抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Mindfulness is an attribute of consciousness long believed to promote well-being. This research provides a theoretical and empirical examination of the role of mindfulness in psychological well-being. The development and psychometric properties of the dispositional Mindful Attention Awareness Scale (MAAS) are described. Correlational, quasi-experimental, and laboratory studies then show that the MAAS measures a unique quality of consciousness that is related to a variety of well-being constructs, that differentiates mindfulness practitioners from others, and that is associated with enhanced selfawareness. An experience-sampling study shows that both dispositional and state mindfulness predict self-regulated behavior and positive emotional states. Finally, a clinical intervention study with cancer patients demonstrates that increases in mindfulness over time relate to declines in mood disturbance and stress. Many philosophical, spiritual, and psychological traditions emphasize the importance of the quality of consciousness for the maintenance and enhancement of well-being (Wilber, 2000). Despite this, it is easy to overlook the importance of consciousness in human well-being because almost everyone exercises its primary capacities, that is, attention and awareness. Indeed, the relation between qualities of consciousness and well-being has received little empirical attention. One attribute of consciousness that has been much-discussed in relation to well-being is mindfulness. The concept of mindfulness has roots in Buddhist and other contemplative traditions where conscious attention and awareness are actively cultivated. It is most commonly defined as the state of being attentive to and aware of what is taking place in the present. For example, Nyanaponika Thera (1972) called mindfulness “the clear and single-minded awareness of what actually happens to us and in us at the successive moments of perception” (p. 5). Hanh (1976) similarly defined mindfulness as “keeping one’s consciousness alive to the present reality” (p. 11). Recent research has shown that the enhancement of mindfulness through training facilitates a variety of well-being outcomes (e.g., Kabat-Zinn, 1990). To date, however, there has been little work examining this attribute as a naturally occurring characteristic. Recognizing that most everyone has the capacity to attend and to be aware, we nonetheless assume (a) that individuals differ in their propensity or willingness to be aware and to sustain attention to what is occurring in the present and (b) that this mindful capacity varies within persons, because it can be sharpened or dulled by a variety of factors. The intent of the present research is to reliably identify these inter- and intrapersonal variations in mindfulness, establish their relations to other relevant psychological constructs, and demonstrate their importance to a variety of forms of psychological well-being.

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The Benefits of Being Present: Mindfulness and Its Role in Psychological Well-Being

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma


 Background: Neoadjuvant anti-PD-(L)1 therapy may offer clinical benefit in resectable, early-stage NSCLC. NeoCOAST (NCT03794544) is a global, randomized phase 2 study of the anti-PD-L1 monoclonal antibody (mAb) durvalumab (D) alone or combined with the anti-CD73 mAb oleclumab (O), the anti-NKG2A mAb monalizumab (M), or the anti-STAT3 antisense oligonucleotide danvatirsen (Da) as neoadjuvant therapy.
 Methods: Pts with previously untreated, cytologically/histologically documented, resectable, Stage I [>2 cm]-IIIA NSCLC and ECOG PS 0-1 were randomized 1:1:1:1 (stratified by lymph node involvement) to receive D 1500 mg IV alone Q4W or combined with O 3000 mg IV Q2W, M 750 mg IV Q2W, or Da 200 mg IV QW, for one 28-day cycle, followed by surgery. Da monotherapy was also given on days 1, 3 and 5 of the week prior to combination treatment. The primary endpoint was investigator-assessed major pathological response (MPR; ≤10% residual viable tumor cells at tumor site and nodes, at surgery). Secondary endpoints were pathological complete response (pCR; no viable tumor cells), safety and tolerability, feasibility of surgery, PK and immunogenicity. Exploratory endpoints included tumor and microbiome biomarkers and blood mRNA signatures.
 Results: From March 2019 to Sept 2020, 84 pts were randomized and 83 received D (n=26), D+O (n=21), D+M (n=20), or D+Da (n=16). MPR occurred in 11.1% (95% CI, 2.4-29.2), 19.0% (95% CI, 5.4-41.9), 30.0% (95% CI, 11.9-54.3), and 31.3% (95% CI, 11.0-58.7%), respectively. pCR occurred in 3.7% (95% CI, 0.1-19.0), 9.5% (95% CI, 1.2-30.4), 10.0% (95% CI, 1.2-31.7%) and 12.5% (95% CI, 1.6-38.3), respectively. Rates of treatment-related AEs were 34.6% with D, 57.1% with D+O, 50.0% with D+M, and 43.8% with D+Da (grade ≥3 in 0%, 4.8%, 0% and 6.3%, respectively). Most pts (76/83; 91.6%) completed surgery with no significant delay; of the 7 pts unable to, 5 had progressive or stage IV disease. Across all arms, MPR was more common in pts with baseline tumor PD-L1 expression ≥1% vs those with <1%. With D, CD73 expression was correlated with greater residual viable tumor cells at surgery; however, with D+O, high CD73 (≥10% tumor cells) was associated with reduced viable tumor cells. Transcriptome analysis of post-treatment and baseline blood samples showed upregulation of genes involved in B cell activation and antigen presentation in pts with MPR in the D+O arm, and upregulation of genes associated with Tregs in pts with MPR in the D+M arm.
 Conclusions: One cycle of D + O, M or Da improved MPR and pCR rates vs D alone, with no new safety signals. Responses were associated with baseline tumor PD-L1 and CD73 expression levels. Pts with MPR receiving D+O or D+M had peripheral transcriptomic signatures related to immune cell function. These data warrant further investigation of these agents in resectable NSCLC.
 Citation Format: Tina Cascone, Rosario García-Campelo, Jonathan Spicer, Walter Weder, Davey Daniel, David Spigel, Maen Hussein, Julien Mazieres, Julio Oliveira, Edwin Yau, Alexander Spira, Raymond Mager, Oday Hamid, Lin-Yang Cheng, Ying Zheng, Jorge Blando, Lara McGrath, Italia Grenga, Yee Soo-Hoo, Rakesh Kumar, Patrick Forde. NeoCOAST: open-label, randomized, phase 2, multidrug platform study of neoadjuvant durvalumab alone or combined with novel agents in patients (pts) with resectable, early-stage non-small-cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT011.

Abstract CT011: NeoCOAST: open-label, randomized, phase 2, multidrug platform study of neoadjuvant durvalumab alone or combined with novel agents in patients (pts) with resectable, early-stage non-small-cell lung cancer (NSCLC)

The basic principles underlying randomized clinical trials have been known for more than 50 years. The Consolidated Standards of Reporting Trials (CONSORT) guidelines, published in 1996 and based on those principles, are a valuable guide to what needs to be reported from any trial within word-limit constraints, but they do not provide guidelines to the decisions that have to be made to generate a trial with credible results. Using these guidelines as do J. C. Coyne, M. Stefanek, and S. C. Palmer (2007) is a misinterpretation of their purpose. Furthermore, Coyne et al. misrepresented the methods and findings of studies of the effects of psychosocial intervention on cancer survival. These errors are systematically reviewed. The results of these questionable analyses led Coyne et al. to recommend stopping research in an area that may be highly productive. Recent developments in the field are summarized. It is a mistaken and dangerous conclusion to declare this or other areas of scientific research off limits.

Use and misuse of the consolidated standards of reporting trials (CONSORT) guidelines to assess research findings: comment on Coyne, Stefanek, and Palmer (2007).

David Spiegel

Papers

Abstract CT011: NeoCOAST: open-label, randomized, phase 2, multidrug platform study of neoadjuvant durvalumab alone or combined with novel agents in patients (pts) with resectable, early-stage non-small-cell lung cancer (NSCLC)

Use and misuse of the consolidated standards of reporting trials (CONSORT) guidelines to assess research findings: comment on Coyne, Stefanek, and Palmer (2007).

Embodying the mind in psychooncology research.

Psychische Belastungen bei Krebserkrankungen

Commentary. The treatment accorded those who treat patients with multiple personality disorder.