Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice.

Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy studied in patients with multiple myeloma exposed to three classes of treatment in the single-arm CARTITUDE-1 study. To assess the effectiveness of cilta-cel compared to real-world clinical practice (RWCP), we performed adjusted comparisons using individual patients' data from CARTITUDE-1 and LocoMMotion, a prospective, multinational study of patients with multiple myeloma triple-class exposed of treatment. Comparisons were performed using inverse probability weighting. In CARTITUDE-1, 113 patients were enrolled, and 97 patients were infused with cilta-cel. In LocoMMotion, 248 patients were enrolled, and 170 patients were included in the comparisons versus infused patients. Ninety-two unique regimens were used in LocoMMotion, most frequently carfilzomib-dexamethasone (13.7%), pomalidomide-cyclophosphamide-dexamethasone (13.3%) and pomalidomidedexamethasone (11.3%). Adjusted comparisons showed that patients treated with cilta-cel were 3.12-fold more likely to respond to treatment than those managed by RWCP (response rate, 3.12, 95% confidence interval [95% CI]: 2.24-4.00), had their risk of progression or death reduced to by 85% (progression-free survival hazard ratio=0.15, 95% CI: 0.08-0.29), and a risk of death lowered by 80% (overall survival hazard ratio HR=0.20, 95% CI: 0.09-0.41). The incremental improvement in healthrelated quality of life from baseline for cilta-cel versus RWCP at week 52, as measured by EORTC QLQ-C30 Global Health Status, was 13.4 (95% CI: 3.5-23.6) and increased to 30.8 (95% CI: 21.8-39.8) when including death as additional information regarding patients' health status. Patients treated with cilta-cel experienced more adverse events than those managed with RWCP (any grade: 100% vs. 83.5%). The results from this study demonstrate improved efficacy outcomes of cilta-cel versus RWCP and highlight its potential as a novel and effective treatment option for patients with multiple myeloma triple-class exposed of antimyeloma treatment. CARTITUDE-1 is registered with clinicaltrials gov. Identifier: NCT03548207. LocoMMotion is registered with clinicaltrials gov. Identifier: NCT04035226.

Deterministic inverse design of Tamm plasmon thermal emitters with multi-resonant control.

Wavelength-selective thermal emitters (WS-EMs) are of interest due to the lack of cost-effective, narrow-band sources in the mid- to long-wave infrared. WS-EMs can be realized via Tamm plasmon polaritons (TPPs) supported by distributed Bragg reflectors on metals. However, the design of multiple resonances is challenging as numerous structural parameters must be optimized simultaneously. Here we use stochastic gradient descent to optimize TPP emitters (TPP-EMs) composed of an aperiodic distributed Bragg reflector deposited on doped cadmium oxide (CdO) film, where layer thicknesses and carrier density are inversely designed. The combination of the aperiodic distributed Bragg reflector with the designable plasma frequency of CdO enables multiple TPP-EM modes to be simultaneously designed with arbitrary spectral control not accessible with metal-based TPPs. Using this approach, we experimentally demonstrated and numerically proposed TPP-EMs exhibiting single or multiple emission bands with designable frequencies, line-widths and amplitudes. This thereby enables lithography-free, wafer-scale WS-EMs that are complementary metal-oxide-semiconductor compatible for applications such as free-space communications and gas sensing.

Engineering the Spectral and Spatial Dispersion of Thermal Emission via Polariton-Phonon Strong Coupling.

Strong coupling between optical modes can be implemented into nanophotonic design to modify the energy-momentum dispersion relation. This approach offers potential avenues for tuning the thermal emission frequency, line width, polarization, and spatial coherence. Here, we employ three-mode strong coupling between propagating and localized surface phonon polaritons, with zone-folded longitudinal optic phonons within periodic arrays of 4H-SiC nanopillars. Energy exchange, mode evolution, and coupling strength between the three polariton branches are explored experimentally and theoretically. The influence of strong coupling upon the angle-dependent thermal emission was directly measured, providing excellent agreement with theory. We demonstrate a 5-fold improvement in the spatial coherence and 3-fold enhancement of the quality factor of the polaritonic modes, with these hybrid modes also exhibiting a mixed character that could enable opportunities to realize electrically driven emission. Our results show that polariton-phonon strong coupling enables thermal emitters, which meet the requirements for a host of IR applications in a simple, lightweight, narrow-band, and yet bright emitter.

Polaritonic Hybrid-Epsilon-near-Zero Modes: Beating the Plasmonic Confinement vs Propagation-Length Trade-Off with Doped Cadmium Oxide Bilayers.

Polaritonic materials that support epsilon-near-zero (ENZ) modes offer the opportunity to design light-matter interactions at the nanoscale through extreme subwavelength light confinement, producing phenomena like resonant perfect absorption. However, the utility of ENZ modes in nanophotonic applications has been limited by a flat spectral dispersion, which leads to small group velocities and extremely short propagation lengths. Here, we overcome this constraint by hybridizing ENZ and surface plasmon polariton (SPP) modes in doped cadmium oxide epitaxial bilayers. This results in strongly coupled hybrid modes that are characterized by an anticrossing in the polariton dispersion and a large spectral splitting on the order of 1/3 of the mode frequency. These hybrid modes simultaneously achieve modal propagation and ENZ mode-like interior field confinement, adding propagation character to ENZ mode properties. We subsequently tune the resonant frequencies, dispersion, and coupling of these polaritonic-hybrid-epsilon-near-zero (PH-ENZ) modes by tailoring the modal oscillator strength and the ENZ-SPP spectral overlap. PH-ENZ modes ultimately leverage the most desirable characteristics of both ENZ and SPP modes, allowing us to overcome the canonical plasmonic trade-off between confinement and propagation length.

Multilayer Noninteracting Dielectric Metasurfaces for Multiwavelength Metaoptics.

Metasurfaces provide a versatile platform for manipulating the wavefront of light using planar nanostructured surfaces. Transmissive metasurfaces, with full 2π phase control, are a particularly attractive platform for replacing conventional optical elements due to their small footprint and broad functionality. However, the operational bandwidth of metasurfaces has been a critical limitation and is directly connected to either their resonant response or the diffractive dispersion of their lattice. While multiwavelength and continuous band operation have been demonstrated, the elements suffer from either low efficiency, reduced imaging quality, or limited element size. Here, we propose a platform that provides for multiwavelength operation by employing tightly spaced multilayer dielectric metasurfaces. As a proof of concept, we demonstrate a multiwavelength metalens doublet (NA = 0.42) with focusing efficiencies of 38% and 52% at wavelengths of 1180 and 1680 nm, respectively. We further show how this approach can be extended to three-wavelength metalenses as well as a spectral splitter. This approach could find applications in fluorescent microscopy, digital imaging, and color routing.

An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical Practice in Europe and the United States for Patients with Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 Insertion Mutations.

INTRODUCTION: Patients with advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of specific treatment guidelines and unmet need for targeted therapies. Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, individual patient data (IPD)-based adjusted analyses versus similar patients in real-world clinical practice (RWCP) were conducted to generate comparative evidence. METHODS: RWCP cohorts were derived from seven European and US real-world sources, comprising patients fulfilling CHRYSALIS Cohort D+ eligibility criteria. Amivantamab was compared with a basket of RWCP treatments. Differences in prognostic characteristics were adjusted for using inverse probability weighting (IPW; average treatment effect among the treated [ATT]). Balance between cohorts was assessed using standardized mean differences (SMDs). Overall response rate (ORR; investigator- [INV] and independent review committee-assessed [IRC]), overall survival (OS), progression-free survival (PFS; INV and IRC) and time-to-next treatment (TTNT) were compared. Binary and time-to-event endpoints were analyzed using weighted logistic regression and proportional hazards regression, respectively. RESULTS: Pre-adjustment, baseline characteristics were comparable between cohorts. IPW ATT-adjustment improved comparability, giving closely matched characteristics. ORR (INV) was 36.8% for amivantamab versus 17.0% for the adjusted EU + US cohort (response rate ratio [RR]: 2.16). Median OS, PFS (INV) and TTNT were 22.77 versus 12.52 months (hazard ratio [HR]: 0.47; p < 0.0001), 6.93 versus 4.17 months (HR: 0.55; p < 0.0001) and 12.42 versus 5.36 months (HR: 0.44; p < 0.0001) for amivantamab versus the adjusted EU + US cohort, respectively. Results were consistent versus EU- and US-only cohorts, and when using IRC assessment. CONCLUSION: Adjusted comparisons demonstrated significantly improved outcomes for amivantamab versus RWCP, highlighting the value of amivantamab in addressing unmet need in patients with advanced EGFR Exon20ins NSCLC following platinum-based therapy. TRIAL REGISTRATION: CHRYSALIS: NCT02609776.

Collective Phonon-Polaritonic Modes in Silicon Carbide Subarrays.

Localized surface phonon polaritons (LSPhPs) can be implemented to engineer light-matter interactions through nanoscale patterning for a range of midinfrared application spaces. However, the polar material systems studied to date have mainly focused on simple designs featuring a single element in the periodic unit cell. Increasing the complexity of the unit cell can serve to modify the resonant near-fields and intra- and inter-unit-cell coupling as well as to dictate spectral tuning in the far-field. In this work, we exploit more complicated unit-cell structures to realize LSPhP modes with additional degrees of design freedom, which are largely unexplored. Collectively excited LSPhP modes with distinctly symmetric and antisymmetric near-fields are supported in these subarray designs, which are based on nanopillars that are scaled by the number of subarray elements to ensure a constant unit-cell size. Moreover, we observe an anomalous mode-matching of the collective symmetric mode in our fabricated subarrays that is robust to changing numbers of pillars within the subarrays as well as to defects intentionally introduced in the form of missing pillars. This work therefore illustrates the hierarchical design of tailored LSPhP resonances and modal near-field profiles simultaneously for a variety of IR applications such as surface-enhanced spectroscopies and biochemical sensing.

Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry.

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel's potential as a novel, effective treatment to address unmet needs in patients with RRMM.

A carbon dioxide, heat and chemical lure trap for the bedbug, Cimex lectularius.

A trap for the collection of bedbugs, Cimex lectularius Linnaeus (Hemiptera: Cimicidae), is described. The trap was baited with CO2 (50-400 mL/min), heat (37.2-42.2 degrees C) and a chemical lure comprised of 33.0 microg proprionic acid, 0.33 microg butyric acid, 0.33 microg valeric acid, 100 microg octenol and 100 microg L-lactic acid, impregnated into a gel. Laboratory studies, conducted in a square arena measuring 183 cm on each side, showed that traps with and without baits captured adult bedbugs, but traps with CO2 emissions of 50-400 mL/min caught significantly (P < 0.05) more bedbugs than traps without CO2. In an infested unoccupied apartment, traps with heat and with or without the chemical lure were tested without CO2 on 29 trap-days and with CO2 on 9 trap-days. The numbers of bedbugs captured were 656 and 5898 in traps without and with CO2, respectively. The numbers of bedbugs of all development stages captured were significantly greater in traps with CO2 (chi2 = 15 942, d.f. = 1, P < 10(-9)). A non-parametric two-way analysis of variance evaluation of six different traps with or without CO2, heat or a chemical lure monitored over 19 trap-days in an infested apartment showed that trap type was highly significant (n = 2833 bedbugs collected) (P < 10(-7)). The trap with CO2, heat and a chemical lure captured more bedbugs than the other traps, but only caught significantly more fourth and fifth instar nymphs than all other traps. Otherwise, the catches in this trap did not differ significantly from those caught by traps that contained CO2 and heat only. The total numbers of bedbugs collected for each trapping date (pooling all six traps) followed an exponential decline over the trapping period. This type of trap, which caught bedbugs in unoccupied apartments with and without furniture, and in an occupied apartment, may have utility in studying the ecology of bedbugs, in detecting bedbug infestations and in reducing numbers of bites by trapping host-seeking bedbugs.

Apolipoprotein D expression in primary brain tumors: analysis by quantitative RT-PCR in formalin-fixed, paraffin-embedded tissue.

Apolipoprotein D (apoD) expression has been shown to correlate both with cell cycle arrest and with prognosis in several types of malignancy, including central nervous system astrocytomas and medulloblastomas. ApoD expression was investigated by real-time quantitative RT-PCR using RNA extracted from 68 formalin-fixed, paraffin-embedded brain specimens. Glyceraldehyde phosphate dehydrogenase was used as an internal control. Quantitation was achieved on all specimens. Sixteen poorly infiltrating WHO grade I glial neoplasms (i.e., pilocytic astrocytomas and gangliogliomas) showed an average 20-fold higher apoD expression level compared with the 20 diffusely infiltrating glial neoplasms (i.e., glioblastoma, anaplastic astrocytoma, oligodendrogliomas; p=0.00004). A small number of exceptions (i.e., two high-expressing glioblastomas and three low-expressing gangliogliomas) were identified. Analyzed as individual tumor groups, poorly infiltrating grade I pilocytic astrocytomas and gangliogliomas differed significantly from each tumor type within the diffusely infiltrating higher-grade category (p<0.05 for each comparison) but not from each other (p>0.05). Conversely, each individual tumor type within the diffusely infiltrating category differed significantly from both pilocytic astrocytomas and gangliogliomas (p<0.05) but did not vary from other infiltrating tumors (p>0.05). Ependymomas, non-infiltrating grade II neoplasms, expressed levels of apoD similar to or lower than levels expressed by the diffusely infiltrating gliomas. Ten medulloblastomas with survival longer than 3 years averaged slightly higher apoD expression than four fatal medulloblastomas; however, this result was not statistically significant and individual exceptions were notable. In 17 of the medulloblastomas, MIB-1 proliferation rates quantitated by image cytometry did not correlate with apoD expression. In addition, apoD expression was 5-fold higher in the slowly proliferating grade I glial neoplasms compared with non-proliferating normal brain tissue (p=0.01), suggesting that apoD expression is not simply an inverse measure of proliferation. ApoD expression measured by quantitative RT-PCR may be useful in the differential diagnosis of primary brain tumors, particularly pilocytic astrocytomas and gangliogliomas.

[Demonstration of a liposoluble ciguateric toxin in Caranx bartholomaei caught in the French West Indies]. / Mise en évidence d'une toxine liposoluble de type ciguatérique chez Caranx bartholomaei pêché aux Antilles françaises.

This report deals with some of the biological and chemical properties of a liposoluble poison extracted from Caranx bartholomaei (yellow jack), a toxic fish from the French West Indies (St Barth's island). Within a single fish, poison concentration is higher in the viscera; toxicity level is uniform throughout the flesh. In the few specimens tested, liver toxicity variations parallel those of flesh. The poison is heat stable so that cooking does not impair the toxicity. It is soluble in acetone, diethyl ether, chloroform, benzene, methanol and ethanol, but insoluble in n. hexane. Crude toxin injection or ingestion induces ciguateric disease in cats, mice or newly born chicken. Crude toxin stability is good after 30 minutes at 90 degrees C in a 0,5 N solution of a weak acid but not of a weak base. In the same conditions, loss of activity is nearly complete with a strong acid or a strong base. Moreover, rapid alkali treatment at room temperature destroys more than 50 per cent of the toxicity. The toxin is eluted by chloroform-methanol (9:1) from a silicic acid column and by acetone-methanol (9,5:0,5) from a Florisil column. DEAE cellulose column chromatography clearly separates the toxin into two lethal components; but thin layer chromatography of crude or fractionated toxin indicates only one toxic band in three different solvent systems. As a conclusion, in spite of a few differences related to instability in alkalin medium and elution from DEAE cellulose, this poison is quite similar to those carried by ciguatoxic fishes from the Pacific area. The differences noted above could be accounted for either by a specific metabolism of the species studied or by differences in the causative agent due to geographical location, or both.

Muscle invasive schistosomal squamous cell carcinoma of the urinary bladder: frequency and prognostic significance of p53, BCL-2, HER2/neu, and proliferation (MIB-1).

Muscle invasion is the usual presentation of schistosomal squamous cell carcinoma of the urinary bladder. It is unclear whether this invasive behavior is secondary to the aggressive nature of the disease or to delay in diagnosis. Fixed paraffin-embedded hematoxylin and eosin-stained sections of 15 cystectomy specimens from 15 patients (14 males, 1 female) (age range, 40 to 67 years), histologically confirmed as schistosomal squamous cell carcinoma, were assessed for grade (G1, n = 3; G2, n = 7; G3, n = 5) and pathological stage (PT category: PT2, n = 4; PT3a, n = 9; PT3b, n = 2). Immunostaining was performed for mutant p53, bcl-2, HER2/neu, and MIB-1 (proliferation), using steam antigen retrieval and an avidin-biotin complex method. Frequency of strong immunoreactivity was high for mutant p53 (73%) and MIB-1 (87% intermediate or high) but low for bcl-2 (20%) and HER2/neu (27%). There was no significant correlation of any of the four markers with either grade or stage. Hence, schistosomal bladder squamous cell carcinoma is felt to be an aggressive carcinoma de novo. The high frequency of mutant p53 expression (73%) and an intermediate to high proliferation index (87%) suggests this. The lack of correlation between histological grade and all four markers studied suggests that grading is not of prognostic value.

The 44Ti(alpha,p) reaction and its implication on the 44Ti yield in supernovae

Cross sections for the 44Ti(alpha,p)47V reaction which significantly affects the yield of 44Ti in supernovae were measured in the energy range 5.7 MeV

Comparison of PT, aPTT, and factor VII values obtained by concurrent sample collection by direct venipuncture and peripheral venous catheters.

STUDY OBJECTIVE: To compare prothrombin time (PT), activated partial thromboplastin time (aPTT), and factor VII values in concurrent blood samples obtained by direct venipuncture and from a peripheral venous catheter. DESIGN: Concurrent samples obtained from catheters and by direct venipuncture were studied. In a separate crossover bioequivalence assessment of DNA-derived factor VIIa (rFVIIa) from two different batches, sample results of each technique were compared. SETTING: University hospital clinical research unit. PATIENTS: Six patients with hemophilia A under nonbleeding conditions. INTERVENTIONS: The patients received a single dose of rFVIIa 70 micrograms/kg administered by intravenous push over 2 minutes. Concurrent blood samples were collected at 2, 3, 4, 6, 8, 10, and 12 hours after rFVIIa administration. Catheter blood samples were drawn from a three-way stopcock attached to an 18-gauge peripheral venous catheter in the patient's forearm and connected to an intravenous solution of 5% dextrose with half normal saline maintained at a rate of 30 ml/hour. Venipuncture samples were drawn from the opposite arm. MEASUREMENTS AND MAIN RESULTS: The PT and aPTT values were determined by using a BBL Fibrometer (PT) and a Coagamate X-2 with automated aPTT reagent. Blood samples were analyzed for factor VII concentration using the Novo Clot assay. The mean venipuncture-obtained PT (8.9 +/- 1.0 sec) and aPTT (48.7 +/- 13.6 sec) values were numerically equivalent to mean catheter-derived PT (9.0 +/- 1.0 sec) and aPTT (48.3 +/- 12.5 sec) results, as were mean venipuncture and catheter-obtained FVII:C values. CONCLUSIONS: The PT and aPTT values determined after venipuncture and through the peripheral catheter were not statistically different (p > 0.05) when compared by paired or unpaired analysis. Similarly, values of FVII:C measured after venipuncture were statistically equivalent to those after sampling through the peripheral catheter. All six patients preferred the catheter method of blood collection over venipuncture.

Severe citrate toxicity complicating volunteer apheresis platelet donation.

We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.