A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. Methods an design: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and precancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. Discussion: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

Earliest evidence for the ivory trade in southern Africa : isotopic and ZooMS analysis of seventh-tenth century AD ivory from KwaZulu-Natal

KwaGandaganda, Ndondondwane and Wosi were major Early Farming Community settlements in what is today the KwaZulu-Natal province of South Africa. These sites have yielded, among other remains, abundant evidence of ivory and ivory working dating to the seventh–tenth centuries ad, pre-dating by approximately 200 years the better-known ivory artefacts from sites in the Limpopo River Valley and surrounding regions. We report the results of carbon, nitrogen and strontium isotope analysis to explore the origins and procurement of this ivory, in combination with Zooarchaeology by Mass Spectrometry (ZooMS) to identify the species of animals from which it was derived. All of the ivory studied using ZooMS was elephant, despite the presence of hippopotamus remains on all three sites. Some ivory was probably obtained from elephant herds that lived close to the sites, in the densely wooded river valleys favoured by both elephants and early farmers. Other material came from savannah environments further afield. Ivory found at these three sites was drawn from different catchments, implying a degree of landscape/resource partitioning even at this early stage. These communities clearly invested substantial effort in obtaining ivory from across the region, which speaks to the importance of this commodity in the economy of the time. We suggest that some ivory items were for local use, but that some may have been intended for more distant markets via Indian Ocean trade

Surgical management of children and young adults with the Wolff-Parkinson-White syndrome

The Wolff-Parkinson-White syndrome, as originally described, includes palpitations, tachycardia, and an abnormal electrocardiogram (short PR interval and wide QRS complex). The clinical manifestations are dependent upon a reentrant tachycardia supported by an accessory connection bridging the atrioventricular junction and frequently appear during the first two decades of life. Palpitations are the usual symptoms; less frequently, severe symptoms, such as syncope and sudden death, may result from very rapid atrioventricular conduction across the accessory connection during atrial fibrillation. We report the surgical management of 30 young patients with this syndrome, including 6 with life-threatening tachycardia. Surgical interruption of the accessory connection(s) was curative in 90% (27/30) of the patients; life-threatening symptoms were eliminated in the other three. Based on the limited knowledge of the natural history of the Wolff-Parkinson-White syndrome, the individual patient symptoms, and the electrophysiologic properties of each patient's accessory pathway(s), an algorithm is presented outlining the treatment options. This experience strongly suggests that surgical treatment of the Wolff-Parkinson-White syndrome is safe, effective, and possibly the preferred treatment for this disorder in selected young symptomatic patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41585/1/380_2005_Article_BF02058591.pd

Assessing human diet and movement in the Tongan maritime chiefdom using isotopic analyses.

The rise of stratified societies fundamentally influences the interactions between status, movement, and food. Using isotopic analyses, we assess differences in diet and mobility of individuals excavated from two burial mounds located at the `Atele burial site on Tongatapu, the main island of the Kingdom of Tonga (c. 500 - 150 BP). The first burial mound (To-At-1) was classified by some archaeologists as a commoner's mound while the second burial mound (To-At-2) was possibly used for interment of the chiefly class. In this study, stable isotope analyses of diet (δ13C, δ15N, and δ34S; n = 41) are used to asses paleodiet and 87Sr/86Sr ratios (n = 30) are analyzed to investigate individual mobility to test whether sex and social status affected these aspects of life. Our results show significant differences in diet between burial mounds and sexes. Those interred in To-At-2 displayed lower δ13C values, indicating they ate relatively more terrestrial plants (likely starchy vegetable staples) compared with To-At-1 individuals. Females displayed significantly lower δ15N values compared with males within the entire assemblage. No differences in δ34S values were observed between sexes or burial mound but it is possible that sea spray or volcanism may have affected these values. One individual displayed the strontium isotopic composition representative of a nonlocal immigrant (outside 2SD of the mean). This suggests the hegemonic control over interisland travel, may have prevented long-term access to the island by non-Tongans exemplifying the political and spiritual importance of the island of Tongatapu in the maritime chiefdom