Laser-direct-drive fusion target design with a high-Z gradient-density pusher shell.

Laser-direct-drive fusion target designs with solid deuterium-tritium (DT) fuel, a high-Z gradient-density pusher shell (GDPS), and a Au-coated foam layer have been investigated through both 1D and 2D radiation-hydrodynamic simulations. Compared with conventional low-Z ablators and DT-push-on-DT targets, these GDPS targets possess certain advantages of being instability-resistant implosions that can be high adiabat (α≥8) and low hot-spot and pusher-shell convergence (CR_{hs}≈22 and CR_{PS}≈17), and have a low implosion velocity (v_{imp}<3×10^{7}cm/s). Using symmetric drive with laser energies of 1.9 to 2.5MJ, 1D lilac simulations of these GDPS implosions can result in neutron yields corresponding to ≳50-MJ energy, even with reduced laser absorption due to the cross-beam energy transfer (CBET) effect. Two-dimensional draco simulations show that these GDPS targets can still ignite and deliver neutron yields from 4 to ∼10MJ even if CBET is present, while traditional DT-push-on-DT targets normally fail due to the CBET-induced reduction of ablation pressure. If CBET is mitigated, these GDPS targets are expected to produce neutron yields of >20MJ at a driven laser energy of ∼2MJ. The key factors behind the robust ignition and moderate energy gain of such GDPS implosions are as follows: (1) The high initial density of the high-Z pusher shell can be placed at a very high adiabat while the DT fuel is maintained at a relatively low-entropy state; therefore, such implosions can still provide enough compression ρR>1g/cm^{2} for sufficient confinement; (2) the high-Z layer significantly reduces heat-conduction loss from the hot spot since thermal conductivity scales as ∼1/Z; and (3) possible radiation trapping may offer an additional advantage for reducing energy loss from such high-Z targets.

Hot-electron preheat and mitigation in polar-direct-drive experiments at the National Ignition Facility.

Target preheat by superthermal electrons from laser-plasma instabilities is a major obstacle to achieving thermonuclear ignition via direct-drive inertial confinement fusion at the National Ignition Facility (NIF). Polar-direct-drive surrogate plastic implosion experiments were performed on the NIF to quantify preheat levels at an ignition-relevant scale and develop mitigation strategies. The experiments were used to infer the hot-electron temperature, energy fraction, and divergence, and to directly measure the spatial hot-electron energy deposition profile inside the imploding shell. Silicon layers buried in the ablator are shown to mitigate the growth of laser-plasma instabilities and reduce preheat, providing a promising path forward for ignition designs at an on-target intensity of about 10^{15}W/cm^{2}.

Bound on hot-spot mix in high-velocity, high-adiabat direct-drive cryogenic implosions based on comparison of absolute x-ray and neutron yields.

In laser-driven implosions for laboratory fusion, the comparison of hot-spot x-ray yield to neutron production can serve to infer hot-spot mix. For high-performance direct-drive implosions, this ratio depends sensitively on the degree of equilibration between the ion and electron fluids. A scaling for x-ray yield as a function of neutron yield and characteristic ion and electron hot-spot temperatures is developed on the basis of simulations with varying degrees of equilibration. We apply this model to hot-spot x-ray measurements of direct-drive cryogenic implosions typical of the direct-drive designs with best ignition metrics. The comparison of the measured x-ray and neutron yields indicates that hot-spot mix, if present, is below a sensitivity estimated as ∼2% by-atom mix of ablator plastic into the hot spot.

Protocol paper: Multi-site, cluster-randomized clinical trial for optimizing functional outcomes of older cancer survivors after chemotherapy.

BACKGROUND: Cancer survivors over the age of 65 have unique needs due to the higher prevalence of functional and cognitive impairment, comorbidities, geriatric syndromes, and greater need for social support after chemotherapy. In this study, we will evaluate whether a Geriatric Evaluation and Management-Survivorship (GEMS) intervention improves functional outcomes important to older cancer survivors following chemotherapy. METHODS: A cluster-randomized trial will be conducted in approximately 30 community oncology practices affiliated with the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participating sites will be randomized to the GEMS intervention, which includes Advanced Practice Practitioner (APP)-directed geriatric evaluation and management (GEM), and Survivorship Health Education (SHE) that is combined with Exercise for Cancer Patients (EXCAP©®), or usual care. Cancer survivors will be recruited from community oncology practices (of participating oncology physicians and APPs) after the enrolled clinicians have consented and completed a baseline survey. We will enroll 780 cancer survivors aged 65 years and older who have completed curative-intent chemotherapy for a solid tumor malignancy within four weeks of study enrollment. Cancer survivors will be asked to choose one caregiver to also participate for a total up to 780 caregivers. The primary aim is to compare the effectiveness of GEMS for improving patient-reported physical function at six months. The secondary aim is to compare effectiveness of GEMS for improving patient-reported cognitive function at six months. Tertiary aims include comparing the effectiveness of GEMS for improving: 1) Patient-reported physical function at twelve months; 2) objectively assessed physical function at six and twelve months; and 3) patient-reported cognitive function at twelve months and objectively assessed cognitive function at six and twelve months. Exploratory health care aims include: 1) Survivor satisfaction with care, 2) APP communication with primary care physicians (PCPs), 3) completion of referral appointments, and 4) hospitalizations at six and twelve months. Exploratory caregiver aims include: 1) Caregiver distress; 2) caregiver quality of life; 3) caregiver burden; and 4) satisfaction with patient care at six and twelve months. DISCUSSION: If successful, GEMS would be an option for a standardized APP-led survivorship care intervention. TRIAL REGISTRATION: ClinicalTrials.govNCT05006482, registered on August 9, 2021.

Experimentally Inferred Fusion Yield Dependencies of OMEGA Inertial Confinement Fusion Implosions.

Statistical modeling of experimental and simulation databases has enabled the development of an accurate predictive capability for deuterium-tritium layered cryogenic implosions at the OMEGA laser [V. Gopalaswamy et al.,Nature 565, 581 (2019)10.1038/s41586-019-0877-0]. In this letter, a physics-based statistical mapping framework is described and used to uncover the dependencies of the fusion yield. This model is used to identify and quantify the degradation mechanisms of the fusion yield in direct-drive implosions on OMEGA. The yield is found to be reduced by the ratio of laser beam to target radius, the asymmetry in inferred ion temperatures from the ℓ=1 mode, the time span over which tritium fuel has decayed, and parameters related to the implosion hydrodynamic stability. When adjusted for tritium decay and ℓ=1 mode, the highest yield in OMEGA cryogenic implosions is predicted to exceed 2×10^{14} fusion reactions.

Direct Measurements of DT Fuel Preheat from Hot Electrons in Direct-Drive Inertial Confinement Fusion.

Hot electrons generated by laser-plasma instabilities degrade the performance of laser-fusion implosions by preheating the DT fuel and reducing core compression. The hot-electron energy deposition in the DT fuel has been directly measured for the first time by comparing the hard x-ray signals between DT-layered and mass-equivalent ablator-only implosions. The electron energy deposition profile in the fuel is inferred through dedicated experiments using Cu-doped payloads of varying thickness. The measured preheat energy accurately explains the areal-density degradation observed in many OMEGA implosions. This technique can be used to assess the viability of the direct-drive approach to laser fusion with respect to the scaling of hot-electron preheat with laser energy.

Investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement.

PURPOSE: The mechanisms of brain metastasis are incompletely understood. Circulating tumor cells travel to the right heart and through the pulmonary circulation, where they may become lung metastases, and can circulate further to the left heart and brain. In patients who develop brain metastases without lung involvement, we hypothesized that cancer cells may travel directly from the right atrium to left atrium via a patent foramen ovale (PFO), akin to paradoxical embolism. If the prevalence of PFO is greater in these individuals compared to the general population (20-30%), PFO may play a role in brain metastasis, and prophylactic closure may provide benefit. Accordingly, we investigated the prevalence of PFO in patients with brain metastases without prior lung involvement. METHODS: We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding or concurrent lung involvement. Nine eligible participants underwent a transcranial Doppler study with intravenous agitated saline to assess for PFO. RESULTS: Among nine participants, primary cancers were breast (n = 6), upper gastrointestinal (n = 2), and thyroid (n = 1). A positive bubble study was identified in 2/9 (22.2%) participants: one female with breast cancer and one male with duodenal adenocarcinoma. No participants developed lung metastases on subsequent chest imaging. CONCLUSION: In this prospective pilot study, we found a similar prevalence of PFO in patients who developed brain metastases without preceding lung involvement compared to estimates for the general population. Through a larger study is needed, the development of brain metastases in these individuals may primarily reflect tumor-specific biological factors diecting metastasis organotropism.

Inferred UV fluence focal-spot profiles from soft x-ray pinhole-camera measurements on OMEGA.

A method was developed with laser-irradiated Au planar foils to characterize the focal spot of UV laser beams on a target at full energy from soft x-ray emission. A pinhole camera with a back-thinned charge-coupled device detector and filtration with thin Be and Al foil filters provides images of the x-ray emission at photon energies <2 keV. This method requires a careful measurement of the relationship between the applied UV fluence and the x-ray signal, which can be described by a power-law dependence. The measured exponent γ ∼ 2 provides a dynamic range of ∼25 for the inferred UV fluence. UV fluence profiles of selected beams were measured for 100-ps and 1-ns laser pulses and were compared to directly measured profiles from an UV equivalent-target-plane diagnostic. The inferred spot size and super-Gaussian order from the x-ray technique agree within several percent with the values measured with the direct UV measurements.

A randomised phase II trial of three dosing regimens of radium-223 in patients with bone metastatic castration-resistant prostate cancer.

BACKGROUND: Radium-223 prolongs overall survival and delays symptomatic skeletal events (SSEs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. The approved radium-223 regimen is 55 kBq/kg every 4 weeks (q4w) for six cycles (standard dose). We investigated different radium-223 regimens in patients with mCRPC. PATIENTS AND METHODS: Patients were randomised 1 : 1 : 1 to radium-223 standard-dose, high-dose (88 kBq/kg q4w for six cycles) or extended-schedule arms (55 kBq/kg q4w for 12 cycles). The primary end point, SSE-free survival (SSE-FS), was compared in patients treated with a high- versus standard-dose regimen, or with a standard dose in an extended (>6 to 12 cycles) versus standard schedule (six cycles). RESULTS: A total of 391 patients were randomised; baseline characteristics were balanced between arms. On-treatment SSEs developed in 37/130 (28%), 42/130 (32%) and 48/131 (37%) patients in the standard-dose, high-dose and extended-schedule arms, respectively. There was no statistically significant difference in SSE-FS in the high- versus standard-dose arms [median 12.9 months versus 12.3 months; hazard ratio (HR) 1.06, 80% confidence interval (CI) 0.88-1.27, P = 0.70], and in the extended- versus standard-schedule arms (median 10.8 months versus 13.2 months; HR 1.26, 80% CI 0.94-1.69, P = 0.31). Overall survival in the three treatment arms was similar. As many as 370 (95%) patients received treatment (median of six cycles) in each arm. Grade ≥3 treatment-emergent adverse events (TEAEs) affected 34% of patients in the standard-dose, 48% in the high-dose and 53% in the extended-schedule arm, causing permanent discontinuation in 9%, 16% and 17% of patients, respectively. CONCLUSION: Radium-223 high-dose or extended-schedule regimens resulted in no change in SSE-FS or other efficacy end points and were associated with more grade ≥3 TEAEs. The extended-schedule regimen (beyond six doses) could not be implemented in a large proportion of patients due to disease progression. Therefore, the standard-dose schedule remains one of the standard therapies for patients with symptomatic mCRPC. TRIAL REGISTRATION: ClinicalTrials.govNCT02023697.

QuantiFERON®-TB Gold In-Tube reliability for immigrants with parasitic infections in Boston, USA.

Accurate testing and treatment for latent tuberculous infection is necessary for tuberculosis elimination. Certain parasite infections are associated with increased tuberculin skin test positivity; species-specific effects on QuantiFERON®-TB Gold In-Tube (QGIT) have not been described. To determine whether infection with helminths or protozoa affects QGIT results. We retrospectively analyzed QGIT and parasite testing results for immigrants screened in Boston, MA, USA, from 2012 to 2017. We also prospectively measured cytokines in QGIT supernatants for a subset (n = 68) with 1) helminths, 2) Blastocystis hominis, 3) other protozoa, and 4) no parasites. Of 527 immigrants screened, 141 (26.8%) were QGIT-positive and 229 (43.4%) had parasites detected: 27/527 (5.1%) had helminths and 202/527 (38.3%) protozoa. Cytokine analysis revealed increased interleukin-10 concentrations with protozoa (P = 0.04), and non-significantly higher T-helper 2 concentrations with helminths compared with no parasites. No significant differences emerged in QGIT positivity or interferon-gamma concentrations in any group. Study results support the use of QGIT in parasite-endemic settings. .

Tripled yield in direct-drive laser fusion through statistical modelling.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

Direct-drive double-shell implosion: A platform for burning-plasma physics studies.

Double-shell ignition designs have been studied with the indirect-drive inertial confinement fusion (ICF) scheme in both simulations and experiments in which the inner-shell kinetic energy was limited to ∼10-15 kJ, even driven by megajoule-class lasers such as the National Ignition Facility. Since direct-drive ICF can couple more energy to the imploding shells, we have performed a detailed study on direct-drive double-shell (D^{3}S) implosions with state-of-the-art physics models implemented in radiation-hydrodynamic codes (lilac and draco), including nonlocal thermal transport, cross-beam energy transfer (CBET), and first-principles-based material properties. To mitigate classical unstable interfaces, we have proposed the use of a tungsten-beryllium-mixed inner shell with gradient-density layers that can be made by magnetron sputtering. In our D^{3}S designs, a 70-µm-thick beryllium outer shell is driven symmetrically by a high-adiabat (α≥10), 1.9-MJ laser pulse to a peak velocity of ∼240 km/s. Upon spherical impact, the outer shell transfers ∼30-40 kJ of kinetic energy to the inner shell filled with deuterium-tritium gas or liquid, giving neutron-yield energies of ∼6 MJ in one-dimensional simulations. Two-dimensional high-mode draco simulations indicated that such high-adiabat D^{3}S implosions are not susceptible to laser imprint, but the long-wavelength perturbations from the laser port configuration along with CBET can be detrimental to the target performance. Nevertheless, neutron yields of ∼0.3-1.0-MJ energies can still be obtained from our high-mode draco simulations. The robust α-particle bootstrap is readily reached, which could provide a viable platform for burning-plasma physics studies. Once CBET mitigation and/or more laser energy becomes available, we anticipate that break-even or moderate energy gain might be feasible with the proposed D^{3}S scheme.

Family caregiver descriptions of stopping chemotherapy and end-of-life transitions.

PURPOSE: The purpose of this study was to describe family caregivers' perspectives of the final month of life of patients with advanced cancer, particularly whether and how chemotherapy was discontinued and the effect of clinical decision-making on family caregivers' perceptions of the patient's experience of care at the end of life (EOL). METHODS: Qualitative descriptive design using semi-structured interviews collected from 92 family caregivers of patients with end-stage cancer enrolled in a randomized clinical trial. We used a phased approach to data analysis including open coding, focused coding, and within and across analyses. RESULTS: We identified three patterns of transitions characterizing the shift away from active cancer treatment: (1) "We Pretty Much Knew," characterized by explicit discussions about EOL care, seemingly shared understanding about prognosis and seamless transitions from disease-oriented treatment to comfort-oriented care, (2) "Beating the Odds," characterized by explicit discussions about disease-directed treatment and EOL care options, but no shared understanding about prognosis and often chaotic transitions to EOL care, and (3) "Left to Die," characterized by no recall of EOL discussions with transitions to EOL occurring in crisis. CONCLUSIONS: As communication and palliative care interventions continue to develop to improve care for patients with advanced cancer, it is imperative that we take into account the different patterns of transition and their unique patient and caregiver needs near the end of life. Our findings reveal considerable, and potentially unwarranted, variation in transitions from active treatment to death.

Origins and Scaling of Hot-Electron Preheat in Ignition-Scale Direct-Drive Inertial Confinement Fusion Experiments.

Planar laser-plasma interaction (LPI) experiments at the National Ignition Facility (NIF) have allowed access for the first time to regimes of electron density scale length (∼500 to 700 µm), electron temperature (∼3 to 5 keV), and laser intensity (6 to 16×10^{14} W/cm^{2}) that are relevant to direct-drive inertial confinement fusion ignition. Unlike in shorter-scale-length plasmas on OMEGA, scattered-light data on the NIF show that the near-quarter-critical LPI physics is dominated by stimulated Raman scattering (SRS) rather than by two-plasmon decay (TPD). This difference in regime is explained based on absolute SRS and TPD threshold considerations. SRS sidescatter tangential to density contours and other SRS mechanisms are observed. The fraction of laser energy converted to hot electrons is ∼0.7% to 2.9%, consistent with observed levels of SRS. The intensity threshold for hot-electron production is assessed, and the use of a Si ablator slightly increases this threshold from ∼4×10^{14} to ∼6×10^{14} W/cm^{2}. These results have significant implications for mitigation of LPI hot-electron preheat in direct-drive ignition designs.

Hypotension during induction of anaesthesia is neither a reliable nor a useful quality measure for comparison of anaesthetists' performance.

BACKGROUND: Identification of statistically reliable outcomes for comparison among anaesthetists is challenging. Time-weighted intraoperative mean arterial pressure <65 mm Hg (AUC 65 ) is associated with increased odds for myocardial damage. We explored retrospectively whether such hypotension before incision was statistically reliable for peer comparison. METHODS: We retrieved electronic data between 2006 and 2015 at a tertiary care, academic hospital in the USA for patients at risk for myocardial damage (inpatient after surgery, ASA physical status ≥III, ≥50 yr of age, and case duration ≥60 min). We determined the percentage of anaesthetists comparable based on caseload and case-mix. The AUC 65 was compared amongst anaesthetists supervising ≥100 cases involving at-risk patients during the last 12 months. RESULTS: Only 14.1% [95% confidence interval (CI) 13.6-14.5%] of cases involved patients who were 'at risk' during the 10 yr study period. A yearly average of 49 ( sd 6) anaesthetists supervised ≥100 cases of any type, of whom only 52% (95% CI 47.1-56.0%) supervised ≥100 cases involving at-risk patients. Thus, nearly half the anaesthetists would have been excluded from peer comparison. During the last 12 months, there were two outliers among 34 evaluable anaesthetists ( P <0.05, controlling for false discovery). However, their contribution to total hypotension amongst cases for all patients was small, because hypotension was widely distributed (e.g. 80% of hypotension attributable to 61.8% of anaesthetists, 95% CI 59.8-63.7%). There was no relationship between the AUC 65 and propofol induction dose. CONCLUSIONS: The AUC 65 of time-weighted pre-incision hypotension is not a suitable metric for comparing anaesthetists. There were few at-risk patients, half the anaesthetists were not evaluable because of their case-mix and caseload, and hypotension was widely distributed.

Piperacillin-induced Thrombocytopenia in a Dual Heart and Kidney Transplant Patient: A Case Report.

BACKGROUND: The present study reports a case of piperacillin-induced thrombocytopenia in a dual heart and kidney transplant patient on January 28, 2016 (taking mycophenolate mofetil and tacrolimus). Before the transplant, the patient was treated with Zosyn twice, with no reports of thrombocytopenia or allergy. However, he was diagnosed with heparin-induced thrombocytopenia and vancomycin allergy during each of those hospitalizations, respectively. Eight months after the transplant, the patient presented with infectious symptoms and was started on Zosyn. RESULTS: One day after starting Zosyn, the patient experienced a drop in platelet count from 6,000/µL from 216,000/µL. Platelets decreased as low as 1 on day 3 of hospitalization. Administration of mycophenolate mofetil, tacrolimus, Bactrim, vancomycin, Zosyn, ranitidine, and Rivaroxaban were discontinued. Platelet counts stabilized the day after Zosyn was discontinued and slowly increased after the patient was treated with 2 doses of intravenous immunoglobulin, 4 units of platelets, and a tapered dose of prednisone. CONCLUSIONS: The patient was initially diagnosed with vancomycin-induced thrombocytopenia but then tested positive for antibodies to piperacillin and negative for antibodies to vancomycin and tazobactam. The patient was discharged with a diagnosis of piperacillin-induced thrombocytopenia. This case report presents a case of piperacillin-induced thrombocytopenia, previously misdiagnosed as vancomycin-induced thrombocytopenia and heparin-induced thrombocytopenia.

Hospitals with briefer than average lengths of stays for common surgical procedures do not have greater odds of either re-admission or use of short-term care facilities.

We considered whether senior hospital managers and department chairs need to be concerned that small reductions in average hospital length of stay (LOS) may be associated with greater rates of re-admission, use of home health care, and/or transfers to short-term care facilities. The 2013 United States Nationwide Readmissions Database was used to study surgical Diagnosis Related Groups (DRG) with 1) national median LOS ≥3 days and 2) ≥10 hospitals in the database that each had ≥100 discharges for the DRG. Dependent variables were considered individually: 1) re-admission within 30 days of discharge, 2) discharge disposition to home health care, and/or 3) discharge disposition of transfer to short-term care facility (i.e., inpatient rehabilitation hospital or skilled nursing facility). While controlling for DRG, each one-day decrease in hospital median LOS was associated with an odds of re-admission nationwide of 0.95 (95% confidence interval [CI] 0.92-0.99; P=0.012), odds of disposition upon discharge being home care of 0.95 (95% CI 0.83-1.10; P=0.64), and odds of transfer to short-term care facility of 0.68 (95% CI 0.54-0.85; P=0.0008). Results were insensitive to the addition of patient-specific data. In the USA, patients at hospitals with briefer median LOS across multiple common surgical procedures did not have a greater risk for either hospital re-admission within 30 days of discharge or transfer to an inpatient rehabilitation hospital or a skilled nursing facility. The generalisable implication is that, across many surgical procedures, DRG-based financial incentives to shorten hospital stays seem not to influence post-acute care decisions.

X-ray self-emission imaging used to diagnose 3-D nonuniformities in direct-drive ICF implosions.

As hydrodynamics codes develop to increase understanding of three-dimensional (3-D) effects in inertial confinement fusion implosions, diagnostics must adapt to evaluate their predictive accuracy. A 3-D radiation postprocessor was developed to investigate the use of soft x-ray self-emission images of an imploding target to measure the size of nonuniformities on the target surface. Synthetic self-emission images calculated from 3-D simulations showed a narrow ring of emission outside the ablation surface of the target. Nonuniformities growing in directions perpendicular to the diagnostic axis were measured through angular variations in the radius of the steepest intensity gradient on the inside of the ring and through changes in the peak x-ray intensity in the ring as a function of angle. The technique was applied to an implosion to measure large 3-D nonuniformities resulting from two dropped laser beam quads at the National Ignition Facility.

Publisher's Note: Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA [Phys. Rev. Lett. 117, 025001 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.025001.