Population pharmacokinetics and exposure-response analyses of polatuzumab vedotin in patients with previously untreated DLBCL from the POLARIX study.

Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) as first-line treatment of diffuse large B-cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using a previously developed popPK model, and exposure-response (ER) analysis, were performed. The popPK analysis showed no clinically meaningful relationship between cycle 6 (C6) antibody-conjugated (acMMAE)/unconjugated MMAE area under the concentration-time curve (AUC) or maximum concentration, and weight, sex, ethnicity, region, mild or moderate renal impairment, mild hepatic impairment, or other patient and disease characteristics. In the ER analysis, C6 acMMAE AUC was significantly associated with longer progression-free and event-free survival (both p = 0.01). An increase of <50% in acMMAE/unconjugated MMAE exposure did not lead to a clinically meaningful increase in adverse events of special interest. ER data and the benefit-risk profile support the use of polatuzumab vedotin 1.8 mg/kg once every 3 weeks with R-CHP for six cycles in patients with previously untreated DLBCL.

Kilohertz volumetric imaging of in-vivo dynamics using squeezed light field microscopy.

Volumetric functional imaging of transient cellular signaling and motion dynamics poses a significant challenge to current microscopy techniques, primarily due to limitations in hardware bandwidth and the restricted photon budget within short exposure times. In response to this challenge, we present squeezed light field microscopy (SLIM), a computational imaging method that enables rapid detection of high-resolution three-dimensional (3D) light signals using only a single, low-format camera sensor area. SLIM pushes the boundaries of 3D optical microscopy, achieving over one thousand volumes per second across a large field of view of 550 µm in diameter and 300 µm in depth. Using SLIM, we demonstrated blood cell velocimetry across the embryonic zebrafish brain and in a free-moving tail exhibiting high-frequency swinging motion. The millisecond temporal resolution also enables accurate voltage imaging of neural membrane potentials in the leech ganglion. These results collectively establish SLIM as a versatile and robust imaging tool for high-speed microscopy applications.

Unraveling the origins of the coexisting localized-interfacial mechanism in oxide-based memristors in CMOS-integrated synaptic device implementations.

The forefront of neuromorphic research strives to develop devices with specific properties, i.e., linear and symmetrical conductance changes under external stimuli. This is paramount for neural network accuracy when emulating a biological synapse. A parallel exploration of resistive memory as a replacement for conventional computing memory ensues. In search of a holistic solution, the proposed memristive device in this work is uniquely poised to address this elusive gap as a unified memory solution. Opposite biasing operations are leveraged to achieve stable abrupt and gradual switching characteristics within a single device, addressing the demands for lower latency and energy consumption for binary switching applications, and graduality for neuromorphic computing applications. We evaluated the underlying principles of both switching modes, attributing the anomalous gradual switching to the modulation of oxygen-deficient layers formed between the active electrode and oxide switching layer. The memristive cell (1R) was integrated with 40 nm transistor technology (1T) to form a 1T-1R memory cell, demonstrating a switching speed of 50 ns with a pulse amplitude of ±2.5 V in its forward-biased mode. Applying pulse trains of 20 ns to 490 ns in the reverse-biased mode exhibited synaptic weight properties, obtaining a nonlinearity (NL) factor of <0.5 for both potentiation and depression. The devices in both modes also demonstrated an endurance of >106 cycles, and their conductance states were also stable under temperature stress at 85 °C for 104 s. With the duality of the two switching modes, our device can be used for both memory and synaptic weight-storing applications.

How P. aeruginosa cells with diverse stator composition collectively swarm.

Swarming is a macroscopic phenomenon in which surface bacteria organize into a motile population. The flagellar motor that drives swarming in Pseudomonas aeruginosa is powered by stators MotAB and MotCD. Deletion of the MotCD stator eliminates swarming, whereas deletion of the MotAB stator enhances swarming. Interestingly, we measured a strongly asymmetric stator availability in the wild-type (WT) strain, with MotAB stators produced at an approximately 40-fold higher level than MotCD stators. However, utilization of MotCD stators in free swimming cells requires higher liquid viscosities, while MotAB stators are readily utilized at low viscosities. Importantly, we find that cells with MotCD stators are ~10× more likely to have an active motor compared to cells uses the MotAB stators. The spectrum of motility intermittency can either cooperatively shut down or promote flagellum motility in WT populations. In P. aeruginosa, transition from a static solid-like biofilm to a dynamic liquid-like swarm is not achieved at a single critical value of flagellum torque or stator fraction but is collectively controlled by diverse combinations of flagellum activities and motor intermittencies via dynamic stator utilization. Experimental and computational results indicate that the initiation or arrest of flagellum-driven swarming motility does not occur from individual fitness or motility performance but rather related to concepts from the "jamming transition" in active granular matter.IMPORTANCEIt is now known that there exist multifactorial influences on swarming motility for P. aeruginosa, but it is not clear precisely why stator selection in the flagellum motor is so important. We show differential production and utilization of the stators. Moreover, we find the unanticipated result that the two motor configurations have significantly different motor intermittencies: the fraction of flagellum-active cells in a population on average with MotCD is active ~10× more often than with MotAB. What emerges from this complex landscape of stator utilization and resultant motor output is an intrinsically heterogeneous population of motile cells. We show how consequences of stator recruitment led to swarming motility and how the stators potentially relate to surface sensing circuitry.

Anisometropia and Amblyopia Outcomes in Early Versus Late Resolution of Congenital Nasolacrimal Duct Obstruction in Older Infants.

PURPOSE: Congenital nasolacrimal duct obstruction is a known risk factor for amblyopia and anisometropia. The purpose of this study was to investigate whether the rate of anisometropia and amblyopia development differed based on the age at CNLDO resolution in older infants. METHODS: This retrospective chart review at a single tertiary children's hospital from 2007 to 2017 compared early versus late spontaneous resolution (cutoff 12 months) and intervention (cutoff 15 months) groups presenting at ≥9 months of age, comparing visual outcomes, including anisometropia (≥1 D of sphere or cylinder) and amblyopia (≥2 levels difference in Teller acuity or optotype testing). Parents/guardians were contacted by phone for missing data on spontaneous resolution or intervention status. RESULTS: A total of 462 patients were included (152 early; 310 late group). The early group presented at a median age of 12.0 (interquartile range: 10.0, 13.0) months, while the late group presented at 21.0 (interquartile range: 15.0, 32.0) months. Unilateral disease occurred in 62% and 59%, respectively. Anisometropia was seen in (12/102) 12% of early versus (25/243) 10% of late patients (p = 0.686, 95% CI: -0.059, 0.088), and amblyopia in (4/131) 3% of early versus (14/286) 5% of late patients (p = 0.322, 95% CI: -0.061, 0.018). In patients presenting <24 months without undergoing surgery, spontaneous resolution occurred in 76% between 12 and 24 months (n = 41). CONCLUSIONS: Anisometropia and amblyopia rates did not significantly differ between early and delayed intervention for congenital nasolacrimal duct obstruction in this retrospective cohort presenting beyond 9 months of age to a children's hospital. This study found frequent late spontaneous resolution.

Type 1 Diabetes Mellitus Management and Islet Cell Therapy: A New Chapter in Patient Care.

Diabetes mellitus (DM) is a complex endocrine disorder characterized by abnormally high levels of glucose, also called hyperglycemia. DM usually occurs when the body does not produce enough insulin or cannot respond to the insulin in the body. Type 1 diabetes mellitus (T1DM) or insulin-dependent diabetes is an autoimmune disease that affects around 8 million people in the world. Patients with T1DM experience an array of symptoms such as polyuria, polydipsia, and weight loss. These patients are prone to immediate life-threatening complications, including hypoglycemia and diabetic ketoacidosis. These patients are also at increased risk of ischemic heart disease, stroke, chronic kidney disease, vision loss, and even damage to nerve endings resulting in neuropathy. In this article, we will discuss type 1 diabetes mellitus and the different treatment options, focusing primarily on the Food and Drug Administration (FDA)-approved first cellular therapy for T1DM, donislecel.

A bi-functional three-terminal memristor applicable as an artificial synapse and neuron.

Due to their significant resemblance to the biological brain, spiking neural networks (SNNs) show promise in handling spatiotemporal information with high time and energy efficiency. Two-terminal memristors have the capability to achieve both synaptic and neuronal functions; however, such memristors face asynchronous programming/reading operation issues. Here, a three-terminal memristor (3TM) based on oxygen ion migration is developed to function as both a synapse and a neuron. We demonstrate short-term plasticity such as pair-pulse facilitation and high-pass dynamic filtering in our devices. Additionally, a 'learning-forgetting-relearning' behavior is successfully mimicked, with lower power required for the relearning process than the first learning. Furthermore, by leveraging the short-term dynamics, the leaky-integrate-and-fire neuronal model is emulated by the 3TM without adopting an external capacitor to obtain the leakage property. The proposed bi-functional 3TM offers more process compatibility for integrating synaptic and neuronal components in the hardware implementation of an SNN.

Respiratory Syncytial Virus Prevention: A New Era of Vaccines.

Respiratory syncytial virus (RSV) is a pathogen that primarily affects the respiratory system, leading to upper and lower respiratory tract infections. Children, individuals aged 60 and above, and individuals with impaired immune systems are more susceptible to developing RSV lower respiratory tract infections (LRTIs), which can result in fatalities in some instances. Symptoms of LRTI include shortness of breath, wheezing, pneumonia, and bronchiolitis. Current management of RSV-LRTI includes conservative and symptomatic treatment. The Food and Drug Administration (FDA) recently approved two vaccines that effectively prevent acute and severe RSV-LRTI requiring hospitalizations. Nirsevimab (Beyfortus) is approved for infants born at 35 weeks of gestation and above. At the same time, RSVPreF3 OA (Arexvy) is recommended for adults aged 60 and older. Both vaccines are effective against the two major strains of RSV and require single doses to induce immunity. In this article, we will discuss the mechanism of action, effectiveness, and side effects of these novel vaccines and their possible impact.

Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non-Asian patients with previously untreated diffuse large B-cell lymphoma in POLARIX.

This ethnic sensitivity analysis used data from the phase III POLARIX study (NCT03274492) to assess polatuzumab vedotin pharmacokinetics (PKs) in Asian versus non-Asian patients with previously untreated diffuse large B-cell lymphoma and examined the appropriateness of extrapolating global study findings to Asian patients. PK and population PK (PopPK) analyses assessed polatuzumab vedotin analyte exposures by ethnicity (Asian [n = 84] vs. non-Asian [n = 345] patients) and region (patients enrolled from Asia [n = 80] vs. outside Asia [n = 349]). In patients from Asia versus outside Asia, observed mean antibody-conjugated monomethyl auristatin E (acMMAE) concentrations were comparable (1.2% lower at cycle [C]1 postdose, 4.4% higher at C4 predose; and 6.8% lower at C4 postdose in patients from Asia). Observed mean unconjugated MMAE was lower in patients from Asia by 6.5% (C1 postdose), 20.0% (C4 predose), and 15.3% (C4 postdose). In the PopPK analysis, C6 area under the curve and peak plasma concentrations were also comparable for acMMAE (6.3% and 3.0% lower in Asian vs. non-Asian patients, respectively) and lower for unconjugated MMAE by 19.1% and 16.7%, respectively. By region, C6 mean acMMAE concentrations were similar, and C6 mean unconjugated MMAE concentrations were lower, in patients enrolled from Asia versus outside Asia, by 3.9%-7.0% and 17.3%-19.7%, respectively. In conclusion, polatuzumab vedotin PKs were similar between Asian and non-Asian patients by ethnicity and region, suggesting PKs are not sensitive to Asian ethnicity and dose adjustments are not required in Asian patients to maintain efficacy and safety.

Proton-Assisted Redox-Based Three-Terminal Memristor for Synaptic Device Applications.

Emerging technologies, i.e., spintronics, 2D materials, and memristive devices, have been widely investigated as the building block of neuromorphic computing systems. Three-terminal memristor (3TM) is specifically designed to mitigate the challenges encountered by its two-terminal counterpart as it can concurrently execute signal transmission and memory operations. In this work, we present a complementary metal-oxide-semiconductor-compatible 3TM with highly linear weight update characteristics and a dynamic range of ∼15. The switching mechanism is governed by the migration of oxygen ions and protons in and out of the channel under an external gate electric field. The involvement of the protonic defects in the electrochemical reactions is proposed based on the bipolar pulse trains required to initiate the oxidation process and the device electrical characteristics under different humidity levels. For the synaptic operation, an excellent endurance performance with over 256k synaptic weight updates was demonstrated while maintaining a stable dynamic range. Additionally, the synaptic performance of the 3TM is simulated and implemented into a four-layer neural network (NN) model, achieving an accuracy of ∼92% in MNIST handwritten digit recognition. With such desirable conductance modulation characteristics, our proposed 3T-memristor is a promising synaptic device candidate to realize the hardware implementation of the artificial NN.

Reliability Evaluation of Board-Level Flip-Chip Package under Coupled Mechanical Compression and Thermal Cycling Test Conditions.

Flip Chip Ball Grid Array (FCBGA) packages, together with many other heterogeneous integration packages, are widely used in high I/O (Input/Output) density and high-performance computing applications. The thermal dissipation efficiency of such packages is often improved through the use of an external heat sink. However, the heat sink increases the solder joint inelastic strain energy density, and thus reduces the board-level thermal cycling test reliability. The present study constructs a three-dimensional (3D) numerical model to investigate the solder joint reliability of a lidless on-board FCBGA package with heat sink effects under thermal cycling testing, in accordance with JEDEC standard test condition G (a thermal range of -40 to 125 °C and a dwell/ramp time of 15/15 min). The validity of the numerical model is confirmed by comparing the predicted warpage of the FCBGA package with the experimental measurements obtained using a shadow moiré system. The effects of the heat sink and loading distance on the solder joint reliability performance are then examined. It is shown that the addition of the heat sink and a longer loading distance increase the solder ball creep strain energy density (CSED) and degrade the package reliability performance accordingly.

cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8+ T cell function and anti-tumor immunity.

B7 ligands (CD80 and CD86), expressed by professional antigen-presenting cells (APCs), activate the main co-stimulatory receptor CD28 on T cells in trans. However, in peripheral tissues, APCs expressing B7 ligands are relatively scarce. This raises the questions of whether and how CD28 co-stimulation occurs in peripheral tissues. Here, we report that CD8+ T cells displayed B7 ligands that interacted with CD28 in cis at membrane invaginations of the immunological synapse as a result of membrane remodeling driven by phosphoinositide-3-kinase (PI3K) and sorting-nexin-9 (SNX9). cis-B7:CD28 interactions triggered CD28 signaling through protein kinase C theta (PKCθ) and promoted CD8+ T cell survival, migration, and cytokine production. In mouse tumor models, loss of T cell-intrinsic cis-B7:CD28 interactions decreased intratumoral T cells and accelerated tumor growth. Thus, B7 ligands on CD8+ T cells can evoke cell-autonomous CD28 co-stimulation in cis in peripheral tissues, suggesting cis-signaling as a general mechanism for boosting T cell functionality.

CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice.

Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (N = 123,509-133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (N = 130,684). Because these GWAS implicated the gene CADM2, we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants in CADM2 in a multi-ancestral 23andMe cohort (N = 3,229,317, European; N = 579,623, Latin American; N = 199,663, African American). Finally, we produced Cadm2 mutant mice and used them to perform a Mouse-PheWAS ("MouseWAS") by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (~6-11%), and moderate genetic correlations (rg = 0.20-0.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such as TCF4 and PTPRF, and also identified nominal associations proximal to DRD2 and CRHR1. PheWAS for CADM2 variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role of CADM2 in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.

Dual receptor T cells mediate effective antitumor immune responses via increased recognition of tumor antigens.

BACKGROUND: Discovery that ~16% of T cells naturally co-express two T-cell receptor (TCR) clonotypes prompts examining the role of dual TCR cells in immune functions. METHODS: Using TCRα-reporter transgenic mice, enabling unambiguous identification of single-TCR and dual-TCR cells, we tested the role of dual TCR cells in antitumor immune responses against immune-responsive syngeneic 6727 sarcoma and immune-resistant B16F10 melanoma. RESULTS: Dual TCR cells were specifically increased among tumor-infiltrating lymphocytes (TILs) in both models, indicating selective advantage in antitumor responses. Phenotype and single-cell gene expression analyses identified dual TCR are predominant during the effective antitumor response, demonstrating selectively increased activation in the TIL compartment and skewing toward an effector memory phenotype. Absence of dual TCR cells impaired immune response to B16F10 but not 6727, suggesting that dual TCR cells may be more influential in responses against poorly immunogenic tumors. Dual TCR cells demonstrated an advantage in recognition of B16F10-derived neoantigens in vitro, providing a mechanistic basis for their antitumor reactivity. CONCLUSIONS: These results discover an unrecognized role for dual TCR cells in protective immune function and identify these cells and their TCRs as a potential resource for antitumor immunotherapy.

The impact of oxygen vacancy defect density on the nonlinearity and short-term plasticity of TiO2-based exponential selector.

The readout margin of the one selector-one RRAM crossbar array architecture is strongly dependent on the nonlinearity of the selector device. In this work, we demonstrated that the nonlinearity of Pt/TiO2/Pt exponential selectors increases with decreasing oxygen vacancy defect density. The defect density is controlled by modulating the sputtering pressure in the oxide deposition process. Our results reveal that the dominant conduction mechanisms of the Pt/TiO2/Pt structure transit from Schottky emission to Poole-Frenkel emission with the increase of sputtering pressure. Such transition is attributed to the rise of oxygen vacancy concentration. In addition, the short-term plasticity feature of the Pt/TiO2/Pt selector is shown to be enhanced with a lower defect density. These results suggest that low defect density is necessary for improved exponential selector performances.

How individual P. aeruginosa cells with diverse stator distributions collectively form a heterogeneous macroscopic swarming population.

Swarming is a macroscopic phenomenon in which surface bacteria organize into a motile population. The flagellar motor that drives swarming in Pseudomonas aeruginosa is powered by stators MotAB and MotCD. Deletion of the MotCD stator eliminates swarming, whereas deletion of the MotAB stator enhances swarming. Interestingly, we measured a strongly asymmetric stator availability in the WT strain, with MotAB stators produced ∼40-fold more than MotCD stators. However, recruitment of MotCD stators in free swimming cells requires higher liquid viscosities, while MotAB stators are readily recruited at low viscosities. Importantly, we find that cells with MotCD stators are ∼10x more likely to have an active motor compared to cells without, so wild-type, WT, populations are intrinsically heterogeneous and not reducible to MotAB-dominant or MotCD-dominant behavior. The spectrum of motility intermittency can either cooperatively shut down or promote flagellum motility in WT populations. In P. aeruginosa , transition from a static solid-like biofilm to a dynamic liquid-like swarm is not achieved at a single critical value of flagellum torque or stator fraction but is collectively controlled by diverse combinations of flagellum activities and motor intermittencies via dynamic stator recruitment. Experimental and computational results indicate that the initiation or arrest of flagellum-driven swarming motility does not occur from individual fitness or motility performance but rather related to concepts from the 'jamming transition' in active granular matter. Importance: After extensive study, it is now known that there exist multifactorial influences on swarming motility in P. aeruginosa , but it is not clear precisely why stator selection in the flagellum motor is so important or how this process is collectively initiated or arrested. Here, we show that for P. aeruginosa PA14, MotAB stators are produced ∼40-fold more than MotCD stators, but recruitment of MotCD over MotAB stators requires higher liquid viscosities. Moreover, we find the unanticipated result that the two motor configurations have significantly different motor intermittencies, the fraction of flagellum-active cells in a population on average, with MotCD active ∼10x more often than MotAB. What emerges from this complex landscape of stator recruitment and resultant motor output is an intrinsically heterogeneous population of motile cells. We show how consequences of stator recruitment led to swarming motility, and how they potentially relate to surface sensing circuitry.

Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial.

In the phase 3 POLARIX study in previously untreated diffuse large B-cell lymphoma, polatuzumab vedotin combined with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with similar safety. Patients were randomized 1:1 to 6 cycles of Pola-R-CHP or R-CHOP plus 2 cycles of rituximab alone. For registration of POLARIX in China, consistency of PFS in an Asia subpopulation (defined as ≥50% of the risk reduction in PFS expected in the global population) was evaluated. Overall, 281 patients were analyzed: 160 patients from Asia in the intention-to-treat (ITT) population of the global study and 121 from an ITT China extension cohort. Of these, 141 were randomized to Pola-R-CHP and 140 to R-CHOP. At data cutoff (28 June 2021; median follow-up 24.2 months), PFS met the consistency definition with the global population, and was superior with Pola-R-CHP vs R-CHOP (hazard ratio, 0.64; 95% confidence interval [CI], 0.40-1.03). Two-year PFS was 74.2% (95% CI, 65.7-82.7) and 66.5% (95% CI, 57.3-75.6) with Pola-R-CHP and R-CHOP, respectively. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). These findings demonstrate consistent efficacy and safety of Pola-R-CHP vs R-CHOP in the Asia and global populations in POLARIX. This trial was registered at https://clinicaltrials.gov/ct2/home as # NCT03274492.

Does plant ecosystem thermoregulation occur? An extratropical assessment at different spatial and temporal scales.

To what degree plant ecosystems thermoregulate their canopy temperature (Tc ) is critical to assess ecosystems' metabolisms and resilience with climate change, but remains controversial, with opinions from no to moderate thermoregulation capability. With global datasets of Tc , air temperature (Ta ), and other environmental and biotic variables from FLUXNET and satellites, we tested the 'limited homeothermy' hypothesis (indicated by Tc & Ta regression slope < 1 or Tc < Ta around midday) across global extratropics, including temporal and spatial dimensions. Across daily to weekly and monthly timescales, over 80% of sites/ecosystems have slopes ≥1 or Tc > Ta around midday, rejecting the above hypothesis. For those sites unsupporting the hypothesis, their Tc -Ta difference (ΔT) exhibits considerable seasonality that shows negative, partial correlations with leaf area index, implying a certain degree of thermoregulation capability. Spatially, site-mean ΔT exhibits larger variations than the slope indicator, suggesting ΔT is a more sensitive indicator for detecting thermoregulatory differences across biomes. Furthermore, this large spatial-wide ΔT variation (0-6°C) is primarily explained by environmental variables (38%) and secondarily by biotic factors (15%). These results demonstrate diverse thermoregulation patterns across global extratropics, with most ecosystems negating the 'limited homeothermy' hypothesis, but their thermoregulation still occurs, implying that slope < 1 or Tc < Ta are not necessary conditions for plant thermoregulation.

Comparison of Apple Watch vs KardiaMobile: A Tale of Two Devices.

Background: The Apple Watch Series 4 (AW4) and the KardiaMobile single bipolar lead model (KM) are 2 of the most popular US Food & Drug Administration (FDA)-approved commercial heart trackers. However, a lack of knowledge remains regarding their rhythm-detection accuracy in real-life clinical situations. This paper aims to determine the practicality of using an AW4 or a KM in modern medical practice, by assessing the accuracy of each in identifying heart rhythms and heart rate. Methods: Participants from the Toronto Heart Centre clinic were enrolled from January 2019 to December 2019. They had a 12-lead electrocardiogram (ECG), followed by wearing the AW4 watch (OS 5.3), and pressing on the KM electrode plates, within the span of 5 minutes of one another. Each session involved a 12-lead ECG, an ECG from each device, and AW4's photoplethysmography function (APPG). Results: Of 200 participants, 162 (81%) were in sinus rhythm, and 38 (19%) had atrial fibrillation. The rhythm-detection accuracy for sinus rhythm was 100% for the AW4, and 99.03% for the KM. For atrial fibrillation, accuracy was 90.48% for the AW4, and 100% for the KM. The heart rate accuracy for sinus rhythm was 94.39% for the KM, 90.65% for the APPG, and 96.26% for the Apple ECG function. The heart rate accuracy for atrial fibrillation was 91.30% for the KM, 82.61% for the APPG, and 86.96% for the Apple ECG function. Conclusions: Both the AW4 and the KM could reliably detect rhythm and heart rate in real-life clinical situations. However, a nonsignificant trend occurred toward better rhythm detection and accuracy with KM, compared with AW4. The difference is mainly due to artifacts (eg, tremors) and the fit of the strap for AW4. The findings have important implications for how these consumer devices can be used in real-life clinical settings.

Contexte: La Apple Watch Series 4 (AW4) et le dispositif KardiaMobile à trois électrodes (KM) sont deux des capteurs cardiaques commerciaux les plus populaires approuvés par la Food & Drug Administration (FDA) des États-Unis. Cependant, les connaissances sont encore insuffisantes en ce qui concerne leur précision à détecter le rythme cardiaque dans des situations cliniques réelles. Cet article vise à déterminer l'utilité de l'AW4 ou du KM dans la pratique médicale moderne, en évaluant la précision de chaque appareil dans la perception des rythmes cardiaques et de la fréquence cardiaque. Méthodologie: Des patients du Toronto Heart Centre ont participé à l'étude de janvier à décembre 2019. Ils ont subi un électrocardiogramme (ECG) à 12 dérivations, puis ont porté la montre AW4 (OS 5.3) et utilisé les électrodes du KM, à intervalles de 5 minutes. Chaque séance comprenait un ECG à 12 dérivations, un ECG réalisé avec chacun des dispositifs et l'utilisation de la fonction de photopléthysmographie de l'AW4. Résultats: Sur les 200 participants, 162 (81 %) étaient en rythme sinusal et 38 (19 %) présentaient une fibrillation auriculaire. Pour ce qui est du rythme cardiaque, la précision de détection chez les patients en rythme sinusal était de 100 % pour l'AW4 et de 99,03 % pour le KM. Pour ceux présentant une fibrillation auriculaire, la précision était de 90,48 % pour l'AW4 et de 100 % pour le KM. En ce qui concerne la fréquence cardiaque, la précision de détection pour le rythme sinusal était de 94,39 % pour le KM, de 90,65 % pour la fonction de photopléthysmographie de l'AW4 et de 96,26 % pour la fonction ECG d'Apple. Chez les patients atteints de fibrillation auriculaire, la précision à détecter la fréquence cardiaque était de 91,30 % pour le KM, de 82,61 % pour la fonction de photopléthysmographie de l'AW4 et de 86,96 % pour la fonction ECG d'Apple. Conclusions: L'AW4 et le KM ont tous deux permis de détecter de manière fiable le rythme cardiaque et la fréquence cardiaque dans des situations cliniques réelles. Soulignons toutefois qu'une tendance non significative s'est dégagée en faveur du KM pour ce qui est de la détection du rythme et de la précision par rapport à l'AW4. La différence s'explique principalement par des interférences (secousses) et par l'ajustement du bracelet avec l'AW4. Ces résultats ont une incidence importante quant à l'utilisation de ces appareils destinés aux consommateurs dans un contexte clinique réel.

Spontaneous Formation of a Ligand-Based 2D Capping Layer on the Surface of Quasi-2D Perovskite Films.

Two-dimensional (2D) Ruddlesden-Popper phase perovskites (RPPs) are attracting growing attention for photovoltaic applications due to their enhanced stability compared to three-dimensional (3D) perovskites. The superior tolerance of 2D RPPs films to moisture and oxygen is mainly attributed to the hydrophobic nature of the introduced long-chain spacer cations (ligands). In this work, it is revealed that a thin capping layer, consisting of self-assembled butylammonium ligands, is spontaneously formed on the top surface of a quasi-2D perovskite film prepared by conventional one-step hot casting. Based on morphological and crystallographic analyses of both the top/bottom surfaces and the interior of quasi-2D perovskite films, the formation process of the 2D capping layer and the assembly of RPPs, comprising both large and small slab thickness (large-n, small-n), is elucidated. The vertical orientation of RPPs that is required for sufficient charge transport for 2D perovskite solar cells (PSCs) is further verified. We propose that the surface capping layer is directly responsible for the long-term stability of 2D PSCs. This work provides detailed insight into the microstructure of quasi-2D RPPs films that should assist the development of strategies for unlocking the full potential of 2D perovskites for high-performance PSCs and other solid-state electronic devices.