Expanding the bandwidth of fluorescence-detected two-dimensional electronic spectroscopy using a broadband continuum probe pulse pair.

We demonstrate fluorescence-detected two-dimensional electronic spectroscopy (F-2DES) with a broadband, continuum probe pulse pair in the pump-probe geometry. The approach combines a pump pulse pair generated by an acousto-optic pulse-shaper with precise control of the relative pump pulse phase and time delay with a broadband, continuum probe pulse pair created using the Translating Wedge-based Identical pulses eNcoding System (TWINS). The continuum probe expands the spectral range of the detection axis and lengthens the waiting times that can be accessed in comparison to implementations of F-2DES using a single pulse-shaper. We employ phase-cycling of the pump pulse pair and take advantage of the separation of signals in the frequency domain to isolate rephasing and non-rephasing signals and optimize the signal-to-noise ratio. As proof of principle, we demonstrate broadband F-2DES on a laser dye and bacteriochlorophyll a.

Early observations with an ERAS pathway for thyroid and parathyroid surgery: Moving the goalposts forward.

BACKGROUND: Enhanced recovery after surgery pathways have become the standard of care in various surgical specialties. In this study, we discuss our initial experience with a staged enhanced recovery after surgery pathway in endocrine surgery and assess the impact of this pathway on select perioperative outcomes and unanticipated admissions. METHODS: We collected information regarding all thyroid/parathyroid surgeries performed by endocrine surgeons at our institution before and after the implementation of the multi-intervention enhanced recovery after surgery pathway. We compared relevant outcomes for all cases 1 year before (n = 479) and 1 year after (n = 166) implementation of the pathway. We also compared outcomes between enhanced recovery after surgery patient groups with varying levels of enhanced recovery after surgery compliance. RESULTS: Enhanced recovery after surgery was associated with a significant decrease in total length of stay (9.2 vs 7.5 hours, P < .0001). Whereas there was no significant decrease in all-cause unanticipated postoperative admissions, there was a decrease in patient-initiated admissions in the Enhanced recovery after surgery group. There was also a significant decrease in mean postoperative morphine milligram equivalents (14.4 vs 16.2 vs 24.8, P = .0015), average daily morphine milligram equivalents (25.6 vs 45.6 vs 53, P < .0001), and average daily pain scores (1.89 vs 2.38 vs 2.74, P = .0045) in the Enhanced recovery after surgery group (particularly with increasing Enhanced recovery after surgery compliance). There were no significant differences in the requirement for postoperative antiemetics or in the post-anesthesia care unit length of stay. CONCLUSION: This study demonstrates a significant benefit from Enhanced recovery after surgery pathways for thyroidectomies and parathyroidectomies, even with initial data and a staggered roll-out plan. Further directions include a follow-up study once we reach a higher level of institutional compliance with all components of the Enhanced Recovery After Surgery pathway and a prospective trial to identify the relative significance of different portions of the Enhanced Recovery after Surgery pathway, particularly the superficial cervical plexus block.

Two-Dimensional Electronic Spectroscopy of the Far-Red-Light Photosystem II Reaction Center.

Understanding the role of specific pigments in primary energy conversion in the photosystem II (PSII) reaction center has been impeded by the spectral overlap of its constituent pigments. When grown in far-red light, some cyanobacteria incorporate chlorophyll-f and chlorophyll-d into PSII, relieving the spectral congestion. We employ two-dimensional electronic spectroscopy to study PSII at 77 K from Synechococcus sp. PCC 7335 cells that were grown in far-red light (FRL-PSII). We observe the formation of a radical pair within ∼3 ps that we assign to ChlD1•-PD1•+. While PheoD1 is thought to act as the primary electron acceptor in PSII from cells grown in visible light, we see no evidence of its involvement, which we attribute to its reduction by dithionite treatment in our samples. Our work demonstrates that primary charge separation occurs between ChlD1 and PD1 in FRL-PSII, suggesting that PD1/PD2 may play an underappreciated role in PSII's charge separation mechanism.

Charge separation in the photosystem II reaction center resolved by multispectral two-dimensional electronic spectroscopy.

The photosystem II reaction center (PSII RC) performs the primary energy conversion steps of oxygenic photosynthesis. While the PSII RC has been studied extensively, the similar time scales of energy transfer and charge separation and the severely overlapping pigment transitions in the Qy region have led to multiple models of its charge separation mechanism and excitonic structure. Here, we combine two-dimensional electronic spectroscopy (2DES) with a continuum probe and two-dimensional electronic vibrational spectroscopy (2DEV) to study the cyt b559-D1D2 PSII RC at 77 K. This multispectral combination correlates the overlapping Qy excitons with distinct anion and pigment-specific Qx and mid-infrared transitions to resolve the charge separation mechanism and excitonic structure. Through extensive simultaneous analysis of the multispectral 2D data, we find that charge separation proceeds on multiple time scales from a delocalized excited state via a single pathway in which PheoD1 is the primary electron acceptor, while ChlD1 and PD1 act in concert as the primary electron donor.

Extracting the excitonic Hamiltonian of a chlorophyll dimer from broadband two-dimensional electronic spectroscopy.

We apply Frenkel exciton theory to model the entire Q-band of a tightly bound chlorophyll dimer inspired by the photosynthetic reaction center of photosystem II. The potential of broadband two-dimensional electronic spectroscopy experiment spanning the Qx and Qy regions to extract the parameters of the model dimer Hamiltonian is examined through theoretical simulations of the experiment. We find that the local nature of Qx excitation enables identification of molecular properties of the delocalized Qy excitons. Specifically, we demonstrate that the cross-peak region, where excitation energy is resonant with Qy while detection is at Qx, contains specific spectral signatures that can reveal the full real-space molecular Hamiltonian, a task that is impossible by considering the Qy transitions alone. System-bath coupling and site energy disorder in realistic systems may limit the resolution of these spectral signatures due to spectral congestion.

Hidden vibronic and excitonic structure and vibronic coherence transfer in the bacterial reaction center.

We report two-dimensional electronic spectroscopy (2DES) experiments on the bacterial reaction center (BRC) from purple bacteria, revealing hidden vibronic and excitonic structure. Through analysis of the coherent dynamics of the BRC, we identify multiple quasi-resonances between pigment vibrations and excitonic energy gaps, and vibronic coherence transfer processes that are typically neglected in standard models of photosynthetic energy transfer and charge separation. We support our assignment with control experiments on bacteriochlorophyll and simulations of the coherent dynamics using a reduced excitonic model of the BRC. We find that specific vibronic coherence processes can readily reveal weak exciton transitions. While the functional relevance of such processes is unclear, they provide a spectroscopic tool that uses vibrations as a window for observing excited state structure and dynamics elsewhere in the BRC via vibronic coupling. Vibronic coherence transfer reveals the upper exciton of the "special pair" that was weakly visible in previous 2DES experiments.

Stones left unturned: Missed opportunities to diagnose primary hyperparathyroidism in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a sequela of primary hyperparathyroidism and an indication for parathyroidectomy. The prevalence of primary hyperparathyroidism in patients with nephrolithiasis is 3% to 5%; however, recent studies suggest that many hypercalcemic patients with nephrolithiasis never undergo workup for primary hyperparathyroidism. Our goal is to evaluate primary hyperparathyroidism screening rates at a tertiary academic health institution and identify opportunities to increase referral rates in patients presenting with nephrolithiasis. METHODS: We retrospectively reviewed 15,725 patients across an academic health system who presented with nephrolithiasis between 2012 and 2020. Calcium levels measured within 6 months of presentation were identified, and those with hypercalcemia (≥10.3 mg/dL) were reviewed if parathyroid hormone levels were measured. Patients with primary hyperparathyroidism were evaluated to see if they were referred to a specialist for treatment. RESULTS: Of 15,725 patients presenting with nephrolithiasis, 12,420 (79%) had calcium levels measured; 630 patients (4.0%) were hypercalcemic, and 207 (33%) had parathyroid hormone levels measured. Patients were more likely to have parathyroid hormone levels sent if they were older, had higher calcium levels, or presented to an outpatient clinic (P = .028, P = .002, P < .001). We identified 89 patients (0.6%) with primary hyperparathyroidism, of which only 35 (39%) were referred for treatment. CONCLUSION: The proportion of patients presenting with nephrolithiasis ultimately diagnosed with primary hyperparathyroidism was significantly lower than others have reported. Additionally, a substantial number of patients with nephrolithiasis did not have calcium and/or parathyroid hormone levels measured. These missed opportunities for diagnosis are critical as early definitive management of primary hyperparathyroidism can prevent recurrent nephrolithiasis and other primary hyperparathyroidism-related end organ effects.

Phase-modulated rapid-scanning fluorescence-detected two-dimensional electronic spectroscopy.

We present a rapid-scanning approach to fluorescence-detected two-dimensional electronic spectroscopy that combines acousto-optic phase-modulation with digital lock-in detection. This approach shifts the signal detection window to suppress 1/f laser noise and enables interferometric tracking of the time delays to allow for correction of spectral phase distortions and accurate phasing of the data. This use of digital lock-in detection enables acquisition of linear and nonlinear signals of interest in a single measurement. We demonstrate the method on a laser dye, measuring the linear fluorescence excitation spectrum as well as rephasing, non-rephasing, and absorptive fluorescence-detected two-dimensional electronic spectra.

Right ventricular thrombus and pulmonary embolism after infliximab therapy for ulcerative colitis.

Infliximab, an antitumour necrosis factor alpha (TNF-alpha)agent, is a cornerstone of treatment of inflammatory bowel disease with a favourable and well-tolerated side effect profile. While the majority of side effects associated with infliximab have been well established, the pathophysiology of infliximab-associated thrombosis remains controversial and poorly defined. We present a case of a young woman with ulcerative colitis who presented with a right ventricular thrombus and bilateral pulmonary emboli after initiation of infliximab and was subsequently found to have underlying factor V Leiden and prothrombin gene mutation. Clinicians should be aware of this potential adverse event associated with anti-TNF agents, especially in individuals with predisposing prothrombotic mutations such as factor V Leiden or prothrombin gene mutation.

Excitonic structure and charge separation in the heliobacterial reaction center probed by multispectral multidimensional spectroscopy.

Photochemical reaction centers are the engines that drive photosynthesis. The reaction center from heliobacteria (HbRC) has been proposed to most closely resemble the common ancestor of photosynthetic reaction centers, motivating a detailed understanding of its structure-function relationship. The recent elucidation of the HbRC crystal structure motivates advanced spectroscopic studies of its excitonic structure and charge separation mechanism. We perform multispectral two-dimensional electronic spectroscopy of the HbRC and corresponding numerical simulations, resolving the electronic structure and testing and refining recent excitonic models. Through extensive examination of the kinetic data by lifetime density analysis and global target analysis, we reveal that charge separation proceeds via a single pathway in which the distinct A0 chlorophyll a pigment is the primary electron acceptor. In addition, we find strong delocalization of the charge separation intermediate. Our findings have general implications for the understanding of photosynthetic charge separation mechanisms, and how they might be tuned to achieve different functional goals.

Mechanistic Study of Charge Separation in a Nonfullerene Organic Donor-Acceptor Blend Using Multispectral Multidimensional Spectroscopy.

Organic photovoltaics (OPVs) based on nonfullerene acceptors are now approaching commercially viable efficiencies. One key to their success is efficient charge separation with low potential loss at the donor-acceptor heterojunction. Due to the lack of spectroscopic probes, open questions remain about the mechanisms of charge separation. Here, we study charge separation of a model system composed of the donor, poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-benzo[1,2-b:4,5-b']dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2-ethylhexyl)benzo[1',2'-c:4',5'-c']dithiophene-4,8-dione) (PBDB-T), and the nonfullerene acceptor, 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITIC), using multidimensional spectroscopy spanning the visible to the mid-infrared. We find that bound polaron pairs (BPPs) generated within ITIC domains play a dominant role in efficient hole transfer, transitioning to delocalized polarons within 100 fs. The weak electron-hole binding within the BPPs and the resulting polaron delocalization are key factors for efficient charge separation at nearly zero driving force. Our work provides useful insight into how to further improve the power conversion efficiency in OPVs.

All up in smoke: vaping-associated lung injury.

The electronic cigarette (EC), was initially introduced as a safe alternative to conventional cigarette smoking While initially seemingly innocuous, over 2800 E-cigarette, or Vaping, product use-associated lung injury (EVALI) cases have been reported in the USA, with a spectrum of clinical severity ranging from mild dyspnea to overt respiratory failure In this report we highlight three EVALI cases whom presented with dyspnea and a variety of non-specific symptoms. Diagnostic imaging demonstrated bilateral reticular infiltrates and ground-glass opacities with lymphadenopathy. Clinically, patients failed to respond to empiric antibiotics but improved after initiating steroids. Consistent with prior case series, our patients reported exposure to EC liquids containing tetrahydrocannabinol (THC)/cannabidiols (CBD) additives, suggesting Vitamin E acetate as the potentially harmful constituent. In this case series and review, we not only summarize prior clinical studies that have evaluated the effects of vaping on cardiopulmonary function as well as case reports on EVALI, but also discuss the pathophysiology of vaping and EVALI. It remains unclear not only why some individuals develop EVALI, but why the clinical and pathological presentations vary. EVALI remains a significant public health concern and clinicians must maintain a high index of suspicion for this novel phenomenon.

Two-dimensional electronic Stark spectroscopy of a photosynthetic dimer.

Stark spectroscopy, which measures changes in the linear absorption of a sample in the presence of an external DC electric field, is a powerful experimental tool for probing the existence of charge-transfer (CT) states in photosynthetic systems. CT states often have small transition dipole moments, making them insensitive to other spectroscopic methods, but are particularly sensitive to Stark spectroscopy due to their large permanent dipole moment. In a previous study, we demonstrated a new experimental method, two-dimensional electronic Stark spectroscopy (2DESS), which combines two-dimensional electronic spectroscopy (2DES) and Stark spectroscopy. In order to understand how the presence of CT states manifest in 2DESS, here, we perform computational modeling and calculations of 2DESS as well as 2DES and Stark spectra, studying a photosynthetic dimer inspired by the photosystem II reaction center. We identify specific cases where qualitatively different sets of system parameters produce similar Stark and 2DES spectra but significantly different 2DESS spectra, showing the potential for 2DESS to aid in identifying CT states and their coupling to excitonic states.

Observation of Ultrafast Coherence Transfer and Degenerate States with Polarization-Controlled Two-Dimensional Electronic Spectroscopy.

Optical spectroscopy is a powerful tool to interrogate quantum states of matter. We present simulation results for the cross-polarized two-dimensional electronic spectra of the light-harvesting system LH2 of purple bacteria. We identify a spectral feature on the diagonal, which we assign to ultrafast coherence transfer between degenerate states. The implication for the interpretation of previous experiments on different systems and the potential use of this feature are discussed. In particular, we foresee that this kind of feature will be useful for identifying mixed degenerate states and for identifying the origin of symmetry breaking disorder in systems like LH2. Furthermore, this may help identify both vibrational and electronic states in biological systems such as proteins and solid-state materials such as hybrid perovskites.

Quantum biology revisited.

Photosynthesis is a highly optimized process from which valuable lessons can be learned about the operating principles in nature. Its primary steps involve energy transport operating near theoretical quantum limits in efficiency. Recently, extensive research was motivated by the hypothesis that nature used quantum coherences to direct energy transfer. This body of work, a cornerstone for the field of quantum biology, rests on the interpretation of small-amplitude oscillations in two-dimensional electronic spectra of photosynthetic complexes. This Review discusses recent work reexamining these claims and demonstrates that interexciton coherences are too short lived to have any functional significance in photosynthetic energy transfer. Instead, the observed long-lived coherences originate from impulsively excited vibrations, generally observed in femtosecond spectroscopy. These efforts, collectively, lead to a more detailed understanding of the quantum aspects of dissipation. Nature, rather than trying to avoid dissipation, exploits it via engineering of exciton-bath interaction to create efficient energy flow.

Efficient Charge Generation via Hole Transfer in Dilute Organic Donor-Fullerene Blends.

Efficient organic photovoltaics (OPVs) require broadband charge photogeneration with near-unity quantum yield. This can only be achieved by exploiting all pathways that generate charge. Electron transfer from organic donors to acceptors has been well-studied and is considered the primary path to charge photogeneration in OPVs. In contrast, much less is known about the hole transfer pathway. Here we study charge photogeneration in an archetypal system comprising tetraphenyldibenzoperiflanthene:C70 blends using our recently developed multispectral two-dimensional electronic spectroscopy (M-2DES), supported by time-dependent density functional theory and fully quantum-mechanical Fermi's golden rule rate calculations. Our approach identifies in real time two rapid charge transfer pathways that are confirmed through computational analysis. Surprisingly, we find that both electron and hole transfer occur with comparable rates and efficiencies, facilitated by donor-acceptor electronic interactions. Our results highlight the importance of the hole transfer pathway for optimizing the efficiency of OPV devices employing small-molecule heterojunctions.

Exploiting chemistry and molecular systems for quantum information science.

The power of chemistry to prepare new molecules and materials has driven the quest for new approaches to solve problems having global societal impact, such as in renewable energy, healthcare and information science. In the latter case, the intrinsic quantum nature of the electronic, nuclear and spin degrees of freedom in molecules offers intriguing new possibilities to advance the emerging field of quantum information science. In this Perspective, which resulted from discussions by the co-authors at a US Department of Energy workshop held in November 2018, we discuss how chemical systems and reactions can impact quantum computing, communication and sensing. Hierarchical molecular design and synthesis, from small molecules to supramolecular assemblies, combined with new spectroscopic probes of quantum coherence and theoretical modelling of complex systems, offer a broad range of possibilities to realize practical quantum information science applications.

Vibronic structure of photosynthetic pigments probed by polarized two-dimensional electronic spectroscopy and ab initio calculations.

Bacteriochlorophyll a (Bchl a) and chlorophyll a (Chl a) play important roles as light absorbers in photosynthetic antennae and participate in the initial charge-separation steps in photosynthetic reaction centers. Despite decades of study, questions remain about the interplay of electronic and vibrational states within the Q-band and its effect on the photoexcited dynamics. Here we report results of polarized two-dimensional electronic spectroscopic measurements, performed on penta-coordinated Bchl a and Chl a and their interpretation based on state-of-the-art time-dependent density functional theory calculations and vibrational mode analysis for spectral shapes. We find that the Q-band of Bchl a is comprised of two independent bands, that are assigned following the Gouterman model to Q x and Q y states with orthogonal transition dipole moments. However, we measure the angle to be ∼75°, a finding that is confirmed by ab initio calculations. The internal conversion rate constant from Q x to Q y is found to be 11 ps-1. Unlike Bchl a, the Q-band of Chl a contains three distinct peaks with different polarizations. Ab initio calculations trace these features back to a spectral overlap between two electronic transitions and their vibrational replicas. The smaller energy gap and the mixing of vibronic states result in faster internal conversion rate constants of 38-50 ps-1. We analyze the spectra of penta-coordinated Bchl a and Chl a to highlight the interplay between low-lying vibronic states and their relationship to photoinduced relaxation. Our findings shed new light on the photoexcited dynamics in photosynthetic systems where these chromophores are primary pigments.