Development and validation of an automated thawing and mixing workcell

Journal ArticleWorking toward a goal of total laboratory automation, we are automating manual activities in our highest volume laboratory section. Because half of all specimens arriving in this laboratory section are frozen, we began by developing an automated workcell for thawing frozen specimens and mixing the thawed specimens to remove concentration gradients resulting from freezing and thawing

Plant and Insect Fossils from the Mayo Indian Village Section (Central Yukon): New Data on Middle Wisconsinan Environments and Glaciation

The Mayo Indian Village Section in central Yukon contains the Mayo Till, representing the Wisconsinan McConnell Glaciation, underlain by fluvial sediments with rare detrital organics. Previous 14C dates from the till or underlying sediments have failed to adequately define the age of the McConnell Glaciation. A new accelerator date (29.6 ka BP) on seeds of Corispermum hyssopifolium from subtill deposits shows that the McConnell Glaciation is probably Late Wisconsinan in age and that it correlates with the Kluane Glaciation (Kluane Lake area), McCauley Glaciation (Snag-Klutlan region) and the glaciation represented by « Till D » at the Tom Creek Section (Liard Plain). This conclusion and a new date on Old Crow tephra mean that the Reid, Mirror Creek and possibly Shakwak glaciations are of lllinoian age. Plant fossils (pollen and seeds) and insect fossils from detrital organics associated with the 29.6 ka BP date portray an essentially treeless environment. Even though typical low arctic plants such as heaths, shrub birch and alder are rare to absent, both pollen and macro-fossils suggest a climate no colder than present low arctic tundra, although, it was probably drier. Spruce may have survived in the region, but only as small groves rather than as a riparian forest.La coupe du village indien de Mayo renferme le Till de Mayo, témoin de la Glaciation de McConnell datant du Wisconsinien, sous lequel se trouvent des sédiments fluviatiles comprenant des matériaux organodétritiques rares. Les datations au 14C du till et des sédiments sous-jacents obtenues antérieurement n'avaient pas permis de dater avec précision l'âge de la Glaciation de McConnell. La nouvelle date de 29,6 ka obtenue par accélérateur sur des graines de Corispermum hyssopifolium provenant des dépôts sous-jacents au till indique que la Glaciation de McConnell date probablement du Wisconsinien supérieur et qu'elle correspond aux glaciations de Kluane (Kluane Lake) et de McCauley (région de Snag-Klutan) et à la glaciation représentée par le "Till D" dans la coupe de Tom Creek (Liard Plain). À partir de cette conclusion et grâce à une nouvelle datation sur le tephra de Old Crow, on peut croire que les glaciations de Reid, de Mirror Creek et probablement de Shakwak sont d'âge illinoien. Les fossiles de végétaux (pollen et graines) et d'insectes trouvés dans les sédiments organodétritiques associés à la date de 29.6 ka BP témoignent d'un milieu en grande partie dépourvu d'arbres. Même si les végétaux caractéristiques du bas Arctique comme les Éricacées, l'aulne et le bouleau arbustif sont rares ou absents, le pollen et les macrofossiles laissent entrevoir un climat qui n'était pas plus froid que le climat actuel de la toundra du bas Arctique, mais probablement plus sec. Les épinettes ont peut-être survécu dans la région mais seulement sous forme de bosquets et non de forêt riparienne.Das Profil aus dem indianischen Dorf Mayo, Zentral-Yukon, enthàlt das Till von Mayo, das die McConnell-Vereisung im Wiskonsinium bezeugt und unter dem sich Flusssedimente mit seltenem organischem Erosionsmaterial befinden. Frùhere 14C-Daten von dem Till oder darunter liegenden Sedimenten fùhrten nicht zu einer adâquaten Bestimmung des Alters der McConnell-Vereisung. Ein neues, mit Hilfe eines Beschleunigers auf Samen von Corispermum hyssopifolium in den Ablagerungen unter dem Till gefundenes Datum (29.6 ka v.u.Z.) zeigt, dass die McConnell-Vereisung môglicherweise im spàten Wiskonsinium stattfand und mit den Vereisungen von Kluane (Kluane-See-Gebiet), McCauley (Snag-Klutlan-Gebiet) und dem durch das "Till D" reprasentierten Profil von Tom Creek (Liard Plain) korreliert. Dièse Folgerung und ein neues Datum auf dem Tephra von Old Crow bedeuten, dass die Vereisungen von Reid, Mirror Creek und môglicherweise Shakwak dem lllinoium zugeordnet werden kônnen. Pflanzenfossile (Pollen und Samen) und Insektenfossile aus organischem Erosionsmaterial, das mit dem 29.6 ka v.u.Z. Datum in Verbindung gebracht wird. zeichnen eine im wesentlichen baumlose Umwelt. Auch wenn typische Pflanzen der unteren Arktis wie Heidekraut, Buschbirke und Erie selten bis nicht vorhanden sind. belegen sowohl Pollen wie Makrofossile ein Klima, das nicht kâlter war als das gegenwàrtig in der Tundra der unteren Arktis herrschende, wenn auch môglicherweise trockener. Fichten haben wohl in dem Gebiet uberlebt aber nur in kleinen Wàldchen und nicht als Uferwald

The multiplicity of caregiving burden: a qualitative analysis of families with prolonged disorders of consciousness.

Objective: To understand the multiple and sometimes conflicting roles substitute decision makers (SDMs) of individuals in a vegetative state (VS), minimally conscious state (MCS), or with locked-in syndrome (LIS) perform while caring for a loved one and the competing priorities derived from these roles.Methods: We conducted semi-structured qualitative interviews using a constructive-grounded theory design. Twelve SDMs, who were also family members for 11 patients, were interviewed at two time points (except one) for a total of 21 in-depth interviews.Results: Participants described that caregiving is often the central role which they identify as their top priority and around which they coordinate and to some extent subordinate their other roles. In addition to caregiving, they participated in a wide variety of roles, which were sometimes in conflict, as they became caregivers for a loved one with chronic and complex needs. SDMs described the caregiver role as complex and intense that lead to physical, emotional, social, and economic burdens.Conclusion: SDMs report high levels of burdens in caring for a person with a prolonged disorder of consciousness. Lack of health system support that recognized the broader context of SDMs lives, including their multiple competing priorities, was a major contributing factor

Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH) and fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI), differ with aging and cerebrovascular disease (CVD) and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals

Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

OBJECTIVE The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. BACKGROUND The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. METHODS Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. RESULTS Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. CONCLUSIONS IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery

Towards the assessment of quality of life in patients with disorders of consciousness

© 2019, Springer Nature Switzerland AG. Purpose: To generate foundational knowledge in the creation of a quality-of-life instrument for patients who are clinically diagnosed as being in a vegetative or minimally conscious state but are able to communicate by modulating their brain activity (i.e., behaviourally nonresponsive and covertly aware). The study aimed to identify a short list of key domains that could be used to formulate questions for an instrument that determines their self-reported quality of life. Methods: A novel two-pronged strategy was employed: (i) a scoping review of quality-of-life instruments created for patient populations sharing some characteristics with patients who are behaviourally nonresponsive and covertly aware was done to compile a set of potentially relevant domains of quality of life; and (ii) a three-round Delphi consensus process with a multidisciplinary panel of experts was done to determine which of the identified domains of quality of life are most important to those who are behaviourally nonresponsive and covertly aware. Five expert groups were recruited for this study including healthcare workers, neuroscientists, bioethicists, quality-of-life methodologists, and patient advocates. Results: Thirty-five individuals participated in the study with an average response rate of 95% per round. Over the three rounds, experts reached consensus on 34 of 44 domains (42 domains were identified in the scoping review and two new domains were added based on suggestions by experts). 22 domains were rated as being important for inclusion in a quality-of-life instrument and 12 domains were deemed to be of less importance. Participants agreed that domains related to physical pain, communication, and personal relationships were of primary importance. Based on subgroup analyses, there was a high degree of consistency among expert groups. Conclusions: Quality of life should be a central patient-reported outcome in all patient populations regardless of patients’ ability to communicate. It remains to be determined how covertly aware patients perceive their circumstances and quality of life after suffering a life-altering injury. Nonetheless, it is important that any further dialogue on what constitutes a life worth living should not occur without direct patient input

Neodymium isotopic variations in North Pacific modern silicate sediment and the insignificance of detrital REE contributions to seawater

The neodymium isotopic composition of the silicate fraction of Holocene pelagic sediments from the North Pacific define two provinces: a central North Pacific province characterized by unradiogenic and remarkably homogeneous [epsilon]Nd (-10.2 +/- 0.5) and a narrow circum-Pacific marginal province characterized by more radiogenic and variable [epsilon]Nd (-4.2 +/- 3.8). The silicate fraction in the central North Pacific is exclusively eolian; based on prevailing wind patterns, meteorological data, and neodymium isotopic data, the only significant sediment source is Chinese loess. Leaching experiments on Chinese loess confirm that leachable Nd is isotopically indistinguishable from bulk and residual silicate Nd. Silicates in the circum-North Pacific marginal province comprise eolian loess, volcanic ash, and hemipelagic sediments derived from volcanic arcs. A compilation of Pacific seawater and Mn nodule [epsilon]Nd data shows no clear spatial variation except for a general decrease from surface to deep waters from -3 to -4 and slightly lower [epsilon]Nd in bottom waters along the western North Pacific due to the incursion of Antarctic Bottom Water. The relative homogeneity of bottom water [epsilon]Nd, which contrasts sharply with the distinctive variation in sediment [epsilon]Nd, plus the large difference between the average [epsilon]Nd of bottom waters and the central North Pacific eolian silicates ( -4 vs. -10), suggests that any contribution of REE to seawater from eolian materials is insignificant. Furthermore, leaching of REE from eolian particles as they sink though the water column must be insignificant because Nd in shallow waters is more radiogenic than Nd in deeper waters. That there is no contrast in the Nd isotopic composition of bottom waters that overlie the central and marginal sediment provinces suggests that the ash and hemipelagic sediments derived from Pacific rim volcanic arcs also contribute minimal REE to seawater. The elimination of eolian, ash, and hemipelagic sediments leaves only near-shore riverine particulates as a possibly significant particulate source of REE to seawater.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31272/1/0000178.pd

Ice Lines, Planetesimal Composition and Solid Surface Density in the Solar Nebula

To date, there is no core accretion simulation that can successfully account for the formation of Uranus or Neptune within the observed 2-3 Myr lifetimes of protoplanetary disks. Since solid accretion rate is directly proportional to the available planetesimal surface density, one way to speed up planet formation is to take a full accounting of all the planetesimal-forming solids present in the solar nebula. By combining a viscously evolving protostellar disk with a kinetic model of ice formation, we calculate the solid surface density in the solar nebula as a function of heliocentric distance and time. We find three effects that strongly favor giant planet formation: (1) a decretion flow that brings mass from the inner solar nebula to the giant planet-forming region, (2) recent lab results (Collings et al. 2004) showing that the ammonia and water ice lines should coincide, and (3) the presence of a substantial amount of methane ice in the trans-Saturnian region. Our results show higher solid surface densities than assumed in the core accretion models of Pollack et al. (1996) by a factor of 3 to 4 throughout the trans-Saturnian region. We also discuss the location of ice lines and their movement through the solar nebula, and provide new constraints on the possible initial disk configurations from gravitational stability arguments.Comment: Version 2: reflects lead author's name and affiliation change, contains minor changes to text from version 1. 12 figures, 7 tables, accepted for publication in Icaru

The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect tumorigenesis in the ApcMin/+ mouse small intestine.

BACKGROUND: Alterations in gene splicing occur in human sporadic colorectal cancer (CRC) and may contribute to tumour progression. The K-ras proto-oncogene encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in CRC. Past studies have established that splicing of both the K-ras oncogene and proto-oncogene is altered in CRC in favour of K-ras 4B. The present study addressed whether the K-Ras 4A proto-oncoprotein can suppress tumour development in the absence of its oncogenic allele, utilising the ApcMin/+ (Min) mouse that spontaneously develops intestinal tumours that do not harbour K-ras activating mutations, and the K-rastmDelta4A/tmDelta4A mouse that can express the K-ras 4B splice variant only. By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively. METHODS: The relative levels of expression of the K-ras splice variants in normal small intestine and small intestinal tumours were quantified by real-time RT-qPCR analysis. Inbred (C57BL/6) ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice were generated and the genotypes confirmed by PCR analysis. Survival of stocks was compared by the Mantel-Haenszel test, and tumour number and area compared by Student's t-test in outwardly healthy mice at approximately 106 and 152 days of age. DNA sequencing of codons 12, 13 and 61 was performed to confirm the intestinal tumours did not harbour a K-ras activating mutation. RESULTS: The K-ras 4A transcript accounted for about 50% of K-ras expressed in the small intestine of both wild-type and Min mice. Tumours in the small intestine of Min mice showed increased levels of K-ras 4B transcript expression, but no appreciable change in K-ras 4A transcript levels. No K-ras activating mutations were detected in 27 intestinal tumours derived from Min and compound mutant Min mice. K-Ras 4A deficiency did not affect mouse survival, or tumour number, size or histopathology. CONCLUSION: The K-Ras 4A proto-oncoprotein does not exhibit tumour suppressor activity in the small intestine, even though the K-ras 4A/4B ratio is reduced in adenomas lacking K-ras activating mutations.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are