Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit.

INTRODUCTION: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). OBJECTIVE: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. METHODS: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. RESULTS: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. CONCLUSION: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

An exploratory study of self-reported complicated grief symptoms in parentally bereaved adults with intellectual disability.

BACKGROUND: Complicated grief involves the experience of grief-related symptoms at a time, and severity, beyond which could be considered adaptive, while persistent complex bereavement disorder (PCBD) has been identified as a condition that requires further study in the typical population. The aims of this study are to (1) explore the symptoms of complicated grief associated with parental bereavement as self-reported by adults with intellectual disabilities (IDs) who have experienced a parental bereavement and (2) conduct an initial examination of how the existing criteria for PCBD apply to this group. METHODS: This study uses a comparative group design, assessing self and staff (proxy) reports for a group of parentally bereaved individuals and a matched group of non-bereaved individuals using the Complicated Grief Questionnaire - ID Self-Report. Participants were 46 individuals with ID, 30 (65%) of whom who had experienced a parental bereavement within the previous 2 years. The age range was 23-67 years (mean = 43.8; SD = 10.3). RESULTS: The results highlight the presence of a range of symptoms of complicated grief in individuals' self-reports, although there was some evidence that separation distress-related symptoms were more apparent. An analysis of individual symptoms showed patterns of higher reports among the bereaved group as would be expected. Comparing staff and self-reports, key criteria showed higher levels in self-reports among the bereaved group. CONCLUSIONS: This study has demonstrated the capacity of people with ID to self-report personal experience of symptoms of complicated grief, when appropriate and accessible assessment tools are used. Some symptoms were more evident among bereaved individuals (compared with non-bereaved participants), and they tended to be from separation distress criteria. This may indicate the relevance of these symptoms for people with ID and question the existing criteria for PCBD in this population, which may have clinical implications for supporting people with ID experiencing a more complicated bereavement response.

Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study.

AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.

A matter of life and death: knowledge about the body and concept of death in adults with intellectual disabilities.

BACKGROUND: An increased awareness of how people with intellectual disabilities (ID) understand death and dying is necessary in supporting life-long learning, post-bereavement support and planning end-of-life care. Previous research suggests that adults with ID have a limited or 'patchy' understanding of the basic biological components of death. However, the relationship between biological understanding of how the body works and conceptualisation of death remains unexplored in this population. METHOD: Thirty adults with ID were interviewed to assess their knowledge of human body function and their understanding of the concept of death. Using pictures, participants were asked if they recognised certain organs, asked to explain the function of various body parts and what would happen if certain body parts were missing or did not work. Participants who referred to 'life' or 'not dying' as the goal of body function were categorised as 'Life Theorisers'. In addition, participants were asked about the causes of death, whether all things die and the status of the body after death. RESULTS: The results support previous studies suggesting that understanding of death in adults with ID varies from partial to full comprehension and is associated with level of ID. Also, death comprehension was positively correlated with total body interview scores and 'Life Theorisers' who understood that body parts maintain life and who spontaneously appealed to 'vitalistic' concepts when reasoning about the human body were also more sophisticated in their understanding of death. CONCLUSION: The study highlights the relationship between knowledge about the goal of human body functioning and death comprehension in adults with ID. The potential that learning to adopt a 'vitalistic' approach to human functioning may have on the acquisition of a greater understanding of death and dying, understanding illness and supporting end-of-life planning is discussed.

Do men and women with intellectual disabilities understand death?

BACKGROUND: Individuals with ID are often withheld information about the death of their loved ones as it has often been thought that they do not understand death or cannot grieve. This grief exacerbates the stress of individuals with ID as they often encounter secondary losses such as transitioning to a care facility. The aim of this study is to investigate men and women with ID understanding death concepts and to what extent. METHOD: Adopting a stratified random sampling method, 156 Chinese people with ID were invited to join the study. One hundred and ten participants were interviewed using simple death related vignettes expanding upon and replicating a published study carried out in Ireland. The understanding of the five death concepts: causality, irreversibility, nonfunctionality, universality and inevitability was examined. The correlates of demographics, bereavement experiences and comprehension were explored. RESULTS: The majority of the participants did understand concepts such as death is irreversible and that the deceased no longer function. One third of the participants understood causality and the universality of death. One fifth understood the inevitability of death. Previous bereavement experiences were correlated with higher understanding. Communication and community skills were correlated with all concepts of death except universality. CONCLUSION: The results indicate that individuals with ID do have a partial to full understanding of the concepts of death. The culture of Hong Kong is one that considers death to be a taboo or unlucky subject. Therefore, the results mirror the the lack of understanding of universality and inevitability concepts as it is forbidden to speak of these concepts. An open and honest environment is encouraged to educate individuals with ID about death and bereavement.

Electrophysiological validation of STN-SNr boundary depicted by susceptibility-weighted MRI.

BACKGROUND: Direct targeting of subthalamic nucleus (STN) without secondary electrophysiological verification during deep brain stimulation (DBS) is replacing atlas-based indirect targeting techniques. Recent groups have reported increased contrast and better delineation of STN and substantia nigra (SNr) in susceptibility-weighted imaging protocols (SWI). We aim to validate the STN-SNr boundary seen in MRI- SWI by correlating with intraoperative microelectrode recordings (MER) as a part of developing a multi-contrast DBS MRI planning protocol. METHODS: Prospective service evaluation involving electrophysiological verification by correlation of MER trajectory and STN-SNr boundary seen in SWI in seven consecutive patients undergoing DBS surgery were analyzed. The angle of inclination of the STN-SNr boundary and DBS trajectory in the coronal plane were calculated. Considering 4-mm dispersion of a coronal 3 MER array, we predicted, measured, and correlated the depths at which each electrode engaged the boundary. RESULTS: All central microelectrodes identified the STN-SNr boundary within 1 mm of the predicted depth with 100 % accuracy. Ninety percent of the lateral MER identified the STN-SNr boundary as predicted from SWI and angle of the encounter of the MER front. CONCLUSIONS: The study demonstrates that STN morphology can be depicted using SWI MRI and coincides reliably with the electrophysiological MER boundary. Thus, this imaging modality can be used to refine STN direct targeting protocols in DBS surgery for PD.

Estimating uncertainty when providing individual cardiovascular risk predictions: a Bayesian survival analysis.

BACKGROUND: Cardiovascular disease (CVD) risk scores provide point estimates of individual risk without uncertainty quantification. The objective of the current study was to demonstrate the feasibility and clinical utility of calculating uncertainty surrounding individual CVD-risk predictions using Bayesian methods. STUDY DESIGN AND SETTING: Individuals with established atherosclerotic CVD were included from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). In 8,355 individuals, followed for median of 8.2 years (IQR 4.2-12.5), a Bayesian Weibull model was derived to predict the 10-year risk of recurrent CVD events. RESULTS: Model coefficients and individual predictions from the Bayesian model were very similar to that of a traditional ('frequentist') model but the Bayesian model also predicted 95% credible intervals (CIs) surrounding individual risk estimates. The median width of the individual 95%CrI was 5.3% (IQR 3.6-6.5) and 17% of the population had a 95%CrI width of 10% or greater. The uncertainty decreased with increasing sample size used for derivation of the model. Combining the Bayesian Weibull model with sampled hazard ratios based on trial reports may be used to estimate individual estimates of absolute risk reduction with uncertainty measures and the probability that a treatment option will result in a clinically relevant risk reduction. CONCLUSION: Estimating uncertainty surrounding individual CVD risk predictions using Bayesian methods is feasible. The uncertainty regarding individual risk predictions could have several applications in clinical practice, like the comparison of different treatment options or by calculating the probability of the individual risk being below a certain treatment threshold. However, as the individual uncertainty measures only reflect sampling error and no biases in risk prediction, physicians should be familiar with the interpretation before widespread clinical adaption.

Persistent infection with neurotropic herpes viruses and cognitive impairment.

BACKGROUND: Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens. RESULTS: PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (ß = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status. CONCLUSIONS: Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.

Prevalence and Correlates of Elevated NT-proBNP in Pregnant Women in the General U.S. Population.

BACKGROUND: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied. OBJECTIVES: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, in a nationally representative sample from the National Health and Nutrition Examination Survey 1999 to 2004. METHODS: We conducted a cross-sectional analysis of 2,134 women (546 pregnant) aged 20 to 40 years without a history of cardiovascular disease. RESULTS: Among pregnant women in the first trimester, the prevalence of elevated NT-proBNP (>125 pg/mL) was 20.0% (SE, 6.6%) compared to 2.4% (SE, 0.8%) among women in the third trimester and 8.0% among nonpregnant women. After adjustment for demographics and cardiovascular risk factors, NT-proBNP was 44% higher (absolute difference 26.4 [95% CI: 11.2-41.6] pg/mL) in the first trimester of pregnancy compared to nonpregnant women. Among pregnant women only, adjusted NT-proBNP was 46% lower (absolute difference -22.2 [95% CI: -36.9 to -7.5] pg/mL) in women in the third trimester compared to women in the first trimester. NT-proBNP was inversely associated with body mass index and with systolic blood pressure. CONCLUSIONS: Women in the first trimester of pregnancy had significantly higher NT-proBNP than those in the third trimester and compared to similarly aged nonpregnant women. The dynamic nature of NT-proBNP should be taken into consideration when ordering NT-proBNP lab tests in pregnant women.

Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs.

Understanding individual differences in the susceptibility to metabolic side effects as a response to antipsychotic therapy is essential to optimize the treatment of schizophrenia. Here, we perform genomewide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects. The analysis sample consisted of 738 schizophrenia patients, successfully genotyped for 492K single nucleotide polymorphisms (SNPs), from the genomic subsample of the Clinical Antipsychotic Trial of Intervention Effectiveness study. Outcomes included 12 indicators of metabolic side effects, quantifying antipsychotic-induced change in weight, blood lipids, glucose and hemoglobin A1c, blood pressure and heart rate. Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. A total of 21 SNPs satisfied this criterion. The top finding indicated that a SNP in Meis homeobox 2 (MEIS2) mediated the effects of risperidone on hip circumference (q=0.004). The same SNP was also found to mediate risperidone's effect on waist circumference (q=0.055). Genomewide significant finding were also found for SNPs in PRKAR2B, GPR98, FHOD3, RNF144A, ASTN2, SOX5 and ATF7IP2, as well as in several intergenic markers. PRKAR2B and MEIS2 both have previous research indicating metabolic involvement, and PRKAR2B has previously been shown to mediate antipsychotic response. Although our findings require replication and functional validation, this study shows the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antipsychotic medication.

Concept of death and perceptions of bereavement in adults with intellectual disabilities.

BACKGROUND: Bereavement is potentially a time of disruption and emotional distress. For individuals with an intellectual disability (ID), a limited understanding of the concept of death may exacerbate this distress. The aim of the present study was to investigate how individuals with ID understand and explain death and make sense of life without the deceased. METHOD: Thirty-four people with ID were interviewed using simple vignettes describing death-related incidents. Participants were asked about the causes of death, the status of the body after death and whether all living things die. In addition, participants were asked about reactions to death and for their views on post-bereavement support. RESULTS: Nearly one quarter of participants had a full understanding and over two-thirds a partial understanding of the concept of death. Death comprehension was positively correlated with cognitive ability and adaptive functioning. While cause of death was predominantly associated with illness and old age, participants viewed death as final and understood that all living things die. The role of religious beliefs was also found to be important for many participants. CONCLUSIONS: The results support earlier findings that suggest people with ID have only a partial understanding of the concept of death leaving them vulnerable to factually incorrect thoughts. The study highlights the considerable scope for making sense of death using religious and spiritual themes and emphasises the need for teaching individuals biological explanations of the life cycle. The results also provide some insight into the views of individuals with ID for carers involved in providing post-bereavement support.

Landscape characteristics influence ranging behavior of Asian elephants at the human-wildlands interface in Myanmar.

CONTEXT: Asian elephant numbers are declining across much of their range driven largely by serious threats from land use change resulting in habitat loss and fragmentation. Myanmar, holding critical range for the species, is undergoing major developments due to recent sociopolitical changes. To effectively manage and conserve the remaining populations of endangered elephants in the country, it is crucial to understand their ranging behavior. OBJECTIVES: Our objectives were to (1) estimate the sizes of dry, wet, and annual ranges of wild elephants in Myanmar; and quantify the relationship between dry season (the period when human-elephant interactions are the most likely to occur) range size and configurations of agriculture and natural vegetation within the range, and (2) evaluate how percentage of agriculture within dry core range (50% AKDE range) of elephants relates to their daily distance traveled. METHODS: We used autocorrelated kernel density estimator (AKDE) based on a continuous-time movement modeling (ctmm) framework to estimate dry season (26 ranges from 22 different individuals), wet season (12 ranges from 10 different individuals), and annual range sizes (8 individuals), and reported the 95%, 50% AKDE, and 95% Minimum Convex Polygon (MCP) range sizes. We assessed how landscape characteristics influenced range size based on a broad array of 48 landscape metrics characterizing aspects of vegetation, water, and human features and their juxtaposition in the study areas. To identify the most relevant landscape metrics and simplify our candidate set of informative metrics, we relied on exploratory factor analysis and Spearman's rank correlation coefficient. Based on this analysis we adopted a final set of metrics into our regression analysis. In a multiple regression framework, we developed candidate models to explain the variation in AKDE dry season range sizes based on the previously identified, salient metrics of landscape composition. RESULTS: Elephant dry season ranges were highly variable averaging 792.0 km2 and 184.2 km2 for the 95% and 50% AKDE home ranges, respectively. We found both the shape and spatial configuration of agriculture and natural vegetation patches within an individual elephant's range play a significant role in determining the size of its range. We also found that elephants are moving more (larger energy expenditure) in ranges with higher percentages of agricultural area. CONCLUSION: Our results provide baseline information on elephant spatial requirements and the factors affecting them in Myanmar. This information is important for advancing future land use planning that takes into account space-use requirements for elephants. Failing to do so may further endanger already declining elephant populations in Myanmar and across the species' range.

Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.

Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems. In the past, evidence for these alterations has been collected piecemeal, limiting our understanding of the interactions among relevant biological systems. Earlier, both hyper- and hyposerotonemia were variously associated with the longitudinal course of schizophrenia, suggesting a disturbance in the central serotonin (5-hydroxytryptamine (5-HT)) function. Using a targeted electrochemistry-based metabolomics platform, we compared metabolic signatures consisting of 13 plasma tryptophan (Trp) metabolites simultaneously between first-episode neuroleptic-naive patients with schizophrenia (FENNS, n=25) and healthy controls (HC, n=30). We also compared these metabolites between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. N-acetylserotonin was increased in FENNS-BL compared with HC (P=0.0077, which remained nearly significant after Bonferroni correction). N-acetylserotonin/Trp and melatonin (Mel)/serotonin ratios were higher, and Mel/N-acetylserotonin ratio was lower in FENNS-BL (all P-values<0.0029), but not after treatment, compared with HC volunteers. All three groups had highly significant correlations between Trp and its metabolites, Mel, kynurenine, 3-hydroxykynurenine and tryptamine. However, in the HC, but in neither of the FENNS groups, serotonin was highly correlated with Trp, Mel, kynurenine or tryptamine, and 5-hydroxyindoleacetic acid (5HIAA) was highly correlated with Trp, Mel, kynurenine or 3-hydroxykynurenine. A significant difference between HC and FENNS-BL was further shown only for the Trp-5HIAA correlation. Thus, some metabolite interactions within the Trp pathway seem to be altered in the FENNS-BL patients. Conversion of serotonin to N-acetylserotonin by serotonin N-acetyltransferase may be upregulated in FENNS patients, possibly related to the observed alteration in Trp-5HIAA correlation. Considering N-acetylserotonin as a potent antioxidant, such increases in N-acetylserotonin might be a compensatory response to increased oxidative stress, implicated in the pathogenesis of schizophrenia.

Glycemic excursions and subclinical cardiac damage in adults with type 2 diabetes: Results from the ADVANCE Trial.

We found that 1,5-anhydroglucitol-a marker of glucose excursions-was not independently associated with subclinical cardiac damage, nor with vascular outcomes, in the ADVANCE Trial. High-sensitivity cardiac troponin T and N-terminal pro-b-type natriuretic peptide provided better prognostic information regarding vascular risk in diabetes than 1,5-anhydroglucitol.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Primary prevention aspirin among the elderly: challenges in translating trial evidence to the clinic.

The ASPirin in Reducing Events in the Elderly trial (ASPREE) contributed important knowledge about primary cardiovascular disease (CVD) prevention among healthy older adults. The finding that daily low-dose aspirin (LDA) does not statistically prevent disability or CVD among adults aged over 70 years when compared with placebo, but does significantly increase risk of haemorrhage, immediately influenced clinical practice guidelines. In this article, we discuss nuances of the trial that may impact the extrapolation of the ASPREE trial results to the everyday individual clinical care of older adults.

Linkage analysis of schizophrenia in African-American families.

While many studies have sought a window into the genetics of schizophrenia, few have focused on African-American families. An exception is the Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS), which seeks to identify novel and known risk variation for schizophrenia by genetic analyses of African-American families. We report a linkage study of diagnostic status in 217 African-American families using the Illumina Linkage Panel. Due to assumed incomplete and time-dependent penetrance, we performed linkage analysis using two different treatments of diagnosis: (1) treating both affected and unaffected individuals as informative for linkage (using the program SIBPAL) and (2) treating only affected individuals as informative (using the program MERLIN). We also explore three definitions of affected status: narrowly defined schizophrenia; one broadened to include schizoaffective disorder; and another including all diagnoses indicating psychosis. Several regions show a decrease in the evidence for linkage as the definition broadens 8q22.1 (rs911, 99.26 cM; SIBPAL p-value [p] goes from 0.006 to 0.02), 16q24.3 (rs1006547, 130.48 cM; p from 0.00095 to 0.0085), and 20q13.2 (rs1022689, 81.73 cM; p from 0.00015 to 0.032). One region shows a substantial increase in evidence for linkage, 11p15.2 (rs722317, 24.27 cM; p from 0.0022 to 0.0000003); MERLIN results support the significance of the SIBPAL results (p=0.00001). Our linkage results overlap two broad, previously-reported linkage regions: 8p23.3-p12 found in studies sampling largely families of European ancestry; and 11p11.2-q22.3 reported by a study of African-American families. These results should prove quite useful for uncovering loci affecting risk for schizophrenia.

Atrazine degradation by stable mixed cultures enriched from agricultural soil and their characterization.

AIMS: The aim of this work was to enrich stable mixed cultures from atrazine-contaminated soil. The cultures were examined for their atrazine biodegradation efficiencies in comparison with J14a, a known atrazine-degrading strain of Agrobacterium radiobacter. The cultures were also characterized to identify community structure and bacterial species present. METHODS AND RESULTS: The cultures were enriched and then stabilized in bacterial media. The stable mixed cultures and J14a were tested in a medium containing 100 microg l(-1) of atrazine. For all cultures, atrazine was removed 33-51% within 7 days and the cell optical density increased from 0.05 to between 0.50 and 0.70. Four isolates designated ND1, ND2, ND3 and ND4 were purified from the mixed cultures and identified based on sequence analysis of the 16 S rRNA gene as Alcaligenes faecalis, Klebsiella ornithinolytica, Bacillus megaterium and Agrobacterium tumefaciens, respectively. An atrazine-degrading gene, atzA, was present in ND2 and ND4. CONCLUSIONS: The stable mixed cultures obtained could degrade atrazine. Klebsiella ornithinolytica ND2 and Ag. tumefaciens ND4 are atrazine degraders. SIGNIFICANCE AND IMPACT OF THE STUDY: The novel stable mixed cultures could be used for bioremediating crop fields contaminated with atrazine. This is the first report of the atzA gene in Kl. ornithinolytica.