89 research outputs found

    Intense slow beams of heavy molecules to test fundamental symmetries

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    Slow molecular beams allow for a very sensitive test of the Standard Model of particle physics. We are particularly interested in measuring the electron electric dipole moment (eEDM) in heavy diatomic polar molecules. The precision of these measurements is limited by the statistical measurement uncertainty. To minimize the latter, we build a cryogenic buffer gas source that produces slow intense beams of SrF (strontium fluoride) molecules. The molecules are further decelerated with a 4.5-meter-long Stark decelerator. After transverse laser-cooling the beam, a very sensitive eEDM measurement can be performed in the future

    The use of hydroxychloroquine as a systemic treatment in erosive lichen planus of the vulva and vagina

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    Erosive lichen planus affecting the vulva and vagina (ELPV) is a rare inflammatory skin disease, presenting with painful erosions and severe scarring.1 The disease course is persistent and often refractory to treatment: up to 45% patients do not experience remission with topical treatments, while evidence for systemic treatments remains scarce.2 Hydroxychloroquine (HCQ) is frequently used in daily practice as a first choice systemic therapy.3 However, little evidence is available on HCQ for ELPV.2 The aim of this study was to analyse the effectiveness and safety of HCQ in ELPV.</p

    Preferences and Experiences Regarding the Use of the Self-Sampling Device in hrHPV Screening for Cervical Cancer

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    BACKGROUND: To improve participation in the Dutch cervical cancer screening, a self-sampling device (SSD) was introduced in 2017 into the Dutch population-based screening programme (PBS) for the early detection of cervical cancer. The aim of this study was to gather potential preferences and experiences that might influence a woman’s decision to use the SSD in the Dutch PBS. METHODS: A scoping review was performed in the PubMed database. Studies that assessed preferences and experiences of women regarding the SSD were included, and preferences and experiences were extracted. In addition, in a qualitative study, the list of potential preferences and experiences specific for the Dutch PBS was extended based on semi-structured interviews with SSD users as well as non-SSD users who recently participated in the PBS, analysed in a structured manner by translating full sentences to key words. RESULTS: Ninety-eight studies were included in the scoping review and 16 interviews were performed. Frequently mentioned reasons for using the SSD, in both the interviews and the literature, were practicality and comfort. Frequently mentioned reasons for not using the SSD were fear of not performing the SSD procedure correctly and doubts on whether the results of the high-risk human papillomavirus (hrHPV) test will be reliable. A new positive experience elicited in the interviews was accessibility. Negative preferences and experiences were not being aware the SSD was an option, and the inconvenience that after an hrHPV-positive test result of the SSD, an additional smear test at the GP is necessary. CONCLUSION: Several preferences and experiences play a role in the choice whether or not to use the SSD. Based on the currently found preferences and experiences, an app will be developed in order to assess which of these are the most important for women participating in the Dutch population-based cervical screening programme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40271-021-00550-y

    High accuracy theoretical investigations of CaF, SrF, and BaF and implications for laser-cooling

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    The NL-eEDM collaboration is building an experimental setup to search for the permanent electric dipole moment of the electron in a slow beam of cold barium fluoride molecules [Eur. Phys. J. D, 72, 197 (2018)]. Knowledge of molecular properties of BaF is thus needed to plan the measurements and in particular to determine an optimal laser-cooling scheme. Accurate and reliable theoretical predictions of these properties require incorporation of both high-order correlation and relativistic effects in the calculations. In this work theoretical investigations of the ground and the lowest excited states of BaF and its lighter homologues, CaF and SrF, are carried out in the framework of the relativistic Fock-space coupled cluster (FSCC) and multireference configuration interaction (MRCI) methods. Using the calculated molecular properties, we determine the Franck-Condon factors (FCFs) for the A2Π1/2→X2Σ1/2+A^2\Pi_{1/2} \rightarrow X^2\Sigma^{+}_{1/2} transition, which was successfully used for cooling CaF and SrF and is now considered for BaF. For all three species, the FCFs are found to be highly diagonal. Calculations are also performed for the B2Σ1/2+→X2Σ1/2+B^2\Sigma^{+}_{1/2} \rightarrow X^2\Sigma^{+}_{1/2} transition recently exploited for laser-cooling of CaF; it is shown that this transition is not suitable for laser-cooling of BaF, due to the non-diagonal nature of the FCFs in this system. Special attention is given to the properties of the A′2ΔA'^2\Delta state, which in the case of BaF causes a leak channel, in contrast to CaF and SrF species where this state is energetically above the excited states used in laser-cooling. We also present the dipole moments of the ground and the excited states of the three molecules and the transition dipole moments (TDMs) between the different states.Comment: Minor changes; The following article has been submitted to the Journal of Chemical Physics. After it is published, it will be found at https://publishing.aip.org/resources/librarians/products/journals

    Deceleration of a supersonic beam of SrF molecules to 120 m/s

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    We report on the deceleration of a beam of SrF molecules from 290 to 120~m/s. Following supersonic expansion, the molecules in the X2ÎŁX^2\Sigma (v=0v=0, N=1N=1) low-field seeking states are trapped by the moving potential wells of a traveling-wave Stark decelerator. With a deceleration strength of 9.6 km/s2^2 we have demonstrated the removal of 85 % of the initial kinetic energy in a 4 meter long modular decelerator. The absolute amount of kinetic energy removed is a factor 1.5 higher compared to previous Stark deceleration experiments. The demonstrated decelerator provides a novel tool for the creation of highly collimated and slow beams of heavy diatomic molecules, which serve as a good starting point for high-precision tests of fundamental physics

    Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme

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    Background: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology.Methods: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (&lt; CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel.Results: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between &lt; CIN2 and CIN3+ for all markers (p &lt; 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p &lt; 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation&gt; 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified.Conclusion: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.</p

    The Paget Trial:topical 5% imiquimod cream for noninvasive vulvar Paget disease

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    BACKGROUND: Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. Most vulvar Paget disease cases are noninvasive; however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for noninvasive vulvar Paget disease is wide local excision, which is challenging because of extensive intraepithelial spread and may cause severe morbidity. Recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. Imiquimod, a topical immune response modifier, has been shown to be effective in a few studies and case reports, and is a promising new treatment modality. OBJECTIVE: To prospectively investigate the efficacy, safety, and effect on quality of life of a standardized treatment schedule with 5% imiquimod cream in patients with noninvasive vulvar Paget disease. STUDY DESIGN: The Paget Trial is a multicenter prospective observational clinical study including 7 tertiary referral hospitals in the Netherlands. A total of 24 patients with noninvasive vulvar Paget disease were treated with topical 5% imiquimod cream 3 times a week for 16 weeks. The primary efficacy outcome was the reduction in lesion size at 12 weeks after the end of treatment. Secondary outcomes were safety, clinical response after 1 year, and quality of life. Safety was assessed by evaluation of adverse events and tolerability of treatment. Quality of life was investigated with 3 questionnaires taken before, during, and after treatment. RESULTS: Data were available for 23 patients, 82.6% of whom responded to therapy. A complete response was reported in 12 patients (52.2%), and 7 patients (30.4%) had a partial response. A histologic complete response was observed in 10 of the 12 patients with a complete response. Patients experienced side effects such as fatigue (66.7%-70.9%) and headaches (16.7%-45.8%), and almost 80% needed painkillers during treatment. Eight patients (34.8%) adjusted the treatment protocol to 2 applications a week, and 3 patients (13.0%) stopped treatment because of side effects after 4 to 11 weeks. Treatment improved quality of life, whereas a slight, temporary negative impact was observed during treatment. Two patients with a complete response developed a recurrence within 1 year after treatment. Follow-up showed 6 patients with a noninvasive recurrence after a median of 31 months (14-46 months) after the end of treatment. CONCLUSION: Topical 5% imiquimod cream can be an effective and safe treatment alternative for noninvasive vulvar Paget disease, particularly when compared with treatment with surgical excision

    Deceleration and Trapping of SrF Molecules

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    We report on the electrostatic trapping of neutral SrF molecules. The molecules are captured from a cryogenic buffer-gas beam source into the moving traps of a 4.5 m long traveling-wave Stark decelerator. The SrF molecules in X2ÎŁ+(v=0,N=1)X^2\Sigma^+(v=0, N=1) state are brought to rest as the velocity of the moving traps is gradually reduced from 190 m/s to zero. The molecules are held for up to 50 ms in multiple electric traps of the decelerator. The trapped packets have a volume (FWHM) of 1 mm3^{3} and a velocity spread of 5(1) m/s which corresponds to a temperature of 60(20)60(20) mK. Our result demonstrates a factor 3 increase in the molecular mass that has been Stark-decelerated and trapped. Heavy molecules (mass>>100 amu) offer a highly increased sensitivity to probe physics beyond the Standard Model. This work significantly extends the species of neutral molecules of which slow beams can be created for collision studies, precision measurement and trapping experiments

    A supersonic laser ablation beam source with narrow velocity spreads

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    A supersonic beam source for SrF and BaF molecules is constructed by combining the expansion of carrier gas (a mixture of 2% SF6 and 98% argon) from an Even-Lavie valve with laser ablation of a barium/strontium metal target at a repetition rate of 10 Hz. Molecular beams with a narrow translational velocity spread are produced at relative values of Δv/v = 0.053(11) and 0.054(9) for SrF and BaF, respectively. The relative velocity spread of the beams produced in our source is lower in comparison with the results from other metal fluoride beams produced in supersonic laser ablation sources. The rotational temperature of BaF is measured to be 3.5 K. The source produces 6 × 108 and 107 molecules per steradian per pulse in the X2ς+ (ν = 0, N = 1) state of BaF and SrF molecules, respectively, a state amenable to Stark deceleration and laser cooling
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