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Generating employment and alleviating poverty are the biggest challenges for regional economic growth in the rural areas of the Northeastern United States. Despite the revival of the economy in much of the nation's heartland, rural areas are still suffering from high poverty and unemployment rates. Self-employment, a measure of entrepreneurship, indicates an opportunity for rural communities to improve the quality of life and accelerate regional economic development. Taking into consideration the problem of unemployment in rural communities, there is a need to focus on generating self-employment opportunities at micro level to enhance economic growth and reduce the per capita income 'gap' between rural and urban areas. The overall objective of the study is to identify and estimate the impacts of self-employment in the economic development of the Northeastern United States. The empirical model of this study is derived from the three-equation simultaneous model of Deller et al. (2001). The study estimated the relationship of employment, population and per capita income to self-employment. Research findings show that employment and population have a positive relationship to self-employment, indicating positive contribution of self-employment to regional economic development. [ABSTRACT FROM AUTHOR]

Develops a crop-decision model for corn production that includes a stochastic soil moisture index variable which is applied to 15 different soil and weather conditions for corn production in Indiana. Beta distribution; Maximum likelihood; Soil moisture; Stochastic production.

Discusses the activities of the Economic Statistics Committee of the American Agricultural Economics Association. Framework for assessing agriculturally related environmental data needs; Geographic information systems; Issues related to environmental dat needs.

The article presents the authors' comments in response to an article by B.J. Bushman and C.A. Anderson on media violence and public aggression in the U.S. The authors say that the article contains data that are incorrect. Bushman and Anderson have made incorrect calculation while showing different set of correlations between media violence and the public aggression.

Background: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare disorder described after vaccination with adenoviral vector-based COVID-19 vaccines. Co-occurring thrombosis with thrombocytopenia reported after vaccination can be a proxy for identification of TTS., Methods: Descriptive database review of all cases of co-occurring (within 42 days) thrombosis with thrombocytopenia in participants in Ad26.COV2.S clinical trials or recipients of Ad26.COV2.S in real-world clinical practice. Cases were retrieved from Janssens' clinical trial and Global Medical Safety databases., Results: There were 34 cases of co-occurring thrombosis with thrombocytopenia in Ad26.COV2.S recipients (46 per 100,000 person-years) and 15 after placebo (75 per 100,000 person-years) in clinical trials. Among Ad26.COV2.S recipients, mean age at the time of the event was 63 years (range 25-85), 82 % were male, mean time-to-onset 112 days (range 8-339) post-last Ad26.COV2.S dose, 26 events occurred post-dose-1, and 7 within a 28-day risk window post-vaccination. Diagnostic certainty was evaluated using Brighton Collaboration, US Centers for Disease Control and Prevention, and European Medicines Agency Pharmacovigilance Risk Assessment Committee case definitions. One case met the highest level of diagnostic certainty for all 3 definitions. There were 355 spontaneous reports of co-occurring thrombosis with thrombocytopenia in the Global Medical Safety database, 47 % males, 85 % within 28-days after vaccination. Twenty-seven cases met the highest level of diagnostic certainty for all definitions, 21 female, 19 with cerebral venous sinus thrombosis, age-range 18-68 years. Time-to-onset was 7-14 days post-vaccination in 20 cases. There were 8 fatalities., Conclusion: TTS induced by Ad26.COV2.S is very rare. Most co-occurring thrombosis with thrombocytopenia does not constitute TTS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Frank Struyf reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Karin Hardt reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Rian Van Rampelbergh reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Georgi Shukarev reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Ajinkya Inamdar reports a relationship with Johnson & Johnson that includes: employment. Javier Ruiz-Guinazu reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Vitalija van Paassen reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Luis Anaya-Velarde reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Camellia Diba reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Marc Ceuppens reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Vicky Cardenas reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Jerald Sadoff reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Macaya Douoguih reports a relationship with Johnson & Johnson that includes: employment and equity or stocks. Gerald A. Soff reports a relationship with Johnson & Johnson that includes: board membership and funding grants. Gerald A. Soff reports a relationship with Amgen that includes: funding grants. Gerald A. Soff reports a relationship with Anthos Therapeutics Inc that includes: funding grants. Gerald A. Soff reports a relationship with Dova Pharmaceuticals that includes: board membership and funding grants. Gerald A. Soff reports a relationship with Sanofi that includes: board membership. Gerald A. Soff reports a relationship with Luzsana (HengruiUSA) iotechnology that includes: board membership., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to examine factors associated with negative job outcomes for nurses during the initial phase of the COVID-19 pandemic, with a focus on nurses of color. The study used data from 3,782 nurses in the Current Population Survey to examine the relationship between nurse characteristics and COVID-19-related inability to work or look for work during May through December 2020. The analysis showed that race and gender did not significantly impact nurses' job outcomes. The odds of a negative impact were increased by age (1.5% per year, p < .05), having a child in the home (43%, p < .01), having no spouse present (36%, p < .01), and working in an outpatient role (48%, p < .001). While race alone was not linked to negative outcomes, nurses of color had higher rates of other factors that were associated with negative outcomes, indicating a need for a more nuanced examination of their work and life contexts and job outcomes throughout the pandemic.

Background: Mental disorders (MDs) are behavioral or mental patterns that cause significant distress or impairment of personal functioning. Previously, temperature has been linked to MDs, but most studies suffered from exposure misclassification due to limited monitoring sites. We aimed to assess whether multiple meteorological factors could jointly trigger MD-related emergency department (ED) visits in warm season, using a highly dense weather monitoring system., Methods: We conducted a time-stratified, case-crossover study. MDs-related ED visits (primary diagnosis) from May-October 2017-2018 were obtained from New York State (NYS) discharge database. We obtained solar radiation (SR), relative humidity (RH), temperature, heat index (HI), and rainfall from Mesonet, a real-time monitoring system spaced about 17 miles (126 stations) across NYS. We used conditional logistic regression to assess the weather-MD associations., Results: For each interquartile range (IQR) increase, both SR (excess risk (ER): 4.9%, 95% CI: 3.2-6.7%) and RH (ER: 4.0%, 95% CI: 2.6-5.4%) showed the largest risk for MD-related ED visits at lag 0-9 days. While temperature presented a short-term risk (highest ER at lag 0-2 days: 3.7%, 95% CI: 2.5-4.9%), HI increased risk over a two-week period (ER range: 3.7-4.5%), and rainfall hours showed an inverse association with MDs (ER: -0.5%, 95% CI: 0.9-(-0.1)%). Additionally, we observed stronger association of SR, RH, temperature, and HI in September and October. Combination of high SR, RH, and temperature displayed the largest increase in MDs (ER: 7.49%, 95% CI: 3.95-11.15%). The weather-MD association was stronger for psychoactive substance usage, mood disorders, adult behavior disorders, males, Hispanics, African Americans, individuals aged 46-65, or Medicare patients., Conclusions: Hot and humid weather, especially the joint effect of high sun radiation, temperature and relative humidity showed the highest risk of MD diseases. We found stronger weather-MD associations in summer transitional months, males, and minority groups. These findings also need further confirmation., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic myelogenous leukemia (CML) is a hematopoietic stem cell malignancy that accounts for 15-20% of all cases of leukemia. CML is caused by a translocation between chromosomes 9 and 22 which creates an abnormal fusion gene, BCR::ABL1. The amount of BCR::ABL1 transcript RNA is a marker of disease progression and the effectiveness of tyrosine kinase inhibitor (TKI) treatment. This study determined the analytical and clinical performance of a droplet digital PCR based assay (QXDx BCR-ABL %IS Kit; Bio-Rad) for BCR::ABL1 quantification. The test has a limit of detection of MR4.7 (0.002%) and a linear range of MR0.3-4.7 (50-0.002%IS). Reproducibility of results across multiple sites, days, instruments, and users was evaluated using panels made from BCR::ABL1 positive patient samples. Clinical performance of the assay was evaluated on patient samples and compared to an existing FDA-cleared test. The reproducibility study noted negligible contributions to variance from site, instrument, day, and user for samples spanning from MR 0.7-4.2. The assay demonstrated excellent clinical correlation with the comparator test using a Deming regression with a Pearson R of 0.99, slope of 1.037 and intercept of 0.1084. This data establishes that the QXDx™ BCR-ABL %IS Kit is an accurate, precise, and sensitive system for the diagnosis and monitoring of CML., Competing Interests: Bio-Rad provided reagents to each site to support this study. D.N.S, P.B., N.S., and S.H. are employees of Bio-Rad. Bio-Rad employees have or may have stock in Bio-Rad. In addition to providing employment, the stated Bio-Rad employees have or may have patents, products in development or marketed products in Bio-Rad. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Coronavirus disease-19 (COVID-19) infection is associated with an uncontrolled systemic inflammatory response. Statins, given their anti-inflammatory properties, may reduce the associated morbidity and mortality. This study aimed to determine the association between statin use prior to hospitalization and in-hospital mortality in COVID-19 patients., Methods: In this retrospective study, clinical data were collected from the electronic medical records of patients admitted to the hospital with confirmed COVID-19 infection from March 1, 2020 to April 24, 2020. A multivariate regression analysis was performed to study the association of pre-admission statin use with in-hospital mortality., Results: Of 255 patients, 116 (45.5%) patients were on statins prior to admission and 139 (54.5%) were not. The statin group had a higher proportion of end stage renal disease (ESRD) (13.8% vs. 2.9%, p = 0.001), diabetes mellitus (63.8% vs. 35.2%, p<0.001), hypertension (87.9% vs. 61.1%, p < 0.001) and coronary artery disease (CAD) (33.6% vs. 5%, p < 0.001). On multivariate analysis, we found a statistically significant decrease in the odds of in-hospital mortality in patients on statins before admission (OR 0.14, 95% CI 0.03- 0.61, p = 0.008). In the subgroup analysis, statins were associated with a decrease in mortality in those with CAD (OR 0.02, 95% CI 0.0003-0.92 p = 0.045) and those without CAD (OR 0.05, 95% CI 0.005-0.43, p = 0.007)., Conclusions: Our study suggests that statins are associated with reduced in-hospital mortality among patients with COVID-19, regardless of CAD status. More comprehensive epidemiological and molecular studies are needed to establish the role of statins in COVID-19., Competing Interests: Declaration of Competing Interest No conflict of interest for any of the authors., (Copyright © 2021. Published by Elsevier Inc.)

Collisions with buildings cause up to 1 billion bird fatalities annually in the United States and Canada. However, efforts to reduce collisions would benefit from studies conducted at large spatial scales across multiple study sites with standardized methods and consideration of species- and life-history-related variation and correlates of collisions. We addressed these research needs through coordinated collection of data on bird collisions with buildings at sites in the United States (35), Canada (3), and Mexico (2). We collected all carcasses and identified species. After removing records for unidentified carcasses, species lacking distribution-wide population estimates, and species with distributions overlapping fewer than 10 sites, we retained 269 carcasses of 64 species for analysis. We estimated collision vulnerability for 40 bird species with ≥2 fatalities based on their North American population abundance, distribution overlap in study sites, and sampling effort. Of 10 species we identified as most vulnerable to collisions, some have been identified previously (e.g., Black-throated Blue Warbler [Setophaga caerulescens]), whereas others emerged for the first time (e.g., White-breasted Nuthatch [Sitta carolinensis]), possibly because we used a more standardized sampling approach than past studies. Building size and glass area were positively associated with number of collisions for 5 of 8 species with enough observations to analyze independently. Vegetation around buildings influenced collisions for only 1 of those 8 species (Swainson's Thrush [Catharus ustulatus]). Life history predicted collisions; numbers of collisions were greatest for migratory, insectivorous, and woodland-inhabiting species. Our results provide new insight into the species most vulnerable to building collisions, making them potentially in greatest need of conservation attention to reduce collisions and into species- and life-history-related variation and correlates of building collisions, information that can help refine collision management., (© 2020 Society for Conservation Biology.)

Concussion is a common brain injury. The American Academy of Neurology provides a definition of concussion: "Concussion is a traumatically, or biomechanically, induced alteration of brain function. Emphasis is placed on a pathophysiological process, or functional disruption, as opposed to anatomic, structural, or tissue injury.". The incidence of mild traumatic brain injury (mTBI) is estimated at 200 per 100 000. The Centers for Disease Control and Prevention (CDC) estimates 3.8 million sport and recreational mTBIs occurring in the United States each year. A more recent CDC assessment estimates 2.5 million concussion injuries in high school sports alone. The controlled environment and opportunity for direct surveillance and observation has made the sports arena the scientific "wet lab" for the study of mTBI natural history, short- and long-term consequences and opportunities to intervene. Quantitative EEG methods have been utilized in the assessment and management of mTBI and lends to provide a cost-effective procedure that has the sensitivities needed to identify pathology where routine visual inspection of the EEG has failed.

There is limited information describing the characteristics and clinical outcomes of patients infected with coronavirus disease 2019 (COVID-19) especially those in underserved urban area with minority population in the United States. This is a retrospective single-center study for patients who were admitted with COVID-19 infection. Data collection was from 1 March through 24 April 2020. Demographic, clinical, laboratory, and treatment data were presented using descriptive statistics and frequencies. The χ 2 test and multivariate logistic regression were used to determine association of risk factors and clinical outcomes. A total of 242 inpatients were included with a mean age of 66 ± 14.75 (±standard deviation). A total of 50% were female and 70% were African American. Comorbidities included hypertension (74%), diabetes mellitus (49%), and 19% had either COPD or asthma. Older age was associated with higher risk of inpatient death odds ratio (OR): 1.056 (95% confidence interval [CI]: 1.023-1.090; P = .001). Inpatient mortality occurred in 70% who needed mechanical ventilation (OR: 29.51; 95% CI: 13.28-65.60; P < .0001), 58% who required continuous renal replacement therapy/hemodialysis (CRRT/HD) (OR: 6.63; 95% CI: 2.74-16.05; P < .0001), and 69% who needed vasopressors (OR: 30.64; 95% CI: 13.56-69.20; P < .0001). Amongst biomarkers of disease severity, only baseline CRP levels (145 ± 116 mg/L) were associated with mortality OR: 1.008 (95% CI: 1.003-1.012; P = .002). Majority of hospitalized patients had hypertension and diabetes. Older age was an independent risk factor for inpatient mortality. Requirement of mechanical ventilation, vasopressor use, and CRRT/HD was associated significantly with inpatient mortality. Higher baseline CRP was significantly associated with inpatient death., (© 2020 Wiley Periodicals LLC.)

Introduction: Emerging data have described poor clinical outcomes from infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) among African American patients and those from underserved socioeconomic groups. We sought to describe the clinical characteristics and outcomes of acute kidney injury (AKI) in this special population., Methods: This is a retrospective study conducted in an underserved area with a predominance of African American patients with coronavirus disease 2019 (COVID-19). Descriptive statistics were used to characterize the sample population. The onset of AKI and relation to clinical outcomes were determined. Multivariate logistic regression was used to determine factors associated with AKI., Results: Nearly half (49.3%) of the patients with COVID-19 had AKI. Patients with AKI had a significantly lower baseline estimated glomerular filtration rate (eGFR) and higher FiO2 requirement and D-dimer levels on admission. More subnephrotic proteinuria and microhematuria was seen in these patients, and the majority had a pre-renal urine electrolyte profile. Patients with hospital-acquired AKI (HA-AKI) as opposed to those with community-acquired AKI (CA-AKI) had higher rates of in-hospital death (52 vs. 23%, p = 0.005), need for vasopressors (42 vs. 25%, p = 0.024), and need for intubation (55 vs. 25%, p = 0.006). A history of heart failure was significantly associated with AKI after adjusting for baseline eGFR (OR 3.382, 95% CI 1.121-13.231, p = 0.032)., Conclusion: We report a high burden of AKI among underserved COVID-19 patients with multiple comorbidities. Those who had HA-AKI had worse clinical outcomes compared to those who with CA-AKI. A history of heart failure is an independent predictor of AKI in patients with COVID-19., (© 2020 S. Karger AG, Basel.)

Measurable residual disease (MRD) that persists after initial therapy is a powerful predictor of relapse and survival in acute lymphoblastic leukemia (ALL). However, the optimal use of this information to influence therapeutic decisions is controversial. Herein, we comprehensively review the role of MRD assessment in adults with ALL, including methods to quantify residual leukemia cells during remission, prognostic impact of MRD across ALL subtypes, and available therapeutic approaches to eradicate MRD. This review presents consensus statements and provides an evidence-based framework for practicing hematologists and oncologists to use MRD information to make rational treatment decisions in adult patients with ALL., (© 2018 Wiley Periodicals, Inc.)

Importance: Numerous studies have demonstrated that long-term outcomes after orthopedic trauma are associated with psychosocial and behavioral health factors evident early in the patient's recovery. Little is known about how to identify clinically actionable subgroups within this population., Objectives: To examine whether risk and protective factors measured at 6 weeks after injury could classify individuals into risk clusters and evaluate whether these clusters explain variations in 12-month outcomes., Design, Setting, and Participants: A prospective observational study was conducted between July 16, 2013, and January 15, 2016, among 352 patients with severe orthopedic injuries at 6 US level I trauma centers. Statistical analysis was conducted from October 9, 2017, to July 13, 2018., Main Outcomes and Measures: At 6 weeks after discharge, patients completed standardized measures for 5 risk factors (pain intensity, depression, posttraumatic stress disorder, alcohol abuse, and tobacco use) and 4 protective factors (resilience, social support, self-efficacy for return to usual activity, and self-efficacy for managing the financial demands of recovery). Latent class analysis was used to classify participants into clusters, which were evaluated against measures of function, depression, posttraumatic stress disorder, and self-rated health collected at 12 months., Results: Among the 352 patients (121 women and 231 men; mean [SD] age, 37.6 [12.5] years), latent class analysis identified 6 distinct patient clusters as the optimal solution. For clinical use, these clusters can be collapsed into 4 groups, sorted from low risk and high protection (best) to high risk and low protection (worst). All outcomes worsened across the 4 clinical groupings. Bayesian analysis shows that the mean Short Musculoskeletal Function Assessment dysfunction scores at 12 months differed by 7.8 points (95% CI, 3.0-12.6) between the best and second groups, by 10.3 points (95% CI, 1.6-20.2) between the second and third groups, and by 18.4 points (95% CI, 7.7-28.0) between the third and worst groups., Conclusions and Relevance: This study demonstrates that during early recovery, patients with orthopedic trauma can be classified into risk and protective clusters that account for a substantial amount of the variance in 12-month functional and health outcomes. Early screening and classification may allow a personalized approach to postsurgical care that conserves resources and targets appropriate levels of care to more patients.

Landscape-scale alterations that accompany urbanization may negatively affect the population structure of wildlife species such as freshwater turtles. Changes to nesting sites and higher mortality rates due to vehicular collisions and increased predator populations may particularly affect immature turtles and mature female turtles. We hypothesized that the proportions of adult female and immature turtles in a population will negatively correlate with landscape urbanization. As a collaborative effort of the Ecological Research as Education Network (EREN), we sampled freshwater turtle populations in 11 states across the central and eastern United States. Contrary to expectations, we found a significant positive relationship between proportions of mature female painted turtles (Chrysemys picta) and urbanization. We did not detect a relationship between urbanization and proportions of immature turtles. Urbanization may alter the thermal environment of nesting sites such that more females are produced as urbanization increases. Our approach of creating a collaborative network of scientists and students at undergraduate institutions proved valuable in terms of testing our hypothesis over a large spatial scale while also allowing students to gain hands-on experience in conservation science., (© 2018 Society for Conservation Biology.)

Background: Activation of the Hedgehog signalling pathway contributes to cancer progression and the development of myeloid leukaemia stem cell therapeutic resistance. We aimed to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose of the selective Hedgehog antagonist PF-04449913 in myeloid malignancies., Methods: We undertook an open-label, dose-finding, standard 3+3 design phase 1 study of PF-04449913 in adult patients with acute myeloid leukaemia, chronic myeloid leukaemia, chronic myelomonocytic leukaemia, myelodysplastic syndrome, or myelofibrosis who were refractory, resistant, or intolerant to previous treatments, at three centres in the USA and one in Italy. Patients who had newly diagnosed, untreated disease were included if they were not eligible for standard treatment options or if standard treatments were not deemed appropriate. Patients received PF-04449913 once daily continuously until disease progression, unacceptable toxic effects, or patient withdrawal for up to 12 28-day cycles. Additional cycles were given if patients showed evidence of clinical benefit. The starting dose was 5 mg and was increased by 100% until the first dose-limiting toxic effect (DLT) and by 50% thereafter, in keeping with a 3+3 clinical trial statistical design. The primary endpoint was first-cycle DLTs. Secondary endpoints were safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity. This trial is registered with ClinicalTrials.gov, number NCT00953758., Findings: Between March 24, 2010, and Sept 7, 2012, 47 patients were enrolled and included in the study: 28 with acute myeloid leukaemia, six with myelodysplastic syndrome, five with chronic myeloid leukaemia (two with chronic-phase and three with blast-phase disease), one with chronic myelomonocytic leukaemia, and seven with myelofibrosis. Patients received PF-04449913 once daily at 5 mg (n=3), 10 mg (n=3), 20 mg (n=4), 40 mg (n=4), 80 mg (n=8), 120 mg (n=3), 180 mg (n=3), 270 mg (n=5), 400 mg (n=9), and 600 mg (n=5). Two patients experienced DLTs (one each in the 80 mg and 600 mg dose groups). The MTD for PF-04449913 was established to be 400 mg once daily. Of the 47 patients enrolled, 28 (60%) experienced treatment-related adverse events, three of which were grade 4 in severity. The most common treatment-related adverse events included dysgeusia (13 [28%] patients), decreased appetite (nine [19%]), and alopecia (seven [15%]). None of the 15 deaths reported were treatment related. Pharmacokinetics seemed to be dose proportional. The mean half-life was 23·9 h (SD 14·0) in the MTD group. Some suggestion of clinical activity was noted in 23 (49%) of 47 patients with haematological malignancies. Based on these results, the recommended phase 2 dose was 200 mg or lower once daily., Interpretation: Based on these findings, PF-04449913 is being tested in phase 2 studies in patients with myelodysplastic syndrome, acute myeloid leukaemia, and myelofibrosis., Funding: Pfizer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Support for Institutional Animal Care and Use Committees (IACUCs) varies among those in animal use-related professions. The authors designed and carried out an anonymous survey to solicit opinions on the structure and organizational functions of IACUCs. They found that most respondents believed a single, institution-based IACUC was an appropriate venue for institutional approval of animal care and use, that their IACUCs represented their institutions' constituencies and that the unaffiliated IACUC members adequately represented their surrounding communities. Respondents believed that members came prepared for IACUC meetings, and a majority agreed that full committee reviews were more thorough than designated member reviews. The quality of veterinary care for animals was deemed to be very good. Participants reported that the status of the person submitting an animal use protocol, the perceived monetary value of a grant associated with a protocol and pressure for a rapid protocol review did not alter the quality of the protocol review. On many of the survey items, opinions of IACUC members differently significantly from those of non-members, and opinions of non-member IACUC administrators differed from those of IACUC chairpersons, perhaps owing to differences in responsibilities and perceived status.

Public health surveillance and epidemiology are the foundations for disease prevention because they provide the factual basis from which agencies can set priorities, plan programs, and take actions to protect the public's health. Surveillance for noninfectious diseases associated with exposure to agents in the environment like lead and pesticides has been a function of state health departments for more than 3 decades, but many state programs do not have adequate funding or staff for this function. Following the efforts to identify core public health epidemiology functions in chronic diseases, injury, and occupational health and safety, a workgroup of public health environmental epidemiologists operating within the organizational structure of the Council of State and Territorial Epidemiologists has defined the essential core functions of noninfectious disease environmental epidemiology that should be present in every state health department and additional functions of a comprehensive program. These functions are described in terms of the "10 Essential Environmental Public Health Services" and their associated performance standards. Application of these consensus core and expanded functions should help state and large metropolitan health departments allocate resources and prioritize activities of their environmental epidemiologists, thus improving the delivery of environmental health services to the public.

Nearly half of all external grants from the US National Institutes of Health require approval by the recipient organization's Institutional Animal Care and Use Committee (IACUC) before the funds can be used for research with animals. Given that large sums of money are spent annually on research involving animals, studies evaluating the strengths, weaknesses and overall effectiveness of IACUCs and similar animal welfare committees are needed. The authors designed and carried out a self-assessment survey on IACUC function and effectiveness. They found that 98% of all respondents believed that their IACUCs advanced animal welfare, but in many instances, veterinarians' responses to individual survey items were significantly different from those of other IACUC members. Protocol compliance, protocol review training and better understanding among non-committee members of the need for regulatory oversight are some areas where improvements could be made. Less than 50% of respondents stated that literature searches to find alternatives to animal use or painful or distressful procedures were helpful.

Purpose: Nilotinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase (CP; CML-CP) and accelerated phase (AP; CML-AP) who are resistant to or intolerant of prior imatinib therapy. In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed., Patients and Methods: Baseline mutation data were assessed in 281 (88%) of 321 patients with CML-CP in the phase II nilotinib registration trial., Results: Among imatinib-resistant patients, the frequency of mutations at baseline was 55%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 40%, and major molecular response (MMR) in 29% of patients without baseline mutations versus 49% (P = .145), 32% (P = .285), and 22% (P = .366), respectively, of patients with mutations. Responses in patients who harbored mutations with high in vitro sensitivity to nilotinib (50% inhibitory concentration [IC(50)] 150 nM; Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR; none achieved CCyR., Conclusion: For most patients with imatinib resistance and with mutations, nilotinib offers a substantial probability of response. However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib.

Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia, regular and accelerated approval. Regular approval requires evidence of clinical benefit, which is generally defined as either prolongation of life or improved quality of life, or an effect on an end point established as a surrogate for clinical benefit. Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure "reasonably likely" to predict clinical benefit, but requires demonstration of clinical benefit after approval as well. The acute leukemias are a heterogeneous and relatively uncommon group of diseases. The design and execution of prospective randomized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up. Thus, the development of novel trial design and inclusion of validated surrogate markers for clinical benefit are needed. To explore some of the issues pertinent to the choice of end points for drug approval in acute leukemia, the Food and Drug Administration invited the American Society of Hematology to participate in the organization and conduct of a joint workshop. In this report, we present the results of that effort.

In designing and setting up a clinical trial, investigators and private sponsors must take into account what costs will or will not be covered by third-party insurers and government payment programs like Medicare and Medicaid. Failure to "cost out" the clinical trials accurately can yield one of two results: either third-party payors are billed improperly, or even illegally, for experimental care, or significant research-related care is not billed, with either the investigating institution, or the research subjects themselves, shouldering the cost. Unfortunately, because Medicare has established different coverage principles to be applied depending on the type of trial being conducted, costing out the trial is not an easy task. This Article looks at the various Medicare coverage principles as they apply to clinical trials, including the 2000 National Coverage Decision and the recent expansion in coverage for Class A Investigational Devices created by the Medicare Prescription Drug, Improvement, and Modernization Act of 2003. The Article then examines how the Medicare secondary payor rule, which states that providers may not bill Medicare for items or services when another party has primary responsibility for those services, relates to clinical trails in light of recent commentary. The Article concludes with the presentation of a general framework that investigators can use to establish a clinical trial budgeting and billing system.

In experimental decerebration of mammals, the cerebral cortex and thalamus are surgically or otherwise inactivated under traditional (pharmacologic) general anesthesia. Once the effects of the pharmacologic anesthesia have dissipated, the animal remains alive, but there is neither pain sensation nor consciousness. Because the Animal Welfare Act and its regulations recognize drugs as the only means to alleviate pain, it is unclear whether a decerebrate animal should be placed in U.S. Department of Agriculture (USDA) pain and distress category D (pain or distress alleviated by drugs) or E (unalleviated pain or distress). We present a rationale for including decerebrate animals in USDA category D. We also provide a general review of decerebration and suggestions for institutional animal care and use committees having to evaluate decerebration protocols.

Early detection represents one of the most promising approaches to reducing the growing cancer burden. It already has a key role in the management of cervical and breast cancer, and is likely to become more important in the control of colorectal, prostate and lung cancer. Early-detection research has recently been revitalized by the advent of novel molecular technologies that can identify cellular changes at the level of the genome or proteome, but how can we harness these new technologies to develop effective and practical screening tests?

In vaccine clinical trials, humoral antibody responses are often used to measure the effect of a vaccine because they correlate with a vaccine's protective efficacy against the target disease. While the concept of a correlate of protection usually refers to establishing a protective level of antibody titre, identifying a clear-cut value is often impossible because vaccine efficacy is not related solely to the antibody titre. We propose examining the relationship between disease protection and the whole distribution of antibody responses rather than a single cut-off level. In particular, we use failure-time models to estimate the relationship between long-term disease breakthroughs and primary antibody responses after vaccination. We apply these models to show that the varicella antibody response measured by glycoprotein enzyme-linked immunosorbent assay 6 weeks after vaccination strongly correlate with protection against varicella (chickenpox); we used 7-year follow-up data from children who received one dose of a live attenuated varicella (Oka/Merck) vaccine. In addition, we explore the potential use of these models to predict long-term disease breakthrough rates and to estimate the predicted vaccine efficacy of a similar varicella vaccine made with a modified manufacturing process., (Copyright 2002 John Wiley & Sons, Ltd.)