The Fragility of Statistically Significant Results in Randomized Clinical Trials for COVID-19

[Importance] Interpreting results from randomized clinical trials (RCTs) for COVID-19, which have been published rapidly and in vast numbers, is challenging during a pandemic. [Objective] To evaluate the robustness of statistically significant findings from RCTs for COVID-19 using the fragility index. [Design, Setting, and Participants] This cross-sectional study included COVID-19 trial articles that randomly assigned patients 1:1 into 2 parallel groups and reported at least 1 binary outcome as significant in the abstract. A systematic search was conducted using PubMed to identify RCTs on COVID-19 published until August 7, 2021. [Exposures] Trial characteristics, such as type of intervention (treatment drug, vaccine, or others), number of outcome events, and sample size. [Main Outcomes and Measures] Fragility index. [Results] Of the 47 RCTs for COVID-19 included, 36 (77%) were studies of the effects of treatment drugs, 5 (11%) were studies of vaccines, and 6 (13%) were of other interventions. A total of 138 235 participants were included in these trials. The median (IQR) fragility index of the included trials was 4 (1-11). The medians (IQRs) of the fragility indexes of RCTs of treatment drugs, vaccines, and other interventions were 2.5 (1-6), 119 (61-139), and 4.5 (1-18), respectively. The fragility index among more than half of the studies was less than 1% of each sample size, although the fragility index as a proportion of events needing to change would be much higher. [Conclusions and Relevance] This cross-sectional study found a relatively small number of events (a median of 4) would be required to change the results of COVID-19 RCTs from statistically significant to not significant. These findings suggest that health care professionals and policy makers should not rely heavily on individual results of RCTs for COVID-19

18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload–induced maladaptive cardiac remodeling

N-3 polyunsaturated fatty acids (PUFAs) have potential cardiovascular benefit, although the mechanisms underlying this effect remain poorly understood. Fat-1 transgenic mice expressing Caenorhabditis elegans n-3 fatty acid desaturase, which is capable of producing n-3 PUFAs from n-6 PUFAs, exhibited resistance to pressure overload–induced inflammation and fibrosis, as well as reduced cardiac function. Lipidomic analysis revealed selective enrichment of eicosapentaenoic acid (EPA) in fat-1 transgenic bone marrow (BM) cells and EPA-metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 transgenic macrophages. BM transplantation experiments revealed that fat-1 transgenic BM cells, but not fat-1 transgenic cardiac cells, contributed to the antiremodeling effect and that the 18-HEPE–rich milieu in the fat-1 transgenic heart was generated by BM-derived cells, most likely macrophages. 18-HEPE inhibited macrophage-mediated proinflammatory activation of cardiac fibroblasts in culture, and in vivo administration of 18-HEPE reproduced the fat-1 mice phenotype, including resistance to pressure overload–induced maladaptive cardiac remodeling

Cube Attacks on Non-Blackbox Polynomials Based on Division Property (Full Version)

The cube attack is a powerful cryptanalytic technique and is especially powerful against stream ciphers. Since we need to analyze the complicated structure of a stream cipher in the cube attack, the cube attack basically analyzes it by regarding it as a blackbox. Therefore, the cube attack is an experimental attack, and we cannot evaluate the security when the size of cube exceeds an experimental range, e.g., 40. In this paper, we propose cube attacks on non-blackbox polynomials. Our attacks are developed by using the division property, which is recently applied to various block ciphers. The clear advantage is that we can exploit large cube sizes because it never regards the cipher as a blackbox. We apply the new cube attack to Trivium, Grain128a, ACORN and Kreyvium. As a result, the secret keys of 832-round Trivium, 183-round Grain128a, 704-round ACORN and 872-round Kreyvium are recovered. These attacks are the current best key-recovery attack against these ciphers

A Modular Approach to the Incompressibility of Block-Cipher-Based AEADs

Incompressibility is one of the most fundamental security goals in white-box cryptography. Given recent advances in the design of efficient and incompressible block ciphers such as SPACE, SPNbox and WhiteBlock, we demonstrate the feasibility of reducing incompressible AEAD modes to incompressible block ciphers. We first observe that several existing AEAD modes of operation, including CCM, GCM(-SIV), and OCB, would be all insecure against white-box adversaries even when used with an incompressble block cipher. This motivates us to revisit and formalize incompressibility-based security definitions for AEAD schemes and for block ciphers, so that we become able to design modes and reduce their security to that of the underlying ciphers. Our new security notion for AEAD, which we name whPRI, is an extension of the pseudo-random injection security in the black-box setting. Similar security notions are also defined for other cryptosystems such as privacy-only encryption schemes. We emphasize that whPRI ensures quite strong authenticity against white-box adversaries: existential unforgeability beyond leakage. This contrasts sharply with previous notions which have ensured either no authenticity or only universal unforgeability. For the underlying ciphers we introduce a new notion of whPRP, which extends that of PRP in the black-box setting. Interestingly, our incompressibility reductions follow from a variant of public indifferentiability. In particular, we show that a practical whPRI-secure AEAD mode can be built from a whPRP-secure block cipher: We present a SIV-like composition of the sponge construction (utilizing a block cipher as its underlying primitive) with the counter mode and prove that such a construction is (in the variant sense) public indifferentiable from a random injection. To instantiate such an AEAD scheme, we propose a 256-bit variant of SPACE, based on our conjecture that SPACE should be a whPRP-secure cipher

Pengaruh Penyuluhan Obat Terhadap Peningkatan Perilaku Pengobatan Sendiri Di Kabupaten Banyumas

Self-medication is the mostly effort to coped health complaint, therefore to drug consume decrease unsuitable, it needed safety socialization to self-medication. The study was take to analyze the effect of drug counseling to self-medication increase in Banyumas regency. In addition to analyze the method effectiveness used in drug counseling to self-medication act. The instrument research used questionnaires in this study and purposive sampling used to took the sample. The respondents were 192 residents whom live in Banyumas regency. The type of research quasi-experimental with non-equivalent control group pretest and posttest research design. The data then analyzed by dependent-sampel t-test to find the effect of counseling to self-medication behavior in α = 0.05. While to find the effectiveness of between discussion group and lecture method by leaflet used independen-sampel t-test in α = 0.05. The results showed there significant different between before and after drug counseling by discussion goup and lecture method used leaflet media, able to self-medication attitude improved such as knowledge and attitude about self-medication (P= 0.000), also it can to know both of methods as effective as to self-medication attitude which showed P=0.05. It\u27s mean both of drug counseling methods used as effective as to self-medication attitude improvement. Key words: self medication attitude, counseling methods, housewife, Banyumas

Clearing A Space for Peer Supporters (II) : An Examination of Transcripts

関西大学ではピア・サポート活動の一環としてKU サポーターズというピア・カウンセリングを主な目的としたコミュニティがある。しかし、メンバーが傾聴の心構えや技術などの専門性にとらわれ、自らが相談活動を行っているという感覚が希薄化してしまうという問題があり、また、解決が簡単に見出せない問題と適切な距離をとり、上手く付き合っていく方略が求められている。そこで本研究では、大学院生2名をリスナーとし、KU サポーターズ所属の大学生12名をフォーカサーとしたClearing a Space（CAS） セッションを各フォーカサーに3回ずつ行った。本論第I部にてFMS第2因子「問題との距離を取る態度」のCAS実施前後の得点に変化が見られた事例のうち3例をここで報告する。これら3例のうち、2例はFMS第2因子において、低得点群から高得点群に移行した例（LH）で、1例は反対に高得点群から低得点群に移行した例（HL）である。逐語記録の検討よりKUサポーターズが問題から距離を置くという方略が身に付いていく様子がみられた。また、LH の2例では主体感覚の賦活化（吉良2002）が示唆された。それらにより、CASやそれによる主体感覚の賦活化がピア・サポート活動に対して有益である可能性が考えられた。In Kansai University, KU Supporters are organized for the purpose of peer counseling as a part of peer support. However, members are faced with issues of peers for which there are no easy answers, and training in specialized listening skills may hinder the spontaneity of the supporters. CAS was conducted on 12 peer supporters for 3 sessions. These sessions were conducted by 2 graduate students. Empirical studies using FMS was reported in the first part of this study. In this paper, CAS sessions from 3 peer supporters were examined in detail. These 3 supporters were selected because 2 of them scored Low to High (LH) and one of them scored High to Low (HL) on FMS-CD during this period. A consideration of these sessions showed that LH supporters acquired the strategy of distancing themselves from issues. In addition, the sense of subjectivity (Kira 2002) of these supporters were activated. CAS and the activation of the sense of subjectivity may benefit peer supporters

Clearing a Space for Peer Supporters (I) : Measured Effects on Stress Coping

本研究の目的は、ピア・サポートで活動するサポータを対象にストレスの対処法略としてClearing A Space（CAS）が有効かどうかを検討することである。ピア・サポートとは学生が学生を支援する活動であり、関西大学においては8つのコミュニティが活動を行っている。そのうちの1つのコミュニティであるKUサポーターズでは、学生の悩みに対して相談活動を行っている。しかし、人間関係などの根本的な解決が難しい問題が存在し、これが活動をするうえでの問題点のひとつに挙げられよう。この問題点に対してCASは問題と距離を置く1つの対処法略として有効であると考えられるため、その有効性を効果測定にて検討した。臨床心理専門職大学院の大学院生2名がピア・サポーター12名に3ヶ月に渡って3セッションのCAS個人指導を行った。この期間の前後にTAC-24及びFMSを実施した。その結果、CASを行うことで、対処方略の一つである回避的思考においてpre-post間で有意差および大きな効果が認められた（W+=2.517, p=.012,r=.73）。これはCASをTAC-24で挙げられていた対処方略の3つの軸を基にして理解すると、①フェルトセンスに対して（情動）、②適度な距離を置く（回避）という③思考活動（認知）を行ったと理解できる。それが①情緒に対して②回避的に関わり③その反応として回避的な思考（認知）をする回避的思考の因子で言い表せられたと考えられる。また、メンバーを問題と距離を置く態度の尺度であるFMS 距離でHigh/Lowの群に分けて検定を行うと、Low群においてCASを行うとFMS距離の得点が有意に増加していたことが確認され、CASを行う事によって悩み事から適切な距離を取って心の余裕を保とうとする態度に対して有意な効果がみられた。This paper aims to determine the effects of Clearing A Space (CAS) as stress coping in a peer support group, the KU Supporters. Kansai University has 8 peer support communities where students support each other. In one of them, the KU Supporters, peer counseling services are provided on a wide range of issues including learning, human relations and campus life. KU Supporters\u27 face challenges on difficult issues such as human relations where solutions are hard to find. Since CAS is a skill where distance is created from issues, CAS may benefit peer supporters. Two graduate clinical psychology students taught CAS on an individual bases to 12 peer supporters for 3 sessions over a 3 month period. TAC-24, a measure of stress coping and FMS, a measure of Focusing attitudes were administered to the 12 students before and after this period. Results indicated that Avoid-Thinking (TAC-24) showed statistically significant increase (W+=2.517. p= .012. r= .73) over this period. When peer supporters were divided into High/Low subgroups on the basis of FMS-CD (Distance) scores, the Low group showed significant increases in FMS-CD scores indicating that they were more able to create distance from issues (t(6)=2.71, p= .035, r= .74.). Moreover, for the Low group, significant increases in Avoid-Thinking on TAC-24 was also observed (t(6)=5.30, p= .002, r= .91). These results suggest that CAS has enhancing effects on stress coping

Fast Correlation Attack Revisited --Cryptanalysis on Full Grain-128a, Grain-128, and Grain-v1

A fast correlation attack (FCA) is a well-known cryptanalysis technique for LFSR-based stream ciphers. The correlation between the initial state of an LFSR and corresponding key stream is exploited, and the goal is to recover the initial state of the LFSR. In this paper, we revisit the FCA from a new point of view based on a finite field, and it brings a new property for the FCA when there are multiple linear approximations. Moreover, we propose a novel algorithm based on the new property, which enables us to reduce both time and data complexities. We finally apply this technique to the Grain family, which is a well-analyzed class of stream ciphers. There are three stream ciphers, Grain-128a, Grain-128, and Grain-v1 in the Grain family, and Grain-v1 is in the eSTREAM portfolio and Grain-128a is standardized by ISO/IEC. As a result, we break them all, and especially for Grain-128a, the cryptanalysis on its full version is reported for the first time

Effective Monotherapy with Amrubicin for a Refractory Extrapulmonary Small-Cell Carcinoma of the Liver

Small-cell carcinoma of the liver is a rare neoplasm, and no standard treatment for it has yet been established. A 72-year-old man with an extensive disease stage of small-cell carcinoma of the liver was treated with systemic chemotherapy consisting of cisplatin and etoposide (PE) followed by irinotecan. Although the masses were markedly decreased once after the sixth course of PE, amrubicin monotherapy as third-line chemotherapy was started because the hepatic masses had increased again. The administration of amrubicin was repeated in 8 courses with regression of the disease, resulting in a 26-month survival since the first-line chemotherapy was started. This is the first case report of a refractory EPSCC successfully treated with amrubicin

Improved Division Property Based Cube Attacks Exploiting Algebraic Properties of Superpoly (Full Version)

The cube attack is an important technique for the cryptanalysis of symmetric key primitives, especially for stream ciphers. Aiming at recovering some secret key bits, the adversary reconstructs a superpoly with the secret key bits involved, by summing over a set of the plaintexts/IV which is called a cube. Traditional cube attack only exploits linear/quadratic superpolies. Moreover, for a long time after its proposal, the size of the cubes has been largely confined to an experimental range, e.g., typically 40. These limits were first overcome by the division property based cube attacks proposed by Todo et al. at CRYPTO 2017. Based on MILP modelled division property, for a cube (index set) $I$, they identify the small (index) subset $J$ of the secret key bits involved in the resultant superpoly. During the precomputation phase which dominates the complexity of the cube attacks, $2^{|I|+|J|}$ encryptions are required to recover the superpoly. Therefore, their attacks can only be available when the restriction $|I|+|J|<n$ is met. In this paper, we introduced several techniques to improve the division property based cube attacks by exploiting various algebraic properties of the superpoly. 1. We propose the ``flag\u27\u27 technique to enhance the preciseness of MILP models so that the proper non-cube IV assignments can be identified to obtain a non-constant superpoly. 2. A degree evaluation algorithm is presented to upper bound the degree of the superpoly. With the knowledge of its degree, the superpoly can be recovered without constructing its whole truth table. This enables us to explore larger cubes $I$\u27s even if $|I|+|J|\geq n$. 3. We provide a term enumeration algorithm for finding the monomials of the superpoly, so that the complexity of many attacks can be further reduced. As an illustration, we apply our techniques to attack the initialization of several ciphers. To be specific, our key recovery attacks have mounted to 839-round TRIVIUM, 891-round Kreyvium, 184-round Grain-128a and 750-round ACORN respectively