People with epilepsy must adopt many self-management behaviors, especially regarding medication adherence, stress management, and sleep quality. In response to the need for theory-based self-management programs that people with epilepsy can easily access, the WebEase Web site was created and tested for feasibility, acceptability, and usability. This article discusses the theoretical background and developmental phases of WebEase and lessons learned throughout the development process. The WebEase research team developed content for the Web site on the basis of social cognitive theory, the transtheoretical model of behavior change, and motivational interviewing. Formative research and development of the WebEase program included a literature search, computer use survey, a focus group, and review by content experts and consumers. The program has 2 main components: 1) the modules, which provide a tailored opportunity for learning, reflection, and goal setting, and 2) MyLog, a place to enter daily information. More than 2.7 million Americans have epilepsy , and livStudies of people with chronic disorders, including epilepsy, show that theory-based programs can foster self-management practices, such as taking medications as prescribed and managing stress and sleep -24. In aThe US Department of Health and Human Services recognizes the potential of technology to help people with chronic disorders overcome such barriers to better manage their health . For exaIn 2005, the Centers for Disease Control and Prevention's Epilepsy Program recognized the dearth of accessible, theory-based self-management programs for people with epilepsy and provided funding to develop an Internet-based epilepsy self-management program. WebEase (Web Epilepsy Awareness Support and Education) was created in response to this initiative. In this article, we discuss the development of WebEase, including formative research and the development of the Web site. We also discuss challenges to the development of a theory-based self-management program in a Web interface and lessons learned.The WebEase development team was composed of an interdisciplinary group of investigators and staff with expertise in epilepsy treatment and care, health education, behavioral research, Web design and development, and program evaluation. The first task the team undertook was to review self-management programs and Web sites. This review provided useful information on the content, delivery, and teaching strategies used in Web site development. Additionally, we specifically reviewed program Web sites that used interactive applications of the constructs from the 3 theoretical models — transtheoretical model of behavior change ,30, sociTo assess the potential market for an Internet-based epilepsy program, we gathered information about computer use from people with epilepsy and their caregivers. The survey was disseminated through 2 epilepsy Web sites, and a paper-and-pencil survey was distributed to patients attending 2 epilepsy clinics in the Atlanta metropolitan area. For both methods, participants were asked to sign a consent document. The survey results showed that more than 95% of the online group and more than 60% of the clinic group had access to computers and the Internet . More thWe conducted a focus group with 6 people who had epilepsy to discuss in more detail some of the issues raised by the survey and to verify its findings. As revealed by the survey, most participants used computers to obtain health information and most expressed interest in an online self-management program. Focus group participants also provided information about the 3 content areas — medication, stress, and sleep management — that would later be incorporated into WebEase. Institutional review board approval was obtained, and informed consent was given for both the computer use survey and the focus group.WebEase components include 3 core modules, a daily log, discussion boards, fact sheets, quizzes, daily poll questions, and links to online resources.The modules for medication, stress, and sleep management are the core of the WebEase program. By working through the modules, participants assess their status in each of these 3 self-management areas, reflect on their behavior, and create a plan for change or to maintain their behavior if no change is required. Each module is composed of 5 submodules, which represent the 5 categories of the stages of change: precontemplation, contemplation, preparation, action, and maintenance. Each submodule is composed of 3 sections: an introductory assessment section (Looking at My Medications), a section devoted to thinking about current behavior (Thinking About My Medications), and a section on goal setting and planning (Planning the Next Steps).The introductory section of a module is the same for everyone. It provides information from participants' daily log (MyLog) and includes a series of questions about their behavior — medication taking, stress, or sleep. Feedback is given to reflect and summarize answers. The information obtained from answers to the questions is used to assign the participant to 1 of the 5 transtheoretical model stages. The second section includes information and activities that vary depending on assigned stage. The focus of the precontemplation stage is supporting positive attitudes toward the behavior and encouraging the participant to think about it; contemplation focuses on comparing the benefits and costs of the behavior and beginning to think about strategies to support it; preparation stresses strategies to support the behavior and the resources this requires; the action phase assesses confidence in one's ability to continue the behavior and the required resources; and maintenance deals with life changes that may interfere with the behavior and contemplating how it fits in one's life. Activities may include 1 or more of the following theory-based strategies: benefits, costs, previous successes, barriers, confidence in making changes, values, reasons for not changing, how life would differ if behavior did or did not change, resources and skills needed, and identification of a support person. The content throughout the modules is delivered by using motivational interviewing principles.Links to fact sheets and other information resources are included. This information prompts a participant to learn about the behavior, strategy, or skill at the time it is presented. Links are also presented to images and audio files that show participants who tell their stories about dealing with challenges related to the behavior.In the third section, Planning the Next Steps, the participant has the choice of making a plan of action that includes specific performance goals. Those in the precontemplation, contemplation, and preparation stages first complete a "readiness scale" to assess how prepared they are to make changes, create strategies, and commit to goals. After receiving feedback on their answers, participants are asked if they are ready to take the next step and make a plan. If so, the module takes them through the process of creating a goal and identifying potential barriers and useful strategies to overcome them. Those in the action and maintenance phases also have the opportunity to create goals and a plan to change or maintain their current behavior.MyLog was designed so that participants can enter daily information about their medications, seizures, stress, and sleep. These data are entered into a database, and feedback is given in 3 ways. First, a text summary of information entered gives averages for each behavior. Second, a set of graphs presents the information visually over a 7-day period. Both the summary and the graphs can be printed. Third, some information entered into MyLog is used within the modules.MyVoice is a series of discussion boards that provides a forum for sharing information and fostering relationships. Discussion boards for the 3 main topics are available to participants during the entire program. They may post questions, respond to one another, and share experiences related to medication, stress, and sleep. During the pilot study, a nurse logged onto the site each day to monitor discussions and identify problems that would require referral to a health care professional.Several components of the program were designed to increase knowledge about medication, stress, and sleep management and were supplemental to the core modules. Fact sheets were developed on each of the 3 areas and were available for participants to read at their leisure throughout the program. In addition, short quizzes and daily poll questions on each topic area were designed to engage participants to learn about epilepsy. Web resources for epilepsy, including the Epilepsy Foundation, the Centers for Disease Control and Prevention, and Epilepsy.com, were linked to encourage participants to learn more about self-management.The design process of the WebEase program used an iterative evaluation process recommended for interactive interventions  and commFour nurses with expertise in the care of people with epilepsy, epilepsy self-management research, and theory-based behavioral interventions served on the content expert panel. At each stage of development, these experts reviewed materials and provided comments and suggestions on aspects such as accuracy of content, organization of information, ease of understanding and use, application of theory, relevance, and acceptability. For each review, the experts completed an evaluation form with questions specific to the content, acceptability, usability, and appropriateness of the information. In response to the experts' comments and suggestions, many changes were made to clarify and enhance the content and improve its presentation and usability.Two people with epilepsy assisted the team by evaluating the acceptability and usability of the Web site during the development phase. After each module was created, these consumers came to our office individually and worked through the site. They logged onto WebEase, and as they navigated it, they told us what they were doing, why they were doing it, what they liked, and what problems they had. Two team members observed each consumer and took notes on comments about content, layout, navigation, relevance of materials, educational soundness, appeal, understanding of key messages, appropriateness of graphics, ease of use, problems encountered, and recommendations for change. The participants also completed a short survey on the amount of material, the site's organization and layout, images, their general opinion of the site, and what they liked, disliked, and would change. The participants' feedback led to several revisions of text, images, and layout.Thirty-seven people with epilepsy agreed to participate in the study to evaluate the acceptability and usability of WebEase and provide an initial test of its behavioral objectives. Participants were recruited from 2 epilepsy clinics. After completing the pretest, participants were able to use each module for 2 weeks. At the end of the 6 weeks, they completed a posttest. The procedure and outcomes of the pilot study are described elsewhere .WebEase was developed and tested during a 2-year period. The extensive work required for its development and testing was facilitated by a team of content, process, and programming experts. The diversity of expertise and skills was critical to the success of the project. During these 2 years, 3 students assisted. They supported the team by aiding in content development, Web site review and revision, participant recruitment, orientation, and data analysis.The primary challenge was communication between Web programmers and content developers. The 2 groups were in 2 different offices in Atlanta and often did not fully understand each other's activities. To facilitate communication, we had several working sessions in which the content developers presented theories to be applied in the program and described how they wanted the constructs and activities translated online, and the programmers offered options to accomplish these ends. Communication was also facilitated by a team member with extensive experience in Web design who spoke the "language" of both groups. Revising the site was often tedious and time consuming. To facilitate the revision process, a content developer and a programmer reviewed the components together while the programmer made changes. This strategy was successful but unfortunately was not implemented until late in the development phase.Our experience confirms the adage that project development always takes longer and costs more than was planned and budgeted. The first 6 months of the program went as planned; however, we were not satisfied with the staging items or the incorporation of motivational interviewing principles in the first version of the site. The overall plan, algorithms, and content were extensively revised. These changes required text to be rewritten for all 3 modules and sections to be reprogrammed. The new versions of the modules were more complex, with more strategies for change and more choices, which resulted in more branching. The team required an additional 6 months to make the changes and refine the modules.For the content development team, incorporating theory-based concepts was often challenging. The overall objective of the program was to use proven behavioral change strategies to promote epilepsy self-management behaviors. Thus, the program could not be limited to educational information. Rather, we needed to design ways to encourage reflection on the behavior and to motivate change. The transtheoretical model, social cognitive theory, and motivational interviewing strategies were designed primarily for face-to-face encounters. The Web interface presented the challenge of trying to use these strategies to make the site interactive in the absence of face-to-face contact. In addition, giving feedback to some comments entered into the program proved difficult without understanding the context in which they were made. Feedback that involved simple reflection, such as repeating the participant's words, was easy to program. More complex feedback, however, required algorithms that accommodated the various general statements that were possible.Based on our experience developing WebEase and the lessons we learned throughout the process, we offer the following recommendations for similar projects. Overall, we recommend that a project's timeline include sufficient time for development and unanticipated revisions. Because feedback on content development and programming is an iterative process, a member of the content development team and the programmer should work side by side at designated times to facilitate communication and troubleshooting. Additionally, the Web site should be designed so that the content development team can make minor revisions, allowing the programmer to focus on broader program issues. Finally, we recommend that developers be willing to allow some flexibility in applying the theoretical frameworks behind their program. As mentioned above, some of the motivational interviewing components did not easily translate to an Internet format without a facilitator. Along with creative incorporation of theoretical constructs, future programs could also make use of other online tools, such as a synchronous, interactive chat. Overall, the initial results are encouraging, and continued development of WebEase can facilitate education and strategies to manage epilepsy for a population with barriers to accessing these services in person. In developing and evaluating this online self-management program, we hope to increase self-management skills and improve the quality of life of people with epilepsy.


Quantitative proteomics technologies have been developed to comprehensively identify and quantify proteins in two or more complex samples. Quantitative proteomics based on differential stable isotope labeling is one of the proteomics quantification technologies. Mass spectrometric data generated for peptide quantification are often noisy, and peak detection and definition require various smoothing filters to remove noise in order to achieve accurate peptide quantification. Many traditional smoothing filters, such as the moving average filter, Savitzky-Golay filter and Gaussian filter, have been used to reduce noise in MS peaks. However, limitations of these filtering approaches often result in inaccurate peptide quantification. Here we present the WaveletQuant program, based on wavelet theory, for better or alternative MS-based proteomic quantification.Trans-Proteomic Pipeline (TPP), a commonly used open source proteomics analysis pipeline.We developed a novel discrete wavelet transform (DWT) and a 'Spatial Adaptive Algorithm' to remove noise and to identify true peaks. We programmed and compiled WaveletQuant using Visual C++ 2005 Express Edition. We then incorporated the WaveletQuant program in the http://systemsbiozju.org/data/WaveletQuant.We showed that WaveletQuant was able to quantify more proteins and to quantify them more accurately than the ASAPRatio, a program that performs quantification in the TPP pipeline, first using known mixed ratios of yeast extracts and then using a data set from ovarian cancer cell lysates. The program and its documentation can be downloaded from our website at  Quantitative proteomics technologies have been developed to comprehensively identify and quantify proteins in two or more complex samples -4. Therehttp://msquant.sourceforge.net/, ZoomQuant . The procedure of wavelet-based de-noising is given as:where 0 <Xu et al.  proposedJ, Wfdenotes DWT coefficient of signal f at position n in scale j. We denoted the correlation of bordered scales as follows:Assuming the largest scale of decomposition is l represents the scale and j <J - l + 1. As the singularity of signals increases along with increasing scales, bordered points affect each other in detailed scales. We chose l = 2 to compute the correlation:where Corr2 is denoted as correlation coefficient of the position n in scale j.where To make correlation coefficient and wavelet coefficient more comparable, we defined the correlation coefficient uniformly:And:NewCorr2 with Wf to obtain the edges of important signals. In summary, by multiplying wavelet coefficients of bordered scales, we computed a correlation coefficient to suppress the noise and to strengthen the signal. Our algorithm improved the identification of real signals and the orientational precision of the identified signals.Then we compared Wf. According to these new values, a noise threshold was re-calculated. If the wavelet coefficients were less than the noise threshold, they were set to zero. The remaining wavelet coefficients were considered signals. Finally, we reconstructed the de-noised signals and used the de-noised peak areas to calculate peptide abundance. Because the Trans-Proteomic Pipeline (TPP) http://tools.proteomecenter.org/software.php is a commonly used open source proteomics analysis pipeline, we decided to build our program into the TPP. We compiled a new TPP package by replacing the ASAPRatio program with the WaveletQuant program. The package and its documentation can be downloaded from our website at http://www.zcni.zju.edu.cn/en/WaveletQuant_for_Quantitative_Proteomics/waveletquant.html or http://systemsbiozju.org/data/WaveletQuant.We programmed and compiled WaveletQuant using Visual C++ 2005 Express Edition. A program flow chart is shown in Figure We compared the performance of our WaveletQuant program with the ASAPRatio program using a dataset generated by mixing different ratios of yeast cell extract grown in heavy vs. light isotopic media. Proteins were mixed in the following ratio 1:2, 1:1.5, 1:1, 1.5:1, 2:1, and then analyzed by LTQ-MS.nd peak could often be mistaken as from the first peak. In Figure We found that the WaveletQuant program was able to perform curve fitting for respective chromatogram pairs and to quantify more accurately the difference of mixed yeast extracts than the original ASAPRatio program. Figures The protein abundance ratios for all proteins obtained by the new algorithm and old algorithm of yeast extract mixtures are summarized in Table We have previously conducted quantitative proteomics studies comparing cisplatin-resistant ovarian cancer cells with cisplatin-sensitive cancer cells . Using thttp://www.qsl.net/kp4md/butrwrth.htm, for which low-frequency excitation signal components down to and including the current ones are transmitted, while high-frequency components, up to and including infinite ones, are blocked. The ASAPRatio program uses the Savitzky-Golay method [We developed a new software for quantitative proteomics using the wavelet transform. Mass spectrometry data are usually noisy. In order to better quantify mass spectrometry data, smoothing filters, such as the moving average filter, Gaussian filter Butterworth low-pass filter, and Savitzky-Golay filter can be used to reduce the noise in MS peaks. The moving average filter was used in the MZmine program . The Gauy method , which py method .In addition, we implemented orthogonal wavelets to decompose signals in our WaveletQuant program. The wavelet transform is different from that used by Lange et al. and Schulz-Trieglaff et al. ,33. ManyWe implemented two methods. First, by combining the advantage of hard threshold and soft threshold, we developed the wavelet-based signal threshold de-noising algorithm to distinguish signals from noise in MS data. Second, we developed the spatial adaptive algorithm, which not only was effective in removing high frequency noise but also was effective for low frequency de-noising. Combining these two algorithms, our WaveletQuant program performs better than the ASAPRatio program on the datasets from yeast that we tested Figures  and 3. FOf note, we also mixed proteins in 1:4 and 4:1 ratios and analyzed them by LTQ-MS. However, due to the limited dynamic range of the routine LC/MS that we performed, the average ratios calculated by both the ASAPRatio and the WaveletQuant programs were far-off from the original mixed ratios, with large standard deviation. This is not surprising as the mixed ratios are outside the dynamic range of a routine LC/MS analysis, which Canterbury et al. estimated to be 0.5 to 2.5 in a systematic analysis . This rehttp://tools.proteomecenter.org/TPP.php. Users can employ the WaveletQuant- implemented TPP pipeline as an alternative to the standard TPP pipeline.Finally, we have implemented our wavelet transform algorithm and developed the WaveletQuant program. As the TPP pipeline is widely used in proteomic data analysis, we incorporated WaveletQuant software into the TPP pipeline We have developed an improved and/or alternative program for quantitative proteomics analysis, which is implemented in the standard TPP pipeline for the convenience of users.• Project name: WaveletQuant• Project home page: http://www.zcni.zju.edu.cn/en/WaveletQuant_for_Quantitative_Proteomics/waveletquant.html or http://systemsbiozju.org/data/WaveletQuant.• Operating systems: Windows 2000, Windows XP or higher• Programming languages: MSVC++ 7.1 or higher• Other requirements: None• License: This is a free software. You can redistribute it and/or modify it under the terms of the GNU Lesser General Public License as published by the Free Software Foundation.LC: Liquid Chromatography; MS: Mass Spectrometry; LTQ: Linear ion Trap Quadrupole; MALDI: Matrix Assisted Laser Desorption/Ionization; SELDI: Surface Enhanced Laser Desorption/Ionization; TOF: Time Of Flight; ICAT: Isotope Coded Affinity Tagging; ITRAQ: Isobaric Tag for Relative and Absolute Quantitation; SILAC: Stable Isotope Labeling with Amino Acids in Cell Culture; DWT: Discrete Wavelet Transform; CWT: Continuous Wavelet Transform; LSM: Local Maximum Search.FM, QM, YC and BL conceived the research. FM and YC implemented the software. DRG, LH, GSO and SL contributed resources and provided guidance for the research. BL, FM, QM and YC wrote and revised the manuscript. All authors read and approved the final manuscript.A detailed description of the wavelet transform process and the spatial Adaptive Algorithm. A detailed description of the wavelet transform process and the spatial Adaptive Algorithm.Click here for fileComparisons of the quantification performance of BSA in a 1:2 ratio. Comparisons of the quantification performance of BSA mixed at 1:2 ratio between our program (Panels B) and ASAPRatio program (Panels A). Panel A and B are sepctra: OR20070625_HS_L-H-1-2_10.06981.06981.4; ions with +3 charge state.Click here for fileComparisons of the quantification performance of BSA in a 1:4 ratio. Comparisons of the quantification performance of BSA mixed at 1:4 ratio between our program (Panels B) and ASAPRatio program (Panels A). Panel A and B are spectra:OR20070625_HS_L-H-1-4_09.06730.06730.3; ions with +2 charge state.Click here for fileComparisons of the quantification performance of BSA in a 4:1 ratio. Comparisons of the quantification performance of BSA mixed at 4:1 ratio between our program (Panels B) and ASAPRatio program (Panels A). Panel A and B are spectra: OR20070625_HS_L-H-4-1.15.10440.10440.3; ions with +2 charge state.Click here for file


How can we get high school students interested in science? Here is a program that matches students with researchers, with the purpose of building a physical model of the protein being investigated in the lab. This student had just realized that the process used by scientists to create modified proteins, and to test the impact of that modification on function, involves engineering the gene for the protein, and then expressing the modified gene in an appropriate system. The excitement of this new insight spread throughout the team as other students picked up this new information and began to reinterpret some elements of “the story” that had been told to them by their scientist mentor at a previous meeting. Their mentor's story about the tumor suppressor maspin and its role in metastasis was now becoming “their story”—as they began to truly understand not only what the maspin protein was and how it functioned, but also the process of science whereby their mentor had designed an experiment that resulted in the data that supported the story. And the story was becoming all the more compelling because the students had in hand a physical model of the maspin protein they had designed and built using rapid prototyping technology , a modified version of RasMol, molecular visualization software that allows users to examine protein structures in a computer environment. Any image of a protein that can be created in RP-RasMol can be exported as a file that can be recognized by rapid prototyping equipment, and then built in an automated, layer-by-layer process using a variety of materials including plaster, nylon, paper, or a liquid photopolymer. After participating in this course, high school teachers, and then their students, become protein model designers and builders.The SMART Team program grew out of a professional development summer course for high school science teachers offered by the MSOE Center for BioMolecular Modeling. In this course, “Genes, Schemes, and Molecular Machines,” teachers explore how current concepts of molecular structure and function can be introduced to students as natural extensions of basic principles of chemistry and physics. In addition, teachers learn how physical models of proteins in the classroom can serve as compelling props that capture the interest of students and stir a desire to learn more. The physical models are based on atomic coordinates and are designed using RP-RasMol (SMART Teams were born in the fall of 2001 when Jeff Anderson, a high school teacher at Riverside University High School in Milwaukee, approached us with an idea for a student project. Jeff had participated in the “Genes and Schemes” summer course, and had heard about a group of his fellow teachers who had just designed and built the first-ever physical models of the ribosome, based on atomic coordinate data published by the Steitz and Noller laboratories . Jeff waNature [During this project, the students met with two researchers who were actively involved in this work, Wei-Jen Tang of the University of Chicago, and John Young, then at the University of Wisconsin–Madison see . Just asNature , he had Since the auspicious beginning of that first fortuitous SMART Team, the program has grown to 14 teams that annually work with researchers in southeastern Wisconsin. The current size of the program is limited only by the capacity of our outreach program to coordinate the teams' activities. Local research labs interested in hosting SMART Teams far exceed the number of teams. The popularity of the program among research labs is a testament to its minimally invasive nature. In contrast to many traditional outreach programs that involve immersive research experiences for small numbers of high school students or teachers, a SMART Team program, recognizing the current pressure felt by researchers to remain productive and maintain research funding, minimizes the formal interactions between the team and lab to only three to five meetings over the course of the project. In addition, the interaction represents a true partnership that occurs on a relatively level playing field in which both parties benefit. The students and their teacher benefit from exposure to the culture of a research lab and the details of a specific research project. The research lab benefits from the refreshing challenge of discussing their project with a novice audience, against a broad background of answering that fundamental question, “Why is this important?” As an added bonus, the research lab receives a copy of the physical model of the protein they are investigating. This physical model becomes a valuable communication tool within the lab.http://www.rpc.msoe.edu/cbm.The development of the SMART Team program has been supported by a Science Education Partnership Award to the MSOE Center for BioMolecular Modeling from the National Center for Research Resources of the National Institutes of Health. In addition to our local program in Wisconsin, approximately 14 additional Remote SMART Teams operate independently each year in high schools from New Jersey to California. More recently, a precollege science education award from the Howard Hughes Medical Institute has funded a project to disseminate this SMART Team program at eight universities across the US, including Rockefeller, Stony Brook, Rutgers, West Virginia University, Washington University, the University of Wisconsin–Madison, Scripps, the University of California, San Diego, the University of California San Francisco, and the Fred Hutchinson Cancer Research Center. Anyone interested in participating in a SMART Team program, either as a scientist mentor or an outreach staff member interested in starting a program at their institution, should contact us via our Web site at


Popliteal cysts, although commonly seen, are rarely associated with motion restriction or calcification. Radiological features are of soft-tissue swelling, with occasional reports of calcifications or small osteochondral bodies inside the cysts. We report a giant osteochondral body in a popliteal cyst, with significant mechanical block to flexion. This type of mass has to be differentiated from synovial osteochondromatosis, calcifications in the cyst, extraosseous and intraarticular osteochondromas. Complete excision of the cyst resulted in complete recovery of range of motion. Popliteal cysts are a common occurrence in orthopedic practice; many of these are innocuous, and are associated with degenerative arthritis or rheumatoid arthritis. Some may have loose calcified bodies in them. When the calcifications or bone formation are visible on standard x-rays, the differential diagnoses becomes more complex. The soft tissue tumors with calcification, such as liposarcoma or synovial sarcoma, are then also considered in difference diagnosis. Other reported causes range from popliteal artery aneurysms or arterovenous malformations, synovial chondromatosis, and post-traumatic loose bodies.13A 53-year-old management executive with no comorbid medical illnesses presented with the complaint of gradually worsening pain in the right knee of 3 years duration. He was an active tennis player, and had to give up active sports due to pain and inability to fully bend his knee; he gradually developed a limp during walking. The patient had been vaguely diagnosed with gout 3 years before presentation, due to elevated serum uric acid and knee pain and had been taking allopurinol tablets orally since then.Physical examination of the right knee revealed a flexion deformity of 5°, with further flexion up to 120° only. There was minimal effusion in the suprapateller pouch. McMurray's test was positive for medial joint pain and click was elicited. A nontender, firm to hard, fixed, nonpulsatile and well defined swelling was palpated in the popliteal fossa, medial to the medial head of gatrocnemius, which became prominent on full extension of the knee. Routine blood investigations, including the uric acid levels were unremarkable.Knee radiographs revealed a heterogeneously calcified, well defined mass measuring 3.8 × 3.2 cm in the popliteal fossa. Moderate degenerative changes in the medial compartment were also noted . The lefAn arthroscopy was planned to address the meniscal and intraarticular pathology; this revealed an undersurface tear of medial meniscus in the posterior horn, extending to the periphery. The inferior flap was excised, and a motorized chondroplasty was done for the worn out medial compartment of the knee. No obvious communication could be found to the popliteal fossa through the posterior capsule. The patient was then shifted into a semilateral position and the lesion was excised through a posteromedial longitudinal incision after retracting the medial head of gastrocnemius laterally. A well-encapsulated mass  was founA popliteal cyst was first described by Baker in 1877;Radiographic evidence of calcification or ossification in the popliteal cyst is rare, and documented cases are mostly of multiple small loose bodies .1239 Sin1233Cases of synovial chondromatosis limited to the popliteal bursa have been reported.3The differential diagnosis may also include soft tissue tumors with calcification, such as liposarcoma or synovial sarcoma; internal calcification in synovial sarcoma, however, is usually peripheral and is less dense.13et al.16Kullmer The unique nature of our case stems from the fact that the size of the osteochondral loose body had become quite large; restriction of flexion was probably due to mechanical restriction, as the range improved significantly after excision. The etiopathogenesis is a matter of conjecture, and we feel that the gradual onset of degeneration lead to fluid and debris accumulation in the popliteal cyst; this underwent some kind of metaplasia and developed into an osteochondral body. The patent communication with the joint ultimately closed down. Since gouty tophi have been implicated as a cause of deposition in the popliteal cyst, our first impression was that of gouty deposits. However, the MRI and histopathological findings both did not show any tophi.Although arthroscopy did not help in the diagnosis of the current condition, its use lies in the fact that intraarticular lesions like meniscal tears can be addressed and communications of cysts into the joint can be localized. MRI gives excellent anatomic and three-dimensional localization and even demonstrated degeneration and meniscal tears, which we believe was part of the contributing pathology.In summary, we report an unusual giant densely calcified osteochondromatous mass lying inside a popliteal cyst, which was responsible for mechanical loss of flexion. Such osteochondromatous lesions should be included in the differential diagnosis of all calcified masses in the popliteal space.


The Hematology fellowship program at Mayo Clinic Rochester began in 1965 followed by the Oncology fellowship program in 1973. The two programs later merged in 1990 and since that time, 115 fellows have completed training . Mayo ClMayo Clinic is a major national and international referral center whereby a wide variety of oncologic and hematologic malignancies and benign hematologic disorders, are seen by fellows during training under the supervision of recognized experts, enhancing the educational experience and providing patients with the best clinical care. Fellows also provide primary oncologic care for patients with common hematologic and oncologic diseases as Mayo Clinic serves as the primary referral center for the local, tri-state region . A unique feature of the program is the autonomy and flexibility afforded to our fellows to organize and schedule their own continuity clinic patients. Throughout their training, fellows accumulate patients to their continuity clinic panel, and are looked upon as the patient's primary oncologic or hematologic caregiver, with significant clinical decision responsibilities. This ensures that by the end of fellowship, they are extremely well prepared for clinical practice. Fellows also obtain specialized training during their time spent in our bone marrow transplant program, which performed approximately 280 autologous and 65 allogeneic transplants in 2009. As a regional transplant center, the program continues to expand with the introduction of umbilical cord transplantation in 2009 and an increase in autologous and allogeneic transplants. The outpatient practice is based at the downtown Mayo Clinic facility , while tMayo Clinic's Hematology and Oncology fellowship program utilizes the state-of-the-art multidisciplinary simulation center and anatomy procedure skills laboratory , to traiMayo Clinic is a National Cancer Institute (NCI)-designated comprehensive cancer center, and therefore provides a rich menu of research opportunities for fellows to pursue during their 18–22 months of dedicated research time. Multiple programs in respective solid tumor groups, women's cancers, drug development, supportive care, and hematologic malignancies provide fellows with opportunities for either laboratory-based or clinically based research. The institution conducts several weekly cancer-related conferences, thereby allowing fellows to learn of ongoing research efforts and to meet face-to-face with investigators who could serve as potential mentors. There are over 300 active clinical trials open at any one time, and Mayo Clinic serves as the primary research base for the NCI-funded North Central Cancer Treatment Group, the Phase II Consortium (a drug development program), seven different highly competitive SPORE grants  in brain, breast, lymphoma, myeloma, ovary, pancreas, and prostate, a community clinical oncology program grant, and a cancer prevention network. Opportunities for basic science, translational, and clinical research are robust on the Mayo Clinic campus. Fellows are involved in writing and development of clinical trials and past and current fellows have been very successful in publishing their research in peer-reviewed journals and presenting abstracts and oral presentations at national and international conferences . FellowsBroadly trained and well-mentored, fellows at the Mayo Clinic possess a diverse set of skills which allow them to achieve excellence in all types of academic or community-based practice. Our fellows, exposed to the principles of the founding fathers of the Mayo Clinic, perpetuate their legacy of dedication to clinical care, research, and education.


The Accreditation Council for Graduate Medical Education (ACGME) requires an annual evaluation of all ACGME-accredited residency and fellowship programs to assess program quality. The results of this evaluation must be used to improve the program. This manuscript describes a metric to be used in conducting ACGME-mandated annual program review of ACGME-accredited anesthesiology residencies and fellowships.A variety of metrics to assess anesthesiology residency and fellowship programs are identified by the authors through literature review and considered for use in constructing a program "report card."Metrics used to assess program quality include success in achieving American Board of Anesthesiology (ABA) certification, performance on the annual ABA/American Society of Anesthesiology In-Training Examination, performance on mock oral ABA certification examinations, trainee scholarly activities (publications and presentations), accreditation site visit and internal review results, ACGME and alumni survey results, National Resident Matching Program (NRMP) results, exit interview feedback, diversity data and extensive program/rotation/faculty/curriculum evaluations by trainees and faculty. The results are used to construct a "report card" that provides a high-level review of program performance and can be used in a continuous quality improvement process.An annual program review is required to assess all ACGME-accredited residency and fellowship programs to monitor and improve program quality. We describe an annual review process based on metrics that can be used to focus attention on areas for improvement and track program performance year-to-year. A "report card" format is described as a high-level tool to track educational outcomes. The Accreditation Council for Graduate Medical Education (ACGME) requires an annual evaluation of all ACGME-accredited residency and fellowship programs. This anWe describe a systematic annual review process for assessing ACGME-accredited anesthesiology residency and fellowship programs that meets ACGME requirements, includes metrics that can be used to assess program quality and provides a model for continuous quality improvement.A literature search was initiated to identify metrics that might be used in this process and each metric identified in the previously published articles we reviewed was considered for inclusion in our annual program assessment. Criteria for inclusion included the ability to accurately access and collect the data with a high level of confidence and the authors' agreement the metric was important in the assessment of program quality. Metrics to be included were also reviewed by our department education committee and a consensus was generated regarding each item. Some previously described metrics, such as the ratio between the number of persons matched through the National Resident Matching Program (NRMP) and the last rank number at which the program filled (rank/match ratio), were eliminated due to concerns regarding the ability to manipulate these data.Metrics selected for inclusion in the annual review of our ACGME-accredited anesthesiology residency and fellowship programs are listed in Table Performance of graduates on the American Board of Anesthesiology (ABA) certification examinations. The ACGME explicitly uses this metric to assess program outcomes. ArguablClinical Anesthesia-3 (CA-3) resident performance on the ABA/American Society of Anesthesiology (ASA) In-Training Examination (ITE) can provide a more contemporary assessment of preparedness for the ABA written certification examination. Our program established expected standards for individual and collective CA-3 performance on the ITE and compares these results to national standards. Performance below expectations on the ITE prompts a review and a written plan of action to improve outcomes.CA-3 resident performance on regularly scheduled mock oral examinations provides an assessment of PGY-level specific preparedness for the ABA oral certification examination. Consistency regarding expected standards for CA-3 performance on program-administered mock ABA oral examinations was established through a faculty development process. To make this process better approximate the ABA oral certification examination, a senior or emeritus faculty member acts as a docent, retired ABA oral board examination questions are used for the examination and the examination is conducted in the exact format of the ABA oral board certification examination. The only major difference is that time is scheduled after the examination to debrief and provide resident feedback. Expectations for CA-3 resident performance are at a level consistent with passing the examination when taken for credit. Performance at a marginal or failing level prompts a review, requires a written plan of action and requires additional practice examinations to improve performance.Resident publications in peer-reviewed journals are included in our annual review as a metric assessing program quality. In order to be included in this metric, the resident must have completed the work resulting in publication during his or her residency training. To assess program performance in resident publication in greater detail, we record additional information including the order of authorship and the impact factor of the journal in which the manuscript is published. Resident publication in non-peer reviewed journals and publication of chapters are considered separately.The number of posters and abstracts completed, accepted and published are similarly recorded.Scholarly activity metrics also include an assessment of resident presentations at regional, national and international meetings.ACGME accreditation outcomes are a key metric in the annual review of our ACGME-accredited residency and fellowship programs. Our programs' goal and expectation for site visit interval is five years. Performance below this standard requires generation of an action plan.Review Committee citations are also monitored as a metric of program quality. We have established two or fewer citations as our programs' goal. Regardless of the total number, an action plan and follow-up report are required to address each citation.Internal reviews (IR). The ACGME requires the Sponsoring Institution to conduct an internal review of each program at the midpoint of the accreditation cycle. This is a separate review that contains distinct elements. If the program receives a five-year accreditation cycle, an internal review is only conducted once every five years. Internal reviews are handled in a manner similar to that used to assess accreditation results. The number of IR suggestions is tracked and all IR suggestions must be addressed in writing, including an action plan to address any concerns. A follow-up report is required to assure the action plan has been implemented and improvement has occurred. Our programs' goal is to have all IR suggestions addressed and corrected within six months. We do not consider the total number of recommendations in the internal review as a metric since the internal review process is a valued mechanism for feedback intended to improve the program and recommendations are encouraged.The anonymous ACGME resident survey is a relatively new metric that can be used to assess program quality and duty hour compliance. We chose ACGME survey results as a key metric in our annual program review due to the confidence residents have in the anonymity of the process. However, the authors recognize survey data may be influenced by a variety of factors including concern about an adverse accreditation action and/or administrative pressure. Duty hours are also measured by resident attestation and duty hour violations can be reported on an anonymous MSGME school "hotline" and/or anonymously reported to our residents association. Non-compliance of greater than 10% on any item requires a written action plan to address the issue(s) and a follow-up report to assure the concern has been addressed and corrected.The number of applications, invitations to interview and interviews conducted are tracked on an annual basis and the outcomes of the match are analyzed. Although the value of standardized examinations in assessing resident quality is limited, we believe most programs consider standardized examination performance as an important metric when selecting residents. As such, they are an indirect measure of the competitiveness of our program related to others. We have established a program goal of 220 for the mean score of matched applicants on Step 1 of the United States Medical Licensing Examination (USMLE) and average USMLE scores are compared year-to-year.Goals can also be established for matched applicant scores on step 2 of the USMLE. Although the content of the questions on step 2 of the USMLE is more directly related to clinical medicine, the immediate value of this metric is lessened because not all applicants receive the results of this examination in time to influence their position on the NRMP rank order list, which probably results in self-selection bias. To address this issue, USMLE step 2 scores for PGY 2 residents  are reviewed and included in our annual program review."Filling" through the NRMP each year is a goal of our program. Although NRMP result analysis and outcomes can be used to establish a rank/match ratio as an index of performance in attracting highly-qualified applicants to the program, this metric is subject to manipulation . Consequently, this metric is analyzed but not used as a direct measure of program quality in our annual program review score card.Post-NRMP survey. An anonymous survey is sent to all applicants ranked high enough to match who chose another program. The survey asks this group of applicants to respond to questions about overall program quality, program structure, interviews with faculty and residents, stipends and benefits, spouse/significant other opportunities, location, diversity, proximity to family, lifestyle issues, opportunities for off-campus rotations and technology support. The results of this survey are analyzed and included in the annual program review. Although some factors are impossible to change (e.g. location of program), all other issues identified are addressed in an action plan and follow-up report. Results of the survey are compared year-to-year.The program director conducts exit interviews with each resident or fellow near program completion. The results of these interviews are used to identify opportunities for program improvement. A key metric is the number of residents or fellows who indicate they would choose the program again. These comments are included in narrative form as an addendum to the report card.The number, type and distribution of cases and procedures recorded by residents and fellows are compared to ABA requirements. We have selected a program goal of exceeding minimum case/procedure experience by at least 20% in every category. If case/procedure experience falls below this standard, an action plan is generated to correct the deficiency, case/procedure numbers are tracked more closely and changes in the resident schedule are made as needed to secure this experience.The percent of women applicants who apply, are invited to interview, interview, are ranked and match is tracked. These numbers are compared to national averages included in the annual education issue of the Journal of the American Medical Association (JAMA). Our proThe percent of under-represented minority (URM) applicants who apply, are invited to interview, interview, are ranked and match are tracked. These numbers are compared to national averages included in the annual education issue of JAMA. To assuA survey of alumni who have graduated in the past year is conducted as part of the annual review. The survey asks about program strengths and weaknesses and suggestions for improvement. It specifically asks for subjects/topics about which graduates of the program felt poorly prepared for independent practice. A key metric in this survey asks residents if they would choose the program again and would recommend it to others.These key evaluations can be conducted using a variety of instruments. In our program, we use an Integrated Scheduling and Evaluation System (ISES) to collect this information. ISES is a validated, behavioral, electronic evaluation and portfolio tool. Resident/fellow evaluations recorded in ISES are ACGME competency and criterion based, with clear anchors describing each domain of evaluation. ISES evaluations are based on a five-point Likert scale with the capability of reporting mean, median and mode values. Outcomes of resident/fellow evaluations of the program, rotations, faculty and curriculum using ISES are important components of the annual program review. Similarly, ISES is used to obtain faculty evaluations of the program that are required components of the annual program review. Residents and faculty are asked to provide a composite program rating annually to facilitate general assessment of the program that can be compared on a year-to-year basis. Our program established goals for each component of the ISES metrics as detailed in figure Our faculty development process includes review of resident evaluations of faculty that are pooled annually to assure confidentiality and are shared with faculty during a personal annual performance review conducted by the department chair. Collective faculty performance based on ISES evaluations is tracked year to year with a goal of improving on an annual basis. Faculty participation in institutional, regional and national development activities is also monitored and is discussed during the annual performance review of each faculty conducted by the department chair.Although qualitative and therefore not specifically included in the metrics, written comments are solicited for items in which they may add value. As is true with resident and faculty evaluation, the comments often provide great value in guiding program change and improvement. In our annual review, comments provided by faculty, residents and fellows are listed and reviewed. The comments often stimulate program change/improvement in areas not easily measured numerically.A composite summary report, including action plans to address areas of concern, is generated in which metrics are compared year-to-year.As described previously, a "report card" can be used to evaluate the quality of residencies and fellowships that is useful for high-level review,4-6. We The annual program review is of value only if action is taken to sustain excellence and/or improve performance. Systematic annual review of anesthesiology residency and fellowship programs requires identification and assessment of broad measures of program quality. We describe an annual program evaluation that meets ACGME requirements, focuses attention on areas for improvement, requires action plans to address these concerns, tracks performance trends year-to-year and guides trainees and faculty in ongoing formative program assessment and program quality improvement. The program "report card" we describe has the advantage of being reproducible and is valuable for tracking performance year-to-year. Color coding provides a high-level assessment of program performance at a glance. There are also several limitations to the annual program review method we describe. The results we report are from only one program and only one specialty. The values assigned to the metrics are arbitrary as they are based on the authors' opinions, historical program controls and the results of using the "report card" methodology in other specialties within Mayo School of Graduate Medical Education. The report card is not comprehensive and other metrics of program quality may be excluded. However, many of the components of our program review could be useful in the evaluation of other anesthesiology programs and they might also be effectively applied to programs in different specialties.An annual program review is required to assess all ACGME-accredited residency and fellowship programs to monitor and improve program quality. We describe an annual review process based on metrics that can be used to focus attention on areas for improvement and track program performance year-to-year. A "report card" format is described as a high-level reproducible tool to track educational outcomes over time.The authors declare that they have no competing interests.SR and TL contributed equally in the creation of the "report card" tool and preparation of the manuscript. Both authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6920/10/13/prepub


On October 8, 2005, an earthquake of magnitude 7.6 hit the Northern parts of Pakistan. In the post-earthquake scenario, overcrowding, improper sewage disposal, contamination of food and drinking water, hasty surgical procedures, and unscreened blood transfusions to earthquake victims most likely promotes the spread of infections already prevalent in the area.The objective of the study reported here was to determine the prevalence of Human Immunodeficiency and Hepatitis C viruses  in the earthquake-affected communities of Pakistan. The samples were analyzed 2 months and then again 11 months after the earthquake to estimate the burden of HIV and HCV in these areas, and to determine any rise in the prevalence of these viral infections as a result of the earthquake.Blood samples were initially collected during December, 2005 to March 2006, from 245 inhabitants of the earthquake-affected areas. These samples were screened for HCV and HIV, using immunochromatography and Enzyme-Linked Immuno-Sorbent Assay (ELISA).Out of 245 samples tested, 8 (3.26%) were found positive for HCV, and 0 (0.0%) for HIV, indicating the existence of HCV infection in the earthquake-stricken areas. The same methods were used to analyze the samples collected in the second round of screening in the same area, in September, 2006 – 11 months after the earthquake. This time 290 blood samples were collected, out of which 16 (5.51%) samples were positive for HCV, and 0 for HIV.A slightly higher prevalence of HCV was recorded 11 months after the earthquake; this increase, however, was not statistically significant. None of the study participants was found HIV-infected. Natural disasters generate mass casualty situations within a very short time -3. DisasOn October 8, 2005, at 08:50:38 am local time, a major earthquake measuring 7.6 on Richter scale hit the Northern areas of Pakistan. The epicenter of this earthquake was in Muzafarabad, about 95 kilometers Northeast of Pakistan's capital, Islamabad [Traumatic injuries contribute significantly to the mortalities incurred during an earthquake -12. ThisFollowing the 2005 earthquake in Pakistan, local health care system in these Northern areas collapsed and help was summoned from all major cities of the country. International aid was also sought by the government, which was reciprocated significantly by the United Nations, the Red Crescent Society and other donor agencies. Not only did these relief organizations provide the necessary field and camp hospitals, but also offered the much-needed healthcare services to the affectees of the earthquake. Emergency health-providing facilities, clinics, operating rooms and laboratories were established in make-shift accommodations around the affected area .The afore-mentioned risk factors were very much into play in the post-earthquake scenario in Northern Pakistan. Overcrowding of displaced population in camps settings, improper sewage disposal, contamination of food and scarcity of drinking water were commonly observed in these areas. Consequently, outbreaks of acute respiratory tract infections (ARTIs), scabies, diarrhea and other infections were recorded in the region .The majority of the patients treated in the immediate aftermath of the earthquake had been admitted with fractures and injuries sustained during the earthquake . In concThe objective of this study was to determine if the October earthquake led to an increase in the prevalence of HCV and HIV in the affected population. We analyzed random blood samples for these two infections from the affected population immediately after, and then 11 month following, the earthquake.This was a repeated cross sectional study in which the samples were initially collected during December, 2005 to March, 2006, starting six weeks after the earthquake. 245 study participants were recruited for this first stage of sampling. The second round of sample collection took place in September 2006, 11 months after the earthquake. The second round had a slightly greater number of participants, amounting to 290. The samples were collected from patients admitted to two camp hospitals in Mansehra, i.e., Italian Hospital in Mansehra and Saudi Field Hospital. Majority of these patients were presented with complaints of bone fractures and other injuries sustained during the earthquake. Some of the study subjects also reported to have undergone surgery and/or either received or donated blood during, or subsequently to, the earthquake aftermath.The study subjects came from all earthquake-affected Northern Pakistani regions, including the towns of Balakot, Mansehra, Batgram, Abbotabad, Garhi Habibullah and Muzaffarabad, among others.The sample population was composed of patients and paramedical staff at different field hospitals set up in the region. These facilities had been established by Italy, Saudi Arabia and other national and international NGOs. In order to diversify the sample population, no restrictions were imposed while recruiting subjects. Consequently, the sample population included farmers, drivers, housewives, students, teachers, army personnel, health workers and others Table .Blood samples were collected aseptically in 5 ml red top vacutainers and left to clot. Sera specimens were separated after centrifugation, aliquoted into 2 ml Eppendorf tubes and stored at -20°C until the time for assay.A written informed consent was obtained from the study participants prior to the collection of blood samples. The following information was given to each participant to ensure they were making an informed choice: a complete description of the aims of the study, infectious agents that were being screened, details of sample collection procedures, potential benefits and risks of their participation in the study, and assurance of confidentiality of any information given as well as of the test results. All donor information and test results were kept confidential.Detection of antibodies to HIV-1 and HIV-2 in the serum was done by rapid immunochromatography kit  according to the manufacturer's guidelines. 50 μl of clear serum was applied to the sample pad with the help of a pipette and sterile tip. The results were noted after 15 minutes. Samples were tested twice for confirmation. Samples were retested on ELISA using SD HIV1/2 ELISA 3.0 . According to the information provided by manufacturers, for both the immunochromatography and SD HIV1/2 ELISA 3.0 tests, relative sensitivity and specificity were, respectively, 100% and 99.8%.Antibodies to HCV were detected using immunochromatography technique . According to the instructions of the manufacturer, 5 μl of clear serum was applied to the sample well followed by two drops of HCV buffer (provided in the kit), and the results were read within 10 minutes. The positive samples were tested twice for confirmation. Samples were retested on ELISA using SD HCV ELISA 3.0 . According to the information provided by manufacturers, for both the immunochromatography and SD HIV1/2 ELISA 3.0 tests, relative sensitivity and specificity were, respectively, 96–99% and 99%.We collected a total of 535 blood samples at two different time points from the 2005 earthquake victims in the Northern areas of Pakistan. The majority of the samples came from Mansehra 81%), Balakot, Abbotabad and other Northern areas of Pakistan  were males and 90 (36.7%) were females, ratio, 1.7:1  and a154 females (53.1%), ratio, 0.88:1  were found positive by ELISA for HCV antibodies. Among the positive samples, male to female ratio was 3.2: 3.3. None of the samples were found positive for HIV by ELISA.In the second round of sample collection, 11 months following the earthquake, another batch of 290 samples was analyzed. 13 of these subjects reported to have been injured during the earthquake and having received surgery, blood transfusion, and/or other forms of medical care. Out of the 290 samples analyzed, 16 (5.51%) were found positive by ELISA for HCV antibodies. This time, among the positive samples, male to female ratio was 1:2. Again, none of the samples were found positive for HIV using ELISA.In our study, HCV infection was found in the earthquake-affected areas of Pakistan. The difference in the incidence of HCV in the two population samples was, however, found statistically nonsignificant by Pearson chi-square test .In the present study we have attempted to evaluate the effects of the earthquake of 2005, in the afflicted community residing in the Northern areas of Pakistan. We analyzed the prevalence, and any potential rise thereof following the disaster, of blood borne infections in the earthquake-afflicted communities HIV and HCV infections were used as indicators of blood-borne infections. We report here that no cases of HIV were found in the earthquake-affected areas immediately or 11 months following the disaster. We, however, recorded a 3.26% prevalence of HCV in the same population immediately following the disaster. Slightly higher (5.51%), albeit statistically non-significant, prevalence of HCV was recorded 11 months after the disaster.Disasters are considered a major public health concern. They may cause an unexpected number of deaths, injuries, or illness in the affected community; may destroy local health infrastructures, or have adverse effects on the environment and the population, increasing the potential risk for communicable diseases and environmental hazards that will increase morbidity, premature death, and diminished quality of life in the future ,21,22.The October 8, 2005 Kashmir earthquake caused massive devastation and a considerable loss of human life. The healthcare services were hit particularly hard, with most of the hospice centers being either completely destroyed or seriously damaged. The affected population comprised mainly rural inhabitants, where health facilities were already lacking ,24. The Prevalence of Hepatitis C and HIV for the Northern parts of Pakistan is relatively unknown. No study has been conducted in the earth-quake affected region that gives us an idea of the status-quo regarding these two infections in particular, and blood-borne infections in general. Therefore, we undertook to investigate the baseline prevalence of these infections and then chart out any change that could be a potential consequence of the earthquake.The reported Hepatitis C seroprevalence in Pakistan, determined from a sample over 47,000 individuals from the city of Islamabad, has been estimated 5.31% . The onlThe purpose of this study was to establish a baseline first for the prevalence of Hepatitis C and HIV in the earthquake-affected population. Our analysis of the first batch of sampling revealed 3.26% of the population positive for HCV antibodies, and none for HIV. This incidence for HCV does not vary much from that reported earlier for other areas of Pakistan. The risk factors for the spread of HCV in this region; including unsafe injection practices, poverty, low literacy rate and poor health-seeking behavior have been charted out in the past . The preWe found no HIV prevalence in the second batch of samples collected 11 months after the earthquake, but the percentage of HCV positive samples was still found to be 5.51%. This rise in HCV prevalence was, however, not found statistically significant.Pakistan has not as yet started experiencing the HIV epidemic . Risk faIn contrast to HIV, a considerable prevalence of Hepatitis C was recorded in the earthquake-affected Northern areas. This observed HCV prevalence may be attributed to a varied mix of factors. The issue of unscreened blood transfusion ranks definitely as the most important contributory factor. Other factors may include the use of unsterilized equipment, lack of awareness and widespread illiteracy in Northern Pakistan. It may be speculated that compromised healthcare and other afore-mentioned factors related to earthquake will aggravate the transmission and prevalence scenario in these areas. The slight increase observed in the two batches studied may be attributed to the variation in the population samples studied in the two instances. The two sample populations indeed were significantly different according to most of the measured parameters Table .At this time, proper guidelines and procedures, implemented urgently, could play a significant role in reducing the spread of blood-borne infections. Mandatory screening of blood and blood products before transfusion, proper sterilization of surgical and dental instruments, and appropriate disposal of infected materials and disposable syringes are among the issues that need to be emphasized ,35,36.The authors declare that they have no competing interests.SA carried out all the experimental work and helped in writing the manuscript. MAR helped with data interpretation and manuscript writing. AK and AF assisted SA in the collection of blood samples and in the administration of questionnaire survey. SUK supervised the work in Mansehra and arranged for partial funding. SHA supervised the work in Karachi, arranged for partial funding and helped in the writing of manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


PRAME/MAPE/OIP4 is a germinal tissue-specific gene that is also expressed at high levels in haematological malignancies and solid tumours. The physiological functions of PRAME in normal and tumour cells are unknown, although a role in the regulation of retinoic acid signalling has been proposed. Sequence homology and structural predictions suggest that PRAME is related to the leucine-rich repeat (LRR) family of proteins, which have diverse functions. Here we review the current knowledge of the structure/function of PRAME and its relevance in leukaemia. MicroarThe regulation of PRAME gene expression is poorly understood, and thus the molecular basis of its expression in malignancies is largely unknown. It has been suggested that AML1-ETO and BCR-ABL fusion proteins may contribute to the up-regulation of PRAME ,29, wherInterestingly, a recent comparative genomic hybridisation study detected microdeletions in the lambda immunoglobulin light chain locus (22q11) in 18% of untreated CLL cases, and also in cases of acute promyelocytic leukaemia and non-Hodgkin's lymphoma . The minPRAME is a member of a multigene family present in humans and other mammals. However, orthologous genes appear to be absent in fish, amphibians and invertebrates. Like several other cancer-testis antigen gene families, PRAME appears to have undergone multiple gene duplications during hominid evolution, and at least 22 PRAME-like genes and 10 pseudogenes have been identified in the human genome . This ra(1/2)L . Ty. Ty42]. (1/2)L . The LRR(1/2)L . However(1/2)L  suggest (1/2)L  and our (1/2)L . Intrace(1/2)L . Thus, tThe subcellular localisation of PRAME has been examined in a number of studies using different cell lines to express recombinant epitope-tagged or GFP-tagged PRAME. Over-expression of PRAME-FLAG and PRAME-GFP proteins in CHO cells (which do not express PRAME) was reported to induce aberrant cell morphology and cell death. However, in transfected cells expressing low levels of the PRAME-GFP, the protein was observed to localise to both the nucleus and perinuclear regions . ConsistPRAME has been reported to function as a repressor of retinoic acid (RA) signalling through interactions with retinoic acid receptors (RARs) and repression of the RARβ2 gene ,48. RARsLRELLCE-473, located close to the C-terminus of PRAME) was found to contribute to interactions with the RARα LBD in vitro [Epping and colleagues demonstrated that over-expressed TAP-tagged PRAME can be co-immunoprecipitated with RARα, with the interaction being dependent on the C-terminus of PRAME . Weak diin vitro . Unlike in vitro .LHARLRELLCELG-475). Thus, it remains to be tested whether mutations in the RAR LBD that disrupt binding to CoRNR box peptides would also disrupt the ability of PRAME to impact on RA signalling. However, until the structure of the PRAME protein is known, it remains unclear, whether any of these motifs are available for protein-protein interactions. In our hands, the binding of PRAME to the LBDs of RARα or other nuclear receptors in GST pulldown (data not shown) or yeast two-hybrid assays XXX(I/L). These motifs mediate ligand-independent binding to nuclear receptors. Two of the seven motifs in PRAME, including the most C-terminal motif, also fit the CoRNR box consensus  can induce proliferation arrest and apoptosis of cancer cell lines, and have shown promise as anticancer agents in preclinical models and clinical trials. In a separate study, Epping and colleagues isolated both RAR and PRAME in a genetic screen for proteins that could block the effects of HDACi on cell proliferation . It was The function of PRAME and its effect on gene expression in leukemic cells remains controversial due to conflicting observations in the literature. While in cell-based models PRAME was reported to down-regulate genes such as S100A4, RARβ2, p21 and Hsp27 , a clinitrans retinoic acid)-induced myeloid differentiation [The role of PRAME in proliferation and differentiation of haematopoietic tissues appears complex. For example, PRAME expression was associated with reduced proliferation of KG-1 leukaemic cells . In the ntiation . HoweverAlthough the role of PRAME in acute leukaemia and other cancers is complex, it has promise both as a cancer biomarker and as a therapeutic target. In AML, PRAME is usually associated with a favourable response to chemotherapy and prolonged survival ,14,54. Tde novo AML have normal cytogenetics and therefore are difficult to risk stratify [Disease risk-stratification is imperative in order to best tailor therapies to meet a patient's individual needs. At least a third of patients with stratify . Thus atstratify . Low PRAstratify . In cancstratify ,59. Furtstratify . PRAME hstratify ,23,24.In addition, PRAME has been shown to be a useful indicator of minimal residual disease (MRD) in both acute and chronic leukaemias ,55,60,61CTAs were originally identified as proteins containing epitopes that induced cell-mediated immune responses in cancer patients. Thus they represent promising candidates for the development of immunotherapies specifically targeting cancer cells . PRAME eHuman PRAME and its paralogues are related to LRR family proteins, some of which are known to have functions in cell immunity and signal transduction. PRAME may therefore serve as an intracellular sensor of pathogen associated molecular particles (PAMPs) or molecules associated with cancer-related inflammation Fig. . To confThe subcellular distribution of PRAME indicates it is likely to have both nuclear and cytoplasmic functions. Although direct interactions with retinoic acid receptors appear weak Fig. , there icis retinoic acid receptor; SRC1: steroid receptor co-activator; HDACi: histone deacetylase inhibitors; ATRA: all-trans retinoic acid; MRD: minimal residual disease.PRAME: preferentially expressed antigen in melanoma; MAPE: melanoma antigen preferentially expressed in tumours; OIP4: opa interacting protein; LRR: leucine-rich repeat; HLA: human leucocyte antigen; BCR: breakpoint cluster region; qPCR: semi-quantitative polymerase chain reaction; CML: chronic myeloid leukaemia; CTA: cancer testis antigen; 5'UTR: 5' untranslated region; AML: acute myeloid leukaemia; ALL: acute lymphoblastic leukaemia; NALP: NACHT-, LRR-and PYD-containing proteins; TLR: toll-like receptor; PAMP: pathogen-associated molecular patterns; GFP: green fluorescent protein; NLS: nuclear localisation signal; RA: retinoic acid; RAR: retinoic acid receptor; HDAC: histone deacetylase; TAP: tandem affinity purification; LBD: ligand binding domain; GST: glutathione S-transferase; ER: oestrogen receptor; RXR: 9-The authors declare that they have no competing interests.FW and DMH reviewed the literature, and wrote and edited the manuscript. FW, KS and JF generated experimental data. PM, JE and DMH performed sequence alignments, motif searches and structure predictions. All authors read and approved the final manuscript.


On May 12, 2008, an earthquake measuring 8.0 on the Richter scale jolted Wenchuan, China, leading to 69,227 deaths and 374,643 injured, with 17,923 listed as missing as of Sept. 25, 2008, and shook the whole nation. We assessed the devastating effects on people's post-earthquake concern about safety and health.From June 4 to July 15, 2008, we surveyed a convenience sample of 2,262 adults on their post-earthquake concern about safety and health. Residents in non-devastated areas  and devastated areas (Sichuan and Gansu Provinces) responded to a questionnaire of 5 questions regarding safety measures, epidemic disease, medical workers, psychological workers, and medication. The ANOVAs showed a significant effect of residential devastation level on the estimated number of safety measures needed, the estimated probability of the outbreak of an epidemic, and the estimated number of medical and psychological workers needed (Ps<0.001). The post-earthquake concern decreased significantly as the level of residential devastation increased. Because of the similarity with the meteorological phenomenon of the eye of a typhoon, we dubbed these findings a “Psychological Typhoon Eye”: the closer to the center of the devastated areas, the less the concern about safety and health a resident felt.Contrary to common perception and ripple effect that the impact of an unfortunate event decays gradually as ripples spread outward from a center, a “Psychological Typhoon Eye” effect was observed where the post-earthquake concern was at its lowest level in the extremely devastated areas. The resultant findings may have implications for Chinese governmental strategies for putting “psychological comfort” into effect. A catastrophic earthquake measuring 8.0 on the Richter scale jolted China's Sichuan Province on May, 12, 2008. Official figures  stated that 69,227 were confirmed dead and 374,643 injured with 17,923 listed as missing We conducted a study to assess whether people's post-earthquake concern about safety and health varied gradually with devastation level from the center of the disaster area. We focused on the potential differences of post-earthquake concern between residents in the non-devastated areas and those in the devastated areas.The survey period was three to eight weeks after the earthquake – from June 4 to July 15, 2008. The study was part of the Emergency Project to Provide Psychological Assistance in Wenchuan Earthquake Areas (No. KKCX1-YW-05) approved by the Institutional Review Board of the Institute of Psychology, Chinese Academy of Sciences. Because the protocol was judged to pose low risk, oral consent was recommended and obtained from study participants.A convenience sample of residents in non-devastated areas as well as devastated areas was surveyed. Five hundred forty two adults living in Fujian Province (South China), Hunan Province  and Beijing (North China) were selected to represent a sample of residents in non-devastated areas. For devastated areas, the sampling frame consisted of 1,720 adults living in eight administrational areas in Sichuan Province and three administrational areas in Gansu Province .Entry criteria included an age of at least 18 years, literacy, and a willingness to provide personal contact information. Respondents were paid a small fee  for each completed questionnaire. Demographic data on the 2,262 respondents are presented in “I am always scared. Can you prescribe some medication to help me get rid of fear?”—— LI Miao-Yu, an 8-year-old girl from Ziping Village, Dujiangyan.Southern People WeeklyThe above quotation comes from an on-the-spot report published on June 1, 2008, in The other four questions were also developed to assess the concern about safety and health. These questions were distributed to residents in both devastated and non-devastated areas. They were mainly represented in a frequency-estimate format, which was proved to reduce judgmental errors and biases To determine the level of residential devastation from all devastated areas, we asked respondents to classify their residency in one of three categories: slightly devastated, moderately devastated, and extremely devastated. We assessed the relationship between post-earthquake concern and the level of residential devastation.The data were analyzed on a personal computer with an SPSS statistical software package (version 16.0 for Windows). Comparison of the different residential devastation levels was completed with the use of one-way analysis of variance. Two-way analysis of variance  followed by Tamhane's post hoc tests was used to compare the mean estimated number of relief workers needed. No imputation of missing values was performed. All P values are two-sided; a P value of less than 0.05 was considered statistically significant.Of the 1,720 residents surveyed in the devastated areas, 53.4 percent (918) reported their residency as slightly devastated, 21 percent (362) moderately devastated, and 25.6 percent (440) extremely devastated.The estimated number of medical doctors needed for every 1,000 residents in the earthquake areas was 117.99±188.21 for residents in the non-devastated areas, 130.46±210.55 for residents in the slightly devastated areas, 98.15±174.08 for residents in the moderately devastated areas, and 75.95±139.40 for residents in the extremely devastated areas. The estimated numbers of psychological workers needed for every 1,000 residents in the earthquake areas were 131.43±226.88 for residents in the non-devastated areas, 149.56±252.12 for residents in the slightly devastated areas, 113.71±226.85 for residents in the moderately devastated areas, and 77.25±177.18 for residents in the extremely devastated areas. There was a significant difference in the type of relief worker , indicating that the estimated need for psychological workers was greater than that for medical doctors; and a significant effect of residential devastation level (P<0.001), indicating that the estimated numbers of relief workers decreased as the residential devastation level increased. There was no significant interaction between the type of relief worker and the residential devastation level (P = 0.287). Residents in the extremely devastated areas reported a lower number of relief workers needed for every 1,000 residents in earthquake areas than residents in the slightly devastated and non-devastated areas (Ps<0.001), with no significant difference between the latter two groups (P = 0.645).The estimated probability of an outbreak of an epidemic showed a significant decrease associated with increased residential devastation level . Residents in the non-devastated areas indicated a higher probability of an outbreak of an epidemic (for a mean of 36.77) than residents in each of the three devastated areas . Residents in the slightly-devastated areas indicated a higher probability of an outbreak of an epidemic than residents in the extremely devastated areas  .There was a similar trend toward a smaller estimated number of safety measures needed with an increasing level of residential devastation . Residents in the non-devastated areas indicated a greater number of safety measures needed (for a mean of 50.49) than those in each of the three devastated areas . Residents in the slightly-devastated areas indicated a greater number of safety measures behavior needed than their counterparts in the moderately  and extremely devastated areas  .There were significant differences in daily dose of medication demanded for an earthquake victim among the three groups of residents in devastated areas  . ResidenIn contrast to the common perception and ripple effect et al. found that in the 1999 Taiwan Chi-Chi Earthquake the number of physicians in the emergency department was insufficient in the initial hours after the earthquake psychological counseling” appeared for the first time in official CPC documents Chen et al. suggested that even people far from the attack would have trauma-related symptoms of stress In a study of stress reactions after the disaster of September 11, 2001, Schuster We also found that, for the sample of residents in devastated areas (Sichuan and Gansu Provinces), those who considered their residency extremely, but not slightly or moderately, devastated indicated a minimum dose for a hypothetical medication. It seems that the strongest resilience is achieved by those who reside in an unexpected place.Taken together, these results suggest a “Psychological Typhoon Eye” effect et al. also found that people living far from the nuclear research reactor perceived it to be riskier than the nearer residents Similar interesting findings have also appeared in risk perception literature. In studying the effect of distance upon risk perception, Guedeney and Mendel reported that in a local attitude survey of a nuclear power station in France anxiety is lower among those living near the nuclear reactor There are several possible/alternative explanations for this effect. One is the “psychological immunization” theory, which assumes that resistance to adverse life events is naturally acquired through repeated exposure Another possible, but more fundamental explanation, of this effect might be Festinger's Theory of Cognitive Dissonance, which states that cognitive dissonance is an uncomfortable psychological state in which the individual experiences two incompatible beliefs or cognitions A potential limitation of our study is that we used a convenience sample rather than a population-based sample. Ideally a population-based random sample should have been collected at least in the non-devastated areas . In the devastated areas, however, a convenience sample may have been the only feasible method of gathering potential respondents, that is to say, we were able to interview only those individuals who were settled in Red Cross tents.If successful, this study should aid risk analysis and policy-making by providing a basis for understanding and predicting public response to disasters. The experience of the Wenchuan Earthquake may have implications for governmental strategies for responding to other major disasters, including heavy blizzards and hand, foot, and mouth disease (HFMD), from which China suffered during the first half of 2008. Future research in earthquake areas should determine the functional role of the factors (remote in time and kinship) that were associated with post-earthquake concern about safety and health in our study.


Background and purpose Low-virulence implant infections are characterized by bacterial colonization of the implant with subsequent biofilm formation. In these cases, soft tissue biopsies often prove to be culture negative. Consequently, detachment of the causative adherent bacteria is crucial for correct microbiological diagnosis. Using an in vitro model, we compared 4 methods of biofilm sampling from metal surfaces.Methods Discs of titanium and steel were incubated in the presence of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Propionibacterium acnes in Mueller Hinton broth. Non-adherent bacteria were removed by repeated rinsing of the discs. 10 parallels of each disc were subjected to 1 of 4 methods for bacterial recovery: (A) sonication of the discs, (B) scraping of the discs using surgical blades followed by streaking of the blades onto agar plates, (C) scraping of the discs followed by vortex mixing of the surgical blades, and (D) scraping of the discs followed by sonication of the surgical blades. Quantitative bacterial cultures were performed for each sampling method.Results With the exception of S. epidermidis on steel, sonication efficiently and reliably dislodged biofilm bacteria. The scraping methods employed did not detach bacteria embedded in biofilm.Interpretation Scraping of metal surfaces is not an adequate method for sampling of biofilm bacteria in vitro. Prosthetic joint infection (PJI) is a devastating complication occurring in about 1% and 2% of patients receiving a hip or knee prosthesis, respectively . WhereasIn order to circumvent the obstacle of the biofilm in retrieving bacteria from the implant surface, alternative strategies have been developed . In the Mechanical scraping of surfaces is often used for specimen collection and is the method of choice for certain infections, e.g. infectious keratitis . In theoIf equally effective, scraping would be preferable to sonication due to its technical simplicity. We here report an in vitro comparison of the recovery of biofilm bacteria from metal surfaces by sonication and by 3 different scraping techniques.Staphylococcus aureus , Staphylococcus epidermidis , Enterococcus faecalis , and Propionibacterium acnes .Sterilized titanium (Ti6Al4V) and steel (AIS1316-L) discs were colonized by 1 of 4 different bacterial strains . All str8 colony forming units/mL (CFU/mL) had been reached in the exponential growth phase. A batch of 40 discs (one study group) was immersed in this bacterial suspension bath and incubated at 35ºC for 24 h on a gently stirring agitator (20 rpm).Confocal scanning laser microscopy (CSLM) was employed to confirm the 24-hour biofilm formation ability of each strain. 8 study groups were examined . BacteriTo remove non-adherent bacteria, the discs were rinsed 6 times in sterile saline. First, the discs for each study group were placed in a sterile plastic tube  containing 25 mL saline and gently vortex mixed  at 100 rpm for 10 seconds. The discs were then transferred to another tube, and the procedure was repeated twice. Each single disc was then transferred to a sterile glass test tube containing 5 mL saline and subjected to vortex mixing at 100 rpm. The single disc rinsing was also repeated 3 times.P. acnes, FAA agar (Merck) was incubated in an anaerobic cabinet for 7 days. The bacteria cultured were enumerated by colony counting. The number of CFU after final rinsing was recorded as a quantitative baseline, facilitating evaluation of the different detachment methods.Aliquots of 50 µL saline were incubated on agar  with 5% ox blood at 35ºC for 3 days. For culture of Each experimental group (10 discs) was subjected to 1 of 4 methods for biofilm detachment and bacterial recovery. The experimental design is summarized in Each single disc was transferred into a sterile plastic container  containing 5 mL saline. The container was sealed and immersed in an ultrasonic bath . Sonication at 30 kHz with a power output of 300W, as specified by the manufacturer, was performed at 37°C for 5 min. After sonication, aliquots of 50 µL were incubated as described above.Thorough scraping of the complete surface of the disc was performed using a sterile surgical blade. The disc was fixed between the thumb and the index finger. 1 surgical blade was used for each disc. Seeding was done by streaking both sides of the surgical blade onto an agar plate, followed by incubation as described above.Scraping was performed as described for method B. After scraping, each single surgical blade was transferred into a glass test tube containing 5 mL saline before vortex mixing at 2,000 rpm for 30 seconds. After vortex mixing, an aliquot of 50 µL from each tube was incubated as described above.Scraping was performed as described for method B. After scraping, each surgical blade was sonicated in 5 mL saline and aliquots of 50 µL were incubated as described above.To prevent contamination, sterile forceps and sterile surgical gloves were used during handling of the discs and the surgical blades. All procedures were performed in a laminar airflow cabinet.S. aureus, S. epidermidis, and E. faecalis. Culture of P. acnes requires anaerobic conditions. Due to the restrained storage capacity in an anaerobic cabinet, we were compelled to reduce the number of agar plates incubated. Hence, only methods A and C were compared for P. acnes.Comparison of methods A, B, C, and D was done for The 4 methods were compared using a Kruskal-Wallis test (SPSS software). 2 group comparisons were computed with Mann-Whitney test. Statistical significance was considered at p ≤ 0.05.S. aureus on titanium and steel discs, S. epidermidis on titanium discs, E. faecalis on titanium and steel discs, and P. acnes on titanium and steel discs. Firstly, sonication of discs (method A) allowed retrieval of more bacteria than any of the scraping techniques , and bacterial growth was observed in only 7 of 10 parallels  and scraping followed by sonication of the surgical blade (method D) . For subsequent culture, the bacteria must still be viable after sonication. Before the study, we had sonicated each of the 4 bacterial strains for 20 min without observing any bactericidal effect (data not shown). In a clinical context, sonication of a large explanted prosthesis is technically demanding and carries a significant risk of contamination during handling. Thus, the encouraging results obtained from scraping the prosthesis and directly inoculating the agar plate indicated that scraping is a beneficial method due to its technical simplicity . HoweverS. epidermidis on steel, we have demonstrated that sonication efficiently dislodges bacteria from biofilms generated in vitro on titanium and steel surfaces. Scraping of metal surfaces cannot be recommended as a method for diagnosis of biofilm-related infection. Further studies on sonication are warranted, as are studies comparing methods for biofilm sampling in vivo.To conclude, with the exception of