The impact of running with and without a guide on short distance running performance for athletes with a vision impairment

Objective This study aimed to investigate the difference of running with or without a guide on running performance (100 m, 200 m and 400 m) for athletes with a vision impairment (VI). Design Data including athletes’ and guides’ sex, age and race times were extracted from 11 elite competitions. Results Male athletes predominantly ran without a guide (100 m = 91.4%, 200 m = 88.1%, 400 m = 84.8%), whereas, female athletes mainly ran with a guide (100 m = 60.5%, 200 m = 80.0%, 400 m = 72.0%). No significant difference in 100 m race times was found between male athletes with or without a guide (p = 0.647). For the 200 m (p = 0.001) and 400 m (p = 0.030), race times were significantly slower for male athletes running with a guide (mean rank 200 m = 36.80, 400 m = 33.57) compared to without a guide (mean rank 200 m = 19.43, 400 m = 21.69). Conversely, 100 m (p = 0.015), 200 m (p = 0.025) and 400 m (p = 0.029) race times were significantly faster for female athletes with (mean rank 100 m = 18.25, 200 m = 13.71, 400 m = 11.00) compared to without a guide (mean rank 100 m = 27.74, 200 m = 22.67, 400 m = 21.69). Conclusions Running with a guide affects VI athletes’ race times. The influence of running with a guide, and the gender mix of VI athlete and guide, should be considered in any research with the aim of establishing a new classification system for VI athletes

Results of the Uncertainty Analysis.

<p>An uncertainty analysis is used to assess the accuracy of the projections made, giving the percentage at which it’s likely to achieve (or exceed) the projected (base) value. (Example: the costs of hospital admission period are likely to be higher than the projections in 37% of the cases.) The uncertainty analysis also gives the averages (certainty equal to 50%) and the confidence intervals (the most likely values ranging from 10% to 90% percentiles).</p><p>Results of the Uncertainty Analysis.</p

Projection of Costs to Manufacture a Liver from iPSCs.

<p>Projection of Costs to Manufacture a Liver from iPSCs.</p

Model Scheme.

<p>Blue and green rectangles represent, respectively, the forecast outputs of the Epidemiology Model and the Treatment Costs Model. Data used to perform the forecasts are shown in red square (refer to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131764#pone.0131764.t001" target="_blank">Table 1</a> for further details on data source).</p

Number of New Patients per MELD score.

<p>(A) Metric evolution over 20-years. (B) Metric forecasts at Years 1, 10 and 20.</p

Discounted costs (per theoretical patient and per liver transplantation phase) and total discounted costs of liver transplantation (per theoretical patient) at Years 1, 10 and 20.

<p>The total weighted treatment costs of a liver transplantation will increase from $1,427,805 per patient in Year 1 to$2,093,789 per patient in Year 20.</p

The profile of athletes with a vision impairment: Exploring demographics and ocular pathologies of athletes in three Paralympic sports

Objective This study aimed to explore the profile of athletes with a vision impairment (VI) who compete in three Paralympic sports (goalball, VI judo and blind football). Design Descriptive and association analyses of the VI athletes’ profile were conducted. Results The typical athlete profile was a male (65.1%), aged 26-34 years (39.7%), from Europe (38.8%), representing a country with a high-income (46.1%) and was diagnosed with a retinal-related ocular pathology (38.9%). In all three sports, the ages of the athletes were similar. In goalball, most athletes were from Europe, represented countries with a high-income and were diagnosed with retinal-, globe-, or neurological-related pathologies. In VI judo, the majority of athletes were from Asia, represented countries with an upper-middle-income and were diagnosed with retinal-, global-, or neurological-related pathologies. In blind football, most athletes were from Europe, represented countries with an upper-middle-income, and were diagnosed with retinal-, neurological-related ocular pathologies, or glaucoma. Conclusions The homogeneity of the athletes’ profile suggests that an effort is needed to target other parts of the VI population to take part in VI sports. Differences in the athletes’ profiles across the sports provides information that may be useful for sport-specific talent identification

Phosphorylation Status of Thymidine Kinase 1 Following Antiproliferative Drug Treatment Mediates 3′-Deoxy-3′-[¹⁸F]-Fluorothymidine Cellular Retention

<div><p>Background</p><p>3′-Deoxy-3′-[¹⁸F]-fluorothymidine ([¹⁸F]FLT) is being investigated as a Positron Emission Tomography (PET) proliferation biomarker. The mechanism of cellular [¹⁸F]FLT retention has been assigned primarily to alteration of the strict transcriptionally regulated S-phase expression of thymidine kinase 1 (TK1). This, however, does not explain how anticancer agents acting primarily through G2/M arrest affect [¹⁸F]FLT uptake. We investigated alternative mechanisms of [¹⁸F]FLT cellular retention involving post-translational modification of TK1 during mitosis.</p><p>Methods</p><p>[¹⁸F]FLT cellular retention was assessed in cell lines having different TK1 expression. Drug-induced phosphorylation of TK1 protein was evaluated by MnCl₂-phos-tag gel electrophoresis and correlated with [¹⁸F]FLT cellular retention. We further elaborated the amino acid residues involved in TK1 phosphorylation by transient transfection of FLAG-pCMV2 plasmids encoding wild type or mutant variants of TK1 into TK1 negative cells.</p><p>Results</p><p>Baseline [¹⁸F]FLT cellular retention and TK1 protein expression were associated. S-phase and G2/M phase arrest caused greater than two-fold reduction in [¹⁸F]FLT cellular retention in colon cancer HCT116 cells (p<0.001). G2/M cell cycle arrest increased TK1 phosphorylation as measured by induction of at least one phosphorylated form of the protein on MnCl₂-phos-tag gels. Changes in [¹⁸F]FLT cellular retention reflected TK1 phosphorylation and not expression of total protein, in keeping with the impact of phosphorylation on enzyme catalytic activity. Both Ser13 and Ser231 were shown to be involved in the TK1 phosphorylation-modulated [¹⁸F]FLT cellular retention; although the data suggested involvement of other amino-acid residues.</p><p>Conclusion</p><p>We have defined a regulatory role of TK1 phosphorylation in mediating [¹⁸F]FLT cellular retention and hence reporting of antiproliferative activity, with implications especially for drugs that induce a G2/M cell cycle arrest.</p></div

Determination of the regulation of TK1 phosphorylation by Cdk1 and Cdk2.

<p>A) Cdk1 and Cdk2 knock-down optimization. Representative western blots, with corresponding densitometry (average of 3 independent experiments) and qPCR analysis. Control refers to non-silenced cells; scramble indicates transfection with non-targeting siRNA. B) Determination of the Cdk responsible for TK1 specific phosphorylation. 5 nM of scramble, Cdk1 or Cdk2 siRNA were used to induce Cdk knock-down for 48 h. Cells were treated O/N with 0.5 µg/ml nocodazole (NOC) following Cdk knock-down. Top two panels represent MnCl₂-phos-tag gel; bottom three panels report 12% SDS-PAGE.</p

Verification of phosphorylated amino acid residues on TK1 protein.

<p>Ost TK1⁻ cells were transiently transfected with FLAG-pCMV2 plasmids coding for TK1 variants. A) Ost TK1⁻ transient transfections with FLAG-pCMV2 plasmids coding for the indicated TK1 variants were resolved (10 µg) on a 75 µM MnCl₂-phos-tag gels and probed for TK1 expression (1∶500). B) [¹⁸F]FLT uptake in Ost TK1⁻ cells transiently transfected with the indicated TK1 constructs. The main figure represents the uptake in control and nocodazole (0.5 µg/ml) treated samples. The y-axis represents mean ± S.E.M. expressed as counts per µg of protein. Significant differences following transient transfection compared to non-transfected cells, and significant changes after nocodazole treatment compared to the untreated sample are highlighted by stars. The inset reports the percentage of radiotracer uptake compared to cells transfected with wild type (WT; 100%) TK1. Significant differences are indicated by stars. C) TK1 expression in transfected cells resolved on 12% SDS-PAGE. β actin was used as loading control.</p