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Background: CALGB 30610 trial demonstrated that once daily thoracic radiotherapy (TRT) was not superior compared to standard twice daily TRT, in patients with limited stage small cell lung cancer. Quality of life outcomes may help oncologists decide the best treatment approach. Methods: A total of 417 patients on CALGB 30610 participated in the quality‐of‐life substudy (CALGB 70702), which included the FACT Trial Outcome Index‐Lung Cancer (FACT‐L TOI), FACT‐Esophageal Cancer (FACT‐E) Eating and Swallowing Indices, ECOG Acute Esophagitis Scale, Hospital Anxiety and Depression Scale (HADS), difficulty swallowing, EQ‐5D, and treatment convenience assessment at baseline, 3, 5, 7, 12, 26, and 52 weeks after starting TRT. Primary end points included FACT‐L TOI and FACT‐E at 12 weeks. Mean changes from baseline were compared between arms using general linear mixed models. Results: FACT‐L worsening was more in the twice daily arm at week 3 (–1.0 vs. –7.0). FACT‐L TOI worsening was less at week 3 (–2.9 vs. –7.6) and greater at week 12 (–7.6 vs. –2.8) in the once daily arm. The once daily arm had a lower EQ‐5D index worsening at 3 weeks (0.01 vs. –0.02). Increase in acute esophagitis score (1.06 vs. 2.89; p <.001) and difficulty swallowing (0.39 vs. 1.14) were greater in the twice daily arm at week 3. A total of 74.5% of patients on the once daily arm felt that treatment was convenient, compared to 67% of patients in the twice daily arm (p =.03). Conclusions: The once daily arm had better quality‐of‐life scores earlier during treatment and was perceived to be more convenient. Patient‐reported outcomes assessing health‐related quality of life were analyzed for 417 patients with limited stage small cell lung cancer who were enrolled on the CALGB 30610 trial comparing once daily versus twice daily radiation concurrent with platinum‐etoposide chemotherapy. Patients on the once daily radiation arm reported better quality of life scores earlier during treatment and perceived this regimen to be more convenient. [ABSTRACT FROM AUTHOR]

Background: Myeloid neoplasms (myelodysplastic syndrome [MDS], myelofibrosis, and chronic myelomonocytic [CMML]) are aggressive hematological malignancies for which, despite recent approvals, novel therapies are needed to improve clinical outcomes. The hedgehog (HH) pathway is one of the main pathways for cancer stem cells survival and several HH inhibitors (HHi) are approved in clinical practice. Methods: Sonidegib (SON), an oral HHi, was tested in this phase 1/1b trial in combination with azacitidine (AZA, 75 mg/m2 days ×7) in patients with newly diagnosed and relapsed/refractory (r/r) chronic MN or acute myeloid leukemia (AML). Results: Sixty‐two patients (28 [45%] newly diagnosed) were treated in this study, including 10 patients in the dose‐finding component and 52 patients in phase 1b. SON 200 mg oral daily on days 1–28 each cycle was deemed the recommended dose for phase 1b. Out of 21 rrAML patients, two achieved response (one complete response/one morphologic leukemia‐free state) with no responses seen in seven r/r MDS/CMML patients. In newly diagnosed AML/MDS, response was seen in six (three had complete remission, two had morphological leukemia‐free status) of 27 patients. Median overall survival was 26.4 and 4.7 months for newly diagnosed MDS and AML, respectively. Safety was satisfactory with common (>20%) side effects including fatigue, constipation, nausea, cough, insomnia, and diarrhea. Only 7% of patients died in the study, and none of the deaths were deemed related to treatment. Conclusions: Our study shows that AZA + SON are a safe combination in a patient with MN. Similar to other hedgehog inhibitors, this combination yielded limited response rate in patients with myeloid neoplasms. Combining sonidegib with azacitidine is safe in patients with myeloid neoplasms. Although outcome was not high for frontline therapy, in the relapsed setting, extended survival was seen. [ABSTRACT FROM AUTHOR]

Keywords: myelofibrosis; prognostic factors; quality of life; survival EN myelofibrosis prognostic factors quality of life survival 1065 1068 4 09/13/22 20220915 NES 220915 Patient-reported outcomes (PROs) have considerable value for survival prediction, and generally include both quality of life (QOL) and symptom measures. The COMFORT-I study enrolled 309 patients (155 ruxolitinib, 154 placebo); 111 (72%) placebo patients ultimately crossed over to ruxolitinib.4 Baseline GHS/QOL was available in 296 patients and did not differ by treatment arm (Table S1). Quality of life independently predicts overall survival in myelofibrosis: Key insights from the COntrolled MyeloFibrosis Study with ORal Janus kinase inhibitor Treatment (COMFORT)-I study. [Extracted from the article]

Background: Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within‐visit and previsit DAs for localized prostate cancer, and minority men were oversampled. Methods: The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12‐item measure) assessed immediately after a urology consultation. Results: Four sites administered the previsit DA (39 patients), 4 sites administered the within‐visit DA (44 patients), 3 sites administered both previsit and within‐visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within‐visit DA study arm, 67% for the previsit DA only arm, 58% for the within‐visit DA only arm, and 58% for the usual‐care arm. Neither the previsit DA nor the within‐visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P =.132 and P =.977, respectively). Conclusions: DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge. This study oversamples minority men and evaluates the effect of 2 decision aids on prostate cancer patients' knowledge. Decision aids are not shown to affect knowledge about prostate cancer treatment options. [ABSTRACT FROM AUTHOR]

Introduction: Infants' right‐hand preference for pointing is associated with higher vocabulary. It is not clear whether the link between right‐hand preference for gesturing and language persists into the preschool years. The primary purpose of the present study was to test whether preschool children's hand preference for referential gestures was associated with their language abilities. Secondarily, we predicted that the children's right‐hand preference would be negatively associated with their visuospatial abilities. We also predicted that monolingual children would show a strong right‐hand preference while bilinguals might show a reduced right‐hand preference. Methods: Monolingual and bilingual children between the ages of four and six years did a storytelling task. Their referential gestures were coded for hand use (right, left, both). We measured language skills (receptive vocabulary, semantic fluency). Results: We found no difference between bilinguals and monolinguals on hand preference. Semantic fluency was a positive predictor and vocabulary a negative predictor of right‐hand preference. Children's visuospatial abilities were not a predictor of right‐hand preference. Conclusion: These results suggest that right‐hand preference may help children select semantically appropriate words out of their existing vocabulary. In other words, this preference may be related to children's construction of the message that they would like to produce. The association between hand preference and language skills persists into the preschool years. [ABSTRACT FROM AUTHOR]

Background: Previous research has shown that pre‐service teachers have low responsibility for student motivation and feel underprepared to deal with motivational issues. As an extension, researchers have designed interventions to shift teachers' beliefs about motivation or equip them with approaches to instruction, but never both. Aims: Following best practices for motivation interventions, we created a one‐session online intervention and tested its efficacy to shift pre‐service teachers' self‐reported beliefs and approaches to instruction to be more supportive of student motivation. The intervention included priming, materials designed for mindsets and/or for approaches to instruction, a consolidation activity, and take‐home materials. Sample: A convenience sample of 384 pre‐service teachers from one Canadian university participated. Methods: We embedded an experimental design into multiple sections of a required assessment course. After completing a pre‐test, participants were randomly assigned to one of four conditions: beliefs‐only, approaches‐only, combined beliefs and approaches, or control. After completing the online module, students received a lecture on assessment practices and motivation. Results: The results from our MANCOVA showed that pre‐service teachers who participated in the beliefs‐only condition reported increased levels of responsibility for student motivation, more growth mindset beliefs, and less fixed mindset beliefs than participants in the other conditions. The approaches‐only condition did not influence self‐reported mastery or performance approaches to instruction and the combined condition had no effect on beliefs or approaches. Conclusions: We discuss the implications for educating pre‐service teachers about student motivation and suggest that beliefs and approaches to instruction need to be addressed separately. [ABSTRACT FROM AUTHOR]

Red pandas (Ailurus fulgens) are small charismatic mammals native across montane southern Asia, now endangered by human impacts. They are considered "living fossils" as the sole member of a distinct family, warranting higher conservation priority. Therefore, ex situ breeding programs were initiated to prevent extinction and act as genetic reservoirs for reintroduction, although complicated by apparent taxonomic subdivision. This study investigated whether the separation of captive red pandas in the North American Species Survival Plan® by putative subspecies was justified. A 383‐bp segment of mitochondrial DNA control region was therefore sequenced from 67 members representing matriarchal lineages of both groups. A network analysis placed the 11 haplotypes found into separate but closely connected clusters, with one group more strongly related than the other. Statistical analyses and diversity indices corroborated differentiation between the two management units. Phylogenetic analyses employing multiple outgroups confirmed, although not robustly, reciprocal monophyly of the four‐ and seven‐haplotype clades representing putative subspecies Ailurus fulgens fulgens and Ailurus fulgens styani, respectively. These empirical results are adequate to justify continued independent management of these zoo subpopulations, but cannot be definitive for taxonomic classification due to limited sampling from their native range. They will, however, be useful in evaluating long‐term genetic diversity changes, focusing management efforts on newly revealed evolutionary limitations, and comparing with an assessment of wild red pandas to determine how representative zoo populations are for reintroduction purposes. Maintaining genetic diversity and population structure of endangered species is essential to protect evolutionary potential and adaptations for long‐term sustainability. Research Highlight: Red pandas from both subpopulations in American zoos were genotyped using mitochondrial DNA sequencing. Data analyses confirmed that the two groups were genetically different, perhaps at the subspecies level, and should continue to be maintained separately. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to assess the impact of trastuzumab on locoregional failure. METHODS: The analysis included 2763 patients with HER2‐positive (HER2+) breast cancer who were randomly assigned to adjuvant doxorubicin (A), cyclophosphamide (C), paclitaxel (T) and trastuzumab (H) (arm A, AC→T [n = 922]; arm B, AC→T→H [n = 988]; arm C, AC→T+H→H [n = 853]). Radiotherapy was given after AC→T concurrently with H. Radiotherapy was given after lumpectomy (L) or after mastectomy (M) with ≥4 positive lymph nodes but was optional for 1 to 3 positive lymph nodes. Locoregional failures at 10 years (LFR10) as first events were compared using competing risk analysis. Results: The median follow‐up was 13.0 years. The first site of failure was local‐only in 96 cases, locoregional in 16 cases, regional in 32 cases, and not specified in 2 cases; LFR10 was 4.8% (95% CI 4.1%‐5.7%). LFR10 was 5.5% (95% CI 4.3%‐7.2%), 4.9% (95% CI 3.7%‐6.4%), and 2.8% (95% CI 1.9%‐4.1%) in arms A, B, and C (B vs A: hazard ratio [HR] 0.91, P =.62; C vs A: HR 0.72, P =.12). For estrogen receptor–positive patients, LFR10 was 3.7% (95% CI 2.8%‐4.8%) and for estrogen receptor–negative patients, it was 6.1% (95% CI 5.0%‐7.4%; HR 0.61, P =.004). Local treatment included L+RT (n = 1044 [38%]), M+RT (n = 1025 [37%]), and M (n = 694 [25%]). LFR10 was 6.% (95% CI 5.0%‐7.8%), 3.0% (95% CI 2.1%‐4.3%), and 5.5% (95% CI 4.0%‐7.4%) for L+RT, M+RT, and M, respectively (M+RT vs L+RT: HR 0.43, P <.001; M vs L+RT: HR 0.88, P =.57). For 1 to 3 positive lymph nodes, LFR10 was 6.5% (95% CI 4.8%‐8.9%), 4.1% (95% CI 2.4%‐7.0%), and 4.3% (95% CI 2.9%‐6.5%) in L+RT, M+RT, and M, respectively (M vs L+RT: HR 0.68, P =.14; M vs M+RT: HR 1.2, P =.6). Conclusion: Low 10‐year LFRs were seen regardless of trastuzumab use. Differences in local therapy in patients with 1 to 3 positive lymph nodes did not appear to improve local control. Local therapy studies for HER2+ and other tumor characteristics are important as the role of local therapies continues to evolve. North Central Cancer Treatment Group N9831 does not show a difference in 10‐year locoregional failure with or without trastuzumab or in patients who have 1 to 3 positive lymph nodes regardless of local treatment. The role of local therapy should be investigated further in this patient population, as trastuzumab has a minimal effect on locoregional failure. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPNs) are characterized by significant symptom burden. Integrative medicine (IM) offers unique symptom management strategies. This study describes IM interventions utilized by MPN patients and the association with symptom burden, quality of life, depression, and fatigue adjusted for lifestyle confounders. MPN patients were surveyed online for IM utilization, MPN symptom burden (MPN‐Symptom Assessment Form Total Symptom Score), depression (Patient Health Questionnaire), fatigue (Brief Fatigue Inventory), and a single question on overall quality of life. Measures were compared by IM participation and adjusted for alcohol and tobacco use, BMI, diet, and MPN type using multiple linear and logistic regression. A total of 858 participants were included in the analysis. Aerobic activity (p =< 0.001) and strength training (p = 0.01) were associated with lower mean symptom burden while massage (p =< 0.001) and support groups (p =< 0.001) were associated with higher levels of symptom burden. Higher quality of life was reported in massage (p = 0.04) and support groups (p = 0.002) while lower quality of life was noted in aerobic activity (p =< 0.001) and strength training (p = 0.001). A lower depression screening score was noted in those participating in aerobic activity (p = 0.006), yoga (p = 0.03), and strength training (p = 0.02). Lower fatigue was noted in those participating in aerobic activity (p =< 0.001) and strength training (p = 0.03) while higher fatigue was noted in those participating in massage (p =< 0.001) and breathing techniques (p = 0.02). Data available on request from the authors. This international survey of MPN patients on IM usage, has shown that patients who participated in a form of IM had a pattern of decreased levels of symptom burden, fatigue, depression, and higher QoL, as adjusted for health lifestyle practices overall. [ABSTRACT FROM AUTHOR]

Background: Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera, and myelofibrosis, have severe function‐limiting symptom burden that is experienced by the majority of patients. Previous studies have suggested that depression may be present in over a quarter of MPN patients, but to date no studies have evaluated the relationship between depression and other variables such as symptoms. Methods: A 70‐item internet based survey regarding fatigue and mood symptoms was developed by a multidisciplinary team of MPN investigators, patients and patient advocates including Patient Health Questionnaire and the Myeloproliferative Neoplasm Symptom Assessment Form was completed by over 1300 patients with MPN diagnosis. Results: There were 309 respondents (23%) with PHQ‐2 scores ≥ 3. In this analysis, we found worse systemic symptom burden in individuals reporting depressive symptoms. Conclusion: This analysis suggests the importance of depression in contributing to as well as confounding symptomatology in MPN patients, and suggests that this critical variable should also be addressed by clinicians and researchers alike when comprehensively assessing symptom burden etiologies. [ABSTRACT FROM AUTHOR]

The missing high‐efficiency Blue OLEDs are still the bottleneck for the power consumption in today's OLED panels. One way to improve the efficiency of the blue pixel is the use of narrow‐type fluorescent emitters in a classical fluorescent stack for top‐emission OLED devices where the optical cavity effect favors narrow over a broader emission. In this paper, we will show how narrow‐type fluorescent emitters can deliver >30% efficiency improvement over traditional commercial fluorescent blue emitters to reach >200 cd/A/CIEy in top‐emission devices. For further efficiency increase, those fluorescent emitters can be combined with TADF emitters which can increase the internal quantum efficiency from 25% to 100%. In order to make such a hyper‐fluorescent system work efficiently, the combination of TADF and fluorescent emitter has to be chosen carefully as they have to match the materials perfectly. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BC) patients with advanced disease have poor outcomes. The use of patient‐reported outcomes (PROs) could lead to improvements in symptom management and hence quality of life (QoL). The aim of this study is to report correlations between selected PROs and QoL and thus to present symptoms that influence QoL. Identification of these symptoms during treatment can lead to earlier symptom management and thus secure improvements in QoL. Methods: BC patients in chemo‐ or immunotherapy for locally advanced or metastatic disease reported weekly PROs for the duration of their treatment. The PROs included EORTC QLQ‐C30 and QLQ‐BLM30 and 45 selected PRO‐CTCAE items. Spearman's correlation analysis was performed for all PRO‐CTCAE items and QLQ‐C30 global QoL and subdomains. Results: In this study, 78 BC patients reported 724 questionnaires. Spearman's analysis showed significant correlations between almost all PRO‐CTCAE items and the expected domain of QoL. The PRO‐CTCAE items with the strongest correlations with QoL were anxiety (F, frequency item) and emotional function (rs = −0.603, P <.0001), concentration (S, severity item) and cognitive function (rs = −0.704, P <.0001), discouraged (F) and emotional function (rs = −0.659, P <.0001), fatigue (S) and role function (rs = −0.659, P <.0001) and sad (F) and emotional function (rs = −0.711, P <.0001). The weakest correlations were found for the PRO‐CTCAE items urinary frequency, incontinence and urge, all with variations in the direction and significance of the correlations. Conclusions: This study delivers information on which PROs may influence QoL for patients in clinical trials or daily clinic. Psychological issues have a strong impact on QoL and should be dealt with during treatment to secure the best possible QoL for BC patients. [ABSTRACT FROM AUTHOR]

Background and objectives: Bulgur, an ancient and traditional food extensively consumed in Turkey and the Middle East, has been gaining popularity elsewhere as a nutritious and convenient cereal product with prolonged shelf life. The cooking, drying, and comminution methods used for bulgur production may affect the color, yield, chemical composition, nutritive quality, and physical properties of bulgur. The objectives of this study were to produce bulgur from high‐amylose and waxy hull‐less barley (Hordeum vulgare L.) varieties and to investigate the effects of different drying methods: hot air, microwave, and superheated steam on the physicochemical and nutritional properties of barley bulgur. Findings: Different drying methods applied in this study for the preparation of barley bulgur had significant effects on the physicochemical and nutritious properties of the final products. Bulgur products from high‐amylose barley (cv. CDC Hilose) contained lower amounts of proteins, but higher amounts of ash, arabinoxylans, resistant starch, total dietary fiber, and vitamin E than bulgur products from waxy barley (cv. CDC Marlina). However, bulgur products from CDC Marlina exhibited significantly higher solubility of β‐glucans compared with bulgur from CDC Hilose. Conclusions: Overall, the optimal quality characteristics in terms of high bulgur yield, short cooking time, low cooking losses, high β‐glucan solubility, and high retention of vitamin E were achieved for bulgur prepared from grain dried with superheated steam at 110°C. The second best results were obtained for bulgur prepared from the microwave‐dried grain. Some differences in composition and properties of bulgur prepared from waxy and high‐amylose barley were related to genetic variations and differences in starch composition. The higher content of total dietary fiber in bulgur products from CDC Hilose was partly attributed to a higher content of resistant starch formed during the processing of this high‐amylose barley. Significance and novelty: Barley has been long considered a wholesome and nutritious grain, and the results of this study clearly showed that it can be used for the preparation of bulgur, a convenient and functional food product. The use of superheated steam as a drying method for the preparation of barley bulgur proved to generate product with superior properties, especially when compared to conventional hot air drying. [ABSTRACT FROM AUTHOR]

Introduction: Some Alzheimer's disease biomarker studies found amyloid changes 20 years or more in advance of expected symptoms, while cognitive changes lagged for more than a decade, but this apparent lag might reflect the sensitivities of the biomarker and cognitive assays used. How far in advance of incident amnestic mild cognitive impairment (MCI) does cognition begin to decline? Methods: Longitudinal neuropsychological study of an apolipoprotein E e4 enriched cohort of cognitively normal individuals at entry. Linear mixed models for MCI converters (n = 65) and nonconverters (n = 719) fitted for each neuropsychological measure; annual changes compared between groups before and after linear model intersections (inflection points). Results: 34 of 35 cognitive measures and 9 of 18 behavioral measures declined faster post‐inflection in the MCI converters; the earliest cognitive inflection point was nearly 20 years in advance of MCI diagnosis. Discussion: The preclinical duration of cognitive and behavioral changes approaches the earliest reported biomarker changes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Behavioral problems in individuals with Alzheimer's disease (AD) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI). Design: Longitudinal observational cohort study. Setting: Academic medical center. Participants: Members of an apolipoprotein E (APOE) ɛ4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory—Revised (NEO‐PI‐R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO‐PI‐R administrations. Intervention: Longitudinal administration of the NEO‐PI‐R and neuropsychological test battery. Measurements: Change in NEO‐PI‐R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow‐up duration in nontransitioners. Results: NEO‐PI‐R neuroticism T‐scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI) = 0.9–4.9 vs 0, 95% CI = −0.7–0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (−4.8, 95% CI = −7.3 to −2.4 vs −1.0, 95% CI = −1.6 to −0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude. Conclusion: Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia. [ABSTRACT FROM AUTHOR]

Background: We aimed to provide a simple, descriptive health-status profile for cancer patients with bone metastases, based on the EuroQol EQ-5D, a tool commonly used to measure health utility scores, and to evaluate its association with the Brief Pain Inventory (BPI), a legacy pain-assessment tool. Although pain is one of five health-status dimensions measured by the EQ-5D, our understanding of how pain relates to the other EQ-5D dimensions is limited.Methods: We derived data from 5500 patients with bone metastases who completed the EQ-5D and BPI. Regression analyses examined how BPI severity and interference scores correlated with EQ-5D utility scores and how BPI items associated with EQ-5D items, for the entire sample and by disease-type subgroup.Results: Regardless of cancer site, the percentage of patients reporting moderate/severe problems in each of the five EQ-5D dimensions were pain/discomfort, 78%; usual activities, 58%; mobility, 55%; anxiety/depression, 57%; and self-care, 26%. BPI pain interference explained more of the variability in the EQ-5D utility scores than did pain severity (R2  = 41% vs. 34%). BPI worst pain, average pain, pain now, interference with general activity, and interference with work significantly predicted EQ-5D pain/discomfort, with odds ratio estimates <1.Conclusions: Pain/discomfort was the worst-rated dimension of the EQ-5D in this population, but the relationship of this item to BPI pain severity was modest, suggesting that the single pain item of the EQ-5D may be of limited utility in studies for which pain is an endpoint.Significance: Health-status dimensions include more than pain. We examine the contribution of pain severity and pain-related functional interference in determining the health status of cancer patients with bone metastases. The pain dimension from a health-status measure may be an inadequate metric in clinical trials/clinical practice when pain is an important outcome. [ABSTRACT FROM AUTHOR]

Hawkes () introduced a powerful multivariate point process model of mutually exciting processes to explain causal structure in data. In this article, it is shown that the Granger causality structure of such processes is fully encoded in the corresponding link functions of the model. A new nonparametric estimator of the link functions based on a time-discretized version of the point process is introduced by using an infinite order autoregression. Consistency of the new estimator is derived. The estimator is applied to simulated data and to neural spike train data from the spinal dorsal horn of a rat. [ABSTRACT FROM AUTHOR]

Background: Symptomatic burden from constitutional symptoms, anemia, and splenomegaly-related symptoms are common and morbidity inducing in patients with myelofibrosis (MF). The authors previously developed a MF-specific instrument for capturing the burden of MF-associated disease-related symptoms, the Myelofibrosis Symptom Assessment Form.Methods: The authors evaluated the usefulness of serial administration of the Myelofibrosis Symptom Assessment Form as an instrument for the assessment of symptomatic burden and improvement in conjunction with the therapeutic clinical trial of the open label phase 2 trial of the JAK1 and JAK2 inhibitor INCB018424 in patients with MF.Results: The analysis cohort of 87 patients treated in this trial demonstrated that the instrument was comprehensive and sensitive to symptoms present at trial enrollment. In addition, baseline Myelofibrosis Symptom Assessment Form symptom scores correlated well with objective parameters such as splenomegaly and impaired performance status assessed by the 6-minute walk test. Serial administration while on therapy with INCB018424 demonstrated the instrument to be sensitive to symptomatic change, and that improvements in symptoms correlated well with objective improvements in both weight loss and performance status (6-minute walk test).Conclusions: The use of the Myelofibrosis Symptom Assessment Form in this phase 2 trial helped characterize the symptomatic improvements observed with use of INCB018424 in MF patients. In an era of many targeted therapies undergoing testing for MF with potential symptomatic benefit, the Myelofibrosis Symptom Assessment Form may provide a useful tool for objective symptomatic assessment and potentially allow some nonrandomized comparison between therapeutic agents. [ABSTRACT FROM AUTHOR]

Many Java applications instantiate objects within the Java heap that are persistent but seldom if ever referenced by the application. Examples include strings, such as error messages, and collections of value objects that are preloaded for fast access. This paper describes a stack-based framework for detecting these 'cold' objects at runtime, with a view to marshaling and sequestering them in designated regions of the heap where they may be preferentially paged out to a backing store, thereby freeing physical memory pages for occupation by more active objects. Furthermore, we evaluate the correctness and efficiency of stack-based approach with an access barrier. The experimental results from a series of SPECjvm2008 benchmarks are presented. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Patients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms.Methods: A total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population.Results: Overall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids.Conclusions: The results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

There is a growing appreciation of the extent of transcriptome variation across individual cells of the same cell type. While expression variation may be a byproduct of, for example, dynamic or homeostatic processes, here we consider whether single-cell molecular variation per se might be crucial for population-level function. Under this hypothesis, molecular variation indicates a diversity of hidden functional capacities within an ensemble of 'identical' cells, and this functional diversity facilitates collective behavior that would be inaccessible to a homogenous population. In reviewing this topic, we explore possible functions that might be carried by a heterogeneous ensemble of cells; however, this question has proven difficult to test, both because methods to manipulate molecular variation are limited and because it is complicated to define, and measure, population-level function. We consider several possible methods to further pursue the hypothesis that 'variation is function' through the use of comparative analysis and novel experimental techniques. [ABSTRACT FROM AUTHOR]

Background: Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs.Methods: A 70-item, Internet-based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center.Results: Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P<.001), current use of alcohol (P<.001), and current tobacco use (P = .0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week (P<.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome (P = .006), diabetes mellitus (P = .045), fibromyalgia (P < 0.001), chronic fatigue syndrome (P = .006), and chronic kidney disease (P = .02). Current use of antidepressants (P<.001), antihistamines (P = .0276), antianxiety medications (P = .0357), and prescription pain medications (P<.001) were found to be associated with worsened fatigue. Nearly 25% of respondents scored > 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P<.0001).Conclusions: The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain. [ABSTRACT FROM AUTHOR]

Background Symptoms suggestive of gastroparesis are non-specific and conflicting reports exist regarding the ability of symptoms to predict the presence of gastroparesis. Our aim, therefore, was to evaluate the relationships between gastroparetic symptoms and their impact on quality of life and determine their relationship with clinical factors and gastric emptying. Methods Gastric emptying scintigraphy, sociodemographic features, health care resource utilization, gastroparetic symptoms, and quality of life using validated questionnaires were obtained from consecutive patients referred for gastric emptying testing ( GET). Descriptive analyses were conducted and logistic regression was performed to evaluate associations with abnormal gastric emptying after controlling for other covariates. Key Results Two hundred and sixty-six patients participated (195 females; mean age, 49.1 ± 17.6 years); 75% met Rome III criteria for functional dyspepsia. Gastric emptying was delayed in 28.2% at 4 h; the delay was mild in 48%, moderate in 20% and severe in 32%. Nausea/emesis and postprandial fullness, but not bloating, were significantly greater in those with delayed emptying. Postprandial fullness was most severe. Weak correlations were identified between symptom severity and the severity of gastric emptying delay. Quality of life was also lower in the delayed emptying group. Logistic regression analysis demonstrated associations between delayed gastric emptying and lower quality of life and increased symptom severity. Conclusions & Inferences In patients referred for GET, gastroparetic symptoms were more severe in those with delayed emptying. A decrease in quality of life in those with delayed gastric emptying was also present; this was not related to the severity of the delay in gastric emptying. [ABSTRACT FROM AUTHOR]

Background There have been conflicting results from studies that have evaluated psychological disturbances in functional dyspepsia ( FD). We conducted a comprehensive survey of psychological measures in patients undergoing gastric emptying testing ( GET) in order to determine the relationship among psychological distress, gastric emptying, and dyspeptic symptoms. Methods Consecutive patients referred for GET were prospectively enrolled. Details regarding patient characteristics, health care utilization, dyspeptic symptoms, quality of life, and psychological dysfunction were obtained. Depression, anxiety, somatization, stress, positive and negative affect, and alexithymia were queried using validated questionnaires. We compared those dyspeptic patients who met Rome III criteria for FD to those who did not meet these criteria. Key Results Two hundred and nine patients (160 female; mean age 46.6 years ± 17.3 years) participated. Around 151 patients (72%) met Rome III criteria for FD. In the entire group, a high level of depression, anxiety, somatization, and perceived stress was present compared to population norms. Health care seeking behavior and symptom severity were greater in those with FD and quality of life was lower compared to non- FD. Gastric emptying did not differentiate the two groups and similar degrees of psychological distress were present whether emptying was delayed or normal. Conclusions & Inferences In patients referred for GET, substantial psychological distress is present. The degree of distress was similar regardless of whether the patient met Rome III FD criteria or not. Further evaluation of psychological dysfunction in FD patients may lead to improved diagnosis and determination of the most appropriate treatment. [ABSTRACT FROM AUTHOR]

Brown adipocytes (BAs) are specialized for adaptive thermogenesis and, upon sympathetic stimulation, activate mitochondrial uncoupling protein (UCP)-1 and oxidize fatty acids to generate heat. The capacity for brown adipose tissue (BAT) to protect against obesity and metabolic disease is recognized, yet information about which signals activate BA, besides β3-adrenergic receptor stimulation, is limited. Using single-cell transcriptomics, we confirmed the presence of mRNAs encoding traditional BAT markers (i.e., UCP1, expressed in 100% of BAs Adrb3, expressed in <50% of BAs) in mouse and have shown single-cell variability (>1000-fold) in their expression at both the mRNA and protein levels. We further identified mRNAs encoding novel markers, orphan GPCRs, and many receptors that bind the classic neurotransmitters, neuropeptides, chemokines, cytokines, and hormones. The transcriptome variability between BAs suggests a much larger range of responsiveness of BAT than previously recognized and that not all BAs function identically. We examined the in vivo functional expression of 12 selected receptors by microinjecting agonists into live mouse BAT and analyzing the metabolic response. In this manner, we expanded the number of known receptors on BAs at least 25-fold, while showing that the expression of classic BA markers is more complex and variable than previously thought.--Spaethling, J. M., Sanchez-Alavez, M., Lee, J., Xia, F. C., Dueck, H., Wang, W., Fisher, S. A., Sul, J.-Y., Seale, P., Kim, J., Bartfai, T., Eberwine, J. Single-cell transcriptomics and functional target validation of brown adipocytes show their complex roles in metabolic homeostasis. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF) are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO) tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms) and cytokines, particularly IL-1, IL-6, IL-8, and TNF-α. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development. [ABSTRACT FROM AUTHOR]

Causal attributions are important social-cognitive predictors of forgiveness. This article presents the Transgression Attribution Questionnaire ( TAQ), a measure of one's negative internal causal attributions of a specific offense. In 4 studies, scores on the TAQ showed initial evidence of estimated internal consistency, temporal stability, and construct validity. Negative internal attributions for the cause of a transgression predicted lower levels of empathy and forgiveness. Furthermore, scores on the TAQ predicted forgiveness over and above the hurtfulness of the offense, relationship commitment, and a general measure of internal causal attributions in relationships. The current research bridges research on internal causal attributions and forgiveness. Implications for the social-cognitive study of forgiveness and the measurement of causal attributions are discussed. [ABSTRACT FROM AUTHOR]

ABSTRACT A three-component three-dimensional seismic data set was acquired over the Lalor volcanogenic massive sulphide deposit near Snow Lake, Manitoba, Canada, to assess the reflectivity of the ore and further validate the potential of three-dimensional reflection seismic methods for deep mineral exploration. The Lalor deposit was chosen as a test site as it provided an intact, well-characterized 25-Mt-deep ore deposit with a rich catalogue of geological and geophysical data, as well as extensive drill-core and drill-hole geophysical and geological logs. An analysis of physical rock properties from borehole logging data indicates that massive sulphides associated with the zinc-rich zones could produce prominent reflections, whereas acoustic impedances of zones with disseminated gold do not sufficiently differ from the impedances of the host rocks to produce reflections. The interpretation of the seismic data is constrained with a detailed three-dimensional lithofacies model constructed from the categorical kriging of 15 lithological units identified in borehole intersections. Processing of the seismic data included prestack dip-moveout and poststack time migration. Final images reveal some strong reflections associated with the zinc-rich massive sulphide zones. The most prominent reflection results from the constructive interference of thin and closely spaced massive sulphide zones and felsic-mafic volcanic rock contacts above and below the mineralization. Contacts between felsic and mafic volcanic rocks, including those that were hydrothermally altered and subsequently metamorphosed, produced prominent and continuous reflections that are used to map the main architecture of the footwall rocks. At depth, a series of continuous and conformable reflections indicate the general geometry of the volcanic sequences in the area of the three-dimensional seismic survey. [ABSTRACT FROM AUTHOR]

To evaluate the impact of a patient-centered symposium as an educational intervention on a broad population of cancer patients. We developed a comprehensive patient symposium. Through voluntary questionnaires, we studied the impact of this cancer symposium on quality of life, cancer-specific knowledge, and symptom management among cancer patients. Symposium attendees were provided surveys prior to and 3 months following the educational intervention. Surveys included (1) EORTC-QLQ-C30; (2) disease understanding tool developed for this conference; (3) validated disease-specific questionnaires. Changes over time were assessed using McNemar's tests and paired t-tests for categorical and continuous variables, respectively. A total of 158 attendees completed the pre-convention survey. Most respondents reported at least "quite a bit" of understanding regarding treatment options, screening modalities, symptomatology, and cancer-related side effects. Attendees endorsed the least understanding of disease-related stress, risk factors, fatigue management, and legal issues related to disease/treatment. At 3 months, there was improvement in understanding (12 of 14 areas of self-reported knowledge especially regarding nutrition, and stress/fatigue management). However, no significant change was seen in QLQ-C30 functioning, fatigue, pain, or insomnia. A patient symposium, as an educational intervention improves a solid knowledge base amongst attendees regarding their disease, increases knowledge in symptom management, but may be insufficient to impact QoL as a single intervention. [ABSTRACT FROM AUTHOR]

Sixty-four transplant-eligible patients with newly diagnosed multiple myeloma ( NDMM) received carfilzomib (days 1, 2, 8, 9, 15, 16), 300 mg/m2 cyclophosphamide (days 1, 8, 15), 100 mg thalidomide (days 1-28) and 40 mg dexamethasone (days 1, 8, 15, 22) in 28-day cycles ( CYKLONE regimen). Carfilzomib was dose-escalated to 15/20, 20/27, 20/36 and 20/45 mg/m2 to determine the maximum tolerated dose ( MTD), which was 20/36 mg/m2. Regardless of attribution, common Grade 3 or higher adverse events were lymphopenia (38%), neutropenia (23%) and anaemia (20%). All peripheral neuropathy (31%) was Grade 1 and considered most likely to be thalidomide-related. Common cardiac or pulmonary events of any grade in ≥5% of patients included dyspnoea (20%) and cough (6%). Overall ( N = 64), 91% of patients achieved a best response of partial response or better across all cycles of treatment, including five patients with complete responses. At the MTD ( n = 29), 59% of patients achieved a very good partial response or better after four cycles (primary end point). Stem cell collection was successful in all patients in whom it was attempted ( n = 42). Progression-free survival and overall survival at 24 months was 76% and 96%, respectively (median follow-up of 17·5 months). CYKLONE appears highly efficacious in NDMM patients, with manageable toxicities. [ABSTRACT FROM AUTHOR]

BACKGROUND Patients with T-cell lymphomas face a poorer prognosis compared with patients with B-cell lymphomas. New therapeutic approaches need to be developed to improve outcomes for these patients. METHODS Forty patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy were prescribed oral lenalidomide at a dose of 25 mg daily on days 1 to 21 of each 28-day cycle, with standardized dose reductions for toxicity. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete and partial response rates, progression-free survival (PFS), overall survival (OS), and safety. The authors also determined duration of response (DoR). RESULTS A total of 40 patients were enrolled in the current study; 1 patient was subsequently deemed ineligible. The ORR was 10 of 39 patients (26%); 3 patients (8%) achieved complete responses and 7 patients achieved partial responses. Three patients had stable disease for ≥5 cycles. The median OS was 12 months (range <1 month to ≥69 months), the median PFS was 4 months (range, <1 month to ≥50 months), and the median DoR was 13 months (range 2 months to ≥37 months), including 5 responses that lasted >1 year. Toxicity was in keeping with the known safety profile of lenalidomide. Among the patients who had recurrent/refractory peripheral T-cell lymphoma (29 patients), the ORR was 24%, the median OS was 12 months, the median PFS was 4 months, and the median DoR was 5 months (range, 2 months to ≥37 months). CONCLUSIONS In the current study, the use of oral lenalidomide monotherapy demonstrated clinically relevant efficacy among patients with systemic T-cell lymphomas. It appears to have excellent potential as an agent in combination therapy for patients with T-cell lymphoma. Cancer 2015;121:716-723. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

* Premise of the study: Spiranthes is a genus of small terrestrial orchids that are most diverse in North America, yet unusually cosmopolitan, including many of conservation concern. Taxonomy based on morphology alone is problematic, but molecular evidence could help resolve evolutionary relationships within the genus. The phylogeny of Spiranthes was reconstructed to evaluate these patterns, particularly among North American and Old World lineages, determine the systematic value of chromosome numbers and phenology, consider aspects of historical biogeography, and provide evidence for the taxonomic status of vulnerable species. * Methods: DNA sequences were produced from 219 samples representing 30 Spiranthes taxa plus one outgroup. Both parsimony and Bayesian inference analyses were applied to individual and combined data matrices generated for nuclear (nrlTS) and plastid (trnL, trnS-G, matK) regions. * Key results: Two major clades were recovered. One contains primarily summer-blooming species from western North America with haploid chromosome number of n = 22. The other clade (largely n = 15) contains midwestern and eastern North American species varying in phenology, although most autumn-flowering taxa within it are monophyletic. Whereas an Old World sub-clade is embedded within the tree, derived from New World ancestors, no genetic differentiation was found between trans-Atlantic specimens of S. romanzoffiana. Most species for which multiple individuals were sampled reflect monophyly in the combined gene tree (including S. lucida positioned on an unusually long branch), but some demonstrate dubious taxonomic status. * Conclusions: This is the most complete phylogenetic reconstruction of Spiranthes published to date and is likely to influence future taxonomic decisions, with important implications for conservation of several threatened orchids. Our discoveries about species distributed outside North America offer important evidence for repeated long-distance dispersal, often coupled with subsequent speciation--an uncommon phenomenon in Orchidaceae. [ABSTRACT FROM AUTHOR]

This study gives a brief overview of the current trends in reversible logic synthesis with emphasis on template matching. The basic building block for reversible circuits considered here is the multiple‐control Toffoli gate. Some approaches to synthesis are reviewed and the challenges are explained. Since many practical functions are not reversible, they must be embedded into reversible ones, if they are to be implemented using reversible logic. The complexity of such embeddings is expounded. A two phase synthesis is described where particular attention is devoted to the optimisation phase via template matching. Insights into the properties of the templates, have led to algorithms that aid the generation of templates. Until recently, the application of templates has been guided by different heuristics. A review of an exact template matching algorithm with a discussion of the implications of such an algorithm is given. Exact matching affects both the generation as well as the application of templates. Results from a prototype implementation are encouraging. [ABSTRACT FROM AUTHOR]

Highlights: [•] Analysis of miRNA expression upon stimulation of macrophages and maturation of dendritic cells. [•] miRNA expression analyses in wild type and miR-155-deficient cells. [•] Identification of miRNAs that are affected by miR-155. [•] MiR-455 is a potential target of C/EBPbeta, which is in turn directly regulated by miR-155. [•] Establishment of a miR-155-dependent miRNA hierarchy in macrophages and dendritic cells. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona. Methods A retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty-seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control. Results Median follow-up was 47.3 months (range, 9.7-139.2 months). The 3-year locoregional control, recurrence-free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty-six patients underwent neck only RT with exclusion of the primary site. Conclusion TLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates. © 2013 Wiley Periodicals, Inc. Head Neck 36: 220-225, 2014 [ABSTRACT FROM AUTHOR]

Despite the recognized importance of the dorsal raphe (DR) serotonergic (5-HT) nuclei in the pathophysiology of depression and anxiety, the molecular components/putative drug targets expressed by these neurons are poorly characterized. Utilizing the promoter of an ETS domain transcription factor that is a stable marker of 5-HT neurons (Pet-l) to drive 5-H neuronal expression of YFP, we identified 5-HT neurons in live acute slices. We isolated RNA from single 5-HT neurons in the ventromedial and lateral wings the DR and performed single-cell RNA-Seq analysis identifying >500 G-protein coupled receptors (GPCRs) including receptors for classical transmitters, lipid signals, and peptides as well as dozens of orphan-GPCRs. Using these data to inform our selection of receptors to assess, we found that oxytocin and lysophosphatidic acid 1 receptors are translated and active in costimulating, with the α1-adrenergic receptor, the firing of DR 5-HT neurons, while the effects of histamine are inhibitory and exerted at H3 histamine receptors. The inhibitory histamine response provides evidence for tonic in vivo histamine inhibition of 5-HT neurons. This study illustrates that unbiased single-cell transcriptomics coupled with functional analyses provide novel insights into how neurons and neuronal systems are regulated. [ABSTRACT FROM AUTHOR]

Abstract: Objective: A National Institute on Aging–sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. Conclusions: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design. [Copyright &y& Elsevier]

Background. Providing equitable access to the full range of reproductive health services over wide geographic areas presents significant challenges to any health system. We present a review of a service provision model which has provided improved access to abortion care; support for complex issues experienced by women seeking nonjudgmental family planning health services; and a mechanism to collect information on access barriers. The toll-free pregnancy options service (POS) of British Columbia Women's Hospital and Health Centre sought to improve access to services and overcome barriers experienced by women seeking abortion. Methods. We describe the development and implementation of a province-wide toll-free telephone counseling and access facilitation service, including establishment of a provincial network of local abortion service providers in the Canadian province of British Columbia from 1998 to 2010. Results. Over 2000 women annually access service via the POS line, networks of care providers are established and linked to central support, and central program planners receive timely information on new service gaps and access barriers. Conclusion. This novel service has been successful in addressing inequities and access barriers identified as priorities before service establishment. The service provided unanticipated benefits to health care planning and monitoring of provincial health care related service delivery and gaps. This model for low cost health service delivery may realize similar benefits when applied to other health care systems where access and referral barriers exist. [ABSTRACT FROM AUTHOR]

BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available from 2318 patients, serial samples were available from 105 patients, and recurrence samples were available from 124 patients. The cutoff sHER2 value for the assay was 15 ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank-sum tests, and Cox regression models. RESULTS There were differences between groups in terms of age, menopausal status, and hormone receptor status. Within treatment arms A, B, and C, patients who had baseline sHER2 levels ≥15 ng/mL had worse disease-free survival than patients who had baseline sHER2 levels <15 ng/mL (arm A: hazard ratio, 1.81; P = .0014; arm B: hazard ratio, 2.08; P = .0015; arm C: hazard ratio, 1.96; P = .01). Among the 124 patients who experienced disease recurrence, sHER2 levels increased from baseline to the time of recurrence in arms A and B but remained unchanged in arm C. Patients who had recurrence sHER2 levels ≥15 ng/mL had a shorter survival after recurrence with a 3-year overall survival rate of 51% compared with 77% for those who had recurrence sHER2 levels <15 ng/mL (hazard ratio, 2.36; 95% confidence interval, 1.19-4.70; P = .01). CONCLUSIONS In patients with early stage, HER2-positive breast cancer, a high baseline sHER2 level was identified as a prognostic marker associated with shorter disease-free survival, and a high sHER2 level at recurrence was predictive of shorter survival. Cancer 2013;119:2675-2682. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Data suggest that weight, and specifically body mass index (BMI), plays a role in breast cancer development and outcome. The authors hypothesized that there would be a correlation between BMI and clinical outcome in patients with early stage, human epidermal receptor 2 (HER2)-positive breast cancer enrolled in the N9831 adjuvant trial. METHODS Patients were grouped according to baseline BMI as follows: normal (BMI <25 kg/m2), overweight (BMI ≥25 kg/m2 and <30 kg/m2), and obese (BMI ≥30 kg/m2). Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Comparisons between treatment arms A, B, and C (chemotherapy with or without trastuzumab) were performed using a stratified Cox proportional hazards model. RESULTS Analysis was completed on 3017 eligible patients. Obese patients were more likely to be older and postmenopausal ( P < .0001 for both), to have larger tumors ( P = .002), and to have positive lymph nodes ( P = .004). In the pooled analysis cohort, differences in DFS among the BMI groups were statistically significant (5-year DFS rate: 82.5%, 78.6%, and 78.5% for normal weight, overweight, and obese women, respectively; log-rank P = .02). The adjusted hazard ratio comparing the DFS of overweight women with the DFS of normal women was 1.30 (95% confidence interval, 1.06-1.61); and, comparing the DFS of obese women with the DFS normal women, the adjusted hazard ratio was 1.31 (95% confidence interval, 1.07-1.59). There were no statistically significant differences in DFS by weight group for women within any trial arm. CONCLUSIONS Patients with early stage, HER2-positive breast cancer and normal BMI had a better 5-year DFS compared with overweight and obese women. The current results indicated that adjuvant trastuzumab improves clinical outcome regardless of BMI. Cancer 2013;119:2447-2454. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]