Trials and Tribulations of

the participants agreed or strongly agreed that the time spent on simulation activities can be of great value,bearing in mind the80-hour work week restrictions.Up to75%of residents agreed or strongly agreed that previous simulation encoun-ters have enhanced their communication,decision making,and teamwork skills,in addition to their patient care and patient safety skills(Table).On the other hand,almost50%of residents dis-agreed or strongly disagreed that the Accredita-tion Council for Graduate Medical Education (ACGME)should mandate the integration of simulation curricula in surgical residency pro-grams.Similarly,almost half the residents did not believe that new technologies should be tested first in a simulated setting,before their use is warranted in clinical medical practice. Several interesting themes emerged from the group discussions.Concern was raised regarding the lack of evidence for efficacy,the use of non-validated teaching methods,and the feasibility and fidelity of currently available simulation models.Some participants believed the educa-tional significance of simulation to be inversely proportional to the level of training,meaning that novices may benefit more from this tool compared to experts.There were also concerns regarding the influence of external forces(public pressure and regulatory institutions)on the direction of simulation training.On the other hand,positive feedback regarding simulation was also noted during these discussions.The benefit of technical skill acquisition in a safe and stress-free learning environment was emphasized.Some participants identified simulation as a preparative training tool that could be useful prior to performing tasks on real patients.While a group of residents regarded simulation as an educational tool that might allow for the acquisition of technical proficiency,the majority agreed that it could not replace training on real patients.

In this survey,Wehbe-Janek et al tabulated interesting resident insights on surgical simula-tion.On one hand,it appears that there is a strong consensus that simulation is an impor-tant element in surgical education amongst surgical residents.On the other,it is clear that much work remains to be done in the areas of validation and simulation fidelity,as well as in making simulation relevant to more advanced levels of training.This report suggests that residents desire robust education but are leary of excessive regulatory oversight.

While the value of simulation becomes increas-ingly apparent in surgical education,its imple-mentation remains inconsistent.An important factor in implementing a simulation curriculum is resident buy-in.Without this,simulators will be left to collect dust.The work by Wehbe-Janek et al sheds light on general surgery resident perspectives

which provides our field of neurosurgery with

surrogate data that can be used as simulation

approaches are designed and implemented.Care-

ful attention to resident feedback will likely be an

important element of success,as simulation

curricula come on line in neurosurgery training

programs.We suspect that residency training

programs that emphasize thoughtful and validated

simulation training may gain a competitive edge in

Neurosurgical education.

T AREK Y.E L A HMADIEH

N AJIB E.E L T ECLE

S ALAH G.A OUN

B YRON K.Y IP

A RUNA G ANJU

B ERNARD R.B ENDOK

REFERENCES

1.Satava RM.Emerging trends that herald the future of

surgical simulation.Surg Clin North Am.2010;90(3):

623-633.

2.Philibert I,Friedmann P,Williams WT.New

requirements for resident duty hours.JAMA.2002;

288(9):1112-1114.

3.Fargen KM,Chakraborty A,Friedman WA.Results of

a national neurosurgery resident survey on duty hour

regulations.Neurosurgery.2011;69(6):1162-1170.

4.Cosman P,Hemli JM,Ellis AM,Hugh TJ.Learning

the surgical craft:a review of skills training options.

ANZ J Surg.2007;77(10):838-845.

5.Stefanidis D,Arora S,Parrack DM,et al.Research

priorities in surgical simulation for the21st century.

Am J Surg.2012;203(1):49-53.

6.Wehbe-Janek H,Colbert CY,Govednik-Horny C,

White BA,Thomas S,Shabahang M.Residents’

perspectives of the value of a simulation curriculum in

a general surgery residency program:a multimethod

study of stakeholder feedback.Surgery.2012;151(6):

815-821.

Trials and Tribulations of

Cancer Immunotherapy:

The Dendritic Cell

Vaccine Shows Promise in

a Phase I Glioblastoma

Multiforme Trial

S ince the publication7years ago of the

landmark paper by Stupp et al survival of

glioblastoma multiforme(GBM)has

reached a plateau,with only limited non-significant

increases in survival.1Despite the most aggres-

sive therapies this devastating malignancy has

a near perfect recurrence rate,accounting for

nearly15%of all brain tumors in adults

between the ages of45and70.2Over the last

few decades however,great strides have been

made in cancer immunotherapy,most notably

with the creation of the human papilloma virus

(HPV)vaccine for cervical cancer,and T-cell

therapies for advanced melanoma.3A short-

coming to these therapies is that they require

the cultivation of substantial amounts of lym-

phocytes using uncommon technical expertise

and facilities.3Less labor-intensive immuno-

therapy modalities like vaccines may prove

more efficacious.

Dendritic cells(DCs)theoretically are a prime

candidate for cancer vaccines.Specifically,they

are known to be the most powerful antigen-

presenting cells(APCs)and are largely responsible

for the initial sensitization of na?ve T-cells to

antigens.Plus they are present in nearly all sites of

pathogen entry.4Thus it seemed reasonable to

harness the power of these cells to achieve the

strongest immunity.Furthermore,DCs can be

derived ex vivo from blood monocytes exposed to

granulocyte-macrophage colony-stimulating fac-

tor(GM-CSF)and interleukin-4(IL-4).5DC

immunotherapy and vaccination has been stud-

ied in a wide variety of cancers,Phuphanich et al

have recently reported the results of a phase I

clinical trial in which patient-derived DCs were

pulsed with multiple tumor-associated antigens

(TAAs)that are expressed on gliomas and known

to be overexpressed in the cancer stem cell(CSC)

population.6

Patients with newly diagnosed or recurrent

GBM who underwent a gross total resection and

were HLA-A1and/or A-2positive were enrolled.

A well understood mechanism for tumors to

avoid immune detection and eradication is

through minimizing the presentation of antigens

to class I major histocompatability complexes

(MHCs).This failure has been partly traced to

mutations and deletions affecting the expression

of human leukocyte antigen(HLA)molecules.7-10

The autologous DC vaccine was prepared from

monocytes obtained through leukapheresis and

cultured ex vivo.To target the DCs to the CSC

population HLA-1restricted TAA’s MAGE1

and AIM-2,and HLA-2restricted TRP-2,

gp100,HER2,and IL13Ra2were pulsed for

16to20hours.Subsequently,sterility was

tested and patients were then given3injections

of the vaccine,and monitored for adverse events

(AE).

Upon analysis of the expression of the TAA’s

targeted by the vaccine,it was shown that

expression of the HLA-1restricted TAA’s

significantly correlated with progression-free

survival(PFS)and overall survival(OS).Addi-

tionally,the expression of HER2and gp100

appeared to exhibit a trend towards longer PFS

NEURO SURGERY VOLUME71|NUMBER6|DECEMBER2012|N19

and OS.In response to vaccine administration, A2epitopes showed significant downregulation (P?.023;Fisher’s exact test)relative to upregulation in3patients where responses were https://www.sodocs.net/doc/6a2868128.html,paratively,the downregulation A1epitope AIM2was not significant yielded a P value of.21(Fisher’s exact test).

The characterization of GBM CSCs has lead to the defining surface marker of this putative cell population:CD133.Cells expressing this marker(CD1331)have been shown to be more resistant to radiation11and chemother-apy,12and be correlated to a poor clinical outcome.6Moreover,CD133positivity has

been reported to increase in recurrence,possibly

owing to the severity and rapid clinical degra-

dation.Intriguingly,the vaccine illustrated

a preferential targeting of CD133positive cells.

Previous studies by this group and others have

consistently shown increased CD133in recur-

rent tumors,especially in recurrent tumors even

after TAA loaded DC vaccination.6In newly

diagnosed and recurrent patients,the CD133

expression was shown to markedly decrease

with1recurrent and1newly diagnosed patient

becoming CD133negative.

Analysis of immune responses7days before

vaccine administration compared to samples

obtained56days after the first vaccine admin-

istration showed a33%positive vaccine

response of..5-fold increase.PFS and OS

and long-term survivors exhibiting increasing

trends towards better survival,however they

were not significant.At a median follow-up of

40.1months,6of the16newly diagnosed

patients showed no evidence of tumor recur-

rence.Median PFS and OS in the newly

diagnosed patients were16.9months and38.4

months respectively.

Figure1.Schema of treatment schedule and events(A)The correlation of quantitative antigen expression on primary tumor from new diagnosed patients(n?13)with progression-free survival(PFS;left set of6graphs)and overall survival(OS;right set of6graphs).Logarithmic plots of antigen expression were determined by qRT-PCR.A significant correlation between HLA-1antigens and PFS and OS was observed while gp100and HER2antigens trended towards a positive correlation in both PFS and OS.(B)Kaplan-Meier estimates of PFS(left panel)and OS(right panel)for newly diagnosed patients(n?16)(Dotted line illustrates95%CI;hash marks are for censored patients.)(C)CD133 expression by RT-PCR in primary tumor and subsequent tumor samples from newly diagnosed and recurrent patients.Expression is calculated relative to GADPH.CD133 expression was negative or decreased in subsequently after vaccine administration(D).With kind permission from Springer Science1Business Media:Cancer Immunology Immunotherapy,Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma,2012Jul31.[Epub ahead of print].

N20|VOLUME71|NUMBER6|https://www.sodocs.net/doc/6a2868128.html,

Despite these median survival times being comparable to current survival,the ICT-107 vaccine illustrated an impressive percent of res-ponders,exhibiting an increased immune res-ponse,33%,higher than recent immunotherapy vaccines trials.A central problem in developing cancer vaccines is that all immunotherapies, vaccines included,are dependent on their ability to generate immune responses to specific and defined targets that must be presented by the tumor cells.Historically this has been the great-est challenge in creating novel vaccines.The immunoediting hypothesis13may partly help to explain the limited success of recent cancer vaccines,and the difficulty in targeting tumor cells.Furthermore,the full potential of den-dritic cells may not have been fully exploited or the hypothesis that DCs are not an effective pathway to pursue may hold true.

Careful re-evaluation of current vaccine design is crucial;the natural course of DCs and their role in the immune system all must be taken into account.Equally important,soluble factors such as IL-12must be considered particularly for their immuno-modulating capabilities.3Finally, clinical trials need to incorporate validated prognostic methods(eg,delayed-type hyper-sensitivity responses,T-cell cytotoxicity assay) to monitor anticancer immune activity in vivo as an intermediary measure of efficacy.4The notion of inducing the body to fight the human body,the central notion of the immune system, works for the copious other maladies that affect the human condition.Advances in our under-standing of neuroimmunology will greatly increase our efficacy with cancer vaccines and reverberate in rational vaccine development, clinical trial designs,and analyses.

D EMIRKAN B.GüRSEL

C ODY D.S CHLAFF

J OHN A.B OOCKVAR REFERENCES

1.Stupp R,Mason WP,van den Bent MJ,et al.

Radiotherapy plus concomitant and adjuvant temo-zolomide for glioblastoma.N Engl J Med.2005;352

(10):987-996.

2.DeVita VT,Hellman S,Rosenberg SA.Cancer,

Principles and Practice of Oncology.Philadelphia,PA: Lippincott,Williams&Wilkins;2001.

3.Koski GK,Cohen PA,Roses RE,Xu S,Czerniecki BJ.

Reengineering dendritic cell-based anti-cancer vac-cines.Immunol Rev.2008;222:256-276.

4.Yong RL,Lonser RR.Immunotherapy trials for

glioblastoma multiforme:promise and pitfalls.World Neurosurg.2012;77(5-6):636-638.

5.Schuler G.Dendritic cells in cancer immunotherapy.

Eur J Immunol.2010;40(8):2123-2130.

6.Phuphanich S,Wheeler CJ,Rudnick JD,et al.Phase I

trial of a multi-epitope-pulsed dendritic cell vaccine

for patients with newly diagnosed glioblastoma

[published online ahead of print].Cancer Immunol

Immunother.2012.

7.Hicklin DJ,Wang Z,Arienti F,Rivoltini L,Parmiani G,

Ferrone S.beta2-Microglobulin mutations,HLA class I

antigen loss,and tumor progression in melanoma.J Clin

Invest.1998;101(12):2720-2729.

8.Meissner M,Reichert TE,Kunkel M,et al.Defects in

the human leukocyte antigen class I antigen process-

ing machinery in head and neck squamous cell

carcinoma:association with clinical outcome.Clin

Cancer Res.2005;11(7):2552-2560.

9.Vitale M,Rezzani R,Rodella L,et al.HLA class I

antigen and transporter associated with antigen

processing(TAP1and TAP2)down-regulation in

high-grade primary breast carcinoma lesions.Cancer

Res.1998;58(4):737-742.

10.Wang Z,Marincola FM,Rivoltini L,Parmiani G,

Ferrone S.Selective histocompatibility leukocyte

antigen(HLA)-A2loss caused by aberrant pre-mRNA

splicing in624MEL28melanoma cells.J Exp Med.

1999;190(2):205-215.

11.Bao S,Wu Q,McLendon RE,et al.Glioma stem

cells promote radioresistance by preferential activa-

tion of the DNA damage response.Nature.2006;

444(7120):756-760.

12.Liu G,Yuan X,Zeng Z,et al.Analysis of gene

expression and chemoresistance of CD1331cancer

stem cells in glioblastoma.Mol Cancer.2006;5:67.

13.Dunn GP,Fecci PE,Curry WT.Cancer immunoe-

diting in malignant glioma.Neurosurgery.2012;71

(2):201-223.

Granulocyte-stimulating

Colony Factor

Neuroprotection for

Thoracic Myelopathy

G ranulocyte-stimulating colony factor

(G-CSF),commercially available as

Neupogen or Neulasta,has long been

used for the treatment of neutropenia in cancer

patients.Several clinical studies have examined

the utility of G-CSF in amyotrophic lateral

sclerosis and ischemic stroke,with ambiguous,

NEURO SURGERY VOLUME71|NUMBER6|DECEMBER2012|N21

如何写先进个人事迹

如何写先进个人事迹 篇一：如何写先进事迹材料 如何写先进事迹材料 一般有两种情况：一是先进个人，如先进工作者、优秀党员、劳动模范等；一是先进集体或先进单位，如先进党支部、先进车间或科室，抗洪抢险先进集体等。无论是先进个人还是先进集体，他们的先进事迹，内容各不相同，因此要整理材料，不可能固定一个模式。一般来说，可大体从以下方面进行整理。 (1)要拟定恰当的标题。先进事迹材料的标题，有两部分内容必不可少，一是要写明先进个人姓名和先进集体的名称，使人一眼便看出是哪个人或哪个集体、哪个单位的先进事迹。二是要概括标明先进事迹的主要内容或材料的用途。例如《王鬃同志端正党风的先进事迹》、《关于评选张鬃同志为全国新长征突击手的材料》、《关于评选鬃处党支部为省直机关先进党支部的材料》等。 (2)正文。正文的开头，要写明先进个人的简要情况，包括：姓名、性别、年龄、工作单位、职务、是否党团员等。此外，还要写明有关单位准备授予他(她)什么荣誉称号，或给予哪种形式的奖励。对先进集体、先进单位，要根据其先进事迹的主要内容，寥寥数语即应写明，不须用更多的文字。 然后，要写先进人物或先进集体的主要事迹。这部分内容是全篇材料

的主体，要下功夫写好，关键是要写得既具体，又不繁琐；既概括，又不抽象；既生动形象，又很实在。总之，就是要写得很有说服力，让人一看便可得出够得上先进的结论。比如，写一位端正党风先进人物的事迹材料，就应当着重写这位同志在发扬党的优良传统和作风方面都有哪些突出的先进事迹，在同不正之风作斗争中有哪些突出的表现。又如，写一位搞改革的先进人物的事迹材料，就应当着力写这位同志是从哪些方面进行改革的，已经取得了哪些突出的成果，特别是改革前后的．经济效益或社会效益都有了哪些明显的变化。在写这些先进事迹时，无论是先进个人还是先进集体的，都应选取那些具有代表性的具体事实来说明。必要时还可运用一些数字，以增强先进事迹材料的说服力。 为了使先进事迹的内容眉目清晰、更加条理化，在文字表述上还可分成若干自然段来写，特别是对那些涉及较多方面的先进事迹材料，采取这种写法尤为必要。如果将各方面内容材料都混在一起，是不易写明的。在分段写时，最好在每段之前根据内容标出小标题，或以明确的观点加以概括，使标题或观点与内容浑然一体。 最后，是先进事迹材料的署名。一般说，整理先进个人和先进集体的材料，都是以本级组织或上级组织的名义；是代表组织意见的。因此，材料整理完后，应经有关领导同志审定，以相应一级组织正式署名上报。这类材料不宜以个人名义署名。 写作典型经验材料-般包括以下几部分： (1)标题。有多种写法，通常是把典型经验高度集中地概括出来，一

关于时间管理的英语作文 manage time

How to manage time Time treats everyone fairly that we all have 24 hours per day. Some of us are capable to make good use of time while some find it hard to do so. Knowing how to manage them is essential in our life. Take myself as an example. When I was still a senior high student, I was fully occupied with my studies. Therefore, I hardly had spare time to have fun or develop my hobbies. But things were changed after I entered university. I got more free time than ever before. But ironically, I found it difficult to adjust this kind of brand-new school life and there was no such thing called time management on my mind. It was not until the second year that I realized I had wasted my whole year doing nothing. I could have taken up a Spanish course. I could have read ten books about the stories of successful people. I could have applied for a part-time job to earn some working experiences. B ut I didn’t spend my time on any of them. I felt guilty whenever I looked back to the moments that I just sat around doing nothing. It’s said that better late than never. At least I had the consciousness that I should stop wasting my time. Making up my mind is the first step for me to learn to manage my time. Next, I wrote a timetable, setting some targets that I had to finish each day. For instance, on Monday, I must read two pieces of news and review all the lessons that I have learnt on that day. By the way, the daily plan that I made was flexible. If there’s something unexpected that I had to finish first, I would reduce the time for resting or delay my target to the next day. Also, I would try to achieve those targets ahead of time that I planed so that I could reserve some more time to relax or do something out of my plan. At the beginning, it’s kind of difficult to s tick to the plan. But as time went by, having a plan for time in advance became a part of my life. At the same time, I gradually became a well-organized person. Now I’ve grasped the time management skill and I’m able to use my time efficiently.

脐带干细胞综述

脐带间充质干细胞的研究进展 间充质干细胞（mesenchymal stem cells,MSC S ）是来源于发育早期中胚层 的一类多能干细胞[1-5]，MSC S 由于它的自我更新和多项分化潜能，而具有巨大的 治疗价值 ,日益受到关注。MSC S 有以下特点：(1)多向分化潜能，在适当的诱导条件下可分化为肌细胞[2]、成骨细胞[3、4]、脂肪细胞、神经细胞[9]、肝细胞[6]、心肌细胞[10]和表皮细胞[11, 12]；(2)通过分泌可溶性因子和转分化促进创面愈合；(3) 免疫调控功能，骨髓源（bone marrow ）MSC S 表达MHC-I类分子，不表达MHC-II 类分子，不表达CD80、CD86、CD40等协同刺激分子，体外抑制混合淋巴细胞反应，体内诱导免疫耐受[11, 15]，在预防和治疗移植物抗宿主病、诱导器官移植免疫耐受等领域有较好的应用前景；(4)连续传代培养和冷冻保存后仍具有多向分化潜能，可作为理想的种子细胞用于组织工程和细胞替代治疗。1974年Friedenstein [16] 首先证明了骨髓中存在MSC S ，以后的研究证明MSC S 不仅存在于骨髓中，也存在 于其他一些组织与器官的间质中：如外周血[17]，脐血[5]，松质骨[1, 18]，脂肪组织[1]，滑膜[18]和脐带。在所有这些来源中，脐血(umbilical cord blood)和脐带(umbilical cord)是MSC S 最理想的来源，因为它们可以通过非侵入性手段容易获 得，并且病毒污染的风险低，还可冷冻保存后行自体移植。然而，脐血MSC的培养成功率不高[19, 23-24]，Shetty 的研究认为只有6%，而脐带MSC的培养成功率可 达100%[25]。另外从脐血中分离MSC S ，就浪费了其中的造血干/祖细胞(hematopoietic stem cells/hematopoietic progenitor cells,HSCs/HPCs) [26, 27]，因此，脐带MSC S (umbilical cord mesenchymal stem cells, UC-MSC S )就成 为重要来源。 一．概述 人脐带约40 g, 它的长度约60–65 cm, 足月脐带的平均直径约1.5 cm[28, 29]。脐带被覆着鳞状上皮，叫脐带上皮，是单层或复层结构，这层上皮由羊膜延续过来[30, 31]。脐带的内部是两根动脉和一根静脉，血管之间是粘液样的结缔组织，叫做沃顿胶质，充当血管外膜的功能。脐带中无毛细血管和淋巴系统。沃顿胶质的网状系统是糖蛋白微纤维和胶原纤维。沃顿胶质中最多的葡萄糖胺聚糖是透明质酸，它是包绕在成纤维样细胞和胶原纤维周围的并维持脐带形状的水合凝胶，使脐带免受挤压。沃顿胶质的基质细胞是成纤维样细胞[32]，这种中间丝蛋白表达于间充质来源的细胞如成纤维细胞的，而不表达于平滑肌细胞。共表达波形蛋白和索蛋白提示这些细胞本质上肌纤维母细胞。 脐带基质细胞也是一种具有多能干细胞特点的细胞，具有多项分化潜能，其 形态和生物学特点与骨髓源性MSC S 相似[5, 20, 21, 38, 46]，但脐带MSC S 更原始，是介 于成体干细胞和胚胎干细胞之间的一种干细胞，表达Oct-4, Sox-2和Nanog等多

英语演讲稿：未来的工作

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