Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10 -7. In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10 -11) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10 -11). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10 -7) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10 -7); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.

Colonoscopy preparation in children: Safety, efficacy, and tolerance of high- versus low-volume cleansing methods

Background: The use of large-volume electrolyte balanced solutions as preparation for colonoscopy often results in poor patient compliance and acceptance. The tolerance, safety, and efficacy of high-versus low volume colon-cleansing methods as preparation for colonoscopy in children were compared by randomized operator-blinded trial. Methods: Twenty-nine children ages 3.6-14.6 years had either high-volume nasogastric balanced polyethylene glycol electrolyte lavage (20 ml/kg/h) until the effluent was clear (n = 15), or two oral doses of sodium phosphate solution (22.5-45 ml) separated by oral fluid intake (n = 14). Results: Both preparations were equally effective. The low-volume preparation was better tolerated and caused less discomfort that the high-volume preparation, judging by serial nurse observations. The incidence of abdominal symptoms, diarrhea, sleep disturbance, and vomiting was not significantly different between the two groups. Both groups had a small reduction in mean hematocrit and serum calcium levels. The sodium phosphate preparation caused increases in mean serum sodium concentrations from 140 to 145 mmol/L and serum phosphate concentrations from 1.41 to 2.53 mmol/L. Ten hours after the commencement of the preanesthetic fast, these concentrations had returned to normal. Conclusions: There are advantages in terms of tolerance, discomfort, and case of administration with acceptable colonic cleansing with the use of the less-invasive oral sodium phosphate low-volume colon-cleansing preparation in children. Safe use requires ensuring an adequate oral fluid intake during the preparation time and avoidance of use in patients with renal insufficiency.

Solid volume fraction estimation of bone:marrow replica models using ultrasound transit time spectroscopy

The acceptance of broadband ultrasound attenuation (BUA) for the assessment of osteoporosis suffers from a limited understanding of both ultrasound wave propagation through cancellous bone and its exact dependence upon the material and structural properties. It has recently been proposed that ultrasound wave propagation in cancellous bone may be described by a concept of parallel sonic rays; the transit time of each ray defined by the proportion of bone and marrow propagated. A Transit Time Spectrum (TTS) describes the proportion of sonic rays having a particular transit time, effectively describing the lateral inhomogeneity of transit times over the surface aperture of the receive ultrasound transducer. The aim of this study was to test the hypothesis that the solid volume fraction (SVF) of simplified bone:marrow replica models may be reliably estimated from the corresponding ultrasound transit time spectrum. Transit time spectra were derived via digital deconvolution of the experimentally measured input and output ultrasonic signals, and compared to predicted TTS based on the parallel sonic ray concept, demonstrating agreement in both position and amplitude of spectral peaks. Solid volume fraction was calculated from the TTS; agreement between true (geometric calculation) with predicted (computer simulation) and experimentally-derived values were R2=99.9% and R2=97.3% respectively. It is therefore envisaged that ultrasound transit time spectroscopy (UTTS) offers the potential to reliably estimate bone mineral density and hence the established T-score parameter for clinical osteoporosis assessment.

Effects of the sensorimotor training volume on sensorimotor function in patients following lower limb arthroplasty

Background Sensorimotor function is degraded in patients after lower limb arthroplasty. Sensorimotor training is thought to improve sensorimotor skills, however, the optimal training stimulus with regard to volume, frequency, duration, and intensity is still unknown. The aim of this study, therefore, was to firstly quantify the progression of sensorimotor function after total hip (THA) or knee (TKA) arthroplasty and, as second step, to evaluate effects of different sensorimotor training volumes. Methods 58 in-patients during their rehabilitation after THA or TKA participated in this prospective cohort study. Sensorimotor function was assessed using a test battery including measures of stabilization capacity, static balance, proprioception, and gait, along with a self-reported pain and function. All participants were randomly assigned to one of three intervention groups performing sensorimotor training two, four, or six times per week. Outcome measures were taken at three instances, at baseline (pre), after 1.5 weeks (mid) and at the conclusion of the 3 week program (post). Results All measurements showed significant improvements over time, with the exception of proprioception and static balance during quiet bipedal stance which showed no significant main effects for time or intervention. There was no significant effect of sensorimotor training volume on any of the outcome measures. Conclusion We were able to quantify improvements in measures of dynamic, but not static, sensorimotor function during the initial three weeks of rehabilitation following TKA/THA. Although sensorimotor improvements were independent of the training volume applied in the current study, long-term effects of sensorimotor training volume need to be investigated to optimize training stimulus recommendations.

Reconciling transport models across scales: The role of volume exclusion

Diffusive transport is a universal phenomenon, throughout both biological and physical sciences, and models of diffusion are routinely used to interrogate diffusion-driven processes. However, most models neglect to take into account the role of volume exclusion, which can significantly alter diffusive transport, particularly within biological systems where the diffusing particles might occupy a significant fraction of the available space. In this work we use a random walk approach to provide a means to reconcile models that incorporate crowding effects on different spatial scales. Our work demonstrates that coarse-grained models incorporating simplified descriptions of excluded volume can be used in many circumstances, but that care must be taken in pushing the coarse-graining process too far.

Sequence variants in three loci influence monocyte counts and erythrocyte volume

Blood cells participate in vital physiological processes, and their numbers are tightly regulated so that homeostasis is maintained. Disruption of key regulatory mechanisms underlies many blood-related Mendelian diseases but also contributes to more common disorders, including atherosclerosis. We searched for quantitative trait loci (QTL) for hematology traits through a whole-genome association study, because these could provide new insights into both hemopoeitic and disease mechanisms. We tested 1.8 million variants for association with 13 hematology traits measured in 6015 individuals from the Australian and Dutch populations. These traits included hemoglobin composition, platelet counts, and red blood cell and white blood cell indices. We identified three regions of strong association that, to our knowledge, have not been previously reported in the literature. The first was located in an intergenic region of chromosome 9q31 near LPAR1, explaining 1.5% of the variation in monocyte counts (best SNP rs7023923, p=8.9x10(-14)). The second locus was located on chromosome 6p21 and associated with mean cell erythrocyte volume (rs12661667, p=1.2x10(-9), 0.7% variance explained) in a region that spanned five genes, including CCND3, a member of the D-cyclin gene family that is involved in hematopoietic stem cell expansion. The third region was also associated with erythrocyte volume and was located in an intergenic region on chromosome 6q24 (rs592423, p=5.3x10(-9), 0.6% variance explained). All three loci replicated in an independent panel of 1543 individuals (p values=0.001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Editorial of "International Journal of Critical Indigenous Studies Volume 1, Number 1, 2008"

We perceive the epistemological boundaries of Critical Indigenous Studies as marked by analyses of contemporary colonising power in its multiple forms in different contexts. This first issue brings together a diverse group of international Indigenous scholars who are politically and intellectually engaged in theorising from their respective standpoints as well as spatial and geographic locations. As such these essays enable dialogue across and within different colonial power contexts addressing epistemological ethical and methodological concerns within the broad field of Indigenous studies. In each essay a connecting theme is the need for intercultural and comparative work and to import Indigenous agency in the writing of history...

Editorial of "International Journal of Critical Indigenous Studies Volume 2, Number 1, 2009"

Over the past two decades neo liberalism has shaped global economic activity. The international reach of the current economic crisis propelled by the subprime mortgage meltdown in the United States has affected Indigenous communities in different ways to those whose investments were depleted by the Wall Street activities of an unregulated corporate and banking sector. Throughout this roller coaster economic ride the low socio-economic position of Indigenous peoples continued in Canada, the United States of America, New Zealand, Hawaii and Australia. The logic, or illogic of capital, failed to extend the boom of the economic upturn to Indigenous peoples, but is poised to extend the repercussions of the current downturn deep into Indigenous lives. The consistency of the Indigenous socio-economic position across these countries, even where treaties exist, indicates that the phenomenon is based on a shared Indigenous reality. In this special edition, the commonality in the way in which Indigenous people are engaged in and positioned by market forces and regulation by their respective nation states is proposed as one of the foundation plates of that Indigenous positioning...

Editorial of "International Journal of Critical Indigenous Studies Volume 2, Number 2, 2009"

This edition of the International Critical Indigenous Studies Journal, our second for 2009 takes alternative understandings as its theme. All four articles in this edition attend to citizenship and Indigenous sovereignty though in different ways...

Editorial of "International Journal of Critical Indigenous Studies Volume 3, Number 1, 2010"

The articles in this edition of the International Journal of Critical Indigenous Studies engage collectively with how different epistemologies and cultural values inform power relations in different locations, situations and contemporary contexts. As a group, these articles demonstrate, over varying facets, how meaning, communicative intent and interpretive effect are constitutive of power relations between Indigenous people and non Indigenous people. Jackie Grey discusses the labour of belonging as played out in a dispute over Indigenous fishing rights in a small New England town of Aquinnah, located on Noepe Island the traditional lands of the Wampanoag in the United States of America. She reveals the ways in which the jurisdiction of non Indigenous belonging operates discursively and materially to preclude Indigenous rights and self determination. Grey's analysis highlights the incommensurability of Indigenous and non Indigenous belonging that are played out in power relations born of colonisation.

Editorial of "International Journal of Critical Indigenous Studies Volume 3, Number 2, 2010"

In this of the International Journal of Critical Indigenous Studies, the articles reveal how competing economies of knowledge, capital and values are operationalised through colonising power within inter-subjective relations. Writing in the Australian context, Greg Blyton demonstrates how tobacco was used by colonists as a means of control and exchange in their relations with Indigenous people. He focuses on the Hunter region of New South Wales, Australia, in the early to mid-nineteenth century to reveal how colonists exchanged tobacco for food, safe passage and Indigenous services. Blyton suggests that these colonial practices enabled tobacco addiction to spread throughout the region, passing from one generation of Indigenous people to another. He asks us to consider the link between the colonial generation of Indigenous tobacco consumption and addiction, and Indigenous mortality rates today whereby twenty percent of deaths are attributed to smoking.

Editorial of "International Journal of Critical Indigenous Studies Volume 4, Number 1, 2011"

This special edition of the International Journal of Critical Indigenous Studies highlights the work of emerging scholars in the field of Indigenous Studies. The five featured authors were all finalists for the prize awarded by the Native American and Indigenous Studies Association (NAISA) to the best post-graduate student paper at the NAISA meeting held in 2010 in Tucson, Arizona. While the breadth of scholarship encompassed by the term ‘Indigenous Studies’ and the global representation of Indigenous peoples at NAISA mean that the topics and approaches vary widely, a common thematic of fraught post-colonial relations can be discerned within all five articles.

Editorial of "International Journal of Critical Indigenous Studies Volume 5, Number 1, 2012"

The first two articles of this edition of the journal testify to the lengthening reach of the discipline of Critical Indigenous Studies that is, remarkably, still in its nascence. Emiel Martens examines the development of Maori filmmaking since the 1980s and takes the opportunity to explore this Indigenous cinema in the context of developments in the New Zealand film industry generally. Shifting from cultural production to renewable energy, Steven M. Hoffman and Thibault Martin remind us that in the effort to satiate the demands for energy, it is often Indigenous peoples who bear adverse consequences. Using a social capital framework, the authors examine the impact of the development of hydroelectric power upon a displaced Aboriginal community and conclude that displacement has resulted in an erosion of cohesive social bonds that once ensured a sustainable way of life.

Editorial of "International Journal of Critical Indigenous Studies, Volume 5, Number 2, 2012"

This edition is marked by a strong Antipodean focus. The first three articles bring a critical Indigenous perspective to areas previously cosseted by Western understandings. Robyn Moore, using critical discourse analysis, takes Australian Prime Minister Julia Gillard’s 2011 ‘Closing the Gap’ speech to task for naturalising Indigenous Australia’s position on the wrong side of the social and economic ‘gap’. She argues that, far from accepting white culpability, Gillard instead polishes cultural deficit understandings of Indigenous disadvantage by framing the social and economic divide in meritocratic terms. In so doing, Moore further argues, Gillard casts a benevolent light upon white Australia.