, the FAOS quality of life subscale was negatively correlated with sway index and area when the platform was stable (both r>=−0.52; p =−0.49; p Conclusions For those with a history of ankle sprain, subjective measures seemed to be related to performance on the least challenging static balance and dynamic balance test. Subjective measures of quality of life and function do not seem to be related to more challenging static balance tests.

The ability to see motion is critical to survival in a dynamic world. Decades of physiological research have established that motion perception is a distinct sub-modality of vision supported by a network of specialized structures in the nervous system. These structures are arranged hierarchically according to the spatial scale of the calculations they perform, with more local operations preceding those that are more global. The different operations serve distinct purposes, from the interception of small moving objects to the calculation of self-motion from image motion spanning the entire visual field. Each cortical area in the hierarchy has an independent representation of visual motion. These representations, together with computational accounts of their roles, provide clues to the functions of each area. Comparisons between neural activity in these areas and psychophysical performance can identify which representations are sufficient to support motion perception. Experimental manipulation of this activity can also define which areas are necessary for motion-dependent behaviors like self-motion guidance.

Introduction: Viral hemorrhagic fever (VHF) outbreaks, with high mortality rates, have often been amplified in African health institutions due to person-to-person transmission via infected body fluids. By collating and analyzing epidemiological data from documented outbreaks, we observed that diagnostic delay contributes to epidemic size for Ebola and Marburg hemorrhagic fever outbreaks. Methodology: We used a susceptible-exposed-infectious-removed (SEIR) model and data from the 1995 outbreak in Kikwit, Democratic Republic of Congo, to simulate Ebola hemorrhagic fever epidemics. Our model allows us to describe the dynamics for hospital staff separately from that for the general population, and to implement health worker-specific interventions. Results: The model illustrates that implementing World Health Organization/US Centers for Disease Control and Prevention guidelines of isolating patients who do not respond to antimalarial and antibacterial chemotherapy reduces total outbreak size, from a median of 236, by 90% or more. Routinely employing diagnostic testing in post-mortems of patients that died of refractory fevers reduces the median outbreak size by a further 60%. Even greater reductions in outbreak size were seen when all febrile patients were tested for endemic infections or when febrile health-care workers were tested. The effect of testing strategies was not impaired by the 1-3 day delay that would occur if testing were performed by a reference laboratory. Conclusion: In addition to improving the quality of care for common causes of febrile infections, increased and strategic use of laboratory diagnostics for fever could reduce the chance of hospital amplification of VHFs in resource-limited African health systems.

Background There is little information on the duration of nasal shedding of EHV-1 from horses with naturally occurring equine herpesvirus myeloencephalopathy (EHM). Objectives To evaluate the duration of nasal shedding of EHV-1 in horses affected by EHM. Animals One hundred and four horses naturally exposed to EHV-1, 20 of which had clinical signs of EHM. Methods All horses on affected premises were monitored. Those horses developing EHM were sampled in a longitudinal outbreak investigation. Nasal swabs were collected daily from 16 of 20 horses affected by EHM. A qPCR was performed on 98 of 246 nasal swab samples to determine nasal shedding duration. Historical and clinical information was analyzed to evaluate potential risk factors for developing EHM and duration of shedding during this outbreak. Results The last day shedding was detected in any horse was Disease Day 9. EHV-1 was detected in two-thirds of horses tested on Disease Days 0–3. The amount of EHV-1 DNA found in nasal swabs varied markedly and was not associated with disease severity or age. The odds of developing EHM were greater for febrile horses (OR = 20.3; 95% CI 3.4–390.3; P = .01) as well as for horses attending the riding clinic (OR = 4.1; 95% CI 0.84–21.65; P = .08). Conclusions and Clinical Importance Biosecurity measures should be implemented for a minimum of 14 days beyond the onset of clinical signs of EHM. Animal managers cannot rely on the severity of clinical signs to predict the duration of EHV-1 shedding.

The refeeding syndrome is increasingly recognised. It is a serious change in electrolytes when nutrition is reintroduced to malnourished patients. Alcohol dependence is a risk factor for the refeeding syndrome. We report a prospective cohort study of 36 alcoholics hospitalised for withdrawal management. We found no evidence of refeeding syndrome in any patient after 3 days of hospitalisation, despite hypomagnesaemia, a risk factor for the refeeding syndrome being prevalent (44% of subjects). Low thiamine levels were infrequent affecting 3/29 (10%). We recommend that in alcoholics admitted for managed withdrawal, risk of refeeding syndrome appears to be low, and routine testing of repeat electrolytes appears unnecessary.

The diagnosis of cirrhosis requires screening for oesophageal varices by upper gastrointestinal endoscopy. In many countries, serological tests and elastography are replacing liver biopsy for diagnosing cirrhosis. The aims of this study were to see whether there was an optimal cut-off of liver stiffness that could predict the presence of large (>F2) oesophageal varices and whether this was disease specific. A total of two hundred and twenty-two patients with all cause cirrhosis (Child class A) were screened, and 211 had successful elastography and are included in the analysis. Of the patients studied, one hundred and thirty-two patients had no or small F1 varices and 79 had large varices. Liver stiffness of 19.8 kPa had a negative predictive value of 91% and a positive predictive value of 55% with an area under the curve (AUC) on receiver operating characteristics (ROC) of 0.73 in differentiating between small and large varices. Seven patients with large varices would have been incorrectly classified. In the 157 patients with hepatitis C as the aetiology of cirrhosis, the negative predictive value was 98% and only one patient was misclassified. Liver stiffness was superior in diagnostic accuracy to platelet count in all patients. A liver stiffness of >19.8 kPa could be utilized as a cut-off for endoscopy and beta blocker utilization, particularly in patients with hepatitis C.

There is anecdotal evidence that a significant number of students studying computing related courses at degree level have difficulty with sub-GCE mathematics. Testing of students' skills is often performed using diagnostic tests and a number of computer-based diagnostic tests exist, which work, essentially, by testing one specific diagnostic skill at a time. This paper proposes using a multiple-choice computer-based diagnostic test where each question has a number of diagnostic skills associated with it in order to allow more flexible questions. A simple measure of a diagnostic skill's competency could be obtained by calculating the number of questions answered correctly, divided by the total number of questions, associated with that skill. However, because a question may have many skills associated with it, if a question is wrong, then each skill is deemed to be problematic, even though there may not be a problem with all skills. A technique has been developed that refines the initial skill competencies and iteratively re-calculates the skills based on all other competencies. Pilots of the new diagnostic test with first year computing students indicate that particular mathematical problems exist for many students, and suggest that the iterative algorithm produces a more precise indication of competencies than a simple competence measure approach.

Hepatic fibrosis is the final common pathway for many different liver insults. Originally considered to be irreversible, hepatic fibrosis is now known to be a dynamic process with a significant potential for resolution. The diagnosis and quantitation of fibrosis have traditionally relied on liver biopsy. However, there are a number of drawbacks including the invasive nature of the procedure, sampling error, and interobserver variability. This article reviews the current role of liver biopsy in the assessment of hepatic fibrosis and discusses the role of the newer noninvasive methods including serum markers and radiologic tests.

Background and Aim: Cyclooxygenase-2 (COX-2), a target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), is upregulated in chronic hepatitis B and may have a role in hepatocellular carcinoma. Little is known about the expression of COX-2 in chronic hepatitis C (HCV) infection. The aim the present study was to evaluate the extent of COX-2 expression in liver biopsies in patients with HCV infection and to determine the effect of treatment with interferon α (IFN). Methods: Percutaneous liver biopsy specimens were retrieved. Following formalin fixation and paraffin embedding, the biopsies were histologically evaluated for inflammation and fibrosis. The extent of COX-2 expression was measured by the avidin biotin immunohistochemical technique using a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according to the number of hepatocytes expressing COX-2. Data were analyzed using Student's t-test. Results: Liver biopsies from 10 patients before and after treatment with IFN were obtained and compared with nine normal liver biopsies. All of the liver biopsies showed some COX-2 expression. COX-2 expression was confined to hepatocytes and bile duct epithelium and was not detected in vascular endothelium or inflammatory cells. The extent of COX-2 expression was greater in hepatitis C infected liver biopsies than in normal biopsies. Following treatment with IFN, there was a greater than threefold reduction in COX-2 expression (P

Background Although drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. Objective We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). Methods We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least 1 differential blood count. We used multivariate Cox proportional hazards models with time-varying antibiotic treatment indicators to assess the effect of demographic data and antibiotic exposures on eosinophilia and subsequent HSRs, including documented rash, renal injury, and liver injury. Possible drug rash with eosinophilia and systemic symptoms (DRESS) syndrome cases were identified and manually validated. Results Of 824 patients (60% male; median age, 60 years; median therapy duration, 41 days), 210 (25%) had eosinophilia, with median peak absolute eosinophil counts of 726/mL (interquartile range, 594-990/mL). Use of vancomycin, penicillin, rifampin, and linezolid was associated with a higher hazard of having eosinophilia. There was a subsequent HSR in 64 (30%) of 210 patients with eosinophilia, including rash (n = 32), renal injury (n = 31), and liver injury (n = 13). Patients with eosinophilia were significantly more likely to have rash (hazard ratio [HR], 4.16; 95% CI, 2.54-6.83; P P = .0009) but not liver injury (HR, 1.75; 95% CI, 0.92-3.33; P = .09). Possible DRESS syndrome occurred in 7 (0.8%) of 824 patients; 4 (57%) were receiving vancomycin. Conclusions Drug-induced eosinophilia is common with parenteral antibiotics. Although most patients with eosinophilia do not have an HSR, eosinophilia increases the hazard rate of having rash and renal injury. DRESS syndrome was more common than previously described.

Academic research has produced many model-based specification and analysis techniques, however, most organisations continue to document requirements as textual statements. To help bridge this gap between academic research and requirements practice, this paper reports an extension to the RESCUE process in which patterns for generating requirements statements from i* system models were manually applied to i* models developed for a complex air traffic control system. The paper reports the results of this application and describes them with examples, the benefits of the approach to the project, and ongoing research to implement these patterns in the REDEPEND modelling tool to make requirements engineers more productive. We review similar work on requirements modelling and expression, and compare our work to it to demonstrate the proposed advance in the state of the art. Finally the paper discusses future uses of requirements generation from model patterns in RESCUE.

To read Emma Speed Sampson's novel The Comings of Cousin Ann today is to discover an intriguing link between sentimental southern fiction popular at the turn of the nineteenth century and the more honest appraisals of the South credited to writers of the twentieth-century Southern Renaissance. I use the word discover deliberately, for though the novel attracted favorable reviews and a general audience when published in 1923, it has gathered dust for the past seventy years. Dated in some ways but modern in many others, it deserves a new audience. It will fascinate scholars and students of southern literature, cultural studies, and women's studies. The author, Emma Speed Sampson, was born in Louisville, Kentucky, in 1868, married a Virginian and spent most of her adult years in Richmond, and died in 1947. Between 1916 and 1940, she published at least twenty-eight novels. Most of these were designed for children and adolescents, including the popular Miss Minerva and Billy series, which Sampson created as a sequel to a novel by Frances Boyd Calhoun following Calhoun's death. She also continued three series begun by her sister Nell: the Molly Brown books, The Tucker Twins series, and The Carter Girls series. But Sampson's most original and serious novel is The Comings of Cousin Ann. Fast moving and playful, it deconstructs the southern belle in particular and the southern romance in general. At first glance, however, the easy-to-read novel may appear to be another of Sampson's works of interest chiefly to youngsters. In outline, the plot involving the young heroine Judith Buck is predictable: the reader never doubts that this beautiful Cinderella will get her Prince Charming or that all will be right with the world by novel's end. But Sampson complicates the narrative by parodying, rather than replicating, the sentimental romance. Rather than a fairy godmother, she gives her Cinderella a chorus of elderly godfathers who, in a nurturing feminine gesture, host a ball for Judith and even design and order the dress, hair ornament, slippers, and hose she will wear to it. Moreover, Sampson refers to the Cinderella story directly several times in the novel, but only to mock it. In excited anticipation of her first ball, Judith says to her mother: I'm going to dance my dress to a rag. Did you ever think that Cinderella may have just danced her dress to rags by twelve o'clock and after all the fairy godmother had nothing to do with it? Cinderella danced every dance with the prince and perhaps he was an awkward prince and tangled his feet in her train. In fact, I am sure he was awkward or he would have caught up with her when she tried to run away, and she with one shoe off and one shoe on. (146) Judith's cleverness and realism here are refreshing, and so are the author's: the godfathers she gives her southern anti-Cinderella are elderly Civil War veterans who, rather than being a momentary convenience to a romantic plot, are fixtures on the porch of a local hotel, where they entertain themselves, as folks so often do in small towns, by gossiping about local happenings and by creating happenings--such as a debutante ball for social outsider Judith--to add excitement to their days. Not that the novel escapes all vestiges of sentimentality. Cousin Ann Peyton's servant Billy is, in some ways, the stereotypical faithful darky of post-Civil War southern romance. And there is no accounting for young Judith Buck's perpetual self-confidence, goodness, and good humor. But the novel's sentimentality is more than balanced by a modernism evident even to its contemporary reviewers. Upon its publication in 1923, a writer for The Literacy Review described the novel as "a sort of quite grown up and more or less up to date Louisa M. Alcott novel" (166). And in The Reviewer the same year, Hunter Stagg praised the novel for its tart tone--"a tartness," he said, that is "not usually found in a Southerner's writings about the South" (68-69). …

The toxic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the small bowel have been reported extensively. A growing number of reports of toxic effects of NSAIDs on the colon have appeared recently. The clinical presentation, endoscopic appearances and histological findings of so-called NSAID colopathy are quite varied, as illustrated by a series of four patients described in this report. Presenting symptoms and signs in this series include iron-deficiency anaemia and crampy abdominal pain, but alteration of bowel habit, weight loss, and even nausea and vomiting have also been described. One patient in this series has large-bowel diaphragms, considered by some to be pathognomonic of NSAID effects. Each of the four patients had right-sided colonic lesions only, possibly supporting a direct toxic effect of NSAIDs. Management usually involves simply stopping the offending NSAID. A review of the literature on this under-recognized entity is presented.

Though they were born only about ten years apart and both grew up in the South, Zora Neale Hurston and Eudora Welty could hardly have lived more different lives. Hurston was motherless from the age of eight and had a troubled relationship with her father, whereas Welty was raised by two loving, sheltering, supportive parents. Hurston left home for good when she was about fourteen, supporting herself through a variety of jobs in Washington, D.C., New York, and several other cities. Welty, on the other hand, lived most of her life in the family home in Jackson, Mississippi. Hurston became known as a flamboyant and sometimes raunchy extrovert, whereas Welty was a furiously private individual invariably described by interviewers as a gracious, self-effacing southern lady. Hurston died in poverty and obscurity at age sixty, whereas Welty was mourned around the world when she died at age ninety-two in 2001. Yet different as their lives were, Hurston and Welty exhibit remarkable similarities as writers. A hint of the similarities appears in the similar criticism that their works have sometimes evoked. Both authors have, on more than one occasion, been accused of not writing serious or significant fiction--in particular, of not addressing the social and racial problems of the South. In a review of Their Eyes Were Watching God published in 1937, Richard Wright accused Hurston of creating a novel that "carries no theme, no message, no thought" (17). Welty faced such criticism especially during the Civil Rights Movement of the 1960s. She recalls that, after three Civil Rights workers were murdered in Mississippi in the early 1960s, a midnight telephone caller asked her, "All right, Eudora Welty, what are you going to do about it? Sit down there with your mouth shut?" ("Must the Novelist Crusade?" 147). In responding to such criticism, Hurston and Welty voice virtually the same philosophy of art. Fiction, they have said, is not the place for lecturing but for reflecting life. In 1936, Hurston reportedly answered criticism of Jonah's Gourd Vine by saying, "I did not make it a lecture on the race problem ... because ... I was writing a novel and not a treatise on sociology. There is where many Negro novelists make their mistakes. They confuse art with sociology" (Ford 8). Welty responded most explicitly in her essay "Must the Novelist Crusade?," published in 1965: "The novelist and the crusader who writes both have their own place--in the novel and the editorial respectively, equally valid whether or not the two happen to be in agreement. In my own view, writing fiction places the novelist and the crusader on opposite sides" (147). For Hurston and Welty, the purpose of the fiction writer is to get at life, not to condone or condemn. As Welty explained, "The character we care about in a novel we may not approve of or agree with--that's beside the point. But he has got to seem alive" (150). In reflecting life in their fiction, both authors draw frequently and generously on the multi-faceted oral culture of the South. In portraying the talking, gossiping, tale-telling, fussing, exaggerating, and evasiveness of small-town and rural southerners, they reveal much about a way of life, its flaws along with its merits. Their use of the oral culture--and its influence on their prose styles--is probably the largest and most complex similarity between the two writers, and it deserves a book-length study. In this short article, I take on instead a smaller, more precise task. My focus is two of their works that could almost have been written by the same person. For years, I have been intrigued by parallels between the Logan Killicks section of Hurston's novel Their Eyes Were Watching God, published in 1937, and Welty's short story "Livvie," first published five years later. "Livvie" is one of a handful of stories in which Welty focuses on black rather than white characters. The premises of "Livvie" and the Logan Killicks section of Their Eyes Were Watching God are the same: a young girl marries a respectable elderly farmer, leads a lonely, isolated existence on his farm, but then is rescued from her isolation and her elderly husband by a younger man, an exciting stranger. …

Because of rising interest in new methods to detect arterial diseases, we compared data from 3 different compliance-related techniques to measure arterial stiffness: systolic pulse contour analysis, diastolic pulse contour analysis (modified Windkessel model), and muscular (brachial) artery compliance by cuff plethysmography. Variables measured in the sitting position were compared with each other, with clinic blood pressures (BPs), and with the cardiac time-tension integral (CTTI) in 63 established hypertensive and 28 age-matched normotensive subjects. Hypertensives demonstrated marginal reductions in C 1 (thought to represent reduced large vessel compliance) and increased central systolic BP augmentation. In contrast, muscular artery compliance tended to be greater in the hypertensives despite normal brachial arterial diameters. C 2 , suggested to be an indicator of small artery properties, was similar in both groups. CTTI was strongly related to systolic pressure ( r =0.81), integrated mean arterial pressure ( r =0.83), and systolic pressure-heart rate product ( r =0.85) and was less strongly related to diastolic ( r =0.71) or pulse pressure ( r =0.57). Weak correlations were observed between CTTI and measured compliance-related variables, which also showed absent or weak correlations among themselves. We conclude that the weak relationships among BP and compliance-related variables could be due to intrinsic differences in the properties of large and small arteries, theoretical methodological weaknesses, measurement artifacts, or intrinsic hemodynamic differences of the sitting position. At present, compliance-related variables provide little additional advantage over cuff BP in the office estimation of cardiac work.

Background —Transgenic mice with constitutive myocardium-targeted expression of a peptide inhibitor of the β-adrenergic receptor kinase (βARKct) have increased in vivo cardiac function and enhanced β-adrenergic receptor (βAR) responsiveness. Methods and Results —In the present study, we created transgenic mice with myocardium-targeted βARKct transgene expression under control of the CARP (cardiac ankyrin repeat protein) promoter, which is active during cardiac development and inactive in the normal adult mouse heart. Consistent with this, adult CARP-βARKct transgenic mice have normal in vivo cardiac contractility and βAR responsiveness indistinguishable from their nontransgenic littermates (NLCs). However, because CARP is in a group of fetal genes activated in the adult ventricle during hypertrophy, we subjected animals to transverse aortic constriction (TAC) to induce pressure overload. Seven days after TAC, CARP-βARKct hearts had elevations in left ventricular mass similar to those in NLCs; however, TAC did induce demonstrable βARKct expression in the transgenic hearts. TAC in NLC mice resulted in an upregulation of myocardial βARK1 and a loss of βAR-mediated inotropic reserve. Importantly, although βARK1 was increased in the hypertrophic CARP-βARKct mice, the in vivo loss of βAR responsiveness was not seen after induced βARKct expression. Conclusions —These results demonstrate that acute βARK1 inhibition can restore lost myocardial βAR responsiveness and inotropic reserve in vivo. Furthermore, these mice demonstrate the novel utility of the CARP promoter as an inducible element responsive to pathophysiological conditions in the adult heart.

Odour pollution is traditionally categorised as a public health issue, controlledv, ia statutory legislation with the emphasis on control rather than prevention. As society demands a higher quality environment, odour pollution increases in importance as an amenity issue. Planning authorities can refuse planning permission on the grounds that the odour nuisance from the proposed development will be detrimental to the amenity of the area. Planningauthorities are therefore in the unique position of being able to prevent odour pollution. Potential odour polluters are under increasing pressure to demonstrate to planning authorities that odour has been minimised as far as possible. The communication of technical odour control data and assessments, through mechanisms such as Environmental Impact Assessments (EIA), is becoming an important part of the decision making process. The lack of specific odour policy and guidance within the planning arena is highlighted. The reconstruction of Derby Sewage Treatment works (STW) is used a a case study to highlight how a technical assessment of odour emissions, using the WRc Sewage Treatment Odour Production (STOP) Model can be successfully used within the planning arena to achieve planning permission with no additional conditions.

A survey of 24 international heart valve banks was conducted to acquire information on heart valve processing techniques used and outcomes achieved. The objective was to provide an overview of heart valve banking activities for tissue bankers, tissue banking associations, and regulatory bodies worldwide. Despite similarities found for basic manufacturing processes, distinct differences in procedural details were also identified. The similarities included (1) use of sterile culture media for procedures, (2) antibiotic decontamination, (3) use of dimethyl sulfoxide (DMSO) as a cryoprotectant, (4) controlled rate freezing for cryopreservation, and (5) storage at ultralow temperatures of below −135°C. Differences in procedures included (1) type of sterile media used, (2) antibiotics combination, (3) temperature and duration used for bioburden reduction, (4) concentration of DMSO used for cryopreservation, and (5) storage duration for released allografts. For most banks, the primary reasons why allografts failed to meet release criteria were positive microbiological culture and abnormal morphology. On average, 85% of allografts meeting release criteria were implanted, with valve size and type being the main reasons why released allografts were not used clinically. The wide variation in percentage of allografts meeting release requirements, despite undergoing validated manufacturing procedures, justifies the need for regular review of important outcomes as cited in this paper, in order to encourage comparison and improvements in the HVBs’ processes.

SUMMARY 1. The pharmacokinetics of a single dose of Cyclosporine A (CsA) administered to sheep by intravenous (i.v.) route were examined. 2. Concomitant administration of ketoconazole was found to increase the area under the blood CsA concentration-time curve (AUC) and was effective when adminstered by the oral or intraperitoneal route. 3. The effects of CsA and ketoconazole on the immune system of sheep were also assessed. 4. A single dose of CsA 5mg/kg resulted in abrogation of in vitro lymphocyte function manifest at 24h after injection of CsA. Normal responsiveness recovered in 48-72h. Numbers of T lymphocytes in peripheral blood were elevated transiently at 48h although no other significant alteration in lymphocyte subsets was observed with this treatment. 5. Concomitant ketoconazole administration enhanced the CsA-induced suppression of in vitro lymphocyte responses. Blood levels of CsA (AUC values to 24h) were significantly elevated with concomitant ketoconazole administration and depression of lymphocyte responses to mitogens were also significantly enhanced. An increase in the proportion of T4 positive cells in the blood was observed at 48h and at 7 days after administration of CsA with ketoconazole. 6. These findings indicate that CsA effectively abrogates immunocompetence in the sheep and this immunosuppressive effect is enhanced by concomitant administration of ketoconazole.

We have assessed the ability of the new amiodarone-like antiarrhythmic agent, SR 33589, to reduce the incidence of ischemia- and reperfusion-induced arrhythmias, in comparison to amiodarone, D-sotalol, and lignocaine. Rats were anesthetized, artificially ventilated, and the thorax opened by a left thoracotomy. Ischemia was induced by left coronary artery ligation, and reperfusion was achieved (after a 5-min period of ischemia) in a separate group of rats by removing the ligature. Agents were given intravenously 5 min before occlusion or orally 4 h before study. During a 20-min period of ischemia, SR 33589 reduced significantly the incidence of ventricular fibrillation (VF) from 80 to 30% (p < 0.05) at 3 mg/kg i.v. and eliminated VF and mortality at 10 mg/kg i.v. In contrast, amiodarone at 10 mg/kg i.v. reduced significantly only the incidence of mortality during ischemia (from 60 to 0%, p < 0.01), while having no significant effect on 3 mg/kg i.v. On reperfusion (after a 5-min period of ischemia), SR 33589 reduced significantly the incidence of mortality (from 90 to 20%, p < 0.01) at 1 mg/kg and eliminated VF and mortality when administered at 3 and 10 mg/kg. Against both ischemia- and reperfusion-induced arrhythmias, approximately 20% of animals showed AV block at the highest dose of SR 33589 tested. This was not observed with lower doses. Amiodarone (10 mg/kg i.v.) eliminated completely reperfusion-induced VF and mortality while having no significant effect at 1 and 3 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

The Republic of Singapore, a small island state lying at the southern extremity of Peninsular Malaysia has, along with other ASEAN nations, stated its commitment to the principle of ‘sustainable development’ and ecological sustainability. This paper presents an assessment of the impact of post-World War II development on the extent and quality of intertidal coastal ecosystems and ecocomplexes in Singapore — specifically on coral reefs, mangroves, and intertidal sand- and mud-flats — and hence an evaluation of Singapore's commitment to maintaining coastal ecosystems and coastal biodiversity. The extent of these habitats was mapped from topographic and hydrographic maps, and estimates of their future area was derived from the Singapore Concept Plan for the year ‘x’ (AD c. 2030).

In the past all engineering students took a drafting class. This involved the use of T-squares, triangles, architectural scales, pounce, eraser shields, bow compasses, pencils, and patience. It gave students a sense of how drawings and diagrams are made and used. As new subjects have come into the curriculum most engineering programs have dropped the drafting requirement, or at least replaced it with a computer-based CAD course. Also dropped, as a consequence, is the ability of engineering students to visually express the ideas they see in class and those that form in their heads. This paper describes the effort to address this change. This project is the result of a joint effort between an engineering and an art professor to empower students with the simple skills of producing reliable hand drawings for their notes and when expressing their design ideas. The result is a one-hour, lunch-time seminar open to engineering and science students to improve their technical freehand sketching techniques. They were coached by both professors in the techniques of hand sketching, including drawing straight and orthogonal lines, circles and ellipses, 2- and 3-D diagrams, graphs and charts, and labeling and lettering. Specific activities were used to gauge the improvement by the students as they progressed through the one-semester mini-course. This paper shares the best and the worst of this endeavor. This work was supported in part by a grant from the Professional Development Committee of SUNY Adirondack.

Kidney segmentation is an essential step in developing any non-invasive Computer-Assisted Diagnostic (CAD) system for the early detection of acute renal rejection. This paper describes a 3-D approach for kidney segmentation from abdominal Computed Tomography (CT) images using a level set-based deformable model. Its evolution is controlled by a specially designed stochastic speed function that accounts for a shape prior and features of image intensity and spatial interactions. The shape prior is learned from the co-aligned 3-D kidney data. The current visual appearances are described with marginal gray level distributions obtained by separating their mixture over the kidney data. The spatial interactions between the kidney voxels are modeled by a 3-D 2nd-order translation and rotation variant Markov-Gibbs Random Field (MGRF) of “object-background” labels with analytically estimated potentials. The proposed approach has been evaluated on the CT data sets of 29 patients, yielding an average volumetric overlap error of 3.71%. The presented results indicate that combing CT images' characteristics into level set evolution leads to more accurate segmentation results.

BackgroundAn important issue in the transplantation of livers procured from cardiac death donors (CDDs) concerns why some centres report equivalent outcomes and others report inferior outcomes in transplantations using CDD organs compared with standard criteria donor (SCD) organs. Resolving this discrepancy may increase the number of usable organs.ObjectivesThis study aimed to test whether differences in cold ischaemic time (CIT) are critical during CDD organ transplantation and whether such differences might explain the disparate outcomes.MethodsResults of CDD liver transplants in our own centre were compared retrospectively with results in a matched cohort of SCD liver recipients. Endpoints of primary non-function (PNF) and ischaemic cholangiopathy (IC) were used because these outcomes are clearly associated with CDD organ use.ResultsIn 22 CDD organ transplants, CIT was a strong predictor of PNF or IC (P= 0.021). Minimising CIT in CDD organ transplants produced outcomes similar to those in a matched SCD organ transplant cohort at our centre and in SCD organ transplant results nationally (1- and 3-year graft and patient survival rates: 90.9% and 73.3% vs. 77.6% and 69.2% in CDD and SCD grafts, respectively. A review of the published literature demonstrated that centres with higher CITs tend to have higher rates of PNF or IC (correlation coefficient: 0.41).ConclusionsThese findings suggest that a targeted effort to minimise CIT might improve outcomes and allow the safer use of CDD organs.

Aim To identify the nature of services for children and young people with progressive neuromuscular disorders (NMD) provided by Children’s Hospices in the UK. Methods A questionnaire requesting aggregate data on the number of patients with a neuromuscular condition was sent to all children’s hospices in the UK, in addition, specific data was collected on services for young people with DMD presenting to a single local hospice. Results 87% of eligible hospices responded (27/31). 756 young people with an NM condition were being cared for by the hospices. These patients accounted for a mean of 17% of the total hospice population (range 5–35%). The age at which young people were required to leave the children’s hospices varied from 18 up to 35 years. 73% of ‘visits’ were described as ‘planned stays’. Although ‘end of life care’ is provided, few young people with NMD died in a hospice. Conclusions Children and young people with NMD form a large proportion of the Children’s Hospice’s caseload. Many valued services provided by children’s hospices are not available through NHS funding. The lack of similar adult based services is a concern as increasing numbers of young people are surviving into adulthood.

BACKGROUND Total-body irradiation, followed by hematopoietic system rescue by bone marrow transplantation (BMT), has been found to improve the response of patients with multiple myeloma to treatment with melphalan. The problems of nonhematopoietic toxicity from whole-body irradiation might be circumvented by using a bone-seeking radiopharmaceutical, such as samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP), to ablate the bone marrow. PURPOSE A mouse model system for multiple myeloma was used to evaluate the potential therapeutic efficacy of sequential therapy with 153Sm-EDTMP, melphalan, and BMT. METHODS Female C57BL/KaLwRij mice were inoculated with 8 x 10(5) 5T33 murine myeloma cells. Treatment protocols were begun 3 or 10 days later, when the myeloma was either confined to bone marrow or disseminated in liver, spleen, and lymph nodes, simulating human multiple myeloma. 153Sm, a potent beta particle-emitting radioisotope of short half-life (46.7 hours), was linked to the bone-seeking chelate EDTMP. Animals in the first treatment group were each given 22.5 MBq 153Sm-EDTMP via the jugular vein (day 3 or 10), followed by 18.5 mg/kg melphalan (maximum tolerated dose) given intraperitoneally 5 days later (day 8 or 15) and syngeneic BMT another 2 days later (day 10 or 17). Survival in groups of six to 10 animals for each time series was compared with that in mice left untreated (control cohort), in mice treated with 153Sm-EDTMP alone (day 3 or 10), or in mice treated with melphalan alone (day 8 or 15). The hematopoietic systems of animals in the latter two treatment groups recovered full function, obviating the necessity of BMT. The end point was onset of paraparesis, at which time the animals were immediately killed by carbon dioxide asphyxiation. RESULTS Median survival in untreated control animals was 23 days in those with localized disease and 24 days in those with disseminated myeloma. Treatment with 153Sm-EDTMP alone improved survival to a median of 29 days when commenced on day 3 and 30 days when begun on day 10. Melphalan treatment alone improved the median survival to 31 days for animals with localized myeloma and 34 days in animals with disseminated disease. Additional improvement in survival to a median of 42 days was achieved in animals treated 3 days after tumor inoculation with sequential 153Sm-EDTMP, melphalan, and BMT; median survival was 40 days using this regimen in animals with disseminated myeloma. CONCLUSIONS Animals in all three treatment protocols survived longer than those left untreated after inoculation with myeloma cells (P < .001). Sequential treatment with 153Sm-EDTMP, melphalan, and BMT was significantly more effective than single-agent treatment (P < .01). No evidence of radiotoxicity was detected in nonhematopoietic organs. IMPLICATIONS The survival advantage conferred by our sequential treatment protocol suggests its potential clinical usefulness in the treatment of multiple myeloma and other hematologic malignancies in humans.

Malignant mesothelioma (MM) is a tumor that is resistant to conventional therapy. Interferon-α (IFN-α) has been used in the treatment of some human tumors, and we have previously demonstrated an in vitro anti-proliferative effect of IFN against MM cell lines. Therefore, the effect of recombinant human IFN-α (IFN-α2a) (Roferon-A, Hoffmann-La Roche) on previously untreated patients with MM has been studied. Twenty-five patients (24 male and 1 female), with a mean age of 59 ± 9.9 years, were treated for 3 months with IFN-α2a. The starting dose was 3 × 106 IU daily increasing to a maximum of 18 × 106 IU daily or as tolerated. All patients had measurable tumor on thoracic CT prior to commencement. CT scans were performed at 6 and 12 weeks to determine tumor response. Twenty patients completed 3 months of treatment. Five patients were withdrawn because of disease progression. Side effects were predictable and dose related. Dose reductions were necessary in 12 patients for grade 2 toxicity. One patient ...

More severe, early onset neuromuscular disorders (NMD) disorders are associated with a shortened life expectancy and thus prevalence data calculated from the population as a whole may underestimate the prevalence of the more severe NMC seen in childhood. It is not known how prevalence varies with ethnicity. Retrospective case note review of patients under 16 years with a diagnosis of a NMD in 2010, under the care of the tertiary regional service. Cases were ascertained using existing databases and data was analysed using chi-squared tests. Prevalence was calculated according to the formula prevalence = number of cases/population at risk ×100,000. Data was collected from 261 patients. The overall prevalence of NMD in Yorkshire was 35.2 per 100,000 with dystrophin related muscle disease being the most common condition with a prevalence of 16.9 per 100,000 males. There was a statistically significant difference between ethnic groups with a total NMD prevalence of 90.2/100,000 in the South Asian population compared to a prevalence of 29.0/100,000 in the White population ( p p p

The struggle to get students to attempt- and complete-assigned homework problems may well be eternal. Many professors have tried different ways to encourage students to get the vital practice that homework offers. This paper details the experience of making group work on the homework the focus of class time, and having the lecturing done by using the "Physics I: Classical Mechanics" lectures available through MIT's OpenCourseWare (OCW) initiative. Students were expected to watch the videos on their own time-making this their "homework" while we would discuss and complete most of the assigned problems in class. Discussed are the benefits and drawbacks of doing this, including student comments.

Fantofarone (SR 33557) is a novel, highly potent calcium channel antagonist representative of a new class of slow channel blockers. In this study, we have assessed its ability to influence cardiac function in two, isolated, perfused heart models and then assessed its ability to modify post-ischaemic functional recovery. In isolated, rat hearts perfused in the Langendorff mode, fantofarone increased coronary flow by 25% at 100 and 1000 nM with no effect on left ventricular pressure or heart rate below 100 nM. In working hearts, fantofarone again increased coronary flow within a similar concentration range. A significant reduction (approximately 40%) was observed in peak systolic pressure and dP/dtmax when hearts were perfused with 1000 nM fantofarone. Working rat hearts were also subjected to a 30 min period of global, low-flow (0.1 ml/min) ischaemia, followed by a 30 min period of reperfusion. Perfusion with 1 or 10 nM fantofarone, began 20 min prior to the onset of ischaemia and continued throughout the ischaemic and reperfusion periods. The addition of 1 nM fantofarone did not cause a significant increase in the recovery of cardiac function during the reperfusion phase. In contrast, perfusion with 10 nM fantofarone resulted in a substantial increase in the recovery of several indices of cardiac function such as aortic output, dP/dtmax and peak systolic pressure. Thus, in the working rat heart, at concentrations which cause minimal alterations to normal cardiac function, fantofarone can improve significantly functional recovery following an ischaemic insult.

SUMMARYGiardiasis is a common waterborne gastrointestinal illness. In 2007, a community giardiasis outbreak occurred in New Hampshire, USA. We conducted a cohort study to identify risk factors for giardiasis, and stool and environmental samples were analysed. Consuming tap water was significantly associated with illness (risk ratio 4·7, 95% confidence interval 1·5–14·4). Drinking-water samples were coliform-contaminated and a suspectGiardiacyst was identified in a home water filter. One well was coliform-contaminated, and testing indicated that it was potentially under the influence of surface water. The well was located 12·5 m from aGiardia-contaminated brook, although the genotype differed from clinical specimens. Local water regulations require well placement at least 15 m from surface water. This outbreak, which caused illness in 31 persons, represents the largest community drinking-water-associated giardiasis outbreak in the USA in 10 years. Adherence to well placement regulations might have prevented this outbreak.

There is no effective therapy for human malignant mesothelioma, and its susceptibility to recombinant cytokines has not been studied extensively. Recombinant human tumor necrosis factor alpha (rHuTNF alpha) was evaluated for its in vitro and in vivo antitumor activity using a human malignant mesothelioma cell line [DeH128(m)], both in culture and heterotransplanted in nude mice. In vitro, rHuTNF alone had no direct antimesothelioma activity assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, but in combination with the transcription inhibitor, dactinomycin (AD), mesothelioma cell metabolic activity was inhibited (80% of control). The effects of this combination of agents were studied on DeH128(m) cells heterotransplanted as subcutaneous tumors in nude mice. In vivo there was no significant inhibition of tumor growth by combined rHuTNF alpha and AD therapy, but the combination produced marked cachexia in doses at which each component (rHuTNF alone or AD alone) was well tolerated. The authors conclude that the well-described in vitro interaction between AD and rHuTNF also operates in vivo to produce cachexia and that the combination of these two agents is likely to have a low therapeutic index in malignant mesothelioma.

Malignant mesothelioma arises in serosal tissues, is locally invasive, and is usually resistant to chemotherapeutic agents used clinically. To determine whether resistance to cytotoxic drugs was an inherent characteristic of mesothelioma cells, we performed in vitro chemosensitivity testing on five fully characterised human malignant mesothelioma cell lines and, for comparison, on three lines representative of clinically drug-resistant solid-tissue carcinomas using the MTT (tetrazolium bromide) assay system. Mesothelioma cell lines were intrinsically resistant to eight common antineoplastic drugs, with concentrations that produced a 50% reduction in optical density (IC50 values) for all drugs being equivalent, if not higher, for mesothelioma cell lines as compared with lung and colon carcinoma cell lines. We then investigated the direct anti-mesothelioma activity of recombinant human cytokines with their antineoplastic properties. All five mesothelioma cell lines were resistant to tumour necrosis factor, but they displayed varying degrees of sensitivity to interferons (IFNs). IFN gamma directly inhibited the growth of two of five mesothelioma lines. IFN alpha displayed little activity against four of five mesothelioma lines. The mesothelioma cells that were sensitive to IFN alpha were resistant to IFN gamma, indicating that sensitivity to IFNs is not a genetic characteristic of malignant mesothelioma cells. Significant interactions between cytokines in combination were not observed.