Terahertz-slicing - an all-optical synchronization for 4th generation light sources.

A conceptually new approach to synchronizing accelerator-based light sources and external laser systems is presented. The concept is based on utilizing a sufficiently intense accelerator-based single-cycle terahertz pulse to slice a thereby intrinsically synchronized femtosecond-level part of a longer picosecond laser pulse in an electro-optic crystal. A precise synchronization of the order of 10 fs is demonstrated, allowing for real-time lock-in amplifier signal demodulation. We demonstrate successful operation of the concept with three benchmark experiments using a 4th generation accelerator-based terahertz light source, i.e. (i) far-field terahertz time-domain spectroscopy, (ii) terahertz high harmonic generation spectroscopy, and (iii) terahertz scattering-type scanning near-field optical microscopy.

The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care: an overview of systematic reviews.

BACKGROUND: Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. METHODS: PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. RESULTS: Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. CONCLUSIONS: This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.

Health utility scores from EQ-5D and health-related quality of life in patients with esophageal cancer: a real-world cross-sectional study.

Esophageal cancer and its treatment can cause serious morbidity/toxicity. These effects on health-related quality of life (HRQOL) can be measured using disease-specific scales such as FACT-E, generic scales such as EQ-5D-3L, or through symptoms. In a two-year cross-sectional study, we compared HRQOL across esophageal cancer patients treated in an ambulatory clinic and across multiple disease states, among patients with all stages of esophageal cancer. Consenting patients completed FACT-E, EQ-5D, a visual analog scale, and patient reported (PR)-ECOG. Symptom complexes were constructed from FACT-E domains. Responses were categorized by disease state: pre-, during, and post-treatment, surveillance, progression, and palliative chemotherapy. Spearman correlation and multivariable linear regression characterized these associations. In total, 199 patients completed 317 questionnaires. Mean FACT-E and subscale scores dropped from baseline through treatment and recovered during post-treatment surveillance (P < 0.001); EQ-5D health utility scores (HUS) displayed a similar pattern but with smaller differences (P = 0.07), and with evidence of ceiling effect. Among patients with stage II/III esophageal cancer, mean EQ-5D HUS varied across disease states (P < 0.001), along with FACT-E and subscales (P < 0.001). Among patients with advanced disease, there was no significant difference between baseline and on-treatment total scores, but improved esophageal cancer-specific scales were noted (P = 0.003). Strong correlation was observed between EQ-5D and FACT-E (R = 0.73), along with physical and functional subscales. In addition, the association between FACT-E and EQ-5D HUS was maintained in a multivariable model (P < 0.001). We interpret these results to suggest that in a real-world clinic setting, FACT-E, EQ-5D HUS, and symptoms were strongly correlated. Most HRQOL and symptom parameters suggested that patients had worse HRQOL and symptoms during curative therapy, but recovered well afterwards. In contrast, palliative chemotherapy had a neutral to positive impact on HRQOL/symptoms when compared to their baseline pre-treatment state.

Multidomain Skyrmion Lattice State in Cu2OSeO3.

Magnetic skyrmions in chiral magnets are nanoscale, topologically protected magnetization swirls that are promising candidates for spintronics memory carriers. Therefore, observing and manipulating the skyrmion state on the surface level of the materials are of great importance for future applications. Here, we report a controlled way of creating a multidomain skyrmion state near the surface of a Cu2OSeO3 single crystal, observed by soft resonant elastic X-ray scattering. This technique is an ideal tool to probe the magnetic order at the L3 edge of 3d metal compounds giving an average depth sensitivity of ∼50 nm. The single-domain 6-fold-symmetric skyrmion lattice can be broken up into domains, overcoming the propagation directions imposed by the cubic anisotropy by applying the magnetic field in directions deviating from the major cubic axes. Our findings open the door to a new way to manipulate and engineer the skyrmion state locally on the surface or on the level of individual skyrmions, which will enable applications in the future.

Néel-type skyrmion lattice with confined orientation in the polar magnetic semiconductor GaV4S8.

Following the early prediction of the skyrmion lattice (SkL)--a periodic array of spin vortices--it has been observed recently in various magnetic crystals mostly with chiral structure. Although non-chiral but polar crystals with Cnv symmetry were identified as ideal SkL hosts in pioneering theoretical studies, this archetype of SkL has remained experimentally unexplored. Here, we report the discovery of a SkL in the polar magnetic semiconductor GaV4S8 with rhombohedral (C3v) symmetry and easy axis anisotropy. The SkL exists over an unusually broad temperature range compared with other bulk crystals and the orientation of the vortices is not controlled by the external magnetic field, but instead confined to the magnetic easy axis. Supporting theory attributes these unique features to a new Néel-type of SkL describable as a superposition of spin cycloids in contrast to the Bloch-type SkL in chiral magnets described in terms of spin helices.

Socioeconomic status and lifestyle behaviours in cancer survivors: smoking and physical activity.

PURPOSE: Smoking cessation and increased physical activity (pa) have been linked to better outcomes in cancer survivors. We assessed whether socioeconomic factors influence changes in those behaviours after a cancer diagnosis. METHODS: As part of a cross-sectional study, a diverse group of cancer survivors at the Princess Margaret Cancer Centre (Toronto, ON), completed a questionnaire about past and current lifestyle behaviours and perceptions about the importance of those behaviours with respect to their health. The influence of socioeconomic indicators on smoking status and physical inactivity at 1 year before and after diagnosis were assessed using multivariable logistic regression with adjustment for clinico-demographic factors. RESULTS: Of 1222 participants, 1192 completed the smoking component. Of those respondents, 15% smoked before diagnosis, and 43% of those smokers continued to smoke after. The proportion of survivors who continued to smoke increased with lower education level (p = 0.03). Of the 1106 participants answering pa questions, 39% reported being physically inactive before diagnosis, of whom 82% remained inactive afterward. Survivors with a lower education level were most likely to remain inactive after diagnosis (p = 0.003). Lower education level, household income, and occupation were associated with the perception that pa had no effect or could worsen fatigue and quality of life (p ≤ 0.0001). CONCLUSIONS: In cancer survivors, education level was a major modifier of smoking and pa behaviours. Lower socioeconomic status was associated with incorrect perceptions about pa. Targeting at-risk survivors by education level should be evaluated as a strategy in cancer survivorship programs.

Evaluation of initial dofetilide dosing recommendation based on actual body weight in overweight and obese patients.

WHAT IS KNOWN AND OBJECTIVE: The dofetilide label recommends using actual body weight (ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients. METHODS: This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m(2)) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight (IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome. RESULTS AND DISCUSSION: Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15). WHAT IS NEW AND CONCLUSION: Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients.

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort.

BACKGROUND: There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). METHODS: This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. RESULTS: Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47-0.66, p < 0.001). CONCLUSION: In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

Non-resonant and non-enhanced Raman correlation spectroscopy.

We present the first non-resonant and non-enhanced Raman correlation spectroscopy experiments. They are conducted on a confocal microscope combined with a Raman spectrometer. The thermal fluctuations of the Raman intensities scattered by dispersions of polystyrene particles of sub-micrometric diameters are measured and analysed by deriving the autocorrelation functions (ACFs) of the intensities. We show that for particles of diameter down to 200 nm, RCS measurements are successfully obtained in spite of the absence of any source of amplification of the Raman signal. For particles of diameter ranging from 200 to 750 nm, the ACFs present a time-decay behaviour in accordance with the model of free Brownian particles. For particles of 1000 nm in diameter, the AFCs present a different behaviour with a much smaller characteristic time. This results from the dynamics of a single-Brownian particle trapped in the confocal volume by the optical forces of the focus spot.

In situ self-assembled organic interface layers for the controlled growth of oligothiophene thin films on ferroelectric Pb(Zr(0.2)Ti(0.8))O3.

We introduce an in situ vacuum procedure for the optimal preparation and analysis of self-assembled monolayers (SAMs) as used in organic molecular electronics on ferroelectric lead zirconate titanate (PZT) substrates. Excellent ordering of oligothiophene semiconductor layers is heavily promoted through the presence of an interfacial bi-functional SAM layer that binds to both the oxidic PZT surface and the organic semiconductor molecules. The described method can be extended to other material combinations, featuring a variety of substrate materials and molecular functionalities.

Comparison of phenotypic methods and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry for the identification of aero-tolerant Actinomyces spp. isolated from soft-tissue infections.

Aero-tolerant Actinomyces spp. are an under-recognised cause of cutaneous infections, in part because identification using conventional phenotypic methods is difficult and may be inaccurate. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) is a promising new technique for bacterial identification, but with limited data on the identification of aero-tolerant Actinomyces spp. This study evaluated the accuracy of a phenotypic biochemical kit, MALDI-TOF MS and genotypic identification methods for the identification of this problematic group of organisms. Thirty aero-tolerant Actinomyces spp. were isolated from soft-tissue infections over a 2-year period. Species identification was performed by 16 s rRNA sequencing and genotypic results were compared with results obtained by API Coryne and MALDI-TOF MS. There was poor agreement between API Coryne and genotypic identification, with only 33% of isolates correctly identified to the species level. MALDI-TOF MS correctly identified 97% of isolates to the species level, with 33% of identifications achieved with high confidence scores. MALDI-TOF MS is a promising new tool for the identification of aero-tolerant Actinomyces spp., but improvement of the database is required in order to increase the confidence level of identification.

Reporting of tobacco use and tobacco-related analyses in cancer cooperative group clinical trials: a systematic scoping review.

BACKGROUND: Continued smoking after a diagnosis of cancer negatively impacts cancer outcomes, but the impact of tobacco on newer treatments options is not well established. Collecting and evaluating tobacco use in clinical trials may advance understanding of the consequences of tobacco use on treatment modalities, but little is known about the frequency of reporting and analysis of tobacco use in cancer cooperative clinical trial groups. PATIENTS AND METHODS: A comprehensive literature search was conducted to identify cancer cooperative group clinical trials published from January 2017-October 2019. Eligible studies evaluated either systemic and/or radiation therapies, included ≥100 adult patients, and reported on at least one of: overall survival, disease/progression-free survival, response rates, toxicities/adverse events, or quality-of-life. RESULTS: A total of 91 studies representing 90 trials met inclusion criteria with trial start dates ranging from 1995 to 2015 with 14% involving lung and 5% head and neck cancer patients. A total of 19 studies reported baseline tobacco use; 2 reported collecting follow-up tobacco use. Seven studies reported analysis of the impact of baseline tobacco use on clinical outcomes. There was significant heterogeneity in the reporting of baseline tobacco use: 7 reported never/ever status, 10 reported never/ex-smoker/current smoker status, and 4 reported measuring smoking intensity. None reported verifying smoking status or second-hand smoke exposure. Trials of lung and head and neck cancers were more likely to report baseline tobacco use than other disease sites (83% versus 6%, P < 0.001). CONCLUSIONS: Few cancer cooperative group clinical trials report and analyze trial participants' tobacco use. Significant heterogeneity exists in reporting tobacco use. Routine standardized collection and reporting of tobacco use at baseline and follow-up in clinical trials should be implemented to enable investigators to evaluate the impact of tobacco use on new cancer therapies.

Clostridioides difficile colonization and infection in a cohort of Australian adults with cystic fibrosis.

BACKGROUND: Little is known about Clostridioides difficile infection (CDI) in patients with cystic fibrosis (CF). The aim of this study was to investigate the prevalence, molecular epidemiology and risk factors for CDI in asymptomatic and symptomatic adults with CF in Western Australia. METHODS: Faecal samples from symptomatic and asymptomatic patients were prospectively collected and tested for the presence of C. difficile by toxigenic culture. Ribotyping was performed by established protocols. Logistic regression analysis was performed to analyse the risk factors for C. difficile colonization and infection. Extensive environmental sampling was performed within the CF clinic in Perth. RESULTS: The prevalence rates of asymptomatic toxigenic and non-toxigenic C. difficile colonization were 30% (14/46 patients) and 24% (11/46 patients), respectively. Fifteen ribotypes (RTs) of C. difficile were identified, of which non-toxigenic RT 039 was the most common. Among the symptomatic patients, the prevalence of toxigenic CDI was 33% (11/33 patients). Impaired glucose tolerance/diabetes mellitus and duration of intravenous antibiotic use in the past 12 months were significantly associated with increased risk of asymptomatic toxigenic C. difficile carriage and CDI. A trend towards higher CF transmembrane conductance regulator modulator treatment was observed in the CDI group. Extensive environmental sampling showed no evidence of toxigenic C. difficile contamination within the CF clinic. CONCLUSIONS: A high prevalence of asymptomatic carriage of toxigenic C. difficile was observed in adults with CF, comparable with that observed in the symptomatic CF population. There was no evidence of direct person-to-person transmission.

Glial fibrillary acidic protein is localized in the lens epithelium.

The epithelium of the mouse lens stains intensely with antisera to glial fibrillary acidic protein (GFAP). A protein co-migrating with GFAP and immunoreactive with antisera to GFAP can be demonstrated in lens epithelium protein extracts by immunoblots. GFAP has previously been considered unique to cells of neural origin, but this study demonstrates that ectodermally derived cells express GFAP or a highly similar protein.

Glia maturation factor: effect on chemical differentiation of glioblasts in culture.

A protein factor from the adult brain increases the concentrations of adenosine 3',5'-monophosphate and S-100 protein in glioblasts in culture. Such changes are correlated with the outgrowth of cell processes.

Implementation of a comprehensive smoking cessation program in cancer care.

Background: Quitting smoking after a cancer diagnosis maximizes treatment-related effects, improves prognosis, and enhances quality of life. However, smoking cessation (sc) services are not routinely integrated into cancer care. The Princess Margaret Cancer Centre implemented a digitally-based sc program in oncology, leveraging an e-referral system (cease) to screen all new ambulatory patients, provide tailored education and advice on quitting, and facilitate referrals. Methods: We adopted the Framework for Managing eHealth Change to guide implementation of the sc program by integrating 6 key elements: governance and leadership, stakeholder engagement, communication, workflow analysis and integration, monitoring and evaluation, and training and education. Results: Incorporating elements of the Framework, we used extensive stakeholder engagement and strategic partnerships to establish a sc program with organizational and provincial accountability. Existing electronic patient-reported assessments were changed to integrate cease. Clinic audits and staff engagement allowed for analysis of workflow, ongoing monitoring and evaluation that aided in establishing a communication strategy, and development of cancer-specific education for patients and health care providers. From April 2016 to March 2018, 22,137 new patients were eligible for screening. Among those new patients, 13,617 (62%) were screened, with 1382 (10%) being current smokers and 532 (4%) having recently quit (within 6 months). Of the current smokers and those who had recently quit, all were advised to quit or to stay smoke-free, and 380 (20%) accepted referral to a sc counselling service. Conclusions: Here, we provide a comprehensive practice blueprint for the implementation of digitally based sc programs as a standard of care within comprehensive cancer centres with high patient volumes.

Combined cancer patient-reported symptom and health utility tool for routine clinical implementation: a real-world comparison of the ESAS and EQ-5D in multiple cancer sites.

Background: We assessed whether the presence and severity of common cancer symptoms are associated with the health utility score (hus) generated from the EQ-5D (EuroQol Research Foundation, Rotterdam, Netherlands) in patients with cancer and evaluated whether it is possible pragmatically to integrate routine hus and symptom evaluation in our cancer population. Methods: Adult outpatients at Princess Margaret Cancer Centre with any cancer were surveyed cross-sectionally using the Edmonton Symptom Assessment System (esas) and the EQ-5D-3L, and results were compared using Spearman correlation coefficients and regression analyses. Results: Of 764 patients analyzed, 27% had incurable disease. We observed mild-to-moderate correlations between each esas symptom score and the hus (Spearman coefficients: -0.204 to -0.416; p < 0.0001 for each comparison), with the strongest associations being those for pain (R = -0.416), tiredness (R = -0.387), and depression (R =-0.354). Multivariable analyses identified pain and depression as highly associated (both p < 0.0001) and tiredness as associated (p = 0.03) with the hus. The ability of the esas to predict the hus was low, at 0.25. However, by mapping esas pain, anxiety, and depression scores to the corresponding EQ-5D questions, we could derive the hus using partial esas data, with Spearman correlations of 0.83-0.91 in comparisons with direct EQ-5D measurement of the hus. Conclusions: The hus derived from the EQ-5D-3L is associated with all major cancer symptoms as captured by the esas. The esas scores alone could not predict EQ-5D scores with high accuracy. However, esas-derived questions assessing the same domains as the EQ-5D-3L questions could be mapped to their corresponding EQ-5D questions to generate the hus, with high correlation to the directly measured hus. That finding suggests a potential approach to integrating routine symptom and hus evaluations after confirmatory studies.

A novel inward rectifier K+ channel with unique pore properties.

We have cloned a novel K+-selective, inward rectifier channel that is widely expressed in brain but is especially abundant in the Purkinje cell layer of the cerebellum and pyramidal cells of the hippocampus. It is also present in a wide array of tissues, including kidney and intestine. The channel is only 38% identical to its closest relative, Kir1.3 (Kir1-ATP-regulated inward rectifier K+ [ROMK] family) and displays none of the functional properties unique to the ROMK class. Kir7.1 has several unique features, including a very low estimated single channel conductance (approximately 50 fS), low sensitivity to block by external Ba2+ and Cs+, and no dependence of its inward rectification properties on the internal blocking particle Mg2+. The unusual pore properties of Kir7.1 seem to be explained by amino acids in the pore sequence that differ from corresponding conserved residues in all other Kir channel proteins. Replacement of one of these amino acids (Met-125) with the Arg absolutely conserved in all other Kir channels dramatically increases its single channel conductance and Ba2+ sensitivity. This channel would provide a steady background K+ current to help set the membrane potential in cells in which it is expressed. We propose that the novel channel be assigned to a new Kir subfamily, Kir7.1.

Optically controlled interparticle distance tuning and welding of single gold nanoparticle pairs by photochemical metal deposition.

We report on the in-situ controlled tuning of the particle gap in single pairs of gold nanodisks by photochemical metal deposition. The optically induced growth of nanodisk dimers fabricated by electron beam lithography leads to a decrease of the interparticle gap width down to 0 nm. Due to the increasing particle size and stronger plasmonic coupling, a smooth redshift of the localized surface plasmon (LSP) resonances is observed in such particle pairs during the growth process. The interparticle gap width, and hence the LSP resonance, can be tuned to any desired spectral position. The experimental results we obtain with this nanoscale fabrication technique are well described by the so-called plasmon ruler equation. Consequently, both the changes in particle diameter as well as in gap width can be characterized in-situ via far-field read-out of the optical properties of the dimers.

Near-field coupling of a single fluorescent molecule and a spherical gold nanoparticle.

Near-field coupling of a single gold nanoparticle (GNP) to a single fluorescent molecule is investigated here for varying separation d between the two. While the emission quantum efficiency of the coupled system generally decreases for d!0, a pronounced near-field enhancement is observed under certain conditions, partly outweighing the efficiency loss at small distances. We report on optimizing these conditions by varying the excitation field direction and the three-dimensional relative configuration between the GNP and the fluorophore. Furthermore, we examine how the sphere diameter, the surrounding medium, as well as the absorption and emission wavelengths of the molecular dipole influence the fluorescence yield. Our results are of high practical relevance for all GNP-mediated application fields such as fluorescence microscopy, scattering near-field optical microscopy, bioanalytics, and medical applications.