Advancing primary care with Artificial Intelligence and Machine Learning.

Primary care is the largest healthcare delivery platform in the US. Facing the Artificial Intelligence and Machine Learning technology (AI/ML) revolution, the primary care community would benefit from a roadmap revealing priority areas and opportunities for developing and integrating AI/ML-driven clinical tools. This article presents a framework that identifies five domains for AI/ML integration in primary care to support care delivery transformation and achieve the Quintuple Aims of the healthcare system. We concluded that primary care plays a critical role in developing, introducing, implementing, and monitoring AI/ML tools in healthcare and must not be overlooked as AI/ML transforms healthcare.

Awareness and Use of Contraceptive Methods and Perceptions of Long-Acting Reversible Contraception Among White and Non-White Women.

Background: Unintended pregnancies continue to account for half of all pregnancies in the United States, primarily due to incorrect or inconsistent use of contraception methods. Long-acting reversible contraception (LARC) methods are safe and highly effective, yet underutilized. Low uptake of LARC may be due to inadequate education, misconceptions, and cultural factors such as race, ethnicity, or religion. This study examined racial differences in contraceptive awareness and use among women seeking care at family health centers. Materials and Methods: Focus groups were used to identify recurrent themes in contraceptive choice of participants and develop a survey, completed by nonpregnant female patients 18-45 years of age from seven family health centers. Results: Among a total of 465 participants, 210 (46.2%) of whom were non-white, awareness of most types of birth control was generally high. Awareness of all types of contraceptives was significantly higher among white than non-white women (p < 0.001). Across most types of contraceptives, use was significantly higher among white women than non-white women with the exception of injectable hormones which were used significantly more often by non-white women (46.0% vs. 28.5%; p < 0.001). Reasons for using LARC did not vary by type nor by race but reasons for not using LARC varied by race and by specific method. Conclusions: Differing patterns of awareness, use, and perceptions of contraceptive methods between white and non-white women were revealed. By understanding factors that influence contraceptive awareness, use, and perceptions, clinicians can better address the contraceptive needs and concerns of their female patients. Clinical Trial # NCT03486743.

Using Machine Learning to Predict Primary Care and Advance Workforce Research.

PURPOSE: To develop and test a machine-learning-based model to predict primary care and other specialties using Medicare claims data. METHODS: We used 2014-2016 prescription and procedure Medicare data to train 3 sets of random forest classifiers (prescription only, procedure only, and combined) to predict specialty. Self-reported specialties were condensed to 27 categories. Physicians were assigned to testing and training cohorts, and random forest models were trained and then applied to 2014-2016 data sets for the testing cohort to generate a series of specialty predictions. Comparing the predicted specialty to self-report, we assessed performance with F1 scores and area under the receiver operating characteristic curve (AUROC) values. RESULTS: A total of 564,986 physicians were included. The combined model had a greater aggregate (macro) F1 score (0.876) than the prescription-only (0.745; P <.01) or procedure-only (0.821; P <.01) model. Mean F1 scores across specialties in the combined model ranged from 0.533 to 0.987. The mean F1 score was 0.920 for primary care. The mean AUROC value for the combined model was 0.992, with values ranging from 0.982 to 0.999. The AUROC value for primary care was 0.982. CONCLUSIONS: This novel approach showed high performance and provides a near real-time assessment of current primary care practice. These findings have important implications for primary care workforce research in the absence of accurate data.

Probing different spin states in xylyl radicals and ions.

Resonant one-color two-photon ionization spectroscopy and mass-selected threshold photoelectron spectroscopy were applied to study the electronic doublet states of the three xylyl (methyl-benzyl) radicals above 3.9 eV as well as the singlet and triplet states of the cations up to 10.5 eV. The experiments are complemented by quantum chemical calculations and Franck-Condon simulations to characterize the transitions and to identify the origin bands, allowing a precise determination of singlet-triplet splittings in the cations. Torsional motions of the methyl group notably affect the D0 → D3 transition of m-xylyl. All other investigated transitions either lead to electronic states with very low rotational barriers or suffer from spectral broadening in excess of methyl torsional energy levels. The methyl internal rotational potential is faithfully reproduced with the most basic ab initio methods, yet hyperconjugation could not be identified as a significant force shaping them. Time-dependent density functional theory describes the excited electronic states better than wave function theory approaches, notably EOM-CCSD.

Biologically Relevant Heterogeneity: Metrics and Practical Insights.

Heterogeneity is a fundamental property of biological systems at all scales that must be addressed in a wide range of biomedical applications, including basic biomedical research, drug discovery, diagnostics, and the implementation of precision medicine. There are a number of published approaches to characterizing heterogeneity in cells in vitro and in tissue sections. However, there are no generally accepted approaches for the detection and quantitation of heterogeneity that can be applied in a relatively high-throughput workflow. This review and perspective emphasizes the experimental methods that capture multiplexed cell-level data, as well as the need for standard metrics of the spatial, temporal, and population components of heterogeneity. A recommendation is made for the adoption of a set of three heterogeneity indices that can be implemented in any high-throughput workflow to optimize the decision-making process. In addition, a pairwise mutual information method is suggested as an approach to characterizing the spatial features of heterogeneity, especially in tissue-based imaging. Furthermore, metrics for temporal heterogeneity are in the early stages of development. Example studies indicate that the analysis of functional phenotypic heterogeneity can be exploited to guide decisions in the interpretation of biomedical experiments, drug discovery, diagnostics, and the design of optimal therapeutic strategies for individual patients.

Fullerenes in Space.

In 1985 the football structure of C60 , buckminsterfullerene was proposed and subsequently confirmed following its macroscopic synthesis in 1990. From the very beginning the role of C60 and C60+ in space was considered, particularly in the context of the enigmatic diffuse interstellar bands. These are absorption features found in the spectra of reddened star light. The first astronomical observations were made around one hundred years ago and despite significant efforts none of the interstellar molecules responsible have been identified. The absorption spectrum of C60+ was measured in a 5 K neon matrix in 1993 and two prominent bands near 9583 Šand 9645 Šwere observed. On the basis of this data the likely wavelength range in which the gas phase C60+ absorptions should lie was predicted. In 1994 two diffuse interstellar bands were found in this spectral region and proposed to be due to C60+ . It took over 20 years to measure the absorption spectrum of C60+ under conditions similar to those prevailing in diffuse clouds. In 2015, sophisticated laboratory experiments led to the confirmation that these two interstellar bands are indeed caused by C60+ , providing the first answer to this century old puzzle. Here, we describe the experiments, concepts and astronomical observations that led to the detection of C60+ in interstellar space.

The Pitt Innovation Challenge (PInCh): Driving Innovation in Translational Research Through an Incentive-Based, Problem-Focused Competition.

PROBLEM: Translational research aims to move scientific discoveries across the biomedical spectrum from the laboratory to humans, and to ultimately transform clinical practice and public health policies. Despite efforts to accelerate translational research through national initiatives, several major hurdles remain. APPROACH: The authors created the Pitt Innovation Challenge (PInCh) as an incentive-based, problem-focused approach to solving identified clinical or public health problems at the University of Pittsburgh Clinical and Translational Science Institute in spring 2014. With input from a broad range of stakeholders, PInCh leadership arrived at the challenge question: How do we empower individuals to take control of their own health outcomes? The authors developed the PInCh's three-round proposal submission and review process as well as an online contest management tool to support the process. OUTCOMES: Ninety-two teams submitted video proposals in round one. Proposals included mobile applications (29; 32%), other information technology (19; 21%), and community program (22; 24%) solutions. Ten teams advanced to the final round, where three were awarded $100,000 to implement their solution over 12 months. In a 6-month follow-up survey, 6/11 (55%) team leaders stated the PInCh helped to facilitate connections outside their normal sphere of collaborators. NEXT STEPS: Additional educational training sessions related to problem-focused research will be developed. The PInCh will be expanded to engage investment and industry communities to facilitate the translation of solutions to clinical practice via commercialization pathways. External organizations and other universities will be engaged to use the PInCh as a mechanism to fuel innovation in their spaces.

Structure and Electronic Transitions of C7H4O2+ and C7H5O2+ Ions: Neon Matrix and Theoretical Studies.

C7H4O2+ and C7H5O2+ ions and the respective neutrals have been investigated by absorption spectroscopy in neon matrixes following mass selection of ions produced from salicylic acid. Three electronic transitions starting at 649.6, 431.0, and 372.0 nm are detected for C7H4O2+ and assigned on the basis of CASPT2 energies and Franck-Condon simulations as the excitations from the X 2A″ to the 1 2A″, 2 2A″, and 3 2A″ electronic states of 6-(oxomethylene)-2,4-cyclohexadien-1-one ion (A+). Absorptions commencing at 366.4 nm are observed for C7H5O2+ and assigned to the 1 2A' ← X 2A' electronic transition of (2-hydroxyphenyl)methanone ion (J+). Neutralization of J+ leads to the appearance of four absorption systems attributed to the 4 2A″, 3 2A″, 2 2A″, and 1 2A″ ← X 2A″ transitions of J with origin bands 291.3, 361.2, 393.8, and 461.2 nm.

Pathway to the identification of C60+ in diffuse interstellar clouds.

The origin of the attenuation of starlight in diffuse clouds in interstellar space at specific wavelengths ranging from the visible to the near-infrared has been unknown since the first astronomical observations around a century ago. The absorption features, termed the diffuse interstellar bands, have subsequently been the subject of much research. Earlier this year four of these interstellar bands were shown to be due to the absorption by cold, gas phase [Formula: see text] molecules. This discovery provides the first answer to the problem of the diffuse interstellar bands and leads naturally to fascinating questions regarding the role of fullerenes and derivatives in interstellar chemistry. Here, we review the identification process placing special emphasis on the laboratory studies which have enabled spectroscopic measurement of large cations cooled to temperatures prevailing in the interstellar medium.This article is part of the themed issue 'Fullerenes: past, present and future, celebrating the 30th anniversary of Buckminster Fullerene'.

Electronic transitions of C5H(+) and C5H: neon matrix and CASPT2 studies.

Two electronic transitions at 512.3 and 250 nm of linear-C5H(+) are detected following mass-selective deposition of m/z = 61 cations into a 6 K neon matrix and assigned to the 1 (1)Π←X (1)Σ(+) and 1 (1)Σ(+)←X (1)Σ(+) systems. Five absorption systems of l-C5H with origin bands at 528,7, 482.6, 429.0, 368.5, and 326.8 nm are observed after neutralization of the cations in the matrix and identified as transitions from the X (2)Π to 1 (2)Δ, 1 (2)Σ (-), 1 (2)Σ(+), 2 (2)Π, and 3 (2)Π electronic states. The assignment to specific structures is based on calculated excitation energies, vibrational frequencies in the electronic states, along with simulated Franck-Condon profiles.

Electronic Characterization of Reaction Intermediates: The Fluorenylium, Phenalenylium, and Benz[f]indenylium Cations and Their Radicals.

Three vibrationally resolved absorption systems commencing at 538, 518, and 392 nm were detected in a 6 K neon matrix after mass-selected deposition of C13 H9 (+) ions (m/z=165) produced from fluorene in a hot-cathode discharge ion source. The benz[f]indenylium (BfI(+) : 538 nm), fluorenylium (FL9(+) : 518 nm), and phenalenylium (PHL(+) : 392 nm) cations are the absorbing molecules. Two electronic systems corresponding to neutral species are apparent at 490 and 546 nm after irradiation of the matrix with λ<260 nm photons and were assigned to the FL9 and BfI radicals, respectively. The strongest peak at 518 nm is the origin of the 2 (1) B2 ←X̃ (1) A1 absorption of FL9(+) , and the 490 nm band is the 2 (2) A2 ←X̃ (2) B1 origin of FL9. The electronic systems commencing at 538 nm and 546 nm were assigned to the 1 (1) A1 ←X̃ (1) A1 and 1 (2) A2 ←X̃ (2) A2 transitions of BfI(+) and BfI. The 392 nm band is the 1 (1) E'←X̃ (1) A1 ' transition of PHL(+). The electronic spectra of C13 H9 (+) /C13 H9 were assigned on the basis of the vertical excitation energies calculated with SAC-CI and MS-CASPT2 methods.

The Electronic Spectrum of the Fulvenallenyl Radical.

The fulvenallenyl radical was produced in 6 K neon matrices after mass-selective deposition of C7H5(-) and C7H5(+) generated from organic precursors in a hot cathode ion source. Absorption bands commencing at λ=401.3 nm were detected as a result of photodetachment of electrons from the deposited C7H5(-) and also by neutralization of C7H5(+) in the matrix. The absorption system is assigned to the 1 (2)B1 ←X (2)B1 transition of the fulvenallenyl radical on the basis of electronic excitation energies calculated with the MS-CASPT2 method. The vibrational excitation bands detected in the spectrum concur with the structure of the fulvenallenyl radical. Employing DFT calculations, it is found that the fulvenallenyl anion and its radical are the global minima on the potential energy surface among plausible structures of C7H5.

Gas Phase Detection of Benzocyclopropenyl.

The gas phase detection of benzocyclopropenyl is reported. In this aromatic resonance stabilized radical, a large angular strain is present due to a three-membered ring annelated to a benzene. The resonant two-color two-photon ionization technique is used to record the D1((2)A2) ← D0((2)B1) electronic transition of this radical after the in situ synthesis in a discharge source. The spectrum features absorptions up to 3300 cm(-1) above the origin band at 19,305 cm(-1). Benzocyclopropenyl is possibly the major product of the bimolecular reaction of benzene and an atomic carbon at low temperatures.

Electronic spectra of oxygen containing polycyclic hydrocarbon cations and the protonated analogues.

The electronic transitions of 9-fluorenone FL(+) and 2,3,6,7-dibenzotropone DBT(+) cations were detected in 6 K neon matrices following a mass-selective deposition. The absorptions at 649.2 and 472.2 nm are assigned to the 2 (2)B1←X̃(2)A2 FL(+) and 2(2)A(')←X̃(2)A(') DBT(+) transitions. Absorption spectra of protonated 9-fluorenone H(+)-FL and 2,3,6,7-dibenzotropone H(+)-DBT have also been measured. Protonation of the oxygenated polycyclic aromatic hydrocarbons is carried out in a hot cathode source via in situ produced protonated ethanol. Vibrationally resolved absorptions commencing at 423.3 nm of H-FL(+) and two band systems of H-DBT(+) with origins at 502.4 and 371.5 nm are assigned to the 2(1)A(')←X̃(1)A(') electronic transition of 9-hydroxy-fluorenyl cation and 1 (1)A←X̃(1)A, 2 (1)A←X̃(1)A of 2,3,6,7-dibenzocycloheptenol cation. The assignments are based on vertical excitation energy calculations with time dependent density functional theory, symmetry adapted cluster configuration interaction, and MS-CASPT2 methods.

Electronic spectra of linear HC5H and cumulene carbene H2C5.

The 1(3)Σu (-)←X(3)Σg (-) transition of linear HC5H (A) has been observed in a neon matrix and gas phase. The assignment is based on mass-selective experiments, extrapolation of previous results of the longer HC2n+1H homologues, and density functional and multi-state CASPT2 theoretical methods. Another band system starting at 303 nm in neon is assigned as the 1(1)A1←X˜(1)A1 transition of the cumulene carbene pentatetraenylidene H2C5 (B).

Electronic Spectroscopy of Resonantly Stabilized Aromatic Radicals: 1-Indanyl and Methyl Substituted Analogues.

The gas-phase electronic spectra of two resonantly stabilized radicals, 1-indanyl (C9H9) and 1-methyl-1-indanyl (C10H11), have been recorded in the visible region using a resonant two-color two-photon ionization (R2C2PI) scheme. The D1(A″) ← D0(A″) origin bands of 1-indanyl and 1-methyl-1-indanyl radicals are observed at 21157 and 20565 cm(­1), respectively. The excitation of a' vibrations in the D1 state is observed up to ∼1500 cm(­1) above the origin band in both cases. The experimental assignments are in agreement with DFT and TD-DFT calculations. The R2C2PI spectrum recorded at m/z = 131 amu (C10H11) features three additional electronic transitions at 21433, 21369, and 17989 cm(­1), which are assigned to the origin bands of 7-methyl-1-indanyl, 2,3,4-trihydronaphthyl, and methyl-4-ethenylbenzyl radicals, respectively.

Electronic transitions of C5H3⁺ and C5H3: neon matrix and CASPT2 studies.

Two absorption systems of C5H3(+) starting at 350 and 345 nm were detected following mass-selective deposition of m/e = 63 ions in a 6 K neon matrix. These are assigned to the 1 (1)A1 ← X (1)A1 electronic transition of 1,2,3,4-pentatetraenylium H2CCCCCH(+) (isomer B(+)) and 1 (1)B2 ← X (1)A1 of penta-1,4-diyne-3-ylium HCCCHCCH(+) (C(+)). The absorptions of neutral C5H3 isomers with onsets at 434.5, 398.3, 369.0, and 267.3 nm are also detected. The first two systems are assigned to the 1 (2)B1 ← X (2)B1 and 1 (2)A2 ← X (2)B1 transitions of isomer B and C, respectively, and the latter two to ethynylcyclopropenyl (A) and 3-vinylidenecycloprop-1-enyl (D) radicals. The structural assignments are based on the adiabatic excitation energies calculated with the MS-CASPT2 method. A vibrational analysis of the electronic spectra, based on the calculated harmonic frequencies, supports this.

Electronic absorption spectra of H2C6O⁺ isomers: produced by ion-molecule reactions.

Three absorption systems with origins at 354, 497, and 528 nm were detected after mass-selected deposition of H2C6O(+) in a 6 K neon matrix. The ions were formed by the reaction of C2O with HC4H(+) in a mixture of C3O2 and diacetylene in a hot cathode source, or by dissociative ionization of tetrabromocyclohexadienone. The 497 and 354 nm systems are assigned to the 1(2)A″ ← X(2)A″ and 2(2)A″ ← X(2)A″ electronic transitions of B(+), (2-ethynylcycloallyl)methanone cation, and the 528 nm absorption to the 1(2)A2 ← X(2)B1 transition of F(+), 2-ethynylbut-3-yn-1-enone-1-ylide, on the basis of calculated excitation energies with CASPT2.

Spectroscopic characterization of C7H3(+) and C7H3˙: electronic absorption and fluorescence in 6 K neon matrices.

Mass selective deposition of C7H3(+) (m/z = 87) into solid neon reveals the 1(1)A1←X(1)A1 electronic absorption system of hepta-1,2,3,4,5,6-heptahexaenylium cation B(+) [H2CCCCCCCH](+) with an origin band at 441.3 nm, 1(1)A'←X(1)A' transition of 2,4-pentadiynylium,1-ethynyl cation C(+) [HCCCHCCCCH](+) starting at 414.6 nm and the 1(1)A1←X(1)A1 one of cyclopropenylium,1,3-butadiynyl cation A(+) [HCCCCC<(CH=CH)](+) with an onset at 322.2 nm. Vibrationally resolved fluorescence was observed for isomer B(+) upon laser excitation of the absorption bands in the 1(1)A1←X(1)A1 transition. After neutralization of the cations in the matrix five absorption systems of the C7H3 neutral radicals starting at 530.3, 479.4, 482.3, 325.0 and 302.5 nm were detected. These were identified as the 1(2)A'←X(2)A' and 2(2)A'←X(2)A' electronic transitions of 2-(buta-1,3-diynyl)cycloprop-2yl-1-1ylidene E˙ [HCCCCC<(C=CH2)]˙, 1(2)B1←X(2)B1 of 1,2,3,4,5,6-heptahexaenyl B˙ [H2CCCCCCCH]˙, 3(2)B1←X(2)B1 of 3-buta-1,3-diynyl-cyclopropenyl A˙ [HCCCCC<(CH=CH)]˙ and 2(2)B1←X(2)A2 transition of 1,2-divinylidene-cyclopropanyl radical F˙ [HCC-cyc-(CCHC)-CCH]˙, respectively. The assignment is based on calculated vertical excitation energies using the CASPT2 method. Comparison of the calculated harmonic vibrational frequencies with those inferred from the spectra supports the assignment.

Laboratory spectroscopy of astrophysically relevant carbon species.

Carbon is one of the most common elements in the solar system, with a fractional abundance of 10(-4) relative to hydrogen. Thus, it is not surprising that over 100 carbon-bearing species have been definitively detected in the interstellar medium via their rotational, infrared, and/or electronic transitions. In order to identify these species, laboratory spectra are needed for comparison to astronomical data. Challenges arise when obtaining laboratory spectra due to the instability of many of these molecules. Over the years, sensitive instrumentation and better techniques for producing these species in situ have been developed to achieve this goal. The use of complementary spectroscopic methods, such as matrix isolation, cavity ringdown, resonance enhanced multiphoton ionization, and ion trapping have led to the identification of several new carbon species at optical and ultraviolet wavelengths. Laboratory spectra have been compared to astronomical data in order to gain further insight into interstellar chemistry. In particular, attempts have been made to identify the carriers of the diffuse interstellar bands, however, with little success. These results are discussed in the following review.