Western Australian adolescent emotional wellbeing during the COVID-19 pandemic in 2020.

BACKGROUND: The impacts of the COVID-19 pandemic have been vast and are not limited to physical health. Many adolescents have experienced disruptions to daily life, including changes in their school routine and family's financial or emotional security, potentially impacting their emotional wellbeing. In low COVID-19 prevalence settings, the impact of isolation has been mitigated for most young people through continued face-to-face schooling, yet there may still be significant impacts on their wellbeing that could be attributed to the pandemic. METHODS: We report on data from 32,849 surveys from Year 7-12 students in 40 schools over two 2020 survey cycles (June/July: 19,240; October: 13,609), drawn from a study of 79 primary and secondary schools across Western Australia, Australia. The Child Health Utility Index (CHU9D) was used to measure difficulties and distress in responding secondary school students only. Using comparable Australian data collected six years prior to the pandemic, the CHU9D was calibrated against the Kessler-10 to establish a reliable threshold for CHU9D-rated distress. RESULTS: Compared to 14% of responding 12-18-year-olds in 2013/2014, in both 2020 survey cycles almost 40% of secondary students returned a CHU9D score above a threshold indicative of elevated difficulties and distress. Student distress increased significantly between June and October 2020. Female students, those in older Grades, those with few friendships or perceived poor quality friendships, and those with poor connectedness to school were more likely to score above the threshold. CONCLUSIONS: In a large dataset collected during the first year of the COVID-19 pandemic, the proportion of secondary school students with scores indicative of difficulties and distress was substantially higher than a 2013/2014 benchmark, and distress increased as the pandemic progressed, despite the low local prevalence of COVID-19. This may indicate a general decline in social and emotional wellbeing exacerbated by the events of the pandemic. TRIAL REGISTRATION: ANZCTRN (ACTRN12620000922976). Retrospectively registered 17/08/2020. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380429&isReview=true .

Conceptual study of energy resolved x-ray measurement and electron temperature reconstruction on ITER with low voltage ionization chambers.

In tokamaks with tungsten-based plasma facing components, such as ITER, pollution of the plasma by heavy impurities is a major concern as it can lead to radiative breakdown. The radiation emitted by such impurities is mainly composed of x-rays in the [0.1; 100] keV range. A diagnostic allowing for the reconstruction of the impurity distribution is of high interest. The ITER requirements for the x-ray measurement system make it mandatory for the detector to provide spectral information. Due to the radiation environment during the ITER nuclear phase, advanced detectors exhibiting high resilience to neutrons and gamma rays, such as gas-filled detectors, are required. The use of Low Voltage Ionization Chambers (LVICs) for this purpose is investigated in this paper. Several anodes have been added to the detector in order to allow for spectral deconvolution. This article presents a conceptual study of the use of a multi-anode LVIC for energy resolved x-ray measurement on ITER. It covers the design of the multi-anode LVIC and its modeling, the method for spectral deconvolution, and its application to energy resolved x-ray tomography, as well as the computation of the electron temperature from the reconstructed local x-ray emissivity.

Modeling a low voltage ionization chamber based tomography system on ITER.

Soft x-ray (SXR) tomography is a key diagnostic method for impurity transport study in tokamaks since it allows for local impurity density reconstruction. The International Thermonuclear Experimental Reactor (ITER) radiative environment in deuterium-deuterium and deuterium-tritium phases will limit the choices of SXR detector technologies, and gas detectors are one of the most promising solutions. In this paper, we, thus, investigate the SXR tomography possibilities on ITER using Low Voltage Ionization Chambers (LVICs). The study contains the development of a LVIC synthetic diagnostic and its application to estimate the LVIC tomographic capabilities in an ITER D-T scenario, including the influence of LVIC parameters and noise in the measurements.

Polycapillary lenses for soft x-ray transmission in ITER: Model, comparison with experiments, and potential application.

Measuring Soft X-Ray (SXR) radiation [0.1 keV; 15 keV] in tokamaks is a standard way of extracting valuable information on the particle transport and magnetohydrodynamic activity. Generally, the analysis is performed with detectors positioned close to the plasma for a direct line of sight. A burning plasma, like the ITER deuterium-tritium phase, is too harsh an environment to permit the use of such detectors in close vicinity of the machine. We have thus investigated in this article the possibility of using polycapillary lenses in ITER to transport the SXR information several meters away from the plasma in the complex port-plug geometry.

In situ wavelength calibration of the edge CXS spectrometers on JET.

A method for obtaining an accurate wavelength calibration over the entire focal plane of the JET edge CXS spectrometers is presented that uses a combination of the fringe pattern created with a Fabry-Pérot etalon and a neon lamp for cross calibration. The accuracy achieved is 0.03 Å, which is the same range of uncertainty as when neglecting population effects on the rest wavelength of the CX line. For the edge CXS diagnostic, this corresponds to a flow velocity of 4.5 km/s in the toroidal direction or 1.9 km/s in the poloidal direction.

Bragg x-ray survey spectrometer for ITER.

Several potential impurity ions in the ITER plasmas will lead to loss of confined energy through line and continuum emission. For real time monitoring of impurities, a seven channel Bragg x-ray spectrometer (XRCS survey) is considered. This paper presents design and analysis of the spectrometer, including x-ray tracing by the Shadow-XOP code, sensitivity calculations for reference H-mode plasma and neutronics assessment. The XRCS survey performance analysis shows that the ITER measurement requirements of impurity monitoring in 10 ms integration time at the minimum levels for low-Z to high-Z impurity ions can largely be met.

Development of a spatially resolving x-ray crystal spectrometer for measurement of ion-temperature (T(i)) and rotation-velocity (v) profiles in ITER.

Imaging x-ray crystal spectrometer (XCS) arrays are being developed as a US-ITER activity for Doppler measurement of T(i) and v profiles of impurities (W, Kr, and Fe) with ∼7 cm (a/30) and 10-100 ms resolution in ITER. The imaging XCS, modeled after a prototype instrument on Alcator C-Mod, uses a spherically bent crystal and 2D x-ray detectors to achieve high spectral resolving power (E/dE>6000) horizontally and spatial imaging vertically. Two arrays will measure T(i) and both poloidal and toroidal rotation velocity profiles. The measurement of many spatial chords permits tomographic inversion for the inference of local parameters. The instrument design, predictions of performance, and results from C-Mod are presented.

Modeling the effect of reflection from metallic walls on spectroscopic measurements.

A modification of JET is presently being prepared to bring operational experience with ITER-like first wall (Be) and divertor (W) materials, geometry and plasma parameters. Reflectivity measurements of JET sample tiles have been performed and the data are used within a simplified model of the JET and ITER vessels to predict additional contributions to quantitative spectroscopic measurements. The most general method to characterize reflectivity is the bidirectional reflection distribution function (BRDF). For extended sources however, such as bremsstrahlung and edge emission of fuel and intrinsic impurities, the results obtained in the modeling are almost as accurate if the total reflectivity with ideal Lambertian angular dependence is used. This is in contrast to the experience in other communities, such as optical design, lighting design, or rendering who deal mostly with pointlike light sources. This result is so far based on a very limited set of measurements and will be reassessed when more detailed BRDF measurements of JET tiles have been made. If it is true it offers the possibility of in situ monitoring of the reflectivity of selected parts of the wall during exposure to plasma operation, while remeasurement of the BRDF is performed during interventions. For a closed vessel structure such as ITER, it is important to consider multiple reflections. This makes it more important to represent the whole of the vessel reasonably accurately in the model, which on the other hand is easier to achieve than for the more complex internal structure of JET. In both cases the dominant contribution is from the first reflection, and a detailed model of the areas intersected by lines of sight of diagnostic interest is required.

Paediatric resuscitation by phone: the call back.

OBJECTIVE: To assess whether the nationwide introduction of standardized paediatric resuscitation training has resulted in an increase in resuscitation knowledge from 1995 and whether this increase in knowledge is greater in those who have attended a resuscitation training course within the last year. METHODS: National telephone survey of paediatric residents. RESULTS: A total of 128 out of a possible 140 residents responded. The mean score in 2002 was significantly higher than in 1995. Those 2002 respondents who had attended a course scored significantly higher than both 1995 respondents, and those 2002 respondents who had not attended a course. There was no significant difference between those 2002 respondents who had not attended a course and the 1995 respondents. CONCLUSION: There has been a significant increase in resuscitation knowledge from 1995 to 2002. This improvement has occurred over a period coinciding with the nationwide introduction of standardized resuscitation training. The authors suggest that this improvement is, in part, due to the introduction of standardized paediatric resuscitation training.

Collisional-radiative study of lithium plasmas.

The sensitivity of lithium plasma models to the underlying atomic data is investigated. Collisional-radiative modeling is carried out with both the Los Alamos and ADAS suite of codes. The effects of plane-wave Born, distorted-wave, and nonperturbative R -matrix with pseudostates and time-dependent close-coupling electron impact atomic data on derived plasma quantities such as the ionization balance and radiated power are studied. Density and temperature regimes are identified where nonperturbative excitation and ionization rate coefficients must be used. The electron temperature and density ranges investigated were 0.2 eV< or = T(e) < or =90 eV and 10(10) cm(-3) < or = N(e) < or = 10(14) cm(-3).

Inferring handedness from lithic evidence.

Until recently research into the origins of human handedness has been hampered by the lack of valid techniques for inferring handedness in pre-modern populations. A method developed by Toth for inferring handedness from lithic evidence, based on orientation of the cortex on lithic flakes, has produced promising results. However, this method is limited in applicability and has a variable signal to noise ratio. The authors describe a separate method, based on the orientation of the cone of percussion in lithic flakes, for inferring handedness from the lithic evidence. This method complements the cortex method. Some preliminary experimental evidence is presented which indicates that handedness can be inferred from lithic evidence using the cone of percussion method. Suggestions for further research are made.

Elevated plasminogen receptor expression occurs as a degradative phase event in cellular apoptosis.

Plasminogen activation (PA) is involved in a variety of extracellular proteolytic events, such as fibrinolysis, cell migration (e.g. angiogenesis, tumour cell invasion, inflammation, wound healing, bacterial invasion), ovulation, tissue remodelling and the activation of other protease classes and growth factors. These diverse roles are due to the specific localization of components of the PA system to extracellular matrices, basement membranes, fibrin and cell surfaces. We have previously reported that PA is dramatically elevated during cycloheximide (CHX)-induced apoptosis in U937 cells due to a concomitant increase in both plasminogen receptors (PLG-R; i.e. specific PLG binding) and cell-surface urokinase plasminogen activator. We now extend this study by showing that the increase in PLG-R (resulting in an increase in specific PLG binding) is a late apoptotic event coincident with propidium iodide uptake and internucleosomal DNA fragmentation but occurring after elevations in phosphatidylserine exposure. Plasminogen was also observed to dramatically increase the rate of CHX-induced apoptosis. We conclude that PA may play a role in the degradative (i.e. late-stage) events of cellular apoptosis.

Increased plasminogen binding is associated with metastatic breast cancer cells: differential expression of plasminogen binding proteins.

Overexpression of urokinase-type plasminogen activator and its receptor correlates with metastatic capacity in breast cancer. In this study we show that the urokinase/urokinase receptor-overexpressing, metastatic human breast cancer cell line MDA-MB-231 (1) bound significantly more cell-surface plasminogen in a lysine-dependent manner and (2) was capable of generating large amounts of plasmin compared with the non-metastatic cell lines MCF-7 and T-47D. In addition, distinct plasminogen binding proteins were detected in the plasma membranes of the cell lines, suggesting heterogeneity of binding proteins. Plasminogen binding was analysed using a combination of dual-colour fluorescence flow cytometry and ligand histochemistry (for comparative and cellular localization of ligand binding), and fluorimetry (for Scatchard analysis). Apart from revealing the greater plasminogen binding capacity of MDA-MB-231 cells, flow cytometry and histochemistry also revealed that, in all three cell lines, non-viable or permeabilized cells bound significantly more plasminogen in a lysine-dependent manner than viable or non-permeabilized cells. Viable MDA-MB-231 cells bound plasminogen with moderate affinity and high capacity (Kd = 1.8 microM, receptor sites per cell 5.0 x 10(7). Our results indicate that differences in cell surface-specific plasminogen binding capacity between cell lines may not be detectable with binding techniques that cannot distinguish between viable and non-viable cells.

Loss of cell viability dramatically elevates cell surface plasminogen binding and activation.

The plasminogen activation cascade is focused at the cell surface by virtue of the presence of plasminogen and plasminogen activator receptors. We have utilized flow cytometric plasminogen (plg) binding and activation assays to examine both plasminogen binding and activation on the surface of specific subpopulations of U937 cells (viable, apoptotic, and dead cells). A direct relationship was found to exist between cell viability (propidium iodide uptake) and the magnitude of lysine-dependent plasminogen binding, with apoptotic and dead subpopulations of cells binding up to 100-fold more plasminogen than viable cells. Despite the high level of lysine-dependent plasminogen binding on dead cells, plasminogen activation was minimal due to low levels of cell-surface urokinase plasminogen activator. Plasminogen activation readily occurred on the surface of apoptotic cells because of a dramatic increase in both lysine-dependent plasminogen binding and endogenous urokinase plasminogen activator. These results indicate that colocalization of plasminogen and urokinase plasminogen activator are paramount for plasminogen activation to proceed on the cell surface. Our data also strongly implicate the involvement of the plasminogen activation cascade in apoptosis, especially on urokinase plasminogen activator-expressing cell types. The current study clearly supports the important role of flow cytometry in cellular plasminogen binding and activation studies.

Expression, purification, and characterization of recombinant human factor X.

A system is described for producing recombinant factor X with properties very similar to human plasma factor X. Optimization of the expression system for factor X resulted in the finding that human kidney cells (293 cells) are superior to the widely utilized baby hamster kidney cells (BHK cells) for the expression of functional factor X. It was also determined that production of factor X by 293 cells requires the substitution of the -2 residue (Thr-->Arg) which affords the removal of the factor X propeptide. Purification of recombinant and plasma factor X is accomplished using a calcium-dependent monoclonal antibody directed against the gla domain. The proteins are comparable by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The rate and extent of activation by the factor X coagulant protein from Russell's viper venom and by factors IXa and VIIIa are similar; activation of the recombinant protein by VIIa and tissue factor is mildly faster. The activated enzymes have the same activity toward a chromogenic substrate and the biologic substrate, prothrombin. Both enzymes have the same apparent affinity for the activated platelet surface as judged by their ability to activate prothrombin. Finally, inhibition by antithrombin, with or without heparin, and inhibition by the tissue factor pathway inhibitor are equivalent. Recombinant factor X produced by this method is therefore well suited for probing structure-function relationships by mutational analysis.

Factor XSt. Louis II. Identification of a glycine substitution at residue 7 and characterization of the recombinant protein.

A molecular defect in factor X (fX) results from a point mutation that causes glycine substitution for gamma-carboxylated glutamic acid at position 7. The variant (fXSt. Louis II) and wild type (fXWT) proteins were produced in a mammalian expression system and characterized. fXSt. Louis II has <1% and approximately 3% of normal clotting activity in modified prothrombin time and partial thromboplastin time assays, respectively. The rate of activation of fXSt. Louis II by factor VIIa and tissue factor is undetectable under conditions that result in complete activation of fXWT; activation by factors VIIIa and IXa is approximately 30% of normal activation. The X-activating protein from Russell's viper venom activates fXSt. Louis II completely but at a reduced rate. Thrombin generation on phoshopolipid vesicles or activated platelets is approximately 30% or approximately 5%, respectively. Membrane-dependent autolysis is markedly reduced for fXSt. Louis II. In reactions that are not surface-dependent, fXSt. Louis II is nearly identical to that of fXWT. The rate of inhibition by antithrombin is indistiguishable, as is the rate of thrombin formation in the absence of phospholipid, with or without factor Va.

Cisplatin nephrotoxicity in a patient with a single kidney.

OBJECTIVE: To describe a patient with a single kidney who experienced cisplatin-associated nephrotoxicity. CASE SUMMARY: A 78-year-old African-American woman with squamous cell carcinoma of the base of her tongue (T4N2M1) was admitted electively to our institution for the first cycle of chemotherapy. Her past medical history was significant for a left nephrectomy secondary to well-differentiated papillary transitional cell carcinoma of the left renal pelvis, hypothyroidism, asthma, and coronary artery disease. Her blood urea nitrogen (BUN) was 27 mg/dL of urea, and serum creatinine was 1.2 mg/dL. On admission she was hydrated adequately, and was treated with an evening dose of cisplatin 100 mg/m2 (180 mg) in 250 mL of NaCl 0.9% solution in a 3-hour infusion, and a 5-day course of fluorouracil 1000 mg/m2 (1800 mg) in a 24-hour infusion. Serum creatinine and BUN concentrations following cisplatin administration were 1.1 mg/dL and 8 mg/dL, respectively. Four days after cisplatin therapy, a decline in renal function was observed, with an increase in serum creatinine and BUN concentrations to 4.0 mg/dL and 31 mg/dL, respectively. These tests remained elevated throughout her hospitalization. With hemodialysis treatments a resolution in altered mental status was observed; however, her chronic renal failure persisted. She was subsequently discharged and followed in the outpatient renal, geriatric, and oncology clinics. DISCUSSION: Cisplatin is a principal chemotherapeutic agent used in the treatment of a variety of solid tumors. Nephrotoxicity is a major complication associated with this compound. Although many clinicians believe that cisplatin nephrotoxicity is unlikely to occur in patients with a single kidney, recent reports have suggested otherwise. The physiologic changes of the aging kidney are such that they should foster cisplatin clearance rather than expose the kidney to the drug's nephrotoxic potential. In addition, evening administration of cisplatin is thought to minimize nephrotoxicity. We describe a 78-year-old woman with a single kidney who developed nephrotoxicity following a single evening dose of cisplatin. Details of the patient's history and cisplatin-associated complication and therapy are discussed. CONCLUSIONS: Cisplatin circadian rhythmic pharmacotherapy to minimize cisplatin toxicity in patients with a single kidney appears to be controversial and needs further evaluation.

Radiotherapy alone compared with radiotherapy and chemotherapy in patients with squamous cell carcinoma of the esophagus.

PURPOSE: The purpose of this study is to determine whether primary treatment with both radiotherapy and chemotherapy is superior to radiotherapy alone in patients with squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: From January 1980 to December 1988, 77 patients from two Veterans Affairs hospitals with clinically staged nonmetastatic squamous cell carcinoma of the esophagus received either radiotherapy alone (RT group) or concomitant radiotherapy and chemotherapy (RT + CT group) with curative intent. Each group originated at a different hospital, but all patients were irradiated in the same radiotherapy department. Chemotherapy consisted of cisplatin and 5-fluorouracil. Forty-two patients received RT alone, and 35 received RT + CT. Locoregional control, disease-free survival, and overall survival rates were compared. RESULTS: Locoregional control, disease-free survival, and overall survival rates were significantly higher in the RT + CT group when compared to RT group, 26% vs 5%, 20%, vs 2%, and 29% vs 7%, respectively, at 2 years (P = .01, 0.02 and 0.02, respectively). The median survival was 14 months for the RT + CT group and 7.5 months for the RT group. There was no difference in the incidence of distant metastases except for bone metastases. No one in the RT + CT group developed bone metastases compared to nine patients in the RT group (P = .01). CONCLUSION: This retrospective analysis shows improved locoregional control, disease-free survival, and survival when chemotherapy consisting of cisplatin and 5-FU is given in addition to radiation for patients with squamous cell carcinoma of the esophagus. Bony metastases were absent in those who received chemotherapy.

Phase II study of amonafide in the treatment of patients with advanced squamous cell carcinoma of the head and the neck. An Illinois Cancer Center study.

Amonafide (nafidimide), a synthetic organic compound with an inhibitory effect on cellular replication, was used in a phase II study conducted by the Illinois Cancer Center in order to assess its efficacy and toxicity in advanced or recurrent squamous cell cancer of the head and neck. Eligible patients had received no more than one prior adjuvant or neoadjuvant chemotherapy, had normal bone marrow, renal and hepatic function, ECOG performance status of 0-2, and bidimensionally measurable disease. Eligible patients were administered amonafide at a starting dose of 300 mg/m2 for five consecutive days every 3 weeks with dose escalation or de-escalation according to established hematologic criteria in the absence of disease progression. Nineteen of 22 entered patients were evaluable for response and all patients were evaluable for toxicity. Eleven of 19 patients achieved stable disease. Median time to progression after start of treatment was 57 days, for the 18 patients for whom the date of progression is known. There were no partial or complete responses. Hematologic toxicity was dose limiting with grade 3-4 neutropenia in 50 percent of patients and 4 deaths associated with neutropenic sepsis. Non-hematologic toxicity was mild to moderate with nausea and vomiting predominating. In this study, amonafide was a myelotoxic, inactive treatment in advanced/recurrent head and neck cancer. Further use in head and neck cancer appears unwarranted.