The effect of a population bottleneck on the evolution of genetic variance/covariance structure.

It is well known that standard population genetic theory predicts decreased additive genetic variance (V(a) ) following a population bottleneck and that theoretical models including interallelic and intergenic interactions indicate such loss may be avoided. However, few empirical data from multicellular model systems are available, especially regarding variance/covariance (V/CV) relationships. Here, we compare the V/CV structure of seventeen traits related to body size and composition between control (60 mating pairs/generation) and bottlenecked (2 mating pairs/generation; average F = 0.39) strains of mice. Although results for individual traits vary considerably, multivariate analysis indicates that V(a) in the bottlenecked populations is greater than expected. Traits with patterns and amounts of epistasis predictive of enhanced V(a) also show the largest deviations from additive expectations. Finally, the correlation structure of weekly weights is not significantly different between control and experimental lines but correlations between necropsy traits do differ, especially those involving the heart, kidney and tail length.

The effects of screw placement on plate strain in 3.5 mm dynamic compression plates and limited-contact dynamic compression plates.

The objective of this study was to evaluate the effect of screw omission on plate strain during axial load to failure and cycling using a Delrin rod gap model. In addition, the differences between the 3.5 mm limited-contact dynamic compression plate (LC-DCP) and the 3.5 mm dynamic compression plate (DCP) were evaluated. Six, 12-hole LC-DCP and DCP plates were applied to Delrin rods with a 1 cm gap located within the central portion of the plate. Six screw configurations were tested with the following variations: three proximal and three distal (six open), four proximal and three distal (five open), four proximal and four distal (four open), five proximal and four distal (three open), five proximal and five distal (two open), six proximal and five distal (one open). Three strain gauges were mounted on each plate within the gap (gauge three) and extended proximally. Additionally, three constructs (six, three, and one open hole) were tested to failure in cyclic loading. The strain measured within the gap (gauge three) was significantly greater than the strain at other gauges for each screw configuration. Strain within the gap did not significantly change with any screw configuration, but did significantly increase at other locations as screws were omitted. Overall, the DCP withstood significantly more cycles than the LC-DCP. Differences were noted within the DCP group with the 6/5 screw configuration lasting for significantly more cycles than the 5/4 and 3/3 constructs. Although overall strain at the gap did not significantly increase with screw omission, the clinical significance remains to be determined.

Effect of Cry3Bb1-expressing transgenic corn on plant-to-plant movement by western corn rootworm larvae (Coleoptera: Chrysomelidae).

Dispersal of larvae of the western corn rootworm, Diabrotica virgifera virgifera LeConte, in specific combinations of transgenic corn expressing the Cry3Bb1 protein and nontransgenic, isoline corn was evaluated in a 2-yr field study. In total, 1,500 viable western corn rootworm eggs were infested in each subplot. Each year, plant damage and larval recovery were evaluated among four pedigree combinations (straight transgenic; straight nontransgenic corn; nontransgenic corn with a transgenic central, infested plant; and transgenic corn with a nontransgenic central, infested plant) on six sample dates between egg hatch and pupation. For each subplot, the infested plant, three successive plants down the row (P1, P2, and P3), the closest plant in the adjacent row of the plot, and a control plant were sampled. The number of western corn rootworm larvae recovered from transgenic rootworm-resistant plants adjacent to infested nontransgenic plants was low and not statistically significant in either 2001 or 2002. In 2001, significantly fewer larvae were recovered from transgenic rootworm-resistant plants than from nontransgenic plants when both were adjacent to infested, nontransgenic plants. In 2002, significantly more neonate western corn rootworm larvae were recovered from nontransgenic plants adjacent to infested, transgenic rootworm-resistant plants than nontransgenic plants adjacent to infested, nontransgenic plants on the second sample date. Together, these data imply that both neonate and later instar western corn rootworm larvae prefer nontransgenic roots to transgenic rootworm-resistant roots when a choice is possible. However, when damage to the infested, nontransgenic plant was high, western corn rootworm larvae apparently moved to neighboring transgenic rootworm-resistant plants and caused statistically significant, although only marginally economic, damage on the last sample date in 2001. Implications of these data toward resistance management plan are discussed.

Epistasis affecting litter size in mice.

Litter size is an important reproductive trait as it makes a major contribution to fitness. Generally, traits closely related to fitness show low heritability perhaps because of the corrosive effects of directional natural selection on the additive genetic variance. Nonetheless, low heritability does not imply, necessarily, a complete absence of genetic variation because genetic interactions (epistasis and dominance) contribute to variation in traits displaying strong heterosis in crosses, such as litter size. In our study, we investigated the genetic architecture of litter size in 166 females from an F2 intercross of the SM/J and LG/J inbred mouse strains. Litter size had a low heritability (h2 = 12%) and a low repeatability (r = 33%). Using interval-mapping methods, we located two quantitative trait loci (QTL) affecting litter size at locations D7Mit21 + 0 cM and D12Mit6 + 8 cM, on chromosomes 7 and 12 respectively. These QTL accounted for 12.6% of the variance in litter size. In a two-way genome-wide epistasis scan we found eight QTL interacting epistatically involving chromosomes 2, 4, 5, 11, 14, 15 and 18. Taken together, the QTL and their interactions explain nearly 49% (39.5% adjusted multiple r2) of the phenotypic variation for litter size in this cross, an increase of 36% over the direct effects of the QTL. This indicates the importance of epistasis as a component of the genetic architecture of litter size and fitness in our intercross population.

Activated eosinophils upregulate the metastasis suppressor molecule E-cadherin on prostate tumor cells.

Cell adhesion molecules (CAMs) play an important role in cancer metastasis by facilitating attachment to vascular endothelia, invasion and spread into secondary tissue sites. We have shown that activated eosinophils (EosA) inhibited the growth of prostate cancer (Pca) cells in vitro. In the present study, we examined the ability of EosA 24 hr conditioned supernatants (EosAcs) to modulate the expression of ICAM-1, VCAM-1, ELAM-1, E-cadherin and N-cadherin expression on human Pca cell lines, Du-145 and PC-3 by flow cytometry. TNF-alpha, IL-10 and IL-12 were also evaluated. ICAM-1, expressed on PC-3 and DU 145 cells, was enhanced by TNF-alpha and IL-10. ELAM-1 was present on DU 145 cells but absent on PC-3. TNF-alpha and IL-10 enhanced ELAM-1 on DU 145, but EosA 24 hr supematants failed to do so. All three cytokines, namely IL-10, IL-12 and TNF-alpha-induced ELAM-1 on PC-3 tumor cells. Although VCAM-1 was absent on DU 145 and PC-3 cells, it was expressed on DU-145 cells after exposure to EosA: tumor cell co-cultures, and was expressed on PC-3 following exposure to IL-10 and IL-12. N-cadherin and E-cadherin were both expressed on DU-145. While N-cadherin was expressed on PC-3 cells, E-cadherin was not. N-cadherin was enhanced on DU-145 and PC-3 cells following exposure to EosA co-culture and upregulated on PC-3 by IL-10 and EosA 24 hr supernatants, but decreased by IL-12. E-cadherin was up-regulated on DU 145 cells following co-culture with EosA and was induced on PC-3 by IL-10 and IL-12, but not by EosA co-culture and 24 hr supematants. In conclusion, inflammatory and non-inflammatory cytokines modulate CAM expression on Pca cells; EosA and EosA 24 hr supernatants also exerted modulatory activity of CAM expression. Most significantly, the metastasis suppressor molecule, E-cadherin was enhanced on DU 145 cells by EosA and induced on PC-3 by IL-10 and IL-12 both of which are produced by EosA. This suggests potential use of these cytokines in immunotherapeutic strategies for prostate cancer and its metastasis.

Eosinophils in a tri-cell multicellular tumor spheroid (MTS)/endothelium complex.

Eosinophils have been found in infiltrates of many different cancers. It is still unclear as to whether they are passive bystanders in the cellular milieu or active cellular agents in host responses. Thus their harmful or helpful nature remains equivocal. We have developed an in vitro tri-cell model of eosinophils, MCF-7 breast tumor cell spheroids and HUVEC endothelial cells to examine the binding and association of eosinophils with both the tumor and the endothelia and the ensuing action of the tumor. Eosinophils bound very rapidly to the tumor spheroid and remained tightly bound throughout the 24 hr culture period. Histological staining of the tri-cell complex revealed highly granulated eosinophils as well as large amounts of degranulated protein diffused throughout the spheroid. IL-5 treatment of eosinophil: MTS complexes resulted in destruction of the tumor cells, particularly those which had grown out from the spheroid onto the endothelial cells. Eosinophils, pretreated with IL-5 before interaction with the tumor or endothelial cells, bound aggressively to the endothelial cells, thereby preventing tumor attachment. This eosinophil tri-cell tumor model system mimics clinical observations with regards to binding to epithelial and endothelial cells, dispersal of granular proteins throughout the tumor and also tumor destruction. Because it closely mirrors in vivo cellular interactions, it allows one to study more closely the mechanism(s) of eosinophil killing, the modulation of eosinophil activity and the testing of therapeutic interventions. The accommodation of the model to tumor invasion, using metastatic tumor cells and extracellular matrices such as matrigel, will help to elucidate a role for eosinophils (and their mediators) in cancer invasion and metastasis.

Contribution of maternal effect QTL to genetic architecture of early growth in mice.

Existing approaches to characterizing quantitative trait loci (QTL) utilize a paradigm explicitly focused on the direct effects of genes, where phenotypic variation among individuals is mapped onto genetic variation of those individuals. For many characters, however, the genotype of the mother via its maternal effect accounts for a considerable portion of the genetically based variation in progeny phenotypes. Thus the focus on direct effect QTL may result in an insufficient or misleading characterization of genetic architecture due to the omission of the potentially important source of genetic variance contributed by maternal effects. We analyze the relative contribution of direct and maternal effect (ME) QTL to early growth in mice using a three-generation intercross of the Small (SM/J) and Large (LG/J) inbred mouse lineages. Using interval mapping and composite interval mapping, direct effect (DE) QTL for early growth (change in body mass during the interval from week 1 to 2) were detected in the F(2) generation of the intercross (n = 510), where no maternal genetic effect variance is present (all individuals are progeny of genetically identical F(1) mothers). ME QTL were detected by treating the phenotypes of cross-fostered F(3) pups as a characteristic of their nurse-dam (n = 168 dams with cross-fostered progeny). Five DE QTL, significant at a chromosome wide level (alpha = 0.05), were detected, with two significant at a genome wide level. FourME QTL significant at the chromosome wide level were detected, with three significant at the genome wide level. A model containing only DE QTL accounted for 11.8% of phenotypic variance, while a model containing only ME QTL accounted for 31.5% of the among litter variance in growth. There was no evidence for pleiotropy of DE and ME loci since there was no overlap between loci detected in these two analyses. Epistasis between all pairs of loci was analyzed for both DEs and MEs. Ten pairs of loci showed significant epistasis for MEs (alpha = 0.05 corrected for multiple comparisons) while four pairs showed significant epistasis for DEs on early growth.

Organizational culture, continuous quality improvement, and medication administration error reporting.

This study explores the relationships among measures of nurses' perceptions of organizational culture, continuous quality improvement (CQI) implementation, and medication administration error (MAE) reporting. Hospital-based nurses were surveyed using measures of organizational culture and CQI implementation. These data were combined with previously collected data on perceptions of MAE reporting. A group-oriented culture had a significant positive correlation with CQI implementation, whereas hierarchical and rational culture types were negatively correlated with CQI implementation. Higher barriers to reporting MAE were associated with lower perceived reporting rates. A group-oriented culture and a greater extent of CQI implementation were positively (but not significantly) associated with the estimated overall percentage of MAEs reported. We conclude that health care organizations have implemented CQI programs, yet barriers remain relative to MAE reporting. There is a need to assess the reliability, validity, and completeness of key quality assessment and risk management data.

Epidemiology of occupational injuries and illnesses in a university population: a focus on age and gender differences.

BACKGROUND: Occupational injuries and illnesses are a major preventable public health problem. METHODS: This study evaluated the incidence, nature, and cause of awarded workers' compensation claims for a large state university and teaching hospital. Rates and types of injury were compared across age and gender. RESULTS: Rates of injury varied over twofold with age, with those 16-25 having the lowest rates of injury and those 36-45 having the highest rates. Claims rates were 1.36-fold higher for women than men. Women had higher rates for injury resulting from lifting, falling, noxious exposures, repetitive motion, and carpal tunnel syndrome. Similarly women had significantly higher rates of claims for pain, sprains, bruises, burns, concussion, and inhalation injury; with lower rates of cuts, ligament injury, and jammed joints. CONCLUSIONS: These group differences suggest the need to examine age and gender job distributions and relevant ergonomic and environmental causative factors.

Hospital bloodborne pathogens programs: program characteristics and blood and body fluid exposure rates.

OBJECTIVE: To describe hospital practices and policies relating to bloodborne pathogens and current rates of occupational exposure among healthcare workers. PARTICIPANTS AND METHODS: Hospitals in Iowa and Virginia were surveyed in 1996 and 1997 about Standard Precautions training programs and compliance. The primary outcome measures were rates of percutaneous injuries and mucocutaneous exposures. RESULTS: 153 (64%) of 240 hospitals responded. New employee training was offered no more than twice per year by nearly one third. Most (79%-80%) facilities monitored compliance of nurses, housekeepers, and laboratory technicians; physicians rarely were trained or monitored. Implementation of needlestick prevention devices was the most common action taken to decrease sharps injuries. Over one half of hospitals used needleless intravenous systems; larger hospitals used these significantly more often. Protected devices for phlebotomy or intravenous placement were purchased by only one third. Most (89% of large and 80% of small) hospitals met the recommended infection control personnel-to-bed ratio of 1:250. Eleven percent did not have access to postexposure care during all working hours. Percutaneous injury surveillance relied on incident reports (99% of facilities) and employee health records (61%). The annual reported percutaneous injury incidence rate from 106 hospitals was 5.3 injuries per 100 personnel. Compared to single tertiary-referral institution rates determined more than 5 years previously, current injury rates remain elevated in community hospitals. CONCLUSIONS: Healthcare institutions need to commit sufficient resources to Standard Precautions training and monitoring and to infection control programs to meet the needs of all workers, including physicians. Healthcare workers clearly remain at risk for injury. Further effective interventions are needed for employee training, improving adherence, and providing needlestick prevention devices.

Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice.

The genetic basis of variation in obesity in human populations is thought to be owing to many genes of relatively small effect and their interactions. The LG/J by SM/J intercross of mouse inbred strains provides an excellent model system in which to investigate multigenic obesity. We previously mapped a large number of quantitative trait loci (QTLs) affecting adult body weight in this cross. We map body composition traits, adiposity, and skeletal size, in a replicate F2 intercross of the same two strains containing 510 individuals. Using interval-mapping methods, we located eight QTLs affecting adiposity (Adip1-8). Two of these adiposity loci also affected tail length (Adip4 and Adip6) along with seven additional tail length QTLs (Skl1-7). A further four QTLs (Wt1-4) affect adult weight but not body composition. These QTLs have relatively small effects, typically about 0.2-0.4 standard deviation units, and account for between 3% and 10% of the variance in individual characters. All QTLs participated in epistatic interactions with other QTLs. Most of these interactions were due to additive-by-additive epistasis, which can nullify the apparent effects of single loci in our population. Adip8 interacts with all the other adiposity QTLs and seems to play a central role in the genetic system affecting obesity in this cross. Only two adiposity QTLs, Adip4 and Adip6, also affect tail length, indicating largely separate genetic control of variation in adiposity and skeletal size. Body size and obesity QTLs in the same locations as those discovered here are commonly found in mapping experiments with other mouse strains.

Nurse experience and education: effect on quality of care.

OBJECTIVE: To describe the relationships between the quality of patient care and the education and experience of the nurses providing that care. BACKGROUND: There is a call for more nurses with baccalaureate degrees and more experienced nurses to work in hospitals. Previous research studies have examined the characteristics, abilities, and work assignments of nurses with and without baccalaureate degrees but have not examined the quality of the patient care delivered. It is generally believed that more experienced nurses provide higher-quality care, but again few studies have actually examined this issue. METHODS: A secondary analysis of data, collected in two previous studies of the relationship between nurse staffing (hours of care, staff mix) and the quality of patient care, was used to determine the relationship between nurses' education and experience and the quality of care provided. The data were collected at the patient care unit level (42 units in study 1 and 39 units in study 2). Quality of care was indicated by lower unit rates of medication errors and patient falls. RESULTS: Controlling for patient acuity, hours of nursing care, and staff mix, units with more experienced nurses had lower medication errors and lower patient fall rates. These adverse occurrence rates on units with more baccalaureate-prepared nurses were not significantly better.

Monitoring adherence to Standard Precautions.

BACKGROUND: Health care workers (HCWs) do not consistently follow Standard Precautions (SP). This is a serious problem because inadequate compliance is associated with increased blood exposure thus predisposing HCWs to bloodborne pathogen transmission. METHODS: The primary goal of this study was to identify institutional factors associated with adequacy of HCW training to monitor coworkers' adherence to SP. Surveys were sent to all community hospital infection control practitioners (ICPs) in Iowa and Virginia. ICPs indicated on a 5-point Likert scale, ranging from strongly disagree to strongly agree, their assessment of HCW training adequacy. Data from another statewide survey of HCWs in Iowa were assessed to validate this outcome measure. Multiple logistic regression models were developed to identify predictors of assessed training adequacy. Independent variables included methods of education, training, approaches to SP compliance assessment, provision of SP reinforcement by clinical leaders, and organizational data. RESULTS: A total of 149 institutions (62%) participated. Models of training program adequacy varied across occupations. Management commitment to SP training programs, leadership support, frequency of providing bloodborne pathogen information, and safety climate were important institutional predictors of assessed adequacy of training. The outcome was validated by demonstrating an association between the ICPs' assessment of HCW training and workers who reported having sufficient information to comply with SP (P <.05). CONCLUSIONS: Institutional safety climate, leadership support, and frequency of education play an important role in HCWs' training adequacy to monitor coworkers' adherence to SP. Occupational groups should be considered independently when strategies are developed to increase compliance. Interventions based on modifiable factors identified by this study may reduce bloodborne pathogen exposure among HCWs.

Dose of case management interventions.

Case management programs need to be evaluated for outcomes achievement and efficient use of resources. As a provider intervention, case management is interactional and situational. Little is known about how to measure the actual dose delivered in order to assess quality and manage outcomes. Case management is interdisciplinary, has identifiable dimensions, and serves as a practical example of conceptualizing and measuring the dosage of a provider's intervention. The basic elements of the dosage of an intervention are amount, frequency, duration, and breadth. A three-dimensional model illustrates dosage of case management.

Rural hospitals and the adoption of managed care strategies.

This research examined the performance of rural hospitals engaged in different levels of managed care activities and identified factors related to performance and competition that affected rural hospitals' likelihood of pursuing managed care as a strategy. The sample studied consisted of 139 rural hospitals in Iowa and Nebraska. Results showed that a relatively high percentage of hospitals were engaged in managed care activities, mainly through contractual arrangements. The study found that high competition in the marketplace increased the likelihood of hospitals pursuing managed care strategies, while high demand markets had a negative association with the likelihood of pursuing a managed care strategy. No significant relationship was detected between poor performance and pursuing a managed care strategy.

Laparoscopic repair of bilateral inguinal hernias in a patient with müllerian agenesis.

OBJECTIVE: To report a case of laparoscopic repair of bilateral inguinal hernias in a patient with müllerian agenesis. DESIGN: Case report. SETTING: Hospital. PATIENT(S): An 18-year-old woman with müllerian agenesis who presented with symptomatic inguinal hernias containing ovaries. INTERVENTION(S): Laparoscopic repair of bilateral inguinal hernias. MAIN OUTCOME MEASURE(S): Hernia repair was accomplished laparoscopically. RESULT(S): Outpatient laparoscopic repair of bilateral inguinal hernias with reduction of ovaries was performed using an extraperitoneal approach without complication. CONCLUSION(S): Laparoscopic approach of inguinal hernias can be an option for surgical repair in patients with müllerian agenesis even when the hernias contain ovaries.

Limitations of secondary data for strategic marketing in rural areas.

Market research is an important element of the strategic marketing process. By understanding the healthcare needs of a market area, hospital and health system managers can set priorities for new services and allocate resources appropriately. The process of market research often begins with an evaluation of health status and socioeconomic indicators collected from secondary sources. Unfortunately, indicators that have been recommended in the literature may not be feasible for use in rural markets because of their lack of statistical precision or inability to differentiate healthcare service needs. This study evaluated the statistical precision and variability of 79 secondary health status and socioeconomic measures reported at the county level in Iowa, USA, a largely rural state. Our findings suggest that many readily available health status and socioeconomic indicators do not discriminate need among rural health care markets. Only six health status and two socioeconomic indicators met our statistical precision and variability criteria. These findings have important implications for managers planning health services in rural localities. Managers of rural health systems may need to employ alternative market research methods, such as analysis of claims-based utilization rates or community health surveys.

The effects of structure, strategy and market conditions on the operating practices of physician-organization arrangements.

Research to date has documented weak or inconsistent associations between market and organizational factors and the adoption of physician-organization arrangements (POAs) (e.g. physician-hospital organizations, management service organizations and independent practice associations) designed to increase physician integration. We argue that POAs may mask considerable variation in how these entities are operated and governed. Further, because the operating policies and practices of POAs are likely to influence more directly the behaviour of physicians than the structural form of the POA, they may be more sensitive to the market and organizational contingencies that encourage integration. This study attempts to test empirically the relative effects of POA type and market, strategic and organization factors on the operating policies and practices of market-based POAs. Results suggest that type of POA, and market, strategic and organizational factors affect risk sharing, physician selection practices, physician monitoring practices and ways in which monitoring information is used to influence physician behaviour in POAs.

Health status and health professional visits in a rural area.

Visits to physicians (MDs), physician assistants (PAs) or nurse practitioners (NPs) by residents of a rural county in the upper-middle west of the United States were analysed in this study. A telephone survey yielded 250 responses. The dependent variable was the natural logarithm of the number of times the respondent had seen a health professional (MD, PA or NP) in the past two years. Predisposing, enabling and medical need variables were tested as potential predictors of visits. Self-rated health status, being unable to perform usual activities, and feeling upset or 'down in the dumps' proved to be important predictors, as was having a usual source of care. Health insurance coverage and family income was not, however. Unexpectedly, smokers also reported more visits. The implications for policy and future research are discussed.

Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria.

Nitric oxide (NO) plays an important role in host resistance to infection with a variety of organisms. Two recent reports from Gabon and Gambia identified associations of malaria disease severity with the inducible NO synthase (NOS2) promoter G-954C and short allele (<11 repeats) pentanucleotide microsatellite polymorphisms, respectively. It was postulated that there would be a correlation of these polymorphisms with malaria disease severity and with measures of NO production in our cohort of Tanzanian children with malaria. In Tanzanian children, 15% were heterozygous or homozygous for the G-954C polymorphism, and 13% had the short-allele microsatellite polymorphism. There was no significant correlation of either polymorphism with disease severity or with measures of NO production and NOS2 expression. Black and white Americans differed significantly in the frequencies of these polymorphisms. The various association of these gene polymorphisms with malaria severity in different populations underscores the complexity of host resistance to malaria.