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Determine the effectiveness and acceptability of a text message intervention (DTEXT) on HbA1c and self-management behaviors for Australian adults with type 2 diabetes.Using intention to treat analysis and generalized estimating equations, this randomized controlled trial of 395 adults determined change in HbA1c at 3 and 6 months between the intervention and control group. Secondary outcomes included change in nutrition, physical activity, blood lipid profile, body mass index, quality of life, self-efficacy, medication taking and program acceptability.No significant difference was observed between the intervention or control group for HbA1c at 3 months (P = 0.23) or 6 months (P = 0.22). Significant improvements were seen in consumption of vegetables at 3 months (P0.001) and 6 months (P = 0.04); fruit at 3 months (P = 0.046) and discretionary sweet foods at 3 months (P = 0.02). No other significant effects seen. The intervention demonstrated high rates of acceptability (94.0%) and minimal withdrawal (1.5%).DTEXT was an acceptable text message intervention that improved some nutritional behaviors in people with type 2 diabetes, but did not significantly improve HbA1c or other outcomes. Further research is required to optimize DTEXT.DTEXT provides an acceptable, feasible form of self-management support that may complement existing diabetes care.

Objectives In 2018, the New South Wales (NSW) Government implemented a State-wide program to reduce the cost barrier to organised sport and physical activity participation. We explored parent/carer’s awareness and children’s engagement in the Active Kids program across socioeconomic groups and used the NSW Population Health Survey (PHS) to validate engagement in the program. Design Cross-sectional. Methods Data were obtained from the 2018 NSW PHS and the Active Kids program registration database. We compared demographic characteristics of children who had registered for the program in the registration database with children in the weighted NSW PHS. Multinomial regression models were used to determine whether socioeconomic status was associated with parent/carer awareness and children’s engagement in the program. Results Parent/carer’s in the most disadvantaged quartile were twice as likely to have never heard of the Active Kids program (OR: 2.04, 95% CIs 1.31, 3.16) or to have heard or the program but not registered (OR: 1.94, 95% CIs 1.26, 3.00), and more than twice as likely to have registered for a voucher, but not followed through and redeemed the voucher (OR: 2.68, 95% CIs 1.27, 5.63) compared with the least disadvantaged quartile. Conclusions The Active Kids program has provided financial support for organised sport and physical activity to a large number of children. However, there are still a substantial proportion of socially disadvantaged groups who are unaware or have not engaged in the program. Further targeted work is required to increase the awareness and engagement in the program for socially disadvantaged groups.

Physical activity (PA) decreases during the transition from childhood to adolescence, with larger declines observed in girls. School-based interventions are considered the most promising approach for increasing adolescents’ PA levels although, it is unclear which types of school-based interventions have the greatest impact. The objective of this systematic review is to assess the impact and design of school-based PA interventions targeting adolescent girls. A systematic search was conducted using four electronic databases (PubMed, Web of Science, SPORTDiscus and PsychInfo). This systematic review was registered with PROSPERO (Registration number: CRD42016037428) and PRISMA guidelines (2009) were followed throughout. Twenty studies were identified as meeting the inclusion criteria and were included in a narrative synthesis. Seventeen studies were eligible for inclusion in a meta-analysis. There was a significant small positive treatment effect for school-based PA interventions for adolescent girls (k=17, g= 0.37, p

Highlights • The Active Kids program reached 75,927 children who were overweight or obese. • The program reached approximately 25% of all eligible children who were overweight and obese. • The prevalence of overweight and obesity was 17.2% and 7.6%, respectively. • There was a clear socio-economic gradient for obesity prevalence., There has been limited population-level success in tackling overweight and obesity. The Active Kids program is a universal intervention that aims to increase participation in structured physical activity and sport among children and adolescents in New South Wales (NSW), Australia. This study examined the prevalence of overweight and obesity across subgroups and by social disadvantage in this large broadly representative sample. A cross-sectional study was conducted including all children (n = 671,375) who registered for an Active Kids Program voucher in 2018. The child’s height and weight were obtained from an online registration form. Among children and adolescents who registered in the Active Kids Program, the prevalence of overweight and obesity was 17.2% and 7.6%, respectively. A large number of children and adolescents who lived in the most disadvantaged areas (n = 99,583; 14.8%) registered for the program. There was a clear socio-economic gradient for obesity prevalence across areas of increasing disadvantage, with children and adolescents living in the most disadvantaged area being 1.87 (95% CIs 1.82, 1.93) times more likely to be overweight or obese. The Active Kids program successfully reached a substantial proportion of children who are overweight and obese from socio-economically disadvantaged areas, providing financial support and opportunities for these children to participate in structured sport and physical activity. However, the program did not reach all children, and additional physical activity promotion strategies may be needed in a comprehensive approach. Nonetheless, these findings support government investment in reaching children who are overweight or obese with large-scale programs.

The sedimentary and biological material preserved in wetlands in semi-arid regions provide a rich repository of paleoclimate and paleoecological archives. These records reflect an underutilized, but typically ignored paleoenvironmental resource in semi-arid settings. The results presented here demonstrate that groundwater-fed wetlands constitute a valuable record of environmental change that not only complement reconstructions from lacustrine settings, but also contribute unique data and insights into climate and landscape change. We use data obtained from sediment cores collected from Loboi wetland, a groundwater-fed wetland located in the Equatorial East African Rift Valley of Kenya, to demonstrate the value of paleoenvironmental datasets extracted from wetland archives. This article relates surficial sedimentary geochemical data (TOC, δ13C, δ15N, C:N, and %C3) at Loboi to the extant macrophytic vegetation. The surficial data are used as an analog to interpret the geochemical signature of three sediment cores and a soil pit. The stratigraphic records show significant variation along a north to south transect through the wetland. The geochemistry indicates that papyrus wetland records are distinctly different from Typha dominated wetland sedimentary signatures. The interpretation of the stratigraphic material is further improved by the inclusion of sub-fossil macrophyte and testate amoebae remains. The extraction and identification of seeds of wetland plants from the sedimentary archive provide invaluable genus to species specific details of wetland ecology. Further, the inclusion of testate amoebae as an indicator of surface hydrological conditions has significantly improved interpretation of the hydrological history of Loboi wetland. The stratigraphic record from Loboi indicates that between ~1100 and 1470 C.E. (Medieval Climatic Anomaly) dry conditions dominated the Loboi region, except for a brief period of wetter conditions between ~1275 and 1345 C.E. Seasonally wetter conditions began to persist between ~1470 and 1630 C.E. Wetland sediments developed after this time as reflected by the sequestration of carbon in the sedimentary record. Recent historic biological and sedimentary proxies reflect increased agrarian impacts on the landscape surrounding Loboi.

Cancer stem cells (CSC) are a distinct subpopulation within a tumor shown to drive tumor progression, metastasis, and recurrence. A review of the literature reveals poor consensus, with the use of a wide variety of surface markers and functional assays to identify and isolate cancer stem cells. Utilizing a novel technology that enables live-cell mRNA quantitation, we have demonstrated the ability to identify and sort viable CSC based on markers associated with stemness in pluripotent cells. Fresh tumor samples from a variety of cancer types were examined by flow cytometry for Nanog expression. Levels of CSC detected ranged from 6% to 19%. This method of CSC detection was cross-validated with other commonly used surface markers with good correlation. Matrigel invasion assays confirmed that CSC isolated using this method are both highly motile and invasive. This approach simplifies the process of identifying viable CSC from fresh tumor tissue, providing a level of accuracy not previously available. This method may also provide a valuable tool for screening and validating new CSC biomarkers.

Background There is growing concern that residents are not receiving the necessary experience to become proficient with medical procedures. We created a structured curriculum to improve resident comprehension, experience and confidence with pediatric procedures. Methods A two-week procedure curriculum commenced with a three-day training course to review 26 pediatric procedures using lectures, videos, demonstrations and simulations. Residents spent the remainder of the rotation as the hospital's on-call procedure resident. Pre- and post-rotation surveys, knowledge testing and procedure logging were used to evaluate course effectiveness, along with follow up metrics a year after completing the rotation. Results were compared to a control group of residents completing their second year of residency who did not participate in the curriculum. Results Participants (N = 35) averaged 67.2 procedures over the 2 weeks, compared to 41.3 procedures for controls (N = 20) during their first 2 years of residency. Participants had a higher confidence than controls (3.0 vs. 2.5 on a five-point scale) and better knowledge (65% vs. 47% correct on testing), both statistically significant. Compared to their own individual pre-rotation scores, participants showed improved knowledge (49% vs. 65%) and confidence (2.0 vs. 3.0), both statistically significant. Long-term follow up showed that these improvements were mostly sustained a year later. Conclusions Overall, interns completing the rotation demonstrated procedure counts, knowledge levels, and confidence greater than rising third year residents. Participants were inclined to have superior confidence in procedures where higher procedure counts were achieved. Most results were sustained over the course of one year.

Recently, we have shown that CXCL12/CXCR4 signaling plays an important role in gemcitabine resistance of pancreatic cancer (PC) cells. Here, we explored the effect of gemcitabine on this resistance mechanism. Our data demonstrate that gemcitabine induces CXCR4 expression in two PC cell lines (MiaPaCa and Colo357) in a dose- and time-dependent manner. Gemcitabine-induced CXCR4 expression is dependent on reactive oxygen species (ROS) generation because it is abrogated by pretreatment of PC cells with the free radical scavenger N-acetyl-L-cysteine. CXCR4 up-regulation by gemcitabine correlates with time-dependent accumulation of NF-κB and HIF-1α in the nucleus. Enhanced binding of NF-κB and HIF-1α to the CXCR4 promoter is observed in gemcitabine-treated PC cells, whereas their silencing by RNA interference causes suppression of gemcitabine-induced CXCR4 expression. ROS induction upon gemcitabine treatment precedes the nuclear accumulation of NF-κB and HIF-1α, and suppression of ROS diminishes these effects. The effect of ROS on NF-κB and HIF-1α is mediated through activation of ERK1/2 and Akt, and their pharmacological inhibition also suppresses gemcitabine-induced CXCR4 up-regulation. Interestingly, our data demonstrate that nuclear accumulation of NF-κB results from phosphorylation-induced degradation of IκBα, whereas HIF-1α up-regulation is NF-κB-dependent. Lastly, our data demonstrate that gemcitabine-treated PC cells are more motile and exhibit significantly greater invasiveness against a CXCL12 gradient. Together, these findings reinforce the role of CXCL12/CXCR4 signaling in gemcitabine resistance and point toward an unintended and undesired effect of chemotherapy.

Objective To determine whether rural residents were at a disadvantage compared with urban residents with regard to the receipt of curative therapy for prostate cancer. Materials and Methods Using the Breast and Prostate Cancer Data Quality and Patterns of Care Study II, patients with prostate cancer who were diagnosed in 2004 were identified. Registrars reviewed the medical records of randomly selected patients with incident prostate cancer (n = 1906). The patients' residential address was geocoded and linked to the census tract from the 2000 U.S. Census. The place of residence was defined as rural or nonrural according to the census tract and rural-urban commuting area categorization. The distance from the residence to the nearest radiation oncology facility was calculated. The odds ratio and 95% confidence intervals associated with receipt of noncurative treatment was calculated from logistic regression models and adjusted for several potential confounders. Results Of the incident patients, 39.1% lived in urban census tracts, 41.5% lived in mixed tracts, and 19.4% lived in rural tracts. Hormone-only or active surveillance was received by 15.4% of the patients. Relative to the urban patients, the odds ratio for noncurative treatment was 1.01 (95% confidence interval 0.59-1.74) for those living in mixed tracts and 0.96 (95% confidence interval 0.52-1.77) for those living in rural tracts. No association was found for noncurative treatment according to the Rural-Urban Commuting Area categorization. The linear trend was null between noncurative treatment and the distance to nearest radiation oncology facility (P = .92). Conclusion The choice of curative treatment did not significantly depend on the patient's place of residence, suggesting a lack of geographic disparity for the primary treatment of prostate cancer.

Purpose The purpose of this survey was to test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and nonacademic US institutions. Methods and Materials A total of 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures such as the use of prescription doses ≥ 75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. Results Among the 354 patients treated with EBRT, the beam energy was recorded in 353 patients. One hundred sixty-seven patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16-23 MV. For intermediate- plus high-risk patients (n = 181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n = 9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85 of 354), weekly electronic portal imaging was obtained as verification films without daily target localization, and the remaining 76% were treated with daily localization of the target using various methods. Conclusions Adherence to defined quality indicators was observed in a majority of patients. Approximately 90% of high-risk patients were treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients received prescription doses ≥75 Gy, consistent with the published results of randomized trials.

Purpose We report on quality of dose delivery to target and normal tissues from low-dose-rate prostate brachytherapy using postimplantation dosimetric evaluations from a random sample of U.S. patients. Methods and Materials Nonmetastatic prostate cancer patients treated with external beam radiotherapy or brachytherapy in 2007 were randomly sampled from radiation oncology facilities nationwide. Of 414 prostate cancer cases from 45 institutions, 86 received low-dose-rate brachytherapy. We collected the 30-day postimplantation CT images of these patients and 10 test cases from two other institutions. Scans were downloaded into a treatment planning system and prostate/rectal contours were redrawn. Dosimetric outcomes were reanalyzed and compared with calculated outcomes from treating institutions. Results Median prostate volume was 33.4 cm3. Reevaluated median V100, D90, and V150 were 91.1% (range, 45.5–99.8%), 101.7% (range, 59.6–145.9%), and 53.9% (range, 15.7–88.4%), respectively. Low gland coverage included 27 patients (39%) with a D90 lower than 100% of the prescription dose (PD), 12 of whom (17% of the entire group) had a D90 lower than 80% of PD. There was no correlation between D90 coverage and prostate volume, number of seeds, or implanted activity. The median V100 for the rectum was 0.3 cm3 (range, 0–4.3 cm3). No outcome differences were observed according to the institutional strata. Concordance between reported and reevaluated D90 values (defined as within ±10%) was observed in 44 of 69 cases. Conclusions Central review of postimplantation CT scans to assess the quality of prostate brachytherapy is feasible. Most patients achieved excellent dosimetric outcomes, yet 17% had less than optimal target coverage by the PD. There was concordance between submitted target-coverage parameters and central dosimetric review in 64% of implants. These findings will require further validation in a larger cohort of patients.

Recent evidence suggests a major role of tumor-stromal interactions in pancreatic cancer pathobiology. The chemokine CXCL12 (stromal cell-derived factor 1 (SDF-1)), abundantly produced by stromal cells, promotes progression, metastasis, and chemoresistance of pancreatic cancer cells. On the other hand, pancreatic tumor cell-derived sonic hedgehog (SHH) acts predominantly on stromal cells to induce desmoplasia and, thus, has a paracrine effect on tumorigenesis and therapeutic outcome. In this study, we examined the association between these two proteins of pathological significance in pancreatic cancer. Our data demonstrate that CXCL12 leads to a dose- and time-dependent up-regulation of SHH in pancreatic cancer cells. CXCL12-induced SHH up-regulation is specifically mediated through the receptor CXCR4 and is dependent on the activation of downstream Akt and ERK signaling pathways. Both Akt and ERK cooperatively promote nuclear accumulation of NF-κB by inducing the phosphorylation and destabilization of its inhibitory protein, IκB-α. Using dominant negative IκB-α, a SHH promoter (deletion mutant) reporter, and chromatin immunoprecipitation assays, we demonstrate that CXCL12 exposure enhances direct binding of NF-κB to the SHH promoter and that suppression of NF-κB activation abrogates CXCL12-induced SHH expression. Finally, our data demonstrate a strong correlative expression of CXCR4 and SHH in human pancreatic cancer tissues, whereas their expression is not observed in the normal pancreas. Altogether, our data reveal a novel mechanism underlying aberrant SHH expression in pancreatic cancer and identify a molecular link facilitating bidirectional tumor-stromal interactions.

Alzheimer disease (AD) is a neurodegenerative disorder characterized histopathologically by the presence of senile plaques (SPs), neurofibrillary tangles, and synapse loss. The main component of SPs is amyloid-β peptide (Aβ), which has been associated with increased oxidative stress, leading to oxidative modification of proteins and consequently to neurotoxicity and neurodegeneration. Low-density lipoprotein receptor-related protein 1 (LRP1) is the primary moiety responsible for the efflux of Aβ from the brain to the blood across the blood-brain barrier. Impaired brain-to-blood transport of Aβ by LRP1 has been hypothesized to contribute to increased levels of Aβ in AD brain. The cause of LRP1 dysfunction is unknown, but we have hypothesized that Aβ oxidizes LRP1, thus damaging its own transporter. Consistent with this notion, we report in this study a significant increase in the levels of the lipid peroxidation product 4-hydroxy-2-nonenal bound to transmembrane LRP1 in AD hippocampus. In contrast, the levels of LRP1-resident 3-nitrotyrosine did not show a significant increase in AD hippocampus compared to age-matched controls. Based on this study, we propose that Aβ impairs its own efflux from the brain by oxidation of its transporter LRP1, leading to increased Aβ deposition in brain, thereby contributing to subsequent cognitive impairment in AD.

We investigated the effect of ethanol on skeletal muscle development using C2C12 cell culture. The ethanol concentrations of 10 mM, 25 mM, and 100 mM, were tested because plasma samples of alcohol-dependent individuals fall within this range. We assessed two specific events in skeletal muscle development, the fusion of myoblasts to form myotubes and the acetylcholine receptor (AChR) clustering associated with neuromuscular synapse formation. We report that ethanol does not effect myotube formation or the viability of myoblasts or myotubes in C2C12 cell culture. However, ethanol does effect AChR clustering on C2C12 myotubes. As motor neurons approach skeletal muscle during development, agrin is released by motor neurons and induces AChR clustering on muscle fibers. In our experiments, agrin was applied to cell cultures during the period when myoblasts fuse to form myotubes. In cell cultures exposed to ethanol during myotube formation, agrin-induced AChR clustering was decreased compared to untreated cultures. In cell cultures exposed to ethanol during myoblast proliferation, with ethanol removed during myotube formation, agrin-induced AChR clustering was unaffected. We conclude that exposure to a physiologically relevant concentration of ethanol during the specific period of myotube formation decreases agrin-induced AChR clustering.

Purpose Quality Research in Radiation Oncology ™ (QRRO ™ ) has embarked on a new national process survey to provide benchmark data that will allow radiation oncologists to assess the quality of care in their own practices by measuring quality indicators (QIs) and comparing individual with national practice. Methods Investigators at QRRO developed QIs on the basis of nationally recognized, evidence-based guidelines such as those of the National Comprehensive Cancer Network, as well as additional emerging QIs for processes involving rapidly emerging technology. They specifically defined the QIs as clinical performance measures. Published results of the national survey database for patients treated in 1998 and 1999 were reviewed and additional analyses conducted to assess data adequacy to measure compliance with these clinical performance measures. Results Examples of workup QIs for breast cancer patients showed that 97% underwent diagnostic bilateral mammography, 96% underwent pathology reviews, 83% underwent the determination of estrogen receptor status, 81% underwent the determination of progesterone receptor status, and 31% underwent the determination of human epidermal growth factor receptor 2 status. Compliance with treatment QIs for field recommendations on the basis of nodal findings can be measured. Of patients with prostate cancer, 90% underwent digital rectal examinations, 99% underwent prostate-specific antigen tests, and 99% had their Gleason scores determined. Compliance with QIs on the basis of prognostic group can also be measured. Conclusions Benchmarking utilization patterns provides a foundation for assessing the appropriateness of cancer care in the future. The QRRO database is a rich data source, and the new survey will provide contemporary benchmark data for these measures.

Alzheimer's disease (AD) brains are characterized by accumulation of amyloid beta protein (Abeta) and neuroinflammation. Increased blood-to-brain influx and decreased brain-to-blood efflux across the blood-brain barrier (BBB) have been proposed as mechanisms for Abeta accumulation. Epidemiological studies suggest that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the progression of AD. We hypothesized that inflammation alters BBB handling of Abeta. Mice treated with lipopolysaccharide (LPS) had increased brain influx and decreased brain efflux of Abeta, recapitulating the findings in AD. Neither influx nor efflux was mediated by LPS acting directly on BBB cells. Increased influx was mediated by a blood-borne factor, indomethacin-independent, blocked by the triglyceride triolein, and not related to expression of the blood-to-brain transporter of Abeta, RAGE. Serum levels of IL-6, IL-10, IL-13, and MCP-1 mirrored changes in Abeta influx. Decreased efflux was blocked by indomethacin and accompanied by decreased protein expression of the brain-to-blood transporter of Abeta, LRP-1. LPS paradoxically increased expression of neuronal LRP-1, a major source of Abeta. Thus, inflammation potentially increases brain levels of Abeta by three mechanisms: increased influx, decreased efflux, and increased neuronal production.

The risk of developing neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) increases with age. AD and PD are the two most common neurodegenerative diseases that currently affect millions of persons within the United States population. While many clues about the mechanisms of these disorders have been uncovered, to date, the molecular mechanisms associated with the cause of these diseases are not completely understood. Furthermore, there are no available cures or preventive treatments for either disorder. Animal models of AD and PD, though not perfect, offer a means to gain knowledge of the basic biochemistry associated with these disorders and with drug efficacy. The field of proteomics which focuses on identifying the dynamic nature of the protein content expressed within a particular cell, tissue, or organism, has provided many insights into these disturbing disorders. Proteomic studies have revealed many pathways that are associated with disease pathogenesis and that may lead to the development of potential therapeutic targets. This review provides a discussion of key findings from AD and PD proteomics-based studies in various animal models of disease.

A wide range of rhizoliths occurs around the margins of Lake Bogoria, Kenya. These include root casts, moulds, tubules, rhizocretions, and permineralised root systems. These rhizoliths are variably composed of opaline silica, calcite, zeolites (mainly analcime), fluorite, and possibly fluorapatite, either alone or in combinations. Some rhizoliths are infilled moulds with detrital silicate grains. Most rhizoliths are in situ, showing both vertical and horizontal orientations. Reworked rhizoliths have been concentrated locally to form dense rhizolites. Hot-spring fluids, concentrated by evapotranspiration and capillary evaporation, have provided most of the silica for the permineralisation of the plant tissues. Precipitation involved the growth of silica nanospheres and microspheres that coalesced into homogeneous masses. Calcite rhizoliths formed following evaporative concentration, evapotranspiration, and (or) CO2 degassing of Ca-bearing runoff water that infiltrated the sediment, or by mixing of runoff with saline, alkaline groundwater. Fluorite precipitated in areas where mixing of hot-spring and meteoric waters occurred, or possibly where hot-spring fluids came into contact with pre-existing calcite. Zeolitic rhizoliths formed during a prolonged period of aridity, when capillary rise and evaporative pumping brought saline, alkaline waters into contact with detrital silicate minerals around roots.

Geometry compression is the coding of 3D geometric data in a form that requires less space to store and less bandwidth to transmit. This 3D geometric data provides a computer graphics system with the scene description necessary to render images. Geometric data is quite large and, therefore, needs effective compression methods to decrease the transmission and storage requirements. A large amount of research has been focused on static geometry compression, but only limited research has addressed animated geometry compression, the compression of temporal sequences of geometric data. The goal of this paper is to represent 3D animation sequences with a reduced set of motion vectors that take advantage of the large data coherence in space and time. We proposed an octree-based motion representation method in which a small set of motion vectors are generated for each frame by analyzing the motion between consecutive frames. The vectors represent the differential motion from a previous frame to the current frame and are used to predict the vertex positions for the new frame. The octree motion representation process generates a hierarchical octree structure for each frame in the sequence. The octree approach can represent 3D animated sequences with high compression factors while maintaining reasonable quality. This approach is easy to implement and have a low cost encoding process and a fast decoding process, which make it very suitable for real time application.

Purpose To determine the national surgical practice patterns of care for operable lung cancer patients treated with radiation. Materials and Methods A nationwide survey of a stratified random sample of institutions was conducted for patients who had non-metastatic lung cancer, Karnofsky Performance Scores (KPS) ≥60, and who had received radiation therapy as definitive or adjuvant treatment. Among 541 patients, representing a weighted sample size of 42,335 patients nationwide, 131 (19.8%) underwent surgery as part of their therapy. Pearson χ 2 statistics were used to analyze characteristics of this subset of patients. Results Of the 131 patients who underwent surgery, 126 patients who had non-small cell lung cancer (NSCLC) were analyzed. Surgical patients were younger, had less weight loss, higher KPS, and higher forced expiratory volume within 1 second (FEV1) values than those treated without surgery. Surgical patients had more stage I/II (53.5% vs 32.2%; p = 0.0004) and less clinical N2/N3 disease (28.8% vs 47.5%; p = 0.002) than nonsurgical patients. Surgery consisted of lobectomy or bilobectomy in 63.2% of patients, pneumonectomy in 23.5%, and wedge resection in 5.9%. Of the patients, 80.4% received radiation in the adjuvant setting and 9.9% in the neoadjuvant setting. Conclusions Patients with non-metastatic lung cancer who are treated surgically and with radiation have clinically less advanced disease than those treated with radiation alone. Most radiation therapy in this setting is administrated postoperatively and secondary to hilar and/or mediastinal nodal involvement undetected before surgery. Improved preoperative nodal staging and neoadjuvant approaches may alter these practice patterns.

The quality of cancer care in the United States should be better than it is. Society has demanded improvement, but much work remains to be done to define and measure both the current quality of care and the steps needed to optimize such care. Various public and private organizations are directing early efforts toward attempts to determine the quality of selected oncology services as a first step in a broad-based quality improvement process. In contrast, the ACR Patterns of Care Study (PCS) for over 30 years has relied on exemplary voluntary engagement by American radiation oncologists in critical self-assessment and self-improvement as a highly effective pathway to improved practice quality. This article provides an overview of the documented historical and recent impact of PCS research findings on practice and describes the deliberate adaptation of the PCS identity and methodology to the quality-sensitive national environment with the new project name Quality Research in Radiation Oncology. The article concludes with a discussion of the rationale for continuing this unique quality improvement initiative and some of the challenges to this imperative that are being faced.

The effects of two major forms of prolactin (PRL) were examined on delayed type hypersensitivity (DTH) responses to Candida albicans . Unmodified PRL (U-PRL) had no effect on the DTH response, whereas a molecular mimic of phosphorylated PRL (S179D PRL) significantly inhibited immune responses to this robust antigen. This effect of S179D PRL was not accompanied by gross alterations in splenic T cell numbers, CD4 / CD8 ratios, or T and B cell activation markers, but did produce a decrease in splenocyte apoptosis. Using gld animals, Fas ligand (FasL) was implicated in the suppressive effects of S179D PRL. Circulating IgG 1 and IgG 2 antibody levels were increased in response to treatment with both forms of PRL, but the effects of S179D PRL were most pronounced. Cytokine changes in the popliteal lymph nodes specific to S179D PRL treatment showed an inhibition of pro-inflammatory cytokines. In conclusion, mice treated with a molecular mimic of phosphorylated prolactin showed a profound inhibition of DTH responses to Candida correlating with an absence of GM-CSF, IL-4, and IL-13 production and a marked reduction in IL-12p70 synthesis.

Background Physical education (PE) lessons and leisure-time represent two important opportunities for adolescents to accumulate moderate-to-vigorous physical activity (MVPA). Purpose Framed by self-determination theory, this study investigated how much of the observed variation in adolescent boys' MVPA levels (during PE and leisure-time) was explained by individual- and class-level motivation. Methods Cross-sectional design. Adolescent boys (N = 61, M = 14.36 years, SD = .48 years) completed motivation questionnaires and wore an accelerometer during a PE lesson and across 7 consecutive days. Results Self-determined motivation toward PE predicted MVPA during PE lessons ( R 2 = .31). Self-determined motivation toward leisure-time physical activity was positively associated with MVPA during leisure-time ( R 2 = .08). Conclusions Findings support the tenets of self-determination theory and suggest that motivation may be an important correlate of adolescent boys' MVPA in PE lessons and during leisure-time. Also, results indicated that teachers' behavior may be an important determinant of MVPA in PE lessons, while individual motivation may be more important in leisure-time.

Purpose: To determine the impact of research findings and evolving technology on the patterns of radiotherapy practice for patients with carcinoma of the uterine cervix. Methods and Materials: Sixty-two radiation therapy facilities participated in the study after having been selected from a random sample, proportionally stratified according to practice type, of all United States facilities. Each facility submitted a list of patients treated during 1992–1994 with radiation for squamous carcinoma of the cervix. Cases for review were randomly selected from each institution after excluding those of patients who had distant metastases or initial hysterectomy. A total of 471 patients’ records were reviewed in the treating institutions to obtain information about patients’ characteristics, diagnostic evaluation, tumor extent, treatment approach, and radiotherapy techniques. Results: Of the 61 facilities that treated eligible cases of intact cervical cancer during the 3-year survey period, 35 (57%) treated fewer than three eligible patients per year. Thirty-four (83%) of 41 non-academic facilities vs. 1 (5%) of 20 academic facilities treated fewer than three patients per year. FIGO stages were I, II, III, and IV in 32%, 40%, 24%, and 3% of patients, respectively. Computed tomography (CT) was the most common method of lymph node evaluation, but surgical evaluation, which was performed in 76 (16%) patients, had increased from previous surveys. Fields were designed using a dedicated simulator in 95% of patients; a dedicated CT unit was used for treatment planning in 119 (30%) cases. External beam irradiation was most often given using a four-field technique at 180 cGy per day on a 10–20 MV linear accelerator. The average daily fraction size had decreased from previous surveys, and 13% of patients were treated with daily doses of 170 cGy or less. Most patients were treated with a combination of external beam and low dose-rate (LDR) intracavitary irradiation. Of 425 patients who had treatment with curative intent that included brachytherapy, 362 (85%) had LDR brachytherapy, 45 (11%) had high dose-rate (HDR) brachytherapy, 3 had a combination of HDR and LDR, and 15 had incomplete information about the brachytherapy dose-rate. Forty-six (23%) of 197 patients with Stages I–IIA disease were treated with radiation followed by extrafascial hysterectomy. Of 111 patients treated with curative intent for Stage III–IV disease, 72 (65%) had a combination of external beam and intracavitary radiation therapy, 22 (20%) had external beam plus interstitial brachytherapy, and 17 (15%) were treated with external beam irradiation only. For patients who completed treatment with curative intent and did not have adjuvant hysterectomy or HDR brachytherapy, the median total dose at point A was 82.5 Gy. For all patients who completed treatment with radiation alone, the median total duration of treatment was 63 days; more than 70 days were taken to complete treatment in 33% of cases. Twenty-nine percent of patients received chemotherapy, usually concurrent with their radiation therapy. Only 27% of these patients were on investigational protocols. Conclusions: Greater participation in well-designed prospective trials might help clinicians address important clinical questions and reduce current inconsistencies in the use of adjuvant treatments. Radiation oncologists should take steps to avoid unnecessary treatment protraction and to improve patient compliance. Future studies will be needed to determine whether the small number of cases being treated in most nonacademic facilities will influence the outcome for patients with invasive cervical carcinoma.

Purpose The Patterns of Care Study performed this first known practice survey to establish a national profile of the delivery of postmastectomy radiotherapy (RT) in operable breast cancer. Methods and materials A Patterns of Care Study research associate collected data from 55 randomly selected institutions. The survey data included 132 items describing the patient, pathologic features, and treatment course for patients with clinical Stage I, II, and IIIA breast cancer undergoing postmastectomy RT in 1998 and 1999. A multivariate analysis was performed to determine the impact of tumor factors and type of treatment facility on the radiation fields used. Results A weighted sample size of 13,720 was obtained from a sampling of 405 patient records. The mean tumor size was 3.5 cm, and the mean number of axillary nodal metastases was 4.55. Lymphatic vascular invasion was noted in 34%, microscopic skin or dermal lymphatic invasion in 16%, positive or close margins in 36%, and extracapsular nodal extension in 23%. Radiotherapy included the chest wall in all cases and the regional nodes in 78%. When nodal RT was delivered, it included a supraclavicular field, supplemental axillary field, and/or an internal mammary field in 98%, 46%, and 23% of cases, respectively. Chest wall and supraclavicular RT was delivered in >90% of instances with 6-MV photons to doses between 45 and 50 Gy. More variation was seen in the delivery of the axillary and internal mammary RT. On multivariate analysis, the presence of four or more positive nodes and treatment at a large-volume facility were the factors most frequently associated with the use of regional radiation fields. Conclusion This Patterns of Care Study survey has demonstrated that breast cancer patients undergoing postmastectomy RT in 1998 and 1999 had a high proportion of factors associated with an increased risk of locoregional failure. The practice patterns established in this study provide a baseline for comparison with future survey results.

To report changing trends in external beam radiotherapy (EBRT) delivery practice for clinically localized prostate cancer as determined from the 1999 survey from the American College of Radiology National Patterns of Care Study.The 1999 survey included a weighted sample of 36,496 patient records obtained from a stratified two-stage sample of 554 patient records. Patients were surveyed from 58 institutions and were treated between January 1999 and December 1999. Of these, 36% (weighted sample size, 13,293; unweighted sample size, 162) were treated with brachytherapy with or without EBRT and 64% (weighted sample size, 23,203; unweighted sample size, 392) were treated with EBRT only. The latter group is the subject of this report. The following trends in clinical practice were analyzed according to prognostic risk groups and other variables and compared with the results of the prior surveys: use of androgen deprivation therapy (ADT) in combination with EBRT, higher prescription dose levels, and administration of elective whole pelvic RT (WPRT).The incidence of ADT use for favorable, intermediate, and unfavorable-risk groups was 31%, 54%, and 79%, respectively. A multivariate logistic regression analysis revealed a statistically significantly increased likelihood of intermediate (p = 0.001) and unfavorable (p0.0001) risk groups treated with ADT in conjunction with EBRT compared with favorable-risk patients. ADT use was more prevalent among treated patients in the 1999 survey than in the 1994 survey (51% vs. 8%, p0.0001). Compared with the prior survey, a greater percentage of patients were treated with higher radiation doses in the 1999 survey (or =72 Gy, 45% in 1999 vs. 3% in 1994, p0.0001). In the 1999 survey, the proportion of patients with favorable, intermediate, and unfavorable tumors treated to dosesor =72 Gy was 43%, 38%, and 60%, respectively, compared with 4%, 3%, and 1%, respectively, in the 1994 survey. Compared with the 1994 survey, a large increase in the number of patients treated with brachytherapy (36% vs. 3%, p0.0001). The frequency of WPRT use decreased from 92% in 1989 to 52% in 1994 to 23% in 1999. For the 1999 survey, a multivariate analysis indicated that unfavorable-risk patients (p = 0.016) and intermediate-risk patients (p = 0.018) were more likely to be treated with WPRT compared with favorable-risk patients. Nevertheless, even among unfavorable-risk patients, a substantial decline had occurred in the use of WPRT for the 1999 survey (70% for the 1994 survey compared with the 31% for the current survey; p = 0.003).The significantly increased use of ADT for high-risk patients and higher radiation doses, especially for intermediate- and high-risk patients, reflects the penetration and growing acceptance of clinical trial results that have demonstrated the efficacy of these treatment approaches. The relatively high proportion of favorable-risk patients treated with high radiation dose levels was greater than expected. A large increase in brachytherapy was observed compared with prior surveys. Most treated patients with high-risk disease did not undergo elective WPRT, which likely reflects the influences of prior trials, stage migration, and the commonly held belief that WPRT provides minimal benefit in the setting of higher radiation doses.

Endothelial cells are the primary targets of circulating immune and inflammatory mediators. We hypothesize that interleukin-18, a proinflammatory cytokine, induces endothelial cell apoptosis. Human cardiac microvascular endothelial cells (HCMEC) were treated with interleukin (IL) 18. mRNA expression was analyzed by ribonuclease protection assay, protein levels by immunoblotting, and cell death by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter analysis. We also investigated the signal transduction pathways involved in IL-18-mediated cell death. Treatment of HCMEC with IL-18 increases 1) NF-kappaB DNA binding activity; 2) induces kappaB-driven luciferase activity; 3) induces IL-1beta and TNF-alpha expression via NF-kappaB activation; 4) inhibits antiapoptotic Bcl-2 and Bcl-X(L); 5) up-regulates proapoptotic Fas, Fas-L, and Bcl-X(S) expression; 6) induces fas and Fas-L promoter activities via NF-kappaB activation; 7) activates caspases-8, -3, -9, and BID; 8) induces cytochrome c release into the cytoplasm; 9) inhibits FLIP; and 10) induces HCME cell death by apoptosis as seen by increased annexin V staining and increased levels of mono- and oligonucleosomal fragmented DNA. Whereas overexpression of Bcl-2 significantly attenuated IL-18-induced endothelial cell apoptosis, Bcl-2/Bcl-X(L) chimeric phosphorothioated 2'-MOE-modified antisense oligonucleotides potentiated the proapoptotic effects of IL-18. Furthermore, caspase-8, IKK-alpha, and NF-kappaB p65 knockdown or dominant negative IkappaB-alpha and dominant negative IkappaB-beta or kinase dead IKK-beta significantly attenuated IL-18-induced HCME cell death. Effects of IL-18 on cell death are direct and are not mediated by intermediaries such as IL-1beta, tumor necrosis factor-alpha, or interferon-gamma. Taken together, our results indicate that IL-18 activates both intrinsic and extrinsic proapoptotic signaling pathways, induces endothelial cell death, and thereby may play a role in myocardial inflammation and injury.

This research examines the mean grain size characteristics, organic carbon content, C/N ratios, and δ13C and δ15N values preserved in Hong Kong marine sediments, and presents data on local sedimentation rates. Studies of piston and gravity cores from four contrasting regions demonstrate a distinct change in sedimentation from the late 15th to early 16th centuries. Particle sizes are stable in older deposits, but become coarser at discrete intervals in younger sequences. Organic matter signatures are also generally stable in the lower parts of cores, but show distinct variability in more recent deposits. The increased variability in the parameters measured commences at about the same depth within individual cores. Organic carbon percentages vary between sites and through time, increasing by up to 40% locally. C/N ratios rise toward the top of some cores, but decrease in others. δ13C values tend to be elevated in the upper sediment sequences, but often decline in the near-surface layers. δ15N shows greater contrasts between cores than δ13C, especially in the Deep Bay area. Sedimentation rates vary spatially and increased through the 20th century, with particularly fast rates having occurred in recent decades. It is suggested that these changes in marine sedimentation reflect, in part, human impacts on land. The onset of organic matter variability pre-dates urbanisation, and possibly reflects farming and/or deforestation. Later changes appear to coincide with rapid urbanisation, industrialisation, and reclamation.

Proapoptotic gene transfer to promote death or to augment killing by DNA-damaging agents represents a promising strategy for cancer therapy. We have constructed an adenoviral Tet-Off trade mark vector with tightly controlled expression of Bid (Ad-Bid) (Clontech, Palo Alto, CA). Using the non-small cell lung cancer cell lines H460, H358, and A549, low dose Ad-Bid was shown to induce high levels of full-length Bid as well as caspase-3 and -9 activity. Although only a small fraction of Bid was processed to truncated Bid (a step inhibited by benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone), Ad-Bid gene transfer resulted in mitochondrial changes consistent with apoptosis (mitochondrial depolarization, cytochrome c release), DNA fragmentation, and a dramatic loss of cell viability. The proapoptotic effects of Ad-Bid were independent of p53 status and were augmented markedly by caspase-8 activators such as the DNA-damaging agent cisplatin. When Ad-Bid and cisplatin were used together, chemosensitivity was restored in p53-null H358 cells, increasing death from 35% following treatment with cisplatin and Ad-LacZ to >90% death with Ad-Bid and cisplatin (Ad-Bid alone induced 50% cell death under these conditions). Ad-Bid can induce apoptosis in malignant cells and enhance chemosensitivity in the absence of p53, suggesting this approach as a potential cancer therapy.

Quasi-regression is a method of Monte Carlo approximation useful for global sensitivity analysis. This paper presents a new version, incorporating shrinkage parameters of the type used in wavelet approximation. As an example application, a black box function from machine learning is analyzed. That function is nearly a sum of functions of one and two variables and the first variable acting alone accounts for more than half of the variance.

Purpose: Over the last two decades, the chance for the cure of localized prostate cancer by radiation has been improved by the widespread use of PSA for early detection and by a number of technical advances in treatment delivery. This study was designed to determine whether the stage of presentation and the quality of radiation treatment delivered are comparable between Caucasian and minority patients nationally and within minority-rich areas. Methods and Materials: A random survey conducted for the Patterns of Care Study in Radiation Oncology of 80 facilities treating patients with radiation in the USA. Of these, 67 comprise the “National Survey” and 13 a “Minority-Rich” survey (>40% of treated patients are minorities). Nine hundred twenty-six men with localized prostate cancer were treated in 1994. Five hundred ninety-five were in the national and 331 in the minority-rich survey. The main outcome measures were the clinical features of Caucasian and minority men at presentation and technical characteristics of the treatment delivered to them. Results: African-American men presented with more advanced disease (higher-presenting PSA and T-stage) than Caucasians in both the national and the minority-rich surveys. Hispanics also presented with later disease and could be grouped with African-American men rather than Caucasians. Overall the stage and PSA at presentation was earlier than seen in the previous Patterns of Care Study survey of 1989. The quality of treatment delivered has improved since 1989, with no distinction seen between those facilities sampled nationally and those within minority-rich areas. Conclusion: African-American and Hispanic men with prostate cancer present for therapy at a later stage than Caucasian men, but when they do, the treatment received is of comparable quality.

Purpose: To determine the patterns of evaluation and treatment in the U.S. of women with early breast cancer treated with breast-conserving surgery and irradiation in 1993–94, and to compare these with a similar survey in 1983 and with the 1992 Standard for Breast Conservation Treatment. Methods and Materials: In 1995–96, 727 randomly selected records of eligible patients treated from 1993–94 at 62 facilities representative of 3 practice types were reviewed. Results: Compared with the Process Survey (PS) in 1983, patients in the 1993–94 study had an older age distribution. In the current study, 70% of patients were ≥ 50 years of age, and 69% were post-menopausal, compared with 59% ≥ 50 years of age and 49% post-menopausal in 1983 ( p = 0.0087 and Conclusion: There was an extensive shift to adherence to the 1992 standard in 1993–94, compared with the 1983 PS, although there is room for improvement in some areas.

Skin cells containing excessive ultraviolet (UV) radiation-induced DNA damage are eliminated by apoptosis that involves the p53 pathway and Fas/Fas-Ligand (Fas-L) interactions. To determine whether dysregulation of apoptosis plays a role in skin cancer development through disruption of Fas/Fas-L interactions, hairless SKH-hr1 mice were exposed to chronic UV irradiation from Kodacel-filtered FS40 lamps for 30 weeks. Their skin was analyzed for the presence of sunburn cells (apoptotic keratinocytes) and for Fas and Fas-L expression at various time points. A dramatic decrease in the numbers of morphologically identified sunburn cells and TUNEL-positive cells was detected as early as 1 week after chronic UV exposure began. After 4 weeks of chronic UV exposure, these cells were barely detectable. This defect in apoptosis was paralleled by an initial decrease in Fas-L expression during the first week of chronic UV irradiation and a complete loss of expression after 4 weeks. Fas expression, however, increased during the course of chronic UV exposure. p53 mutations were detected in the UV-irradiated epidermis as early as 1 week after irradiation began and continued to accumulate with further UV exposure. Mice exposed to chronic UV began to develop skin tumors after approximately 8 weeks, and all mice had multiple skin tumors by 24 weeks. Most of the tumors expressed Fas but not Fas-L. We conclude that chronic UV exposure may induce a loss of Fas-L expression and a gain in p53 mutations, leading to dysregulation of apoptosis, expansion of mutated keratinocytes, and initiation of skin cancer.

Purpose: To describe the relationship between socioeconomic variables and the treatment of patients with radiotherapy for cervix cancer. Methods and Materials: Sixty-two institutions were randomly selected from a list of all radiotherapy facilities in the United States. From these we randomly selected and reviewed 471 cases of squamous cell carcinoma treated during 1992 to 1994. To create an additional minority-rich sample, we randomly selected 215 additional cases from 17 randomly selected institutions that admitted > 40% minority patients. The median household income of each patient's neighborhood was determined by matching her zip code to data from the 1990 United States Census. Results: Patients who lived in low-income neighborhoods, who had only Medicaid coverage, or who were treated at large academic or minority-rich institutions tended to have a poorer initial performance status, higher-stage or bulky central disease, and a lower pretreatment hemoglobin level. Ability to complete treatment did not correlate with ethnicity or income. However, noncompliant patients tended to be treated at minority-rich institutions and were more often ≤ 40 or > 60 years old. Patients who completed definitive treatment were more likely to have had ≤ 1 low-dose-rate intracavitary implants if they were black, came from a low-income neighborhood, were covered by Medicaid or Medicare only, or were treated at a minority-rich institution. Patients who were treated in academic institutions received higher mean radiation doses to Point A (83.8 Gy) than those treated in research- or non–research-participating facilities (79.4 and 80.9 Gy, respectively; p = 0.002). Patients who received their radiation therapy in facilities that treated an average of ≤ 3 patients per year also received lower mean doses to Point A (79.1 vs. 83.0 Gy; p = 0.001). Conclusion: The treatment received by patients who belonged to minority groups, came from low-income neighborhoods, or were treated in large, minority-rich institutions differed in several respects from that of white, higher income patients. Larger, more detailed studies will be needed to clarify the reasons for these differences and to define any influence on treatment outcome.

To document national standards of care for patients receiving radiotherapy as part of curative treatment for Hodgkin's disease.A national survey was conducted of 61 institutions treating 275 patients with Stages I-III Hodgkin's disease and representing six facility type strata. Pretreatment evaluation, radiotherapy treatment parameters, and use of combined modality therapy were assessed.Ann Arbor stage for the 275 patients was as follows: IA, 69 (25%); IB, 7 (3%); IIA, 123 (45%); IIB, 36 (13%); IIIA 23 (8%), IIIB, 14 (5%); unknown, 3 (1%). Pretreatment evaluation included complete blood count for 93%, sedimentation rate in 29%, chest CT in 88%, abdominal CT scan in 87%, and bone marrow biopsy in 81%. Lymphangiograms were obtained in 50% of cases; laparotomy was performed in 46%. The yield of positive findings in the spleen at laparotomy was 6.5 % overall. Facility differences with respect to staging were seen only for the use of gallium scans, which were more commonly used in academic centers (44% vs. 15-23% elsewhere, p0.001). Radiotherapy was delivered with a linear accelerator in 94% of cases. Treatment simulation was performed for 94% and individualized blocks constructed for 95% overall; however, freestanding facilities had a lower rate of performance of these procedures (78% vs. 98-99% for simulation and 88% vs. 96-99% for customized blocking, p0.001). The mean supradiaphragmatic dose was 36.74 Gy and the mean subdiaphragmatic dose was 33.81 Gy. Planned combined modality therapy was given in 36% of patients. The use of combined modality therapy by stage was as follows: IA, 11%; IB, 43%; IIA, 30%; IIB, 68%; IIIA, 57%; IIIB, 100%. Chemotherapy was completed prior to radiation in 80% of cases and generally consisted of ABVD (32%), an alternating regimen (25%), or MOPP (22%). Among Stage I/II patients, use of chemotherapy was associated with reduced radiation doses (mean supradiaphragmatic dose 34.53 Gy vs. 38.43 Gy and mean subdiaphragmatic dose 31.27 Gy vs. 34.51 Gy), and reduced volumes of treatment (87% vs. 28% treated to one side of the diaphragm only). Laparotomy was not associated with decreased supra- or subdiaphragmatic radiation doses or decreased volumes of treatment.With the exception of gallium scans, pretreatment evaluation is relatively uniform across facility strata. Increased understanding of prognostic factors in Hodgkin's disease and greater use of planned combined modality therapy for higher risk patients appears to have contributed to a decreased use of and low yield of positive findings for laparotomy. Laparotomy was not associated with reduced radiation volumes or doses. Freestanding radiation facilities had a lower rate than other facility types for the performance of treatment simulation and customized patient blocking.

Hybrids of equidistribution and Monte Carlo methods of integration can achieve the superior accuracy of the former while allowing the simple error estimation methods of the latter. In particular, randomized (0, m , s )-nets in base b produce unbiased estimates of the integral, have a variance that tends to zero faster than 1/ n for any square integrable integrand and have a variance that for finite n is never more than e ≐2.718 times as large as the Monte Carlo variance. Lower bounds than e are known for special cases. Some very important ( t , m , s )-nets have t >0. The widely used Sobol' sequences are of this form, as are some recent and very promising nets due to Niederreiter and Xing. Much less is known about randomized versions of these nets, especially in s >1 dimensions. This paper shows that scrambled ( t , m , s )-nets enjoy the same properties as scrambled (0, m , s )-nets, except the sampling variance is guaranteed only to be below b t [( b +1)/( b −1)] s times the Monte Carlo variance for a least-favorable integrand and finite n .

We have assessed radiation therapy physics quality assurance (QA) elements in the United States and compared the results with the Patterns of Care Study (PCS) Consensus Guidelines for Treatment Planning and the American College of Radiology (ACR) Standard for Radiation Oncology Physics for External Beam Therapy. Data were obtained during PCS site visits to 73 facilities randomly selected from the 1,321 radiation therapy facilities in the United States: 21 academic, 26 hospital, and 26 freestanding. The following is a representative sample of results. The estimated national averages for facilities having QA programs for treatment planning systems, simulators, accelerators, film processors, and blocking systems are 44%, 79%, 94%, 62%, and 55%, respectively. Only 63% of facilities obtain an independent check of their accelerator calibrations from a source outside the facility. Twenty-six percent of facilities surveyed did not have in vivo dosimetry capability. These results and others in the study were compared with PCS consensus guidelines and ACR standards. This is the first such study performed in the United States, and the results establish a baseline for future studies. A recommendation for a comprehensive national physics QA study is based on deficiencies found in this study and the implementation of new technologies in radiation therapy.

This report presents results from the facilities surveys that are useful for radiation oncology practices facing the challenges of managed care. Facilities surveys collect data from the entire census of facilities practicing megavoltage radiation therapy. Data include equipment, personnel, and patient load. The data presented show that most, but not all, facilities throughout the United States are adequately equipped in terms of highest energy treatment machine, type of treatment planning computer, simulation, and quality assurance programs. The data also present the variation in percentage of new cancer cases receiving radiation therapy and repeat patients as a percentage of new radiation therapy cases by census region. The data show trends in patient load per type of personnel from 1974 to 1994, including a marked decrease in new patients per therapist. The distributions of patient load per type of personnel for academic, hospital-based, and freestanding facilities in 1994 show that academic facilities are larger and treat more patients per treatment machine. Academic facilities used more therapists per machine than other facilities.

The purpose of this article is to describe the methodology used by the Patterns of Care Study to conduct surveys of the practice of radiation oncology that not only provide national averages for process and outcome measures but also allow comparisons among important subgroups. The article describes how the sample design assures that these analyses are possible and presents methods used for data collection and analysis.

Purpose : To conduct a study of the process of treatment planning and treatment of adenocarcinoma of the rectum and sigmoid in the United States, and to compare survery results to consensus guidelines. Methods and Materials : A consensus committee developed guidelines for the radiotherapeutic management of adenocarcinoma of the rectum and sigmoid, and also developed a survey form that was used to gather data to evaluate the practice patterns for patients treated in 1989 and 1990 against the consensus guidelines. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the US: 21 academic, 26 hospital based, and 26 free standng. During the site visits, the radiotherapy records were examined by the surveyor physicist and radiation oncologist to extract and record and the required data. Data collected included items related to treatment specific parameters, including treatment planning considerations. Analyses included stratification as to the typs of institutions, academic, hospital based, or free standing. Results: For many treatment parameters there are discrepancies between the patterns of practice determined by the surveys and the consensus guidelines for radiotherapy treatment of adenocarcinoma of the rectum and sigmoid. Significant differences in practice among the stratified institution types were found in only a few parameters.

The 1989 Patterns of Care Study included treatment planning for early breast cancer. A Consensus Committee of radiation physicists and oncologists determined current guidelines and developed questionnaires to determine treatment planning and delivery processes used by the participating institutions (e.g., use of portal films). This article presents and analyzes the results of that survey.The survey included 449 respondents, distributed as follows: 136 (30%) from Strata I (academic facilities); 169 (38%) from Strata II (hospital based facilities); and 144 (32%) from Strata III (freestanding facilities). The treatment planning procedures surveyed included: whether individualized tissue compensators are used, whether inhomogeneity corrections are used in dose calculations, the use of computerized tomography, whether isodose distributions for external beam tangents and interstitial implants are generated, the use of lymphoscintigraphy, immobilization devices, simulations, portal films, etc.The survey results demonstrated that out of 305 patients from Strata I and II institutions, 237 (78%) had simulated tangential fields. Consistent with this finding is that 76% of patients from Strata I and II institutions were immobilized, while only 51% of Strata III patients were. Moreover, only 18 out of the 449 (4%) of cases did not have any type of external beam dose distribution calculated--presumably, in these cases missing tissue compensation would be unlikely. On the other hand, 41% of the Strata II, 27% of Strata III, but only 19% of Strata I (p0.0002) cases received CT. Surprisingly, 19% of the Strata I, 35% of the Strata II, and 25% of the Strata III (p = 0.0011) patients received lymphoscintigraphy, perhaps reflecting the use of wide tangents to encompass the internal mammary nodes in these patients. In terms of optimizing treatments, 74% of Strata I, 70% of Strata II, and 78% of Strata III patients had wedges used on both tangential fields, although in 5, 12, and 14%, respectively, no beam modification of any sort was used. Furthermore, it should be noted that in 7% of the Strata I, 23% of Strata II, and 37% of Strata III cases there was no attempt to reduce the divergence of the tangential fields into the lung. On the other hand, if one considers the 135 (of 449) patients where matching of the tangential and supraclavicular fields was applicable, 41% of Strata I, 22% of Strata II and 46% of Strata III patients had those fields matched in a vertical plane, which would involve sophisticated alignment procedures. Quality control of treatment delivery was high: 97% of all surveyed received portal films at least once. The use of thermoluminescent dosimetry (TLD) to measure the dose to the contralateral breast was of little interest: only 4 of the 305 Strata I and II patients received in vivo measurements.This national survey has established the patterns of treatment planning for early breast cancer. It shows a generally consistent approach-although a number of statistically significant variations have been identified.

Tumor necrosis factor receptor p75 (TNF-R p75) is a 75-kDa type I transmembrane protein expressed predominantly on cells of hematopoietic lineage. TNF-R p75 belongs to the TNF receptor superfamily characterized by cysteine-rich extracellular regions composed of three to six disulfide-linked domains. In the present report we have characterized, for the first time, the complete gene structure for human TNF-R p75, which spans approximately 43 kbp. The gene consists of 10 exons (ranging from 34 base pairs to 2.5 kilobase pairs) and nine introns (343 base pairs to 19 kilobase pairs). Consensus elements for transcription factors involved in T cell development and activation were noted in the 5'-flanking region including T cell factor-1, Ikaros, AP-1, CK-2, interleukin-6 receptor E (IL-6RE), ISRE, GAS, NF-kappaB, and Sp1. The unusual (GATA)n and (GAA)(GGA) repeats found within intron 1 may prove useful for further genome analysis within the 1p36 chromosomal locus. Characterization of the human TNF-R p75 gene structure will permit further assessment of its involvement in normal hematopoietic cell development and function, autoimmune disease, and nonrandom translocations in hematopoietic malignancies.

Soils in forests sprayed aerially with DDT in 1958-1967 have been sampled for persistence of residues at intervals since then and most recently in 1993. Results of all the samples are presented and show persistence through 30 years, with evidence of decline of residue only in the third decade. The metabolites of DDT--DDE and DDD--increased over time, each comprising about a third of total residue in 1993. Residue continues to be held in the organic mat with little evidence of movement downward to the inorganic soil horizons.

Purpose : To evaluate the influence of dose fractionation and other factors on the development of late complications in mandibular bone, muscle, and mucosa of the oral cavity after external beam radiation therapy for carcinoma of the tonsil. Methods and Materials : A retrospective analysis was made of the results in 676 patients treated with a spectrum of fractionation regimens in nine centers during the years 1976–1985. Only severe (Grades 3–4) late complications were analyzed. Purpose : With more than 5 years follow-up, it was found that total dose was a factor for all three types of compliations, but that in other respects, the radiobiology of late-(>3 months) developing mucosal ulcerations was different from that for mandibular necrosis and muscle injury. Dose per fraction was a significant factor for bone and muscle (estimated α/β values of 0.85 Gy and 3.1 Gy, respectively). By contrast, mucosa showed no influence on response from change in fraction size over the range of approximately 1.0–3.5 Gy. Complications in bone and muscle were not related to overall treatment duration, whereas there was a significant inverse relationship for mucosa breakdown. The rate of development of complications was fastest in mucosa and slowest in bone. The appearance of complications by 4 years after treatment was about 80% of those developing by 8 years in the mucosa, 66% in muscle, and about 50% in bone. The high α/β ration, inverse relationship with overall treatment duration, and faster development of mucosal complications suggests that they may develop as a consequence of earlier mucosal injury. As anticipated, adequate retrospective analysis of acute complications could not be amde even when objective criteria such as weight loss, unplanned delays in completing treatment, or hospitalizations during treatment were the measures. Field size was a significant factor for mandible complications, but not for muscle or mucosa. Conclusions : The radiobiological characteristics of bone and muscle were those characteristics of other late-responding tissues, whereas late sequelae in mucosa had radiobiological parameters similar to those for acute responses. Field size was a significant factor for bone complications but not for others.

Purpose: To conduct a survey of the proces of treatment planning for the radiation treatment of Hodgkin's Disease in the United States, and to compare survey results with consensus guidelines as determined by recognized experts. Methods and Materials: A consensus committee developed guidelines for the radiotherapeutic management of Hodgkin's Disease. A series of survey forms were designed to evaluate the standards of practice and compare these with the consensus guidelines. A total of 61 facilities divided evenly into the strata of academic, hospital based, and free standing had eligible Hodgkin's Disease cases. There were 275 eligible cases of Hodgkin's Disease. Data collected from the radiation oncology records included treatment-specific parameters such as energy, dose, blocking, and calculations, as well as treatment planning practices. Statistical analysis was performed on each data element and for all institution strata. Results: For a number of treatment parameters, there were some discrepancies noted between the current United States practice and the consensus guidelines. Some significant differences were found in practice between the stratified institution types. A representative sample of results are: the majority of Hodgkin's Disease patients are treated with x-ray energies in the recommended range, between 4 and 10 MV. Standard mantle (for upper extended field treatment) and modified spade (for lower extended field treatments) are the fields of choice for all types of facilities. The consensus guidelines recommended that dose calculations at multiple points be obtained; however, 15% of patients in the survey received only a single point calculation. Current irregular field dosimetry calculation software does not take account of inhomogeneities. Thirty percent of Hodgkin's Disease patients do not receive a gap calculation for the abutment of upper and lower extended fields. In 70% of treatment fields, no compensation is used. Very few patients receive any kind of in vivo dosimetry check. Conclusions: The survey served to verfify that, in general, Hodgkin's Disease treatment planning at all strata of institution has kept pace with recommended practice as delineated in current literature and texts. Small pockets of practice still need improvement in technique and equipment. Changes in practice were identified that can contribute to improved dose uniformity and accuracy.