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.

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.

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.

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.

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.

X-ray Free Electron Laser Determination of Crystal Structures of Dark and Light States of a Reversibly Photoswitching Fluorescent Protein at Room Temperature.

The photochromic fluorescent protein Skylan-NS (Nonlinear Structured illumination variant mEos3.1H62L) is a reversibly photoswitchable fluorescent protein which has an unilluminated/ground state with an anionic and cis chromophore conformation and high fluorescence quantum yield. Photo-conversion with illumination at 515 nm generates a meta-stable intermediate with neutral trans-chromophore structure that has a 4 h lifetime. We present X-ray crystal structures of the cis (on) state at 1.9 Angstrom resolution and the trans (off) state at a limiting resolution of 1.55 Angstrom from serial femtosecond crystallography experiments conducted at SPring-8 Angstrom Compact Free Electron Laser (SACLA) at 7.0 keV and 10.5 keV, and at Linac Coherent Light Source (LCLS) at 9.5 keV. We present a comparison of the data reduction and structure determination statistics for the two facilities which differ in flux, beam characteristics and detector technologies. Furthermore, a comparison of droplet on demand, grease injection and Gas Dynamic Virtual Nozzle (GDVN) injection shows no significant differences in limiting resolution. The photoconversion of the on- to the off-state includes both internal and surface exposed protein structural changes, occurring in regions that lack crystal contacts in the orthorhombic crystal form.

Spatio-temporal characterization of intense few-cycle 2 µm pulses.

We present a variant of spatially encoded spectral shearing interferometry for measuring two-dimensional spatio-temporal slices of few-cycle pulses centered around 2 µm. We demonstrate experimentally that the device accurately retrieves the pulse-front tilt caused by angular dispersion of two-cycle pulses. We then use the technique to characterize 500-650 µJ pulses from a hollow fiber pulse compressor, with durations as short as 7.1 fs (1.3 optical cycles).

Absolute Configuration from Different Multifragmentation Pathways in Light-Induced Coulomb Explosion Imaging.

The absolute configuration of individual small molecules in the gas phase can be determined directly by light-induced Coulomb explosion imaging (CEI). Herein, this approach is demonstrated for ionization with a single X-ray photon from a synchrotron light source, leading to enhanced efficiency and faster fragmentation as compared to previous experiments with a femtosecond laser. In addition, it is shown that even incomplete fragmentation pathways of individual molecules from a racemic CHBrClF sample can give access to the absolute configuration in CEI. This leads to a significant increase of the applicability of the method as compared to the previously reported complete break-up into atomic ions and can pave the way for routine stereochemical analysis of larger chiral molecules by light-induced CEI.

Role of tunnel ionization in high harmonic generation from substituted benzenes.

We theoretically study high-harmonic generation in toluene, ortho-xylene and fluorobenzene driven by a 1.8 µm ultrashort pulse. We find that the chemical substitutions have a strong influence on the amplitude and phase of the emission from the highest occupied molecular orbital, despite having a small influence on the orbital itself. We show that this influence is due to the tunnel ionization step, which depends critically on the sign and amplitude of the asymptotic part of the wave function. We discuss how these effects would manifest in phase-sensitive high-harmonic generation spectroscopy experiments.

Practical witness for electronic coherences.

The origin of the coherences in two-dimensional spectroscopy of photosynthetic complexes remains disputed. Recently, it has been shown that in the ultrashort-pulse limit, oscillations in a frequency-integrated pump-probe signal correspond exclusively to electronic coherences, and thus such experiments can be used to form a test for electronic vs. vibrational oscillations in such systems. Here, we demonstrate a method for practically implementing such a test, whereby pump-probe signals are taken at several different pulse durations and used to extrapolate to the ultrashort-pulse limit. We present analytic and numerical results determining requirements for pulse durations and the optimal choice of pulse central frequency, which can be determined from an absorption spectrum. Our results suggest that for numerous systems, the required experiment could be implemented by many ultrafast spectroscopy laboratories using pulses of tens of femtoseconds in duration. Such experiments could resolve the standing debate over the nature of coherences in photosynthetic complexes.

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.

Experimental realization of optical eigenmode super-resolution.

We experimentally demonstrate the feasibility of a super-resolution technique based on eigenmode decomposition. This technique has been proposed theoretically but, to the best of our knowledge, has not previously been realized experimentally for optical imaging systems with circular apertures. We use a standard diffraction-limited 4f imaging system with circular apertures for which the radial eigenmodes are the circular prolate spheroidal functions. For three original objects with different content of angular information we achieve 45%, 49%, and 89% improvement of resolution over the Rayleigh limit. The work presented can be considered as progress towards the goal of reaching the quantum limits of super-resolution.

An integrated randomized intervention to reduce behavioral and psychosocial risks: pregnancy and neonatal outcomes.

While biomedical risks contribute to poor pregnancy and neonatal outcomes in African American (AA) populations, behavioral and psychosocial risks (BPSR) may also play a part. Among low income AA women with psychosocial risks, this report addresses the impacts on pregnancy and neonatal outcomes of an integrated education and counseling intervention to reduce BPSR, as well as the contributions of other psychosocial and biomedical risks. Subjects were low income AA women ≥18 years living in the Washington, DC, metropolitan area and seeking prenatal care. Subjects (n = 1,044) were screened for active smoking, environmental tobacco smoke exposure (ETSE), depression, or intimate partner violence (IPV) and then randomized to intervention (IG) or usual care (UCG) groups. Data were collected prenatally, at delivery, and postpartum by maternal report and medical record abstraction. Multiple imputation methodology was used to estimate missing variables. Rates of pregnancy outcomes (miscarriage, live birth, perinatal death), preterm labor, Caesarean section, sexually transmitted infection (STI) during pregnancy, preterm birth (<37 weeks), low birth weight (<2,500 g), very low birth weight (<1,500 g), small for gestational age, neonatal intensive care unit (NICU) admission, and >2 days of hospitalization were compared between IG and UCG. Logistic regression models were created to predict outcomes based on biomedical risk factors and the four psychosocial risks (smoking, ETSE, depression, and IPV) targeted by the intervention. Rates of adverse pregnancy and neonatal outcomes were high and did not differ significantly between IG and UCG. In adjusted analysis, STI during the current pregnancy was associated with IPV (OR = 1.41, 95% CI 1.04-1.91). Outcomes such as preterm labor, caesarian section in pregnancy and preterm birth, low birth weight, small for gestational age, NICU admissions and >2 day hospitalization of the infants were associated with biomedical risk factors including preexisting hypertension and diabetes, previous preterm birth (PTB), and late initiation of prenatal care, but they were not significantly associated with active smoking, ETSE, depression, or IPV. Neither the intervention to reduce BPSR nor the psychosocial factors significantly contributed to the pregnancy and neonatal outcomes. This study confirms that biomedical factors significantly contribute to adverse outcomes in low income AA women. Biomedical factors outweighed psychosocial factors in contributing to adverse pregnancy and neonatal outcomes in this high-risk population. Early identification and management of hypertension, diabetes and previous PTB in low income AA women may reduce health disparities in birth outcomes. Level of evidence I.

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.

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.