Showing papers by "University of Alberta published in 2007"

HMDB: The human metabolome database

Abstract: The Human Metabolome Database (HMDB) is currently the most complete and comprehensive curated collection of human metabolite and human metabolism data in the world. It contains records for more than 2180 endogenous metabolites with information gathered from thousands of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the HMDB also contains an extensive collection of experimental metabolite concentration data compiled from hundreds of mass spectra (MS) and Nuclear Magnetic resonance (NMR) metabolomic analyses performed on urine, blood and cerebrospinal fluid samples. This is further supplemented with thousands of NMR and MS spectra collected on purified, reference metabolites. Each metabolite entry in the HMDB contains an average of 90 separate data fields including a comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, biofluid concentrations, disease associations, pathway information, enzyme data, gene sequence data, SNP and mutation data as well as extensive links to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided. The HMDB is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. The HMDB is available at: www.hmdb.ca

Evolution of genes and genomes on the Drosophila phylogeny.

Abstract: Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis.

Abstract: Although chronic wounds are common, treatment for these disabling conditions remains limited and largely ineffective. In this study, we examined the benefit of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing. Using an excisional wound splinting model, we showed that injection around the wound and application to the wound bed of green fluorescence protein (GFP)(+) allogeneic BM-MSCs significantly enhanced wound healing in normal and diabetic mice compared with that of allogeneic neonatal dermal fibroblasts or vehicle control medium. Fluorescence-activated cell sorting analysis of cells derived from the wound for GFP-expressing BM-MSCs indicated engraftments of 27% at 7 days, 7.6% at 14 days, and 2.5% at 28 days of total BM-MSCs administered. BM-MSC-treated wounds exhibited significantly accelerated wound closure, with increased re-epithelialization, cellularity, and angiogenesis. Notably, BM-MSCs, but not CD34(+) bone marrow cells in the wound, expressed the keratinocyte-specific protein keratin and formed glandular structures, suggesting a direct contribution of BM-MSCs to cutaneous regeneration. Moreover, BM-MSC-conditioned medium promoted endothelial cell tube formation. Real-time polymerase chain reaction and Western blot analysis revealed high levels of vascular endothelial growth factor and angiopoietin-1 in BM-MSCs and significantly greater amounts of the proteins in BM-MSC-treated wounds. Thus, our data suggest that BM-MSCs promote wound healing through differentiation and release of proangiogenic factors. Disclosure of potential conflicts of interest is found at the end of this article.

Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation.

Abstract: T(H)17 lymphocytes appear to be essential in the pathogenesis of numerous inflammatory diseases. We demonstrate here the expression of IL-17 and IL-22 receptors on blood-brain barrier endothelial cells (BBB-ECs) in multiple sclerosis lesions, and show that IL-17 and IL-22 disrupt BBB tight junctions in vitro and in vivo. Furthermore, T(H)17 lymphocytes transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons and promote central nervous system inflammation through CD4+ lymphocyte recruitment.

Species abundance distributions: moving beyond single prediction theories to integration within an ecological framework

Abstract: Species abundance distributions (SADs) follow one of ecologys oldest and most universal laws – every community shows a hollow curve or hyperbolic shape on a histogram with many rare species and just a few common species. Here, we review theoretical, empirical and statistical developments in the study of SADs. Several key points emerge. (i) Literally dozens of models have been proposed to explain the hollow curve. Unfortunately, very few models are ever rejected, primarily because few theories make any predictions beyond the hollow-curve SAD itself. (ii) Interesting work has been performed both empirically and theoretically, which goes beyond the hollow-curve prediction to provide a rich variety of information about how SADs behave. These include the study of SADs along environmental gradients and theories that integrate SADs with other biodiversity patterns. Central to this body of work is an effort to move beyond treating the SAD in isolation and to integrate the SAD into its ecological context to enable making many predictions. (iii) Moving forward will entail understanding how sampling and scale affect SADs and developing statistical tools for describing and comparing SADs. We are optimistic that SADs can provide significant insights into basic and applied ecological science.

Effects of Aerobic and Resistance Exercise in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Multicenter Randomized Controlled Trial

Abstract: Purpose Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects. Patients and Methods We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy–Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema. Results The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. ...

A Tale of Two Cities: Competing Logics and Practice Variation in the Professionalizing of Mutual Funds

Abstract: This article examines practice diffusion in an environment where competing logics exist, specifically investigating how trustee and performance logics that were rooted in different locations (Boston and New York) led to variation in how mutual funds established contracts with independent professional money management firms. This focus on competing logics redirects institutional research away from isomorphism and the segregation of institutional and technical forces and toward an appreciation of how multiple forms of rationality underlie change in organizational fields. Implications for the dominant two-stage institutional model of diffusion and for research on institutions, organizations, and professions are discussed.

Drought sensitivity shapes species distribution patterns in tropical forests.

Abstract: Tropical forests are among the most diverse plant communities on Earth and provide a variety of ecosystem services. They have therefore received widespread attention from policy makers and conservation organizations. Now a common assumption about them — that humid tropical forests are generally water saturated — is brought into question. An assessment of species distribution patterns across the Isthmus of Panama shows that drought plays a large role in structuring plant communities in these tropical forests. Changes in soil moisture availability due to climate change and habitat fragmentation are therefore likely to hit tropical species dramatically. Water availability directly shapes local and regional species distributions in tropical forests. This mechanistic understanding of the factors shaping species distributions is critical for improving vegetation–climate models used to project shifts in tropical forest composition, diversity and ecosystem function under changing precipitation patterns associated with past and future global climate change. Although patterns of tree species distributions along environmental gradients have been amply documented in tropical forests1,2,3,4,5,6,7, mechanisms causing these patterns are seldom known. Efforts to evaluate proposed mechanisms have been hampered by a lack of comparative data on species’ reactions to relevant axes of environmental variation1. Here we show that differential drought sensitivity shapes plant distributions in tropical forests at both regional and local scales. Our analyses are based on experimental field assessments of drought sensitivity of 48 species of trees and shrubs, and on their local and regional distributions within a network of 122 inventory sites spanning a rainfall gradient across the Isthmus of Panama. Our results suggest that niche differentiation with respect to soil water availability is a direct determinant of both local- and regional-scale distributions of tropical trees. Changes in soil moisture availability caused by global climate change and forest fragmentation are therefore likely to alter tropical species distributions, community composition and diversity.

Adalimumab for Maintenance Treatment of Crohn's Disease: Results of the CLASSIC II Trial

Abstract: Background: Adalimumab induced clinical remission after four weeks in patients with active Crohn’s disease in the CLASSIC I trial. Objective: To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn’s disease in a follow-on randomised controlled trial (CLASSIC II). Methods: In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re-randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week. With non-response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI Results: Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p Conclusions: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn’s disease naive to anti-TNF treatment.

Stewardship vs. Stagnation: An Empirical Comparison of Small Family and Non‐Family Businesses*

Abstract: Two major perspectives can be construed in the literature concerning the nature of family owned businesses (FOBs). The first implies that these enterprises have unique charac- teristics of stewardship. FOB owners are said to care deeply about the long-term prospects of the business, in large part because their family's fortune, reputation and future are at stake. Their stewardship is said to be manifested by unusual devotion to the continuity of the company, by more assiduous nurturing of a community of employees, and by seeking out closer connections with customers to sustain the business. The second perspective is less flattering. It proposes that FOBs are unusually subject to stagnation: they are said to face unique resource restrictions, embrace conservative strategies, eschew growth, and be doomed to short lives. This paper develops and examines the merits of the two perspectives, neither of which has been systematically articulated or researched. It does so in an empirical study of only small firms that are owned and managed by their founder. Within this sample, it compares firms that are FOBs, that is, family owned and managed, with non-FOBs, that is, owned and managed by a founder with no other relative involved in the business. The findings show significant support for all three aspects of the stew- ardship perspective of FOBs, and no support for any elements of the stagnation perspective.

New Practice Creation: An Institutional Perspective on Innovation

Abstract: Neoinstitutionalists have developed a rich array of theoretical and empirical insights about how new practices become established via legitimacy and diffusion, but have paid scant attention to their origins. This blind spot has been reinforced by recent work on institutional entrepreneurship which has too often celebrated the actions of a single or small number of actors, and deflected attention away from the emergent, multilevel nature of how new kinds of activities emerge and provide a foundation for the creation of a new practice. In this paper, we examine the case of the creation of active money management practice in the US mutual fund industry, drawing on both institutional and practice scholarship, to develop a process model of new practice creation that redirects attention toward the multiplicity of actors that interactively produce change.

Long term pharmacotherapy for obesity and overweight: updated meta-analysis

Abstract: Objective To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status. Design Updated meta-analysis of randomised trials. Data sources Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006. Studies reviewed Double blind randomised placebo controlled trials of approved anti-obesity dugs used in adults (age over 18) for one year or longer. Results 30 trials of one to four years’ duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine lowered concentrations of high density lipoprotein cholesterol and triglycerides but raised blood pressure and pulse rate. Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders. Conclusions Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

The relationship between nursing leadership and patient outcomes: a systematic review update

Abstract: Aim Our aim was to describe the findings of a systematic review of studies that examine the relationship between nursing leadership practices and patient outcomes. Background As healthcare faces an economic downturn, stressful work environments, upcoming retirements of leaders and projected workforce shortages, implementing strategies to ensure effective leadership and optimal patient outcomes are paramount. However, a gap still exists in what is known about the association between nursing leadership and patient outcomes. Methods Published English-only research articles that examined leadership practices of nurses in formal leadership positions and patient outcomes were selected from eight online bibliographic databases. Quality assessments, data extraction and analysis were completed on all included studies. Results A total of 20 studies satisfied our inclusion criteria and were retained. Current evidence suggests relationships between positive relational leadership styles and higher patient satisfaction and lower patient mortality, medication errors, restraint use and hospital-acquired infections. Conclusions The findings document evidence of a positive relationship between relational leadership and a variety of patient outcomes, although future testing of leadership models that examine the mechanisms of influence on outcomes is warranted. Implications for nursing management Efforts by organisations and individuals to develop transformational and relational leadership reinforces organisational strategies to improve patient outcomes.

Special Paper: Adakite-Like Rocks: Their Diverse Origins and Questionable Role in Metallogenesis

Abstract: Based on a compilation of published sources, rocks referred to as adakites show the following geochemical and isotopic characteristics: SiO2 ≥56 wt percent, Al2O3 ≥15 wt percent, MgO normally <3 wt percent, Mg number ≈0.5, Sr ≥400 ppm, Y ≤18 ppm, Yb ≤1.9 ppm, Ni ≥20 ppm, Cr ≥30 ppm, Sr/Y ≥20, La/Yb ≥20, and 87Sr/86Sr ≤0.7045. Rocks with such compositions have been interpreted to be the products of hybridization of felsic partial melts from subducting oceanic crust with the peridotitic mantle wedge during ascent and are not primary magmas. High Mg andesites have been interpreted to be related to adakites by partial melting of asthenospheric peridotite contaminated by slab melts. The case for these petrogenetic models for adakites and high Mg andesites is best made in the Archean, when higher mantle geotherms resulted in subducting slabs potentially reaching partial melting temperatures at shallow depths before dehydration rendered the slab infusible. In the Phanerozoic these conditions were likely only met under certain special tectonic conditions, such as subduction of young (≤25-m.y.-old) oceanic crust. Key adakitic geochemical signatures, such as low Y and Yb concentrations and high Sr/Y and La/Yb ratios, can be generated in normal asthenosphere-derived tholeiitic to calc-alkaline arc magmas by common upper plate crustal interaction and crystal fractionation processes and do not require slab melting. An assessment of several arc volcanic suites from around the world shows that most adakite-like compositions are generated in this way and do not reflect source processes. Similarly, rare adakite-like intrusive rocks associated with some porphyry Cu deposits are the evolved products of extensive crustal-level processing of calc-alkaline basalt-andesite-dacite-rhyolite series magmas. If slab melts contribute to such magmas, their geochemical signatures would have been obliterated or rendered ambiguous by subsequent extensive open-system processes. In Archean terranes, where adakitic and high Al tonalite-trondhjemite-granodiorite (TTG) magma series rocks are more common, porphyry Cu deposits are rare and, where found, are associated with normal calc-alkaline suites rather than adakites. The two different magma series are compositionally distinct in terms of several major and trace element parameters. Common upper plate magmatic processes such as melting-assimilation-storage-homogenization (MASH) and assimilation-fractional-crystallization (AFC) affecting normal arc magmas can be demonstrated to explain the distinctive compositions of most adakite-like arc rocks, including high Mg andesites and especially those rare examples associated with porphyry Cu deposits. In contrast, slab melting can in most cases neither be proved nor disproved and is therefore unsatisfactory as a unique factor in porphyry Cu genesis.

Institutional Rationality and Practice Variation: New Directions in the Institutional Analysis of Practice

Abstract: In this paper, I highlight how popular understandings of neoinstitutionalism as a theory of isomorphism need to be revised as institutionalists have shifted attention towards the study of organizational heterogeneity. As part of this shift, old emphases on arational mimicry and stability have been replaced with new emphases on institutional rationality and ongoing struggle and change. I discuss these new directions and the implications for the study of accounting practice. I argue that given recent efforts by institutionalists to account for actors and practice diversity, there is an important opportunity for dialogue with practice theorists, such as those drawing on Actor Network Theory, and the creation of a more comprehensive approach to the study of practice that attends to both institutional and micro-processual dynamics.

Navigating sites for narrative inquiry

Abstract: Narrative inquiry is a methodology that frequently appeals to teachers and teacher educators. However, this appeal and sense of comfort has advantages and disadvantages. Some assume narrative inquiries will be easy to design, live out, and represent in storied formats in journals, dissertations, or books. For the authors, though, narrative inquiry is much more than the telling of stories. There are complexities surrounding all phases of a narrative inquiry and, in this article, the authors pay particular attention to thinking about the design of narrative inquiries that focus on teachers’ and teacher educators’ own practices. They outline three commonplaces and eight design elements for consideration in narrative inquiry. They illustrate these elements using recently completed narrative inquiries. In this way, the authors show the complex dimensions of narrative inquiry, a kind of inquiry that requires particular kinds of wakefulness.

NXY-059 for the Treatment of Acute Ischemic Stroke

Abstract: Background The free-radical–trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke–Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke We sought confirmation of efficacy in a second, larger trial Methods We enrolled 3306 patients with acute ischemic stroke in a randomized, double-blind trial to receive a 72-hour infusion of intravenous NXY-059 or placebo within 6 hours after the onset of stroke symptoms Our primary end point was the distribution of disability scores on the modified Rankin scale at 90 days We examined scores on neurologic and activities-of-daily-living scales as secondary end points We also tested the hypothesis that NXY-059 would reduce alteplase-related intracranial hemorrhages Results The efficacy analysis was based on 3195 patients Prognostic factors were well balanced between the treatment groups Mortality was equal in the two groups, and adverse-event rates were similar The distribution of

Septic Acute Kidney Injury in Critically Ill Patients: Clinical Characteristics and Outcomes

Abstract: Sepsis is the most common cause of acute kidney injury (AKI) in critical illness, but there is limited information on septic AKI. A prospective, observational study of critically ill patients with septic and nonseptic AKI was performed from September 2000 to December 2001 at 54 hospitals in 23 countries. A total of 1753 patients were enrolled. Sepsis was considered the cause in 833 (47.5%); the predominant sources of sepsis were chest and abdominal (54.3%). Septic AKI was associated with greater aberrations in hemodynamics and laboratory parameters, greater severity of illness, and higher need for mechanical ventilation and vasoactive therapy. There was no difference in enrollment kidney function or in the proportion who received renal replacement therapy (RRT; 72 versus 71%; P = 0.83). Oliguria was more common in septic AKI (67 versus 57%; P < 0.001). Septic AKI had a higher in-hospital case-fatality rate compared with nonseptic AKI (70.2 versus 51.8%; P < 0.001). After adjustment for covariates, septic AKI remained associated with higher odds for death (1.48; 95% confidence interval 1.17 to 1.89; P = 0.001). Median (IQR) duration of hospital stay for survivors (37 [19 to 59] versus 21 [12 to 42] d; P < 0.0001) was longer for septic AKI. There was a trend to lower serum creatinine (106 [73 to 158] versus 121 [88 to 184] mumol/L; P = 0.01) and RRT dependence (9 versus 14%; P = 0.052) at hospital discharge for septic AKI. Patients with septic AKI were sicker and had a higher burden of illness and greater abnormalities in acute physiology. Patients with septic AKI had an increased risk for death and longer duration of hospitalization yet showed trends toward greater renal recovery and independence from RRT.

A checklist for ecological management of landscapes for conservation

Abstract: The management of landscapes for biological conservation and ecologically sustainable natural resource use are crucial global issues. Research for over two decades has resulted in a large literature, yet there is little consensus on the applicability or even the existence of general principles or broad considerations that could guide landscape conservation. We assess six major themes in the ecology and conservation of landscapes. We identify 13 important issues that need to be considered in developing approaches to landscape conservation. They include recognizing the importance of landscape mosaics (including the integration of terrestrial and aquatic areas), recognizing interactions between vegetation cover and vegetation configuration, using an appropriate landscape conceptual model, maintaining the capacity to recover from disturbance and managing landscapes in an adaptive framework. These considerations are influenced by landscape context, species assemblages and management goals and do not translate directly into on-the-ground management guidelines but they should be recognized by researchers and resource managers when developing guidelines for specific cases. Two crucial overarching issues are: (i) a clearly articulated vision for landscape conservation and (ii) quantifiable objectives that offer unambiguous signposts for measuring progress.

Telemonitoring or structured telephone support programmes for patients with chronic heart failure: systematic review and meta-analysis

Abstract: Objective To determine whether remote monitoring (structured telephone support or telemonitoring) without regular clinic or home visits improves outcomes for patients with chronic heart failure Data sources 15 electronic databases, hand searches of previous studies, and contact with authors and experts Data extraction Two investigators independently screened the results Review methods Published randomised controlled trials comparing remote monitoring programmes with usual care in patients with chronic heart failure managed within the community Results 14 randomised controlled trials (4264 patients) of remote monitoring met the inclusion criteria: four evaluated telemonitoring, nine evaluated structured telephone support, and one evaluated both Remote monitoring programmes reduced the rates of admission to hospital for chronic heart failure by 21% (95% confidence interval 11% to 31%) and all cause mortality by 20% (8% to 31%); of the six trials evaluating health related quality of life three reported significant benefits with remote monitoring, and of the four studies examining healthcare costs with structured telephone support three reported reduced cost and one no effect Conclusion Programmes for chronic heart failure that include remote monitoring have a positive effect on clinical outcomes in community dwelling patients with chronic heart failure

New Results on Stability of Discrete-Time Systems With Time-Varying State Delay

Abstract: This note is concerned with the stability analysis of discrete-time systems with time-varying state delay. By defining new Lyapunov functions and by making use of novel techniques to achieve delay dependence, several new conditions are obtained for the asymptotic stability of these systems. The merit of the proposed conditions lies in their less conservativeness, which is achieved by circumventing the utilization of some bounding inequalities for cross products between two vectors and by paying careful attention to the subtle difference between the terms Sigmam=k-dk k-1(middot) and Sigma m=k-dM k-1(middot), which is largely ignored in the existing literature. These conditions are shown, via several examples, to be much less conservative than some existing result

Heterochrony and allometry: the analysis of evolutionary change in ontogeny

Abstract: The connection between development and evolution has become the focus of an increasing amount of research in recent years, and heterochrony has long been a key concept in this relation. Heterochrony is defined as evolutionary change in rates and timing of developmental processes; the dimension of time is therefore an essential part in studies of heterochrony. Over the past two decades, evolutionary biologists have used several methodological frameworks to analyse heterochrony, which differ substantially in the way they characterize evolutionary changes in ontogenies and in the resulting classification, although they mostly use the same terms. This review examines how these methods compare ancestral and descendant ontogenies, emphasizing their differences and the potential for contradictory results from analyses using different frameworks. One of the two principal methods uses a clock as a graphical display for comparisons of size, shape and age at a particular ontogenic stage, whereas the other characterizes a developmental process by its time of onset, rate, and time of cessation. The literature on human heterochrony provides particularly clear examples of how these differences produce apparent contradictions when applied to the same problem. Developmental biologists recently have extended the concept of heterochrony to the earliest stages of development and have applied it at the cellular and molecular scale. This extension brought considerations of developmental mechanisms and genetics into the study of heterochrony, which previously was based primarily on phenomenological characterizations of morphological change in ontogeny. Allometry is the pattern of covariation among several morphological traits or between measures of size and shape; unlike heterochrony, allometry does not deal with time explicitly. Two main approaches to the study of allometry are distinguished, which differ in the way they characterize organismal form. One approach defines shape as proportions among measurements, based on considerations of geometric similarity, whereas the other focuses on the covariation among measurements in ontogeny and evolution. Both are related conceptually and through the use of similar algebra. In addition, there are close connections between heterochrony and changes in allometric growth trajectories, although there is no one-to-one correspondence. These relationships and outline links between different analytical frameworks are discussed.

Do the stories they tell get them the money they need? the role of entrepreneurial narratives in resource acquisition

Abstract: Adopting a narrative approach to resource acquisition research, we examine the effects of storytelling on a firm’s ability to secure capital. We argue that narratives help leverage resources by conveying a comprehensible identity for an entrepreneurial firm, elaborating the logic behind proposed means of exploiting opportunities and embedding entrepreneurial endeavors within broader discourses. Qualitative analyses of all 1996–2000 initial public offering prospectuses in three high-tech industries reveal how identity constructions, story elaboration, and contextual embedding are invoked within narratives. Our quantitative findings show how these aspects of an entrepreneurial narrative impact resource acquisition net of previously emphasized factors.

Contribution of SHANK3 Mutations to Autism Spectrum Disorder

Abstract: Mutations in SHANK3, which encodes a synaptic scaffolding protein, have been described in subjects with an autism spectrum disorder (ASD). To assess the quantitative contribution of SHANK3 to the pathogenesis of autism, we determined the frequency of DNA sequence and copy-number variants in this gene in 400 ASD-affected subjects ascertained in Canada. One de novo mutation and two gene deletions were discovered, indicating a contribution of 0.75% in this cohort. One additional SHANK3 deletion was characterized in two ASD-affected siblings from another collection, which brings the total number of published mutations in unrelated ASD-affected families to seven. The combined data provide support that haploinsufficiency of SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing.