Influence of meteorological variables and air pollutants on measurements from automatic pollen sampling devices.

This study examines the influence of meteorological factors and air pollutants on the performance of automatic pollen monitoring devices, as part of the EUMETNET Autopollen COST ADOPT-intercomparison campaign held in Munich, Germany, during the 2021 pollen season. The campaign offered a unique opportunity to compare all automatic monitors available at the time, a Plair Rapid-E, a Hund-Wetzlar BAA500, an OPC Alphasense, a KH-3000 Yamatronics, three Swisens Polenos, a PollenSense APS, a FLIR IBAC2, a DMT WIBS-5, an Aerotape Sextant, to the average of four manual Hirst traps, under the same environmental conditions. The investigation aimed to elucidate how meteorological factors and air pollution impact particle capture and identification efficiency. The analysis showed coherent results for most devices regarding the correlation between environmental conditions and pollen concentrations. This reflects on one hand, a significant correlation between weather and airborne pollen concentration, and on the other hand the capability of devices to provide meaningful data under the conditions under which measurements were taken. However, correlation strength varied among devices, reflecting differences in design, algorithms, or sensors used. Additionally, it was observed that different algorithms applied to the same dataset resulted in different concentration outputs, highlighting the role of algorithm design in these systems (monitor + algorithm). Notably, no significant influence from air pollutants on the pollen concentrations was observed, suggesting that any potential difference in effect on the systems might require higher air pollution concentrations or more complex interactions. However, results from some monitors were affected to a minor degree by specific weather variables. Our findings suggest that the application of real-time devices in urban environments should focus on the associated algorithm that classifies pollen taxa. The impact of air pollution, although not to be excluded, is of secondary concern as long as the pollution levels are similar to a large European city like Munich.

Association of free maternal and fetal ropivacaine after epidural analgesia for intrapartum caesarean delivery: a prospective observational trial.

BACKGROUND: Ropivacaine is present in plasma in both protein-bound and free forms. The free form is responsible for the occurrence of toxic side effects. During obstetric epidural analgesia, free ropivacaine enters the fetal circulation depending on various factors. The aim of this study was to analyse a potential association between ropivacaine concentrations in maternal and fetal plasma and hence the extent of fetal exposure to ropivacaine. METHODS: In this prospective monocentre study, parturients who met the following criteria were included in the study: 1. epidural administration as part of obstetric anaesthesia, and 2. subsequent intrapartum caesarean delivery, which 3. was performed after an epidural bolus administration of ropivacaine within the existing epidural analgesia. Total and free ropivacaine concentrations were analysed in maternal blood at baseline, prior to epidural bolus administration for caesarean delivery, and in maternal and fetal (umbilical venous, oxygenated) blood at delivery. The results are presented as mean ±â€¯SD or median (25/75th percentile). RESULTS: We screened 128 parturients who went into labour at term and requested epidural analgesia, of whom 39 were ultimately included in the study. An intrapartum caesarean delivery was performed after the epidural application of 207 (166/276) mg ropivacaine during an epidural treatment period of 577 (360/1010) min. Total and free ropivacaine concentrations were 1402 ±â€¯357 ng/ml and 53 ±â€¯46 ng/ml, respectively, in maternal venous blood and 457 ±â€¯243 ng/ml and 43 ±â€¯27 ng/ml, respectively, in fetal blood. The maternal total and free ropivacaine concentrations were significantly correlated (r = 0.873; P < 0.0001). CONCLUSION: The results of the present study suggest that determining the concentration of free ropivacaine in maternal blood may be a feasible option for estimating neonatal exposure to ropivacaine.

Design of the first fusion experiment to achieve target energy gain G>1.

In this work we present the design of the first controlled fusion laboratory experiment to reach target gain G>1 N221204 (5 December 2022) [Phys. Rev. Lett. 132, 065102 (2024)10.1103/PhysRevLett.132.065102], performed at the National Ignition Facility, where the fusion energy produced (3.15 MJ) exceeded the amount of laser energy required to drive the target (2.05 MJ). Following the demonstration of ignition according to the Lawson criterion N210808, experiments were impacted by nonideal experimental fielding conditions, such as increased (known) target defects that seeded hydrodynamic instabilities or unintentional low-mode asymmetries from nonuniformities in the target or laser delivery, which led to reduced fusion yields less than 1 MJ. This Letter details design changes, including using an extended higher-energy laser pulse to drive a thicker high-density carbon (also known as diamond) capsule, that led to increased fusion energy output compared to N210808 as well as improved robustness for achieving high fusion energies (greater than 1 MJ) in the presence of significant low-mode asymmetries. For this design, the burnup fraction of the deuterium and tritium (DT) fuel was increased (approximately 4% fuel burnup and a target gain of approximately 1.5 compared to approximately 2% fuel burnup and target gain approximately 0.7 for N210808) as a result of increased total (DT plus capsule) areal density at maximum compression compared to N210808. Radiation-hydrodynamic simulations of this design predicted achieving target gain greater than 1 and also the magnitude of increase in fusion energy produced compared to N210808. The plasma conditions and hotspot power balance (fusion power produced vs input power and power losses) using these simulations are presented. Since the drafting of this manuscript, the results of this paper have been replicated and exceeded (N230729) in this design, together with a higher-quality diamond capsule, setting a new record of approximately 3.88MJ of fusion energy and fusion energy target gain of approximately 1.9.

Hohlraum Reheating from Burning NIF Implosions.

As fusion experiments at the National Ignition Facility (NIF) approach and exceed breakeven, energy from the burning capsule is predicted to couple to the gold walls and reheat the hohlraum. On December 5, 2022, experiment N221204 exceeded target breakeven, historically achieving 3.15 MJ of fusion energy from 2.05 MJ of laser drive; for the first time, energy from the igniting capsule reheated the hohlraum beyond the peak laser-driven radiation temperature of 313 eV to a peak of 350 eV, in less than half a nanosecond. This reheating effect has now been unambiguously observed by the two independent Dante calorimeter systems across multiple experiments, and is shown to result from reheating of the remnant tungsten-doped ablator by the exploding core, which is heated by alpha deposition.

Complexity of patients with or without infectious disease consultation in tertiary-care hospitals in Germany.

PURPOSE: Patients seen by infectious disease (ID) specialists are more complex compared to patients treated by other subspecialities according to Tonelli et al. (2018). However, larger studies on the complexity of patients related to the involvement of ID consultation services are missing. METHODS: Data of patients being treated in 2015 and 2019 in four different German university hospitals was retrospectively collected. Data were collected from the hospitals' software system and included whether the patients received an ID consultation as well as patient clinical complexity level (PCCL), case mix index (CMI) and length of stay (LOS) as a measurement for the patients' complexity. Furthermore, a comparison of patients with distinct infectious diseases treated with or without an ID consultation was initiated. RESULTS: In total, 215.915 patients were included in the study, 3% (n = 6311) of those were seen by an ID consultant. Patients receiving ID consultations had a significantly (p < 0.05) higher PCCL (median 4 vs. 0), CMI (median 3,8 vs. 1,1) and deviation of the expected mean LOS (median 7 days vs. 0 days) than patients in the control group. No differences among hospitals or between years were observed. Comparing patients with distinct infectious diseases treated with or without an ID consultation, the differences were confirmed throughout the groups. CONCLUSION: Patients receiving ID consultations are highly complex, frequently need further treatment after discharge and have a high economic impact. Thus, ID specialists should be clinically trained in a broad spectrum of diseases and treating these complex patients should be sufficiently remunerated.

Diagnosing the origin and impact of low-mode asymmetries in ignition experiments at the National Ignition Facility.

Inertial confinement fusion ignition requires high inflight shell velocity, good energy coupling between the hotspot and shell, and high areal density at peak compression. Three-dimensional asymmetries caused by imperfections in the drive symmetry or target can grow and damage the coupling and confinement. Recent high-yield experiments have shown that low-mode asymmetries are a key degradation mechanism and contribute to variability. We show the experimental signatures and impacts of asymmetry change with increasing implosion yield given the same initial cause. This letter has implications for improving robustness to a key degradation in ignition experiments.

[Mechanisms of action and clinical application of diuretics in intensive care medicine]. / Wirkmechanismen und klinische Anwendung von Diuretika in der Intensivmedizin.

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures.

Reduced mixing in inertial confinement fusion with early-time interface acceleration.

In inertial confinement fusion (ICF) implosions, the interface between the cryogenic DT fuel and the ablator is unstable to shock acceleration (the Richtmyer-Meshkov instability, RM) and constant acceleration (Rayleigh-Taylor instability, RT). Instability growth at this interface can reduce the final compression, limiting fusion burnup. If the constant acceleration is in the direction of the lighter material (negative Atwood number), the RT instability produces oscillatory motion that can stabilize against RM growth. Theory and simulations suggest this scenario occurred at early times in some ICF experiments on the National Ignition Facility, possibly explaining their favorable performance compared to one-dimensional simulations. This characteristic is being included in newer, lower adiabat designs, seeking to improve compression while minimizing ablator mixing into the fuel.

Non-invasive assessment of muscle compartment elasticity by pressure-related ultrasound in pediatric trauma: a prospective clinical study in 25 cases of forearm shaft fractures.

BACKGROUND: Soft-tissue swelling after limb fractures in pediatric patients is well known to be a risk factor for developing acute compartment syndrome (ACS). Clinical assessment alone is uncertain in specific cases. Recently, we proposed a non-invasive ultrasound-based method to objectify muscle compartment elasticity for monitoring. We hypothesize a strong correlation between the soft-tissue swelling after stabilization of upper limb fractures and the compartment elasticity objectified with a novel ultrasound-based approach in pediatric trauma. PATIENTS AND METHODS: In a prospective clinical study, children suffering forearm fractures but not developing an ACS were included. The muscle compartment elasticity of the m. flexor carpi ulnaris was assessed after surgical intervention by a non-invasive, ultrasound-based method resulting in a relative elasticity (RE in %) in both the control (healthy limb) and study group (fractured limb). Soft-tissue swelling was categorized in four different levels (0-3) and correlated with the resulting RE (%). RESULTS: The RE in the study group (15.67%, SD ± 3.06) showed a significantly decreased level (p < 0.001) compared with the control (22.77%, SD ± 5.4). The categorized grade of soft-tissue swelling resulted in a moderate correlation with the RE (rs = 0.474). CONCLUSIONS: The presented study appears to represent a novel approach to assess the posttraumatic pressure changes in a muscle compartment after fracture stabilization non-invasively. In this first clinical study in pediatric cases, our measurement method represents a low-cost, easy, and secure approach that has the potential to substitute invasive measurement of suspected ACS in muscle compartment conditions. Further investigations in lager cohorts are required to prove its daily clinical practicability and to confirm the expected reliability.

Evaluation of the diagnostic accuracy of a point-of-care device to measure concentrations of nonesterified fatty acids in serum and whole blood.

The objective of this study was to compare measurements of nonesterified fatty acids (NEFA) between the gold standard diagnostic laboratory method and a handheld NEFA meter (Qucare Pro meter, DFI Co. Ltd.). Three experiments were conducted to study the usability of the meter. In experiment 1 we compared results of the meter obtained from measurements in serum and whole blood with results of the gold standard method. Based on the results of experiment 1 we compared the results measured by the meter in whole blood with results obtained from the gold standard method on a larger scale, as we wanted to omit the step of centrifugation with the cow-side test. In experiment 3 we determined the influence of ambient temperature on measurements. Overall, blood samples of 231 cows were collected between 14 and 20 d in milk. The Spearman correlation coefficients (ρ) were calculated and Bland-Altman plots were created to compare the accuracy of the NEFA meter with the gold standard. In addition, in experiment 2 receiver operating characteristic (ROC) curve analyses were performed, to define thresholds for the NEFA meter to detect cows with a NEFA concentration above 0.3, 0.4, and 0.7 mEq/L. In experiment 1, there was a high correlation between NEFA concentrations in whole blood and serum determined by the NEFA meter and the gold standard (ρ = 0.90 for measurement in whole blood; ρ = 0.93 for measurement in serum). In experiment 2, the measurement in whole blood with the NEFA meter was compared with the gold standard. Despite a lower correlation (ρ = 0.79) the ROC curve analyses revealed a high specificity and a moderate sensitivity for lower cut-points (i.e., 0.3 and 0.4 mEq/L). The NEFA meter underestimated especially high concentration of >0.7 mEq/L. Considering thresholds of 0.3, 0.4, and 0.7 mEq/L measured by the gold standard test, sensitivity and specificity were 59.1% and 96.7%, 79.0% and 95.4%, and 86.4% and 95.6%, respectively, when using 0.3, 0.3, and 0.4 mEq/L as thresholds for the NEFA meter. Accuracy was 74.1%, 88.3%, and 93.8% for the 3 thresholds tested. Experiment 3 showed that measurements should be conducted at approximately 21°C (ρ = 0.73) as correlations were poor at 6.2°C and 15.1°C (ρ = 0.18 and 0.22, respectively).

Higher temperatures directly increase germ cell number, promoting feminization of red-eared slider turtles.

In many reptile species, gonadal sex is affected by environmental temperature during a critical period of embryonic development-a process known as temperature-dependent sex determination (TSD).1 The oviparous red-eared slider turtle, Trachemys scripta, has a warm-female/cool-male TSD system and is among the best-studied members of this group.2 When incubated at low temperatures, the somatic cells of the bipotential gonad differentiate into Sertoli cells, the support cells of the testis, whereas at high temperatures, they differentiate into granulosa cells, the support cells of the ovary.3 Here, we report the unexpected finding that temperature independently affects the number of primordial germ cells (GCs) in the embryonic gonad at a time before somatic cell differentiation has initiated. Specifically, embryos incubated at higher, female-inducing temperatures have more GCs than those incubated at the male-inducing temperature. Furthermore, elimination of GCs in embryos incubating at intermediate temperatures results in a strong shift toward male-biased sex ratios. This is the first evidence that temperature affects GC number and the first evidence that GC number influences sex determination in amniotes. This observation has two important implications. First, it supports a new model in which temperature can impact sex determination in incremental ways through multiple cell types. Second, the findings have important implications for a major unresolved question in the fields of ecology and evolutionary biology-the adaptive significance of TSD. We suggest that linking high GC number with female development improves female reproductive potential and provides an adaptive advantage for TSD.

Novel approach for efficient resonance tracking in photoacoustic gas sensor systems based on a light-induced wall signal.

Photoacoustic gas sensing is a method suited for the detection of radiation absorbing molecular species in the gas phase. Due to the backgroand-free detection, it has considerable benefits in the measurement of very low concentrations down to the parts-per-trillion range. Yet in resonant systems, the resonance frequency depends on several parameters like temperature or gas composition and therefore must be continuously determined. In the present work, we propose a new method of tracking the resonance frequency using a photoacoustic signal generated at the walls of the resonant cell. The method has been evaluated with two different photoacoustic setups intended for the detection of NO2. We further propose an algorithm for finding the resonance frequency and evaluated the performance thereof. With this method, it is possible to detect the resonance frequency of a cylindrical and a dumbbell-shaped cell in less than two seconds and with an accuracy < 0.06% and < 0.2%, respectively.

Alpha heating of indirect-drive layered implosions on the National Ignition Facility.

In order to understand how close current layered implosions in indirect-drive inertial confinement fusion are to ignition, it is necessary to measure the level of alpha heating present. To this end, pairs of experiments were performed that consisted of a low-yield tritium-hydrogen-deuterium (THD) layered implosion and a high-yield deuterium-tritium (DT) layered implosion to validate experimentally current simulation-based methods of determining yield amplification. The THD capsules were designed to reduce simultaneously DT neutron yield (alpha heating) and maintain hydrodynamic similarity with the higher yield DT capsules. The ratio of the yields measured in these experiments then allowed the alpha heating level of the DT layered implosions to be determined. The level of alpha heating inferred is consistent with fits to simulations expressed in terms of experimentally measurable quantities and enables us to infer the level of alpha heating in recent high-performing implosions.

Open retropubic radical prostatectomy: Still a well-established surgical technique for prostate cancer management.

INTRODUCTION: The surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. METHODS: We identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. RESULTS: We analyzed 1095 patients. The median follow-up was 93.4 months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89,1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (p<0.001, 95% CI). Limitations include retrospective and single center study design. CONCLUSIONS: ORP is a surgical procedure that provides excellent oncological- and early continence-rates.

Immunotherapy and cardiovascular diseases: novel avenues for immunotherapeutic approaches.

As current therapies for cardiovascular disease (CVD), predominantly based on lipid lowering, still face an unacceptable residual risk, novel treatment strategies are being explored. Besides lipids, inflammatory processes play a major role in the pathogenesis of atherosclerosis, the underlying cause of the majority of CVD. The first clinical trials targeting the interleukin-1ß-inflammasome axis have shown that targeting this pathway is successful in reducing cardiovascular events but did not decrease overall CVD mortality. Hence, novel and improved immunotherapeutics to treat CVD are being awaited.

Handgrip and finger flexion strength in children: A cross-sectional assessment of age-related normative data and application as a clinical functional marker in paediatric neuromuscular disorders.

BACKGROUND: The aim of this study was to evaluate handgrip and finger flexion strength (HGFS) as functional marker for disease progression in children with neuromuscular disorders (NMD) and present normative data in a paediatric healthy cohort. METHODS: We applied the fixed hand and finger dynamometer HFD 200 to assess HGFS under standardised, isometric and biomechanical conditions. In our cross-sectional study HGFS was analysed in n = 233 paediatric healthy controls (HC) and a cohort of n = 33 children with NMD between five and 18 years. In seven children with spinal muscular atrophy (SMA), HGFS were assessed prior to and under treatment with nusinersen over a two months period. HGFS of children with NMD was correlated with respiratory parameters, anthropometric data, hand function and motor scores. RESULTS: Patients with NMD exhibited a heterogenous HGFS pattern. HGFS was lower than in HC (p < 0.001). Children with SMA gained a significant increase in strength after two months of treatment (p < 0.05, r = 0.75-0.9). CONCLUSION: HGFS is a sensitive functional marker in paediatric NMD to identify minimal changes in distal muscle strength. HGFS may evolve as a sensitive outcome measure to monitor upcoming therapeutic interventions in particular for non-ambulant patients with NMD.

Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases.

Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-promoting from bystander immune cells. Here, we investigate the landscape of non-communicable inflammatory skin diseases (ncISD) by spatial transcriptomics resulting in a large repository of 62,000 spatially defined human cutaneous transcriptomes from 31 patients. Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.e. >125 times less compared to the mean expression of all other genes over lesional skin sections. Nevertheless, cytokine expression is limited to lesional skin and presented in a disease-specific pattern. Leveraging a density-based spatial clustering method, we identify specific responder gene signatures in direct proximity of cytokines, and confirm that detected cytokine transcripts initiate amplification cascades of up to thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and heterogeneous infiltrates of ncISD, only a low number of cytokine transcripts and their translated proteins promote disease by initiating an inflammatory amplification cascade in their local microenvironment.

Antimicrobial Activity of Ceftolozane-Tazobactam, Ceftazidime-Avibactam, and Cefiderocol against Multidrug-Resistant Pseudomonas aeruginosa Recovered at a German University Hospital.

Multidrug-resistant (MDR) Pseudomonas aeruginosa increasingly causes health care-associated infections. In this study, we determined the activity of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against 223 MDR P. aeruginosa clinical isolates recovered from 2013 to 2017 at the University Hospital Frankfurt by using MIC test strips. Furthermore, we evaluated the presence of genes encoding major ß-lactamases, such as VIM, IMP, NDM, GIM, SPM, and KPC; the extended spectrum ß-lactamase (ESBL)-carbapenemase GES; and the virulence-associated traits ExoS and ExoU, as in particular ExoU is thought to be associated with poor clinical outcome. For MDR P. aeruginosa isolates, the MIC50/MIC90 values of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol were 8/>256 mg/L, 16/>256 mg/L, and 0.25/1 mg/L, respectively. Cefiderocol showed the highest susceptibility rate (97.3%) followed by ceftazidime-avibactam (48.4%) and ceftolozane-tazobactam (46.6%). In 81 (36.3%) isolates, carbapenemase gene blaVIM was detected, and in 5 (2.2%) isolates, blaGES was detected (with a positive association of exoU and blaVIM). More than half of the isolates belong to the so-called international P. aeruginosa "high-risk" clones, with sequence type 235 (ST235) (24.7%) being the most prevalent. This study underlines that ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol are important options for the treatment of infections due to MDR P. aeruginosa, with cefiderocol currently being the most active available antipseudomonal ß-lactam agent. According to our clinical experience, the outcome of cefiderocol therapy (8 patients) was favorable especially in cases of MDR P. aeruginosa-associated complicated urinary tract infections. IMPORTANCE After testing ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against a collection of 233 multidrug-resistant (MDR) Pseudomonas aeruginosa, we showed that cefiderocol is the most active antipseudomonal ß-lactam agent (susceptibility rates were 46.6%, 48.4%, and 97.4%, respectively). The most prevalent one was sequence type 235 (ST235) (24.7%), followed by ST244, ST175, and ST233, with all belonging to the top 10 P. aeruginosa high-risk clones with worldwide distribution. Our data indicate that during surveillance studies special attention should be paid to the MDR and highly virulent VIM- and ExoU-producing variant of ST235. Furthermore, in the case of infections caused by carbapenemase-producing MDR P. aeruginosa, cefiderocol is the preferred treatment option, while outcomes of complicated urinary tract infections and hospital-acquired pneumonia with cefiderocol were favorable.

Design of an inertial fusion experiment exceeding the Lawson criterion for ignition.

We present the design of the first igniting fusion plasma in the laboratory by Lawson's criterion that produced 1.37 MJ of fusion energy, Hybrid-E experiment N210808 (August 8, 2021) [Phys. Rev. Lett. 129, 075001 (2022)10.1103/PhysRevLett.129.075001]. This design uses the indirect drive inertial confinement fusion approach to heat and compress a central "hot spot" of deuterium-tritium (DT) fuel using a surrounding dense DT fuel piston. Ignition occurs when the heating from absorption of α particles created in the fusion process overcomes the loss mechanisms in the system for a duration of time. This letter describes key design changes which enabled a ∼3-6× increase in an ignition figure of merit (generalized Lawson criterion) [Phys. Plasmas 28, 022704 (2021)1070-664X10.1063/5.0035583, Phys. Plasmas 25, 122704 (2018)1070-664X10.1063/1.5049595]) and an eightfold increase in fusion energy output compared to predecessor experiments. We present simulations of the hot-spot conditions for experiment N210808 that show fundamentally different behavior compared to predecessor experiments and simulated metrics that are consistent with N210808 reaching for the first time in the laboratory "ignition."