Beyond mobile phone displays: Flat panel display technology for biomedical applications

Organ-on-Chips (OoCs) have emerged as a human-specific experimental platform for preclinical research and therapeutics testing that will reduce the cost of pre-clinical drug development, provide better physiological relevance and replace animal testing. Yet, the lack of standardization and cost-effective fabrication technologies can hamper wide-spread adoption of OoCs. In this work we validate the use of flat panel display (FPD) technology as an enabling and cost-effective technology platform for biomedical applications by demonstrating facile integration of key OoC modules like microfluidics and micro electrode arrays (MEAs) in the standardized 96-well plate format. Individual and integrated modules were tested for their biological applicability in OoCs. For microelectrode arrays we demonstrate 90–95% confluency, 3 days after cell seeding and >70% of the initial mitochondrial cell activity for microfluidic devices. Thus highlighting the biocompatibility of these modules fabricated using FPD technology. Furthermore, we provide two examples of monolithically integrated microfluidics and microelectronics, i.e. integrated electronic valves and integrated MEAs, that showcase the strength of FPD technology applied to biomedical device fabrication. Finally, the merits and opportunities provided by FPD technology are discussed through examples of advanced structures and functionalities that are unique to this enabling platform

2,4-Dinitrophenol, the inferno drug: a netnographic study of user experiences in the quest for leanness.

Background: Despite not being licensed for human consumption, the Internet has triggered renewed, widespread interest and availability of 2,4-Dinitrophenol (DNP). DNP, a cellular metabolic poison, causes thermogenesis resulting in fat burning and weight loss. Whilst extensively available for purchase online, research on user experiences of DNP is limited. Methods: A netnographic approach was used to describe user experiences of DNP via online public websites. Public websites discussing DNP were identified and a purposeful sample selected. Discussion threads were downloaded and a textual qualitative analysis conducted. Four themes containing 71 categories were generated. Results: There exists a plethora of communal folk pharmacological advice and recommendations for DNP manufacture and use, together with associated harms and outcomes. The efficacy and untoward effects of DNP were described and discussed alongside the notion that DNP should only be used by experienced bodybuilders. Dosage and regimes for optimal use were also described. Conclusion: This unique study provides a rich examination of the knowledge, attitudes, and motivations of DNP users, illustrating the significant role of online public websites in sharing information. Further understanding of DNP users and the online communities in which they reside is warranted to facilitate engagement and formulate appropriate and effective policy responses

Evolutionary genetic dissection of human interferons

As revealed by population genetic analyses, different human interferon genes evolved under distinct selective constraints and signatures of positive selection vary according to geographic region, suggesting that some sequence changes may have conferred an advantage by increasing resistance to viral infection

Copernicus Marine Service Ocean State Report

This is the final version. Available from Taylor & Francis via the DOI in this record

Genetic Variation in the HSD17B1 Gene and Risk of Prostate Cancer

Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17β-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Δ5-androsterone-3β,17β-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites

Plutonic foundation of a slow-spreading ridge segment : oceanic core complex at Kane Megamullion, 23°30′N, 45°20′W

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q05014, doi:10.1029/2007GC001645.We mapped the Kane megamullion, an oceanic core complex on the west flank of the Mid-Atlantic Ridge exposing the plutonic foundation of a ∼50 km long, second-order ridge segment. The complex was exhumed by long-lived slip on a normal-sense detachment fault at the base of the rift valley wall from ∼3.3 to 2.1 Ma (Williams, 2007). Mantle peridotites, gabbros, and diabase dikes are exposed in the detachment footwall and in outward facing high-angle normal fault scarps and slide-scar headwalls that cut through the detachment. These rocks directly constrain crustal architecture and the pattern of melt flow from the mantle to and within the lower crust. In addition, the volcanic carapace that originally overlay the complex is preserved intact on the conjugate African plate, so the complete internal and external architecture of the paleoridge segment can be studied. Seafloor spreading during formation of the core complex was highly asymmetric, and crustal accretion occurred largely in the footwall of the detachment fault exposing the core complex. Because additions to the footwall, both magmatic and amagmatic, are nonconservative, oceanic detachment faults are plutonic growth faults. A local volcano and fissure eruptions partially cover the northwestern quarter of the complex. This volcanism is associated with outward facing normal faults and possible, intersecting transform-parallel faults that formed during exhumation of the megamullion, suggesting the volcanics erupted off-axis. We find a zone of late-stage vertical melt transport through the mantle to the crust in the southern part of the segment marked by a ∼10 km wide zone of dunites that likely fed a large gabbro and troctolite intrusion intercalated with dikes. This zone correlates with the midpoint of a lineated axial volcanic high of the same age on the conjugate African plate. In the central region of the segment, however, primitive gabbro is rare, massive depleted peridotite tectonites abundant, and dunites nearly absent, which indicate that little melt crossed the crust-mantle boundary there. Greenschist facies diabase and pillow basalt hanging wall debris are scattered over the detachment surface. The diabase indicates lateral melt transport in dikes that fed the volcanic carapace away from the magmatic centers. At the northern edge of the complex (southern wall of the Kane transform) is a second magmatic center marked by olivine gabbro and minor troctolite intruded into mantle peridotite tectonite. This center varied substantially in size with time, consistent with waxing and waning volcanism near the transform as is also inferred from volcanic abyssal-hill relief on the conjugate African plate. Our results indicate that melt flow from the mantle focuses to local magmatic centers and creates plutonic complexes within the ridge segment whose position varies in space and time rather than fixed at a single central point. Distal to and between these complexes there may not be continuous gabbroic crust, but only a thin carapace of pillow lavas overlying dike complexes laterally fed from the magmatic centers. This is consistent with plate-driven flow that engenders local, stochastically distributed transient instabilities at depth in the partially molten mantle that fed the magmatic centers. Fixed boundaries, such as large-offset fracture zones, or relatively short segment lengths, however, may help to focus episodes of repeated melt extraction in the same location. While no previous model for ocean crust is like that inferred here, our observations do not invalidate them but rather extend the known diversity of ridge architecture.NSF Grants OCE-0118445, OCE-0624408 and OCE-0621660 supported this research. B. Tucholke was also supported by the Henry Bryant Bigelow Chair in Oceanography at Woods Hole Oceanographic Institution

Baby Business: a randomised controlled trial of a universal parenting program that aims to prevent early infant sleep and cry problems and associated parental depression

<p>Abstract</p> <p>Background</p> <p>Infant crying and sleep problems (e.g. frequent night waking, difficulties settling to sleep) each affect up to 30% of infants and often co-exist. They are costly to manage and associated with adverse outcomes including postnatal depression symptoms, early weaning from breast milk, and later child behaviour problems. Preventing such problems could improve these adverse outcomes and reduce costs to families and the health care system. Anticipatory guidance-i.e. providing parents with information about normal infant sleep and cry patterns, ways to encourage self-settling in infants, and ways to develop feeding and settling routines <it>before </it>the onset of problems-could prevent such problems. This paper outlines the protocol for our study which aims to test an anticipatory guidance approach.</p> <p>Methods/Design</p> <p>750 families from four Local Government Areas in Melbourne, Australia have been randomised to receive the <it>Baby Business </it>program (intervention group) or usual care (control group) offered by health services. The <it>Baby Business </it>program provides parents with information about infant sleep and crying via a DVD and booklet (mailed soon after birth), telephone consultation (at infant age 6-8 weeks) and parent group session (at infant age 12 weeks). All English speaking parents of healthy newborn infants born at > 32 weeks gestation and referred by their maternal and child health nurse at their first post partum home visit (day 7-10 postpartum), are eligible. The primary outcome is parent report of infant night time sleep as a problem at four months of age and secondary outcomes include parent report of infant daytime sleep or crying as a problem, mean duration of infant sleep and crying/24 hours, parental depression symptoms, parent sleep quality and quantity and health service use. Data will be collected at two weeks (baseline), four months and six months of age. An economic evaluation using a cost-consequences approach will, from a societal perspective, compare costs and health outcomes between the intervention and control groups.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of a program which aims to prevent both infant sleeping and crying problems and associated postnatal depression symptoms. If effective, it could offer an important public health prevention approach to these common, distressing problems.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN63834603">ISRCTN63834603</a></p

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations

<p>Abstract</p> <p>Background</p> <p>Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations.</p> <p>Results</p> <p>We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations.</p> <p>Conclusion</p> <p>These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.</p

A review of friction models in interacting joints for durability design.

This paper presents a comprehensive review of friction modelling to provide an understanding of design for durability within interacting systems. Friction is a complex phenomenon and occurs at the interface of two components in relative motion. Over the last several decades, the effects of friction and its modelling techniques have been of significant interests in terms of industrial applications. There is however a need to develop a unified mathematical model for friction to inform design for durability within the context of varying operational conditions. Classical dynamic mechanisms model for the design of control systems has not incorporated friction phenomena due to non-linearity behaviour. Therefore, the tribological performance concurrently with the joint dynamics of a manipulator joint applied in hazardous environments needs to be fully analysed. Previously the dynamics and impact models used in mechanical joints with clearance have also been examined. The inclusion of reliability and durability during the design phase is very important for manipulators which are deployed in harsh environmental and operational conditions. The revolute joint is susceptible to failures such as in heavy manipulators these revolute joints can be represented by lubricated conformal sliding surfaces. The presence of pollutants such as debris and corrosive constituents has the potential to alter the contacting surfaces, would in turn affect the performance of revolute joints, and puts both reliability and durability of the systems at greater risks of failure. Key literature is identified and a review on the latest developments of the science of friction modelling is presented here. This review is based on a large volume of knowledge. Gaps in the relevant field have been identified to capitalise on for future developments. Therefore, this review will bring significant benefits to researchers, academics and industrial professionals