Structure of the moiré exciton captured by imaging its electron and hole.

Interlayer excitons (ILXs) - electron-hole pairs bound across two atomically thin layered semiconductors - have emerged as attractive platforms to study exciton condensation1-4, single-photon emission and other quantum information applications5-7. Yet, despite extensive optical spectroscopic investigations8-12, critical information about their size, valley configuration and the influence of the moiré potential remains unknown. Here, in a WSe2/MoS2 heterostructure, we captured images of the time-resolved and momentum-resolved distribution of both of the particles that bind to form the ILX: the electron and the hole. We thereby obtain a direct measurement of both the ILX diameter of around 5.2 nm, comparable with the moiré-unit-cell length of 6.1 nm, and the localization of its centre of mass. Surprisingly, this large ILX is found pinned to a region of only 1.8 nm diameter within the moiré cell, smaller than the size of the exciton itself. This high degree of localization of the ILX is backed by Bethe-Salpeter equation calculations and demonstrates that the ILX can be localized within small moiré unit cells. Unlike large moiré cells, these are uniform over large regions, allowing the formation of extended arrays of localized excitations for quantum technology.

Performance-limiting nanoscale trap clusters at grain junctions in halide perovskites.

Halide perovskite materials have promising performance characteristics for low-cost optoelectronic applications. Photovoltaic devices fabricated from perovskite absorbers have reached power conversion efficiencies above 25 per cent in single-junction devices and 28 per cent in tandem devices1,2. This strong performance (albeit below the practical limits of about 30 per cent and 35 per cent, respectively3) is surprising in thin films processed from solution at low-temperature, a method that generally produces abundant crystalline defects4. Although point defects often induce only shallow electronic states in the perovskite bandgap that do not affect performance5, perovskite devices still have many states deep within the bandgap that trap charge carriers and cause them to recombine non-radiatively. These deep trap states thus induce local variations in photoluminescence and limit the device performance6. The origin and distribution of these trap states are unknown, but they have been associated with light-induced halide segregation in mixed-halide perovskite compositions7 and with local strain8, both of which make devices less stable9. Here we use photoemission electron microscopy to image the trap distribution in state-of-the-art halide perovskite films. Instead of a relatively uniform distribution within regions of poor photoluminescence efficiency, we observe discrete, nanoscale trap clusters. By correlating microscopy measurements with scanning electron analytical techniques, we find that these trap clusters appear at the interfaces between crystallographically and compositionally distinct entities. Finally, by generating time-resolved photoemission sequences of the photo-excited carrier trapping process10,11, we reveal a hole-trapping character with the kinetics limited by diffusion of holes to the local trap clusters. Our approach shows that managing structure and composition on the nanoscale will be essential for optimal performance of halide perovskite devices.

A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer.

BACKGROUND: In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab. METHODS: Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor ß receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive. RESULTS: This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available. CONCLUSIONS: The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort. TRIAL REGISTRATION: Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).

mHealth apps for gestational diabetes mellitus that provide clinical decision support or artificial intelligence: A scoping review.

AIMS: Gestational diabetes (GDM) is the most common metabolic disorder of pregnancy, requiring complex management and empowerment of those affected. Mobile health (mHealth) applications (apps) are proposed for streamlining healthcare service delivery, extending care relationships into the community, and empowering those affected by prolonged medical disorders to be equal collaborators in their healthcare. This review investigates mHealth apps intended for use with GDM; specifically those powered by artificial intelligence (AI) or providing decision support. METHODS: A scoping review using the novel Survey Tool approach for collaborative literature Reviews (STaR) process was performed. RESULTS: From 18 papers, 11 discrete GDM-based mHealth apps were identified, but only 3 were reasonably mature with only one currently in use in a clinical setting. Two-thirds of the apps provided condition-relevant contextual user feedback that could aid in patient self care. However, although each app targeted one or more components of the GDM clinical pathway, no app addressed the entirety from diagnosis to postpartum. CONCLUSIONS: There are limited mHealth apps for GDM that incorporate AI or AI-based decision support. Many exist only to record patient information like blood glucose readings or diet, provide generic patient education or advice, or to reduce adverse events by providing medication or appointment alerts. Significant barriers remain that continue to limit the adoption of mHealth apps in clinical care settings. Further research and development are needed to deliver intelligent holistic mHealth apps using AI that can truly reduce healthcare resource use and improve outcomes by enabling patient self care in the community.

Subgroups from regression trees with adjustment for prognostic effects and postselection inference.

Identification of subgroups with differential treatment effects in randomized trials is attracting much attention. Many methods use regression tree algorithms. This article addresses 2 important questions arising from the subgroups: how to ensure that treatment effects in subgroups are not confounded with effects of prognostic variables and how to determine the statistical significance of treatment effects in the subgroups. We address the first question by selectively including linear prognostic effects in the subgroups in a regression tree model. The second question is more difficult because it falls within the subject of postselection inference. We use a bootstrap technique to calibrate normal-theory t intervals so that their expected coverage probability, averaged over all the subgroups in a fitted model, approximates the desired confidence level. It can also provide simultaneous confidence intervals for all subgroups. The first solution is implemented in the GUIDE algorithm and is applicable to data with missing covariate values, 2 or more treatment arms, and outcomes subject to right censoring. Bootstrap calibration is applicable to any subgroup identification method; it is not restricted to regression tree models. Two real examples are used for illustration: a diabetes trial where the outcomes are completely observed but some covariate values are missing and a breast cancer trial where the outcome is right censored.

High-Temperature Terahertz Optical Diode Effect without Magnetic Order in Polar FeZnMo_{3}O_{8}.

We present a terahertz spectroscopic study of polar ferrimagnet FeZnMo_{3}O_{8}. Our main finding is a giant high-temperature optical diode effect, or nonreciprocal directional dichroism, where the transmitted light intensity in one direction is over 100 times lower than intensity transmitted in the opposite direction. The effect takes place in the paramagnetic phase with no long-range magnetic order in the crystal, which contrasts sharply with all existing reports of the terahertz optical diode effect in other magnetoelectric materials, where the long-range magnetic ordering is a necessary prerequisite. In FeZnMo_{3}O_{8}, the effect occurs resonantly with a strong magnetic dipole active transition centered at 1.27 THz and assigned as electron spin resonance between the eigenstates of the single-ion anisotropy Hamiltonian. We propose that the optical diode effect in paramagnetic FeZnMo_{3}O_{8} is driven by single-ion terms in magnetoelectric free energy.

Variation in Generic Drug Manufacturers' Product Characteristics.

OBJECTIVES: Studies suggest appearance may be an important factor in medication nonadherence. This study was undertaken to characterize the range of appearances and costs of 16 oral solid generic medications in four major chronic diseases/conditions. METHODS: We identified frequently prescribed medications in four therapeutic classes-antidiabetics, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), beta blockers, and heart failure drugs-and verified that each had at least three generic manufacturer sources in 2016. The color, shape, scoring, and size for each formulation were compared. Prices were determined based on manufacturers' self-reported wholesale acquisition costs effective December 31, 2016. RESULTS: We identified 40 unique manufacturers for the antidiabetics, 35 for the statins, 38 for the beta blockers, and 71 for the heart failure agents. For all 16 drugs across all four disease states, there was an average of three colors, two shapes, 11 manufacturers, and four appearances when color and shape together are considered. The cost variance per drug ranged from 2% to more than 62,253%. CONCLUSION: Substantial appearance variation among generically equivalent products raises the strong possibility that patients may experience product switches that could increase the likelihood of nonadherence. Our data support the need to further study drug appearance changes and interventions as a potential factor affecting chronic disease adherence outcomes.

Differential expression of VEGFR2 protein in HER2 positive primary human breast cancer: potential relevance to anti-angiogenic therapies.

BACKGROUND: Clinically relevant predictive biomarkers to tailor anti-angiogenic therapies to breast cancer (BRC) patient subpopulations are an unmet need. METHODS: We analyzed tumor vascular density and VEGFR2 protein expression in various subsets of primary human BRCs (186 females; Mean age: 59 years; range 33-88 years), using a tissue microarray. Discrete VEGFR2+ and CD34+ tumor vessels were manually scored in invasive ductal, lobular, mixed ductal-lobular and colloid (N = 139, 22, 18, 7) BRC cores. RESULTS: The observed CD34+ and VEGFR2+ tumor vascular counts in individual cases were heterogeneous. Mean CD34+ and VEGFR2+ tumor vessel counts were 11 and 3.4 per tumor TMA core respectively. Eighty-nine of 186 (48%) cases had >10 CD34+ tumor vessels, while 97/186 (52%) had fewer CD34+ vessels in each TMA core. Of 169 analyzable cores in the VEGFR2 stained TMA, 90 (53%) showed 1-5 VEGFR2+ tumor vessels/TMA core, while 42/169 (25%) cores had no detectable VEGFR2+ tumor vessels. Thirteen of 169 (8%) cases also showed tumor cell (cytoplasmic/membrane) expression of VEGFR2. Triple-negative breast cancers (TNBCs) appeared to be less vascular (Mean VD = 9.8, range 0-34) than other breast cancer subtypes. Overall, VEGFR2+ tumor vessel counts were significantly higher in HER2+ as compared to HR+ (p = 0.04) and TNBC (p = 0.02) tissues. Compared to HER2- cases, HER2+ breast cancers had higher VEGFR2+ tumor vessel counts (p = 0.007). CONCLUSION: Characterization of pathologic angiogenesis in HER2+ breast cancer provides scientific rationale for future investigation of clinical activity of agents targeting the VEGF/VEGFR2 axis in this clinically aggressive breast cancer subtype.

Identification of subgroups with differential treatment effects for longitudinal and multiresponse variables.

We describe and evaluate a regression tree algorithm for finding subgroups with differential treatments effects in randomized trials with multivariate outcomes. The data may contain missing values in the outcomes and covariates, and the treatment variable is not limited to two levels. Simulation results show that the regression tree models have unbiased variable selection and the estimates of subgroup treatment effects are approximately unbiased. A bootstrap calibration technique is proposed for constructing confidence intervals for the treatment effects. The method is illustrated with data from a longitudinal study comparing two diabetes drugs and a mammography screening trial comparing two treatments and a control. Copyright © 2016 John Wiley & Sons, Ltd.

PON1 Q192R genetic variant and response to clopidogrel and prasugrel: pharmacokinetics, pharmacodynamics, and a meta-analysis of clinical outcomes.

Clopidogrel and prasugrel are antiplatelet therapies commonly used to treat patients with cardiovascular disease. They are both pro-drugs requiring biotransformation into active metabolites. It has been proposed that a genetic variant Q192R (rs662 A>G) in PON1 significantly alters the biotransformation of clopidogrel and affects clinical outcomes; however, this assertion has limited support. The relationship between this variant and clinical outcomes with prasugrel has not been studied. We genotyped PON1 Q192R in 275 healthy subjects treated with clopidogrel or prasugrel and 2922 patients with an ACS undergoing PCI randomized to treatment with clopidogrel or prasugrel in the TRITON-TIMI 38 trial. A meta-analysis was performed including 13 studies and 16,760 clopidogrel-treated patients. Among clopidogrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.62) or change in platelet aggregation (P = 0.51). Consistent with these results, in clopidogrel-treated patients in TRITON-TIMI 38, there was no association between Q192R and the rates of CV death, myocardial infarction, or stroke (RR 11.2 %, QR 8.6 %, and QQ 9.3 %; P = 0.66) or stent thrombosis (RR 2.4 %, QR 0.7 %, and QQ 1.6 %, P = 0.30), with patients with the putative at-risk Q variant having numerically lower event rates. Likewise, among prasugrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.88), change in platelet aggregation (P = 0.97), or clinical outcomes (P = 0.72). In a meta-analysis, the Q variant was not significantly associated with MACE (QQ vs. RR 1.22, 95 % CI 0.84-1.76) or stent thrombosis (QQ vs. RR OR 1.36, 95 % CI 0.77-2.38). Furthermore, when restricted to the validation studies, the OR (95 % CI) for MACE and stent thrombosis were 0.99 (0.77-1.27) and 1.23 (0.74-2.03), respectively. In the present study, the Q192R genetic variant in PON1 was not associated with the pharmacologic or clinical response to clopidogrel, nor was it associated with the response to prasugrel. The meta-analysis reinforced a lack of a significant association between Q192R and cardiovascular outcomes in clopidogrel-treated patients.

Ultrafast properties of femtosecond-laser-ablated GaAs and its application to terahertz optoelectronics.

We report on the first terahertz (THz) emitter based on femtosecond-laser-ablated gallium arsenide (GaAs), demonstrating a 65% enhancement in THz emission at high optical power compared to the nonablated device. Counter-intuitively, the ablated device shows significantly lower photocurrent and carrier mobility. We understand this behavior in terms of n-doping, shorter carrier lifetime, and enhanced photoabsorption arising from the ablation process. Our results show that laser ablation allows for efficient and cost-effective optoelectronic THz devices via the manipulation of fundamental properties of materials.

A regression tree approach to identifying subgroups with differential treatment effects.

In the fight against hard-to-treat diseases such as cancer, it is often difficult to discover new treatments that benefit all subjects. For regulatory agency approval, it is more practical to identify subgroups of subjects for whom the treatment has an enhanced effect. Regression trees are natural for this task because they partition the data space. We briefly review existing regression tree algorithms. Then, we introduce three new ones that are practically free of selection bias and are applicable to data from randomized trials with two or more treatments, censored response variables, and missing values in the predictor variables. The algorithms extend the generalized unbiased interaction detection and estimation (GUIDE) approach by using three key ideas: (i) treatment as a linear predictor, (ii) chi-squared tests to detect residual patterns and lack of fit, and (iii) proportional hazards modeling via Poisson regression. Importance scores with thresholds for identifying influential variables are obtained as by-products. A bootstrap technique is used to construct confidence intervals for the treatment effects in each node. The methods are compared using real and simulated data.

Correction: Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-ßRI inhibitor galunisertib.

[This corrects the article DOI: 10.1371/journal.pone.0222259.].

Unraveling the varied nature and roles of defects in hybrid halide perovskites with time-resolved photoemission electron microscopy.

With rapidly growing photoconversion efficiencies, hybrid perovskite solar cells have emerged as promising contenders for next generation, low-cost photovoltaic technologies. Yet, the presence of nanoscale defect clusters, that form during the fabrication process, remains critical to overall device operation, including efficiency and long-term stability. To successfully deploy hybrid perovskites, we must understand the nature of the different types of defects, assess their potentially varied roles in device performance, and understand how they respond to passivation strategies. Here, by correlating photoemission and synchrotron-based scanning probe X-ray microscopies, we unveil three different types of defect clusters in state-of-the-art triple cation mixed halide perovskite thin films. Incorporating ultrafast time-resolution into our photoemission measurements, we show that defect clusters originating at grain boundaries are the most detrimental for photocarrier trapping, while lead iodide defect clusters are relatively benign. Hexagonal polytype defect clusters are only mildly detrimental individually, but can have a significant impact overall if abundant in occurrence. We also show that passivating defects with oxygen in the presence of light, a previously used approach to improve efficiency, has a varied impact on the different types of defects. Even with just mild oxygen treatment, the grain boundary defects are completely healed, while the lead iodide defects begin to show signs of chemical alteration. Our findings highlight the need for multi-pronged strategies tailored to selectively address the detrimental impact of the different defect types in hybrid perovskite solar cells.

Safety and activity of the TGFß receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer.

BACKGROUND: We assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGFß) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with ≤2 systemic regimens. METHODS: This was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1-14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase. RESULTS: The galunisertib recommended phase II dose (RP2D) when co-administered with durvalumab 1500 mg Q4W was 150 mg two times per day. No dose-limiting toxicities were recorded. Among 32 patients treated with galunisertib RP2D, 1 patient had partial response, 7 had stable disease, 15 had objective progressive disease, and 9 were not evaluable. Disease control rate was 25.0%. Median overall survival and progression-free survival were 5.72 months (95% CI: 4.01 to 8.38) and 1.87 months (95% CI: 1.58 to 3.09), respectively. Pharmacokinetic profiles for combination therapy were comparable to those published for each drug. There was no association between potential biomarkers and treatment outcomes. CONCLUSION: Galunisertib 150 mg two times per day co-administered with durvalumab 1500 mg Q4W was tolerable. Clinical activity was limited. Studying this combination in patients in an earlier line of treatment or selected for predictive biomarkers of TGFß inhibition might be a more suitable approach. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02734160.

First-In-Human Phase I Study of a Next-Generation, Oral, TGFß Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer.

PURPOSE: A novel, selective, next-generation transforming growth factor beta (TGFß) receptor type-1 small molecule inhibitor, LY3200882, demonstrated promising preclinical data. This first-in-human trial evaluated safety, tolerability, recommended phase II dose (RP2D), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882 as monotherapy or with other anticancer agents in patients with advanced cancer. PATIENTS AND METHODS: This phase I multicenter study of oral LY3200882 (NCT02937272) comprised dose escalation, monotherapy expansion in grade 4 glioma, and combination therapy in solid tumors (LY3200882 and PD-L1 inhibitor LY3300054), pancreatic cancer (LY3200882, gemcitabine, and nab-paclitaxel), and head and neck squamous cell cancer (LY3200882, cisplatin, and radiation). RESULTS: Overall, 139 patients with advanced cancer were treated. The majority (93.5%) of patients experienced ≥1 treatment-emergent adverse events (TEAE), with 39.6% LY3200882-related. Grade 3 LY3200882-related toxicities were only observed in combination therapy arms. One patient in the pancreatic cancer arm experienced cardiovascular toxicity. The LY3200882 monotherapy RP2Ds were established in two schedules: 50 mg twice a day 2-weeks-on/2-weeks-off and 35 mg twice a day 3-weeks-on/1-week-off. Four patients with grade 4 glioma had durable Revised Assessment in Neuro Oncology (RANO) partial responses (PR) with LY3200882 monotherapy (n = 3) or LY3200882-LY3300054 combination therapy (n = 1). In treatment-naïve patients with advanced pancreatic cancer, 6 of 12 patients achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 PR and 3 of 12 patients demonstrated stable disease, for an overall 75% disease-control rate with the combination of LY3200882, gemcitabine, and nab-paclitaxel. CONCLUSIONS: LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in pancreatic cancer. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced pancreatic cancer are warranted.

Experimental measurement of the intrinsic excitonic wave function.

An exciton, a two-body composite quasiparticle formed of an electron and hole, is a fundamental optical excitation in condensed matter systems. Since its discovery nearly a century ago, a measurement of the excitonic wave function has remained beyond experimental reach. Here, we directly image the excitonic wave function in reciprocal space by measuring the momentum distribution of electrons photoemitted from excitons in monolayer tungsten diselenide. By transforming to real space, we obtain a visual of the distribution of the electron around the hole in an exciton. Further, by also resolving the energy coordinate, we confirm the elusive theoretical prediction that the photoemitted electron exhibits an inverted energy-momentum dispersion relationship reflecting the valence band where the partner hole remains, rather than that of conduction band states of the electron.

Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease.

AIMS: The metabolic pathways leading to the formation of prasugrel and clopidogrel active metabolites differ. We hypothesized that decreased CYP2C19 activity affects the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. METHODS AND RESULTS: Ninety-eight patients with coronary artery disease (CAD) taking either clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD were genotyped for variation in six CYP genes. Based on CYP genotype, patients were segregated into two groups: normal function (extensive) metabolizers (EM) and reduced function metabolizers (RM). Plasma active metabolite concentrations were measured at 30 min, 1, 2, 4, and 6 h post-LD and during the MD period on Day 2, Day 14, and Day 29 at 30 min, 1, 2, and 4 h. Vasodilator-stimulated phosphoprotein (VASP) and VerifyNow P2Y12 were measured predose, 2, and 24 +/- 4 h post-LD and predose during the MD period on Day 14 +/- 3 and Day 29 +/- 3. For clopidogrel, active metabolite exposure was significantly lower (P = 0.0015) and VASP platelet reactivity index (PRI, %) and VerifyNow P2Y(12) reaction unit (PRU) values were significantly higher (P < 0.05) in the CYP2C19 RM compared with the EM group. For prasugrel, there was no statistically significant difference in active metabolite exposure or pharmacodynamic response between CYP2C19 EM and RM. Variation in the other five genes demonstrated no statistically significant differences in pharmacokinetic or pharmacodynamic responses. CONCLUSION: Variation in the gene encoding CYP2C19 in patients with stable CAD contributes to reduced exposure to clopidogrel's active metabolite and a corresponding reduction in P2Y(12) inhibition, but has no significant influence on the response to prasugrel.

Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-ßRI inhibitor galunisertib.

BACKGROUND: Transforming growth factor beta (TGF-ß) signalling is involved in the development of hepatocellular carcinoma (HCC). We followed changes in biomarkers during treatment of patients with HCC with the TGF-ßRI/ALK5 inhibitor galunisertib. METHODS: This phase 2 study (NCT01246986) enrolled second-line patients with advanced HCC into one of two cohorts of baseline serum alpha-fetoprotein (AFP): Part A (AFP ≥1.5x ULN) or Part B (AFP <1.5x ULN). Baseline and postbaseline levels of AFP, TGF-ß1, E-cadherin, selected miRNAs, and other plasma proteins were monitored. RESULTS: The study enrolled 149 patients (Part A, 109; Part B, 40). Median OS was 7.3 months in Part A and 16.8 months in Part B. Baseline AFP, TGF-ß1, E-cadherin, and an additional 16 plasma proteins (such as M-CSF, IL-6, ErbB3, ANG-2, neuropilin-1, MIP-3 alpha, KIM-1, uPA, IL-8, TIMP-1, ICAM-1, Apo A-1, CA-125, osteopontin, tetranectin, and IGFBP-1) were found to correlate with OS. In addition, a range of miRs were found to be associated with OS. In AFP responders (21% of patients in Part A with decrease of >20% from baseline) versus non-responders, median OS was 21.5 months versus 6.8 months (p = 0.0015). In TGF-ß1 responders (51% of all patients) versus non-responders, median OS was 11.2 months versus 5.3 months (p = 0.0036). CONCLUSIONS: Consistent with previous findings, both baseline levels and changes from baseline of circulating AFP and TGF-ß1 function as prognostic indicators of survival. Future trials are needed to confirm and extend these results.

Directly visualizing the momentum-forbidden dark excitons and their dynamics in atomically thin semiconductors.

Resolving momentum degrees of freedom of excitons, which are electron-hole pairs bound by the Coulomb attraction in a photoexcited semiconductor, has remained an elusive goal for decades. In atomically thin semiconductors, such a capability could probe the momentum-forbidden dark excitons, which critically affect proposed opto-electronic technologies but are not directly accessible using optical techniques. Here, we probed the momentum state of excitons in a tungsten diselenide monolayer by photoemitting their constituent electrons and resolving them in time, momentum, and energy. We obtained a direct visual of the momentum-forbidden dark excitons and studied their properties, including their near degeneracy with bright excitons and their formation pathways in the energy-momentum landscape. These dark excitons dominated the excited-state distribution, a surprising finding that highlights their importance in atomically thin semiconductors.