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Natural landscapes subject to disturbances have a patchy structure that is important to many species living in these landscapes. This structure may be modified when the disturbance regime is altered by either climatic change or human influences (e.g., fire suppression), yet little is known about how this structure will change. I used a GIS (geographic information system)-based spatial model and data on historical changes in fire sizes and intervals to simulate the effects of settlement and fire suppression on the structure of the landscape in the Boundary Waters Canoe Area, Minnesota. I used seven measures to assess change in landscape structure. Settlement and fire suppression altered some but not all components of landscape structure. Settlement produced an immediate significant effect on some measures (age, shape, Shannon diversity, richness, and angular second moment), but no effect on other measures (size, fractal dimension). In contrast, suppression produced an immediate re- sponse in fewer measures (shape, Shannon diversity, richness), a delay for several decades in the case of some measures (age, fractal dimension), and a delay for hundreds of years in the case of other measures (size, angular second moment). Landscapes that have been altered by settlement and fire suppression cannot be restored using traditional methods of prescribed burning, which will simply produce further alter- ation. Causes of landscape change cannot be separated without control landscapes that lack prescribed burning, fire suppression, or other alterations of the natural fire regime.

Large disturbances such as fires and floods are landscape processes that may alter the structure of landscapes in nature reserves. Landscape structure may in turn influence the viability of species and the functioning of ecosystems. Past reserve design and management strategies have been focussed on species and ecosystems rather than on landscape-scale processes, such as disturbance. An essential feature of a natural disturbance regime is the variation in disturbance attributes (e.g., size, timing, intensity, spatial location). Although some past reserve management policies have included natural disturbances, perpetuating disturbance variation has not been the explicit goal of either reserve design or management. To design a reserve to perpetuate the natural disturbance process requires consideration of: (1) the size of the reserve in relation to maximum expected disturbance size, (2) the location of the reserve in relation to favored disturbance initiation and export zones and in relation to spatial variation in the disturbance regime, and (3) the feasibility of disturbance control at reserve boundaries, or in reserve buffers. Disturbance management possibilities are constrained by the design of the reserve and the reserve goals. Where a natural disturbance regime is not feasible, then it is important that the managed disturbance regime mimic historical variation in disturbance sizes and other attributes as well as possible. Manipulating structure on the landscape scale to restore landscapes thought to have been altered by historical disturbance control is premature given our understanding of spatial disturbance processes in landscapes.

Patients with ischemic heart disease and preserved ventricular function experience considerable morbidity and mortality despite standard medical therapy.To compare benefits and harms of using angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.Two independent investigators screened citations for trials of at least 6 months' duration that compared ACE inhibitors, ARBs, or combination therapy with placebo or active control and reported any of several clinical outcomes.Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 [95% CI, 0.81 to 0.94]) and nonfatal myocardial infarction (RR, 0.83 [CI, 0.73 to 0.94]) but increase the RR for syncope (RR, 1.24 [CI, 1.02 to 1.52]) and cough (RR, 1.67 [CI, 1.22 to 2.29]) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 [CI, 0.77 to 1.00]) but not for the individual components. Moderate-strength evidence (1 trial; 25 620 participants) showed similar effects on total mortality (RR, 1.07 [CI, 0.98 to 1.16]) and myocardial infarction (RR, 1.08 [CI, 0.94 to 1.23]) but an increased risk for discontinuations because of hypotension (P0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.Many studies either did not assess or did not report harms in a systematic manner. Many studies did not adequately report benefits or harms by various patient subgroups.Adding an ACE inhibitor to standard medical therapy improves outcomes, including reduced risk for mortality and myocardial infarctions, in some patients with stable ischemic heart disease and preserved ventricular function. Less evidence supports a benefit of ARB therapy, and combination therapy seems no better than ACE inhibitor therapy alone and increases harms.Agency for Healthcare Research and Quality.

Thienopyridine antiplatelet drugs have been used for 15 years for the prevention of coronary stent thrombosis in patients undergoing percutaneous coronary intervention with stent placement. Ticlopidine, the first approved thienopyridine, has in large part been replaced by clopidogrel, a more potent and better tolerated thienopyridine. Now, prasugrel, the newest agent, is currently available for use in the United States. Although prasugrel is similar to clopidogrel, it is about 10 times more potent and has a quicker onset of action. Data from the largest trial comparing clopidogrel and prasugrel indicate that this increased potency and quicker onset of prasugrel equate to a reduction in major adverse cardiovascular events, although higher rates of major bleeding were reported. Prasugrel also differs from clopidogrel in that it may be less prone to drug-drug interactions and patient nonresponsiveness, although further research is needed in both of these areas. Given the totality of data available, prasugrel appears to be a promising treatment option for patients with acute coronary syndromes who are undergoing percutaneous coronary interventions.

To the Editor: We read with great interest the meta-analysis by Ho and Tan1 on the impact of prophylactic corticosteroid use on atrial fibrillation in adult patients undergoing cardiac surgery. In their meta-analysis, Ho and Tan demonstrate that perioperative corticosteroid use significantly reduces the relative risk (RRR) of postoperative atrial fibrillation by 25%. They conducted subgroup analysis, stratifying studies to low-dose ( 10 000 mg) groups, and then used meta-regression to assess whether the antifibrillatory (among other) …

Background Green tea catechins (GTCs) with or without caffeine have been studied in randomized controlled trials (RCTs) for their effect on anthropometric measures and have yielded conflicting results. Objective The objective was to perform a systematic review and meta-analysis of RCTs of GTCs on anthropometric variables, including body mass index (BMI), body weight, waist circumference (WC), and waist-to-hip ratio (WHR). Design A systematic literature search of MEDLINE, EMBASE, CENTRAL, and the Natural Medicines Comprehensive Database was conducted through April 2009. RCTs that evaluated GTCs with or without caffeine and that reported BMI, body weight, WC, or WHR were included. The weighted mean difference of change from baseline (with 95% CIs) was calculated by using a random-effects model. Results Fifteen studies (n = 1243 patients) met the inclusion criteria. On meta-analysis, GTCs with caffeine decreased BMI (-0.55; 95% CI: -0.65, -0.40), body weight (-1.38 kg; 95% CI: -1.70, -1.06), and WC (-1.93 cm; 95% CI: -2.82, -1.04) but not WHR compared with caffeine alone. GTC ingestion with caffeine also significantly decreased body weight (-0.44 kg; 95% CI: -0.72, -0.15) when compared with a caffeine-free control. Studies that evaluated GTCs without concomitant caffeine administration did not show benefits on any of the assessed anthropometric endpoints. Conclusions The administration of GTCs with caffeine is associated with statistically significant reductions in BMI, body weight, and WC; however, the clinical significance of these reductions is modest at best. Current data do not suggest that GTCs alone positively alter anthropometric measurements.

Objective: To empower clinicians to discern when health-related quality-of-life (HRQoL) evidence from a single trial, or from constituent trials within a systematic review or meta-analysis, is compelling enough to after clinical practice. Data Sources: To determine the criteria that would be most useful in assessing the quality of HRQoL data, recommendation statements or consensus guidelines that offer guidance to those conducting HRQoL trials were located through a MEDLINE search (1950–April 2009) using the search terms health-related quality of life and recommendations or guidelines. Study Selection and Data Extraction: Recommendation statements or consensus guidelines that offer guidance to investigators conducting HRQoL trials were evaluated to determine what criteria would be the most useful in assessing the quality of HRQoL data. Data Synthesis: We discuss how quality of HRQoL data may be assessed by evaluating the following broad questions: (1) Is the HRQoL analysis hypothesis-driven? (2) How is HRQoL being measured? (3) Are the HRQoL data being collected adequately and analyzed correctly? and (4) To what extent do investigators discuss the results of HRQoL analyses? Using select examples from the literature on chronic obstructive pulmonary disease, we applied the 4 broad questions in the assessment of their quality. Also, the use of scoring systems for quality rating for HRQoL data is discussed and applied to the example cases. Conclusions: HRQoL data are an important outcome because they capture treatment impact on physical, social, and psychological well-being. Assessing the quality and usefulness of HRQoL data requires an understanding of the advantages, limitations, and caveats of their use. Because of the potential lack of quality in HRQoL outcomes, clinicians should thoroughly assess the validity and usefulness of the evaluation. Tools are available to aid clinicians and decisionmakers in the assessment of HRQoL outcomes, but additional research needs to be conducted on the topic of quality assessment of HRQoL studies to improve the usefulness of these evaluations to clinicians.

Prasugrel is a new P2Y(12) receptor antagonist that has been investigated for the treatment of atherothrombosis in patients with cardiovascular disease undergoing percutaneous coronary intervention (PCI). Similar to other thienopyridines, prasugrel is a prodrug that requires biologic conversion to active metabolites. Studies have demonstrated the ability of prasugrel to selectively and irreversibly inhibit ADP-induced platelet aggregation to a greater degree than clopidogrel. In a large randomized, double-blind, double-dummy clinical trial, it was demonstrated that treatment with prasugrel (n = 6813; 60 mg loading dose followed by 10 mg/day) significantly reduced the incidence of a composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke during the median follow-up of 14.5 months, compared with clopidogrel (n = 6795; 300 mg loading dose followed by 75 mg/day) in patients with acute coronary syndromes scheduled to undergo PCI. The number of patients who would need to be treated with prasugrel instead of clopidogrel in order to prevent one primary efficacy outcome was 46. Landmark analyses found that prasugrel not only reduced the incidence of individual clinical endpoints and stent thrombosis during the loading dose phase (randomization to 3 days), but also that these benefits continued throughout the maintenance phase (from 3 days until the end of the trial). Nonsurgical-related Thrombolysis In Myocardial Infarction (TIMI)-major and life-threatening bleeds were significantly more frequent in patients receiving prasugrel compared with clopidogrel. Patients with a history of stroke or transient ischemic attack (TIA) seem to be at especially high risk for bleeding, as well as patients aged >75 years and those weighing

Study Objective. To assess the comparative efficacy of pharmacologic agents for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Design. Traditional and mixed-treatment comparison (MTC) meta-analyses of randomized controlled trials. Patients. A total of 31,020 patients with COPD from 43 trials. Measurements and Main Results. A systematic literature search of various databases (through October 2007) was performed to identify randomized controlled trials of long-acting β2-agonists, tiotropium, inhaled corticosteroids, and/or combination therapy with an inhaled corticosteroid and a long-acting β2-agonist in patients with COPD. Forty-three trials were included. Both meta-analyses were used to evaluate the occurrence of one or more episodes of COPD exacerbation, overall mortality, and patient withdrawal rates. With MTC analysis, long-acting β2-agonists, tiotropium, inhaled corticosteroids, and combination inhaled corticosteroid-long-acting β2-agonist therapy each decreased the odds of having an exacerbation by 16%, 31%, 15%, and 24%, respectively, compared with placebo. Moreover, tiotropium use reduced the odds of having at least one exacerbation by 18% compared with long-acting β2-agonists and by 19% compared with inhaled corticosteroids alone. Each of the four drug classes was associated with significant odds reductions in patient withdrawals (26–41%) compared with placebo, and both tiotropium and combination therapy significantly decreased the odds of patient withdrawals compared with long-acting β2-agonists or inhaled corticosteroids alone. Only combination therapy was associated with a mortality benefit, showing a 29% reduction compared with placebo and a 25% reduction compared with long-acting β2-agonists alone. Compared with combination therapy, tiotropium use reduced exacerbations by 9% and increased mortality by only 4%. These findings did not demonstrate significant changes in the sensitivity or subgroup analyses, which were performed to evaluate the effect of heterogeneity among the included studies. Conclusions. Combination inhaled corticosteroid-long-acting β2-agonist therapy was associated with the greatest positive effect on outcomes in patients with COPD. Of the bronchodilator monotherapies, tiotropium was associated with lower odds of having a COPD exacerbation or withdrawal from a study compared with long-acting β2-agonists. Conclusion: Our MTC meta-analysis provides a useful and comprehensive evaluation of the beneficial effects of various therapeutic drug classes on outcomes in patients with COPD. Combination inhaled corticosteroid-long-acting β2-agonist therapy had the greatest positive effect on outcomes. Of the bronchodilator monotherapies, tiotropium was associated with lower odds of having an exacerbation or withdrawing from a study compared with long-acting β2-agonists.

The U.S. Fish and Wildlife Service's recent recovery plan for one of the most carefully watched threatened species worldwide, the Northern Spotted Owl (Strix occidentalis caurina), recommended a major departure in conservation strategies in the northwestern United States. Due to concern about fire, the plan would switch from a reserve to a no-reserve strategy in up to 52% of the owl's range. Fuel treatments (e.g., thinning) at regular intervals also would occur on up to 65-70% of dry forests in this area. Estimations of fire risk, however, were based on less than a decade of data and an anecdotal assessment of a single, large fire. We found that decadal data are inherently too short, given infrequent large fires, to accurately predict fire risk and trends. Rates of high-severity fire, based on remote-sensing data, are far lower than reported in the plan and in comparison with the rate of old-forest recruitment. In addition, over a 22-year period, there has been no increase in the proportion of high-severity fire. Our findings refute the key conclusions of the plan that are the basis for major changes in conservation strategies for the Spotted Owl. The best available science is needed to address these strategies in an adaptive-management framework. From the standpoint of fire risk, there appears to be ample time for research on fire and proposed treatment effects on Spotted Owls before designing extensive management actions or eliminating reserves.

Purpose. A case of probable enoxaparin-induced hepatotoxicity is described. Summary. A 29-year-old woman sought treatment from a pulmonologist for a dry, hacking, constant cough not relieved by fast-acting inhalers or narcotic cough medications that had lasted for three weeks. Her primary care physician had earlier made a preliminary diagnosis of pertussis and prescribed a short course of azithromycin and corticosteroids, which did not help relieve the symptoms. Computed tomography angiography of her chest revealed multiple bilateral pulmonary emboli with a moderate clot burden, which resulted in her hospitalization. The pulmonary emboli were thought to be associated with her oral contraceptive, which was discontinued at hospital admission. Anticoagulant therapy was initiated with subcutaneous enoxaparin and oral warfarin. Beginning the second day of therapy, the patient complained of nausea and associated vomiting. Diagnostic procedures did not reveal any liver, kidney, splenic, or pancreatic abnormalities. The results of laboratory tests revealed elevated levels of hepatic enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST). Tests for hepatitis A, B, and C were negative. Enoxaparin therapy was discontinued, and the patient was maintained on oral warfarin. Clinical and laboratory signs of liver injury resolved over the next few days, with a return to baseline levels of AST and ALT levels over the subsequent months. According to the Naranjo et al. adverse-reaction probability scale, enoxaparin was the probable cause of hepatotoxicity in this patient. Conclusion. A woman receiving enoxaparin every 12 hours developed signs and symptoms of hepatotoxicity after the second dose. The case was unusual in the rapidity and magnitude of hepatic enzyme elevation.

Global warming may have many consequences for natural ecosystems, including a change in disturbance regimes. No current model of landscapes subject to disturbance incorporates the effect of climatic change on disturbances on decade to century time scales, or addresses quantitative changes in landscape structure as disturbances occur. A new computer simulation model, DISPATCH, which makes use of a geographical information system for managing spatial data, has been developed for these purposes. The concept and structure of the DISPATCH model are described here, and a hypothetical example of its use is illustrated, but the model requires refinement before it can be used to predict the effects of global warming on specific landscapes. The model includes provisions for (1) temporally varying weather conditions and their effect on disturbance sizes, and (2) the effect of spatial variation in vegetation condition and physical setting on the probability of disturbance initiation and spread. The potential use of the model is illustrated with a hypothetical example in which the age structure of disturbance patches is monitored for a 250-year period as weather fluctuates. The model run suggests that landscape structure fluctuates even if a disturbance regime remains constant.

Objective To perform a meta-analysis of randomized placebo-controlled trials evaluating catechol-O-methyltransferase (COMT) inhibitors or monoamine oxidase type B (MAO-B) inhibitors in addition to levodopa versus levodopa alone for the treatment of advanced Parkinson's disease (PD). Methods A systematic literature search was performed between 1990 and October 2007. The primary outcome measures assessed were the reduction in scores of Unified Parkinson's Disease Rating Scale (UPDRS) total, activities of daily living (ADL) and motor scores from baseline. Other efficacy and safety endpoints were also evaluated. Results A total of 13 trials (n = 3775 subjects) were included in the meta-analysis. As compared to placebo, COMT and MAO-B inhibitor use resulted in greater improvement in UPDRS total score (weighted mean difference [WMD] −2.13, 95%CI −0.46 to −0.20; and WMD −5.03, 95%CI −7.38 to −2.68) ADL scores (WMD −0.99, 95%CI −1.56 to −0.43; and WMD −1.48, 95%CI −2.13 to −0.83) and motor scores (WMD −1.50, 95%CI −2.70 to −0.30; and WMD −3.19, 95%CI −4.57 to −1.80) as well as increase in “on” time, reduction in “off” time and decreased need in levodopa dose compared to placebo. Incidences of dyskinesia were significantly higher with the COMT and MAO-B inhibitors compared to placebo. Conclusion The use of COMT or MAO-B inhibitors plus levodopa is superior to levodopa alone at reducing PD symptoms in patients with advanced PD. While combination therapies with COMT or MAO-B inhibitor plus levodopa seem especially useful amongst PD patients with wearing-off phenomenon, they are associated with more adverse events.

Post-cardiothoracic surgery (CTS) complications (e.g. myocardial injury, renal dysfunction, atrial fibrillation) may occur as a result of enhanced systemic inflammation, perhaps provoked by an oxidative stress response. N-acetylcysteine (NAC) is a free radical scavenger antioxidant agent that may attenuate this physiologic response and reduce post-CTS complications. Thus, a meta-analysis was performed to help characterize the potential beneficial effects of perioperative NAC administration in patients undergoing CTS. A systematic literature search in MEDLINE, EMBASE and the Cochrane Library was conducted through April 2008. A search strategy using medical subject headings and text keywords was performed. Results are reported as odds ratios or weighted mean differences with accompanying 95% confidence intervals (CIs). Studies were pooled using a fixed-effect model. The primary outcomes included atrial fibrillation (AF), myocardial infarction (MI), stroke, acute kidney injury (AKI), need for renal replacement therapy (RRT), mortality and total hospital length-of-stay (LOS). Upon meta-analysis of 13 trials (n=1338 subjects), the use of NAC appeared to statistically significantly lower the odds of developing post-CTS AF by 36% (95%CI 2-58%) (n=6 studies). This corresponded to an 8% (1-15%) pooled risk difference and a number-needed-to-treat of 13. NAC did not appear to significantly alter any of the other meta-analysis endpoints. The exclusion of the study utilizing only oral NAC therapy and the study with lower internal validity did not affect the overall conclusions of our meta-analysis. Currently, the most compelling data for using NAC in CTS patients is in post-CTS AF prevention. However, additional, larger randomized controlled trials evaluating this and other postoperative complication endpoints are needed.

PURPOSE We performed a meta-analysis of randomized placebo-controlled trials of nonergot dopamine agonists (NEDAs) for the treatment of restless legs syndrome. METHODS A systematic literature search was conducted through July 2007. The primary outcome measures assessed were the percentage of responders to medication as determined by the Clinical Global Impression-Improvement (CGI-I) scale and the adjusted mean change in the International Restless Legs Syndrome Study Group Scale (IRLS) score from baseline compared with placebo. Meta-regression analysis was performed to evaluate the impact of study duration on the primary outcomes. Safety endpoints were also evaluated. RESULTS A total of 14 trials (n = 3,197 subjects) were included in the meta-analysis. NEDA use resulted in greater response as measured by the CGI-I scale (relative risk [RR] 1.36; 95% CI, 1.24 to 1.49; P

Nonsteroidal anti-inflammatory drug (NSAID) use may reduce the incidence of post-cardiothoracic surgery (CTS) atrial fibrillation (AF). The cerebrovascular and cardiovascular safety of using NSAIDs for post-CTS AF has not been determined.To evaluate whether NSAIDs could reduce the incidence of post-CTS atrial fibrillation without increasing patients' risk of stroke or myocardial infarction (MI).Patients (n = 555) undergoing CTS from the Atrial Fibrillation Suppression Trials I, II and III were evaluated in this nested cohort study. Demographic, surgical and medication use characteristics were prospectively collected as part of the AFIST trials. Endpoints included post-CTS atrial fibrillation, stroke, MI and the need for red blood cell transfusion. Multivariable logistic regression was used to control for potential confounders and calculate adjusted odds ratios with 95% confidence intervals.The population was 67.8 +/- 8.6 years old and 77.1% male with 127 (22.9%) patients receiving an NSAID postoperatively. Overall, 14.6% underwent valve surgery, 6.1% had prior AF, 12.6% had heart failure and 84.0% and 44.1% received postoperative beta-blockade and prophylactic amiodarone. NSAID use was associated with reductions in the adjusted odds of post-CTS atrial fibrillation (0.54 (0.32-0.90)) and the need for RBC transfusions (0.63 (0.41-0.97)). No elevation in the odds of developing stroke (1.10 (0.21-5.66)) or MI (1.70 (0.40-7.10)) was observed.Patients were not randomized to receive NSAIDs versus a control. We may not have had adequate power to evaluate stoke or MI in this analysis.NSAIDs decreased the odds of developing post-CTS atrial fibrillation, further supporting the hypothesis of inflammation as a trigger for post-CTS atrial fibrillation. The need for RBC transfusions was also reduced with NSAID use. We may have been underpowered to evaluate stroke or MI incidence, but the qualitative elevations in these variables suggest more safety data is needed before NSAIDs can be routinely recommended.

The aim of this article is to determine the association between commonly used antihypertensive agents and the incidence of cancer.We conducted a mixed treatment comparison meta-analysis of randomized, controlled (placebo, active, or untreated control) trials of antihypertensive drugs. A systematic literature search was conducted through June 2007. The primary outcome measure assessed was the incidence of cancer. Mixed treatment comparison meta-analysis was used to combine direct, within-trial, and between-drug comparisons with indirect evidence from the other trials. The indirect comparisons, which safeguard within-trial randomized findings, were constructed from trials with one treatment in common. Results are reported as odds ratios with 95% credible intervals.In total, 27 studies (56 treatment arms, 126137 patients enrolled, and 5868 cancers identified during follow-up) were included in the base-case analysis. They were hypertension, prehypertension, heart failure, coronary artery disease, or renal disease trials and patients were randomized to one of the five major antihypertensive drug classes or to placebo/untreated control. With the placebo/untreated control group as the referent comparison, the odds for developing cancer were 0.99 (0.80-1.24) for angiotensin-converting enzyme inhibitors; 1.12 (0.87-1.47) for angiotensin receptor blockers; 1.00 (0.78-1.32) for beta-adrenergic blockers; 0.94 (0.73-1.19) for diuretics and 0.95 (0.79-1.13) for calcium channel blockers. In sensitivity analyses, the results were not altered to any noteworthy extent including exclusion of studies under 3 years duration.Based on the totality of the clinical trial literature, commonly used antihypertensive drugs are not associated with increased odds of developing cancer.

The probable causes of spatial variation in the diversity of plant communities on a global and local scale have been widely investigated, but the regional scale has received little attention. It remains unclear how disturb- ance affects diversity in wetlands and riparian vegetation. This study examines the hypothesis that regional varia- tion in the richness of riparian wetlands is related to variation in macro-environment and flood potential. Vascular plant species richness was sampled in 0.1 ha plots at 115 riparian sites scattered over a 300 km length of the western slope of the Rocky Mountains in western Colorado, USA. The relationship between macro-envi- ronmental variables (e.g. drainage basin area), disturb- ance indicators, and species richness was analyzed using correlation analysis and multiple regression analysis. Total richness varied between 20 and 87 species (average 50.6) per 0.1 ha, and was highest in subalpine riparian forests from 2600-3650 m a.s.l. (57.8 species / 0.1 ha). Tree and shrub richness were highest in lower elevation, larger drainage basins, forb and graminoid richness were highest in higher elevation, smaller drainage basins. These opposing trends resulted in no net trend in total richness with elevation. Regression models for total rich- ness were poor, suggesting that other variables must be important. The intermediate disturbance hypothesis and other single-factor hypotheses are not supported as expla- nations of the regional pattern of variation in richness.

Purpose. A meta-analysis of randomized, controlled trials that evaluated the effect of the macrolide antibiotic, azithromycin, on clinical outcomes in patients with coronary artery disease (CAD) was conducted. Methods. A systematic literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews was conducted using specific search terms. Randomized, controlled trials comparing azithromycin or placebo in secondary CAD patients with adequately reported data on mortality and clinical cardiac endpoints were included. A random-effects model was used. Results. Six studies ( n = 13,778) met the inclusion criteria. The trials varied in their design. On meta-analysis, azithromycin resulted in a nonsignificant reduction in mortality versus placebo (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.77–1.09; p = 0.31). Four trials reported the rate of nonfatal myocardial infarction (MI). Azithromycin did not have an effect on the rate of nonfatal MI versus placebo (OR, 0.95; 95% CI, 0.80–1.13; p = 0.57). Five trials reported rates of hospitalization in which no significant difference was seen with azithromycin versus placebo (OR, 0.97; 95% CI, 0.80–1.17; p = 0.76). Six trials were used to evaluate the composite cardiovascular endpoint. Again, no significant benefit was seen with azithromycin versus placebo (OR, 0.93; 95% CI, 0.84–1.03; p = 0.218). Conclusion. Meta-analysis showed that azithromycin does not appear to reduce the frequency of recurrent cardiac events in patients with CAD. Results from ongoing trials may clarify the role of azithromycin in the secondary prevention of coronary events.

To review the available literature addressing preventive strategies of post-cardiothoracic surgery atrial fibrillation (post-CTS atrial fibrillation).Pertinent articles related to the etiology, risk factors, and preventive strategies were identified through a MEDLINE search (1966-March 2007) using the MeSH terms atrial fibrillation, cardiothoracic surgery, cardiac surgery, etiology, neurohormonal, sympathetic, volume, fluid, inflammation, risk factors, operative, pacing, beta-adrenergic blockers, amiodarone, sotalol, calcium-channel blockers, magnesium, HMG-CoA reductase inhibitors, statins, fatty acids, PUFA, steroids, and nonsteroidal antiinflammatory drugs.Articles evaluated were limited to human studies, published in the English language, with a Jadad score greater than 3. References of identified articles were reviewed for additional pertinent articles.Post-CTS atrial fibrillation most commonly occurs on the second or third postoperative day, with an incidence of 20-50%. Etiology theories include neurohormonal activation, volume overload, and inflammation. Studies examining nonpharmacologic therapies have shown that maintenance of the anterior epicardial fat pad is not a viable prophylactic strategy. Biatrial cardiac pacing, especially in combination with amiodarone, is a viable preventive option. Withdrawal of preoperative beta-blockers places patients at higher risk for atrial fibrillation; these drugs should be continued postoperatively. Evidence exists supporting the use of amiodarone, sotalol, and magnesium in addition to beta-blockers. Since most of these strategies work by attenuating neurohormonal activation, adverse events, including hypotension and bradycardia, are of concern. Adding agents with antiinflammatory properties, including hydroxymethylglutaryl coenzyme A reductase inhibitors or corticosteroids, may prove to be of benefit. Additional studies using novel therapies are needed in addition to established preventive strategies.Available evidence supports the continuation of preoperative beta-blockers, as well as prophylactic amiodarone, sotalol, and magnesium. Other novel therapies, mostly targeting inflammation, are under investigation and may provide additional strategies.

A 58-year-old man went to his physician with complaints of midepigastric pain, flatulence, belching, and shortness of breath. During a physical examination, the patient was in no acute distress. The patient underwent an ultrasound examination, which revealed cholelithiasis, a laparoscopic cholecystectomy, which revealed chronic gallbladder disease, and esophagogastroduodenoscopy, which revealed gastritis, a hiatal hernia, and a phytobezoar. To treat the bezoar, the patient was given Adolph's Meat Tenderizer 1 teaspoonful in 8 oz of water before each meal for 7 days. This product contains papain, a proteolytic enzyme, that is thought to cleave protein linkages within bezoars. The patient's symptoms resolved with no adverse events reported, and follow-up endoscopy revealed resolution of the phytobezoar. Although a few other agents are used to treat phytobezoars, little clinical data exist on their safety and effectiveness. Adolph's Meat Tenderizer appears to be a safe and effective treatment for patients with a phytobezoar.

A 38-year-old Caucasian man with a medical history significant for inflammatory bowel disease (IBD) and mesalamine use presented to the emergency department with stabbing, pleuritic, substernal chest pain over the previous 2 days. Findings of leucocytosis, elevated cardiac enzymes and inflammatory markers, T-wave or ST-segment abnormalities and left ventricular systolic dysfunction suggested mesalamine-induced myocarditis. However, a cardiac MRI confirmed the diagnosis. Signs and symptoms improved within days of withdrawal of mesalamine, and initiation of corticosteroids and follow-up studies within the next year were unremarkable. Importantly, the diagnosis of mesalamine-induced myocarditis confirmed via cardiac MRI is a step rarely performed in published cases.

In their publication in EP-Europace , Vrijens and Heidbuchel1 conclude twice-daily (BID) dosing of non-vitamin K antagonist (VKA) oral anticoagulants ‘may be more forgiving in patients with suboptimal adherence’ than once-daily (OD) dosing. The authors submit the above conclusion is ‘exemplified’ by the PLATO trial, which compared OD clopidogrel to BID ticagrelor in acute coronary syndrome patients; suggesting the reduced rate of cardiovascular events with BID ticagrelor was the result of a ‘greater degree of continuity of drug action’ in the presence of suboptimal adherence.1,2 This theory ignores potential differences in antiplatelet potency between agents, in …

Background While the mechanism underlying the development of post-cardiothoracic surgery atrial fibrillation has not been fully elucidated, it has been suggested that inflammation may play a causative role. Corticosteroids have been traditionally used to reduce inflammation, and when administered perioperatively, they may decrease the incidence of atrial fibrillation. Objective The purpose of this study was to investigate the effects of corticosteroid administration on the incidence of post-cardiothoracic surgery atrial fibrillation and resultant hospital length of stay. Methods A systematic literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews through July 2006 was conducted using specific search terms. A review of cardiology abstracts and a manual review of references were also performed. Studies that met the following criteria were included: randomized, controlled trials comparing patients receiving perioperative corticosteroids or placebo and reporting data on post-cardiothoracic surgery atrial fibrillation. A random-effects model was used. Results Nine of the 1396 citations initially identified, representing 990 patients, met the inclusion criteria. Upon meta-analysis, corticosteroids significantly lowered patients' odds of developing post-cardiothoracic surgery atrial fibrillation by 45% (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.39–0.78) and reduced hospital length of stay by approximately 1.6 days (weighted mean difference −1.59; 95% CI −2.96 to −0.21). Reductions in the incidence of post-cardiothoracic surgery atrial fibrillation appeared greatest in patients receiving intermediate doses of corticosteroid (50–210 mg dexamethasone equivalent), while both lower (up to 8 mg) and higher (236–2850 mg) dosing resulted in blunted effects. Conclusion Corticosteroids appear to reduce the incidence of post-cardiothoracic surgery atrial fibrillation and shorten hospital length of stay in randomized controlled trials.

Group-randomized trials often involve repeat observations on the same participants. When there are no more than two observations from each participant, standard mixed-model regression methods for a pretest–posttest design can be used. When there are more than two observations from each participant, random coefficients models may be useful. This paper describes the random coefficients analysis appropriate to data from an extended nested cohort design and presents the methods for power analysis and sample size calculations based on that analysis. We provide estimates for the parameters required for those calculations for a number of adolescent health behaviours. We also show how the estimates can be used to plan a future trial. Copyright © 2006 John Wiley & Sons, Ltd.

Scattered reports indicate that the number of fires or area burned has increased recently in parts of the northern temperate zone, but is climatic change responsible? Annual number of fires and area burned have generally increased since about 1950 in Canada and Sweden (Stocks 1991), the Rocky Mountains (Qu and Omi 1994; Fig. 5.1a) and the western United States (Arno 1996; Fig. 5.1b). However, trends in fire statistics may in part reflect increasing ability to monitor fires (Ryan 1976; Qu and Omi 1994). Moreover, in Canada and in Yellowstone National Park, trends are dominated by a few exceptional fire years in the 1980s (Stocks 1991; Balling, Meyer, and Wells 1992a). Also suppression of fires decades ago may have increased fuel loads, leading to the larger fires seen now (Covington and Moore 1994). Finally the landscape may shape potential responses to climatic change, leading to disequilibrium between climate and fires (Baker 1995). Identifying a climatic signal in historical fire data may thus require more understanding of how climate, fuels, the landscape, and land-use practices separately and jointly shape fire regimes. To organize a discussion of the present state of understanding in the Rocky Mountains, I contrast a view that emphasizes how broad-scale patterns of climate and fuels control fire regimes, with a contingent view in which local spatial constraints and historical legacies may limit general trends. While these perspectives on what is important underlie models, empirical studies, and theories, they are seldom explicit. Models that represent the broad-scale view, for example, suggest that fires may hasten the response of vegetation to climatic

Learning Objectives: Heart-rate-complexity (HRC) calculated off-line was associated with injury severity, mortality, and the performance of life-saving interventions in animal and human studies. We hypothesized that real-time automatic HRC measurements by the Aesculon monitor (Cardiotronic-Osypka Medical, USA) are associated with hemodynamic status and mortality. Methods: Spontaneously breathing consciously sedated swine were shed 65% of blood volume over 1 hour, then were randomized to 3 groups: control (C, n=7); transfusion of shed blood (TSB, n=7); or endovascular balloon occlusion of the aorta (REBOA) (Pryor Medical, Arvada, CO) for up to 60 minutes followed by TSB (n=21). Epinephrine boluses were given if mean arterial pressure (MAP) 40 mmHg in the TSB and REBOA groups. After resuscitative interventions, animals were followed for 240 min or death. Aesculon monitor performed continuous, real-time measurements of HRC, i.e. sample entropy (SampEn) and multiscale entropy (MSE). At 30 minutes after all interventions, heart rate (HR), MAP, Lactate (Lac), and HRC metrics were assessed for their association with death using logistic regression and receiver-operating-characteristic (ROC) curve analysis. Results: All animals died in group C, 2/7 in group TSB, and 1/21 in group REBOA. SampEn and MSE decreased with hemorrhage and increased after interventions (TSB or REBOA+TSB). After resuscitative interventions, HRC metrics individually were associated with death: SampEn p=0.0002, area under the curve (AUC) =.88; MSE p=0.002, AUC=.83; both SampEn and MSE together p=0.0005, AUC=.90. Traditional vital signs were also associated with death: HR, p=0.02, AUC .72; MAP, p=0.01, AUC .85; Lac p=0.05, AUC=.69; and for all three metrics together p0.03, AUC=0.85. When traditional and HRC variables were combined into a single model the overall AUC was .93, p=0.003.

Learning Objectives: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) using generic balloon catheters placed into the descending aorta under fluoroscopy has been used to treat hemorrhagic shock in animal models. We tested a new non-image guided 7F ER-REBOA catheter (Pryor Medical Arvada, CO) for its potential to improve survival in a 100% lethal model of hemorrhagic shock. We hypothesized that ER-REBOA, placed without fluoroscopic guidance, improves survival. Methods: Spontaneously breathing, consciously sedated, sexually mature male Sinclair pigs undergone computerized exponential hemorrhage of 65% of their blood volume over 1 hour via an arterial line. Animals were then randomized into groups of 7 animals each including: negative control (NC), no resuscitation; positive control (PC), immediate transfusion of shed blood (TSB); ER30; 30 min of ERREBOA then TSB; ER60, 60 min of ER-REBOA then TSB; ER, 60 min of ERREBOA with TSB after 30 min of REBOA. After balloon deflation, epinephrine was given if mean arterial pressure was under 40 mm Hg. Up to 20 min of mechanical ventilation (FiO2 .21, RR 12, TV 10 ml/kg, ZEEP) was provided if animal suffered respiratory arrest. Animals were monitored for 240 min post-hemorrhage or until death. Survival was assessed via Kaplan-Meier analysis. Balloon placement was verified via post-mortem CT scan and at necropsy. Results: ER-REBOA was placed successfully in 100% of cases without fluoroscopy. Survival in the NC and PC groups was 0 and 71% respectively. Analysis showed significantly higher survival in the ER-REBOA groups: 100% in ER30 and ER60 groups and 86% in ER (p0.001). Epinephrine was given to 4/7 PC animals and to 6/7, 7/7, and 2/7 animals in ER30, ER60, and ER groups respectively. Ventilation support was given to 1/7, 2/7, and 3/7 in the ER30, ER60, and ER groups and to 2/7 in the PC group respectively.

Dry forests of the western United States (ponderosa pine, dry mixed conifer) are often considered at risk of uncharacteristic severe fires, but recent research has found historically extensive severe fire. This has left divergent perspectives about how to restore dry forests, protect people and infrastructure from fire, and interpret the ecological effects of large fires, such as the 2013 Rim fire, a human-set 104,000 ha fire in the western Sierra Nevada Mountains. To help resolve this uncertainty, I used new methods to reconstruct historical forest structure and fire and test 11 hypotheses about them, using A.D. 1865–1885 General Land Office surveys, across 330,000 ha of Sierran mixed-conifer forests. The reconstructions show these historical forests were open and park-like in places, but generally dense, averaging 293 trees/ha; shade-tolerant trees and large trees were abundant, but smaller (

Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a new class of antihyperglycemic agents that block renal sodium and glucose reabsorption and may reduce blood pressure (BP). We assessed the BP lowering ability of these agents using meta-analytic techniques. PubMed, SCOPUS, and Cochrane Central were searched through October 2013. We included fully published randomized controlled trials (RCTs) that evaluated SGLT2 inhibitors in patients with type-2 diabetes mellitus and reported change in systolic and/or diastolic BP. Subgroup analyses were performed for placebo-controlled trials and those with active controls. We also conducted meta-regression to assess for a dose-response effect, and whether baseline BP, changes in body weight, heart rate, and hematocrit were associated with the BP effects. Twenty-seven RCTs (n = 12,960 participants) were included. SGLT2 inhibitors significantly reduced both systolic BP (weighted mean difference, −4.0 mm Hg; 95% confidence interval, −4.4 to −3.5) and diastolic BP (weighted mean difference, −1.6 mm Hg; 95% confidence interval, −1.9 to −1.3) from baseline. Only canagliflozin had a significant dose-response relationship with SBP ( P = .008). Significant reductions in body weight and hematocrit were seen with the SGLTs. SGLTs had no significant effect on the incidence of orthostatic hypotension ( P > .05). SGLT2 inhibitors significantly reduce BP in patients with type 2 diabetes.

Accuracy of small-area, fire-interval estimation methods has been inadequately assessed, thus we conducted modern calibration and historical testing of the traditional composite-fire-interval and a newer all-tree-fire-interval method for estimating population mean fire intervals. We tested in eight areas, at four scales, using 30 small plots across ponderosa pine forests on the South Rim of Grand Canyon National Park. In modern calibration, individual-plot all-tree-fire-intervals were equal to population mean fire intervals in all plots. Across the eight areas, a mean-plot version of the all-tree-fire-interval method never failed, whereas mean-plot versions of composite-fire-intervals failed in 37.5–100% of areas. Pooled composite-fire-intervals, the traditional method, failed in all subareas. In historical testing, pooled and mean-plot all-tree-fire-interval methods and two variations of a mean-plot composite-fire-interval method had the lowest mean relative errors. Again, pooled composite-fire-intervals performed poorly across the eight areas. Overall, in modern and historical tests, the mean-plot all-tree-fire-interval method outperformed all others, but highly filtered mean-plot composite-fire-intervals were fairly accurate in historical tests. Both could be reliable methods, if replicated in small plots averaged over 600–1000-ha landscapes, but for small areas, the all-tree-fire-interval method outperformed others. However, for general use, there may be more value in spatially explicit, landscape-scale methods, rather than any small-area method.

This article addresses the analytic problems associated with a design in which one identifiable group is allocated to each treatment condition and members of those groups are measured to assess the intervention. Such designs are often called quasi-experiments if the groups are not randomized to conditions and group-randomized trials if the groups are randomized. They present special problems, and previous reports have argued against their use in efficacy or effectiveness trials. Even so, this design still appears with surprising frequency. This article presents the results from a new simulation study that underscores the analytic problems associated with this design.

The vegetation of Dinosaur National Monument and surrounding lands (∼298,000 ha) was reconstructed using General Land Office (GLO) survey records. This historical dataset was compared to two modern digital datasets to determine how vegetation has changed over 90 years. Net declines of 3–7% occurred in pinon-juniper woodland and 12–19% in montane shrubland, along with corresponding 16–26% increases in sagebrush shrublands. Shorter natural and human-caused fire rotations of 188–216 years appear to be driving woodland contraction. Pinon-juniper expansion was concentrated, but not strictly confined to areas near historical pinon-juniper-sagebrush ecotones, and was particularly favored at elevations of 2000–2400 m and on slopes of 10–30%. Shorter recent fire rotations in sagebrush appear linked to cheatgrass expansion. Fire exclusion has had no net effect on fire rotations in the study area, as these rotations are generally shorter, not longer than historical rotations. If trends continue, a landscape outside the historical range of variability with significantly more early seral sagebrush and grassland and less pinon-juniper woodland will emerge. Declines of pinon-juniper in the study area are similar to the recent loss of woodland in Mesa Verde National Park, Colorado, and suggest that historical woodlands on the Colorado Plateau may be declining due to an excess of fire since Euro-American settlement. If the goal is to maintain and restore the integrity of the natural vegetation and landscape of the study area, managers could suspend further resource-management burning, reduce unintentional human-set fires, and seek direct control of cheatgrass. Spatially complex patterns of woodland stability, recovery, contraction, and expansion show that century-scale data are needed across large landscapes to discern net trends in landscape change needed for ecological restoration, management, and understanding impending future change.

ObjectiveTo conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF).Patients and methodsWe searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF.ResultsEighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results.ConclusionsCost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.

The Minnesota Heart Health Program was a community trial of cardiovascular disease prevention methods that was conducted from 1980 to 1990 in three Upper Midwestern communities with three matched comparison communities. A 5- to 6-year intervention program used community-wide and individual health education in an attempt to decrease population risk. A major hypothesis was that the incidence of validated fatal and nonfatal coronary heart disease and stroke in 30- to 74-year-old men and women would decline differentially in the education communities after the health promotion program was introduced. This hypothesis was investigated using mixed-model regression. The intervention effect was modeled as a series of annual departures from a linear secular trend after a 2-year lag from the start of the intervention program. In the education communities, 2,394 cases of coronary heart disease and 818 cases of stroke occurred, with 2,526 and 739 cases, respectively, being seen in the comparison communities. The overall decline in coronary heart disease incidence was 1.8 percent per year in men (p = 0.03) and 3.6 percent per year in women (p = 0.007). For stroke, there were no significant secular trends. The authors recently published findings showing minimal effects of sustained intervention on risk factor levels. In the current report, there was no evidence of a significant intervention effect on morbidity or mortality, either for coronary heart disease or for stroke.

Dry western forests (e.g., ponderosa pine and mixed conifer) were thought to have been historically old and park-like, maintained by low-severity fires, and to have become denser and more prone to high-severity fire. In the Pacific Northwest, early aerial photos (primarily in Washington), showed that dry forests instead had variable-severity fires and forest structure, but more detail is needed. Here I used pre-1900 General Land Office Surveys, with new methods that allow accurate reconstruction of detailed forest structure, to test eight hypotheses about historical structure and fire across about 400,000 ha of dry forests in Oregon's eastern Cascades. The reconstructions show that only about 13.5% of these forests had low tree density. Forests instead were generally dense (mean = 249 trees/ha), but density varied by a factor of 2–4 across about 25,000-ha areas. Shade-tolerant firs historically were 17% of trees, dominated about 12% of forest area, and were common in forest understories. Understory trees and shrubs dominated on 83.5%, and were dense across 44.8% of forest area. Small trees (10–40 cm dbh) were >50% of trees across 72.3% of forest area. Low-severity fire dominated on only 23.5%, mixed-severity fire on 50.2%, and high-severity fire on 26.2% of forest area. Historical fire included modest-rotation (29–78 years) low-severity and long-rotation (435 years) high-severity fire. Given historical variability in fire and forest structure, an ecological approach to restoration would restore fuels and manage for variable-severity fires, rather than reduce fuels to lower fire risk. Modest reduction in white fir/grand fir and an increase in large snags, down wood, and large trees would enhance recovery from past extensive logging and increase resiliency to future global change. These forests can be maintained by wildland fire use, coupled, near infrastructure, with prescribed fires that mimic historical low-severity fires.

Cheatgrass, a non-native annual grass, dominates millions of hectares in semiarid ecosystems of the Intermountain West (USA). Post-fire invasions can reduce native species diversity and alter ecological processes. To curb cheatgrass invasion, land managers often seed recently burned areas with perennial competitor species. We sampled vegetation within burned (1–9 years post-fire) and nearby unburned (representing pre-fire) piñon–juniper (Pinus edulis–Juniperus osteosperma) woodland and sagebrush (Artemisia sp.) in western Colorado to analyze variables that might explain cheatgrass cover after fire. A multiple regression model suggests higher cheatgrass cover after fire with: (1) sagebrush v. piñon–juniper; (2) higher pre-fire cover of annual forbs; (3) increased time since fire; (4) lower pre-fire cover of biological soil crust; and (5) lower precipitation the year before fire. Time since fire, which coincided with higher precipitation, accounts for most of the variability in cheatgrass cover. No significant difference was found in mean cheatgrass cover between seeded and unseeded plots over time. However, negative relationships with pre-fire biological soil crust cover and native species richness suggest livestock-degraded areas are more susceptible to post-fire invasion. Proactive strategies for combating cheatgrass should include finding effective native competitors and restoring livestock-degraded areas.

We analyzed 17 photographs, taken between 1873 and 1915, that illustrate widespread mortality in subalpine forests of western Colorado. Eight of these photographs, reproduced here, contain three general patterns of mortality, interpreted to result from spruce beetle (Dendroctonus rufipennis) attacks, fires, and wind. Tree-ring chronologies at four of the sites corroborated the role of spruce beetle in killing the trees visible in the photographs. The photographs and tree-ring dates suggest that the spruce beetle outbreak occurred between the 1850s and the 1880s, and affected forests from central New Mexico to north-central Colorado. Spruce beetle outbreaks are a significant type of natural disturbance in these forests. The relative contribution of beetles and fires to subalpine forest structure is in need of further research. The sequence and spatial configuration of disturbances by spruce beetles, fire, and wind varies, and can be spatially heterogeneous, even on small land areas. In such areas, forest responses to uniformly applied disturbance controls (e.g., fire suppression) will be spatially heterogeneous, not affecting all parts of the landscape uniformly.