Accurate Hybrid Density Functionals with UW12 Correlation.

In previous work, we suggested a single-parameter hybrid functional containing a novel correlation contribution based on the Unsöld approximation, UW12. This model resembles the explicitly correlated part of MP2-F12 theory and can be written as an explicit formula in terms of the single-particle reduced density matrix. Here, we further investigate hybrid functionals containing UW12 correlation and in particular look at functionals with a large fraction of exact exchange to reduce the self-interaction error. We suggest two new hybrid functionals B-LYP-osUW12 and fB-LYP-osUW12. On the test sets we use, our best hybrid functional overall (B-LYP-osUW12) is of similar accuracy to the best double hybrids considered while eliminating the need for virtual orbitals.

Immediate effect of kinesiology tape on ankle stability.

BACKGROUND: Lateral ankle sprain is one of the most common musculoskeletal injuries, particularly among the sporting population. Due to such prevalence, many interventions have been tried to prevent initial, or further, ankle sprains. Current research shows that the use of traditional athletic tape can reduce the incidence of sprain recurrence, but this may be at a cost to athletic performance through restriction of motion. Kinesiology tape, which has become increasingly popular, is elastic in nature, and it is proposed by the manufacturers that it can correct ligament damage. Kinesiology tape, therefore, may be able to improve stability and reduce ankle sprain occurrence while overcoming the problems of traditional tape. AIM: To assess the effect of kinesiology tape on ankle stability. METHODS: 27 healthy individuals were recruited, and electromyography (EMG) measurements were recorded from the peroneus longus and tibialis anterior muscles. Recordings were taken from the muscles of the dominant leg during induced sudden ankle inversion perturbations using a custom-made tilting platform system. This was performed with and without using kinesiology tape and shoes, creating four different test conditions: barefoot(without tape), shoe(without tape), barefoot(with tape) and shoe(with tape). For each test condition, the peak muscle activity, average muscle activity and the muscle latency were calculated. RESULTS: No significant difference (p>0.05) was found by using the kinesiology tape on any of the measured variables while the wearing of shoes significantly increased all the variables. CONCLUSION: Kinesiology tape has no effect on ankle stability and is unable to nullify the detrimental effects that shoes appear to have.

Electrophotocatalytic C-H Functionalization of Ethers with High Regioselectivity.

The highly regioselective electrophotocatalytic C-H functionalization of ethers is described. These reactions are catalyzed by a trisaminocyclopropenium (TAC) ion at mild electrochemical potential with visible light irradiation. Ethers undergo oxidant-free coupling with isoquinolines, alkenes, alkynes, pyrazoles, and purines with typically high regioselectivity for the less-hindered α-position. The reaction is proposed to operate via hydrogen atom transfer (HAT) from the substrate to the photoexcited TAC radical dication, thus demonstrating a new reactivity mode for this electrophotocatalyst.

Electrophotocatalysis with a Trisaminocyclopropenium Radical Dication.

Visible-light photocatalysis and electrocatalysis are two powerful strategies for the promotion of chemical reactions. Here, these two modalities are combined in an electrophotocatalytic oxidation platform. This chemistry employs a trisaminocyclopropenium (TAC) ion catalyst, which is electrochemically oxidized to form a cyclopropenium radical dication intermediate. The radical dication undergoes photoexcitation with visible light to produce an excited-state species with oxidizing power (3.33 V vs. SCE) sufficient to oxidize benzene and halogenated benzenes via single-electron transfer (SET), resulting in C-H/N-H coupling with azoles. A rationale for the strongly oxidizing behavior of the photoexcited species is provided, while the stability of the catalyst is rationalized by a particular conformation of the cis-2,6-dimethylpiperidine moieties.

Oxidizable Ketones: Persistent Radical Cations from the Single-Electron Oxidation of 2,3-Diaminocyclopropenones.

Single electron oxidation of 2,3-diaminocyclopropenones is shown to give rise to stable diaminocyclopropenium oxyl (DACO) radical cations. Cyclic voltammetry reveals reversible oxidations in the range of +0.70-1.10 V (vs. SCE). Computational, EPR, and X-ray analysis support the view that the oxidized species is best described as a cyclopropenium ion with spin density located on the heteroatom substituents, including 23.5 % on oxygen. The metal-ligand behavior of the DACO radical is also described.

The effects of joint disease, inhibitors and other complications on health-related quality of life among males with severe haemophilia A in the United States.

INTRODUCTION: Health-related quality of life (HRQoL) is reduced among persons with haemophilia. Little is known about how HRQoL varies with complications of haemophilia such as inhibitors and joint disease. Estimates of preference-based HRQoL measures are needed to model the cost-effectiveness of prevention strategies. AIM: We examined the characteristics of a national sample of persons with severe haemophilia A for associations with two preference-based measures of HRQoL. METHODS: We analysed utility weights converted from EuroQol 5 Dimensions (EQ-5D) and the Short Form 6 Dimensions (SF-6D) scores from 1859 males aged ≥14 years with severe haemophilia A treated at 135 US haemophilia treatment centres in 2005-2011. Bivariate and regression analyses examined age-group-specific associations of HRQoL with inhibitor status, overweight/obesity, number of bleeds, viral infections, indicators of liver and joint disease, and severe bleeding at the time of the first HRQoL measurement. RESULTS: Overall mean HRQoL utility weight values were 0.71 using the SF-6D and 0.78 using the EQ-5D. All studied patient characteristics except for overweight/obesity were significantly associated with HRQoL in bivariate analyses. In a multivariate analysis, only joint disease was significantly associated with utility weights from both HRQoL measures and across all age groups. After adjustment for joint disease and other variables, the presence of an inhibitor was not significantly associated with HRQoL scores from either of the standardized assessment tools. CONCLUSION: Clinically significant complications of haemophilia, especially joint disease, are strongly associated with HRQoL and should be accounted for in studies of preference-based health utilities for people with haemophilia.

Trends of lack of health insurance among US adults aged 18-64 years: findings from the Behavioral Risk Factor Surveillance System, 1993-2014.

OBJECTIVE: To examine the prevalence of lack of health insurance and its changes over time among adult residents (aged 18-64 years) in 50 states and the District of Columbia (DC). STUDY DESIGN: Cross-sectional surveys. METHODS: We aggregated annual state-based Behavioral Risk Factor Surveillance System (BRFSS) data from 1993 through 2014 to provide nationwide and state-based prevalence estimates for lack of insurance among adults aged 18-64 years. The adjusted prevalence was estimated using log-linear regression analyses with a robust variance estimator after controlling for demographic variables. The trend was assessed separately for the periods 1993-2010 and 2011-2014 due to methodologic changes in the BRFSS. RESULTS: From 1993 through 2010, the adjusted prevalence of lack of health insurance increased by 0.54% (P < 0.0001) annually (range: 16.3% in 1995 to 19.1% in 2005); this prevalence decreased significantly in 2014 (15.1%). In 2014, Georgia, Mississippi, and Texas had the highest adjusted prevalences (range: 23.0-24.6%) of lack of health insurance, and DC, Massachusetts, and Rhode Island had the lowest (range: 6.2-10.1%). The changes in the prevalence of lack of insurance over time varied significantly by state. CONCLUSIONS: The nationwide prevalence of lack of health insurance decreased significantly in the past few years, especially in 2014 when about one-seventh of Americans aged 18-64 years reported lack of health insurance coverage. The huge variations in the prevalence of lack of health insurance and its changes over time among states suggest continuing efforts to ensure healthcare access for all Americans are needed to improve the overall health of the population.

Registered Replication Report: Strack, Martin, & Stepper (1988).

According to the facial feedback hypothesis, people's affective responses can be influenced by their own facial expression (e.g., smiling, pouting), even when their expression did not result from their emotional experiences. For example, Strack, Martin, and Stepper (1988) instructed participants to rate the funniness of cartoons using a pen that they held in their mouth. In line with the facial feedback hypothesis, when participants held the pen with their teeth (inducing a "smile"), they rated the cartoons as funnier than when they held the pen with their lips (inducing a "pout"). This seminal study of the facial feedback hypothesis has not been replicated directly. This Registered Replication Report describes the results of 17 independent direct replications of Study 1 from Strack et al. (1988), all of which followed the same vetted protocol. A meta-analysis of these studies examined the difference in funniness ratings between the "smile" and "pout" conditions. The original Strack et al. (1988) study reported a rating difference of 0.82 units on a 10-point Likert scale. Our meta-analysis revealed a rating difference of 0.03 units with a 95% confidence interval ranging from -0.11 to 0.16.

Positive Affect and Cognitive Restoration: Investigating the Role of Valence and Arousal.

Positive moods are thought to restore self-control resources following depletion. However, it is not well understood whether this effect is due to affective valence (pleasantness), arousal (activation), or a combination of both. Across four studies, we set out to investigate the role of positive moods on cognitive and behavioral measures of self-regulation in an ego-depletion paradigm. In studies 1 and 2, we independently manipulated affective valence and arousal and assessed self-regulation with a Stroop task. Results did not suggest a restorative effect of either on cognitive resources. In study 3, we employed both behavioral (the 'handgrip task') and cognitive (Stroop) assessments of self-regulation. Again, no significant effect of mood was observed on the Stroop task. Additionally, participants did not persist significantly longer on the handgrip task following a positive mood induction. Finally, in study 4, high vs. low states of arousal were manipulated and self-regulation was assessed via pre- and post-manipulation Stroop performance. In study 4, Stroop performance improved slightly more across time points for those in the high arousal condition than for those in the low arousal condition. Therefore, across four studies, we failed to find a consistent pattern of results suggesting that positive moods restore cognitive resources.

Tracking psychosocial health in adults with epilepsy--estimates from the 2010 National Health Interview Survey.

OBJECTIVE: This study provides population-based estimates of psychosocial health among U.S. adults with epilepsy from the 2010 National Health Interview Survey. METHODS: Multinomial logistic regression was used to estimate the prevalence of the following measures of psychosocial health among adults with epilepsy and those without epilepsy: 1) the Kessler-6 scale of serious psychological distress; 2) cognitive limitation, the extent of impairments associated with psychological problems, and work limitation; 3) social participation; and 4) the Patient-Reported Outcome Measurement Information System Global Health Scale. RESULTS: Compared with adults without epilepsy, adults with epilepsy, especially those with active epilepsy, reported significantly worse psychological health, more cognitive impairment, difficulty in participating in some social activities, and reduced health-related quality of life (HRQOL). CONCLUSIONS: These disparities in psychosocial health in U.S. adults with epilepsy serve as baseline national estimates of their HRQOL, consistent with Healthy People 2020 national objectives on HRQOL.

In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [(11)C]-(+)-PHNO.

Drug addiction has been associated with deficits in mesostriatal dopamine (DA) function, but whether this state extends to behavioral addictions such as pathological gambling (PG) is unclear. Here we used positron emission tomography and the D3 receptor-preferring radioligand [(11)C]-(+)-PHNO during a dual-scan protocol to investigate DA release in response to oral amphetamine in pathological gamblers (n=12) and healthy controls (n=11). In contrast with human neuroimaging findings in drug addiction, we report the first evidence that PG is associated with greater DA release in dorsal striatum (54-63% greater [(11)C]-(+)-PHNO displacement) than controls. Importantly, dopaminergic response to amphetamine in gamblers was positively predicted by D3 receptor levels (measured in substantia nigra), and related to gambling severity, allowing for construction of a mechanistic model that could help explain DA contributions to PG. Our results are consistent with a hyperdopaminergic state in PG, and support the hypothesis that dopaminergic sensitization involving D3-related mechanisms might contribute to the pathophysiology of behavioral addictions.

Development and psychometric evaluation of the public health surveillance well-being scale.

PURPOSE: To develop and psychometrically evaluate the brief Public Health Surveillance Well-Being Scale (PHS-WB) that captures mental, physical, and social components of well-being. METHODS: Using data from 5,399 HealthStyles survey respondents, we conducted bi-factor, item response theory, and differential item functioning analyses to examine the psychometric properties of a pool of 34 well-being items. Based on the statistical results and content considerations, we developed a brief 10-item well-being scale and assessed its construct validity through comparisons of demographic subgroups and correlations with measures of related constructs. RESULTS: Based on the bi-factor analyses, the items grouped into both an overall factor and individual domain-specific factors. The PHS-WB scale demonstrated good internal consistency (alpha = 0.87) and correlated highly with scores for the entire item pool (r = 0.94). The well-being scale scores differed as expected across demographic groups and correlated with global and domain-specific measures of similar constructs, supporting its construct validity. CONCLUSION: The 10-item PHS-WB scale demonstrates good psychometric properties, and its high correlation with the item pool suggests minimal loss of information with the use of fewer items. The brief PHS-WB allows for well-being assessment on national surveys or in other situations where a longer form may not be feasible.

Reduced incidence and severity of experimental autoimmune arthritis in mice expressing catalytically inactive A disintegrin and metalloproteinase 8 (ADAM8).

A disintegrin and metalloproteinase 8 (ADAM8), a catalytically active member of the ADAMs family of enzymes, is expressed primarily on immune cells and thus probably involved in inflammatory responses. ADAM8 is also produced by chondrocytes, and recombinant ADAM8 can induce cartilage catabolism. We therefore decided to test the role of ADAM8 in autoimmune inflammatory arthritis using transgenic mice expressing catalytically inactive ADAM8. Transgenic DBA/1J mice expressing an inactivating point mutation in the ADAM8 gene to change Glu330 to Gln330 (ADAM8(EQ)) were generated to evaluate the proteolytic function of ADAM8 in an lipopolysaccharide-synchronized collagen-induced arthritis (LPS-CIA) model of autoimmune arthritis. The systemic inflammatory reaction to LPS was also evaluated in these mice. Expression profiling of paw joints from wild-type mice revealed that ADAM8 mRNA levels increased at the onset of clinical arthritis and correlated well with cellular macrophage markers. When subjected to LPS-CIA, ADAM8(EQ) mice demonstrated decreased incidence and severity of clinical arthritis compared to wild-type mice. Histological examination of paw joints from ADAM8(EQ) mice confirmed marked attenuation of synovial inflammation, cartilage degradation and bone resorption when compared to wild-type mice. However, transgenic mice and wild-type mice responded similarly to LPS-induced systemic inflammation with regard to mortality, organ weights, neutrophil sequestration and serum cytokine/chemokine production. We conclude that ADAM8 proteolytic activity plays a key role in the development of experimental arthritis and may thus be an attractive target for the treatment of arthritic disorders while minimizing risk of immunocompromise.

Effects of the atypical stimulant modafinil on a brief gambling episode in pathological gamblers with high vs. low impulsivity.

Pathological gambling (PG) is a serious psychiatric disorder afflicting 1-3% of the general population. Experimental evidence indicates shared neurochemical substrates for PG and psychostimulant addiction. Impulsivity characterizes one key subtype of PG. Therefore, medications that ameliorate psychostimulant addiction and impulsive syndromes might also benefit impulsive PG subjects. The atypical stimulant, modafinil reduces cocaine abuse and impulsivity in patients with ADHD. The present study sought to determine if modafinil (200 mg) would reduce the reinforcing effects of slot machine gambling in PG subjects, and if this effect was stronger in high (H-I) vs. low (L-I) impulsivity subjects (N = 20). A placebo-controlled, double-blind, counterbalanced, repeated measures design was employed. Apart from bet size, which declined uniformly in both groups under drug, modafinil had bi-directional effects in the two groups. In H-I subjects, the drug decreased desire to gamble, salience of Gambling words, disinhibition and risky decision-making. In L-I subjects, modafinil increased scores on these indices. Modafinil also differentially affected blood pressure response to the game in the two groups. These findings for modafinil appear to fit well with a growing literature demonstrating bi-directional effects of D2 agonists as a function of trait impulsivity. Impulsivity could critically moderate medication response in PG.

Low-dose diazepam primes motivation for alcohol and alcohol-related semantic networks in problem drinkers.

Considerable research with animals indicates that the GABA-benzodiazepine (BZ) system plays a key role in alcohol reinforcement. However, only limited research appears to have assessed this issue directly in humans. The present study investigated whether low-dose diazepam would cross-prime motivation for alcohol in problem drinkers. Twelve male problem drinkers (Alcohol Dependence Scale; ADS score > or =9) received oral diazepam (5 mg) and placebo, in a counterbalanced manner on separate sessions. There were three measures of primed motivation for alcohol: self-reported desire for alcohol, consumption of placebo beer in an ostensible taste test procedure, and automatically executed vocal reading responses to Alcohol versus Neutral words on a computer-based task. Diazepam significantly increased beer consumption, and produced a marginally significant increase in reported desire for alcohol. On the reading task, diazepam significantly decreased response latency to Alcohol words relative to Neutral words. Latency to Alcohol words correlated significantly with beer consumption under the drug. Moreover, response latency to Alcohol words under the drug also predicted ADS scores. Thus, severity of dependence was directly linked with vulnerability to a BZ priming effect on motivation for alcohol. These findings provide direct evidence that the GABA-BZ system plays an important role in alcohol reinforcement in problem drinkers.

Exercise training increases the näive to memory T cell ratio in old mice.

Aging is associated with changes in T cells including involution of the thymus gland and an imbalance in the proportion of näive (CD44lo) and memory (CD44hi) T cells in the periphery. Reversal of these changes may improve immunity in the aged. We sought to determine whether 4 months of moderately intense treadmill running (EXC; 5 days/week, 45 min/day, 13-22 m/min) in 2 month (Y) and 18 month (O) old male Balb/c mice would alter T lymphocyte profiles in the thymus and spleen when compared to sedentary controls (CON). Splenocytes and thymocytes were harvested 24-48 h after the last exercise session and analyzed using immunofluorescence and flow cytometry. While there were significant age-related changes (lower cell number, altered subsets) in the thymuses of O when compared to Y mice, exercise training failed to affect any of these measures in mice of either age. Aged mice exhibited a significantly (p < .05) higher percentage of splenic memory cells and a lower percentage of näive cells in both the CD4 and CD8 T cell subsets. Interestingly, exercise training significantly (p < .05) increased the percentage of näive and decreased the percentage of memory cells in both the CD4+ (69.6+/-1.7% näive and 30.4+/-1.7% memory for OCON vs. 75.0+/-1.5% näive and 25.0+/-1.5% memory in OEXC) and CD8+ (60.0+/-2.6% näive and 40.0+/-2.6% memory in OCON vs. 76.7+/-2.7% näive and 23.3+/-2.7% memory in OEXC) T cells subsets in O, but not Y, mice. This effect was due to a decrease in the absolute number of memory cells and not an increase in the absolute number of näive cells. We conclude that 4 months of EXC has little restorative effect on the thymus in aged mice, but can restore the percentages of näive and memory cells in the spleen towards that of young mice, perhaps due to removal of memory cells.

Acetaminophen, aspirin, and chronic renal failure.

BACKGROUND: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect METHODS: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics RESULTS: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated CONCLUSIONS: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.

Acute subjective and physiological responses to smoking in adolescents.

AIMS: To determine the topography of cigarette smoking and the subjective and physiological effects of abstinence and nicotine in adolescents who smoke on a daily versus a non-daily basis. DESIGN: Repeated measures experiment, non-blinded, involving a single test session. SETTING: Human psychopharmacology laboratory. PARTICIPANTS: Twenty-one daily and 21 non-daily adolescent cigarette smokers (21 females; 21 males; age 13-18 years) with life-time use greater than 10 cigarettes, responding to radio and print advertisements. INTERVENTION: Overnight abstinence from cigarettes followed by smoking of a single cigarette furnished by the participant at test. MEASUREMENTS: The Fagerstrom Test for Nicotine Dependence, saliva nicotine and cotinine, expired air carbon monoxide (CO), heart rate (HR), self-report scales and smoking topography. Most measurements were performed before and after smoking. FINDINGS: Saliva nicotine, CO and HR increased, and self-reported intention and desire to smoke decreased, after smoking (p < 0.001). Fagerstrom scores indicated greater dependence and desire to smoke in daily than in non-daily smokers. HR increased substantially over pre-smoking levels in both groups. Puff topography did not differ between the groups, although collectively these participants appeared to take smaller and more puffs than adult smokers tested under similar conditions. CONCLUSION: This study provides initial evidence that adolescent cigarette smokers self-administer physiologically active doses of nicotine very early in their smoking careers. Nicotine dependence in adolescents appears to be a function of the current frequency of cigarette use, and subjective-behavioral consequences of abstinence and smoking are evident even in non-daily smokers.

Self-reported body mass index and health-related quality of life: findings from the Behavioral Risk Factor Surveillance System.

OBJECTIVE: To examine the relationship between self-reported body mass index (BMI) and health-related quality of life in the general adult population in the United STATES: RESEARCH METHODS AND PROCEDURES: Using data from 109,076 respondents in the 1996 Behavioral Risk Factor Surveillance System, we examined how self-reported BMI is associated with five health-related quality of life measures developed by the Centers for Disease Control and Prevention for population health surveillance. RESULTS: After adjusting for age, gender, race or ethnicity, educational attainment, employment status, smoking status, and physical activity status, participants with a self-reported BMI of <18.5 kg/m(2) and participants with a self-reported BMI of > or =30 kg/m(2) reported impaired quality of life. Compared with persons with a self-reported BMI of 18.5 to <25 kg/m(2), odds ratios (ORs) of poor or fair self-rated health increased among persons with self-reported BMIs of <18.5 (1.57, 95% confidence interval [CI]: 1.31 to 1.89), 25 to <30 kg/m(2) (1.12, 95% CI: 1.04 to 1.20), 30 to <35 kg/m(2) (1.65, 95% CI: 1.50 to 1.81), 35 to <40 kg/m(2) (2.58, 95% CI: 2.21 to 3.00), and > or =40 kg/m(2) (3.23, 95% CI: 2.63 to 3.95); ORs for reporting > or =14 days of poor physical health during the previous 30 days were 1.44 (95% CI: 1.21 to 1.72), 1.04 (95% CI: 0.96 to 1.14), 1.32 (95% CI: 1.19 to 1.47), 1.80 (95% CI: 1.52 to 2.13), and 2.37 (95% CI: 1.90 to 2.94), respectively; ORs for having > or =14 days of poor mental health during the previous 30 days were 1.18 (95% CI: 0.97 to 1.42), 1.02 (95% CI: 0.95 to 1.11), 1.22 (95% CI: 1.10 to 1.36), 1.68 (95% CI: 1.42 to 1.98), and 1.66 (95% CI: 1.32 to 2.09), respectively. DISCUSSION: In the largest study to date, low and increased self-reported BMI significantly impaired health-related quality of life. Particularly, deviations from normal BMI affected physical functioning more strongly than mental functioning.

Risk factors for subsequent invasive breast cancer and breast cancer death after ductal carcinoma in situ: a population-based case-control study in Sweden.

In a case-control study derived from a cohort of 4661 women with a primary carcinoma in situ of the breast, we investigated age at diagnosis, mode of detection, tumor characteristics, and primary therapy, as prognostic factors for developing invasive breast cancer or dying from breast cancer. From all of the women with a primary carcinoma in situ reported to the Swedish Cancer Registry from 1960 through 1992, we selected as cases all of the women with a ductal carcinoma in situ who later died of breast cancer (n = 39) or who developed a subsequent invasive cancer in either breast (n = 118). From this cohort, we also selected controls matched to the cases by year of diagnosis and health care region. We conducted univariate and multivariate analyses to study the association between risk of invasive cancer or death and the different risk factors. Large size, diameter > or = 25 mm [odds ratio (OR), 3.5; 95% confidence interval (CI), 1.1-11.4] and multifocality (OR, 3.9; 95% CI, 1.2-12.7) increased the risk of breast cancer death in univariate analysis. Postoperative radiotherapy (OR, 0.1; 95% CI, 0.0-1.0) and mastectomy (OR, 0.1-95% CI, 0.0-0.5) lowered the risk of an ipsilateral invasive cancer in multivariate analysis. The risk pattern by treatment category differed between those who had an ipsilateral invasive cancer and those who either had a contralateral cancer or died from breast cancer. The driving forces behind local and generalized disease may differ. Because confounding by indication may influence the effects of different treatments, the results should be interpreted with caution.