Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.

Randomized, controlled trial investigating short-term health-related quality of life with doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: European Organization for Research and Treatment of Cancer Breast Cancer Group, Investigational Drug Branch for Breast Cancer and the New Drug Development Group Study.

PURPOSE: To compare health-related quality of life (HRQOL) in patients with metastatic breast cancer receiving the combination of doxorubicin and paclitaxel (AT) or doxorubicin and cyclophosphamide (AC) as first-line chemotherapy treatment. PATIENTS AND METHODS: Eligible patients (n = 275) with anthracycline-naive measurable metastatic breast cancer were randomly assigned to AT (doxorubicin 60 mg/m(2) as an intravenous bolus plus paclitaxel 175 mg/m(2) as a 3-hour infusion) or AC (doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation of paclitaxel (200 mg/m(2)) and cyclophosphamide (750 mg/m(2)) was planned at cycle 2 to reach equivalent myelosuppression in the two groups. HRQOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the EORTC Breast Module at baseline and the start of cycles 2, 4, and 6, and 3 months after the last cycle. RESULTS: Seventy-nine percent of the patients (n = 219) completed a baseline measure. However, there were no statistically significant differences in HRQOL between the two treatment groups. In both groups, selected aspects of HRQOL were impaired over time, with increased fatigue, although some clinically significant improvements in emotional functioning were seen, as well as a reduction in pain over time. Overall, global quality of life was maintained in both treatment groups. CONCLUSION: This information is important when advising women patients of the expected HRQOL consequences of treatment regimens and should help clinicians and their patients make informed treatment decisions.

Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist.

Interleukin-1 beta (IL1β) is a proinflammatory cytokine that mediates arthritic pathologies. Our objectives were to evaluate pain and limb dysfunction resulting from IL1β over-expression in the rat knee and to investigate the ability of local IL1 receptor antagonist (IL1Ra) delivery to reverse-associated pathology. IL1β over-expression was induced in the right knees of 30 Wistar rats via intra-articular injection of rat fibroblasts retrovirally infected with human IL1β cDNA. A subset of animals received a 30 µl intra-articular injection of saline or human IL1Ra on day 1 after cell delivery (0.65 µg/µl hIL1Ra, n = 7 per group). Joint swelling, gait, and sensitivity were investigated over 1 week. On day 8, animals were sacrificed and joints were collected for histological evaluation. Joint inflammation and elevated levels of endogenous IL1β were observed in knees receiving IL1β-infected fibroblasts. Asymmetric gaits favoring the affected limb and heightened mechanical sensitivity (allodynia) reflected a unilateral pathology. Histopathology revealed cartilage loss on the femoral groove and condyle of affected joints. Intra-articular IL1Ra injection failed to restore gait and sensitivity to preoperative levels and did not reduce cartilage degeneration observed in histopathology. Joint swelling and degeneration subsequent to IL1β over-expression is associated limb hypersensitivity and gait compensation. Intra-articular IL1Ra delivery did not result in marked improvement for this model; this may be driven by rapid clearance of administered IL1Ra from the joint space. These results motivate work to further investigate the behavioral consequences of monoarticular arthritis and sustained release drug delivery strategies for the joint space.

Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer.

BACKGROUND: The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy. METHODS/DESIGN: Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk⁻¹ of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO₂peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO₂peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO₂peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks). DISCUSSION: EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO₂peak and other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy. TRIAL REGISTRATION: NCT01186367.

The effects of sleep hypoxia on coagulant factors and hepatic inflammation in emphysematous rats.

OBJECTIVES: To develop a sleep hypoxia (SH) in emphysema (SHE) rat model and to explore whether SHE results in more severe hepatic inflammation than emphysema alone and whether the inflammation changes levels of coagulant/anticoagulant factors synthesized in the liver. METHODS: Seventy-five rats were put into 5 groups: SH control (SHCtrl), treated with sham smoke exposure (16 weeks) and SH exposure (12.5% O(2), 3 h/d, latter 8 weeks); emphysema control (ECtrl), smoke exposure and sham SH exposure (21% O(2)); short SHE (SHEShort), smoke exposure and short SH exposure (1.5 h/d); mild SHE (SHEMild), smoke exposure and mild SH exposure (15% O(2)); standard SHE (SHEStand), smoke exposure and SH exposure. Therefore, ECtrl, SHEShort, SHEMild and SHEStand group were among emphysematous groups. Arterial blood gas (ABG) data was obtained during preliminary tests. After exposure, hepatic inflammation (interleukin -6 [IL-6] mRNA and protein, tumor necrosis factor α [TNFα] mRNA and protein) and liver coagulant/anticoagulant factors (antithrombin [AT], fibrinogen [FIB] and Factor VIII [F VIII]) were evaluated. SPSS 11.5 software was used for statistical analysis. RESULTS: Characteristics of emphysema were obvious in emphysematous groups and ABGs reached SH criteria on hypoxia exposure. Hepatic inflammation parameters and coagulant factors are the lowest in SHCtrl and the highest in SHEStand while AT is the highest in SHCtrl and the lowest in SHEStand. Inflammatory cytokines of liver correlate well with coagulant factors positively and with AT negatively. CONCLUSIONS: When SH is combined with emphysema, hepatic inflammation and coagulability enhance each other synergistically and produce a more significant liver-derivative inflammatory and prothrombotic status.

Where does energy R&D come from? Examining crowding out from energy R&D

Recent efforts to endogenize technological change in climate policy models demonstrate the importance of accounting for the opportunity cost of climate R&D investments. Because the social returns to R&D investments are typically higher than the social returns to other types of investment, any new climate mitigation R&D that comes at the expense of other R&D investment may dampen the overall gains from induced technological change. Unfortunately, there has been little empirical work to guide modelers as to the potential magnitude of such crowding out effects. This paper considers both the private and social opportunity costs of climate R&D. Addressing private costs, we ask whether an increase in climate R&D represents new R&D spending, or whether some (or all) of the additional climate R&D comes at the expense of other R&D. Addressing social costs, we use patent citations to compare the social value of alternative energy research to other types of R&D that may be crowded out. Beginning at the industry level, we find no evidence of crowding out across sectors-that is, increases in energy R&D do not draw R&D resources away from sectors that do not perform R&D. Given this, we proceed with a detailed look at alternative energy R&D. Linking patent data and financial data by firm, we ask whether an increase in alternative energy patents leads to a decrease in other types of patenting activity. While we find that increases in alternative energy patents do result in fewer patents of other types, the evidence suggests that this is due to profit-maximizing changes in research effort, rather than financial constraints that limit the total amount of R&D possible. Finally, we use patent citation data to compare the social value of alternative energy patents to other patents by these firms. Alternative energy patents are cited more frequently, and by a wider range of other technologies, than other patents by these firms, suggesting that their social value is higher. © 2011 Elsevier B.V.

Benefits and Effects of Interactive Gaming Exercise as Compared to Traditional Exercise Techniques: An Investigation of the Relationship Between Physical Activity Levels and Mode of Activity in College Students

Gemstone Team F.I.T.N.E.S.S. (Fun Interactive Techniques for New Exercise and Sport Styles)

Emergent group level navigation: an agent-based evaluation of movement patterns in a folivorous primate.

The foraging activity of many organisms reveal strategic movement patterns, showing efficient use of spatially distributed resources. The underlying mechanisms behind these movement patterns, such as the use of spatial memory, are topics of considerable debate. To augment existing evidence of spatial memory use in primates, we generated movement patterns from simulated primate agents with simple sensory and behavioral capabilities. We developed agents representing various hypotheses of memory use, and compared the movement patterns of simulated groups to those of an observed group of red colobus monkeys (Procolobus rufomitratus), testing for: the effects of memory type (Euclidian or landmark based), amount of memory retention, and the effects of social rules in making foraging choices at the scale of the group (independent or leader led). Our results indicate that red colobus movement patterns fit best with simulated groups that have landmark based memory and a follow the leader foraging strategy. Comparisons between simulated agents revealed that social rules had the greatest impact on a group's step length, whereas the type of memory had the highest impact on a group's path tortuosity and cohesion. Using simulation studies as experimental trials to test theories of spatial memory use allows the development of insight into the behavioral mechanisms behind animal movement, developing case-specific results, as well as general results informing how changes to perception and behavior influence movement patterns.

Effects of Web-Based Self-Reporting: College Students’ Self-Efficacy Regarding Fruit and Vegetable Intake

This study evaluated the effect of an online diet-tracking tool on college students’ self-efficacy regarding fruit and vegetable intake. A convenience sample of students completed online self-efficacy surveys before and after a six-week intervention in which they tracked dietary intake with an online tool. Group one (n=22 fall, n=43 spring) accessed a tracking tool without nutrition tips; group two (n=20 fall, n=33 spring) accessed the tool and weekly nutrition tips. The control group (n=36 fall, n=60 spring) had access to neither. Each semester there were significant changes in self-efficacy from pre- to post-test for men and for women when experimental groups were combined (p<0.05 for all); however, these changes were inconsistent. Qualitative data showed that participants responded well to the simplicity of the tool, the immediacy of feedback, and the customized database containing foods available on campus. Future models should improve user engagement by increasing convenience, potentially by automation.

Maternal Effects of Respiratory Syncytial Virus Infection during Pregnancy.

Given the illness and deaths caused by respiratory syncytial virus (RSV) infection during the first year of life, preventing infant RSV infections through maternal vaccination is intriguing. However, little is known about the extent and maternal effects of RSV infection during pregnancy. We describe 3 cases of maternal RSV infection diagnosed at a US center during winter 2014. Case-patient 1 (26 years old, week 33 of gestation) received a diagnosis of RSV infection and required mechanical ventilation. Case-patient 2 (27 years old, week 34 of gestation) received a diagnosis of infection with influenza A(H1N1) virus and RSV and required mechanical ventilation. Case-patient 3 (21 years old, week 32 of gestation) received a diagnosis of group A streptococcus pharyngitis and RSV infection and was monitored as an outpatient. Clarifying the effects of maternal RSV infection could yield valuable insights into potential maternal and fetal benefits of an effective RSV vaccination program.

Effects of exercise intensity on salivary antimicrobial proteins and markers of stress in active men

In the present study, we assessed the effects of exercise intensity on salivary immunoglobulin A (s-IgA) and salivary lysozyme (s-Lys) and examined how these responses were associated with salivary markers of adrenal activation. Using a randomized design, 10 healthy active men participated in three experimental cycling trials: 50% maximal oxygen uptake (VO2max), 75%VO2max, and an incremental test to exhaustion. The durations of the trials were the same as for a preliminary incremental test to exhaustion (22.3 min, sx = 0.8). Timed, unstimulated saliva samples were collected before exercise, immediately after exercise, and 1 h after exercise. In the incremental exhaustion trial, the secretion rates of both s-IgA and s-Lys were increased. An increase in s-Lys secretion rate was also observed at 75%VO2max. No significant changes in saliva flow rate were observed in any trial. Cycling at 75%VOmax and to exhaustion increased the secretion of alpha-amylase and chromogranin A immediately after exercise; higher cortisol values at 75%VO2max and in the incremental exhaustion trial compared with 50%VO2max were observed 1 h immediately after exercise only. These findings suggest that short-duration, high-intensity exercise increases the secretion rate of s-IgA and s-Lys despite no change in the saliva flow rate. These effects appear to be associated with changes in sympathetic activity and not the hypothalamic - pituitary - adrenal axis.

The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure).Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.

Cognitive inhibition and interference in dissociative indentity disorder: the effects of anxiety on specific executive functions:The effects of anxiety on specific executive functions

Using an experimentally based, computer-presented task, this study assessed cognitive inhibition and interference in individuals from the dissociative identity disorder (DID; n=12), generalized anxiety disorder (GAD; n=12) and non-clinical (n=12) populations. Participants were assessed in a neutral and emotionally negative (anxiety provoking) context, manipulated by experimental instructions and word stimuli. The DID sample displayed effective cognitive inhibition in the neutral but not the anxious context. The GAD sample displayed the opposite findings. However, the interaction between group and context failed to reach significance. There was no indication of an attentional bias to non-schema specific negative words in any sample. Results are discussed in terms of the potential benefit of weakened cognitive inhibition during anxious arousal in dissociative individuals.

The Effects of Social Class and Ethnicity on Gender Differences in GCSE Attainment: A Secondary Analysis of the Youth Cohort Study of England and Wales 1997-2001

This article is based upon a secondary analysis of the Youth Cohort Study of England and Wales 1998 and examines the effects of social class and ethnicity on gender differences in GCSE attainment for those who left school in 1997 (n = 14,662). The article shows that both social class and ethnicity exert a far greater influence on the GCSE performance of boys and girls than gender. Moreover, the article also shows that an interaction effect is present between social class and gender and also between ethnicity and gender in relation to their impact upon GCSE attainment. More specifically, the findings suggest that a strong correlation exists such that the lower the overall levels of educational attainment for any group (whether that group is defined in terms of social class or ethnicity), the higher the gender differences that exist between those within that group.

The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye movements or CANTAB neuropsychological test performance. Haloperidol was associated with impaired SWM, which correlated with the degree of dysphoria/akathisia, but no other drug effects on CANTAB measures were detected. We conclude that the effect of antipsychotics on LI is both modality and pharmacologically dependent and that further research using a wider range of antipsychotic compounds is necessary to clarify the cognitive effects of these drugs, and to determine whether there are important differences between them.