CLINICAL TRIAL ENROLLMENT IN A MULTIDISCIPLINARY PROSTATE CANCER

Purpose: Clinical oncology trials are hampered by low accrual rates. Less than 5% of adult cancer patients are treated on a clinical trial. We aimed to evaluate clinical trial enrollment in our Multidisciplinary Prostate Cancer Clinic and to assess if a clinical trial initiative, introduced in 2006, increased our trial enrollment.Methods: Prostate cancer patients with non-metastatic disease who were seen in the clinic from 2004 to 2008 were included in the analysis. Men were categorized by whether they were seen before or after the clinical trial enrollment initiative started in 2006. The initiative included posting trial details in the clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with documentation of trials offered to them. Univariate and multivariate (MVA) logistic regression analysis evaluated the impact of patient characteristics and the clinical trial initiative on clinical trial enrollment.Results: The majority of the 1,370 men were white (83%), and lived within the surrounding counties or state (69.4%). Median age was 64.2 years. Seventy-three point five percent enrolled in at least one trial and 28.5% enrolled in more than one trial. Sixty-seven percent enrolled in laboratory studies, 18% quality of life studies, 13% novel studies, and 3.7% procedural studies. On MVA, men seen in later years (p < 0.0001) were more likely to enroll in trials. The proportion of men enrolling increased from 38.9% to 84.3% (p<0.0001) after the clinical trial initiative. On MVA, older men (p < 0.0001) were less likely to enroll in clinical trials. There was a trend toward men in the high-risk group being more likely to participate in clinical trials (p = 0.056). There was a second trend for men of Hispanic, Asian, Native American and Indian decent being less likely to participate in clinical trials (p = 0.054).Conclusion: Clinical trial enrollment in the multidisciplinary clinic increased after introduction of a clinical trial initiative. Older men were less likely to enroll in trials. We speculate we achieved high enrollment rates because 1) specific trials are discussed at time of treatment recommendations, 2) we provide a letter documenting offered trials and 3) we introduce patients to the research team at the same clinic visit if they are interested in trial participation.

Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function.

INTRODUCTION: The objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis. METHODS: Twenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP). RESULTS: MAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003). CONCLUSIONS: The MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.

Transforming growth factor-β and inflammation in vascular (type IV) Ehlers-Danlos syndrome.

BACKGROUND Vascular Ehlers-Danlos syndrome (VEDS) causes reduced life expectancy because of arterial dissections/rupture and hollow organ rupture. Although the causative gene, COL3A1, was identified >20 years ago, there has been limited progress in understanding the disease mechanisms or identifying treatments. METHODS AND RESULTS We studied inflammatory and transforming growth factor-β (TGF-β) signaling biomarkers in plasma and from dermal fibroblasts from patients with VEDS. Analyses were done in terms of clinical disease severity, genotype-phenotype correlations, and body composition and fat deposition alterations. VEDS subjects had increased circulating TGF-β1, TGF-β2, monocyte chemotactic protein-1, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and leptin and decreased interleukin-8 versus controls. VEDS dermal fibroblasts secreted more TGF-β2, whereas downstream canonical/noncanonical TGF-β signaling was not different. Patients with COL3A1 exon skipping mutations had higher plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and VEDS probands had abnormally high plasma C-reactive protein versus affected patients identified through family members before any disease manifestations. Patients with VEDS had higher mean platelet volumes, suggesting increased platelet turnover because of ongoing vascular damage, as well as increased regional truncal adiposity. CONCLUSIONS These findings suggest that VEDS is a systemic disease with a major inflammatory component. C-reactive protein is linked to disease state and may be a disease activity marker. No changes in downstream TGF-β signaling and increased platelet turnover suggest that chronic vascular damage may partially explain increased plasma TGF-β1. Finally, we found a novel role for dysregulated TGF-β2, as well as adipocyte dysfunction, as demonstrated through reduced interleukin-8 and elevated leptin in VEDS.

RC-NDN: Raptor Codes Enabled Named Data Networking

Information-centric networking (ICN) has been proposed to cope with the drawbacks of the Internet Protocol, namely scalability and security. The majority of research efforts in ICN have focused on routing and caching in wired networks, while little attention has been paid to optimizing the communication and caching efficiency in wireless networks. In this work, we study the application of Raptor codes to Named Data Networking (NDN), which is a popular ICN architecture, in order to minimize the number of transmitted messages and accelerate content retrieval times. We propose RC-NDN, which is a NDN compatible Raptor codes architecture. In contrast to other coding-based NDN solutions that employ network codes, RC-NDN considers security architectures inherent to NDN. Moreover, different from existing network coding based solutions for NDN, RC-NDN does not require significant computational resources, which renders it appropriate for low cost networks. We evaluate RC-NDN in mobile scenarios with high mobility. Evaluations show that RC-NDN outperforms the original NDN significantly. RC-NDN is particularly efficient in dense environments, where retrieval times can be reduced by 83% and the number of Data transmissions by 84.5% compared to NDN.

Conjoint regulation of glucagon concentrations via plasma insulin and glucose in dairy cows

Insulin and glucagon are glucoregulatory hormones that contribute to glucose homeostasis. Plasma insulin is elevated during normoglycemia or hyperglycemia and acts as a suppressor of glucagon secretion. We have investigated if and how insulin and glucose contribute to the regulation of glucagon secretion through long term (48 h) elevated insulin concentrations during simultaneous hypoglycemia or euglycemia in mid-lactating dairy cows. Nineteen Holstein dairy cows were randomly assigned to 3 treatment groups: an intravenous insulin infusion (HypoG, n = 5) to decrease plasma glucose concentrations (2.5 mmol/L), a hyperinsulinemic-euglycemic clamp to study effects of insulin at simultaneously normal glucose concentrations (EuG, n = 6) and a 0.9% saline infusion (NaCl, n = 8). Plasma glucose was measured at 5-min intervals, and insulin and glucose infusion rates were adjusted accordingly. Area under the curve of hourly glucose, insulin, and glucagon concentrations on day 2 of infusion was evaluated by analysis of variance with treatments as fixed effect. Insulin infusion caused an increase of plasma insulin area under the curve (AUC)/h in HypoG (41.9 ± 8.1 mU/L) and EuG (57.8 ± 7.8 mU/L) compared with NaCl (13.9 ± 1.1 mU/L; P < 0.01). Induced hyperinsulinemia caused a decline of plasma glucose AUC/h to 2.3 ± 0.1 mmol/L in HypoG (P < 0.01), whereas plasma glucose AUC/h remained unchanged in EuG (3.8 ± 0.2 mmol/L) and NaCl (4.1 ± 0.1 mmol/L). Plasma glucagon AUC/h was lower in EuG (84.0 ± 6.3 pg/mL; P < 0.05) and elevated in HypoG (129.0 ± 7.0 pg/mL; P < 0.01) as compared with NaCl (106.1 ± 5.4 pg/mL). The results show that intravenous insulin infusion induces elevated glucagon concentrations during hypoglycemia, although the same insulin infusion reduces glucagon concentrations at simultaneously normal glucose concentrations. Thus, insulin does not generally have an inhibitory effect on glucagon concentrations. If simultaneously glucose is low and insulin is high, glucagon is upregulated to increase glucose availability. Therefore, insulin and glucose are conjoint regulatory factors of glucagon concentrations in dairy cows, and the plasma glucose status is the key factor to decide if its concentrations are increased or decreased. This regulatory effect can be important for the maintenance of glucose homeostasis if insulin secretion is upregulated by other factors than high glucose such as high plasma lipid and protein concentrations at simultaneously low glucose.

Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study.

Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (β = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (β = -0.27 (-0.51,-0.02); β = -0.19 (-0.34,-0.05), respectively) and TNF-α (β = -0.16 (-0.30,-0.01); β = -0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (β = -0.20 (-0.39,-0.02); β = -0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs.

Selective Transport of Zinc, Manganese, Nickel, Cobalt and Cadmium in the Root System and Transfer to the Leaves in Young Wheat Plants

• Background and Aims The uptake, translocation and redistribution of the heavy metals zinc, manganese, nickel, cobalt and cadmium are relevant for plant nutrition as well as for the quality of harvested plant products. The long-distance transport of these heavy metals within the root system and the release to the shoot in young wheat (Triticum aestivum ‘Arina’) plants were investigated. • Methods After the application of 65Zn, 54Mn, 63Ni, 57Co and 109Cd for 24 h to one seminal root (the other seminal roots being excised) of 54-h-old wheat seedlings, the labelled plants were incubated for several days in hydroponic culture on a medium without radionuclides. • Key Results The content of 65Zn decreased quickly in the labelled part of the root. After the transfer of 65Zn from the roots to the shoot, a further redistribution in the phloem from older to younger leaves was observed. In contrast to 65Zn, 109Cd was released more slowly from the roots to the leaves and was subsequently redistributed in the phloem to the youngest leaves only at trace levels. The content of 63Ni decreased quickly in the labelled part of the root, moving to the newly formed parts of the root system and also accumulating transiently in the expanding leaves. The 54Mn content decreased quickly in the labelled part of the root and increased simultaneously in leaf 1. A strong retention in the labelled part of the root was observed after supplying 57Co. • Conclusions The dynamics of redistribution of 65Zn, 54Mn, 63Ni, 57Co and 109Cd differed considerably. The rapid redistribution of 63Ni from older to younger leaves throughout the experiment indicated a high mobility in the phloem, while 54Mn was mobile only in the xylem and 57Co was retained in the labelled root without being loaded into the xylem.

Circulating oxidized low-density lipoprotein is associated with echolucent plaques in the femoral artery independently of hsCRP in 61-year-old men.

OBJECTIVES The aim of the study was to test the hypothesis that circulating markers of inflammation (high-sensitive C-reactive protein, hsCRP) and oxidative modification of lipids (oxidized low-density lipoprotein, oxLDL) were associated with the occurrence of echolucent rather than echogenic femoral artery plaques in a cross-sectional population based cohort of 513, 61-year-old men. BACKGROUND The relationships between circulating oxLDL, hsCRP and the occurrence of echolucent plaques in the femoral artery have not previously been investigated. METHODS The levels of circulating oxLDL and hsCRP were determined in plasma by ELISA. Plaque occurrence, size and echogenicity were measured by B-mode ultrasound in the right femoral artery. Assessment of plaque echogenicity was based on the classification (grades 1-4) proposed by Gray-Weale et al. RESULTS A higher frequency of echolucent femoral plaques was observed in subjects with the metabolic syndrome and current smokers (p=0.01 and p<0.001, respectively) as well as with increasing levels of oxLDL and hsCRP (p=0.002 and p=0.005, respectively). In a multiple logistic regression analysis oxLDL and current smokers turned out to be independent associated with the presence of echolucent femoral artery plaques. CONCLUSIONS The results of the present study support our hypothesis that circulating oxLDL is a marker of an unstable echolucent plaque phenotype in the femoral artery in man.

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers

INTRODUCTION The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. METHODS In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. RESULTS Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 μm (95% confidence interval [CI]: 1082-1287) and increased by 93 μm (95% CI: 25-161) and 108 μm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 μm per each 10-mmHg raise in SBP at 1 year and an increase of 39 μm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. CONCLUSION Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. IMPLICATIONS Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. Our findings emphasize the importance of focusing not only on smoking cessation among smokers, but to simultaneously control other CVRFs, particularly blood pressure, in order to prevent future cardiovascular disease.

Variations of clinopyroxene/melt element partitioning during assimilation of olivine/peridotite by low-Mg diorite magma

The effects of crystal chemistry and melt composition on the control of clinopyroxene/melt element partitioning (D) during the assimilation of olivine/peridotite by felsic magma have been investigated in Mesozoic high-Mg diorites from North China. The assimilation resulted in significant increase of Mg, Cr and Ni and only slight (< 30%) decrease of incompatible elements of the magma, and the compositional variations have been mirrored by the normally and reversely zoned clinopyroxene microphenocrysts formed at the early stage of the magma evolution. The Mg# [100 × Mg / (Mg + Fe)] values of the reversely zoned clinopyroxenes increase from 65 to 75 in the core to 85–90 in the high-Mg midsection, and reduce back to 73–79 at the rim. Trace element profiles across all these clinopyroxene domains have been measured by LA-ICP-MS. The melt trace element composition has been constrained from bulk rock analyses of the fine-grained low- and high-Mg diorites. Clinopyroxene/melt partition coefficients for rare earth elements (REE) and Y in the high-Mg group zonings (Mg# > 73–79, DDy < 1.2) are positively correlated with tetrahedral IVAl and increase by a factor of 3–4 as tetrahedral IVAl increases from 0.01 to 0.1 per formula unit (pfu). These systematic variations are interpreted to be controlled by the clinopyroxene composition. In contrast, partition coefficients for low-Mg group zonings (Mg# < 75–79, DDy > 1.2) are elevated by up to an order of magnitude (for REE and Y) or more (for Zr and Hf) at similar IVAl, indicating dominant control of melt composition/structure. DZr and DHf show a larger sensitivity to the compositional change of crystal and melt than DREE. DTi values for the low- and high-Mg zonings show a uniform dependence on IVAl. DSr and DLi are insensitive to the compositional change of clinopyroxene and melt, resulting in Sr depletions in the clinopyroxene zonings with elevated REE without crystallization of plagioclase. Our observations show that crystal chemistry and melt composition/structure may alternatively control clinopyroxene/melt partitioning during the assimilation of peridotite by felsic magma, and may be useful for deciphering clinopyroxene compositions and related crust–mantle processes.

STUDIES ON THE PATTERNS OF NUCLEOTIDE AND AMINO ACID SUBSTITUTION (ELECTROPHORESIS, MUTATION RATE, SELECTION, BASE, COMPOSITION)

Theoretical and empirical studies were conducted on the pattern of nucleotide and amino acid substitution in evolution, taking into account the effects of mutation at the nucleotide level and purifying selection at the amino acid level. A theoretical model for predicting the evolutionary change in electrophoretic mobility of a protein was also developed by using information on the pattern of amino acid substitution. The specific problems studied and the main results obtained are as follows: (1) Estimation of the pattern of nucleotide substitution in DNA nuclear genomes. The pattern of point mutations and nucleotide substitutions among the four different nucleotides are inferred from the evolutionary changes of pseudogenes and functional genes, respectively. Both patterns are non-random, the rate of change varying considerably with nucleotide pair, and that in both cases transitions occur somewhat more frequently than transversions. In protein evolution, substitution occurs more often between amino acids with similar physico-chemical properties than between dissimilar amino acids. (2) Estimation of the pattern of nucleotide substitution in RNA genomes. The majority of mutations in retroviruses accumulate at the reverse transcription stage. Selection at the amino acid level is very weak, and almost non-existent between synonymous codons. The pattern of mutation is very different from that in DNA genomes. Nevertheless, the pattern of purifying selection at the amino acid level is similar to that in DNA genomes, although selection intensity is much weaker. (3) Evaluation of the determinants of molecular evolutionary rates in protein-coding genes. Based on rates of nucleotide substitution for mammalian genes, the rate of amino acid substitution of a protein is determined by its amino acid composition. The content of glycine is shown to correlate strongly and negatively with the rate of substitution. Empirical formulae, called indices of mutability, are developed in order to predict the rate of molecular evolution of a protein from data on its amino acid sequence. (4) Studies on the evolutionary patterns of electrophoretic mobility of proteins. A theoretical model was constructed that predicts the electric charge of a protein at any given pH and its isoelectric point from data on its primary and quaternary structures. Using this model, the evolutionary change in electrophoretic mobilities of different proteins and the expected amount of electrophoretically hidden genetic variation were studied. In the absence of selection for the pI value, proteins will on the average evolve toward a mildly basic pI. (Abstract shortened with permission of author.) ^

The impact of nutrition intervention on glycemic control in a pediatric type 1 diabetes mellitus population

Aim: The goal of this study was to evaluate the change in hemoglobin A1C and glycemic control after nutrition intervention among a population of type 1 diabetic pediatric patients. Methods: Data was collected from all type 1 diabetic patients who were scheduled for a consultation with the diabetes/endocrine RD from January 2006 through December 2006. Two groups were compared, those who kept their RD appointment and those who did not keep their appointment. The main outcome measure was HgbA1C. An independent samples t-test compared the two groups with respect to change in HbgA1C before and after the most recent scheduled appointment with the RD. Baseline characteristics were used as covariates and analyzed and controlled for using analysis of covariance (ANCOVA). Results: There was no difference in HgbA1c after either attending an RD appointment or not having attended an RD appointment. Those who arrived for and attended their RD appointment and those who did not arrive for and attend their RD appointment, had statistically different HgbA1C's before their scheduled appointment as well as after the RD appointment. However, the two groups were not equal at the beginning of the study period. Discussion: A study design with inclusion criteria of a specified range of HgbA1C values within which the study subjects needed to fall, would have potentially eliminated the difference between the two groups at the beginning of the study period. Conducting either another retrospective study that controlled for the initial HgbA1C value or conducting a prospective study that designated a range of HgbA1C values would be worth investigating to evaluate the impact of medical nutrition therapy intervention and the role of the RD in diabetes management. It is an interesting finding that there was a significant difference in the initial HgbA1c for those who came to the RD appointment compared to those who did not come. The fact that in this study those who did not arrive for their RD appointment had worse control of their diabetes suggests that this is a high-risk group. Targeting diabetes education toward this group of patients may prove to be beneficial. ^

Does parental monitoring influence the use of alcohol and drugs among inner city 7th grade students?

Objective. To examine associations between parental monitoring and adolescent alcohol/drug use. ^ Methods. 981 7th grade students from 10 inner-city middle schools were surveyed at the 3 month follow-up of an HIV, STD, and pregnancy prevention program. Data from 549 control subjects were used for analyses. Multinomial logistic regression was used to examine associations between five parental monitoring variables and substance use, coded as: low risk [never drank alcohol or used drugs (0)], moderate risk [drank alcohol, no drug use (1)], and high risk [both drank alcohol and used drugs or just used drugs (2)]. ^ Results. Participants were 58.3% female, 39.6% African American, 43.8% Hispanic, mean age 13.3 years. Lifetime alcohol use was 47.9%. Lifetime drug use was 14.9%. Adjusted for gender, age, race, and family structure, each individual parental monitoring variable (perceived parental monitoring, less permissive parental monitoring, greater supervision (public places), greater supervision (teen clubs), and less time spent with older teens) was significant and protective for the moderate and high risk groups. When all 5 variables were entered into a single model, only perceived parental monitoring was significantly associated (OR=0.40, 95% CI 0.29-0.55) for the moderate risk group. For the high risk group, 3 variables were significantly protective (perceived parental monitoring OR=0.28, CI 0.18-0.42, less time spent with older teens OR=0.75, CI 0.60-0.93, and greater supervision (public places) OR=0.79, CI 0.64-0.99). ^ Conclusion. The association between parental monitoring and substance abuse is complex and varied for different risk levels. Implications for intervention development are addressed. ^

Cost-effectiveness analysis of a 2-stage community-based hepatocellular carcinoma screening program in Taiwan

Hepatocellular carcinoma (HCC) has been ranked as the top cause of death due to neoplasm malignancy in Taiwan for years. The high incidence of HCC in Taiwan is primarily attributed to high prevalence of hepatitis viral infection. Screening the subjects with liver cirrhosis for HCC was widely recommended by many previous studies. The latest practice guideline for management of HCC released by the American Association for the Study of Liver Disease (AASLD) in 2005 recommended that the high risk groups, including cirrhotic patients, chronic HBV/HCV carriers, and subjects with family history of HCC and etc., should undergo surveillance.^ This study aims to investigate (1) whether the HCC screening program can prolong survival period of the high risk group, (2) what is the incremental cost-effectiveness ratio of the HCC screening program in Taiwan, as compared with a non-screening strategy from the payer perspective, (3) which high risk group has the lowest ICER for the HCC screening program from the insurer's perspective, in comparison with no screening strategy of each group, and (4) the estimated total cost of providing the HCC screening program to all high risk groups.^ The high risk subjects in the study were identified from the communities with high prevalence of hepatitis viral infection and classified into three groups (cirrhosis group, early cirrhosis group, and no cirrhosis group) at different levels of risk to HCC by status of liver disease at the time of enrollment. The repeated ultrasound screenings at an interval of 3, 6, and 12 months were applied to cirrhosis group, early cirrhosis group, and no cirrhosis group, respectively. The Markov-based decision model was constructed to simulate progression of HCC and to estimate the ICER for each group of subjects.^ The screening group had longer survival in the statistical results and the model outcomes. Owing to the low HCC incidence rate in the community-based screening program, screening services only have limited effect on survival of the screening group. The incremental cost-effectiveness ratio of the HCC screening program was $3834 per year of life saved, in comparison with the non-screening strategy. The estimated total cost of each group from the screening model over 13.5 years approximately consumes 0.13%, 1.06%, and 0.71% of total amount of adjusted National Health Expenditure from Jan 1992 to Jun 2005. ^ The subjects at high risk of developing HCC to undergo repeated ultrasound screenings had longer survival than those without screening, but screening was not the only factor to cause longer survival in the screening group. The incremental cost-effectiveness ratio of the 2-stage community-based HCC screening program in Taiwan was small. The HCC screening program was worthy of investment in Taiwan. In comparison with early cirrhosis group and no cirrhosis group, cirrhosis group has the lowest ICER when the screening period is less than 19 years. The estimated total cost of providing the HCC screening program to all high risk groups consumes approximately 1.90% of total amount of adjusted 13.5-year NHE in Taiwan.^

Whence a healthy mind: Correlation of physical fitness and academic performance among schoolchildren

Background. Public schools are a key forum in the fight for child health because of the opportunities they present for physical activity and fitness surveillance. However, because schools are evaluated and funded on the basis of standardized academic performance rather than physical activity, empirical research evaluating the connections between fitness and academic performance is needed to justify curriculum allocations to physical activity. ^ Methods. Analyses were based on a convenience sample of 315,092 individually-matched standardized academic (TAKS™) and fitness (FITNESSGRAM®) test records collected by 13 Texas school districts under state mandates. We categorized each fitness result in quintiles by age and gender and used a mixed effects regression model to compare the academic performance of the top and bottom fitness groups for each fitness test and grade level combination. ^ Results. All fitness variables except BMI showed significant, positive associations with academic performance after sociodemographic covariate adjustments, with effect sizes ranging from 0.07 (95% CI: 0.05,0.08) in girls trunklift-TAKS reading to 0.34 (0.32,0.35) in boys cardiovascular-TAKS math. Cardiovascular fitness showed the largest inter-quintile difference in TAKS score (32-75 points), followed by curl-ups. After an additional adjustment for BMI and curl-ups, cardiovascular associations peaked in 8th-9 th grades (maximum inter-quintile difference 142 TAKS points; effect size 0.75 (0.69,0.82) for 8th grade girls math) and showed dose-response characteristics across quintiles (p<0.001 for both genders and outcomes). BMI analysis demonstrated limited, non-linear association with academic performance after adjustment for sociodemographic, cardiovascular fitness and curl-up variables. Low-BMI Hispanic high school boys showed significantly lower TAKS scores than the moderate (but not high) BMI group. High-BMI non-Hispanic white high school girls showed significantly lower scores than the moderate (but not low) BMI group. ^ Conclusions. In this study, fitness was strongly and significantly related to academic performance. Cardiovascular fitness showed a distinct dose-response association with academic performance independent of other sociodemographic and fitness variables. The association peaked in late middle to early high school. The independent association of BMI to academic performance was only found in two sub-groups and was non-linear, with both low and high BMI posing risk relative to moderate BMI but not to each other. In light of our findings, we recommend that policymakers consider PE mandates in middle-high school and require linkage of academic and fitness records to facilitate longitudinal surveillance. School administrators should consider increasing PE time in pursuit of higher academic test scores, and PE practitioners should emphasize cardiovascular fitness over BMI reduction.^