Radiation Oncology Training in the Philippines: Bridging Gaps for Improved Cancer Care in Low- and Middle-Income Countries.

PURPOSE: Radiation oncology in the Philippines, a large lower- and middle-income country in Southeast Asia, is facing a critical shortage in manpower, with only 113 radiation oncologists (ROs) over 55 radiotherapy (RT) centers serving 100 million population. Paramount to workforce expansion is ensuring that training programs can produce adequately trained specialists. In this study, we describe the current state of radiation oncology training programs in the Philippines. METHODS: This is a cross-sectional observational analysis of the nine radiation oncology residency training programs in the Philippines. Data were collected from a survey of the program directors, the Philippine Radiation Oncology Society database, and a PubMed literature search. RESULTS: Eight of the nine programs are in the National Capital Region. Since program standardization in 2005, there have been 82 four-year residency graduates, with up to 18 new graduates annually. Faculty-to-trainee ratio ranges from 0.5 to 2.67. In terms of technology, all programs have intensity-modulated RT and high-dose-rate brachytherapy, but only six are equipped with computed tomography-based image guidance and stereotactic capabilities. Clinical education schemes vary per institution regarding curriculum implementation, resident activities, and methods of evaluation. Required resident case logs are not met for lung, GI, genitourinary, bone and soft tissue, and hematologic malignancies. In total, there are only 22 resident-led publications from 10 unique individuals in two training programs. CONCLUSION: Program expansions are warranted to meet the projected demand for ROs in the Philippines, but training programs must first improve key aspects of staffing, technology, clinical education, and research. Addressing training challenges related to resource limitations necessitates local and international collaborations with higher-capacity centers to bridge gaps for continued quality improvement with the aim of ultimately delivering better overall cancer care.

Travel-Time Disparities in Access to Proton Beam Therapy for Cancer Treatment.

Importance: Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials. Objective: To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups. Design, Setting, and Participants: This population-based cross-sectional study analyzed travel times to proton facilities in the US. Census tract variables in the contiguous US were measured between January 1, 2017, and December 31, 2021. Statistical analysis was performed from September to November 2023. Exposures: Drive time in minutes to nearest proton facility. Population totals and prevalence of specific factors measured from the American Community Survey: age; race and ethnicity; insurance, disability, and income status; vehicle availability; broadband access; and urbanicity. Main Outcomes and Measures: Poor access to proton facilities was defined as having a drive-time commute of at least 4 hours to the nearest location. Median drive time and percentage of population with poor access were calculated for the entire population and by population subgroups. Univariable and multivariable odds of poor access were also calculated for certain population subgroups. Results: Geographic access was considered for 327 536 032 residents of the contiguous US (60 594 624 [18.5%] Hispanic, 17 974 186 [5.5%] non-Hispanic Asian, 40 146 994 [12.3%] non-Hispanic Black, and 195 265 639 [59.6%] non-Hispanic White; 282 031 819 [86.1%] resided in urban counties). The median (IQR) drive time to the nearest proton facility was 96.1 (39.6-195.3) minutes; 119.8 million US residents (36.6%) lived within a 1-hour drive of the nearest proton facility, and 53.6 million (16.4%) required a commute of at least 4 hours. Persons identifying as non-Hispanic White had the longest median (IQR) commute time at 109.8 (48.0-197.6) minutes. Multivariable analysis identified rurality (odds ratio [OR], 2.45 [95% CI, 2.27-2.64]), age 65 years or older (OR, 1.09 [95% CI, 1.06-1.11]), and living below the federal poverty line (OR, 1.22 [1.20-1.25]) as factors associated with commute times of at least 4 hours. Conclusions and Relevance: This cross-sectional study of drive-time access to proton beam therapy found that disparities in access existed among certain populations in the US. These results suggest that such disparities present a barrier to an emerging technology in cancer treatment and inhibit equitable access to ongoing clinical trials.

Facile Synthesis of Band Gap-Tunable Kappa-Carrageenan-Mediated C,S-Doped TiO2 Nanoparticles for Enhanced Dye Degradation.

Semiconducting nanoparticles (SNPs) have garnered significant attention for their role in photocatalysis technology, offering a cost-effective and highly efficient method for breaking down organic dyes. Of particular significance within SNP-based photocatalysis are tunable band gap TiO2 nanoparticles (NPs), which demonstrate remarkable enhancement in photocatalytic efficiency. In the present work, we introduce an approach for the synthesis of TiO2 NPs using kappa-carrageenan (κ-carrageenan), not just as a reducing and stabilizing agent but as a dopant for the resulting TiO2 NPs. During the synthesis of TiO2 NPs in the presence of sulfate-rich carrageenan, the process predominantly leaves residual sulfur and carbon. The presence of residual carbon, in conjunction with sulfur doping, as indicated by fast FTIR spectra, XPS, and EDX, leads to a significant reduction in the band gap of the resulting composite to 2.71 eV. The reduction of composite band gap yields remarkable degradation of methylene blue (99.97%) and methyl orange (97.84%). This work presents an eco-friendly and highly effective solution for the swift removal of environmentally harmful organic dyes.

Late-onset lymphopenia during radiation is associated with an increased risk of tumor recurrence in newly diagnosed pediatric medulloblastoma.

BACKGROUND: Recent data found a correlation between lymphopenia occurring early during craniospinal radiation therapy (RT) and risk of disease recurrence in newly diagnosed childhood medulloblastoma. However, the population included patients who received chemotherapy prior to or during RT. Here, we investigate the effect of lymphopenia during RT in patients with newly diagnosed pediatric medulloblastoma who were chemotherapy-naïve. PROCEDURE: We analyzed 79 patients with newly diagnosed medulloblastoma (ages 2-21 years) treated between 1997 and 2013 with craniospinal RT. Log-rank tests were used to determine survival differences, and Cox proportional hazards regression was used to assess associations between patient characteristics and lymphopenia with disease recurrence risk. RESULTS: Eighty-three percent of patients (62/75) had grade ≥3 lymphopenia by RT Week 3, with 95% developing grade ≥3 lymphopenia at some point during therapy. There was no difference in incidence of lymphopenia between those who received proton beam RT (93%) versus photon (97%). Twenty-four of 79 (30%) patients developed disease recurrence at an average 27.0 months after diagnosis. There was higher risk of disease recurrence in patients with grade ≥3 lymphopenia during RT Week 4 (log-rank p = .016; Cox p = .03) and Week 5 (log-rank p = .024; Cox p = .032); after adjusting for clinical risk group, only grade ≥3 lymphopenia at Week 4 remained prognostic (Cox p = .04). No correlation was found between risk of tumor recurrence and early lymphopenia (RT Weeks 0-3) or absolute lymphocyte count (ALC) below the median at any time during RT. CONCLUSIONS: Lymphopenia during RT Weeks 4 and 5 correlates with increased risk of tumor recurrence in pediatric patients with newly diagnosed medulloblastoma.

Comprehensive radiotherapy for pediatric Ewing Sarcoma: Outcomes of a prospective proton study.

BACKGROUND AND PURPOSE: Patients with Ewing Sarcoma (EWS) are treated with multimodality therapy which includes radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) to the primary site for localized and metastatic EWS. MATERIALS AND METHODS: Forty-two children with EWS (33 localized, 9 metastatic) treated between 2007 and 2020 were enrolled on 2 prospective registry protocols for pediatric patients undergoing PRT. PRT was delivered by passive scatter (74 %), pencil-beam scanning (12 %) or mixed technique (14 %). Treated sites included the spine (45 %), pelvis/sacrum (26 %), skull/cranium (14 %), extraosseous (10 %), and chest wall (5 %). Median radiation dose was 54 Gy-RBE (range 39.6-55.8 Gy-RBE). Patients with metastatic disease received consolidative RT to metastatic sites (4 at the time of PRT to the primary site, 5 after completion of chemotherapy). Median follow-up time was 47 months after PRT. RESULTS: The 4-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83 %, 71 %, and 86 %, respectively. All local failures (n = 6) were in-field failures. Tumor size ≥ 8 cm predicted for inferior 4-year LC (69 % vs 95 %, p = 0.04). 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72 % vs 67 %, p = 0.70; 89 % vs 78 %, p = 0.38, respectively). CONCLUSION: In conclusion, LC for pediatric patients with EWS treated with PRT was comparable to that of historical patients who received photon-RT. Tumor size ≥ 8 cm predicted increased risk of local failure. Patients with metastatic disease, including non-pulmonary only metastases, received radiation therapy to all metastatic sites and had favorable survival outcomes.

Dopamine-Functionalized Gold Nanoparticles for Colorimetric Detection of Histamine.

Histamine, a primary biogenic amine (BA) generated through the decarboxylation of amino acids, concentration increases in protein-rich foods during deterioration. Thus, its detection plays a crucial role in ensuring food safety and quality. This study introduces an innovative approach involving the direct integration of dopamine onto gold nanoparticles (DCt-AuNP), aiming at rapid histamine colorimetric detection. Transmission electron microscopy revealed the aggregation of uniformly distributed spherical DCt-AuNPs with 12.02 ± 2.53 nm sizes upon the addition of histamine to DCt-AuNP solution. The Fourier-transform infrared (FTIR) spectra demonstrated the disappearance of the dicarboxy acetone peak at 1710 cm-1 along with the formation of well-defined peaks at 1585 cm-1, and 1396 cm-1 associated with the N-H bending modes and the aromatic C=C bond stretching vibration in histamine molecule, respectively, confirming the ligand exchange and interactions of histamine on the surface of DCt-AuNPs. The UV-vis spectra of the DCt-AuNP solution exhibited a red shift and a reduction in surface plasmon resonance (SPR) peak intensity at 518 nm along with the emergence of the 650 nm peak, signifying aggregation DCt-AuNPs with increasing histamine concentration. Notably, color transitions from wine-red to deep blue were observed in the DCt-AuNP solution in response to histamine, providing a reliable colorimetric signal. Dynamic Light Scattering (DLS) characterization showed a significant increase in the hydrodynamic diameter, from ∼15 to ∼1690 nm, confirming the interparticle cross-linking of DCt-AuNPs in the presence of histamine. This newly developed DCt-AuNP sensor provides colorimetric results in less than a minute that exhibits a remarkable naked-eye histamine detection threshold of 1.57 µM and a calculated detection limit of 0.426 µM, making it a promising tool for the rapid and sensitive detection of histamine.

Effects of a culturally informed model of care for Aboriginal and Torres Strait Islander patients with acute coronary syndrome in a tertiary hospital in Australia: a pre-post, quasi-experimental, interventional study.

BACKGROUND: Aboriginal and Torres Strait Islander (Indigenous) peoples with cardiac disease in Australia have worse outcomes than non-Indigenous people with cardiac disease. We hypothesised that the implementation of a culturally informed model of care for Indigenous patients hospitalised with acute coronary syndrome (ACS) would improve their clinical outcomes. METHODS: For this pre-post, quasi-experimental, interventional study, cohorts of Indigenous patients before and after the implementation of a model of care were compared. The novel, culturally informed, multidisciplinary-team model of care was a local programme of care developed to reduce morbidity and mortality from cardiac conditions among Indigenous Australians. All index admissions in the 24-month pre-implementation period (Jan 1 2013, to Dec 31, 2014) were analysed, as were all index admissions in the 12-month post-implementation period (Oct 1, 2015, to Sept 30, 2016). Comparisons were also made with non-Indigenous cohorts in the same timeframes. Admissions were excluded if the patient did not survive to hospital discharge. The study was conducted at Princess Alexandra Hospital, a tertiary hospital in metropolitan Brisbane (QLD, Australia). Data on presentation, comorbidities, investigations, treatment, and for outcomes were manually collected from a consolidated clinical information application. Mortality data were obtained from the Queensland Registry of Births, Deaths, and Marriages. The primary outcome was a composite of death, acute myocardial infarction, unplanned revascularisation, and cardiac readmission at 90 days after index admission, assessed in all patients. FINDINGS: The Indigenous cohorts included 199 patients admitted with ACS before the model of care was implemented (85 [43%] were female and 114 [57%] were male) and 119 admitted post-implementation (62 [52%] were female and 57 [48%] were male). The non-Indigenous cohorts included 440 patients with ACS before the model of care was implemented (140 [32%] were female and 300 [68%] were male) and 467 admitted post-implementation (143 [31%] were female and 324 [69%] were male). Compared with the pre-implementation group, Indigenous patients admitted post-implementation had a significant reduction in the primary outcome (67 [34%] of 199 vs 24 [20%] of 119; hazard ratio 0·60, 95% CI 0·40-0·90; p=0·012), which was driven by a reduction in unplanned cardiac readmissions (64 [32%] of 199 vs 21 [18%] of 119; 0·55, 0·35-0·85; p=0·0060). There was no significant change in non-Indigenous patients between the pre-implementation and post-implementation timeframes in the composite endpoint at 90 days (81 [18%] of 440 vs 93 [20%] of 467; 1·08, 0·83-1·41; p=0·54). Pre-implementation, there was significantly more incidence of the primary outcome in Indigenous patients than non-Indigenous patients (p<0·0001), with no significant difference in the post-implementation period (p=0·92). INTERPRETATION: Clinical outcomes for Indigenous patients admitted to a tertiary hospital in Australia improved after implementation of a culturally informed model of care, with a reduction in the disparity in incidence of primary endpoints that existed between Indigenous and non-Indigenous patients before implementation. FUNDING: Queensland Department of Health Aboriginal and Torres Strait Islander Health Division (now First Nations Health Office).

Development of High-Performance Coconut Oil-Based Rigid Polyurethane-Urea Foam: A Novel Sequential Amidation and Prepolymerization Process.

The utilization of coconut diethanolamide (p-CDEA) as a substitute polyol for petroleum-based polyol in fully biobased rigid polyurethane-urea foam (RPUAF) faces challenges due to its short chain and limited cross-linking capability. This leads to compromised cell wall resistance during foam expansion, resulting in significant ruptured cells and adverse effects on mechanical and thermal properties. To address this, a novel sequential amidation-prepolymerization route was employed on coconut oil, yielding a hydroxyl-terminated poly(urethane-urea) prepolymer polyol (COPUAP). Compared to p-CDEA, COPUAP exhibited a decreased hydroxyl value (496.3-473.2 mg KOH/g), an increase in amine value (13.464-24.561 mg KOH/g), and an increase in viscosity (472.4-755.8 mPa·s), indicating enhanced functionality of 34.3 mgKOH/g and chain lengthening. Further, COPUAP was utilized as the sole B-side polyol in the production of RPUAF (PU-COPUAP). The improved functionality of COPUAP and its improved cross-linking capability during foaming have significantly improved cell morphology, resulting in a remarkable 4.7-fold increase in compressive strength (132-628 kPa), a 3.5-fold increase in flexural strength (232-828 kPa), and improved insulation properties with a notable decrease in thermal conductivity (48.02-34.52 mW/m·K) compared to PU-CDEA in the literature. Additionally, PU-COPUAP exhibited a 16.5% increase in the water contact angle (114.93° to 133.87°), attributing to the formation of hydrophobic biuret segments and a tightly packed, highly cross-linked structure inhibiting water penetration. This innovative approach sets a new benchmark for fully biobased rigid foam production, delivering high load-bearing capacity, exceptional insulation, and significantly improved hydrophobicity.

Flexible Polyurethane Foams Modified with Novel Coconut Monoglycerides-Based Polyester Polyols.

Coconut oil, a low-molecular-weight vegetable oil, is virtually unutilized as a polyol material for flexible polyurethane foam (FPUF) production due to the high-molecular-weight polyol requirement of FPUFs. The saturated chemistry of coconut oil also limits its compatibility with widely used polyol-forming processes, which mostly rely on the unsaturation of vegetable oil for functionalization. Existing studies have only exploited this resource in producing low-molecular-weight polyols for rigid foam synthesis. In this present work, high-molecular-weight polyester polyols were synthesized from coconut monoglycerides (CMG), a coproduct of fatty acid production from coconut oil, via polycondensation at different mass ratios of CMG with 1:5 glycerol:phthalic anhydride. Characterization of the CMG-based polyol (CMGPOL) products showed number-average molecular weights between 1997 and 4275 g/mol, OH numbers between 77 and 142 mg KOH/g, average functionality between 4.8 and 5.8, acid numbers between 4.49 and 23.56 mg KOH/g, and viscosities between 1.27 and 89.57 Pa·s. The polyols were used to synthesize the CMGPOL-modified PU foams (CPFs) at 20 wt % loading. The modification of the foam formulation increased the monodentate and bidentate urea groups, shown using Fourier transform infrared (FTIR) spectroscopy, that promoted microphase separation in the foam matrix, confirmed using atomic force microscopy (AFM) and differential scanning calorimetry (DSC). The implications of the structural change to foam morphology and open cell content were investigated using a scanning electron microscope (SEM) and gas pycnometer. The density of the CPFs decreased, while a significant improvement in their tensile and compressive properties was observed. Also, the CPFs exhibited different resiliency with a correlation to microphase separation. These findings offer a new sustainable polyol raw material that can be used to modify petroleum-based foam and produce flexible foams with varying properties that can be tailored to meet specific requirements.

Treatment and outcomes of clear cell sarcoma of the kidney: A report from the Children's Oncology Group studies AREN0321 and AREN03B2.

BACKGROUND: On the fifth National Wilms Tumor Study, treatment for clear cell sarcoma of the kidney (CCSK) included combined vincristine, doxorubicin, cyclophosphamide, and etoposide (regimen I) plus radiation therapy (RT), yielding 5-year event-free survival (EFS) rates of 100%, 88%, 73%, and 29% for patients who had with stage I, II, III, and IV disease, respectively. In the Children's Oncology Group study AREN0321 of risk-adapted therapy, RT was omitted for stage I disease if lymph nodes were sampled, and carboplatin was added for stage IV disease (regimen UH-1). Patients who had stage II/III disease received regimen I with RT. METHODS: Four-year EFS was analyzed for patients enrolled on AREN0321 and on those enrolled on AREN03B2 who received AREN0321 stage-appropriate chemotherapy. RESULTS: Eighty-two patients with CCSK enrolled on AREN0321, 50 enrolled on AREN03B2 only. The 4-year EFS rate was 82.7% (95% confidence interval [CI], 74.8%-91.4%) for AREN0321 and 89.6% (95% CI, 81.3%-98.7%) for AREN03B2 only (p = .28). When combining studies, the 4-year EFS rates for patients who had stage I (n = 10), II (n = 47), III (n = 65), and IV (n = 10) disease were 90% (95% CI, 73.2%-100.0%), 93.4% (95% CI, 86.4%-100.0%), 82.8% (95% CI, 74.1%-92.6%), and 58.3% (95% CI, 34%-100.0%), respectively. There were no local recurrences among seven patients with stage I disease who were treated without RT. One stage I recurrence occurred in the brain, which was the most common site of relapse overall. Among patients with local stage III tumors, neither initial procedure type, margin status, nor lymph node involvement were prognostic. CONCLUSIONS: Patients with stage I CCSK had excellent outcomes without local recurrences when treated without RT. Patients with stage IV disease appeared to benefit from a carboplatin-containing regimen, although their outcomes remained unsatisfactory. Further research is needed to improve outcomes for patients with advanced-stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365).

Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review.

PURPOSE: Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation. METHODS AND MATERIALS: A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies. RESULTS: Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD22; assuming α/ß value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD22 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46). CONCLUSIONS: Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD22 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.

Patients with Heart Failure: Internet Use and Mobile Health Perceptions.

BACKGROUND: Heart failure is a complex clinical syndrome noted on approximately 1 in 8 death certificates in the United States. Vital to reducing complications of heart failure and preventing hospital readmissions is adherence to heart failure self-care routines. Mobile health offers promising opportunities for enhancing self-care behaviors by facilitating tracking and timely reminders. OBJECTIVE: We sought to investigate three characteristics of heart failure patients with respect to their heart failure self-care behaviors: (1) internet use to search for heart failure information; (2) familiarity with mobile health apps and devices; and (3) perceptions of using activity trackers or smartwatches to aid in their heart failure self-care. METHODS: Forty-nine heart failure patients were asked about their internet and mobile health usage. The structured interview included questions adapted from the Health Information National Trends Survey. RESULTS: Over 50% of the patients had utilized the internet to search for heart failure information in the past 12 months, experience using health-related apps, and thoughts that an activity tracker or smartwatch could help them manage heart failure. Qualitative analysis of the interviews revealed six themes: trust in their physicians, alternatives to mobile health apps, lack of need for mobile health devices, financial barriers to activity tracker and smartwatch ownership, benefits of tracking and reminders, and uncertainty of their potential due to lack of knowledge. CONCLUSIONS: Trust in their physicians was a major factor for heart failure patients who reported not searching for health information on the internet. While those who used mobile health technologies found them useful, patients who did not use them were generally unaware of or unknowledgeable about them. Considering patients' preferences for recommendations from their physicians and tendency to search for heart failure information including treatment and management options, patient-provider discussions about mobile health may improve patient knowledge and impact their usage.

Automated Assessment of the DWI-FLAIR Mismatch in Patients with Acute Ischemic Stroke: Added Value to Routine Clinical Practice.

BACKGROUND AND PURPOSE: The DWI-FLAIR mismatch is used to determine thrombolytic eligibility in patients with acute ischemic stroke when the time since stroke onset is unknown. Commercial software packages have been developed for automated DWI-FLAIR classification. We aimed to use e-Stroke software for automated classification of the DWI-FLAIR mismatch in a cohort of patients with acute ischemic stroke and in a comparative analysis with 2 expert neuroradiologists. MATERIALS AND METHODS: In this retrospective study, patients with acute ischemic stroke who had MR imaging and known time since stroke onset were included. The DWI-FLAIR mismatch was evaluated by 2 neuroradiologists blinded to the time since stroke onset and automatically by the e-Stroke software. After 4 weeks, the neuroradiologists re-evaluated the MR images, this time equipped with automated predicted e-Stroke results as a computer-assisted tool. Diagnostic performances of e-Stroke software and the neuroradiologists were evaluated for prediction of DWI-FLAIR mismatch status. RESULTS: A total of 157 patients met the inclusion criteria. A total of 82 patients (52%) had a time since stroke onset of ≤4.5 hours. By means of consensus reads, 81 patients (51.5%) had a DWI-FLAIR mismatch. The diagnostic accuracy (area under the curve/sensitivity/specificity) of e-Stroke software for the determination of the DWI-FLAIR mismatch was 0.72/90.0/53.9. The diagnostic accuracy (area under the curve/sensitivity/specificity) for neuroradiologists 1 and 2 was 0.76/69.1/84.2 and 0.82/91.4/73.7, respectively; both significantly (P < .05) improved to 0.83/79.0/86.8 and 0.89/92.6/85.5, respectively, following the use of e-Stroke predictions as a computer-assisted tool. The interrater agreement (κ) for determination of DWI-FLAIR status was improved from 0.49 to 0.57 following the use of the computer-assisted tool. CONCLUSIONS: This automated quantitative approach for DWI-FLAIR mismatch provides results comparable with those of human experts and can improve the diagnostic accuracies of expert neuroradiologists in the determination of DWI-FLAIR status.

Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders.

The standard treatment for Langerhans cell histiocytosis (LCH) is chemotherapy, although the failure rates are high. Since MAP-kinase activating mutations are found in most cases, BRAF- and MEK-inhibitors have been used successfully to treat patients with refractory or relapsed disease. However, data on long-term responses in children are limited and there are no data on the use of these inhibitors as first-line therapy. We treated 34 patients (26 with LCH, 2 with juvenile xanthogranuloma, 2 with Rosai-Dorfman disease, and 4 with presumed single site-central nervous system histiocytosis) with dabrafenib and/or trametinib, either as first line or after relapse or failure of chemotherapy. Sixteen patients, aged 1.3-21 years, had disease that was recurrent or refractory to chemotherapy, nine of whom had multisystem LCH with risk-organ involvement. With a median treatment duration of 4.3 years, 15 (94%) patients have sustained favorable responses. Eighteen patients, aged 0.2-45 years, received an inhibitor as first-line treatment. All of these have had sustained favorable responses, with a median treatment duration of 2.5 years. Three patients with presumed isolated central nervous system/pituitary stalk histiocytosis had stabilization or improvement of their disease. Overall, inhibitors were well tolerated. Five patients with single-system LCH discontinued therapy and remain off therapy without recurrence. In contrast, all four patients with multisystem disease who discontinued therapy had to restart treatment. Our data suggest that children suffering from histiocytoses can be treated safely and effectively with dabrafenib or trametinib. Additional studies are, however, needed to determine the long-term safety and optimal duration of therapy.

The value of serial echocardiography in risk assessment of patients with paroxysmal atrial fibrillation.

Progression from paroxysmal to persistent atrial fibrillation (AF) is associated with increased morbidity and mortality. We examined the association of left atrial (LA) remodeling by serial echocardiography, and AF progression over an extended follow-up period. Two-hundred ninety patients (mean age 61  ±  11 years, 73% male) who underwent transthoracic echocardiography performed at first presentation for non-valvular paroxysmal AF (PAF) and repeat echocardiogram 1-year later, were followed for progression to persistent AF. LA and left ventricular (LV) dimensions, volumes, LA reservoir, conduit and booster pump strains, LV global longitudinal systolic strain (GLS) assessed by 2D speckle tracking, and PA-TDI (time delay between electrical and mechanical LA activation- reflecting the extent of LA fibrosis) were compared on serial echocardiography. Sixty-nine (24%) patients developed persistent AF over a mean follow-up period of 6.3 years. At baseline, patients with subsequent persistent AF had larger LA dimensions (46 mm vs. 42 mm, p < 0.001), indexed LA volumes (41 ml/m2 vs. 34 ml/m2, p < 0.001), lower LA reservoir and conduit strain (17.6% vs. 27.6%, p < 0.001; 10.5% vs. 16.3%, p < 0.001; respectively) and longer PA-TDI (155 ms vs. 132 ms, p < 0.001) compared to the PAF group. Patients with subsequent persistent AF showed over time significant enlargement in LA volumes (from 37.7 ml/m2 to 42.4 ml/m2, p < 0.001), lengthening of PA-TDI (from 142.2 ms to 162.2 ms, p = 0.002), and decline in LA reservoir function (from 21.9% to 18.1%, p = 0.024) after adjusting for age, gender, diabetes and LV GLS. There were no changes in LA diameter, LA conduit or booster pump function. Conversely, the PAF group showed no decline in LA function. Patients who developed persistent AF had larger LA size and impaired LA function and atrial conduction times at baseline, compared to patients who remained PAF. Over the 1-year time course of serial echocardiographic evaluation, there was progression of LA remodeling in patients who subsequently developed persistent AF, but not in patients who remained in PAF.

Validation of an automated contouring and treatment planning tool for pediatric craniospinal radiation therapy.

Purpose: Treatment planning for craniospinal irradiation (CSI) is complex and time-consuming, especially for resource-constrained centers. To alleviate demanding workflows, we successfully automated the pediatric CSI planning pipeline in previous work. In this work, we validated our CSI autosegmentation and autoplanning tool on a large dataset from St. Jude Children's Research Hospital. Methods: Sixty-three CSI patient CT scans were involved in the study. Pre-planning scripts were used to automatically verify anatomical compatibility with the autoplanning tool. The autoplanning pipeline generated 15 contours and a composite CSI treatment plan for each of the compatible test patients (n=51). Plan quality was evaluated quantitatively with target coverage and dose to normal tissue metrics and qualitatively with physician review, using a 5-point Likert scale. Three pediatric radiation oncologists from 3 institutions reviewed and scored 15 contours and a corresponding composite CSI plan for the final 51 test patients. One patient was scored by 3 physicians, resulting in 53 plans scored total. Results: The algorithm automatically detected 12 incompatible patients due to insufficient junction spacing or head tilt and removed them from the study. Of the 795 autosegmented contours reviewed, 97% were scored as clinically acceptable, with 92% requiring no edits. Of the 53 plans scored, all 51 brain dose distributions were scored as clinically acceptable. For the spine dose distributions, 92%, 100%, and 68% of single, extended, and multiple-field cases, respectively, were scored as clinically acceptable. In all cases (major or minor edits), the physicians noted that they would rather edit the autoplan than create a new plan. Conclusions: We successfully validated an autoplanning pipeline on 51 patients from another institution, indicating that our algorithm is robust in its adjustment to differing patient populations. We automatically generated 15 contours and a comprehensive CSI treatment plan for each patient without physician intervention, indicating the potential for increased treatment planning efficiency and global access to high-quality radiation therapy.

Two phase-matching regimes in high-order harmonic generation.

High-order harmonic generation (HHG) provides scalable sources of coherent extreme ultraviolet radiation with pulse duration down to the attosecond time scale. Efficient HHG requires the constructive interplay between microscopic and macroscopic effects in the generation volume, which can be achieved over a large range of experimental parameters from the driving field properties to those of the generating medium. Here, we present a systematic study of the harmonic yield as a function of gas pressure and medium length. Two regimes for optimum yield are identified, supporting the predictions of a recently proposed analytical model. Our observations are independent on the focusing geometry and, to a large extent, on the pulse duration and laser intensity, providing a versatile approach to HHG optimization.

Producing polyglycerol polyester polyol for thermoplastic polyurethane application: A novel valorization of glycerol, a by-product of biodiesel production.

The production of biodiesel generates glycerol as a by-product that needs valorization. Glycerol, when converted to polyglycerol, is a potential polyol for bio-based thermoplastic polyurethane (TPU) production. In this study, a novel polyglycerol polyester polyol (PPP) was developed from refined glycerol and coconut oil-based polyester polyol. Glycerol was first converted to glycerol acetate and then polymerized with coconut oil-based polyester polyol (CPP) as secondary polyol and phthalic anhydride. The resulting PPP polymerized at 220 °C and OH:COOH molar ratio of 2.5 exhibited an OH number of <100 mg KOH·g sample-1, an acid number of <10 mg KOH·g sample-1, and a molecular weight (MW) of 3697 g mol-1 meeting the polyol requirement properties for TPU (Handlin et al., 2001; Parcheta et al., 2020) [1-2]. Fourier-transform infrared (FTIR) spectroscopic characterization determined that higher reaction temperatures increase the polymerization rate and decrease the OH and acid numbers. Further, higher OH:COOH molar ratios decrease the polymerization rate and acid number, and increase the OH number. Gel permeation chromatography determined the molecular weight of PPP and suggested two distinct molecular structures which differ only in the number of moles of CPP in the structure. A differential scanning calorimetric (DSC) experiment on a sample of PPP-based polyurethane revealed that it was able to melt and remelt after 3 heating cycles which demonstrates its thermoplastic ability. The novel PPP derived from the glycerol by-product of biodiesel industries can potentially replace petroleum-derived polyols for TPU production.

The role of surgery in recurrent ependymomas.

OBJECTIVE: The role of surgery in recurrent ependymomas and its contribution to the outcome are not well defined. While gross-total resection (GTR) has shown benefit in newly diagnosed patients with improvement in progression-free survival (PFS), its impact after recurrence is not known. Its role in distant relapses or multiple local recurrences is similarly less well understood. The objective of this study was to investigate whether GTR could prolong survival after recurrence. METHODS: In this paper, the authors identified patients with ependymomas who underwent surgery at Texas Children's Hospital for recurrent ependymomas between December 2000 and December 2021. Surgical treatment was stratified as GTR, subtotal resection (STR), or a biopsy. Kaplan-Meier analysis was performed for PFS and overall survival (OS), and the log-rank test was used to assess statistical significance. The Cox regression model was used for multivariable analysis. RESULTS: Forty children were identified with a first ependymoma recurrence and follow-up data were collected. The median age was 5.46 years (95% CI 4.52-6.39 years) with a mean follow-up of 3.92 years (95% CI 2.42-5.42 years). In 26 patients (65%), the original tumor was located in the infratentorial space. Twenty-nine patients (72.5%) presented with local recurrence. Within this group, the 5-year PFS rates for the GTR and STR groups were 40.1% and 26.8%, respectively. The 5- and 10-year OS rates were 58.3% and 50% in the GTR group and 51% and 16.7% in the STR group, respectively. Fifteen patients presented with a second recurrence. The 5-year PFS and OS rates in patients who had GTR after a second recurrence were 33% and 50%, respectively. CONCLUSIONS: GTR of local recurrent ependymomas can result in long-term survival in first and second recurrences. Further and larger studies are necessary to elucidate the role of surgery in distal recurrences.