Responses of New Zealand forest birds to management of introduced mammals.

Over the past 1000 years New Zealand has lost 40-50% of its bird species, and over half of these extinctions are attributable to predation by introduced mammals. Populations of many extant forest bird species continue to be depredated by mammals, especially rats, possums, and mustelids. The management history of New Zealand's forests over the past 50 years presents a unique opportunity because a varied program of mammalian predator control has created a replicated management experiment. We conducted a meta-analysis of population-level responses of forest birds to different levels of mammal control recorded across New Zealand. We collected data from 32 uniquely treated sites and 20 extant bird species representing a total of 247 population responses to 3 intensities of invasive mammal control (zero, low, and high). The treatments varied from eradication of invasive mammals via ground-based techniques to periodic suppression of mammals via aerially sown toxin. We modeled population-level responses of birds according to key life history attributes to determine the biological processes that influence species' responses to management. Large endemic species, such as the Kaka (Nestor meridionalis) and New Zealand Pigeon (Hemiphaga novaeseelandiae), responded positively at the population level to mammal control in 61 of 77 cases for species ≥20 g compared with 31 positive responses from 78 cases for species <20 g. The Fantail (Rhipidura fuliginosa) and Grey Warbler (Gerygone igata), both shallow endemic species, and 4 nonendemic species (Blackbird [Turdus merula], Chaffinch [Fringilla coelebs], Dunnock [Prunella modularis], and Silvereye [Zosterops lateralis]) that arrived in New Zealand in the last 200 years tended to have slight negative or neutral responses to mammal control (59 of 77 cases). Our results suggest that large, deeply endemic forest birds, especially cavity nesters, are most at risk of further decline in the absence of mammal control and, conversely suggest that 6 species apparently tolerate the presence of invasive mammals and may be sensitive to competition from larger endemic birds.

Respuestas de Aves Habitantes de Bosques Neozelandeses al Manejo de Mamíferos Introducidos Resumen En los últimos 1000 años, Nueva Zelanda ha perdido entre el 40% y 50% de las especies de aves. De estas extinciones, más de la mitad se puede atribuir a la depredación por mamíferos introducidos. Las poblaciones existentes de aves de bosque todavía están siendo depredadas por mamíferos, principalmente ratas, zarigüeyas y mustélidos. La historia de manejo de los bosques en Nueva Zelanda durante los recientes 50 años representa una oportunidad única porque un programa variado de control de mamíferos depredadores ha creado un experimento de manejo replicado. Realizamos un metaanálisis de las respuestas a nivel poblacional de las aves de bosque ante diferentes niveles de control de mamíferos registrados en toda Nueva Zelanda. Recolectamos datos de 32 sitios tratados de manera única y de 20 especies existentes de aves que representan un total de 247 respuestas poblacionales a tres intensidades de control de mamíferos invasores (cero, bajo y alto). Los tratamientos variaron desde la erradicación de los mamíferos invasores por vía de técnicas terrestres hasta la eliminación periódica de los mamíferos por medio de toxinas dispersadas por vía aérea. Modelamos las respuestas a nivel poblacional de las aves de acuerdo con los atributos de historia de vida importantes para determinar los procesos biológicos que influyen sobre las respuestas de las especies al manejo. Las especies endémicas grandes, como la kaka (Nestor meridionalis) y la paloma de Nueva Zelanda (Hemiphaga novaeseelandiae), respondieron positivamente a nivel poblacional al control de mamíferos en 61 de los 77 casos para especies con un peso ≥20 g comparado con 31 respuestas positivas de 78 casos para especies con un peso <20 g. El ave cola de abanico (Rhipidura fuliginosa) y la curruca gris (Gerygone igata), ambas especies endémicas someras, junto con cuatro especies no endémicas (el mirlo [Turdus merula], el pinzón [Fringilla coelebs], el acentor [Prunella modularis] y el pájaro de anteojos [Zosterops lateralis]) que arribaron a Nueva Zelanda en los últimos 200 años presentaron una tendencia hacia las respuestas negativas o neutrales al control de mamíferos (59 de 77 casos). Nuestros resultados sugieren que las aves endémicas grandes y que habitan en las profundidades del bosque, especialmente aquellas que anidan en cavidades, tienen el mayor riesgo de vivir una declinación en el futuro si el control de mamíferos se ausenta. A la inversa, nuestros resultados también sugieren que seis especies aparentemente toleran la presencia de mamíferos invasores y podrían ser vulnerables a la competencia generada por aves endémicas de mayor tamaño.

Quantifying hydrologic controls on local- and landscape-scale indicators of coastal wetland loss.

BACKGROUND AND AIMS: Coastal wetlands have evolved to withstand stressful abiotic conditions through the maintenance of hydrologic feedbacks between vegetation production and flooding. However, disruption of these feedbacks can lead to ecosystem collapse, or a regime shift from vegetated wetland to open water. To prevent the loss of critical coastal wetland habitat, we must improve understanding of the abiotic-biotic linkages among flooding and wetland stability. The aim of this research was to identify characteristic landscape patterns and thresholds of wetland degradation that can be used to identify areas of vulnerability, reduce flooding threats and improve habitat quality. METHODS: We measured local- and landscape-scale responses of coastal wetland vegetation to flooding stress in healthy and degrading coastal wetlands. We hypothesized that conversion of Spartina patens wetlands to open water could be defined by a distinct change in landscape configuration pattern, and that this change would occur at a discrete elevation threshold. KEY RESULTS: Despite similarities in total land and water cover, we observed differences in the landscape configuration of vegetated and open water pixels in healthy and degrading wetlands. Healthy wetlands were more aggregated, and degrading wetlands were more fragmented. Generally, greater aggregation was associated with higher wetland elevation and better drainage, compared with fragmented wetlands, which had lower elevation and poor drainage. The relationship between vegetation cover and elevation was non-linear, and the conversion from vegetated wetland to open water occurred beyond an elevation threshold of hydrologic stress. CONCLUSIONS: The elevation threshold defined a transition zone where healthy, aggregated, wetland converted to a degrading, fragmented, wetland beyond an elevation threshold of 0.09 m [1988 North American Vertical Datum (NAVD88)] [0.27 m mean sea level (MSL)], and complete conversion to open water occurred beyond 0.03 m NAVD88 (0.21 m MSL). This work illustrates that changes in landscape configuration can be used as an indicator of wetland loss. Furthermore, in conjunction with specific elevation thresholds, these data can inform restoration and conservation planning to maximize wetland stability in anticipation of flooding threats.

Climate and plant controls on soil organic matter in coastal wetlands.

Coastal wetlands are among the most productive and carbon-rich ecosystems on Earth. Long-term carbon storage in coastal wetlands occurs primarily belowground as soil organic matter (SOM). In addition to serving as a carbon sink, SOM influences wetland ecosystem structure, function, and stability. To anticipate and mitigate the effects of climate change, there is a need to advance understanding of environmental controls on wetland SOM. Here, we investigated the influence of four soil formation factors: climate, biota, parent materials, and topography. Along the northern Gulf of Mexico, we collected wetland plant and soil data across elevation and zonation gradients within 10 estuaries that span broad temperature and precipitation gradients. Our results highlight the importance of climate-plant controls and indicate that the influence of elevation is scale and location dependent. Coastal wetland plants are sensitive to climate change; small changes in temperature or precipitation can transform coastal wetland plant communities. Across the region, SOM was greatest in mangrove forests and in salt marshes dominated by graminoid plants. SOM was lower in salt flats that lacked vascular plants and in salt marshes dominated by succulent plants. We quantified strong relationships between precipitation, salinity, plant productivity, and SOM. Low precipitation leads to high salinity, which limits plant productivity and appears to constrain SOM accumulation. Our analyses use data from the Gulf of Mexico, but our results can be related to coastal wetlands across the globe and provide a foundation for predicting the ecological effects of future reductions in precipitation and freshwater availability. Coastal wetlands provide many ecosystem services that are SOM dependent and highly vulnerable to climate change. Collectively, our results indicate that future changes in SOM and plant productivity, regulated by cascading effects of precipitation on freshwater availability and salinity, could impact wetland stability and affect the supply of some wetland ecosystem services.

Detection and visualization of differential splicing in RNA-Seq data with JunctionSeq.

Although RNA-Seq data provide unprecedented isoform-level expression information, detection of alternative isoform regulation (AIR) remains difficult, particularly when working with an incomplete transcript annotation. We introduce JunctionSeq, a new method that builds on the statistical techniques used by the well-established DEXSeq package to detect differential usage of both exonic regions and splice junctions. In particular, JunctionSeq is capable of detecting differential usage of novel splice junctions without the need for an additional isoform assembly step, greatly improving performance when the available transcript annotation is flawed or incomplete. JunctionSeq also provides a powerful and streamlined visualization toolset that allows bioinformaticians to quickly and intuitively interpret their results. We tested our method on publicly available data from several experiments performed on the rat pineal gland and Toxoplasma gondii, successfully detecting known and previously validated AIR genes in 19 out of 19 gene-level hypothesis tests. Due to its ability to query novel splice sites, JunctionSeq is still able to detect these differences even when all alternative isoforms for these genes were not included in the transcript annotation. JunctionSeq thus provides a powerful method for detecting alternative isoform regulation even with low-quality annotations. An implementation of JunctionSeq is available as an R/Bioconductor package.

QoRTs: a comprehensive toolset for quality control and data processing of RNA-Seq experiments.

BACKGROUND: High-throughput next-generation RNA sequencing has matured into a viable and powerful method for detecting variations in transcript expression and regulation. Proactive quality control is of critical importance as unanticipated biases, artifacts, or errors can potentially drive false associations and lead to flawed results. RESULTS: We have developed the Quality of RNA-Seq Toolset, or QoRTs, a comprehensive, multifunction toolset that assists in quality control and data processing of high-throughput RNA sequencing data. CONCLUSIONS: QoRTs generates an unmatched variety of quality control metrics, and can provide cross-comparisons of replicates contrasted by batch, biological sample, or experimental condition, revealing any outliers and/or systematic issues that could drive false associations or otherwise compromise downstream analyses. In addition, QoRTs simultaneously replaces the functionality of numerous other data-processing tools, and can quickly and efficiently generate quality control metrics, coverage counts (for genes, exons, and known/novel splice-junctions), and browser tracks. These functions can all be carried out as part of a single unified data-processing/quality control run, greatly reducing both the complexity and the total runtime of the analysis pipeline. The software, source code, and documentation are available online at http://hartleys.github.io/QoRTs.

Weaker resource diffusion effect at coarser spatial scales observed for egg distribution of cabbage white butterflies.

Mobile organisms frequently forage for patchy resources; e.g. herbivorous insects searching for host plants. The resource diffusion hypothesis predicts that insect herbivores, such as Pieris rapae butterflies, are disproportionally attracted to more isolated, or 'diffused', host plants. Surprisingly little is known about how this response to variation in resource density manifests itself at different spatial scales. We measured the outcome of oviposition by P. rapae butterflies foraging among groups of host plants, with plant density experimentally varied to achieve comparability between three nested scales: fine (1 × 1 m), medium (6 × 6 m), and coarse (36 × 36 m). Hierarchical linear models were used to measure density-dependent responses in the number of eggs laid per plant, with plant density measured at nested spatial scales. At a fine scale, isolated plants received significantly more eggs, while at medium and coarse scales the differences were less pronounced, and tended towards a neutral distribution of eggs across plants. Larger plants also tended to receive more eggs. Since multiple processes, acting at multiple scales, are likely to be the rule rather than the exception in ecology, methods for detecting and characterising multi-scale responses are important to ensure a robust transfer of ecological models from one situation to another.

PleioGRiP: genetic risk prediction with pleiotropy.

MOTIVATION: Although several studies have used Bayesian classifiers for risk prediction using genome-wide single nucleotide polymorphism (SNP) datasets, no software can efficiently perform these analyses on massive genetic datasets and can accommodate multiple traits. RESULTS: We describe the program PleioGRiP that performs a genome-wide Bayesian model search to identify SNPs associated with a discrete phenotype and uses SNPs ranked by Bayes factor to produce nested Bayesian classifiers. These classifiers can be used for genetic risk prediction, either selecting the classifier with optimal number of features or using an ensemble of classifiers. In addition, PleioGRiP implements an extension to the Bayesian search and classification and can search for pleiotropic relationships in which SNPs are simultaneously associated with two or more distinct phenotypes. These relationships can be used to generate connected Bayesian classifiers to predict the phenotype of interest either using genetic data alone or in combination with the secondary phenotype(s). AVAILABILITY: PleioGRiP is implemented in Java, and it is available from http://hdl.handle.net/2144/4367. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia.

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21-5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry.

Relative roles of climatic suitability and anthropogenic influence in determining the pattern of spread in a global invader.

Because invasive species threaten the integrity of natural ecosystems, a major goal in ecology is to develop predictive models to determine which species may become widespread and where they may invade. Indeed, considerable progress has been made in understanding the factors that influence the local pattern of spread for specific invaders and the factors that are correlated with the number of introduced species that have become established in a given region. However, few studies have examined the relative importance of multiple drivers of invasion success for widespread species at global scales. Here, we use a dataset of >5,000 presence/absence records to examine the interplay between climatic suitability, biotic resistance by native taxa, human-aided dispersal, and human modification of habitats, in shaping the distribution of one of the world's most notorious invasive species, the Argentine ant (Linepithema humile). Climatic suitability and the extent of human modification of habitats are primarily responsible for the distribution of this global invader. However, we also found some evidence for biotic resistance by native communities. Somewhat surprisingly, and despite the often cited importance of propagule pressure as a crucial driver of invasions, metrics of the magnitude of international traded commodities among countries were not related to global distribution patterns. Together, our analyses on the global-scale distribution of this invasive species provide strong evidence for the interplay of biotic and abiotic determinants of spread and also highlight the challenges of limiting the spread and subsequent impact of highly invasive species.

Listening to the nurse pays off: an integrated Nurse HealthLine programme was associated with significant cost savings.

AIM: To estimate the relationship between adherence to nurse recommendations about where to seek care and expenditures for health-care services received by callers to a Nurse HealthLine telephone-based triage programme. METHODS: Health-care utilization and claims data from callers to the Nurse HealthLine were included. Adherent callers were those who followed the nurse recommendations, while those who did not were classified as non-adherent. Programme-related savings were estimated using differences in downstream health-care expenditures between adherent and non-adherent callers after using multivariate modelling to adjust for between-group differences. RESULTS: Fifty-five per cent of callers were adherent. Nurses were over three times as likely (41% vs. 13%) to recommend seeking a higher level of care (e.g. emergency room vs. urgent care). Regression analyses showed that the impact of getting members to the appropriate place of care was associated with significant annual savings of $13.8 million (P < 0.05), attributable mostly to Medicare, generating a positive return on investment of $1.59. CONCLUSIONS: This is the first known Nurse HealthLine triage programme exclusively for Medicare beneficiaries with supplemental coverage. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should consider promoting telephone-based triage programmes as complementary to clinical nursing, which has a direct impact on health-care utilization and costs.

Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors.

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), female breast cancer (OR = 1.42, 95% CI = 1.27-1.58), thyroid cancer (OR = 1.48, 95% CI = 1.31-1.67), squamous cell carcinoma (OR = 1.20, 95% CI = 1.00-1.44) and melanoma (OR = 1.60, 95% CI = 1.31-1.96); however, the association for colorectal cancer was not significant (OR = 1.19, 95% CI = 0.94-1.52). An investigation of joint associations between PRSs and radiotherapy found more than additive increased risks of basal cell carcinoma, and breast and thyroid cancers. For survivors with radiotherapy exposure, the cumulative incidence of subsequent cancer by age 50 years was increased for those with high versus low PRS. These findings suggest a degree of shared genetic etiology for these malignancy types in the general population and survivors, which remains evident in the context of strong radiotherapy-related risk.

Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident.

Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.

Inflated expectations: Rare-variant association analysis using public controls.

The use of publicly available sequencing datasets as controls (hereafter, "public controls") in studies of rare variant disease associations has great promise but can increase the risk of false-positive discovery. The specific factors that could contribute to inflated distribution of test statistics have not been systematically examined. Here, we leveraged both public controls, gnomAD v2.1 and several datasets sequenced in our laboratory to systematically investigate factors that could contribute to the false-positive discovery, as measured by λΔ95, a measure to quantify the degree of inflation in statistical significance. Analyses of datasets in this investigation found that 1) the significantly inflated distribution of test statistics decreased substantially when the same variant caller and filtering pipelines were employed, 2) differences in library prep kits and sequencers did not affect the false-positive discovery rate and, 3) joint vs. separate variant-calling of cases and controls did not contribute to the inflation of test statistics. Currently available methods do not adequately adjust for the high false-positive discovery. These results, especially if replicated, emphasize the risks of using public controls for rare-variant association tests in which individual-level data and the computational pipeline are not readily accessible, which prevents the use of the same variant-calling and filtering pipelines on both cases and controls. A plausible solution exists with the emergence of cloud-based computing, which can make it possible to bring containerized analytical pipelines to the data (rather than the data to the pipeline) and could avert or minimize these issues. It is suggested that future reports account for this issue and provide this as a limitation in reporting new findings based on studies that cannot practically analyze all data on a single pipeline.

Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5' olfactory receptor gene cluster.

In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or beta thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E-08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E-21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in gamma-globin gene expression.

The widespread collapse of an invasive species: Argentine ants (Linepithema humile) in New Zealand.

Synergies between invasive species and climate change are widely considered to be a major biodiversity threat. However, invasive species are also hypothesized to be susceptible to population collapse, as we demonstrate for a globally important invasive species in New Zealand. We observed Argentine ant populations to have collapsed in 40 per cent of surveyed sites. Populations had a mean survival time of 14.1 years (95% CI = 12.9-15.3 years). Resident ant communities had recovered or partly recovered after their collapse. Our models suggest that climate change will delay colony collapse, as increasing temperature and decreasing rainfall significantly increased their longevity, but only by a few years. Economic and environmental costs of invasive species may be small if populations collapse on their own accord.

Detection parameters for managing invasive rats in urban environments.

Effective mitigation of the impacts of invasive ship rats (Rattus rattus) requires a good understanding of their ecology, but this knowledge is very sparse for urban and peri-urban areas. We radiomarked ship rats in Wellington, New Zealand, to estimate detection parameters (σ, ε0, θ, and g0) that describe the process of an animal encountering a device (bait stations, chew cards and WaxTags) from a distance, and then approaching it and deciding whether to interact with it. We used this information in simulation models to estimate optimal device spacing for eradicating ship rats from Wellington, and for confirming eradication. Mean σ was 25.37 m (SD = 11.63), which equates to a circular home range of 1.21 ha. The mean nightly probability of an individual encountering a device at its home range center (ε0) was 0.38 (SD = 0.11), whereas the probability of interacting with the encountered device (θ) was 0.34 (SD = 0.12). The derived mean nightly probability of an individual interacting with a device at its home range center (g0) was 0.13 (SD = 0.08). Importantly, σ and g0 are intrinsically linked through a negative relationship, thus g0 should be derived from σ using a predictive model including individual variability. Simulations using this approach showed that bait stations deployed for about 500 days using a 25 m × 25 m grid consistently achieved eradication, and that a surveillance network of 3.25 chew cards ha-1 or 3.75 WaxTags ha-1 active for 14 nights would be required to confidently declare eradication. This density could be halved if the surveillance network was deployed for 28 nights or if the prior confidence in eradication was high (0.85). These recommendations take no account of differences in detection parameters between habitats. Therefore, if surveillance suggests that individuals are not encountering devices in certain habitats, device density should be adaptively revised. This approach applies to initiatives globally that aim to optimise eradication with limited funding.

Invasive Urban Mammalian Predators: Distribution and Multi-Scale Habitat Selection.

A barrier to successful ecological restoration of urban green spaces in many cities is invasive mammalian predators. We determined the fine- and landscape-scale habitat characteristics associated with the presence of five urban predators (black and brown rats, European hedgehogs, house mice, and brushtail possums) in three New Zealand cities, in spring and autumn, in three green space types: forest fragments, amenity parks, and residential gardens. Season contributed to variations in detections for all five taxa. Rodents were detected least in residential gardens; mice were detected more often in amenity parks. Hedgehogs were detected least in forest fragments. Possums were detected most often in forest fragments and least often in residential gardens. Some of this variation was explained by our models. Proximity of amenity parks to forest patches was strongly associated with presence of possums (positively), hedgehogs (positively), and rats (negatively). Conversely, proximity of residential gardens to forest patches was positively associated with rat presence. Rats were associated with shrub and lower canopy cover and mice with herb layer cover. In residential gardens, rat detection was associated with compost heaps. Successful restoration of biodiversity in these cities needs extensive, coordinated predator control programmes that engage urban residents.

Ancestry of African Americans with sickle cell disease.

The inheritance of genetic disease depends on ancestry that must be considered when interpreting genetic association studies and can provide insights when comparing traits in a population. We compared the genetic profiles of African Americans with sickle cell disease to those of Black Africans and Caucasian populations of European descent and found that they are less genetically admixed than other African Americans and have an ancestry similar to Yorubans, Mandenkas and Bantu.

Hippocampal morphometry in population-based incident Alzheimer's disease and vascular dementia: the HAAS.

BACKGROUND: Hippocampal changes may be a useful biomarker for Alzheimer's disease if they are specific to dementia sub-type. We compare hippocampal volume and shape in population-based incident cases of Alzheimer's disease and vascular dementia (VaD). METHODS: Participants are Japanese-American men from the Honolulu Asia Aging Study. The following analysis is based on a sub-group of men with mild incident Alzheimer's disease (n=24: age=82.5 ± 4.6) or incident VaD (n=14: age=80.5 ± 4.5). To estimate hippocampal volume, one reader, blinded to dementia diagnosis, manually outlined the left and right formation of the hippocampus using published criteria. We used 3-D mapping methods developed at the Laboratory of Neuro Imaging (LONI) to compare regional variation in hippocampal width between dementia groups. RESULTS: Hippocampal volume was about 5% smaller in the Alzheimer's disease group compared to the VaD group, but the difference was not significant. Hippocampal shape differed between the two case groups for the left (p<0.04) but not right (p<0.21) hippocampus. The specific region of the hippocampus that most consistently differed between the Alzheimer's disease and VaD cases was in the lateral portion of the left hippocampus. Our interpretation of this region is that it intersects the CA1 sub-region to a great extent but also includes the dentate gyrus (and hilar region) and subiculum. CONCLUSION: As indicated by shape analysis, there are some differences in atrophy localisation between the Alzheimer's disease and VaD cases, despite the finding that volume of the hippocampi did not differ. These findings suggest hippocampal atrophy in Alzheimer's disease may be more focal than in VaD.

Severe sickle cell anemia is associated with increased plasma levels of TNF-R1 and VCAM-1.

Sickle cell anemia (SCA, HBB glu6val) is characterized by multiple complications and a high degree of phenotypic variability: some subjects have only sporadic pain crises and few acute hospitalizations, while others experience multiple serious complications, high levels of morbidity, and accelerated mortality [1]. The tumor necrosis factor-α (TNF-α) signaling pathway plays important roles in inflammation and the immune response; variation in this pathway might be expected to modify the overall severity of SCA through the pathway's effects on the vascular endothelium [2,3]. We examined plasma biomarkers of TNF-α activity and endothelial cell activation for associations with SCA severity in 24 adults (12 mild, 12 severe). Two biomarkers, tumor necrosis factor-α receptor-1 (TNF-R1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in subjects with severe SCA. Along with these biomarker differences, we also examined data from a genome-wide association study (GWAS) using SCA severity as a disease phenotype, and found evidence of genetic association between disease severity and a single nucleotide polymorphism (SNP) in VCAM1, which codes for VCAM-1, and several SNPs in ARFGEF2, a gene involved in TNF-R1 release [4].