Predicting the duration of reach-to-grasp movements to objects with asymmetric contact surfaces.

The duration of reach-to-grasp movements is influenced by the size of the contact surfaces, such that grasping objects with smaller contact surface areas takes longer. But what is the influence of asymmetric contact surfaces? In Experiment 1a, participants reached-to-lift wooden blocks off a table top, with the contact locations for the thumb and index finger varying in surface size. The time taken to lift the block was driven primarily by the thumb contact surface, which showed a larger effect size for the dependent variable of movement duration than the index finger's contact surface. In Experiment 1b participants reached-to-grasp (but not lift) the blocks. The same effect was found with duration being largely driven by contact surface size for the thumb. Experiment 2 tested whether this finding generalised to movements towards conical frusta grasped in a different plane mounted off the table top. Experiment 2 showed that movement duration again was dictated primarily by the size of the thumb's contact surface. The thumb contact surface was the visible surface in experiments 1 and 2 so Experiment 3 explored grasping when the index finger's contact surface was visible (participants grasped the frusta with the index finger at the top). An interaction between thumb and finger surface size was now found to determine movement duration. These findings provide the first empirical report of the impact of asymmetric contact surfaces on prehension, and may have implications for scientists who wish to model reach-to-grasp behaviours

Approximate affine linear relationship between L1 norm objective functional values and L2 norm constraint bounds

For an optimization problem with an norm objective function subject to an norm inequality constraint, this paper shows that there is an approximately linear relationship between the norm objective functional values and the norm specifications. This relationship is verified through the use of random and real world industrial data. The obtained results can be employed for 1) estimating the norm output objective functional value without solving the optimization problem numerically; 2) providing an insight for defining the norm specification in which a simple method is proposed in this paper; and 3) testing whether the obtained solutions are the globally optimal solutions or not. These advantages are demonstrated via the use of random data

Longitudinal Research on Alcohol Problems: The Flow of Risk, Problems, and Disorder over Time

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65764/1/j.1530-0277.1996.tb01753.x.pd

Paradigm shift in public administration: Implications for teaching in professional training programs

10.1111/j.1540-6210.2009.02085.xPublic Administration Review69SUPPL.

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD

OMERACT Filter 2.1: Elaboration of the Conceptual Framework for Outcome Measurement in Health Intervention Studies

Objective: The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 framework was developed in 2014 to aid core outcome set development by describing the full universe of “measurable aspects of health conditions” from which core domains can be selected. This paper provides elaborations and updated concepts (OMERACT Filter 2.1). Methods: At OMERACT 2018, we discussed challenges in the framework application caused by unclear or ambiguous wording and terms and incompletely developed concepts. Results: The updated OMERACT Filter 2.1 framework makes benefits and harms explicit, clarifies concepts, and improves naming of various terms. Conclusion: We expect that the Filter 2.1 framework will improve the process of core set development

Women We Loved: Paradoxes of public and private in the biographical television drama

Broadcast to critical acclaim and relatively large audiences for its niche channel, the Women We Loved season consisted of biographical dramatisations of three prominent female figures of 20th-century British culture. These dramas shared in common narratives that centre on the two aspects of ‘the public’ and ‘the private’: the tension between public career and personal life and the discrepancy between celebrity persona and private individual. Combining theoretical insights from feminist studies of biography with close textual analysis, this article analyses how performance, aesthetics and narrative express the ambivalent placement of their protagonists between public and private spheres

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively