失败的价值

我为我的讲话选择了这个题目：“失败的价值（The Virtues of Failure）”，你们可能会奇怪：怎么今天我竞希望谈论失败呢？首先，失败对我是司空见惯的。第二．我相信创新性的研究是无数次失败和极少几次成功的混合。对科学界以外的许多人或刚开始做研究的学生们来说．这一事实也许并不那么显而易见。我们在报纸上和科学杂志上重视或强调的总是所获得的成就．其中文章给人的印象是，成功的次数大大超过了失败次数。这一错误观念又常常被一些口头讲话所加强：演讲者往往把研究工作讲得让人听起来像是不费什么力气的事．那不过是一步接一步的逻辑步骤罢了。然而上述印象实在是一种误导，每个研究者都知道这一点。真正的研究乃是一部由错误组成的喜剧．其中错误的事情一件接着一件发生。不妨用丘吉尔（Winston Churchill）的话来说，研究进展其实是怀着永不衰减的热情．

4例器官移植后淋巴增殖性疾病皮肤损害的临床和病理特点

Background:Posttransplantation lymphoproliferative disorders (PTLDs) are lymphoid proliferations that can develop in recipients of solid organ or allogeneic bone marrow transplants. They are clinically and pathologically heterogeneous and range from polyclonal hyperplastic lesions to malignant lymphomas. Although extranodal involvement in PTLD is common, cutaneous presentation is rare, with only 19 cases reported previously. Observations: We describe 4 patients with cutaneous presentations of PTLD. All patients had relatively lateonset PTLD (>1 year after transplantation) with a median of 8 years from organ allograft to tumor diagnosis. The extent, number, and anatomic location of skin lesions varied from a localized patch to widespread nodules. None of the patients exhibited systemic symptoms at the time of PTLD diagnosis. Pathological findings ranged from plasmacytic hyperplasia to monomorphic PTLD. In situ hybridization detected EpsteinBarr virus messenger RNA in all 3 cases with evaluable tissue. All patients underwent reduction in immunosuppressive therapy and received other individualized treatments. Median followup was 2.5 years. At the most recent followup, 3 patients were in complete remission and 1 had residual disease. Conclusions: In this study, PTLD lesions presenting in the skin responded to therapy. Despite their relatively late occurrence after transplantation, most of these cases were positive for EpsteinBarr virus. As observedwith other cutaneous lymphomas, the PTLDs with predominant skin involvement had a relatively favorable outcome.

USPACE-洗砚池的岁月流淌

闊合CROX将豪森丽都商务楼的M层,改造为“办公＋生活”共享空间,宣告临沂新共享经济时代的来临,带来了城市的变革.过去典型的写字楼每层楼分租给不同公司,进出大楼的人群没有任何交流,如何有效的创造一种有利于资源互通的平台,并能与当地的文化结合,进而产生新的城市活力,是设计重要的挑战.

对银屑病皮损面积和严重指数的再思考:面积的影响应该增加

Background: The Psoriasis Area and Severity Index (PASI) is the most frequently used clinical severity scale in clinical trials. Drug approval often depends on a 75%improvement in the baseline PASI score, also known as a PASI 75 or Delta PASI 75. This benchmark may be an overly stringent way to determine the success of psoriasis treatments as Delta PASIs appear to under-represent true clinical improvement. This discrepancy may relate to the way numerical values are assigned to the degree of body surface area (BSA) involvement. Objectives: To assesswhether altering the BSA component of the PASI formula so that it is weighted more heavily will result in a calculated change in psoriasis severity that more closely reflects patient assessment of improvement. Models developed included the Psoriasis Log-based Area and Severity Index (PLASI), which assigns values to the BSA score based on a linear scale using logarithms to define the intervals, and the Psoriasis Exact Area and Severity Index (PEASI), which uses the actual BSA as the multiplicative factor in the area score. Methods: Data were abstracted retrospectively fromtwo clinical trials involving psoriasis treatments that used the PASI. The same trained psoriasis graders were involved in both trials. In these trials, baseline and end-point PASI worksheets were completed that included the actual clinician-estimated BSA involvement (0-100%) for each of the four areas (head, upper extremities, trunk and lower extremities). In one of the trials, patients were asked to assess the percentage improvement in their psoriasis at the end of the treatment window. PASIs and Delta PASIs were recalculated based on the newmodels and all scoring systemswere validated by analysing their relationship to patients’self-assessments. Results: Clinical improvements under the new grading systems translated into greater percentage changes than calculated using the Delta PASI formula. Specifically, the Delta PASI 50 translated to a Delta PLASI 57.2 and Delta PEASI 61.1; Delta PASI 75 was equivalent to Delta PLASI 85.7 and Delta PEASI 91.7. Importantly,Delta PASI tended to be systematically lower than patients’self-assessment, while Delta PLASI and Delta PEASI better matched patients’self-assessments using a best-fit model. Conclusions: These results suggest that the Delta PASI underestimates percentage improvement when compared with measures of patient’s self-assessment, while Delta PLASI and Delta PEASI correlate better. Prospective studies will have to be performed to confirm these relationships, but weighting BSA more heavily in the severity score may result in a more accurate reflection of clinical status.

面部磨削术可预防非黑色素皮肤癌

Objective: To determine the effect of facial skin resurfacing for treatment of actinic keratoses (AKs) and prophylaxis against new primary basal and squamous cell carcinomas in individuals with previous nonmelanoma skin cancer (NMSC) or severe photodamage. Design: Randomized, prospective 5-year trial. Setting: Dermatology and otolaryngology clinics of a Veterans Affairs hospital. Patients: Thirty-four patients with a history of facial or scalp AKs or basal or squamous cell carcinoma were enrolled. Five of 7 eligible patients who declined study-related treatment were used as controls. Twenty-seven patients were randomized to 3 treatment arms; 3 patients were discontinued from the study. Interventions: Carbon dioxide laser resurfacing, 30%trichloroacetic acid peel, or 5%fluorouracil cream applied twice daily for 3 weeks. Main Outcome Measures: Reduction in the number of AKs was measured 3 months after treatment. The incidence of new NMSC in treated areas was assessed between January 1, 2001, and June 30, 2005. Times from baseline to diagnosis of first skin cancer were compared between the treatment and control groups. Results: Treatment with fluorouracil, trichloroa- cetic acid, or carbon dioxide laser resulted in an 83%to 92%reduction in AKs (P≤.03), a lower incidence of NMSC compared with the control group (P<.001)-, and a trend toward longer time to development of new skin cancer compared with the control group (P=.07). However, no significant differences were noted among the treatment groups. Conclusion: All 3 modalities demonstrated benefit for AK reduction and skin cancer prophylaxis compared with controls and warrant further study in a larger trial.

清创术和角膜瓣缝合法治疗原位激光角膜磨镶术后的角膜上皮植入研究

Objectives: To evaluate the efficacy and safety of mechanical debridement and suturing of the laser in situ keratomileusis (LASIK) flap in the treatment of cl inically significant epithelial ingrowth after LASIK. Methods: In a retrospectiv e study, 20 eyes (n=19 patients) in which clinically significant epithelial ingr owth developed after LASIK were treated with lifting of the flap, scraping of th e epithelial ingrowth, and flap suturing. Primary outcome measurements including recurrence of ingrowth, uncorrected visual acuity (VA), manifest refraction, be st spectacle-corrected VA, and complications were evaluated at the last postope rative examination. Results: At the last postoperative examination (mean±SD, 10 .5 ±14.3 months; range, 1.5-64 months), 100%of eyes had no recurrence of clin ically significant epithelial ingrowth. The uncorrected VA changed from 20/20 or better in 7 eyes (35%) and 20/40 or better in 15 eyes (75%) preoperatively to 20/20 or better in 9 eyes (45%) and 20/40 or better in 16 eyes (80%) at the l ast follow-up examination. There was no significant change in the mean logarith m of the minimum angle of resolution (logMAR) uncorrected VA before (mean±SD, 0 .3±0.5; range, -0.1 to 1.7) and after surgery (mean±SD, 0.2±0.4; range, -0. 1 to 1.7) (P=.40). Mean±SD spherical equivalent changed from -0.21±0.82 diopt ers (D) (range, -1.25 to 1.00 D) preoperatively to -0.53±0.89D (range, -2.50 to 0.38 D) at last follow-up (P=.30). No eyes lost 2 or more lines of best spe ctacle-corrected VA, and there were no complications as sociated with the treatment. Conclusions: Suturing the LASIK flap in addition to mechanical debridement of epithelial ingrowth is a safe and effective treatme nt for clinically significant epithelial ingrowth after LASIK.

控制良好的自身免疫性肝炎在终止治疗前不进行肝脏活检也是同样安全的

背景:自身免疫性肝炎在终止治疗后可出现复发,尤其是在那些肝酶恢复正常但并未取得组织学缓解的患者。欧洲肝脏研究协会(EASL)和美国肝病研究协会(AASLD)的指南均推荐在终止治疗前要进行肝脏活检。本研究的目的是评估那些经免疫抑制治疗疾病控制良好的成人患者在终止治疗后的临床结局,无论其在终止治疗前有没有进行肝活检。方法:本研究为回顾性观察研究,研究对象是经组织学证实的成人自身免疫性肝炎患者,其接受了2年免疫抑制治疗,且在终止治疗前6个月内天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)一直维持或接近正常水平。排除青少年自身免疫性肝炎、既往曾接受过治疗或采用了激素和硫唑嘌呤之外药物治疗的患者。主要结局指标是终止治疗后1年复发率。结果:满足纳入标准的34例连续病例纳入研究,其中24例在终止治疗前未行肝活检,10例行肝活检。两组一般资料、免疫抑制剂使用情况、治疗前肝硬化程度和肝酶水平的差异均无统计学意义。25%的患者在终止治疗后1年内出现肝酶升高,但未行肝活检组与行肝活检组1年复发率的差异并无统计学意义(20.8%vs.30.0%,P=0.57)。结论:经2年免疫抑制治疗疗效甚佳的成人自身免疫性肝炎患者,在终止治疗前无需行肝活检。

美国国家自然地标：弗朗科尼亚峡谷

在美国新罕布什州中北部,有一著名的山区:白山。南北走向的93号州际公路纵穿白山地区,公路途径的一个重要“关口”便是弗朗科尼亚峡谷。这一峡谷本来只是一条并不出众的溪谷,后来在数次冰斯中被冰川侵蚀成一个典型的U型冰川谷。