Determination and correction of spectral phase from principal component analysis of coherent phonons.

Measuring the spectral phase of a pulse is key for performing wavelength resolved ultrafast measurements in the few femtosecond regime. However, accurate measurements in real experimental conditions can be challenging. We show that the reflectivity change induced by coherent phonons in a quantum material can be used to infer the spectral phase of an optical probe pulse with few-femtosecond accuracy.

A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

BACKGROUND: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. METHODS: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. RESULTS: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. CONCLUSIONS: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.

Educating Family Physician Residents for Anesthetic Preoperative Evaluation and Assessment.

Introduction: Encounters for preoperative assessments are common within primary care offices, so it is imperative that family medicine residents learn how to perform preoperative evaluations. We assessed family medicine residents' knowledge of preoperative evaluation in preparation for surgery by providing a pre- and post-test alongside a didactic seminar. Methods: A didactic seminar on preoperative evaluations was presented at a family medicine resident didactics session by two senior anesthesiology residents. A 16-question, multiple choice test was used as both a pre-test and post-test to assess family medicine residents' knowledge. Results: A total of 31 participants took the pre-test (residents = 24; medical students = 7), and 30 participants took the post-test (residents = 23; medical students = 7). Mean scores and standard deviations were calculated for both tests with an average score of 37.50% ± 10.58% and 45.42% ± 11.12% on the pre- and post-test, respectively. Using the Kruskal-Wallis test, residents showed a significant improvement in test scores following the didactic presentation (p = 0.041), while overall results (residents and medical students) also reported a significant difference (p = 0.004). Conclusions: Our results demonstrated that educating family medicine residents and medical students on preoperative evaluation showed significant, quantifiable gains in knowledge following a brief didactic presentation. Given the current gap between guidelines and practice, our results emphasize the need for a formal medical school and residency-based curriculum related to preoperative patient evaluation.

Use of a focus group-based cognitive interview methodology to validate a cooking behavior survey among African-American adults.

Disparities in diet-related diseases persist among African-Americans despite advances in risk factor identification and evidence-based management strategies. Cooking is a dietary behavior linked to improved dietary quality and cardiometabolic health outcomes. However, epidemiologic studies suggest that African-American adults report a lower frequency of cooking at home when compared to other racial groups, despite reporting on average cooking time. To better understand cooking behavior among African-Americans and reported disparities in behavior, we sought to develop a survey instrument using focus group-based cognitive interviews, a pretesting method that provides insights into a survey respondent's interpretation and mental processing of survey questions. A comprised survey instrument was developed based on input from a community advisory board, a literature review, and a content review by cooking behavior experts. The cognitive interview pretesting of the instrument involved African-American adults (n = 11) at risk for cardiovascular disease who were recruited from a community-based participatory research study in Washington, D.C., to participate in a focus group-based cognitive interview. Cognitive interview methodologies included the verbal think-aloud protocol and the use of retrospective probes. Thematic analysis and evaluation of verbalized cognitive processes were conducted using verbatim transcripts. Five thematic themes related to the survey were generated: (1) Clarity and relevancy of question items; (2) influence of participants' perspectives and gender roles; (3) participant social desirability response to questions; (4) concern regarding question intent. Eleven survey items were determined as difficult by participants. Cooking topics for these items were: cooking practices, cooking skills, cooking perception (how one defines cooking), food shopping skills, and socialization around cooking. Question comprehension and interpreting response selections were the most common problems identified. Cognitive interviews are useful for cooking research as they can evaluate survey questions to determine if the meaning of the question as intended by the researcher is communicated to the respondents-specific implications from the results that apply to cooking research include revising questions on cooking practice and skills. Focus-group-based cognitive interviews may provide a feasible method to develop culturally grounded survey instruments to help understand disparities in behavior for culturally relevant diet behaviors such as cooking.

Use of a community advisory board to build equitable algorithms for participation in clinical trials: a protocol paper for HoPeNET.

INTRODUCTION: Participation from racial and ethnic minorities in clinical trials has been burdened by issues surrounding mistrust and access to healthcare. There is emerging use of machine learning (ML) in clinical trial recruitment and evaluation. However, for individuals from groups who are recipients of societal biases, utilisation of ML can lead to the creation and use of biased algorithms. To minimise bias, the design of equitable ML tools that advance health equity could be guided by community engagement processes. The Howard University Partnership with the National Institutes of Health for Equitable Clinical Trial Participation for Racial/Ethnic Communities Underrepresented in Research (HoPeNET) seeks to create an ML-based infrastructure from community advisory board (CAB) experiences to enhance participation of African-Americans/Blacks in clinical trials. METHODS AND ANALYSIS: This triphased cross-sectional study (24 months, n=56) will create a CAB of community members and research investigators. The three phases of the study include: (1) identification of perceived barriers/facilitators to clinical trial engagement through qualitative/quantitative methods and systems-based model building participation; (2) operation of CAB meetings and (3) development of a predictive ML tool and outcome evaluation. Identified predictors from the participant-derived systems-based map will be used for the ML tool development. ETHICS AND DISSEMINATION: We anticipate minimum risk for participants. Institutional review board approval and informed consent has been obtained and patient confidentiality ensured.

Multi-mode excitation drives disorder during the ultrafast melting of a C4-symmetry-broken phase.

Spontaneous C4-symmetry breaking phases are ubiquitous in layered quantum materials, and often compete with other phases such as superconductivity. Preferential suppression of the symmetry broken phases by light has been used to explain non-equilibrium light induced superconductivity, metallicity, and the creation of metastable states. Key to understanding how these phases emerge is understanding how C4 symmetry is restored. A leading approach is based on time-dependent Ginzburg-Landau theory, which explains the coherence response seen in many systems. However, we show that, for the case of the single layered manganite La0.5Sr1.5MnO4, the theory fails. Instead, we find an ultrafast inhomogeneous disordering transition in which the mean-field order parameter no longer reflects the atomic-scale state of the system. Our results suggest that disorder may be common to light-induced phase transitions, and methods beyond the mean-field are necessary for understanding and manipulating photoinduced phases.

An achromatic pump-probe setup for broadband, few-cycle ultrafast spectroscopy in quantum materials.

In this work, we present an achromatic pump-probe setup covering the visible (VIS) to near-infrared (NIR) wavelength regions (500-3000 nm) for few-cycle pulses. Both the pump and probe arms can work either in the VIS or the NIR wavelength regions, making our setup suitable for multi-color, broadband pump-probe measurements. In particular, our setup minimizes time-smearing due to the phase front curvature, an aspect of ultrafast spectroscopy that has been missing from previous works and allowing us to achieve sub-20-fs temporal resolution. We demonstrate the capabilities of our setup by performing measurements on Pr0.5Ca1.5MnO4. We pump and probe in both wavelength regions with a range of pump fluences and demonstrate how the observed dynamics depend strongly on the probe wavelength. Furthermore, the observation of a 16.5 THz phonon demonstrates the high temporal resolution of the setup.

Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients.

Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available. Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups. Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892-0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935-0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1-3 cancer subgroups. Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.

Quantitative hyperspectral coherent diffractive imaging spectroscopy of a solid-state phase transition in vanadium dioxide.

Solid-state systems can host a variety of thermodynamic phases that can be controlled with magnetic fields, strain, or laser excitation. Many phases that are believed to exhibit exotic properties only exist on the nanoscale, coexisting with other phases that make them challenging to study, as measurements require both nanometer spatial resolution and spectroscopic information, which are not easily accessible with traditional x-ray spectromicroscopy techniques. Here, we use coherent diffractive imaging spectroscopy (CDIS) to acquire quantitative hyperspectral images of the prototypical quantum material vanadium oxide across the vanadium L 2,3 and oxygen K x-ray absorption edges with nanometer-scale resolution. We extract the full complex refractive indices of the monoclinic insulating and rutile conducting phases of VO2 from a single sample and find no evidence for correlation-driven phase transitions. CDIS will enable quantitative full-field x-ray spectromicroscopy for studying phase separation in time-resolved experiments and other extreme sample environments where other methods cannot operate.

Laser-induced transient magnons in Sr3Ir2O7 throughout the Brillouin zone.

Although ultrafast manipulation of magnetism holds great promise for new physical phenomena and applications, targeting specific states is held back by our limited understanding of how magnetic correlations evolve on ultrafast timescales. Using ultrafast resonant inelastic X-ray scattering we demonstrate that femtosecond laser pulses can excite transient magnons at large wavevectors in gapped antiferromagnets and that they persist for several picoseconds, which is opposite to what is observed in nearly gapless magnets. Our work suggests that materials with isotropic magnetic interactions are preferred to achieve rapid manipulation of magnetism.

Extracting sub-cycle electronic and nuclear dynamics from high harmonic spectra.

We present a new methodology for measuring few-femtosecond electronic and nuclear dynamics in both atoms and polyatomic molecules using multidimensional high harmonic generation (HHG) spectroscopy measurements, in which the spectra are recorded as a function of the laser intensity to form a two-dimensional data set. The method is applied to xenon atoms and to benzene molecules, the latter exhibiting significant fast nuclear dynamics following ionization. We uncover the signature of the sub-cycle evolution of the returning electron flux in strong-field ionized xenon atoms, implicit in the strong field approximation but not previously observed directly. We furthermore extract the nuclear autocorrelation function in strong field ionized benzene cations, which is determined to have a decay of [Formula: see text] fs, in good agreement with the [Formula: see text] fs obtained from direct dynamics variational multi-configuration Gaussian calculations. Our method requires minimal assumptions about the system, and is applicable even to un-aligned polyatomic molecules.

Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up.

BACKGROUND: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. METHODS: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. RESULTS: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963-0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929-0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956-0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980-0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947-0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. CONCLUSIONS: The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.

Measurement of 10 fs pulses across the entire Visible to Near-Infrared Spectral Range.

Tuneable ultrafast laser pulses are a powerful tool for measuring difficult-to-access degrees of freedom in materials science. In general these experiments require the ability to address resonances and excitations both above and below the bandgap of materials, and to probe their response at the timescale of the fastest non-trivial internal dynamics. This drives the need for ultrafast sources capable of delivering 10-15 fs duration pulses tuneable across the entire visible (VIS) and near infrared (NIR) range, 500- 3000 nm, as well as the characterization of these sources. Here we present a single frequency-resolved optical gating (FROG) system capable of self-referenced characterization of pulses with 10 fs duration across the entire VIS-NIR spectral range. Our system does not require auxiliary beams and only minor reconfiguration for different wavelengths. We demonstrate the system with measurements of pulses across the entire tuning range.

Dietary Intake, Physical Activity and Metabolic Syndrome in African Americans, Hispanics and Whites.

OBJECTIVE: The objective of the study was to compare the dietary intakes and physical activity levels among Whites, African Americans, and Hispanics with and without metabolic syndrome (MetS). DESIGN: The study was based on secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. SETTING: The NHANES's target population is the civilian, noninstitutionalized U.S. SUBJECTS: The sample was made up of 2,449 subjects aged 40 years or more, of both genders, and of three ethnic groups (African Americans, Whites and Hispanics). RESULTS: Mean intakes of food energy, total fat, total saturated fatty acids, total monounsaturated fatty acids, cholesterol, lycopene, selenium and sodium were significantly higher in Whites with MetS. African-Americans with MetS had significantly lower dietary intakes of beta-carotene and total sugars. Also, mean vitamin A and beta-carotene intakes were significantly lower in the Hispanic subjects with MetS. Vigorous and moderate physical activity levels were significantly lower in African Americans and Hispanics with MetS. Computer use was significantly higher in Whites with MetS. CONCLUSIONS: Variables significantly predictive of MetS were age, male gender, African-American ethnicity, BMI, and lycopene intake.

Attosecond soft X-ray high harmonic generation.

High harmonic generation (HHG) of an intense laser pulse is a highly nonlinear optical phenomenon that provides the only proven source of tabletop attosecond pulses, and it is the key technology in attosecond science. Recent developments in high-intensity infrared lasers have extended HHG beyond its traditional domain of the XUV spectral range (10-150 eV) into the soft X-ray regime (150 eV to 3 keV), allowing the compactness, stability and sub-femtosecond duration of HHG to be combined with the atomic site specificity and electronic/structural sensitivity of X-ray spectroscopy. HHG in the soft X-ray spectral region has significant differences from HHG in the XUV, which necessitate new approaches to generating and characterizing attosecond pulses. Here, we examine the challenges and opportunities of soft X-ray HHG, and we use simulations to examine the optimal generating conditions for the development of high-flux, attosecond-duration pulses in the soft X-ray spectral range. This article is part of the theme issue 'Measurement of ultrafast electronic and structural dynamics with X-rays'.

Predictive Factors of Vitamin D Inadequacy among Older Adults in the United States.

Optimal serum vitamin D levels are reported to be associated with many health benefits; however, few studies have determined predictive factors using national level data. An assessment of predictive factors for vitamin D inadequacy was conducted using National Health and Nutrition Examination Survey (NHANES) 2001-2006 data. Using the study sample including adults aged 40 years or more, data analysis was performed using the weighted multivariate logistic regression statistical procedure. The prevalence of vitamin D inadequacy (serum vitamin D <20 ng/ml) was 37.3%. Non-Hispanic Blacks were 6.4 times more likely to demonstrate vitamin D inadequacy compared to non-Hispanic Whites (ORadj=6.351; 95% CI 5.338, 7.555; p<0.0001). Also, female gender was a significant predictor of vitamin D inadequacy (ORadj=1.499; 95% CI 1.315, 1.708; p<0.0001) in multivariate models. Subjects who reported not taking vitamin D supplements in the past 30 days were more than twice as likely to be vitamin D inadequate compared with those who had taken dietary supplements containing vitamin D (ORadj=2.225; 95% CI 1.903, 2.601; p<0.0001). In conclusion, the strongest predictor of vitamin D inadequacy was non-Hispanic Black ethnicity. Other potential predictors included smoking, non-use of vitamin D supplements, abnormal BMI, collecting samples in winter, female gender, perception of own health condition as not excellent, lack of health care, and older age. More focused interventions targeting groups of United States residents with vitamin D inadequacy are needed.

Direct characterization of tuneable few-femtosecond dispersive-wave pulses in the deep UV.

Dispersive wave emission (DWE) in gas-filled hollow-core dielectric waveguides is a promising source of tuneable coherent and broadband radiation, but so far the generation of few-femtosecond pulses using this technique has not been demonstrated. Using in-vacuum frequency-resolved optical gating, we directly characterize tuneable 3 fs pulses in the deep ultraviolet generated via DWE. Through numerical simulations, we identify that the use of a pressure gradient in the waveguide is critical for the generation of short pulses.

Apparatus for soft x-ray table-top high harmonic generation.

There has been considerable recent interest in tabletop soft X-ray attosecond sources enabled by the new generation of intense, few-cycle laser sources at operating wavelengths longer than 800 nm. In our recent work [Johnson et al., Sci. Adv. 4(5), eaar3761 (2018)], we have demonstrated a new regime for the generation of X-ray attosecond pulses in the water window (284-540 eV) by high-harmonic generation, which resulted in soft X-ray fluxes of ≈109 photons/s and a maximum photon energy of 600 eV, an order of magnitude and 50 eV higher, respectively, than previously attained with few-cycle drivers. Here we present the key elements of our apparatus for the generation and detection of soft X-ray high harmonic radiation in the water window. Of critical importance is a differentially pumped gas target capable of supporting the multi-atmospheric pressures required to phase-match the high energy emission while strongly constraining the gas density, suppressing the effects of ionization and absorption outside the interaction region.