Using Publicly Available Data to Quantify Plant-Pollinator Interactions and Evaluate Conservation Seeding Mixes in the Northern Great Plains.

Concern over declining pollinators has led to multiple conservation initiatives for improving forage for bees in agroecosystems. Using data available through the Pollinator Library (npwrc.usgs.gov/pollinator/), we summarize plant-pollinator interaction data collected from 2012-2015 on lands managed by the U.S. Fish and Wildlife Service and private lands enrolled in U.S. Department of Agriculture conservation programs in eastern North Dakota (ND). Furthermore, we demonstrate how plant-pollinator interaction data from the Pollinator Library and seed cost information can be used to evaluate hypothetical seeding mixes for pollinator habitat enhancements. We summarize records of 314 wild bee and 849 honey bee (Apis mellifera L.) interactions detected on 63 different plant species. The wild bee observations consisted of 46 species, 15 genera, and 5 families. Over 54% of all wild bee observations were represented by three genera-Bombus, Lassioglossum, and Melissodes. The most commonly visited forbs by wild bees were Monarda fistulosa, Sonchus arvensis, and Zizia aurea. The most commonly visited forbs by A. mellifera were Cirsium arvense, Melilotus officinalis, and Medicago sativa. Among all interactions, 13% of A. mellifera and 77% of wild bee observations were made on plants native to ND. Our seed mix evaluation shows that mixes may often need to be tailored to meet the unique needs of wild bees and managed honey bees in agricultural landscapes. Our evaluation also demonstrates the importance of incorporating both biologic and economic information when attempting to design cost-effective seeding mixes for supporting pollinators in a critically important part of the United States.

Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization.

UNLABELLED: The potency and breadth of the recently isolated neutralizing human monoclonal antibodies to HIV-1 have stimulated interest in their use to prevent or to treat HIV-1 infection. Due to the antigenically diverse nature of the HIV-1 envelope (Env), no single antibody is highly active against all viral strains. While the physical combination of two broadly neutralizing antibodies (bNAbs) can improve coverage against the majority of viruses, the clinical-grade manufacturing and testing of two independent antibody products are time and resource intensive. In this study, we constructed bispecific immunoglobulins (IgGs) composed of independent antigen-binding fragments with a common Fc region. We developed four different bispecific IgG variants that included antibodies targeting four major sites of HIV-1 neutralization. We show that these bispecific IgGs display features of both antibody specificities and, in some cases, display improved coverage over the individual parental antibodies. All four bispecific IgGs neutralized 94% to 97% of antigenically diverse viruses in a panel of 206 HIV-1 strains. Among the bispecific IgGs tested, VRC07 × PG9-16 displayed the most favorable neutralization profile. It was superior in breadth to either of the individual antibodies, neutralizing 97% of viruses with a median 50% inhibitory concentration (IC50) of 0.055 µg/ml. This bispecific IgG also demonstrated in vivo pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for the prevention and treatment of HIV-1 infection in humans. IMPORTANCE: To prevent or treat HIV-1 infection, antibodies must potently neutralize nearly all strains of HIV-1. Thus, the physical combination of two or more antibodies may be needed to broaden neutralization coverage and diminish the possibility of viral resistance. A bispecific antibody that has two different antibody binding arms could potentially display neutralization characteristics better than those of any single parental antibody. Here we show that bispecific antibodies contain the binding specificities of the two parental antibodies and that a single bispecific antibody can neutralize 97% of viral strains with a high overall potency. These findings support the use of bispecific antibodies for the prevention or treatment of HIV-1 infection.

Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 µg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 µg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

Targeting chromatin to improve radiation response.

Chromatin, the structure formed by the wrapping of approximately 146 base pairs of DNA around an octamer of histones, has a profound impact on numerous DNA-based processes. Chromatin modifications and chromatin remodellers have recently been implicated in important aspects of the DNA damage response including facilitating the initial sensing of the damage as well as subsequent recruitment of repair factors. Radiation is an effective cancer therapy for a large number of tumours, and there is considerable interest in finding approaches that might further increase the efficacy of radiotherapy. The use of radiation leads to the generation of DNA damage and, therefore, agents that can affect the sensing and repair of DNA damage may have an impact on overall radiation efficacy. The chromatin modifications as well as chromatin modifiers that have been associated with the DNA damage response will be summarized in this review. An emphasis will be placed on those processes that can be pharmacologically manipulated with currently available inhibitors. The rationale for the use of these inhibitors in combination with radiation will also be described.

Effect of dietary interventions in the maintenance of normoglycaemia in glycogen storage disease type 1a: a systematic review and meta-analysis.

BACKGROUND: Untreated glycogen storage disease (GSD)-1a patients experience hypoglycaemia and growth retardation. The present study examined the effects of dietary interventions on the maintenance of normoglycaemia. METHODS: Clinical trials were identified from EMBASE (January 1980 to November 2011), MEDLINE (January 1948 to November 2011) and the Cochrane Central Register of Controlled Trials (2011, Issue 4). The intermittent administration of uncooked cornstarch was compared with: (i) continuous nocturnal feeding of dextrose; (ii) modified uncooked cornstarch; and (iii) dextrose and an uncooked cornstarch-dextrose mixture. One author extracted the data, and assessed the trial eligibility and risk of bias. Quality assessment and data extraction were conducted and checked independently. RESULTS: Of 41 articles retrieved, five controlled trials (49 participants) were identified with follow-up at 2 days to 14 years. Results from three nonrandomised controlled trials comparing uncooked cornstarch with continuous nocturnal feeding of dextrose were pooled in a meta-analysis based on a fixed-effect model. Twenty-six participants (three trials) receiving uncooked cornstarch showed a significant increase in blood glucose concentration: mean difference (MD) 0.62 mmol L(-1) [95% confidence interval (CI) = 0.23-1.00] (P = 0.002), 21 (two trials) increased serum insulin: MD 62.37 pmol L(-1) (95% CI = 32.19-92.55) (P < 0.0001) and 22 (three trials) increased plasma total cholesterol: MD 0.68 mmol L(-1) (95% CI = 0.17- 1.20) (P = 0.01) compared to continuous nocturnal feeding of dextrose. Twenty-eight subjects (three trials) showed decreased plasma lactate after nocturnal feeding: MD -0.42 mmol L(-1) (95% CI = -0.58 to -0.25) (P < 0.00001). CONCLUSIONS: Short- to long-term overnight intermittent administration of uncooked cornstarch prevents nocturnal hypoglycaemia in GSD-1a children more effectively than continuous nocturnal feeding of dextrose.

A guide for identification and continuing care of adult congenital heart disease patients in primary care.

BACKGROUND: Surgical and other advances in the treatment and care of congenital heart disease have resulted in a significant increase in the number of adults with congenital heart disease (ACHD), many of whom have no regular cardiology follow-up. Optimised care for ACHD patients requires continuity of specialist and shared care and education of practitioners and patients. The challenges for managing ACHD were identified by a Health Needs Assessment in the North West and are addressed within the UK Department of Health's ACHD Commissioning Guide. MATERIALS AND METHODS: An ACHD model of care was recommended in the North West of England and developed by the three North West Cardiac & Stroke Networks. Within this, a Task Group focused on the role of primary care in the identification and continuing care of ACHD patients. A feasibility study demonstrated that existing diagnostic Read Codes can identify ACHD patients on general practice registers. An ACHD Toolkit was developed to provide algorithms to guide the appropriate management of ACHD patients through primary, secondary and/or specialist ACHD care and to improve education/knowledge amongst primary care staff about ACHD and its wider implications. RESULTS: Early findings during the development of this Toolkit illustrate a wide disparity of provision between current and optimal management strategies. Patients lost to follow-up have already been identified and their management modified. CONCLUSIONS: By focusing on identifying ACHD patients in primary care and organising/delivering ACHD services, the ACHD Toolkit could help to improve quality, timeliness of care, patient experience and wellbeing.

Bivariate genetic modelling of the response to an oral glucose tolerance challenge: a gene x environment interaction approach.

AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes.

The - 11391 G/A polymorphism of the adiponectin gene promoter is associated with metabolic syndrome traits and the outcome of an energy-restricted diet in obese subjects.

Adiponectin is an adipose tissue-specific hormone that is commonly decreased in obese subjects. Furthermore, single-nucleotide polymorphisms (SNPs) of the adiponectin gene have been associated with metabolic phenotypes. The present study investigated whether the adiponectin gene promoter variant -11391 G/A (rs17300539) could predict the risk of developing traits characterizing the metabolic syndrome (MetS) and the impact of weight management. The -11391 G/A SNP was genotyped in 180 Spanish volunteers (BMI: 31.4+/-3.2 kg/m (2); age: 35+/-5 years). Clinical measurements were determined at baseline, following an 8-week low-calorie diet (LCD), and at 32 and 60 weeks. At baseline, the GG genotype was associated with higher HOMA-IR, insulin and triacylglyceride concentrations than other genotypes (p<0.05) and was also related with a higher risk of insulin resistance (OR: 2.437, p=0.025) and MetS clinical manifestations (OR: 3.236, p=0.003). Following the LCD, the increased risk in GG subjects compared with others disappeared (p>0.05). By 32 weeks after dietary therapy (n=84), GG carriers had recovered the risk of metabolic comorbidities (OR: 2.420, p=0.043). This risk was even more evident after 60 weeks (OR: 2.875, p=0.014). These data show an increased risk of insulin resistance and MetS complications in obese subjects of the -11391 GG genotype. The risk was markedly reduced during an energy-restricted diet, but was not sustained. Carriage of the A allele therefore confers protection from weight regain, and the effect is particularly evident 32-60 weeks after the dietary intervention, when improvement in GG subjects had disappeared.

TUB is a candidate gene for late-onset obesity in women.

AIMS/HYPOTHESES: We recently reported significant associations between BMI and three TUB single nucleotide polymorphisms (SNPs) in two Dutch cohorts enriched for type 2 diabetes. Here, we attempted a replication of these associations in a large population-based cohort of female twins comprehensively phenotyped for measures of general and central obesity. METHODS: Two TUB SNPs (rs2272382, rs2272383) and a third (rs1528133), 22 kb distal to RIC3, were genotyped in 2694 Europid women from the St Thomas' UK Adult Twin Registry (Twins UK) (mean age +/- SD: 47.6 +/- 12.7 years; 42.8% postmenopausal). We explored the hypothesis that TUB is a candidate gene for late-onset obesity in humans through testing the interaction of the SNPs by menopausal status. RESULTS: In the whole cohort, none of the three SNPs showed a significant main effect on measures of general or central obesity. However, for central obesity the rs2272382 SNP showed a significant interaction with menopausal status (p = 0.036). Postmenopausal women homozygous for the minor allele of rs2272382 showed significantly more general obesity (p = 0.022) and central obesity (p = 0.009) than carriers of the major allele. Differences (beta [95% CI]) between the two genotype groups were 0.92 kg/m2 (0.03-1.81) for BMI (p = 0.036), 2.73 cm (0.62-4.84) for waist circumference (p = 0.013) and 2.43% (0.27-4.60) for per cent central fat (p = 0.027). These associations were confirmed by a sibling transmission disequilibrium test for central obesity, waist circumference and per cent central fat. CONCLUSIONS/INTERPRETATION: We have replicated associations of TUB SNP rs2272382 with measures of general and central obesity in normal postmenopausal women. These findings confirm TUB as a candidate gene for late-onset obesity in humans.

Localization and signaling of the receptor protein tyrosine kinase Tyro3 in cortical and hippocampal neurons.

Protein phosphorylation serves as a critical biochemical regulator of short-term and long-term synaptic plasticity. Receptor protein tyrosine kinases (RPTKs) including members of the trk, eph and erbB subfamilies have been shown to modulate signaling cascades that influence synaptic function in the central nervous system (CNS). Tyro3 is one of three RPTKs belonging to the "TAM" receptor family, which also includes Axl and Mer. Tyro3 is the most widely expressed of these receptors in the CNS. Despite recent advances suggesting roles for members of this receptor family in the reproductive and immune systems, their functions in the CNS remain largely unexplored. In an effort to elucidate the roles of Tyro3 and its ligand, the protein growth arrest-specific gene6 (Gas6) in the hippocampus and cortex, we performed a detailed study of the localization and signaling of Tyro3 polypeptides in rat hippocampal and cortical neurons. Tyro3 was readily detected in dendrites and in the soma where it was distributed in a punctate pattern. Tyro3 exhibited only a limited level of co-localization with postsynaptic density protein-95 (PSD-95), suggesting that while located within dendrites, it was not confined to the postsynaptic compartment. In addition, Tyro3 was also identified in the axons and growth cones of immature neurons. The prominent expression of Tyro3 in dendrites suggested that it may be capable of modulating signaling pathways triggered by synaptic transmission. We have provided evidence in support of this role by demonstrating that Gas6 induced the phosphorylation of Tyro3 in cortical neurons in vitro, resulting in the recruitment of the mitogen-activated protein kinase (MAPK) and the phosphoinositide-3 kinase (PI(3)K) signaling pathways. As these pathways play critical roles in the induction of hippocampal long-term potentiation (LTP), these findings suggest that Tyro3 signaling may influence synaptic plasticity in the dendritic compartment of hippocampal and cortical neurons.

SHP-2 and PI3-kinase genes PTPN11 and PIK3R1 may influence serum apoB and LDL cholesterol levels in normal women.

Insulin regulates apoB metabolism via activation of PI3K or regulation of MTP via MAPK/ERK signalling. SHP-2 enhances both pathways through increased IRS-1 phosphorylation. We hypothesized that variants in the SHP-2 gene PTPN11 and PI3K p85alpha subunit gene PIK3R1 may influence fasting levels of plasma apoB and/or LDL cholesterol. We tested association of tagging SNPs (tSNPs) in each gene with serum lipids in a large sample of unselected population-based Caucasian female twins (n=2771, mean age 47.4+/-12.5 years) and then tested interaction between tSNPs in determining apoB and LDL levels. PTPN11 tSNP rs11066322 was associated with apoB (P=0.007) and rs11066320 was associated with LDL cholesterol (P=0.016). PIK3R1 tSNP rs251406 was associated with apoB (P=0.0003) and rs706713 was associated with LDL cholesterol (P=0.009). PTPN11 tSNP rs11066322 interacted with PIK3R1 tSNP rs251406 in determining serum apoB levels (P=0.012) and with PIK3R1 tSNP rs40318 in determining LDL cholesterol levels (P=0.009). Association of single tSNPs with both apoB and LDL cholesterol as well as interactions between the two genes suggest that variants influencing SHP-2 activity may modulate the acute pathway by which insulin regulates these lipids.

Running wheel exercise enhances recovery from nigrostriatal dopamine injury without inducing neuroprotection.

Forced use of the forelimb contralateral to a unilateral injection of the dopaminergic neurotoxin 6-hydroxydopamine can promote recovery of motor function in that limb and can significantly decrease damage to dopamine terminals. The present study was conducted to determine (1) whether a form of voluntary exercise, wheel running, would improve motor performance in rats with such lesions, and (2) whether any beneficial effects of wheel running are attributable to ameliorating the dopaminergic damage. In experiment 1, rats were allowed to run in exercise wheels or kept in home cages for 2 1/2 weeks, then given stereotaxic infusions of 6-hydroxydopamine into the left striatum. The rats were replaced into their original environments (wheels or home cages) for four additional weeks, and asymmetries in forelimb use were quantified at 3, 10, 17, and 24 days postoperatively. After killing, dopaminergic damage was assessed by both quantifying 3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([(125)I]RTI-55) binding to striatal dopamine transporters and counting tyrosine hydroxylase-positive cells in the substantia nigra. Exercised 6-hydroxydopamine-infused rats showed improved motor outcomes relative to sedentary lesioned controls, effects that were most apparent at postoperative days 17 and 24. Despite this behavioral improvement, 6-hydroxydopamine-induced loss of striatal dopamine transporters and tyrosine hydroxylase-positive nigral cells in exercised and sedentary groups did not differ. Since prior studies suggested that forced limb use improves motor performance by sparing nigrostriatal dopaminergic neurons from 6-hydroxydopamine damage, experiment 2 used a combined regimen of forced plus voluntary wheel running. Again, we found that the motor performance of exercised rats improved more rapidly than that of sedentary controls, but that there were no differences between these groups in the damage produced by 6-hydroxydopamine. It appears that voluntary exercise can facilitate recovery from partial nigrostriatal injury, but it does so without evident sparing of dopamine nerve terminals.

Phosphatidylinositol 3-kinase p85alpha regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population.

AIMS/HYPOTHESIS: Phosphatidylinositol 3-kinase (PI3K) couples the leptin and insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2. Hence, defective activation of PI3K could be a novel mechanism of peripheral leptin or insulin resistance. We investigated associations of tagging single-nucleotide polymorphisms (tSNPs) in the PI3K p85alpha regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction. MATERIALS AND METHODS: Eight tSNPs were genotyped in 2,778 women (mean age 47.4+/-12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). RESULTS: SNP rs1550805 was associated with serum leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2%) showed higher serum leptin concentration (p=0.007) and body fat measures (p< or =0.001 for all), and those with haplotype 221 (frequency 38.7%) showed higher fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with subjects with the most common haplotype, 111 (frequency 45.5%). CONCLUSIONS/INTERPRETATION: Association of the PIK3R1 SNP rs1550805 with serum leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1 or IRS2 in response to leptin.

AMP-kinase alpha2 subunit gene PRKAA2 variants are associated with total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol in normal women.

BACKGROUND: 5'-AMP-activated protein kinase (AMPK) inactivates critial ensymes in fatty acid and cholesterol synthesis. We hypothesised that the serum lipid profile may be influenced by genetic variation in the AMPK catalytic alpha2 subunit. METHOD: We examined association of 5 tagging SNPs (tSNPs) in the PRKAA2 gene with serum lipids in 2777 normal Caucasian females (mean age 47.4+/-12.5 years). RESULTS: All tSNPs were associated with total- and LDL-cholesterol, (p<0.001 to 0.034), explaining variances of 0.13-0.59% and 0.11-0.55% respectively. One haplotype (frequency 34.7%) showed lower total- and LDL-cholesterol compared with the most common haplotype (frequency 45.7%) (p< or =0.001), explaining 0.78% of total- and 0.75% of LDL-cholesterol. Another haplotype (frequency 10.5%) was significantly associated with lower HDL-cholesterol (p = 0.005), explaining 0.59% of variance. CONCLUSIONS: PRKAA2 gene variants are significantly associated with serum lipoproteins in a large sample of normal female Caucasians.

Common polymorphisms in SOCS3 are not associated with body weight, insulin sensitivity or lipid profile in normal female twins.

AIMS/HYPOTHESIS: Inhibition of signal transduction by suppressor of cytokine signalling-3 (SOCS-3) potentially influences resistance to insulin and leptin. The aim of this study was to test the association between three single-nucleotide polymorphisms (SNPs) representative of common linkage disequilibrium clusters in SOCS3 (rs4969169, rs12953258 and rs8064821) and obesity measures, insulin sensitivity measures and serum lipids in the general population. METHODS: The three SNPs, which had rare allele frequencies >0.06, were genotyped in 2,777 female twins of European extraction (mean age 47.4+/-12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). RESULTS: Minor allele frequencies were as follows: rs4969169=0.067, rs12953258=0.097 and rs8064821=0.101. Individual SOCS3 SNPs were not associated with general or central obesity, or with two indices of insulin sensitivity (homeostasis model assessment and insulin sensitivity measure). CONCLUSIONS/INTERPRETATION: The results do not indicate that any of the three SNPs studied are associated with obesity, insulin measures or lipid measures.

Characteristics of patients and patterns of psychiatric service use in ethnic minorities.

BACKGROUND: The differential uptake of psychiatric services by ethnic minorities has been widely reported. Less attention has been given to comparisons of these patients and variations in the types of interventions they receive. AIMS: To assess whether for people accessing psychiatric services in the UK, differences exist across ethnic groups both in their sociodemographic characteristics and patterns of mental health care utilisation. METHODS: All adults resident in an inner city health district and using psychiatric services during a six-month period were identified. Demographic, clinical and service use data were collected from staff and records. These were compared across black Caribbean, Indian, Pakistani, Irish and white ethnic groups for two broad diagnostic categories: psychotic/bipolar and depressive/neurotic disorders. RESULTS: There were significant differences between ethnic groups on most demographic variables in each of the diagnostic categories. There were variations in the level of contact with different mental health professionals. The only significant difference in the use of specific services was for those with psychotic/bipolar disorders, black Caribbean patients being more likely to be detained in hospital compulsorily. CONCLUSIONS: Ethnic diversity both in the characteristics of patients and their patterns of psychiatric care should be addressed when planning and developing services.

What's hot in animal biosafety?

In recent years, the emergence or re-emergence of critical issues in infectious disease and public health has presented new challenges and opportunities for laboratory animal care professionals. The re-emergence of bioterrorism as a threat activity of individuals or small groups has caused a heightened awareness of biosecurity and improved biosafety. The need for animal work involving high-risk or high-consequence pathogens and for arthropod-borne diseases has stimulated renewed interest in animal biosafety matters, particularly for work in containment. Application of these principles to animals retained in outdoor environments has been a consequence of disease eradication programs. The anticipated global eradication of wild poliovirus has prompted the promulgation of new biosafety guidelines for future laboratory and animal work. Increased concern regarding the use of biologically derived toxins and hazardous chemicals has stimulated a new categorization of facility containment based on risk assessment. Recognition that prion disease agents and other high-consequence pathogens require safe handling and thorough destruction during terminal decontamination treatment has led to the development of new biosafety guidelines and technologies. The implementation of these guidelines and technologies will promote state-of-the-art research while minimizing risk to laboratory animals, researchers, and the environment.

Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males.

We previously demonstrated an association between the insulin-like growth factor 2 (IGF2) gene 3'-untranslated region (3'-UTR) ApaI polymorphism and body mass index (BMI) in over 2500 middle-aged Caucasoid males. In the same cohort, we have now tested association with 11 more markers, including seven novel single nucleotide polymorphisms (SNPs), spanning >30 kb across the IGF2 gene. Three SNPs showed significant positive associations with BMI: 6815 A/T in the IGF2 P1 promoter (P = 0.00012, n = 2394) and the newly identified SNPs 1156 C/T in intron 2 (P = 0.017, n = 1567) and 1926 C/G in the 3'-UTR (P = 0.0062, n = 1872). There was strong pairwise linkage disequilibrium (LD) between the ApaI and 1926 C/G sites, whereas LD between ApaI and 6815 A/T, and between ApaI and 1156 T/C, was minimal. Univariately 6815 A/T, 1156 T/C and ApaI explained 1.03, 1.02 and 0.67% of the variation in BMI. Multi-way analysis of variance (ANOVA) models showed that 6815 A/T and 1156 T/C explained a further 0.4 and 0.8% of the variation beyond that accounted for by ApaI and the association of 1926 C/G with BMI disappeared after adjustment. The 6815 A/T, 1156 T/C and ApaI markers in effect constitute independent affirmations of our original hypothesized candidate gene region. In a stepwise multi-way ANOVA model, all three terms were significantly independently associated with BMI. The total proportion of BMI variance explained by this model was 2.25%, strongly suggesting that IGF2 genetic variation is a significant determinant of body weight in middle-aged males.

Realizing positive returns from your e-health investments.

Although the healthcare industry still is in the beginning stages of e-health adoption and has yet to achieve a significant return on e-health investments, healthcare organizations can anticipate increasingly positive results over time. To capitalize on the potential of e-health, financial managers need to adopt a clear, concise approach to valuing e-health investment options, making investment decisions, and managing an organization's return on invested capital. Key actions to take are developing a strategy, looking beyond cost reduction to other advantages of e-health strategies, understanding the needs of the stakeholders, becoming comfortable with experimentation, having realistic expectations, and instituting a process for valuing e-health investments that does not duplicate valuation processes for traditional information technology projects.