Burning plasma achieved in inertial fusion.

Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3 through two different implosion concepts4-7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.

Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study.

BACKGROUND: Pembrolizumab is a new standard of care for patients with platinum-treated, metastatic urothelial carcinoma (UC). Nab-paclitaxel is active in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC. PATIENTS AND METHODS: PEANUT was an open-label, single-arm, phase II trial that included patients who had failed one or two chemotherapy regimens, including platinum chemotherapy. Biomarker analyses focused on programmed cell-death ligand-1 combined positive score (CPS) and comprehensive genomic profiling on tumor samples and circulating tumor DNA. Patients received 200 mg pembrolizumab on day 1 (D1), and 125 mg/m2 nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) according to RECIST (v1.1). The assumption was to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). RESULTS: Between January 2019 and January 2020, the PEANUT study enrolled 70 patients: 24% had failed two prior systemic therapies; 31% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1; and 28.6% had liver metastases. After a median follow-up of 9.8 months, 40 patients have relapsed (57.1%). The median PFS was 5.9 months [95% confidence interval (CI) 3.1-11.5]. The confirmed objective response rate (ORR) was 38.6% (95% CI 27-51) with 17 partial responses and 10 complete responses (14.3%). The median duration of response was not reached. Five patients (7.1%) had ongoing responses lasting >12 months. The most common any-grade treatment-related adverse events included alopecia (71.4%), neutropenia (32.9%), and peripheral neuropathy (34.3%). Neither tumor mutational burden nor CPS was significantly associated with PFS at univariable analyses. The single-arm design of the trial was the major limitation. CONCLUSIONS: Pembrolizumab combined with nab-paclitaxel, as second- and third-line chemoimmunotherapy for metastatic UC, showed a favorable safety profile, durable PFS, and a clinically meaningful ORR in these preliminary analyses. This combination warrants additional randomized studies in earlier disease stages. CLINICALTRIALS. GOV NUMBER: ClinicalTrials.govNCT03464734; https://clinicaltrials.gov/ct2/show/NCT03464734.

Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study☆.

BACKGROUND: Initial studies of preoperative checkpoint inhibition before radical cystectomy (RC) have shown promising pathologic complete responses. We aimed to analyze the survival outcomes of patients enrolled in the PURE-01 study (NCT02736266). PATIENTS AND METHODS: We report the results of the secondary end points of PURE-01 in the final population of 143 patients. In particular, we report the event-free survival (EFS) outcomes, defined as the time from the first cycle of pembrolizumab to radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy (NAC), recurrence after RC, or death from any cause. Other end points were recurrence-free survival (RFS) and overall survival (OS). Subgroup analyses were carried out, including pathological response category, clinical complete responses (CR) assessed via multiparametric magnetic resonance imaging (mpMRI), and molecular subtyping. Cox regression analyses for EFS were also carried out. RESULTS: After a median [interquartile range (IQR)] follow-up of 23 (15-29) months, 12- and 24-month EFS were 84.5% [95% confidence interval (CI): 78.5-90.9] and 71.7% (62.7-82). The prognosis was favorable across all the different pathological response subgroups, with the exception of ypN+ (N = 21), showing a 24-month RFS (95% CI) of 39.3% (19.2% to 80.5%). A statistically significant EFS benefit was observed in patients with a clinical CR (P = 0.002). Programmed cell-death-ligand-1 combined positive score was significantly associated with longer EFS in multivariable analyses. Four patients refused RC after clinical evidence of CR, and none of them have recurred after a median follow-up of 10 months (IQR: 11-15). The claudin-low subtype displayed a numerically longer EFS after pembrolizumab and RC compared with the other subtypes. CONCLUSIONS: The EFS results from PURE-01 revealed that the immunotherapy effect was maintained post-RC in most patients. Pembrolizumab compared favorably with neoadjuvant chemotherapy, irrespective of the biomarker status. Molecular subtyping may be a useful tool to select the patients who are predicted to benefit the most from neoadjuvant pembrolizumab.

Plasma Collision in a Gas Atmosphere.

We present a study on the impact of a gas atmosphere on the collision of two counterpropagating plasmas (gold and carbon). Imaging optical Thomson scattering data of the plasma collision with and without helium in between have been obtained at the Omega laser facility. Without gas, we observed large scale mixing of colliding gold and carbon ions. Once ambient helium is added, the two plasmas remain separated. The difference in ionic temperature is consistent with a reduction of the maximum Mach number of the flow from M=7 to M=4. It results in a reduction of a factor ∼10 of the counterstreaming ion-ion mean free path. By adding a low-density ambient gas, it is possible to control the collision of two high-velocity counterstreaming plasma, transitioning from an interpenetrating regime to a regime in agreement with a hydrodynamic description.

Measurement of Kinetic-Scale Current Filamentation Dynamics and Associated Magnetic Fields in Interpenetrating Plasmas.

We present the first local, quantitative measurements of ion current filamentation and magnetic field amplification in interpenetrating plasmas, characterizing the dynamics of the ion Weibel instability. The interaction of a pair of laser-generated, counterpropagating, collisionless, supersonic plasma flows is probed using optical Thomson scattering (TS). Analysis of the TS ion-feature revealed anticorrelated modulations in the density of the two ion streams at the spatial scale of the ion skin depth c/ω_{pi}=120 µm, and a correlated modulation in the plasma current. The inferred current profile implies a magnetic field amplitude ∼30±6 T, corresponding to ∼1% of the flow kinetic energy, indicating that magnetic trapping is the dominant saturation mechanism.

Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1 inhibitors at five institutes. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mb of sequenced DNA and reported as mutations/Mb. Potential biomarkers of response and time to progression were analyzed by univariate and multivariate analyses. Once TMB was confirmed as a predictive biomarker, a larger dataset of 18 140 unique CRC patients was analyzed to define the relevance of the identified TMB cut-point. RESULTS: A total of 22 patients were treated with PD-1/L1 inhibitors including 19 with pembrolizumab monotherapy. Among tested variables, TMB showed the strongest association with objective response (OR; P < 0.001) and PFS, by univariate (P < 0.001) and multivariate analysis (P < 0.01). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37 and 41 mutations/Mb. All 13 TMBhigh cases responded, while 6/9 TMBlow cases had progressive disease. The median PFS for TMBhigh has not been reached (median follow-up >18 months) while the median PFS for TMBlow was 2 months. A TMB of 37.4 mutations/Mb in a large MSI-H mCRC population (821/18, 140 cases; 4.5%) evaluated by NGS corresponded to the 35th percentile cut-point. CONCLUSIONS: TMB appears to be an important independent biomarker within MSI-H mCRC to stratify patients for likelihood of response to ICPIs. If validated in prospective studies, TMB may play an important role in guiding the sequencing and/or combinations of ICPIs in MSI-H mCRC.

Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.

Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed. Patients and methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes. Results: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P < 0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P < 0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%). Conclusions: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.

Patterns of prostate-specific antigen testing by remoteness of residence and socio-economic status: An Australian population-based study.

OBJECTIVE: Describes the variation in prostate cancer testing by the remoteness of residence and socio-economic status groups in Australia. DESIGN: A national population-based descriptive study using Medicare data extracted by the Department of Health (formerly the Department of Health and Ageing). SETTING: Australia. PARTICIPANTS: All men, with a Medicare-reimbursed prostate-specific antigen test conducted in Australia between 2002 and 2017, were included. We focused on "screening and case finding" tests (Medicare Benefits Schedule item number 66655) from 1 April 2005 to 31 December 2009, to describe testing differences in subgroups. Groups were categorised into State and Territory, socio-economic status and region of residence. A negative binomial regression model was fitted to measure the incidence rate ratios of those who had a screening prostate-specific antigen test by group. MAIN OUTCOME MEASURES: Age-standardised testing rates and incidence rate ratios. RESULTS: Between 2002 and 2017, 11 588 775 screening prostate-specific antigen tests were reimbursed by the Department of Human Services. During 2005-2009, 52% of all Australian men, aged 40 years and over, had a screening test. The incidence rate ratios differed by State and Territory. Men aged 40 years and over, living in very remote areas, were 43% less likely to have had a screening test than residents of major cities. Prostate-specific antigen testing rates fell in all age groups between 2007 and 2009 and 2017. CONCLUSIONS: The prostate-specific antigen testing behaviour differs between community groups in Australia. Men were less likely to have had a screening prostate-specific antigen test the farther they lived from the major cities. This highlights the need for a more targeted approach to achieve an equitable and evidence-based prostate cancer care across all sectors of the community.

Highly Resolved Measurements of a Developing Strong Collisional Plasma Shock.

The structure of a strong collisional shock front forming in a plasma is directly probed for the first time in laser-driven gas-jet experiments. Thomson scattering of a 526.5 nm probe beam was used to diagnose temperature and ion velocity distribution in a strong shock (M∼11) propagating through a low-density (ρ∼0.01 mg/cc) plasma composed of hydrogen. A forward-streaming population of ions traveling in excess of the shock velocity was observed to heat and slow down on an unmoving, unshocked population of cold protons, until ultimately the populations merge and begin to thermalize. Instabilities are observed during the merging, indicating a uniquely plasma-phase process in shock front formation.

Fusion Energy Output Greater than the Kinetic Energy of an Imploding Shell at the National Ignition Facility.

A series of cryogenic, layered deuterium-tritium (DT) implosions have produced, for the first time, fusion energy output twice the peak kinetic energy of the imploding shell. These experiments at the National Ignition Facility utilized high density carbon ablators with a three-shock laser pulse (1.5 MJ in 7.5 ns) to irradiate low gas-filled (0.3 mg/cc of helium) bare depleted uranium hohlraums, resulting in a peak hohlraum radiative temperature ∼290 eV. The imploding shell, composed of the nonablated high density carbon and the DT cryogenic layer, is, thus, driven to velocity on the order of 380 km/s resulting in a peak kinetic energy of ∼21 kJ, which once stagnated produced a total DT neutron yield of 1.9×10^{16} (shot N170827) corresponding to an output fusion energy of 54 kJ. Time dependent low mode asymmetries that limited further progress of implosions have now been controlled, leading to an increased compression of the hot spot. It resulted in hot spot areal density (ρr∼0.3 g/cm^{2}) and stagnation pressure (∼360 Gbar) never before achieved in a laboratory experiment.

Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies.

BACKGROUND: Relapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease. PATIENTS AND METHODS: From a series of 85 686 clinical cases, DNA was extracted from 40 µm of formalin-fixed paraffin embedded (FFPE) sections for 623 consecutive SGC. CGP was carried out on hybridization-captured, adaptor ligation-based libraries (mean coverage depth, >500×) for up to 315 cancer-related genes. Tumor mutational burden was determined on 1.1 Mb of sequenced DNA. All classes of alterations, base substitutions, short insertions/deletions, copy number changes, and rearrangements/fusions were determined simultaneously. RESULTS: The clinically more indolent SGC including adenoid cystic carcinoma, acinic cell carcinoma, polymorphous low-grade adenocarcinoma, mammary analog secretory carcinoma, and epithelial-myoepithelial carcinomas have significantly fewer genomic alterations, TP53 mutations, and lower tumor mutational burden than the typically more aggressive SGCs including mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified, carcinoma NOS, and carcinoma ex pleomorphic adenoma. The more aggressive SGCs are commonly driven by ERBB2 PI3K pathway genomic alterations. Additional targetable GAs are frequently seen. CONCLUSIONS: Genomic profiling of SGCs demonstrates important differences between traditionally indolent and aggressive cancers. These differences may provide therapeutic options in the future.

Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations.

Background: We sought to identify genomic alterations (GAs) in salivary mucoepidermoid carcinomas. Patients and methods: DNA was extracted from 48 mucoepidermoid carcinomas. Comprehensive genomic profiling (CGP) including the calculation to tumor mutational burden (TMB) was performed on hybridization-captured adaptor ligation-based libraries of 315 cancer-related genes plus introns from 28 genes frequently rearranged for cancer and evaluated for all classes of GAs. Results: A total of 183 GAs were found in 80 unique genes. High-grade tumors had more GAs (mean 5 ± 3.8) compared with low (2.3 ± 1.4) or intermediate (2.6 ± 1.5) (P = 0.019). TP53 GAs were seen in all tumor grades (41.7%) but were most common in high-grade malignancies (56%) (P = 0.047). CDKN2A GAs were seen in 41.6% of tumors. PI3K/mTOR pathway activation, including PI3KCA mutations, were more common in high grade (52%) than in low- and intermediate-grade tumors (4.3%) (P = 0.007). BAP1 GAs were observed in 20.8% of tumors and BRCA1/2 GAs present in 10.5% of specimens. ERBB2 amplifications were seen in only 8.3% of tumors. The TMB for this patient group was relatively low with only 5 (10%) of cases having greater than 10 mutations/megabase of sequenced DNA. Conclusion: CGP of salivary mucoepidermoid carcinomas revealed diverse GAs that may lead to customized treatment options for patients with these rare tumors.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Refractive Index Seen by a Probe Beam Interacting with a Laser-Plasma System.

We report the first complete set of measurements of a laser-plasma optical system's refractive index, as seen by a second probe laser beam, as a function of the relative wavelength shift between the two laser beams. Both the imaginary and real refractive index components are found to be in good agreement with linear theory using plasma parameters measured by optical Thomson scattering and interferometry; the former is in contrast to previous work and has implications for crossed-beam energy transfer in indirect-drive inertial confinement fusion, and the latter is measured for the first time. The data include the first demonstration of a laser-plasma polarizer with 85%-87% extinction for the particular laser and plasma parameters used in this experiment, complementing the existing suite of high-power, tunable, and ultrafast plasma-based photonic devices.

Transition from Collisional to Collisionless Regimes in Interpenetrating Plasma Flows on the National Ignition Facility.

A study of the transition from collisional to collisionless plasma flows has been carried out at the National Ignition Facility using high Mach number (M>4) counterstreaming plasmas. In these experiments, CD-CD and CD-CH planar foils separated by 6-10 mm are irradiated with laser energies of 250 kJ per foil, generating ∼1000 km/s plasma flows. Varying the foil separation distance scales the ion density and average bulk velocity and, therefore, the ion-ion Coulomb mean free path, at the interaction region at the midplane. The characteristics of the flow interaction have been inferred from the neutrons and protons generated by deuteron-deuteron interactions and by x-ray emission from the hot, interpenetrating, and interacting plasmas. A localized burst of neutrons and bright x-ray emission near the midpoint of the counterstreaming flows was observed, suggesting strong heating and the initial stages of shock formation. As the separation of the CD-CH foils increases we observe enhanced neutron production compared to particle-in-cell simulations that include Coulomb collisions, but do not include collective collisionless plasma instabilities. The observed plasma heating and enhanced neutron production is consistent with the initial stages of collisionless shock formation, mediated by the Weibel filamentation instability.

Citation indices for social media articles in urology.

OBJECTIVE: To evaluate the impact of publications on urological participation in social media (SoMe) by virtue of citations in the urological and non-urological literature. MATERIALS AND METHODS: On 15 March 2016, a PubMed search was undertaken using the names of the major SoMe platforms in current use and associated with the field of urology. The search term 'urolog*' was used to specifically capture articles that could be associated with 'urology', 'urologist' or 'urological'. Exclusion criteria for analysis included non-English language articles, articles published for the first time online in any form after 1 March 2015, articles irrelevant to the topic of SoMe, and letters of correspondence. Included articles were then searched in Google Scholar and citations analysed to determine if citations were from the urological literature or non-urological literature. Citations from non-urological journals were considered to be as such even if authored by urologists and on the subject of urology and SoMe. RESULTS: Prior to exclusions as defined in the methods, our PubMed search yielded 232 articles of which 17 were non-English language and 66 had been published after 1 March 2015. Allowing for 12 months after the most recent articles were published, we found that the mean number of total citations in any journal was 20.8. There were more citations in journals not specific to urology, with 8.3 citations in urological journals, compared to 12.6 citations in non-urological journals. CONCLUSION: Urological SoMe journal articles are highly cited, particularly in the non-urological literature. It is likely that the magnitude of citations has positively contributed to the impact factors of the almost all journals publishing these manuscripts.

Two-photon absorption measurements of deep UV transmissible materials at 213 nm.

We report on two-photon absorption measurements at 213 nm of deep UV transmissible media, including LiF, MgF2, CaF2, BaF2, sapphire (Al2O3), and high-purity grades of fused-silica (SiO2). A high-stability 24 ps Nd:YAG laser operating at the 5th harmonic (213 nm) was used to generate a high-intensity, long-Rayleigh-length Gaussian focus inside the samples. The measurements of the fluoride crystals and sapphire indicate two-photon absorption coefficients between 0.004 and 0.82 cm/GW. We find that different grades of fused silica performed near identically for two-photon absorption; however, there are differences in linear losses associated with purity. A low two-photon absorption cross section is measured for MgF2, making it an ideal material for the propagation of high-intensity deep UV lasers.

Comprehensive genomic profiling of anal squamous cell carcinoma reveals distinct genomically defined classes.

BACKGROUND: Squamous cell cancers of the anal canal (ASCC) are increasing in frequency and lack effective therapies for advanced disease. Although an association with human papillomavirus (HPV) has been established, little is known about the molecular characterization of ASCC. A comprehensive genomic analysis of ASCC was undertaken to identify novel genomic alterations (GAs) that will inform therapeutic choices for patients with advanced disease. PATIENTS AND METHODS: Hybrid-capture-based next-generation sequencing of exons from 236 cancer-related genes and intronic regions from 19 genes commonly rearranged in cancer was performed on 70 patients with ASCC. HPV status was assessed by aligning tumor sequencing reads to HPV viral genomes. GAs were identified using an established algorithm and correlated with HPV status. RESULTS: Sixty-one samples (87%) were HPV-positive. A mean of 3.5 GAs per sample was identified. Recurrent alterations in phosphoinositol-3-kinase pathway (PI3K/AKT/mTOR) genes including amplifications and homozygous deletions were present in 63% of cases. Clinically relevant GAs in genes involved in DNA repair, chromatin remodeling, or receptor tyrosine kinase signaling were observed in 30% of cases. Loss-of-function mutations in TP53 and CDKN2A were significantly enhanced in HPV-negative cases (P < 0.0001). CONCLUSIONS: This is the first comprehensive genomic analysis of ASCC, and the results suggest new therapeutic approaches. Differing genomic profiles between HPV-associated and HPV-negative ASCC warrants further investigation and may require novel therapeutic and preventive strategies.

High Power Dynamic Polarization Control Using Plasma Photonics.

We report the first experimental demonstration of a plasma wave plate based on laser-induced birefringence. An elliptically polarized input was converted into a nearly ideal circularly polarized beam using an optical system composed of a second laser beam and a plasma. The results are in excellent agreement with linear theory and three-dimensional simulations up to phase delays exceeding π/4, thus establishing the feasibility of laser-plasma photonic devices that are ultrafast, damage-resistant, and easily tunable.