PubMed Health⌕ Search

Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 19 recordsLinked to original sources

Experiences with dose finding in patients in early drug development: the use of biomarkers in early decision making.

With the increasing cost and complexity of drug development, biomarkers will play an increasing role in the early phases. Biomarkers can be classified into target, mechanistic, or outcome with varying degrees of linkage to disease or treatment effect. They can be used to determine proof of concept by characterising the efficacy or safety profiles, or determining differentiation from any competitor drugs. PK/PD modelling of biomarker data for novel and marketed compounds can be used to predict outpatient dose response. Subsequent simulations may replace or reduce the size and cost of larger phase 2b outpatient studies. Two examples of biomarkers and PK/PD modelling used to characterise dose response are presented. Penile plethysmography (RigiScan Plus) in male erectile dysfunction and phenylephrine challenge urethral pressure in benign prostatic hyperplasia are used to reduce time and cost to reach major exploratory development decision points in these indications.

Biomarkers↗

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3-161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.

Adolescent↗

CYP2E1-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane in mice.

1-bromopropane (1-BrP) induces dose- and time-dependent reproductive organ toxicity and reduced sperm motility in rodents. The contribution of cytochrome P4502E1 (CYP2E1) to both 1-BrP metabolism and the induction of male reproductive toxicity was investigated using wild-type (WT) and Cyp2e1-/- mice. In gas uptake inhalation studies, the elimination half-life of [1,2,3-(13)C]-1-BrP was longer in Cyp2e1-/- mice relative to WT (3.2 vs. 1.3 h). Urinary metabolites were identified by 13C nuclear magnetic resonance. The mercapturic acid of 1-bromo-2-hydroxypropane (2OHBrP) was the major urinary metabolite in WT mice, and products of conjugation of 1-BrP with glutathione (GSH) were insignificant. The ratio of GSH conjugation to 2-hydroxylation increased 5-fold in Cyp2e1-/- mice relative to WT. After 1-BrP exposure, hepatic GSH was decreased by 76% in WT mice vs. 47% in Cyp2e1-/- mice. Despite a 170% increase in 1-BrP exposure in Cyp2e1-/- vs. WT mice, sperm motility in exposed Cyp2e1-/- mice did not change relative to unexposed matched controls. This suggests that metabolites produced through CYP2E1-mediated oxidation may be responsible for 1-BrP-induced sperm toxicity. Both 1-BrP and 2OHBrP inhibited the motility of sperm obtained from WT mice in vitro. However, only 2OHBrP reduced the motility of sperm obtained from Cyp2e1-/- mice in vitro, suggesting that conversion of parent compound to 2OHBrP within the spermatozoa may contribute, at least in part, to reduced motility. Overall, these data suggest that metabolism of 1-BrP is mediated in part by CYP2E1, and activation of 1BrP via this enzyme may contribute to the male reproductive toxicity of this chemical.

Acetylcysteine↗

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Arabidopsis↗

Autonomic control of bronchial blood flow and airway dimensions during strenuous exercise in sheep.

BACKGROUND: During exercise and recovery the transient and steady-state changes in autonomic activity regulating lower airway blood flow and dimensions are unknown. The aim of this study was to define changes in bronchial blood flow (Q(br)) and dimensions during moderate and strenuous exercise, and to analyse the role of vagal and sympathetic nerves. METHODS: Nine ewes (34-44kg) underwent left thoracotomy during general anaesthesia (thiopentone/isoflurane) and either (5 sheep=Group 1) a pulsed Doppler transducer was placed on the bronchial artery, or (4 sheep=Group 2) a pulsed Doppler transducer was placed on the bronchial artery, and transit-time and single crystal sonomicrometers were mounted on the left main bronchus. These measured continuously Q(br), bronchial circumference (Circ(br)) and wall thickness (Th(br)). Aortic pressure (P(a)) and central venous pressure catheters were placed in the superficial cervical artery and vein. Trained sheep exercised on a horizontal treadmill, i.e. Group 1, moderate exercise 2.2mph over 1.6, 6min recovery, for analysis of changes in Q(br) before and after cholinoceptor blockade; Group 2, strenuous exercise 4.4mph over 2, 10min recovery for analysis of changes in Q(br) and airway dimensions, before and after cholinoceptor plus alpha(1)-, alpha(2)-adrenoceptor blockade. beta-adrenoceptor systems were intact. RESULTS: In Group 1 during moderate exercise P(a) and heart rate (HR) rose. Q(br) and blood flow conductance (C(br)) fell immediately to 83% (P<0.001) before returning toward resting levels, but fell when exercise ceased to 89% (P<0.01) before recovering. Prior cholinoceptor blockade abolished the immediate fall in Q(br) and C(br), but not the recovery vasoconstriction. Later in recovery the bronchial bed dilated progressively over 6min (P<0.05). In Group 2 during strenuous exercise P(a) and HR rose substantially. Q(br) and C(br) fell to 68% and 54% (P<0.001), respectively, and there was early vasoconstriction in recovery. Circ(br) fell immediately and remained at 93% (P<0.01), and did not recover fully when exercise ceased. Th(br) did not change during or after exercise. Prior cholinoceptor plus alpha-adrenoceptor block caused P(a) and Q(br) to fall slightly during exercise, but the bronchovascular constriction during and after exercise was abolished, as was circumferential shortening in the airway. CONCLUSIONS: At exercise onset and steady-state, resetting the arterial baroreflex upward in sheep increases parasympathetic cholinergic vasoconstrictor activity and causes bronchial wall and bronchovascular smooth muscle contraction in concert with sympathetic adrenergic constriction of systemic vascular beds. Whether the known sigmoid baroreflex control of tracheal smooth muscle tension at rest is extended to tracheobronchial smooth muscle and its circulation during exercise is yet to be determined.

Acetylcholine↗

Sex differences in gout epidemiology: evaluation and treatment.

BACKGROUND: Little is known about the characteristics, evaluation and treatment of women with gout. OBJECTIVE: To examine the epidemiological differences and differences in treatment between men and women in a large patient population. METHODS: The data from approximately 1.4 million people who were members of seven managed care plans in the USA for at least 1 year between 1 January 1999 and 31 December 2003 were examined. Adult members who had pharmacy benefits and at least two ambulatory claims specifying a diagnosis of gout were identified. In addition, men and women who were new users of urate-lowering drugs (ULDs) were identified to assess adherence with recommended surveillance of serum urate levels within 6 months of initiating urate-lowering treatment. RESULTS: A total of 6133 people (4975 men and 1158 women) with two or more International Classification of Disease-9 codes for gout were identified. As compared with men with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of new users of urate-lowering treatment had appropriate surveillance of serum urate levels post-initiation of urate-lowering treatment. After controlling for age, comorbidities, gout treatments, number of ULD dispensings and health plan, women were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to receive the recommended serum urate level testing. CONCLUSIONS: Women with gout were older, had greater comorbidities and more often used diuretics and received appropriate surveillance of serum urate levels, suggesting that the factors leading to gout as well as monitoring of treatment are very different in women and men.

Adult↗

Effects of graded exercise on bronchial blood flow and airway dimensions in sheep.

Exercise stimulus-response relationships for airway blood supply and dimensions have not been described in mammalian species. These relationships are vital for postulates concerning integrated reflex factors normally controlling the airways and which may underlie the asthma syndromes of exercise. This study defines airways stimulus-response relationships in exercising sheep. Ewes between 35 and 40kg were instrumented at left thoracotomy under thiopentone/isoflurane general anaesthesia. Pulsed Doppler ultrasonic transducers were mounted on the bronchial artery, and transit-time plus single-crystal sonomicrometers on the left main bronchus. These recorded simultaneously and continuously bronchial blood flow (Q(br)) and conductance (C(br)), bronchial circumference (Circ(br)) and wall thickness (Th(br)). In Protocol 1 (P1), four sheep ran duplicate 5min protocols on a horizontal treadmill at continuous step-up-and-down speeds of 1min duration, namely, 0.8, 1.6, 2.2, 1.6 and 0.8mph (moderate exercise), followed by 10min recovery. In P2, four sheep ran duplicate 2min protocols at constant 4mph (strenuous exercise), and in P3, one sheep ran duplicate protocols each of 3min at 2.2, 4.4 and 6mph (severe exercise). Regression analysis and repeated measures ANOVA were used to assess differences between times, runs and exercise intensity. In P1, airway effects were directly related to graded exercise effort sustained over 5min. Peak effects occurred at 2.2mph, except for Th(br). Heart rate and P(a) rose (to 156% and 111% of resting, respectively), and Q(br) and C(br) fell (to 83% and 75%; both P<0.001). Circ(br) fell to 96% (P=0.02), and Th(br) rose at low speeds early and late, and thinned at the highest speed. In P2 and P3 for all variables the steady-state effects were systematically greater than for P1 (4.4mph: C(br) to 43%, Circ(br) to 93%; 6.6mph: C(br) to 25%, Circ(br) to 82%). There was no significant recovery hyperaemia, but there was residual post-exercise bronchoconstriction. The exercise stimulus-response relationships from rest to a maximal 6mph for sheep airway circumference and its bronchial circulation are inverse and functionally constrictor.

Animals↗

An international study on starting tumour necrosis factor-blocking agents in ankylosing spondylitis.

OBJECTIVES: To determine the type and proportion of patients with ankylosing spondylitis who rheumatologists consider to be candidates for treatment with tumour necrosis factor (TNF)-blocking agents, and to what extent this is in agreement with the ASsessment in Ankylosing Spondylitis (ASAS) international working group recommendations on initiation of treatment with anti-TNF agents. METHODS: Participants were rheumatologists from 10 different countries, who were considered to be experts in treating patients with ankylosing spondylitis and in the use of anti-TNF treatment, but were unaware of the ASAS recommendations (unpublished at the time of study in 2003). The first 10 consecutive patients with ankylosing spondylitis seen by the rheumatologist were evaluated as to whether the patient was a candidate for anti-TNF treatment. Thereafter, a metrologist assessed the patient for disease activity and severity, and collected data on demographics and treatment. RESULTS: Complete data were available for 1207 of the 1284 patients and were used for analysis. Overall, the rheumatologists indicated that they would initiate TNF-blocking agents in 49.3% of patients, ranging from 37.2% patients in Canada to 78.3% in Australia. These candidates had higher disease activity, higher levels of acute-phase reactants, worse spinal mobility, worse function, more often hip involvement and a higher prevalence of sick leave. Of all patients considered to be candidates, 40% did not fulfil ASAS recommendations with respect to previous use of non-steroidal anti-inflammatory drugs (NSAIDs; at least two NSAIDs) or Bath Ankylosing Spondylitis Disease Activity Index (>or=4). Conversely, 36% of patients who did not fulfil the NSAID or BASDAI recommendations were still considered to be candidates for TNF-blocking treatment. OBJECTIVE: variables, such as C reactive protein, erythrocyte sedimentation rate or magnetic resonance activity, were considered less important than disease activity in the decision on starting TNF-blocking drugs. The only important objective criterion was rapid radiographic progression. CONCLUSION: Rheumatologists wanted to initiate TNF-blocking drugs in roughly half of the patients with ankylosing spondylitis. However, there was a wide variation across countries and doctors. Rheumatologists considered both disease activity and severity to be determinants of starting TNF blockers, but their decision was often in disagreement with ASAS recommendations.

Adult↗

Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy and oncolytic adenovirotherapy have been investigated extensively in xenografic human tumor models established in immunocompromised nude mice. However, the effects of these therapies on syngeneic murine tumors in immunocompetent settings were not well documented. We hypothesized that TRAIL gene therapy used with an oncolytic adenovirus would overcome the weaknesses of the two therapies used individually. In this study, we evaluated the antitumor effects of an oncolytic adenovirus, Delta24, in both human and murine breast cancer cell lines. We also analyzed the effects of TRAIL gene therapy combined with oncolytic virotherapy in these cancer cells. Our results showed that Delta24 can replicate and help the E1-deleted adenovector replicate in murine cancer cells. We also found that these two therapies combined had greater antitumor activity than either one alone in both human and murine breast cancer cells lines and in the syngeneic breast cancer models established in immunocompetent mice. Moreover, Delta24 virotherapy alone and combined with TRAIL gene therapy dramatically reduced the spontaneous liver metastasis that originated in the subcutaneous 4T1 tumor established in Balb/c mice. These findings provide important considerations in the development and preclinical assessments of oncolytic virotherapy.

Adenoviridae↗

Effect of low vitamin A status on fat deposition and fatty acid desaturation in beef cattle.

A group of Angus beef cattle was removed from temperate pastures and fed a very low beta-carotene cereal-based ration in a feedlot for over 300 d. Half the group was supplemented weekly with retinyl palmitate (at the rate of 60,000 IU vitamin A/100 live weight (LW)/day), sufficient to offset clinical vitamin A deficiency; the other half received no supplement. Blood was sampled from all animals at biweekly intervals to assess beta-carotene and vitamin A status. Adipose tissue was sampled by biopsy on three occasions throughout the experimental period and at slaughter to assess FA composition. Muscle was sampled at slaughter to determine the intramuscular fat content. The mean plasma concentration of beta-carotene of all animals fell from an initial value of 20.1 to 5.2 microg/mL at 14 d, to 1.4 microg/mL at 35 d, and to zero at 105 d. Mean vitamin A in plasma was not significantly different between the treatment groups initially. The values then rose to almost twice their initial values by 35 d, but subsequently fell to below initial values by day 119. Thereafter, plasma vitamin A of the supplemented group was significantly greater than that of the unsupplemented group (P < 0.05). Muscle samples at slaughter from supplemented animals contained significantly (P < 0.01) more intramuscular lipid (13.0 vs. 9.6%). Major changes occurred over time in FA composition in both groups. Saturated FA decreased as monounsaturated FA increased over the first 60 d. An index of desaturation of FA was significantly lower (P < 0.001) in the vitamin A-supplemented group than in the nonsupplemented group. M.P. of the adipose tissue of nonsupplemented animals was 32.3 degrees C, significantly less (P< 0.05) than that of supplemented animals (34.1 degrees C). Feeding vitamin A was associated with less intramuscular fat but with a less desirable (less unsaturated, more solid) FA profile.

Adipose Tissue↗

The fate of organs refused locally and transplanted elsewhere.

UNLABELLED: The number of kidney allografts procured from deceased donors has been fairly constant in the past few years, while organs from living donors steadily increase. In our program, existing protocols refused some kidneys which were subsequently accepted and transplanted at other hospitals. Thus, a review of our criteria to accept kidneys became necessary. METHODS: We studied the outcome of all kidneys refused by us but transplanted in other programs between 2002 and 2004. The data analyzed included ID no. donor, transplant center, procurement date, donor age, ischemic times, recipient alive or dead, creatinine level (when it was offered), initial function, hypertension, diabetes mellitus, biopsy, reason why the kidney was not accepted in our program, kidney functioning or lost, and cause of graft failure. The chi-square, Fisher, and t tests were used to analyze our data; P values of <.05 were regarded as significant. RESULTS: Originally 137, we excluded kidneys exported due to mandatory sharing (26 of 137 = 18.97%) and multiorgan placement (10 of 137 = 7.3%). Thus, 101 kidneys were not accepted by us because they did not meet the existing criteria of our program, but were accepted elsewhere. Reasons for nonacceptance were divided into donor quality, donor social history, donor age, donor size/weight, positive serological test, as well as organ preservation time, organ anatomical damage, elevated creatinine, abnormal urinalysis, abnormal biopsy, and decreased urine output. Donor issues were 66 of 101 (65.3%) with a graft loss of 13.6%, and organ issues were 35 of 101 (34.7%) with a graft loss of 66.6%. Donor quality totaled 24 of 66 (36.4%) and donor social history totaled 20 of 66 (30.3%); these were the most common causes for kidney nonacceptance related to donor issues. Reasons related to organ quality included elevated creatinine (15 of 35 = 42.9%; graft loss, 46.6%), and abnormal biopsy (9 of 35 = 25.7%; graft loss, 11.1%) and organ anatomical damage (4 of 35 = 11.4%; graft loss, 75%) (P = .42). Graft loss was more frequent with creatinine levels above 2.4 mg/dL (P < .001, RR gf = 1.5). Long-term fate of these 101 kidneys transplanted elsewhere: 82 (81.2%) were still working while 19 (18.8%) were lost. The causes of graft loss were renal artery thrombosis (42.1%), renal venous thrombosis (26.3%), death for other reasons (15.8%), graft never worked (10.5%), and ESRD (5.7%). The results suggest that the criteria for refusal related to donor issues, including hypertension, diabetes mellitus, donor age and donor size, should be revised owing to the low percentage of graft loss. Other donor issues such as positive serological test and donor social history (drug use, alcoholism) represent a serious potential risk for the health of recipients; for this reason, considering these persons as possible donors is very difficult irrespective of the graft outcome. Kidney refusals related to organ issues (especially elevated creatinine and anatomical damage) due to the very high percentage of graft loss should be considered high risk and probably be excluded. The increase in the demand of kidneys to be transplanted is a very important reason for a continuous and systematic review of donor exclusion criteria in every transplant program. The results presented here have helped us to improve both our outcomes and utilizations based on scientific evidence.

Cadaver↗

Long-term outcome of high-dose melphalan and autologous stem cell transplantation for AL amyloidosis.

Light chain (AL) amyloidosis is the result of a clonal plasma cell expansion, in which amyloidogenic monoclonal light chains deposit in various tissues resulting in organ dysfunction and organ failure. The median survival of patients with AL amyloidosis without therapy is 10-14 months. Several phase II studies report haematological and clinical remission in up to 50% of patients after high-dose melphalan and autologous stem cell transplantation. We analysed retrospectively the long-term outcome of 19 patients treated in this way between August/1996 and December/2001. We observed a relatively high treatment-related mortality of 26%, but 12 patients (63%) were high-risk candidates. Eight patients (42%) surviving longer than 100 days achieved haematological remission and long-term survival, whereas 6 (32%) obtained no clear benefit from high-dose therapy. However, 62% of patients survived beyond 2 years and the median survival from transplant was 48 months (range 0-104 months).

Adult↗

Chemokine receptors expressed on T cells in packed red blood cell units change over storage time.

The transfusion of blood products is associated with adverse events that are related to the leukocytes in stored units of blood. These leukocytes have been shown to promote the elaboration of inflammatory cytokines. However, the status of a set of key inflammatory mediators, chemokine receptors, expressed on T lymphocytes in stored red blood cell (RBC) units is largely unknown. We investigated the expression pattern of selected chemokine receptors on T cells from non-leukocyte-reduced RBC units over storage time. Selecting segments from stored RBC units, we evaluated the T-cell subsets for the chemokine receptors CXCR3 and CCR4 by flow cytometry. Statistical analysis was performed by regression analysis. We analysed 30 samples stored between 5 and 38 days. The CD4+ T cells expressing CXCR3 increased by 0.27% daily (P= 0.02), whereas the expression of CCR4 declined by 0.40% daily (P < 0.001). Though the expression of the chemokine receptors on CD8+ cells followed the same trend, the changes were statistically nonsignificant. This study suggests that a longer duration of storage is associated with a higher expression of chemokine receptor CXCR3 and a lower expression of CCR4 on T cells in RBC units, suggesting a pro-inflammatory Th1 bias. The clinical significance of these changes in the setting of adverse transfusion events needs further evaluation.

Antigens, CD↗

Anticancer activity of 5-benzylidene-2-phenylimino-1, 3-thiazolidin-4-one (BPT) analogs.

We recently identified two compounds of 5-benzylidene-2-phenylimino-1,3-thiazolidin-4-one (BPT) analog, 5-(4-methylbenzylidene)-2-phenylamino-1,3-thiazolidin-4-one (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-phenylimino-1,3-thiazolidin-4-one (DBPT), that can effectively induce apoptosis in cancer cells but not in normal cells, independently of P-glycoprotein status. To further investigate the antitumor activity of BPT analogs, we obtained 18 commercially available analogs of BPT and synthesized 7 analogs in our lab, and analyzed their antitumor activity in various cancer cells, including paclitaxel- and vinorelbine-sensitive and -resistant human lung cancer cells. Two of the compounds were more potent than MMPT or DBPT in induction of apoptosis in certain cancer cell lines and remained tumor selective. Seven compounds did not induce any cytotoxic effects in any of the cell lines tested at the highest concentration tested (31 microM). The other compounds induced cytotoxic effects in some cancer cells but not in others or were less potent than MMPT and DBPT. Cell uptake studies showed that analogs that effectively induced cell killing in paclitaxel- and vinorelbine-resistant cells could be taken up easily by those cells despite their high levels of P-glycoprotein expression. These data further demonstrate that thiazolidinone analogs are not P-glycoprotein substrates and could be useful for treatment of P-glycoprotein overexpressing refractory cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Surface complexation studied via combined grazing-incidence EXAFS and surface diffraction: arsenate on hematite (0001) and (10-12).

X-ray diffraction [crystal-truncation-rod (CTR)] studies of the surface structure of moisture-equilibrated hematite reveal sites for complexation not present on the bulk oxygen-terminated surface, and impose constraints on the types of inner-sphere sorption topologies. We have used this improved model of the hematite surface to analyze grazing-incidence EXAFS results for arsenate sorption on the c (0001) and r (10-12) surfaces measured in two electric vector polarizations. This work shows that the reconfiguration of the surface under moist conditions is responsible for an increased adsorption density of arsenate complexes on the (0001) surface relative to predicted ideal termination, and an abundance of "edge-sharing" bidentate complexes on both studied surfaces. We consider possible limitations on combining the methods due to differing surface sensitivities, and discuss further analysis possibilities using both methods.

Adsorption↗

Efficient radiation production in long implosions of structured gas-puff Z pinch loads from large initial radius.

We have proposed and demonstrated successfully a new approach for generating high-yield K-shell radiation with large-diameter gas-puff Z pinches. The novel load design consists of an outer region plasma that carries the current and couples energy from the driver, an inner region plasma that stabilizes the implosion, and a high-density center jet plasma that radiates. It increased the Ar K-shell yield at 3.46 MA in 200 ns implosions from 12 cm initial diameter by a factor of 2, to 21 kJ, matching the yields obtained earlier on the same accelerator with 100 ns implosions. A new "pusher-stabilizer-radiator" physical model is advanced to explain this result.

Journal Article↗