Showing papers by "University of Colorado Denver published in 2006"

Costly Punishment Across Human Societies

Abstract: Recent behavioral experiments aimed at understanding the evolutionary foundations of human cooperation have suggested that a willingness to engage in costly punishment, even in one-shot situations, may be part of human psychology and a key element in understanding our sociality. However, because most experiments have been confined to students in industrialized societies, generalizations of these insights to the species have necessarily been tentative. Here, experimental results from 15 diverse populations show that (i) all populations demonstrate some willingness to administer costly punishment as unequal behavior increases, (ii) the magnitude of this punishment varies substantially across populations, and (iii) costly punishment positively covaries with altruistic behavior across populations. These findings are consistent with models of the gene-culture coevolution of human altruism and further sharpen what any theory of human cooperation needs to explain.

Parks and Peoples: The Social Impact of Protected Areas

Abstract: This review examines the social, economic, and political effects of environmental conservation projects as they are manifested in protected areas. We pay special attention to people living in and displaced from protected areas, analyze the worldwide growth of protected areas over the past 20 years, and offer suggestions for future research trajectories in anthropology. We examine protected areas as a way of seeing, understanding, and producing nature (environment) and culture (society) and as a way of attempting to manage and control the relationship between the two. We focus on social, economic, scientific, and political changes in places where there are protected areas and in the urban centers that control these areas. We also examine violence, conflict, power relations, and governmentality as they are connected to the processes of protection. Finally, we examine discourse and its effects and argue that anthropology needs to move beyond the current examinations of language and power to attend to the ways in which protected areas produce space, place, and peoples.

Right Ventricular Function and Failure Report of a National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure

Abstract: Knowledge about the role of the right ventricle in health and disease historically has lagged behind that of the left ventricle. Less muscular, restricted in its role to pumping blood through a single organ, and less frequently or obviously involved than the left ventricle in diseases of epidemic proportions such as myocardial ischemia, cardiomyopathy, or valvulopathy, the right ventricle has generally been considered a mere bystander, a victim of pathological processes affecting the cardiovascular system. Consequently, comparatively little attention has been devoted to how right ventricular dysfunction may be best detected and measured, what specific molecular and cellular mechanisms contribute to maintenance or failure of normal right ventricular function, how right ventricular dysfunction evolves structurally and functionally, or what interventions might best preserve right ventricular function. Nevertheless, even the proportionately limited information related to right ventricular function, its impairment in various disease states, and its impact on the outcome of those diseases suggests that the right ventricle is an important contributor and that further understanding of these issues is of pivotal importance. For this reason, the National Heart, Lung, and Blood Institute convened a working group charged with delineating in broad terms the current base of scientific and medical understanding about the right ventricle and identifying avenues of investigation likely to meaningfully advance knowledge in a clinically useful direction. The following summary represents the presentations and discussions of this working group. The right ventricle is affected by and contributes to a number of disease processes, including perhaps most notably pulmonary hypertension caused by a variety of lung or pulmonary vascular diseases (cor pulmonale). Other diseases affect the right ventricle in different ways, including global, left ventricular–, or right ventricular–specific cardiomyopathy; right ventricular ischemia or infarction; pulmonary or tricuspid valvular heart disease; and left-to-right shunts. The right ventricle pumps the same …

Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia.

Abstract: Background Hyponatremia (serum sodium concentration, <135 mmol per liter) is a predictor of death among patients with chronic heart failure and cirrhosis. At present, therapy for acute and chronic hyponatremia is often ineffective and poorly tolerated. We investigated whether tolvaptan, an orally active vasopressin V 2 -receptor antagonist that promotes aquaresis — excretion of electrolyte-free water — might be of benefit in hyponatremia. Methods In two multicenter, randomized, double-blind, placebo-controlled trials, the efficacy of tolvaptan was evaluated in patients with euvolemic or hypervolemic hyponatremia. Patients were randomly assigned to oral placebo (223 patients) or oral tolvaptan (225) at a dose of 15 mg daily. The dose of tolvaptan was increased to 30 mg daily and then to 60 mg daily, if necessary, on the basis of serum sodium concentrations. The two primary end points for all patients were the change in the average daily area under the curve for the serum sodium concentration from baseline to day 4 and the change from baseline to day 30. Results Serum sodium concentrations increased more in the tolvaptan group than in the placebo group during the first 4 days (P<0.001) and after the full 30 days of therapy (P<0.001). The condition of patients with mild or marked hyponatremia improved (P<0.001 for all comparisons). During the week after discontinuation of tolvaptan on day 30, hyponatremia recurred. Side effects associated with tolvaptan included increased thirst, dry mouth, and increased urination. A planned analysis that combined the two trials showed significant improvement from baseline to day 30 in the tolvaptan group according to scores on the Mental Component of the Medical Outcomes Study 12-item Short-Form General Health Survey. Conclusions In patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V 2 -receptor antagonist, was effective in increasing serum sodium concentrations at day 4 and day 30. (ClinicalTrials.gov numbers, NCT00072683 [SALT-1] and NCT00201994 [SALT-2].)

Effect of Weight Loss With Lifestyle Intervention on Risk of Diabetes

Abstract: OBJECTIVE —Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants. RESEARCH DESIGN AND METHODS —For this study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up. RESULTS —A total of 1,079 participants were aged 25–84 years (mean 50.6 years, BMI 33.9 kg/m2). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35–0.51]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence. CONCLUSIONS —Interventions to reduce diabetes risk should primarily target weight reduction.

ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression

Abstract: Dynamic regulation of diverse nuclear processes is intimately linked to covalent modifications of chromatin. Much attention has focused on methylation at lysine 4 of histone H3 (H3K4), owing to its association with euchromatic genomic regions. H3K4 can be mono-, di- or tri-methylated. Trimethylated H3K4 (H3K4me3) is preferentially detected at active genes, and is proposed to promote gene expression through recognition by transcription-activating effector molecules. Here we identify a novel class of methylated H3K4 effector domains--the PHD domains of the ING (for inhibitor of growth) family of tumour suppressor proteins. The ING PHD domains are specific and highly robust binding modules for H3K4me3 and H3K4me2. ING2, a native subunit of a repressive mSin3a-HDAC1 histone deacetylase complex, binds with high affinity to the trimethylated species. In response to DNA damage, recognition of H3K4me3 by the ING2 PHD domain stabilizes the mSin3a-HDAC1 complex at the promoters of proliferation genes. This pathway constitutes a new mechanism by which H3K4me3 functions in active gene repression. Furthermore, ING2 modulates cellular responses to genotoxic insults, and these functions are critically dependent on ING2 interaction with H3K4me3. Together, our findings establish a pivotal role for trimethylation of H3K4 in gene repression and, potentially, tumour suppressor mechanisms.

Hypoxia-Induced Pulmonary Vascular Remodeling Cellular and Molecular Mechanisms

Abstract: Chronic hypoxic exposure induces changes in the structure of pulmonary arteries, as well as in the biochemical and functional phenotypes of each of the vascular cell types, from the hilum of the lung to the most peripheral vessels in the alveolar wall. The magnitude and the specific profile of the changes depend on the species, sex, and the developmental stage at which the exposure to hypoxia occurred. Further, hypoxia-induced changes are site specific, such that the remodeling process in the large vessels differs from that in the smallest vessels. The cellular and molecular mechanisms vary and depend on the cellular composition of vessels at particular sites along the longitudinal axis of the pulmonary vasculature, as well as on local environmental factors. Each of the resident vascular cell types (ie, endothelial, smooth muscle, adventitial fibroblast) undergo site- and time-dependent alterations in proliferation, matrix protein production, expression of growth factors, cytokines, and receptors, and each resident cell type plays a specific role in the overall remodeling response. In addition, hypoxic exposure induces an inflammatory response within the vessel wall, and the recruited circulating progenitor cells contribute significantly to the structural remodeling and persistent vasoconstriction of the pulmonary circulation. The possibility exists that the lung or lung vessels also contain resident progenitor cells that participate in the remodeling process. Thus the hypoxia-induced remodeling of the pulmonary circulation is a highly complex process where numerous interactive events must be taken into account as we search for newer, more effective therapeutic interventions. This review provides perspectives on each of the aforementioned areas.

Assessing Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

Abstract: Background: Prostate-specifi c antigen (PSA) testing is the primary method used to diagnose prostate cancer in the United States. Methods to integrate other risk factors associated with prostate cancer into individualized risk prediction are needed. We used prostate biopsy data from men who par ticipated in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer. Methods: We included 5519 men from the placebo group of the PCPT who underwent prostate biopsy, had at least one PSA measurement and a digital rectal examination (DRE) performed during the year before the biopsy, and had at least two PSA measurements performed during the 3 years before the prostate biopsy. Logistic regression was used to model the risk of prostate cancer and high-grade disease associated with age at biopsy, race, family history of prostate cancer, PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations were created from the estimated logistic regression models. All statistical tests were two-sided. Results: A total of 1211 (21.9%) men were diagnosed with prostate cancer by prostate biopsy. Variables that predicted prostate cancer included higher PSA level, positive family history of prostate cancer, and abnormal DRE result, whereas a previous negative prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA velocity contributed independent prognostic information. Higher PSA level, abnormal DRE result, older age at biopsy, and African American race were predictive for high-grade disease (Gleason score ≥ 7) whereas a previous negative prostate biopsy reduced this risk. Conclusions: This predictive model allows an individualized assessment of prostate cancer risk and risk of high-grade disease for men who undergo a prostate biopsy. [J Natl Cancer Inst 2006;98:529 – 34]

Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial.

Abstract: ContextDespite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown.ObjectiveTo determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer.Design, Setting, and PatientsRandomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy.InterventionMen were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211).Main Outcome MeasuresPrimary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications.ResultsAmong the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse–free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%).ConclusionsIn men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant.Trial Registrationclinicaltrials.gov Identifier: NCT00394511

Prevalence, Predictors, and Outcomes of Premature Discontinuation of Thienopyridine Therapy After Drug-Eluting Stent Placement: Results From the PREMIER Registry

Abstract: Background— Although drug-eluting stents (DES) significantly reduce restenosis, they require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy after DES placement for acute myocardial infarction (MI) are unknown. Methods and Results— We used prospectively collected data from a 19-center study of MI patients to examine the prevalence and predictors of thienopyridine discontinuation 30 days after DES treatment. We then compared the mortality and cardiac hospitalization rates for the next 11 months between those who stopped and those who continued thienopyridine therapy. Among 500 DES-treated MI patients who were discharged on thienopyridine therapy, 68 (13.6%) stopped therapy within 30 days. Those who stopped were older, less likely to have completed high school or be married, more likely to avoid health care because of cost, and more likely to have had preexisting cardiovascular disease or anemia at presentatio...

Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy

Abstract: Summary Background Appropriate timing of androgen deprivation treatment (ADT) for prostate cancer is controversial. Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed. Methods Eligible patients from 36 institutes in the USA were randomly assigned in 1988–93 to receive immediate ADT (n=47) or to be observed (n=51), with ADT to be given on detection of distant metastases or symptomatic recurrences. Patients were followed up every 3 months for the first year and every 6 months thereafter. The primary endpoint was progression-free survival; secondary endpoints were overall and disease-specific survival. Analysis was by intention to treat. To ensure that the treatment groups were comparable, we did a retrospective central pathology review of slides and regraded the Gleason scores for available samples. This trial predates the requirement for clinical trial registration. Findings At median follow-up of 11·9 years (range 9·7–14·5 for surviving patients), men assigned immediate ADT had a significant improvement in overall survival (hazard ratio 1·84 [95% CI 1·01–3·35], p=0·04), prostate-cancer-specific survival (4·09 [1·76–9·49], p=0·0004), and progression-free survival (3·42 [1·96–5·98], p Interpretation Early ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy, compared with those who receive deferred treatment. The beneficial effects of early ADT, rather than an imbalance in risk factors, are likely to explain the differences in outcomes between treatments.

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report

Abstract: There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus A Scientific Statement From the American Heart Association and the American Diabetes Association

Abstract: The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: The ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

Measurement of Adherence in Pharmacy Administrative Databases: A Proposal for Standard Definitions and Preferred Measures

Abstract: Background:A variety of measures have been developed to calculate refill adherence from administrative data such as pharmacy claims databases. These measures have focused on improving the accuracy of adherence measures or clarifying the evaluation time frame. As a result, there are many measures used to assess adherence that may or may not be comparable or accurate.Objective:To compare available refill adherence measures.Methods:A systematic literature review was conducted to identify current or recently used measures of calculating adherence from administrative data. A MEDLINE search (January 1990–March 2006) was undertaken using the search terms adherence or compliance in the title combined with administrative, pharmacy, or records in any field, including subheadings medical, nursing, and hospital records. Non-English articles were excluded. Seven hundred fifteen articles were available for review. Review articles and letters were excluded from measure selection, but were included in the search terms an...

Individual and Combined Effects of Postpartum Depression in Mothers and Fathers on Parenting Behavior

Abstract: BACKGROUND. Pediatric anticipatory guidance has been associated with parenting behaviors that promote positive infant development. Maternal postpartum depression is known to negatively affect parenting and may prevent mothers from following anticipatory guidance. The effects of postpartum depression in fathers on parenting is understudied. OBJECTIVE. Our purpose with this work was to examine the effects of maternal and paternal depression on parenting behaviors consistent with anticipatory guidance recommendations. METHODS. The 9-month-old wave of data from a national study of children and their families, the Early Childhood Longitudinal Study, provided data on 5089 2-parent families. Depressive symptoms were measured with a short form of the Center for Epidemiologic Studies Depression Scale. Interviews with both parents provided data on parent health behaviors and parent-infant interactions. Logistic and linear regression models were used to estimate the association between depression in each parent and the parenting behaviors of interest. These models were adjusted for demographic and socioeconomic status indicators. RESULTS. In this national sample, 14% of mothers and 10% of fathers exhibited levels of depressive symptoms on the Center for Epidemiologic Studies Depression Scale that have been associated with clinical diagnoses, confirming other findings of a high prevalence of postpartum maternal depression but highlighting that postpartum depression is a significant issue for fathers as well. Mothers who were depressed were ∼1.5 times more likely to engage in less healthy feeding and sleep practices with their infant. In both mothers and fathers, depressive symptoms were negatively associated with positive enrichment activity with the child (reading, singing songs, and telling stories). CONCLUSIONS. Postpartum depression is a significant problem in both mothers and fathers in the United States. It is associated with undesirable parent health behaviors and fewer positive parent-infant interactions.

Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression.

Abstract: Background Neuromyelitis optica (NMO)–IgG is a specific autoantibody marker for NMO. It binds selectively to aquaporin 4 (AQP4), which is highly concentrated in astrocytic foot processes at the blood-brain barrier and is not restricted to optic nerve and spinal cord. Although it is conventionally believed that the brain is spared, brain imaging abnormalities are not uncommon in patients with NMO. Objective To investigate the location of brain lesions that are distinctive for NMO with respect to the localization of AQP4 in mammalian brain. Design Observational, retrospective case series. Setting Clinical serologic cohort of patients tested for NMO-IgG for whom brain MRI images were available. Patients We identified 120 patients seropositive for NMO-IgG for whom brain magnetic resonance images were available. Main Outcome Measure Magnetic resonance imaging abnormalities. Results In 8 patients we observed recurring and distinctive magnetic resonance imaging abnormalities in the hypothalamic and periventricular areas that corresponded to brain regions of high AQP4 expression. Conclusion The distribution of NMO-characteristic brain lesions corresponds to sites of high AQP4 expression.

Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2

Abstract: Covalent modifications of histone tails have a key role in regulating chromatin structure and controlling transcriptional activity. In eukaryotes, histone H3 trimethylated at lysine 4 (H3K4me3) is associated with active chromatin and gene expression. We recently found that plant homeodomain (PHD) finger of tumour suppressor ING2 (inhibitor of growth 2) binds H3K4me3 and represents a new family of modules that target this epigenetic mark. The molecular mechanism of H3K4me3 recognition, however, remains unknown. Here we report a 2.0 A resolution structure of the mouse ING2 PHD finger in complex with a histone H3 peptide trimethylated at lysine 4. The H3K4me3 tail is bound in an extended conformation in a deep and extensive binding site consisting of elements that are conserved among the ING family of proteins. The trimethylammonium group of Lys 4 is recognized by the aromatic side chains of Y215 and W238 residues, whereas the intermolecular hydrogen-bonding and complementary surface interactions, involving Ala 1, Arg 2, Thr 3 and Thr 6 of the peptide, account for the PHD finger's high specificity and affinity. Substitution of the binding site residues disrupts H3K4me3 interaction in vitro and impairs the ability of ING2 to induce apoptosis in vivo. Strong binding of other ING and YNG PHD fingers suggests that the recognition of H3K4me3 histone code is a general feature of the ING/YNG proteins. Elucidation of the mechanisms underlying this novel function of PHD fingers provides a basis for deciphering the role of the ING family of tumour suppressors in chromatin regulation and signalling.

Impact of medication therapy discontinuation on mortality after myocardial infarction.

Abstract: Background: Nonadherence to medications is common, but the determinants and consequences are poorly defined. The objectives of this study were to identify patient and myocardial infarction (MI) treatment factors associated with medication therapy discontinuation and to assess the impact of medication discontinuation 1 month after MI on 12-month mortality. Methods: This was a multicenter prospective cohort of patients with MI enrolled in the Prospective Registry Evaluating Myocardial Infarction: Event and Recovery study.Theoutcomeswereuseofaspirin,-blockers,and statins at 1 month after MI hospitalization among patients discharged with all 3 medications as well as 12month mortality. Results: Of 1521 patients discharged with all 3 medications,184discontinueduseofall3medications,56discontinued use of 2 medications, 272 discontinued use of 1 medication, and 1009 continued taking all 3 medications at 1 month. In multivariable analyses, patients not graduating from high school (odds ratio [OR], 1.76; 95%confidenceinterval[CI],1.20-2.60)weremorelikely to discontinue use of all medications. The effect of increasing age on medication therapy discontinuation was greater for females (OR, 1.77; 95% CI, 1.34-2.34) than males (OR, 1.23; 95% CI, 1.02-1.47). Patients who discontinued use of all medications at 1 month had lower 1-yearsurvival(88.5%vs97.7%;log-rankP.001)comparedwithpatientswhocontinuedtotake1ormoremedication(s). In multivariable survival analysis, medication therapy discontinuation was independently associated with higher mortality (hazards ratio, 3.81; 95% CI, 1.887.72). Results were consistent when evaluating discontinuation of use of aspirin, -blockers, and statins separately.

Guidelines for colonoscopy surveillance after polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society

Abstract: Adenomatous polyps are the most common neoplastic findings uncovered in people who undergo colorectal screening or have a diagnostic workup for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas as well as missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which demonstrated clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance be 3 years after polypectomy for most patients. In 2003, these guidelines were updated, colonoscopy was recommended as the only follow-up examination, and stratification at baseline into lower and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have demonstrated that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present paper, a careful analytic approach was designed addressing all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be more definitely stratified at their baseline colonoscopy into those at lower or increased risk for a subsequent advanced neoplasia. People at increased risk have either three or more adenomas, or high-grade dysplasia, or villous features, or an adenoma ≥1 cm in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have one or two small (<1 cm) tubular adenomas with no high-grade dysplasia can have a follow up in 5 to 10 years, whereas people with hyperplastic polyps only should have a 10-year follow up as average-risk people. Recent papers have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians' concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase utilization of the recommendations by endoscopists. Adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.

Outcomes of patients with differentiated thyroid carcinoma following initial therapy.

Abstract: This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients. The study setting was a prospectively followed multi-institutional registry. Patients were stratified as low risk (stages I and II) or high risk (stages III and IV). Treatments employed included near-total thyroidectomy, administration of radioactive iodine, and thyroid hormone suppression therapy. Outcome measures were overall survival, disease-specific survival, and disease-free survival. Near-total thyroidectomy, radioactive iodine, and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients. Near-total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid hormone suppression therapy, both predicted improved overall survival in stage II patients. No treatment modality, including lack of radioactive iodine, was associated with altered survival in stage I patients. Based on our overall survival data, we confirm that near-total thyroidectomy is indicated in high-risk patients. We also conclude that radioactive iodine therapy is beneficial for stage II, III, and IV patients. Importantly, we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients, but are achieved with modest suppression in stage II patients. We were unable to show any impact, positive or negative, of specific therapies in stage I patients.

Eviction for Conservation: A Global Overview

Abstract: Displacement resulting from the establishment and enforcement of protected areas has troubled relationships between conservationists and rural groups in many parts of the world. This paper examines one aspect of dis- placement: eviction from protected areas. We examine divergent opinions about the quality of information available in the literature. We then examine the literature itself, discussing the patterns visible in nearly 250 reports we compiled over the last two years. We argue that the quality of the literature is not great, but that there are signs that this problem is primarily concentrated in a few regions of the world. We show that there has been a remarkable surge of publications about relocation after 1990, yet most protected areas reported in these publications were established before 1980. This reflects two processes, first a move within research circles to recover and rediscover pro- tected areas' murky past, and second stronger enforcement of existing legisla- tion. We review the better analyses of the consequences of relocation from protected areas which are available and highlight areas of future research.

Understanding and Addressing the Epidemic of Obesity: An Energy Balance Perspective

Abstract: The intent of this paper is to address the obesity epidemic, which is a term used to describe the sudden and rapid increase in obesity rates that began in the 1980s and continues unabated today. Since 1980, the entire population, regardless of starting weight, is gradually gaining weight. This has led to escalating obesity rates and to obesity being considered one of the most serious public health challenges facing the world. At one level, the obesity epidemic is a classic gene-environment interaction where the human genotype is susceptible to environmental influences that affect energy intake and energy expenditure. It is also a problem of energy balance. Understanding the etiology of obesity requires the study of how behavioral and environmental factors have interacted to produce positive energy balance and weight gain. Reversing the epidemic of obesity will require modifying some combination of these factors to help the population achieve energy balance at a healthy body weight. While body weight is strongly influenced by biological and behavioral factors, changes in the environment promoting positive energy balance have been most responsible for the obesity epidemic. Our best strategy for reversing the obesity epidemic is to focus on preventing positive energy balance in the population through small changes in diet and physical activity that take advantage of our biological systems for regulating energy balance. Simultaneously, we must address the environment to make it easier to make better food and physical activity choices. This is a very long-term strategy for first stopping and then reversing the escalating obesity rates, but one that can, over time, return obesity rates to pre-1980s levels.

Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates.

Abstract: Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, elicitation of non-Gal pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.

Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines.

Abstract: The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, produce 9% to 27% response rates in NSCLC patients. E-Cadherin, a calcium-dependent adhesion molecule, plays an important role in NSCLC prognosis and progression, and interacts with EGFR. The zinc finger transcriptional repressor, ZEB1, inhibits E-cadherin expression by recruiting histone deacetylases (HDAC). We identified a significant correlation between sensitivity to gefitinib and expression of E-cadherin, and ZEB1, suggesting their predictive value for responsiveness to EGFR-tyrosine kinase inhibitors. E-Cadherin transfection into a gefitinib-resistant line increased its sensitivity to gefitinib. Pretreating resistant cell lines with the HDAC inhibitor, MS-275, induced E-cadherin along with EGFR and led to a growth-inhibitory and apoptotic effect of gefitinib similar to that in gefitinib-sensitive NSCLC cell lines including those harboring EGFR mutations. Thus, combined HDAC inhibitor and gefitinib treatment represents a novel pharmacologic strategy for overcoming resistance to EGFR inhibitors in patients with lung cancer.