Greenhouse gas production from an intermittently dosed cold-climate wastewater treatment wetland.

This study explores the greenhouse gas (GHG) fluxes of nitrous oxide (N2O), methane (CH4) and carbon dioxide (CO2) from a two-stage, cold-climate vertical-flow treatment wetland (TW) treating ski area wastewater at 3 °C average water temperature. The system is designed like a modified Ludzack-Ettinger process with the first stage a partially saturated, denitrifying TW followed by an unsaturated nitrifying TW and recycle of nitrified effluent. An intermittent wastewater dosing scheme was established for both stages, with alternating carbon-rich wastewater and nitrate-rich recycle to the first stage. The system has demonstrated effective chemical oxygen demand (COD) and total inorganic nitrogen (TIN) removal in high-strength wastewater over seven years of winter operation. Following two closed-loop, intensive GHG winter sampling campaigns at the TW, the magnitude of N2O flux was 2.2 times higher for denitrification than nitrification. CH4 and N2O emissions were strongly correlated with hydraulic loading, whereas CO2 was correlated with surface temperature. GHG fluxes from each stage were related to both microbial activity and off-gassing of dissolved species during wastewater dosing, thus the time of sampling relative to dosing strongly influenced observed fluxes. These results suggest that estimates of GHG fluxes from TWs may be biased if mass transfer and mechanisms of wastewater application are not considered. Emission factors for N2O and CH4 were 0.27 % as kg-N2O-N/kg-TINremoved and 0.04 % kg-CH4-C/kg-CODremoved, respectively. The system had observed seasonal emissions of 600.5 kg CO2 equivalent of GHGs estimated over 130-days of operation. These results indicate a need for wastewater treatment processes to mitigate GHGs.

Enhancing quantitative approaches for assessing community resilience.

Scholars from many different intellectual disciplines have attempted to measure, estimate, or quantify resilience. However, there is growing concern that lack of clarity on the operationalization of the concept will limit its application. In this paper, we discuss the theory, research development and quantitative approaches in ecological and community resilience. Upon noting the lack of methods that quantify the complexities of the linked human and natural aspects of community resilience, we identify several promising approaches within the ecological resilience tradition that may be useful in filling these gaps. Further, we discuss the challenges for consolidating these approaches into a more integrated perspective for managing social-ecological systems.

Temperature, plant species and residence time effects on nitrogen removal in model treatment wetlands.

Total nitrogen (TN) removal in treatment wetlands (TWs) is challenging due to nitrogen cycle complexity and the variation of influent nitrogen species. Plant species, season, temperature and hydraulic loading most likely influence root zone oxygenation and appurtenant nitrogen removal, especially for ammonium-rich wastewater. Nitrogen data were collected from two experiments utilizing batch-loaded (3-, 6-, 9- and 20-day residence times), sub-surface TWs monitored for at least one year during which temperature was varied between 4 and 24 °C. Synthetic wastewater containing 17 mg/l N as NH4 and 27 mg/l amino-N, 450 mg/l chemical oxygen demand (COD), and 13 mg/l SO4-S was applied to four replicates of Carex utriculata, Schoenoplectus acutus and Typha latifolia and unplanted controls. Plant presence and species had a greater effect on TN removal than temperature or residence time. Planted columns achieved approximately twice the nitrogen removal of unplanted controls (40-95% versus 20-50% removal) regardless of season and temperature. TWs planted with Carex outperformed both Typha and Schoenoplectus and demonstrated less temperature dependency. TN removal with Carex was excellent at all temperatures and residence times; Schoenoplectus and Typha TN removal improved at longer residence times. Reductions in TN were not accompanied by increases in NO3, which was consistently below 1 mg/l N.

Patterns in body mass distributions: sifting among alternative hypotheses.

Understanding how animals interact with their environment is critical for evaluating, mitigating and coping with anthropogenic alteration of Earth's biosphere. Researchers have attempted to understand some aspects of these interactions by examining patterns in animal body mass distributions. Energetic, phylogenetic, biogeographical, textural discontinuity and community interaction hypotheses have been advanced to explain observed patterns. Energetic and textural discontinuity hypotheses focus upon the allometry of resource use. The community interaction hypothesis contends that biotic interactions within assemblages of species are of primary importance. Biogeographical and phylogenetic hypotheses focus on the role of constraints on the organization of communities. This paper examines and organizes these various propositions about species body mass distributions and discusses the multiple competing hypotheses, how their predictions vary, and possible methods by which the hypotheses can be distinguished and tested. Each of the hypotheses is partial, and explains some elements of pattern in body mass distributions. The scale of appropriate application, relevance and interpretation varies among the hypotheses, and the mechanisms underlying observed patterns are likely to be multicausal and vary with scale.

Assessing state-wide biodiversity in the Florida Gap analysis project.

The Florida Gap (Fl-Gap) project provides an assessment of the degree to which native animal species and natural communities are or are not represented in existing conservation lands. Those species and communities not adequately represented in areas being managed for native species constitute 'gaps' in the existing network of conservation lands. The United States Geological Survey Gap Analysis Program is a national effort and so, eventually, all 50 states will have completed it. The objective of Fl-Gap was to provide broad geographic information on the status of terrestrial vertebrates, butterflies, skippers and ants and their respective habitats to address the loss of biological diversity. To model the distributions and potential habitat of all terrestrial species of mammals, breeding birds, reptiles, amphibians, butterflies, skippers and ants in Florida, natural land cover was mapped to the level of dominant or co-dominant plant species. Land cover was classified from Landsat Thematic Mapper (TM) satellite imagery and auxiliary data such as the national wetlands inventory (NWI), soils maps, aerial imagery, existing land use/land cover maps, and on-the-ground surveys. Wildlife distribution models were produced by identifying suitable habitat for each species within that species' range. Mammalian models also assessed a minimum critical area required for sustainability of the species' population. Wildlife species richness was summarized against land stewardship ranked by an area's mandates for conservation protection.

Potential complication of bioabsorbable screw fixation for osteochondritis dissecans of the knee.

The 3 cases presented describe loosening or failure of bioabsorbable screws in the treatment of osteochondritis dissecans (OCD). In case 1, a 17-year-old boy with OCD of the medial femoral condyle was treated with bioabsorbable screw fixation. Six months after surgery, the patient had an acute episode of pain with effusion. Arthroscopic examination revealed 2 of the 4 screws backed out, causing cartilage damage to the corresponding tibial plateau. The shafts of the remaining 2 screws had completely absorbed, leaving the unabsorbed screw heads as intra-articular loose bodies in the knee. Unpredictable and inconsistent degradation of the screws is believed to be the mechanism for screw back-out and cartilage damage.

Influence of Helicobacter pylori on reactive oxygen-induced gastric epithelial cell injury.

Risk factors for gastric cancer are receiving renewed attention in light of the recent positive association of Helicobacter pylori infection with gastric cancer. The effect of H.pylori on the balance between oxidants and antioxidants in the stomach is not well known. In this study, we investigated if exposure of gastric cells to H. pylori increases oxidant-associated gastric epithelial cell injury. A human gastric epithelial cell line (AGS) was grown on 96-well clusters, then exposed overnight to either live H.pylori (four cagA(+) and four cagA(-)) or broth culture supernatant from an isogenic H.pylori cagA(+) strain with and without vacA activity. Incubation of AGS cells with cagA(+) and cagA(-) H.pylori strains before exposure to reactive oxygen species (ROS) reduced cell viability on average to 73.7% and 39.5% of controls, respectively. The percent viability of cells exposed to ROS after incubation with control broth, vacA(-) broth and vacA(+) broth was 97.7%, 70.5% and 63.5%, respectively. Experiments were then performed to evaluate the effects of H.pylori exposure on the activities of ROS-scavenging enzymes [catalase, glutathione peroxidase and superoxide dismutase (SOD)] and formation of 8-hydroxy-2-deoxyguanosine (8-OH-dG) adducts in AGS cells. Overnight exposure to cagA(-) strains reduced catalase activity by 42%; in contrast, exposure to cagA(+) H.pylori strains increased catalase activity by 51%. Glutathione peroxidase activity increased with exposure to both cagA(-) and cagA(+) strains by 95% and 240%, respectively. Total SOD activity increased 156% after exposure to cagA(+) strains and was marginally increased (52%) with exposure to cagA(-) strains. CuZn-SOD protein levels, assayed by enzyme-linked immunosorbent assay, were not significantly altered by exposure to H.pylori strains; however, Mn-SOD concentrations were significantly increased (P: < 0.02) after exposure to both cagA(-) and cagA(+) H.pylori strains. Exposure of AGS cells to cagA(+) and cagA(-) H.pylori was associated with, on average, 44.5 and 99.0 8-OH-dG/10(6) dG, respectively. The increase in catalase, glutathione peroxidase and SOD activity is associated with fewer 8-OH-dG DNA adducts and reduced susceptibility of AGS cells to lethal injury from ROS after exposure to cagA(+) H.pylori strains when compared with exposure to cagA(-) H.pylori strains. Alteration in the activity of ROS-scavenging enzymes by the presence of H. pylori may in part be responsible for the increased risk of gastric cancer in persons infected with H.pylori.

Helicobacter pylori inhibits gastric cell cycle progression.

Helicobacter pylori infection of the gastric mucosa is associated with changes in gastric epithelial cell proliferation. In vitro studies have shown that exposure to H. pylori inhibits proliferation of gastric cells. This study sought to investigate the cell cycle progression of gastric epithelial cell lines in the presence and absence of H. pylori. Unsynchronized and synchronized gastric epithelial cell lines AGS and KatoIII were exposed to H. pylori over a 24-h period. Cell cycle progression was determined by flow cytometry using propidium iodide (PI), and by analysis of cyclin E, p21, and p53 protein expression using Western blots. In the absence of H. pylori 40, 45, and 15% of unsynchronized AGS cells were in G(0)-G(1), S, and G(2)-M phases, respectively, by flow cytometry analysis. When AGS cells were cultured in the presence of H. pylori, the S phase decreased 10% and the G(0)-G(1) phase increased 17% after 24 h compared with the controls. KatoIII cells, which have a deleted p53 gene, showed little or no response to H. pylori. When G1/S synchronized AGS cells were incubated with media containing H. pylori, the G(1) phase increased significantly (25%, P < 0.05) compared with controls after 24 h. In contrast, the control cells were able to pass through S phase. The inhibitory effects of H. pylori on the cell cycle of AGS cells were associated with a significant increase in p53 and p21 expression after 24 h. The expression of cyclin E was downregulated in AGS cells following exposure of AGS cells to H. pylori for 24 h. This study shows that H. pylori-induced growth inhibition in vitro is predominantly at the G(0)-G(1) checkpoint. Our results suggest that p53 may be important in H. pylori-induced cell cycle arrest. These results support a role for cyclin-dependent kinase inhibitors in the G(1) cell cycle arrest exerted by H. pylori and its involvement in changing the regulatory proteins, p53, p21, and cyclin E in the cell cycle.

Importance of the medial meniscus in the anterior cruciate ligament-deficient knee.

The incidence of meniscal tears in the chronically anterior cruciate ligament-deficient knee is increased, particularly in the medial meniscus because it performs an important function in limiting knee motion. We evaluated the role of the medial meniscus in stabilizing the anterior cruciate ligament-deficient knee and hypothesized that the resultant force in the meniscus is significantly elevated in the anterior cruciate ligament-deficient knee. To test this hypothesis, we employed a robotic/universal force-moment sensor testing system to determine the increase in the resultant force in the human medial meniscus in response to an anterior tibial load following transection of the anterior cruciate ligament. We also measured changes in the kinematics of the knee in multiple degrees of freedom following medial meniscectomy in the anterior cruciate ligament-deficient knee. In response to a 134-N anterior tibial load, the resultant force in the medial meniscus of the anterior cruciate ligament-deficient knee increased significantly compared with that in the meniscus of the intact knee; it increased by a minimum of 10.1 N (52%) at full knee extension to a maximum of 50.2 N (197%) at 60 degrees of flexion. Medial meniscectomy in the anterior cruciate ligament-deficient knee also caused a significant increase in anterior tibial translation in response to the anterior tibial load, ranging from an increase of 2.2 mm at full knee extension to 5.8 mm at 60 degrees of flexion. Conversely, coupled internal tibial rotation in response to the load decreased significantly, ranging from a decrease of 2.5 degrees at 15 degrees of knee flexion to 4.7 degrees at 60 degrees of flexion. Our data confirm the hypothesis that the resultant force in the medial meniscus is significantly greater in the anterior cruciate ligament-deficient knee than in the intact knee when the knee is subjected to anterior tibial loads. This indicates that the demand on the medial meniscus in resisting anterior tibial loads is increased in the anterior cruciate ligament-deficient knee compared with in the intact knee, suggesting a mechanism for the increased incidence of medial meniscal tears observed in chronically anterior cruciate ligament-deficient patients. The large changes in kinematics due to medial meniscectomy in the anterior cruciate ligament-deficient knee confirm the important role of the medial meniscus in controlling knee stability. These findings suggest that the reduction of resultant force in the meniscus may be a further motive for reconstructing the anterior cruciate ligament, with the goal of preserving meniscal integrity.

A method for establishing primary cultures of human gastric epithelial cells.

Long-term culture of human gastric epithelial cells has been difficult, and at present no normal human gastric epithelial cell lines are readily available. As part of our experiments to study pathogenesis of H. pylori, a bacterium that infects the stomach, we developed methods to culture normal human gastric epithelial cells. Primary cultures of human gastric epithelial cells can be established from gastric biopsies taken at upper G.I. endoscopy. Enzymatically isolated gastric epithelial-like cells are present in tight colonies on culture dishes within 24 hours of placing the cells in culture. Cells isolated stain positively for cytokeratin and produce neutral mucins, indicating that they are mucin secreting epithelial cells, consistent with gastric epithelial cells. Epithelial cells can be maintained up to 4 weeks in culture with evidence of DNA synthesis up through the first week of culture.

Effects of Helicobacter pylori on proliferation of gastric epithelial cells in vitro.

OBJECTIVE: H. pylori infection of the gastric mucosa has been associated with an increase in gastric epithelial cell proliferation. However, in vitro adherence of H. pylori to gastric epithelial cells is associated with reduced cell proliferation. Reduction of epithelial cell proliferation may contribute to ulcer formation and delay ulcer healing. The following study was undertaken to elucidate the ability of cagA-positive and -negative strains to impede gastric epithelial cell proliferation. METHODS: A human gastric adenocarcinoma cell line (AGS) was overlaid with either cagA-positive or cagA-negative H. pylori strains suspended in cell culture medium. Proliferation of AGS cells was analyzed by performing direct cell counts and by measuring metabolism of a soluble tetrazolium compound (MTS), after exposure to H. pylori for 24 h. RESULTS: When compared with control cells cultured in medium alone, AGS cell proliferation was reduced by 45.6% and 28.5% due to exposure to cagA-negative and cagA-positive strains, respectively. When bacterial-induced cytotoxicity was assessed by measuring release of lactose dehydrogenase (LDH) into the culture medium, cagA-positive strains were shown to induce significantly more cytotoxicity than cagA-negative strains. CONCLUSIONS: These experiments demonstrate that H. pylori exposure to AGS cells significantly reduces cell proliferation. However, cagA-positive strains that induce more cell injury reduce cell proliferation to a lesser extent than cagA-negative strains. Persistent replication of gastric epithelial cells injured by exposure to cagA-positive strains may be partially responsible for the stronger association with gastric cancer in persons infected with cagA-positive H. pylori strains.

Injury and reconstruction of the anterior cruciate ligament and knee osteoarthritis.

OBJECTIVE: The objective of this study was to study injury and reconstruction of the anterior cruciate ligament (ACL) and their effects on knee osteoarthritis. DESIGN: This manuscript discusses the function of knee ligaments, including the basic mechanical properties, the structural properties of their respective bone-ligament-bone complexes, as well as their time- and history-dependent viscoelastic characteristics. The in-situ forces in the ACL and its replacement grafts and knee kinematics before and after ACL reconstruction are also examined. RESULTS: A robotic/universal force-moment sensor (UFS) testing system has been developed which offers a unique method in determining the multiple-degree of freedom knee kinematics and in-situ forces in human cadaveric knees. Under a 110 N anterior tibial load we found at flexion angles of 15 degrees or lower, there was a significantly larger in-situ force in the PL bundle (approximately 75 N) of the ACL as compared to the AM bundle (approximately 35 N)(P < 0.05). We also found that a quadruple semitendinosus and gracilis tendon ACL graft may be better at fully restoring in-situ forces for the whole range of knee flexion when compared to a bone-patellar tendon-bone ACL graft. CONCLUSIONS: The robotic/UFS testing system allows us to determine knee kinematics and the in-situ forces in cadaveric knees in a non-invasive, non-contact manner. Additionally, the ability to reproduce kinematics during testing allows us to evaluate ACL and ACL graft function under external and simulated muscle loading conditions. Finally, we can also examine many of the variables of ACL reconstructions that affect knee kinematics and graft forces including graft tensioning, graft type, graft placement and tibial positioning during graft fixation.

Early expression of marker genes in the rabbit medial collateral and anterior cruciate ligaments: the use of different viral vectors and the effects of injury.

Gene therapy is a technique that may offer advantages over current methods of cytokine delivery to ligaments. To determine if implanted genes could be expressed in normal and injured knee ligaments, the medial collateral ligament and anterior cruciate ligament were studied in 18 rabbits. A retroviral ex vivo technique using allograft medial collateral ligament and anterior cruciate ligament fibroblasts and an adenoviral in vivo technique were compared as methods for delivering the LacZ marker gene to knee ligaments. Bilateral knee surgeries were performed, and the rabbits were equally divided into three groups. Group 1 received the retrovirus and the medial collateral ligament was ruptured, Group 2 received the adenovirus and the medial collateral ligament was ruptured, and Group 3 received the adenovirus and the medial collateral ligament was not injured. The anterior cruciate ligament was not injured in any group. The medial collateral and anterior cruciate ligaments of the right knees received 10(6) allografted, transduced ligament fibroblasts or 10(9) adenovirus particles, whereas the ligaments of the left knee received a similar volume of saline solution only. Equal numbers of rabbits were killed at 10 days, 3 weeks, and 6 weeks following the procedure. Ligament samples were stained with X-gal to detect the expression of the LacZ gene product, beta-galactosidase. LacZ gene expression was evident in ruptured and uninjured medial collateral ligaments as well as in the anterior cruciate ligament. The expression lasted between 10 days and 3 weeks in the medial collateral and anterior cruciate ligaments with use of the retrovirus and between 3 and 6 weeks in the medial collateral ligament and at least 6 weeks in the anterior cruciate ligament with the adenovirus. The length of gene expression in the ruptured and uninjured medial collateral ligaments did not differ. These preliminary studies indicate that gene transfer to normal and injured knee ligaments is possible.

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5. 22 x 10(-4); SIBPAL Pempirical value <3 x 10(-5)) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 10(-3); SIBPAL Pempirical value <1 x 10(-3)) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.

The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament. An in vivo study.

We report a biologic approach to improve medial collateral ligament healing using growth factors normally expressed in healing tissue. Our previous in vitro work demonstrated that platelet-derived growth factor-BB and transforming growth factor-beta 1 promoted fibroblast proliferation and matrix synthesis, respectively. There-fore, these growth factors were used in vivo to determine whether they could improve medial collateral ligament healing, whether this effect was dose-dependent, and if combinations of growth factors could improve healing more than individual growth factors. Thirty-seven rabbits had various doses of growth factors applied to the ruptured right medial collateral ligaments using a fibrin sealant delivery vehicle. The five groups consisted of 1) two groups receiving two doses of platelet-derived growth factor-BB, 2) two groups receiving two doses of this growth factor plus transforming growth factor-beta 1, and 3) one group receiving fibrin sealant only. After sacrifice at 6 weeks, biomechanical and histologic evaluations of the healing ligament were performed. Femur-medial collateral ligament-tibia complexes of the knees given the higher dose of platelet-derived growth factor-BB had ultimate load, energy absorbed to failure, and ultimate elongation values that were 1.6, 2.4, and 1.6 times greater than the same complexes of the control group. Adding transforming growth factor-beta 1 did not lead to any further increase in the structural properties of the complex compared with treatment with platelet-derived growth factor-BB. These encouraging results suggest that use of platelet-derived growth factor-BB may improve the quality of the healing medial collateral ligament, and that it may also have a similar potential for promoting healing of other ligaments.

The effects of age on rabbit MCL fibroblast matrix synthesis in response to TGF-beta 1 or EGF.

In this study, we examined the effects of age on collagen and total protein synthesis by ligament fibroblasts in response to growth factors. Three different doses of transforming growth factor-beta 1 (TGF-beta 1) or epidermal growth factor (EGF) were individually added to in vitro fibroblast cultures from the medial collateral ligament (MCL) of skeletally immature (age 3 months), mature (age 12 months) and senescent (age 48-51 months) rabbits. Analysis of the effects of age revealed that fibroblasts from senescent rabbits produced significantly less collagen in response to TGF-beta 1 or EGF stimulation when compared to fibroblasts from immature rabbits. Furthermore, increased age was found to result in significant reductions in the baseline levels of collagen synthesis but not total protein synthesis. Additionally, collagen and total protein synthesis by MCL fibroblasts were significantly affected by the TFG-beta 1 dose, but not by the EGF dose. When fibroblasts were normalized to their own controls, the increase in collagen and total protein synthesis due to TGF-beta 1 and EGF for the senescent group were found to be greater than those for the skeletally immature rabbits at all doses. This demonstrates that MCL fibroblasts from senescent rabbits are responsive to growth factors.

A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish.

The most characteristic features of bipolar affective disorder (manic-depressive illness) are episodes of mania (bipolar I, BPI) or hypomania (bipolar II, BPII) interspersed with periods of depression. Manic-depressive illness afflicts about one percent of the population, and if untreated, is associated with an approximately 20% risk of suicide. Twin, family and adoption studies provide compelling evidence for a partial genetic aetiology, but the mode(s) of inheritance has not been identified. Nonetheless, the majority of genetic linkage studies have assumed classical mendelian inheritance attributable to a single major gene. Although segregation analyses have yielded inconsistent results (with most studies rejecting a single locus inheritance model), the best single gene model is dominant inheritance if only BPI is considered. Reported linkages of bipolar affective disorder on chromosomes 11, 18, 21 and X have been difficult to substantiate, and additional studies are required for replication or exclusion of these regions. We now present the results of our genome-wide linkage analyses that provide evidence that regions on chromosomes 6, 13 and 15 harbour susceptibility loci for bipolar affective disorder, suggesting that bipolar affective disorder in the Old Order Amish is inherited as a complex trait.

Linkage analyses of chromosome 18 markers do not identify a major susceptibility locus for bipolar affective disorder in the Old Order Amish.

Previously reported linkage of bipolar affective disorder to DNA markers in the pericentromeric region of chromosome 18 was reexamined in a larger homogeneous sample of Old Order Amish families. Four markers (D18S21, D18S53, D18S44, and D18S40) were examined in three kindreds containing 31 bipolar I (BP I) individuals. Although linkage findings were replicated in the one previously studied Amish pedigree containing four BP I individuals, linkage to this region was excluded in the larger sample. If a susceptibility locus for bipolar disorder is located in this region of chromosome 18, it is of minor significance in this population.

Complex segregation analyses of old order Amish families ascertained through bipolar I individuals.

Specific genetic hypotheses about the mode of transmission of bipolar affective disorders were examined by performing complex segregation analyses of Old Order Amish families. The analyses were performed on 1) the total set of 42 families including 689 relatives, 2) a subset of 19 families consisting of those kindreds sharing common ancestors within three generations that contained 333 relatives, and 3) a subset of 23 more distantly related families with 356 relatives. When all 42 families were included in the analyses, the specific mode of transmission that could be distinguished was dependent upon the diagnostic scheme used in the analysis. An autosomal dominant mode of inheritance could be rejected when relatives with bipolar I, atypical bipolar, major depressive disorder, and hypomania were included as affected. When analyses included only the subset of families more closely related, an autosomal dominant inheritance model was found to be consistent with transmission of BP I disorder. It was not possible to distinguish between other transmission models with broader diagnostic schemes in this subset of families. Finally, results of analyses on the subset of more distantly related families suggest that there is a significant proportion of Old Order Amish families in which the genetic factors contributing to the expression of bipolar illness are either polygenic or oligogenic.