Women's knowledge about cervical cancer risk factors, screening, and reasons for non-participation in cervical cancer screening programme in Estonia

<p>Abstract</p> <p>Background</p> <p>The attendance rate in Estonian cervical cancer screening programme is too low therefore the programme is hardly effective. A cross-sectional population based survey was performed to identify awareness of cervical cancer risk factors, reasons why women do not want to participate in cervical screening programme and wishes for better organisation of the programme.</p> <p>Method</p> <p>An anonymous questionnaire with a covering letter and a prepaid envelope was sent together with the screening invitation to 2942 randomly selected women. Results are based on the analysis of 1054 (36%) returned questionnaires.</p> <p>Results</p> <p>Main reasons for non-participation in the national screening programme were a recent visit to a gynaecologist (42.3%), fear to give a Pap-smear (14.3%), long appointment queues (12.9%) and unsuitable reception hours (11.8%). Fear to give a Pap-smear was higher among women aged 30 and 35 than 50 and 55 (RR 1.46; 95% CI: 0.82-2.59) and women with one or no deliveries (RR 1.56, 95% CI: 0.94-2.58). In general, awareness of cervical cancer risk factors is poor and it does not depend on socio-demographic factors. Awareness of screening was higher among Estonians than Russians (RR 1.64, 95% CI: 1.46-1.86). Most women prefer to receive information about screening from personally mailed invitation letters (74.8%).</p> <p>Conclusions</p> <p>Women need more information about cervical cancer risk factors and the screening programme. They prefer personally addressed information sharing. Minority groups should be addressed in their own language. A better collaboration with service providers and discouraging smears outside the programme are also required.</p

Tokenizer Choice For LLM Training: Negligible or Crucial?

The recent success of LLMs has been predominantly driven by curating the training dataset composition, scaling of model architectures and dataset sizes and advancements in pretraining objectives, leaving tokenizer influence as a blind spot. Shedding light on this underexplored area, we conduct a comprehensive study on the influence of tokenizer choice on LLM downstream performance by training 24 mono- and multilingual LLMs at a 2.6B parameter scale, ablating different tokenizer algorithms and parameterizations. Our studies highlight that the tokenizer choice can significantly impact the model's downstream performance, training and inference costs. In particular, we find that the common tokenizer evaluation metrics fertility and parity are not always predictive of model downstream performance, rendering these metrics a questionable proxy for the model's downstream performance. Furthermore, we show that multilingual tokenizers trained on the five most frequent European languages require vocabulary size increases of factor three in comparison to English. While English-only tokenizers have been applied to the training of multi-lingual LLMs, we find that this approach results in a severe downstream performance degradation and additional training costs of up to 68%, due to an inefficient tokenization vocabulary

The second physical therapy summit on global health: developing an action plan to promote health in daily practice and reduce the burden of non-communicable diseases

Based on indicators that emerged from The First Physical Therapy Summit on Global Health (2007), the Second Summit (2011) identified themes to inform a global physical therapy action plan to integrate health promotion into practice across the World Confederation for Physical Therapy (WCPT) regions. Working questions were: (1) how well is health promotion implemented within physical therapy practice; and (2) how might this be improved across five target audiences (i.e. physical therapist practitioners, educators, researchers, professional body representatives, and government liaisons/consultants). In structured facilitated sessions, Summit representatives (n=32) discussed: (1) within WCPT regions, what is working and the challenges; and (2) across WCPT regions, what are potential directions using World CaféTM methodology. Commonalities outweighed differences with respect to strategies to advance health-focused physical therapy as a clinical competency across regions and within target audiences. Participants agreed that health-focused practice is a professional priority, and a strategic action plan was needed to develop it as a clinical competency. The action plan and recommendations largely paralleled the principles and objectives of the World Health Organization's non-communicable diseases action plan. A third Summit planned for 2015 will provide a mechanism for follow-up to evaluate progress in integrating health-focused physical therapy within the profession.info:eu-repo/semantics/acceptedVersio

Enhanced Proliferation of Monolayer Cultures of Embryonic Stem (ES) Cell-Derived Cardiomyocytes Following Acute Loss of Retinoblastoma

Background: Cardiomyocyte (CM) cell cycle analysis has been impeded because of a reliance on primary neonatal cultures of poorly proliferating cells or chronic transgenic animal models with innate compensatory mechanisms. Methodology/Principal Findings: We describe an in vitro model consisting of monolayer cultures of highly proliferative embryonic stem (ES) cell-derived CM. Following induction with ascorbate and selection with puromycin, early CM cultures are.98 % pure, and at least 85 % of the cells actively proliferate. During the proliferative stage, cells express high levels of E2F3a, B-Myb and phosphorylated forms of retinoblastoma (Rb), but with continued cultivation, cells stop dividing and mature functionally. This developmental transition is characterized by a switch from slow skeletal to cardiac TnI, an increase in binucleation, cardiac calsequestrin and hypophosphorylated Rb, a decrease in E2F3, B-Myb and atrial natriuretic factor, and the establishment of a more negative resting membrane potential. Although previous publications suggested that Rb was not necessary for cell cycle control in heart, we find following acute knockdown of Rb that this factor actively regulates progression through the G1 checkpoint and that its loss promotes proliferation at the expense of CM maturation. Conclusions/Significance: We have established a unique model system for studying cardiac cell cycle progression, and show in contrast to previous reports that Rb actively regulates both cell cycle progression through the G1 checkpoint an

Characteristics of Pos19 - A Small Coding RNA in the Oxidative Stress Response of Rhodobacter sphaeroides.

The phototrophic bacterium Rhodobacter sphaeroides induces several small RNAs (sRNAs) when singlet oxygen (1O2) levels are elevated, a situation also referred to as photo-oxidative stress. An RNA-seq study identified the RSs0019 sRNA, which is renamed Pos19 (photo-oxidative stress induced sRNA 19). Pos19 is part of the RpoE regulon and consequently induced upon 1O2 and peroxide stress. The 219 nt long Pos19 transcript contains a small open reading frame (sORF) of 150 nt, which is translated in vivo. Over-expression of Pos19 results in reduced mRNA levels for several genes, of which numerous are involved in sulfur metabolism. The negative effect on the potential targets is maintained even when translation of the sORF is abolished, arguing that regulation is entailed by the sRNA itself. Reporter studies further revealed that regulation of the most affected mRNA, namely RSP_0557, by Pos19 is Hfq-dependent. Direct binding of Pos19 to Hfq was shown by co-immunoprecipitation. Physiological experiments indicated Pos19 to be involved in the balance of glutathione biosynthesis. Moreover, a lack of Pos19 leads to elevated reactive oxygen species levels. Taken together our data identify the sRNA Pos19 as a coding sRNA with a distinct expression pattern and potential role under oxidative stress in the phototrophic bacterium R. sphaeroides

ETEX: A European Tracer Experiment; Observations, Dispersion Modelling and Emergency Response.

In the fall of 1994 perfluorocarbon tracers were released in Monterfil, France. During 4 days the evolution of the tracer cloud, as measured by 168 ground stations in Europe, were compared with model simulations. In contrast with Chernobyl, predictions can now be made available almost immediately after an emergency is reported. The quality of and consensus between predictions is still immature. Data assimilation offers good prospects for improvement.JRC.(EI)-Environment Institut

Pos19 influences GSH and ROS levels.

<p>(A) Measurement of total intracellular glutathione (GSH). GSH was measured using Ellmann’s reagent (DTNB) in cell samples from three <i>R</i>. <i>sphaeroides</i> strains: an empty vector control (pRK16S), a strain with a constitutive, plasmid-borne over-expression of Pos19 under the control of the 16S rRNA promoter (pRK16S::Pos19), and the Pos19 mutant (ΔPos19). The relative GSH amount is depicted in percent; the GSH amount of the empty vector control (pRK16S) was set to 100 percent. All results represent the mean of nine independent biological experiments with technical duplicates. Error bars reflect the standard error of mean. The level of significance compared to the control (pRK16S) is indicated († 0.05 < p < 0.1 and * p < 0.05). (B) Inhibition zone assay using 10 mM methylene blue (MB) in the light, 500 mM tBOOH, 1 M and 2 M hydrogen peroxide (H₂O₂), and 500 mM diamide_. The diameter of the zones of inhibition was measured for the three <i>R</i>. <i>sphaeroides</i> strains described above for the GSH assay. The data represent the mean of three independent experiments with technical duplicates. The error bars represent the standard error of mean. (C) Effect of Pos19 on ROS levels. Determination of intracellular levels of ROS in the control strain (pRK16S) compared to Pos19 over-expression (pRK16S::Pos19) and mutant (ΔPos19). ROS generated by the cells were analyzed after reaction with 10 μM 2,7-dihydrodichlorofluorescein diacetate. The fluorescence intensity was normalized to the optical densities of the samples. The resulting values are presented in arbitrary units (AU). The data represent the mean of three independent experiments. The error bars indicate the standard error of mean. The level of significance compared to the control (pRK16S) is indicated (* p < 0.05).</p

Pos19 is induced by singlet oxygen and peroxides.

<p>(A) Graphical representation of the Pos19 locus in <i>R</i>. <i>sphaeroides</i> wild-type strain 2.4.1. The <i>pos19</i> gene is located on chromosome 2 between <i>cxp</i> and <i>fadB</i>. The conserved RpoE-dependent promoter (P_RpoE) and the Rho-independent terminator (lollipop structure) are indicated. (B) Northern blot for stress-dependent Pos19 induction. <i>R</i>. <i>sphaeroides</i> wild-type 2.4.1 cultures were treated with stress-generating chemicals and samples collected at time points 0 and 7 min. Singlet oxygen (¹O₂) was generated by the addition of 0.2 μM methylene blue in the presence of high light intensities (800 W m^-2). Hydrogen peroxide (H₂O₂) and <i>tert</i>-butyl hydroperoxide (tBOOH) were added in final concentrations of 1 mM and 300 μM, respectively. 250 μM of paraquat (PQ) were used for the generation of superoxide radicals (O₂^‒). 5S rRNA was probed as loading control. (C) Northern blot for RpoE-dependent Pos19 expression. The <i>R</i>. <i>sphaeroides</i> wild-type (wt), the Pos19 over-expression (pPos19), RpoH_I and RpoH_II mutant strains, as well as a strain lacking the <i>rpoE-chrR</i> locus (TF18), were treated with the indicated stress-generating chemicals as described above. Samples were collected at the indicated time points. 5S rRNA was probed as loading control.</p

Pos19 is a coding sRNA.

<p>(A) Detailed illustration of the <i>pos19</i> gene. Relevant features are shown in bold. The -35 and -10 motifs of the RpoE-dependent promoter are marked. The 219 nt long sRNA (shaded in grey) contains two potential ORFs with lengths of 150 (Start1) and 135 nt (Start2). The Rho-independent terminator (italic letters) was predicted by TransTermHP [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163425#pone.0163425.ref027" target="_blank">27</a>] and correlates with the 3’ end mapped by 3’ RACE. The Shine-Dalgarno (SD) sequence, the two start codons as well as one internal codon (Codon16) were mutated according to the chart below the sequence. (B) <i>In vivo</i> translation of the Pos19-sORF was monitored by translational <i>lacZ</i> fusions. A 300 bp fragment containing the RpoE-dependent promoter and the first 178 bp of the <i>pos19</i> gene (including codons 1–48) was fused to the promoter-less <i>lacZ</i> gene on reporter plasmid pPHU236. The wild-type (wt) sORF was subsequently mutated as shown in (A). The fusion plasmids and control plasmid pPHU236 were transferred to <i>R</i>. <i>sphaeroides</i> ΔPos19 or strain TF18, which lacks the <i>rpoE-chrR</i> locus. The corresponding strains were subjected to ¹O₂ stress for 60 min with samples collected at the indicated time points. ß-galactosidase activities were measured from biological triplicates with technical duplicates. Error bars represent the standard error of the mean. (C) <i>In vivo</i> translation of the Pos19-sORF was monitored by translational eCFP fusion. The Pos19 peptide, C-terminally fused to eCFP (Pos19^up+ORF), was detected with a polyclonal anti-GFP antibody on a Western blot. Cultures were stressed as described for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163425#pone.0163425.g001" target="_blank">Fig 1</a> and samples were withdrawn at the indicated time points. The amount of total protein extracts is shown in brackets. Protein from a strain carrying the pBE_eCFP::eCFP with 16S rRNA promoter (16S) was used as control. The size difference between control and Pos19 fusion of around 4 kDa corresponds to molecular weight of the predicted Pos19 peptide.</p