FOXP3+ regulatory T-cell counts correlate with histological response in Crohn's colitis treated with infliximab

Crohn's disease is a chronic inflammatory bowel disease of unknown aetiology. Mucosal inflammatory dysregulation is likely important, with increased production of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFα). The chimeric monoclonal antibody, infliximab, inhibits TNFα and promotes intestinal mucosal healing. Despite this, many patients still require surgical intervention. Patients who have undergone colonic resection post-infliximab therapy, show markedly variable morphological response to treatment. FOXP3+ CD4+ regulatory T-cells have been shown to have a protective role in autoimmune/inflammatory diseases and their sequestration to the bowel is found in those treated with infliximab. We examined the immunohistochemical profile of lymphoid aggregates in tissue sections from post-infliximab Crohn's colitis resection specimens, classified as morphological responders or non-responders, defined in relation to the absence/presence of mucosal ulceration and active inflammation, and a control group. Results indicated no significant diffences in CD68-positive cell counts but increased FOXP3-positive (P = 0.02) and CD4-positive (P = 0.05) cell counts in responders versus non-responders. Untreated control scores were similar to non-responders. Although based on small study numbers, our results suggest an association between upregulation of FOXP3+/CD4+ regulatory T-cells and morphological response to infliximab therapy. This represents a possible quantitative methodology for monitoring therapeutic response to infliximab therapy, based on immunohistochemical evaluation of endoscopic biopsy specimens.

Discovering subgroups of patients from DNA copy number data using NMF on compacted matrices

In the study of complex genetic diseases, the identification of subgroups of patients sharing similar genetic characteristics represents a challenging task, for example, to improve treatment decision. One type of genetic lesion, frequently investigated in such disorders, is the change of the DNA copy number (CN) at specific genomic traits. Non-negative Matrix Factorization (NMF) is a standard technique to reduce the dimensionality of a data set and to cluster data samples, while keeping its most relevant information in meaningful components. Thus, it can be used to discover subgroups of patients from CN profiles. It is however computationally impractical for very high dimensional data, such as CN microarray data. Deciding the most suitable number of subgroups is also a challenging problem. The aim of this work is to derive a procedure to compact high dimensional data, in order to improve NMF applicability without compromising the quality of the clustering. This is particularly important for analyzing high-resolution microarray data. Many commonly used quality measures, as well as our own measures, are employed to decide the number of subgroups and to assess the quality of the results. Our measures are based on the idea of identifying robust subgroups, inspired by biologically/clinically relevance instead of simply aiming at well-separated clusters. We evaluate our procedure using four real independent data sets. In these data sets, our method was able to find accurate subgroups with individual molecular and clinical features and outperformed the standard NMF in terms of accuracy in the factorization fitness function. Hence, it can be useful for the discovery of subgroups of patients with similar CN profiles in the study of heterogeneous diseases.

Power and Energy Implications of the Number of Threads Used on the Intel Xeon Phi

Energy consumption has become an important area of research of late. With the advent of new manycore processors, situations have arisen where not all the processors need to be active to reach an optimal relation between performance and energy usage. In this paper a study of the power and energy usage of a series of benchmarks, the PARSEC and the SPLASH- 2X Benchmark Suites, on the Intel Xeon Phi for different threads configurations, is presented. To carry out this study, a tool was designed to monitor and record the power usage in real time during execution time and afterwards to compare the r

Mapping neutral, ion and electron number densities within laser ablated plasma plumes

Spatially and temporally varying neutral, ion and electron number densities have been mapped out within laser ablated plasma plumes expanding into vacuum. Ablation of a magnesium target was performed using a KrF laser, 30 ns pulse duration and 248 nm wavelength. During the initial stage of plasma expansion (t <EQ 100 ns) interferometry has been used to obtain line averaged electron number densities, for laser power densities on target in the range 1.3 - 3.0 X 108 W/cm2. Later in the plasma expansion (t equals 1 microsecond(s) ) simultaneous absorption and laser induced fluorescence spectroscopy has been used to determine 3D neutral and ion number densities, for a power density equal to 6.7 X 107 W/cm2. Two distinct regions within the plume were identified. One is a fast component (approximately 106 cm-1) consisting of ions and neutrals with maximum number densities observed to be approximately 30 and 4 X 1012 cm-3 respectively, and the second consists of slow moving neutral material at a number density of up to 1015 cm-3. Additionally a Langmuir probe has been used to obtain ion and electron number densities at very late times in the plasma expansion (1 microsecond(s) <EQ t <EQ 15 microsecond(s) ). A copper target was ablated using a Nd:YAG laser, 7.5 ns duration and 532 nm (2 (omega) ) wavelength, with a power density on target equal to 6 X 108 W/cm2. Two regions within the plume with different velocities were observed. Within a fast component (approximately 3 X 106 cms-1) electron and ion number densities of the order 5 X 1012 cm-3 were observed and within the second slower component (approximately 106 cms-1) electron and ion number densities of the order 1 - 2 X 1013 cm-3 were determined.

Distributed Massive MIMO in Cellular Networks: Impact of Imperfect Hardware and Number of Oscillators

Distributed massive multiple-input multiple-output (MIMO) combines the array gain of coherent MIMO processing with the proximity gains of distributed antenna setups. In this paper, we analyze how transceiver hardware impairments affect the downlink with maximum ratio transmission. We derive closed-form spectral efficiencies expressions and study their asymptotic behavior as the number of the antennas increases. We prove a scaling law on the hardware quality, which reveals that massive MIMO is resilient to additive distortions, while multiplicative phase noise is a limiting factor. It is also better to have separate oscillators at each antenna than one per BS.

A multi-proxy chronological reconstruction of palaeosalinity in the eastern Limfjord, Denmark

The Jutland peninsula in northern Denmark is home to the Limfjord, one of the largest estuarine bodies of water in the region. Human inhabitance of the Limfjord’s surrounding coastlines stretches back further than 7,800 cal BP, with anthropogenic influence on the landscape beginning approximately 6,000 cal BP. Understanding how the Limfjord as a system has changed throughout time is useful in comprehending subsistence patterns and anthropogenic influence. This research is part of a larger project aimed at discerning subsistence patterns and environmental change in the region. Following the Younger Dryas, as the Fennoscandian ice sheet began to melt, Denmark experienced isostatic rebound, which contributed to the complex sea level history in the region. Between ice melt and isostatic rebound, the Jutland peninsula experienced many transgression and regression events. Connections to surrounding seas have shifted throughout time, with most attention focused on the western connection of the Limfjord with the North Sea, which has experienced numerous closures and subsequent re-openings throughout the Holocene. Furthermore, the Limfjord-North Sea connection has been the focal point of research because of the west to east water flow in the system, and the present day higher salinity in the west compared to the east. Little to no consideration has been paid to the influence of the Kattegat and Baltic on the Limfjord until now. A 10m sediment core was taken from Sebbersund (near Nibe, Limfjord), along the connection between the Limfjord and the Kattegat in the east to understand how the eastern part of the system has changed and differed from changes observed in the west. The Sebbersund sequence spans a majority of the Holocene, from 9600 cal BP to 1030 cal BP, determined via radiocarbon dating of terrestrial macrofossils and bulk sediment. Over this time period palaeoenvironmental conditions were reconstructed through the use of geochemical analyses (13C, 15N, C:N), physical sediment analyses, dinoflagellate cyst abundances and molluscan analyses. apart from two instances of low salinity, one at the top and one at the bottom of the core, the sequence has a strong marine signal for a majority of the Holocene. Radiocarbon dating of bulk sediment samples showed the presence of old carbon in the system, creating an age offset between 1,300 ± 200 and 2,800 ± 200 calibrated 14C years compared to the age-depth curve based on the terrestrial macrofossils. This finding, along with the strong marine influence in the system, discerned through geochemical data, dinoflagellate cyst and mollusc counts, is important for obtaining accurate radiocarbon ages in the region and stresses the importance of understanding both the marine and freshwater reservoir effects. The marine dominance in the eastern Limfjord differs from the west, which is characterized by a number of freshwater events when the North Sea connection was closed off during the Holocene. The eastern connection was open to the Kattegat throughout a large portion of the Holocene, with influx of open ocean water entering the system during periods of higher sea level.

The paradox of invasion: Reeves’ muntjac deer invade the British Isles from a limited number of founding females

High levels of genetic diversity and high propagule pressure are favoured by conservation biologists as the basis for successful reintroductions and ensuring the persistence of populations. However, invasion ecologists recognize the ‘paradox of invasion’, as successful species introductions may often be characterized by limited numbers of individuals and associated genetic bottlenecks. In the present study, we used a combination of high-resolution nuclear and mitochondrial genetic markers to investigate the invasion history of Reeves' muntjac deer in the British Isles. This invasion has caused severe economic and ecological damage, with secondary spread currently a concern throughout Europe and potentially globally. Microsatellite analysis based on eight loci grouped all 176 introduced individuals studied from across the species' range in the UK into one genetic cluster, and seven mitochondrial D-loop haplotypes were recovered, two of which were present at very low frequency and were related to more common haplotypes. Our results indicate that the entire invasion can be traced to a single founding event involving a low number of females. These findings highlight the fact that even small releases of species may, if ignored, result in irreversible and costly invasion, regardless of initial genetic diversity or continual genetic influx.

Response of soil microbial communities to single and multiple doses of an organic pollutant

The effect of 100 μg 1,2-dichlorobenzene (1,2-DCB) g^-1 dry weight (dw) of soil introduced either as a single dose or multiple (10 fortnightly) doses of 10 μg g^-1 dw, on the microbial biomass, diversity of culturable bacterial community and the rate of 1,2-DCB mineralisation, were compared. After 22 weeks exposure both application regimes significantly reduced total bacterial counts and viable fungal hyphal length. The single dose had the greatest overall inhibitory effect, although the extent of inhibition varied throughout the study. Total culturable bacterial counts, determined after 22 weeks exposure showed little response to 1,2-DCB, but pseudomonad counts in single and multiple treatments were reduced to 9.7 and 0.147%, respectively, of the numbers detected in the control soil. The effect of 1,2-DCB application on the taxonomic composition of the culturable bacteria community was determined by fatty acid methyl ester (FAME) analysis. Compared to control soils, the single dose treatment had a lower percentage of Arthrobacter and Micrococcus. Multiple applications had a significant effect upon pseudomonad abundance, which represented only 2% of the identified community, compared to 45.6% in the control. The multi-dosed soils contained a high percentage of bacilli (> 25%). The effects of 1,2-DCB applications on the metabolic potential of the soil microbial community was determined by BIOLOG profiling. The number of carbon compounds utilised by the community in the multi-dosed soils (49 positives) was significantly less (P < 0.05) than detected in the single dose treatment (76) and control (66). The rate of 1,2-DCB mineralisation, determined by ¹⁴CO₂ production from radiolabelled [UL-¹⁴C] 1,2-DCB, declined throughout the study, and after 22 weeks was slightly but significantly (P < 0.05) lower in the multiply- than the singly-dosed soils. The differential response to 1,2-DCB treatments was attributed to its reduced bioavailability in soils after a single exposure, compared to multiple applications.

Magnetic Characteristics of a High-layer-number NiFe/FeMn Multilayer

We report the static & dynamic magnetic characteristics of a high-layer-number NiFe/FeMn multilayer test structure with potential applications in broadband absorber and filter devices. To allow fine control over the absorption linewidths and to understand the mechanisms governing the resonances in a tailored structure similar to that expected to be used in real world applications, the multilayer was intentionally designed to have layer thickness and interface roughness variations. Magnetometry measurements show the sample has complex hysteresis loops with features consistent with single ferromagnetic film reversals. Structural characterisation by transmission electron microscopy allows us to correlate the magnetic properties with structural features. Analysis of resonance frequencies from broadband ferromagnetic resonance measurements as a function of field magnitude and orientation provide values of the local exchange bias, rotatable anisotropy, and uniaxial anisotropy fields for specific layers in the stack and explain the observed mode softening. The linewidths of the multilayer are adjustable around the bias field, approaching twice that seen at larger fields, allowing control over the bandwidth of devices formed from the structure.

What counts and what is being counted – The social organization of knowledge on the front lines of emergency medical services.

Paramedics are trained to use specialized medical knowledge and a variety of medical procedures and pharmaceutical interventions to “save patients and prevent further damage” in emergency situations, both as members of “health-care teams” in hospital emergency departments (Swanson, 2005: 96) and on the streets – unstandardized contexts “rife with chaotic, dangerous, and often uncontrollable elements” (Campeau, 2008: 3). The paramedic’s unique skill-set and ability to function in diverse situations have resulted in the occupation becoming ever more important to health care systems (Alberta Health and Wellness, 2008: 12).
Today, prehospital emergency services, while varying, exist in every major city and many rural areas throughout North America (Paramedics Association of Canada, 2008) and other countries around the world (Roudsari et al., 2007). Services in North America, for instance, treat and/or transport 2 million Canadians (over 250,000 in Alberta alone ) and between 25 and 30 million Americans annually (Emergency Medical Services Chiefs of Canada, 2006; National EMS Research Agenda, 2001). In Canada, paramedics make up one of the largest groups of health care professionals, with numbers exceeding 20,000 (Pike and Gibbons, 2008; Paramedics Association of Canada, 2008). However, there is little known about the work practices of paramedics, especially in light of recent changes to how their work is organized, making the profession “rich with unexplored opportunities for research on the full range of paramedic work” (Campeau, 2008: 2).

This presentation reports on findings from an institutional ethnography that explored the work of paramedics and different technologies of knowledge and governance that intersect with and organize their work practices. More specifically, my tentative focus of this presentation is on discussing some of the ruling discourses central to many of the technologies used on the front lines of EMS in Alberta and the consequences of such governance practices for both the front line workers and their patients. In doing so, I will demonstrate how IE can be used to answer Rankin and Campbell’s (2006) call for additional research into “the social organization of information in health care and attention to the (often unintended) ways ‘such textual products may accomplish…ruling purposes but otherwise fail people and, moreover, obscure that failure’ (p. 182)” (cited in McCoy, 2008: 709).