The violent youth of bright and massive cluster galaxies and their maturation over 7 billion years

In this study, we investigate the formation and evolution mechanisms of the brightest cluster galaxies (BCGs) over cosmic time. At high redshift (z ∼ 0.9), we selected BCGs and most massive cluster galaxies (MMCGs) from the Cl1604 supercluster and compared them to low-redshift (z ∼ 0.1) counterparts drawn from the MCXC meta-catalogue, supplemented by Sloan Digital Sky Survey imaging and spectroscopy. We observed striking differences in the morphological, colour, spectral, and stellar mass properties of the BCGs/MMCGs in the two samples. High-redshift BCGs/MMCGs were, in many cases, star-forming, late-type galaxies, with blue broad-band colours, properties largely absent amongst the low-redshift BCGs/MMCGs. The stellar mass of BCGs was found to increase by an average factor of 2.51 ± 0.71 from z ∼ 0.9 to z ∼ 0.1. Through this and other comparisons, we conclude that a combination of major merging (mainly wet or mixed) and in situ star formation are the main mechanisms which build stellar mass in BCGs/MMCGs. The stellar mass growth of the BCGs/MMCGs also appears to grow in lockstep with both the stellar baryonic and total mass of the cluster. Additionally, BCGs/MMCGs were found to grow in size, on average, a factor of ∼3, while their average Sérsic index increased by ∼0.45 from z ∼ 0.9 to z ∼ 0.1, also supporting a scenario involving major merging, though some adiabatic expansion is required. These observational results are compared to both models and simulations to further explore the implications on processes which shape and evolve BCGs/MMCGs over the past ∼7 Gyr

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Implementation and Analysis of Minimum Starting-tag Fair Queuing

隨著網路技術的快速發展，相對應的需求也紛紛產生。其中如何在有限的頻寬服務之中，提供服務品質(quality of service)的保證，並滿足最多的服務要求更是一個重要的課題。在所有提供服務品質保證的努力之中，路由器上(Router)之封包排班演算法(packet scheduling algorithms)是影響最直接的部分。藉由封包排班演算法的發展，本論文期望能夠對有限頻寬之下服務品質的提供有所助益。 本論文將實作最小起始標籤公平排班法(MSFQ；Minimum Starting-tag Fair Queuing)，其為一個經理論證明具有良好延遲時間上限(Delay Bound)、公平性(Fairness)與演算法複雜度(Time Complexity)表現的封包排班演算法。並提供一個快速及有效率的時作平台，將時作網路測試環境的流程複雜度降至最低。 本論文以Linux為發展目標平台，依據Linux內部之Linux Advanced Routing計劃之架構，建構最小起始標籤公平排班法於Linux的核心(kernel)之中，並修改與Linux Advanced Routing相關之系統程式套件iproute2以啟動最小起始標籤公平排班法，最後得到一個以最小起始標籤公平排班法為封包排班演算法之路由器。 本論文將會驗證所提出的最小起始標籤公平排班法之延遲時間上限以及公平性，並與其他Linux中之封包排班演算法互相比較。藉由實際測試後分析結果我們將可得知本論文的最小起始標籤公平排班法為一個有效率、延遲時間表現良好的路由器演算法。本論文實作的過程，也提供了一個實作其他網路理論的參考，包括其他封包排班演算法、新的架構等皆可以使用本論文所建立的流程快速而有效率的加以完成。Minimum Starting-tag Fair Queuing (MSFQ)[1] is an efficient packet scheduling algorithm with theoretically proved in performance metrics such as delay bound, fairness, and time complexity. However, MSFQ algorithm didn't have any implementation yet. In this paper, we established a configurable routing system based on Linux with MSFQ as the routing scheduling algorithm. In the process of implementation, we designed and improved the internal part of data structures, embedded MSFQ algorithm into Linux kernel according to structures of Linux Network Traffic Control [2] extended from Linux advanced routing project called iproute2 [3]. In order to boot MSFQ from kernel, we also modified ‘tc' package in iproute2 project. An analysis model is built to evaluate the performance of proposed routing system. The comparison between MSFQ algorithm and other scheduling algorithms built in Linux kernel such as prio, sfq, etc. is also provided. The result of implementation proved the behaviors of MSFQ both theoretically and essentially. We also offered an easier and faster process to implement other algorithms so that any new algorithms will be implemented and verified more efficiently.1. 序論 1.1 研究動機 1.2 研究目的 1.3 論文架構 2. 文獻探討 2.1 Linux Advanced Routing: iproute2 2.2 其他Linux內建演算法 2.2.1 fifo (First-In-First-Out 2.2.2 tbf (Token Bucket Filter) 2.2.3 sfq (Stochastic Fair Queuing 2.2.4 prio (3-band Priority Scheduler 2.2.5 Other Queuing Disciplines 2.3 MSFQ 2.3.1 Generalized Process Sharing 2.3.2 Weighted Fair Queueing 2.3.3 MSFQ 3. 系統架構及實作步驟 3.1 程式流程 3.2 資料結構設計 3.3 複雜度分析 3.4 實作成果 4. 效能分析比較 4.1 分析模組(Analysis Models)與分析工具 4.2 實驗結果與比較 5. 討論與建議 5.1 實作過程之問題紀錄 5.2 討論 5.3 未來方向 參考文獻(Bibliography 附錄一 iproute2套件之程式碼修補檔 附錄二 Linux核心進階路由功能之程式碼修補

A Study on Novel Visual Secret Sharing Schemes

視覺密碼學(Visual Cryptography)是機密分享(Secret Sharing)領域下的一個新興領域，在原本機密分享的架構及環境下，多了一個解密不需要電腦運算的限制條件，分享影像交由參與者分別攜帶，只需要疊合起來就能觀看解密的結果。在這個新的特性之下，視覺密碼學在缺乏電腦運算能力、傳統技術無法運作時，仍然能夠正常進行解密，在緊急情況下提供一個良好的解決技術。在現有的視覺密碼學研究中，仍然有許多尚待改進的地方，例如目前絕大部分視覺密碼學方法所產生的分享影像在視覺上近似雜訊，若能使分享影像看來更自然，能夠有效的保護分享影像的安全。另外，仍未有技術能夠達到不同組合解出不同機密，同時在最基礎的兩張分享影像疊合時，也未能解密出多張的不同機密影像。 因此在本論文中，首先我們提出一個使分享影像具有意義的新方法，以像素轉換為基礎，比起現有方法具備更高機密解析度，而且能夠結合其他同類型方法達到更好的效果。接著，本論文提出了一個新的具備廣義型還原架構的視覺機密分享方法，不限制解密條件，同時可以讓各組參與者解密出不同的機密影像，進一步減少了限制條件。最後本論文提出一個視覺密碼學方法，能夠在兩張分享影像中藏入多張機密影像，使兩張分享影像可以一次藏入多量的機密，而不必攜帶多量的分享影像，比起現有方法只能將最多兩張機密影像藏入，依照本論文所推導出的關係公式，在放大倍率可以接受的狀況下，能解出任意張數的機密影像。本論文所提方法在現有技術的基礎上，深入研究視覺密碼學，以推廣其應用。Visual cryptography is a rising sub-field in the research of secret sharing. Except the properties of secret sharing, the decryption does not need any computation that the secret image reveals in human vision by just stacking the shares together. Therefore, visual cryptography is capable for emergency and special situations. However, there are plenty of rooms for improving in visual cryptography. For example, share images of current visual secret sharing schemes look like noise. It would be easy to hide the share images if the shares look like natural pictures. Also, different participants can only decrypt the same secret, and only one secret image can be decrypted from the participants. Therefore, we develop a new visual secret sharing scheme based on pixel swapping to generate two meaningful share images that the stacking results are better than existing schemes. In addition, the proposed scheme can cooperate with other schemes to enhance the quality. Then a new generalized visual secret sharing scheme is developed in this dissertation that different combination of shares can decrypt different secret images. Finally, a new idea to share multiple secret images in two share images is designed. Currently, the number of secrets is limited by two for two share images. According to the proposed relationship, the number is extended to general in our scheme with reasonable expanding ratio. The proposed schemes in this dissertation extend the research of visual cryptography and may be applied to more applications.致謝 I 中文摘要 II Abstract III Contents IV Contents of Tables VI Contents of Figures VII 1 Introduction 1 2 Related Works 10 2.1 Related Works of Meaningful Share Images 10 2.1.1 Error-Diffusion Halftoning Techniques 10 2.1.2 Data Hiding by Conjugate Error Diffusion 12 2.2 Related Works of Generalized Access Structure 14 2.2.1 Definition of an Access Structure 14 2.2.2 Visual Cryptography for General Access Structure 15 2.3 Related Works of Multiple Secrets 17 2.3.1 Chen and Wu''s Visual Secret Sharing Scheme for Two Secret Images 17 2.3.2 The Ring Shadow Image Technology 19 3 A Data Hiding Scheme Using Pixel Swapping for Halftone Images 23 3.1 The Proposed Scheme 23 3.2 Experimental Results 27 3.3 Analyses of the Proposed Scheme 32 3.3.1 Performance of the Proposed Scheme 32 3.3.2 Decision of the Swapping Conditions for Security 34 3.3.3 Comparisons of the Proposed Scheme 35 3.3.4 Radius in the Proposed Scheme 37 4 A Generalized Visual Secret Sharing Scheme for Multiple Secrets 39 4.1 The Proposed Scheme 39 4.1.1 Definitions of the Access Structure 39 4.1.2 Generation of the Constructional Matrix 40 4.2 Experimental Results 44 4.3 Analysis of the Proposed Scheme 48 5 Visual Secret Sharing for Multiple Secrets 50 5.1 The Proposed Scheme 50 5.1.1 The Decryption Model of the Proposed Scheme 51 5.1.2 The Encryption Process of the Proposed Scheme 52 5.2 Comparisons and Experimental Results 59 6 Conclusions and Future Works 65 References 6