Species Diversity and Phylogeographical Affinities of the Branchiopoda (Crustacea) of Churchill, Manitoba, Canada

The region of Churchill, Manitoba, contains a wide variety of habitats representative of both the boreal forest and arctic tundra and has been used as a model site for biodiversity studies for nearly seven decades within Canada. Much previous work has been done in Churchill to study the Daphnia pulex species complex in particular, but no study has completed a wide-scale survey on the crustacean species that inhabit Churchill's aquatic ecosystems using molecular markers. We have employed DNA barcoding to study the diversity of the Branchiopoda (Crustacea) in a wide variety of freshwater habitats and to determine the likely origins of the Churchill fauna following the last glaciation. The standard animal barcode marker (COI) was sequenced for 327 specimens, and a 3% divergence threshold was used to delineate potential species. We found 42 provisional and valid branchiopod species from this survey alone, including several cryptic lineages, in comparison with the 25 previously recorded from previous ecological works. Using published sequence data, we explored the phylogeographic affinities of Churchill's branchiopods, finding that the Churchill fauna apparently originated from all directions from multiple glacial refugia (including southern, Beringian, and high arctic regions). Overall, these microcrustaceans are very diverse in Churchill and contain multiple species complexes. The present study introduces among the first sequences for some understudied genera, for which further work is required to delineate species boundaries and develop a more complete understanding of branchiopod diversity over a larger spatial scale

Related and unrelated donor transplantation for β-thalassemia major: results of an international survey.

We studied 1110 patients with β-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available

Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish

BACKGROUND: Population heterogeneity may be a significant confounding factor hampering detection and verification of late onset Alzheimer's disease (LOAD) susceptibility genes. The Amish communities located in Indiana and Ohio are relatively isolated populations that may have increased power to detect disease susceptibility genes. METHODS: We recently performed a genome scan of dementia in this population that detected several potential loci. However, analyses of these data are complicated by the highly consanguineous nature of these Amish pedigrees. Therefore we applied the Combinatorial Mismatch Scanning (CMS) method that compares identity by state (IBS) (under the presumption of identity by descent (IBD)) sharing in distantly related individuals from such populations where standard linkage and association analyses are difficult to implement. CMS compares allele sharing between individuals in affected and unaffected groups from founder populations. Comparisons between cases and controls were done using two Fisher's exact tests, one testing for excess in IBS allele frequency and the other testing for excess in IBS genotype frequency for 407 microsatellite markers. RESULTS: In all, 13 dementia cases and 14 normal controls were identified who were not related at least through the grandparental generation. The examination of allele frequencies identified 24 markers (6%) nominally (p ≤ 0.05) associated with dementia; the most interesting (empiric p ≤ 0.005) markers were D3S1262, D5S211, and D19S1165. The examination of genotype frequencies identified 21 markers (5%) nominally (p ≤ 0.05) associated with dementia; the most significant markers were both located on chromosome 5 (D5S1480 and D5S211). Notably, one of these markers (D5S211) demonstrated differences (empiric p ≤ 0.005) under both tests. CONCLUSION: Our results provide the initial groundwork for identifying genes involved in late-onset Alzheimer's disease within the Amish community. Genes identified within this isolated population will likely play a role in a subset of late-onset AD cases across more general populations. Regions highlighted by markers demonstrating suggestive allelic and/or genotypic differences will be the focus of more detailed examination to characterize their involvement in dementia

Dementia Revealed: Novel Chromosome 6 Locus for Late-Onset Alzheimer Disease Provides Genetic Evidence for Folate-Pathway Abnormalities

Genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) have consistently observed strong evidence of association with polymorphisms in APOE. However, until recently, variants at few other loci with statistically significant associations have replicated across studies. The present study combines data on 483,399 single nucleotide polymorphisms (SNPs) from a previously reported GWAS of 492 LOAD cases and 496 controls and from an independent set of 439 LOAD cases and 608 controls to strengthen power to identify novel genetic association signals. Associations exceeding the experiment-wide significance threshold () were replicated in an additional 1,338 cases and 2,003 controls. As expected, these analyses unequivocally confirmed APOE's risk effect (rs2075650, ). Additionally, the SNP rs11754661 at 151.2 Mb of chromosome 6q25.1 in the gene MTHFD1L (which encodes the methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like protein) was significantly associated with LOAD (; Bonferroni-corrected P = 0.022). Subsequent genotyping of SNPs in high linkage disequilibrium () with rs11754661 identified statistically significant associations in multiple SNPs (rs803424, P = 0.016; rs2073067, P = 0.03; rs2072064, P = 0.035), reducing the likelihood of association due to genotyping error. In the replication case-control set, we observed an association of rs11754661 in the same direction as the previous association at P = 0.002 ( in combined analysis of discovery and replication sets), with associations of similar statistical significance at several adjacent SNPs (rs17349743, P = 0.005; rs803422, P = 0.004). In summary, we observed and replicated a novel statistically significant association in MTHFD1L, a gene involved in the tetrahydrofolate synthesis pathway. This finding is noteworthy, as MTHFD1L may play a role in the generation of methionine from homocysteine and influence homocysteine-related pathways and as levels of homocysteine are a significant risk factor for LOAD development

Association between history and physical examination factors and change in lumbar multifidus muscle thickness after spinal manipulation in patients with low back pain

Understanding the clinical characteristics of patients with low back pain (LBP) who display improved lumbar multifidus (LM) muscle function after spinal manipulative therapy (SMT) may provide insight into a potentially synergistic interaction between SMT and exercise. Therefore, the purpose of this study was to identify the baseline historical and physical examination factors associated with increased contracted LM muscle thickness one week after SMT. Eighty-one participants with LBP underwent a baseline physical examination and ultrasound imaging assessment of the LM muscle during submaximal contraction before and one week after SMT. The relationship between baseline examination variables and 1-week change in contracted LMthickness was assessed using correlation analysis and hierarchicalmultiple linear regression. Four variables best predicted themagnitude of increases in contractedLMmuscle thickness afterSMT.When combined, these variables suggest that patients with LBP, (1) that are fairly acute, (2) have at least amoderately good prognosiswithout focal and irritable symptoms, and (3) exhibit signs of spinal instability, may be the best candidates for a combined SMT and lumbar stabilization exercise (LSE) treatment approach

Intra-rater Reliability of Ultrasound Imaging of Wrist Extensor Muscles in Patients With Tetraplegia

(i) To determine the intra-rater reliability and precision of the ultrasound cross-sectional area (CSA) measurements of the wrist extensors in individuals with spinal cord injury (SCI), and (ii) to determine whether tetraplegia has a negative influence on the reliability and precision for these measurements. A repeated-measures cross-sectional study. Clinical hospital and academic settings. The study was conducted with 20 men with SCI (9 paraplegia and 11 tetraplegia) and 10 able-bodied controls. Ultrasound images were captured of the right side extensor carpi radialis-longus (ECRL) and the extensor digitorum communis (EDC) were captured in 2 sessions separated by 48-72 hours. The intraclass correlation coefficients for the CSA measurements of the ECRL and EDC muscles were greater than 0.87 for all 3 groups. The standard error of the measure (SEM) ranged from 0.11-0.22 cm(2) for the ECRL and 0.13-0.27 cm(2) for the EDC. The minimal detectable change of ECL ranged from 0.16 to 0.31 cm(2) and of EDC from 0.19 to 0.38 cm(2). The group differences in muscle CSA of both muscles were found; these differences were greater than the calculated minimal detectable changes. The intraclass correlation coefficients were lower and the SEMs and minimal detectable changes were higher for the group with tetraplegia compared with the able-bodied controls and the group with paraplegia. This study documented substantial intra-rater reliability of measurements of the ECRL and ECD CSA by using ultrasound images, which support the use of this technique to effectively evaluate the musculoskeletal changes after SCI and during rehabilitation. Skeletal muscle atrophy in persons with tetraplegia might have a negative influence on the reliability and precision of these CSA measurements; however, these differences in reliability and precision are not of clinical significance

What is an Entrepreneurial Opportunity?

The nature and source of entrepreneurial opportunity are important issues for understanding how markets function and come into being. In addition to describing the forum held on the topic and summarizing the contributions of the articles that appear in the special issue, this article shares a number of lessons learned during the workshop and the editorial process. We explore three of the most important reasons for confusion about the opportunity construct: (1) the “objectivity” of opportunity, (2) the perceived importance of one particular individual in determining the direction of the social world and (3) what distinguishes the sub-class of “entrepreneurial” opportunity from the broader category of opportunity in general. Finally, we offer some directions for future research by illuminating important issues that emerged from the workshop but that remain largely unanswered by the papers of this special issue. Copyright Springer Science+Business Media, LLC 2007creation, discovery, entrepreneurial opportunity, knowledge, strategy, D5, L26, M13,