Latinos report higher rates of depression and anxiety than US whites but are less likely to receive care. Transmedia storytelling interventions accessible on the Internet via smartphones, tablets, and computers hold promise for reducing reluctance to explore or get help for symptoms because they are private, convenient, and can reach large numbers of people, including Latinas with mental health needs.The purpose of this study was to examine the feasibility, acceptability, and preliminary efficacy of a mental health transmedia intervention for Latinas with elevated symptoms of depression, anxiety, or both.A total of 28 symptomatic English-speaking Latina women aged 21 to 48 years participated in a 6-week study using a within-group design. All aspects of the study were completed via telephone or Internet. Participants used their personal devices to engage the Web-based transmedia intervention (in English) that included story-based videos, a data-informed psychotherapeutic video, an interactive video sequence, and a blog written from the point of view of one of the characters with links to mental health resources. Perceived confidence to get help and perceived importance for seeking immediate help were both measured using single-item questions. Participants completed surveys at baseline (via telephone) and 1 and 6 weeks after media engagement that measured various factors, including depression  and anxiety . A telephone interview was conducted within 72 hours of media engagement. Action taken or intentions to get help (single-item question) and talking about the videos with others (single-item question) were measured 1 and 6 weeks after media engagement. Repeated measures analysis of variance was used to assess change in depression (PHQ-8) and anxiety (GAD-7) before transmedia engagement and 1 and 6 weeks after. Spearman correlations evaluated the association of confidence and importance of getting help with action taken, anxiety, and depression.F2,54=9.0, P<.001) and anxiety  significantly reduced across time. Higher levels of confidence were significantly associated with actions taken at 1 (P=.005) and 6 weeks (P=.04), and higher levels of importance were significantly associated with actions taken at 1 (P=.009) and 6 weeks (P=.003). Higher levels of confidence were associated with lower levels of depression (P=.04) and anxiety (P=.01) at 6 weeks.All 28 Latinas (English speakers) who engaged with the transmedia remained in the 6-week study. Within 1 week of transmedia engagement, 39% of women took action to get help, and 82% discussed the media with others. Symptoms of depression (Preliminary findings indicate a culturally tailored mental health transmedia intervention is a feasible approach that holds promise for engaging large numbers of symptomatic English-speaking Latina women to begin the process of seeking help, as well as decreasing symptoms of anxiety and depression. Latinos are the largest ethnic minority group in the United States , and theAlthough only able to reach a small audience, an attractive fotonovela booklet created by Cabassa and colleagues  was usedTransmedia, a form of digital edutainment, moves beyond telenovela viewing and holds promise for innovative interventions because, as a communication technology, it offers a convenient methodology for reaching and affecting large numbers of individuals including those in need. As Latinos have the highest usage of smartphones among US adults (18-49 years)  and highEast Los High that reached viewers in all 50 US states and 163 countries during its first season [East Los High has focused on sexual and reproductive health, no transmedia interventions to date have focused specifically on topics related to adult Latinas’ emotional health experiences or dealing with symptoms of depression or anxiety. The demand for story-based media is increasing among US Latinos who, according to Nielsen’s Digital Consumer Report [Transmedia that includes health messages has become increasingly popular among the growing numbers of English-speaking Latinos in the United States through Wise Entertainment’s hit show, t season . It combt season  unique pt season  that canr Report , watch mWith the goal of using transmedia in an intervention, we drew upon our previous research data to enhance understanding of key issues for English-speaking Latinas associated with their experiences of depression or anxiety, as well as resilience and coping. We used those deidentified data to create a transmedia intervention called “Catalina: Confronting My Emotions” that was offered to women struggling with mental health symptoms. The purpose of this study was to examine the feasibility of a mental health transmedia intervention for English-speaking Latinas with moderate-to-severe symptoms of depression or anxiety. The first aim was to examine feasibility in terms of implementation, demand, and acceptability of a 6 week “Catalina” transmedia intervention. The second aim was to test the preliminary efficacy of the transmedia intervention to spur change in symptoms, perceived confidence and perceived importance of seeking help, and actions taken to get help.With guidance from the University of California, Los Angeles Institutional Review Board (UCLA IRB), we used deidentified data from the Principal Investigator’s (PI) previous mental health studies with English-speaking and second generation Latinas as groundwork for creating composite characters and a storyline. Then, the PI teamed up with a Latino writer-director from Hollywood who created the scripts (in English) for the drama. Content validity for scripts was obtained from a community advisory board of four mental health therapists in two waves of critique, with a focus on making the scripts realistic and culturally appropriate. All four therapists had experience working with English-speaking adult Latinas and two of the four were Latinas themselves. The script was revised after each wave of input from the therapists. Casting was done in Hollywood, Latino or Latina actors were hired, and the video scenes were filmed and edited. Theater testing was done using preliminary versions of the videos, with a community sample of 19 Latina adults. Feedback regarding relatability of the characters and cultural appropriateness of the storyline was collected using focus groups and individual interviews. Feedback led to the final editing of the media. Simultaneously, a computer programmer collaborated with the PI to create an interactive feature and the Web page that was designed to match the look and feel of the videos. It included photos, captions, and links to all the videos and the resource-rich blog, including contact information and links to local and Web-based resources plus hotlines for mental health services.Approval was granted by the UCLA IRB for a mixed-methods study with a one-group pretest and posttest design in a particular geographic target zone (approximately 22-mile diameter) within a much larger metropolitan area of Southern California. Purposive sampling methods were used for community-based recruitment from May 2015 to August 2015. The research was designed so that participants could complete all aspects of the study entirely over the phone and Internet.Inclusion criteria limited enrollment to those who self-identified as Latina women aged 21 to 55 years who read and spoke English and who scored above the threshold at screening for depression on the Patient Health Questionnaire (PHQ-9)  or the bA total of 63 women called the study phone. Of the 63 callers, 28 were ineligible based on the inclusion criteria, including 6 who expressed suicidal ideation (they were further screened and referred using a suicide protocol), 10 who scored below threshold for both depression and anxiety, 4 who did not speak English, 2 who did not identify as Latinas, 4 who did not complete the screening, and 2 who reported they had only called to inquire for a friend. Thus, 35 women moved on to be screened and met eligibility requirements. Of them, 4 did not complete the Web-based informed consent after screening, 2 consented but did not participate beyond giving consent, 1 consented but later contacted the research assistant (RA) to report she could not gain access to the Internet on her phone. A final total of 28 eligible women moved beyond consent, and all of them completed the study; that is, there was no attrition over the 6 weeks of data collection.Fliers were distributed at nine partner sites including women’s health clinics, parenting centers, social service sites, and a large catholic church in the geographic target zone. The fliers, printed in color and featuring a photo of the Latina main character from the story, invited adult Latinas who were struggling with feelings of sadness or worry to call if they wanted to participate in a media-based study. After giving verbal consent, callers were screened by the RA, a psychiatric mental health nurse practitioner (second author). The RA administered the PHQ-9  and the All enrolled participants were assigned a confidential identification number for deidentification purposes, and media was made accessible via a password protected “Catalina” website after they completed the Web-based informed consent using a link sent to them in a text message  or email. Participants first completed at time 1 the online survey and then accessed the website that included an introductory video along with a series of links that were sequentially arranged to guide the viewer. Link number five led to a series of coordinated short video segments wherein Veronica (the nurse-therapist character) directly asked the viewer specific questions inspired by motivational interviewing (MI)  in a seqAt all points, viewers were free to decide if and when they would click any links to engage with the surveys or media. The Web page included a reminder for participants to call the study phone after engaging with the media to schedule a one-to-one interview with the RA within 72 hours of media exposure. The qualitative telephone interview explored women’s perceptions of the media in a way that protected women’s privacy. As reported elsewhere (in process), the individual interviews were audiorecorded, transcribed, and analyzed. Participants were sent a text message 1 and 6 weeks after engaging in the media, which provided a link to Web-based surveys (time 3 and time 4) that included the PHQ-8 and GAD-7 plus survey questions about perceptions related to the importance of getting immediate help, confidence they could get help, and intentions or action taken. To compensate for their time, gift cards to a local retailer were mailed, emailed, or texted to participants at three points see .As few studies have examined the integration of health information into transmedia storylines, Bowen’s  standardr=.79) in a sample of 3000 women from obstetrician or gynecologist clinics. In another study with 6000 patients, the PHQ-9 demonstrated good sensitivity (88.0%) and specificity (88.0%) to discriminate between depressed and nondepressed individuals at the cut-point of 10 or higher [not at all for the suicidal ideation item on the scale indicated possible suicidal ideation [The PHQ-9  is a 9-ir higher . Merz anr higher  did a stideation , and ther=.997) was found [After screening, the PHQ-8 was used to measure the severity of depression over the past 2 weeks . For thias found .not at all to nearly every day. GAD-7 scores indicating either moderate (≥10) or severe (≥15) anxiety represented study eligibility. Anxiety severity was assessed at screening and 1 and 6 weeks after engaging the transmedia intervention . In a study by Mills and colleagues [The GAD-7 is a 7-item questionnaire for anxiety and was used to screen for and measure the severity of anxiety over the preceding 2 weeks in this study . Responslleagues  with a cFor the interactive video sequence with Veronica, questions were fashioned after Rollnick and Miller’s  MI rulerAction taken and intentions to take action to get mental health care or support were assessed using Web-based surveys at time 3 and time 4 see , with a Included in the time 2 telephone interview (scheduled after engaging the transmedia intervention) was a single-item Likert question with a 10-point range that was used to measure how much the women related to the main character . Possible responses ranged from 1 to 10, with 1 meaning they did not relate to her at all and 10 meaning they completely related to her. Another single-item Likert question was asked to measure how comfortable women would be seeing someone such as the nurse-therapist character (Veronica) for counseling (1 indicated there were not comfortable and 10 indicated they were very comfortable).Women were asked if they thought about or talked about the videos with family members, friends, or anyone else since viewing the media. These questions were asked as part of the Web-based surveys 1 and 6 weeks after engaging with the media  accessed the transmedia intervention Web page, (2) accessed and watched all videos, (3) completed all minutes of each video, and (4) answered the Web-based MI interactive questions.Descriptive statistics were computed for sample characteristics. To assess feasibility in terms of implementation, descriptive statistics were used to compute how many women accessed, engaged, and navigated the Web page and answered the MI interactive questions (by typing within answer boxes) without assistance. To assess demand, descriptive statistics were used to compute how many women watched and completed all minutes of each video. To assess acceptability, descriptive statistics were used to compute relatability to the main character, desirability of seeing the nurse-therapist character, and the number of women who used or shared information on Veronica’s blog. Limited efficacy was assessed using repeated measures analysis of variance to assess change over time for anxiety and depression symptoms and Spearman correlations to evaluate the association of perceived confidence and importance of getting immediate help with anxiety, depression, and action taken.Of the 28 participants who completed the Web-based consent form and accessed the media Web page see , 23 womeSee In terms of TV viewing habits, most participants reported that they watched TV shows about characters in a comedy or drama on a weekly basis. Over half of the sample watched story-based dramas or comedies several times weekly, and over three-quarters of the sample watched telenovelas on a weekly basis. In terms of the Internet, all participants reported that they watched videos, movies, or story-based shows via a smartphone, tablet, or computer on a weekly basis see .As noted above (see Participants), 1 woman enrolled in the study but did not have Internet access on her phone so did not stay in the study. Of the 28 women who enrolled and had access to the Internet, all engaged the media using a smartphone, tablet or computer, and all stayed in the study throughout the 6 weeks.In terms of Bowen’s feasibility criteria of implementation , all 28 The website tracker of user plays for each video showed that all 28 women in the sample watched all the videos. Of the total, 27 women completed all minutes of all videos; however, 1 woman stopped the 14-min video approximately 2.5 min before its ending.The mean relatability score for how much women related to the main character  was 6.95 on a 10-point scale. The mean desirability score for how comfortable women would be seeing the nurse-therapist character for counseling (Veronica) was 8.13 on a 10-point scale. Within 6 weeks of viewing, 20 of the 28 women  used or shared with others the blog or information from the blog.F2,54=9.0, P<.001); there was a linear decrease  with scores at screening significantly higher than at 1 week  and 6 weeks after exposure to the media . A quadratic function also describes the pattern (P=.008) showing a “curve,” with greater decrease between screening and 1 week post media than from 1 to 6 weeks after media exposure  and at 6 weeks post media exposure . Even though results showed a continuing decrease across time, there was a lessening of the decrease from week 1 to week 6 post media exposure such that the week 1 and week 6 scores were not significantly different  and with lower levels of anxiety symptoms .Six weeks after media exposure, symptoms of depression and anxiety were both significantly correlated with perceived confidence that participants could take action to get immediate help. That is, higher levels of confidence were associated with lower levels of depression symptoms (Spearman ρ (rho): −.399, P=.14), nor was it significantly correlated with depression . These moderate but nonsignificant effects indicated that higher perceived levels of importance were associated with lower levels of depression and anxiety.Six weeks after media exposure, women’s perceived level of importance of getting help for their emotions was not significantly correlated with anxiety symptoms  reported they had already used the resources from the blog including links and contact information of local resources for support or therapy and hotline numbers. In addition, within 1 week, 25 women  reported thinking about the videos during the week, and 23 women  reported they had already talked about the videos and transmedia with friends or family. Six weeks after exposure to the media, 8 women  reported they had used resources from the blog, and 21 women  reported they were still spending time thinking about the videos. At time 4, a total of 22 women  reported they had talked about the videos since time 3 when they completed the last set of Web-based questions 5 weeks earlier.P=.005) and 6 weeks after engaging with the media . Higher levels of confidence were associated with higher levels of intentions or taking action to get help both 1 week and 6 weeks after engaging with the media.Women’s level of perceived confidence in their ability to seek help was significantly associated with intentions or taking action to get help both 1 week after  and 6 weeks after engaging with the media . Higher levels of importance were associated with higher levels of intentions or taking action to get help both 1 and 6 weeks after engaging with the media.Women’s perceptions of the importance of getting help for their emotions was significantly associated with intentions or taking action to get help both 1 week after  used resources from the resource-rich blog. This included referral sites and hotlines that women used to gain knowledge about the available resources, to gather information, or to make an appointment for services. Moreover, the participants found the transmedia to be socially valuable, with the majority  sharing it with those in their social circle within days of viewing it for the first time. Rather than keeping their experience of the transmedia to themselves, most of the women in our sample told friends and family about the transmedia intervention without delay. These findings highlight the convenient and strategic design of the transmedia website. Participants who determined that they (or a friend) could benefit from services just as Catalina did, could readily access resources.Finally, the intervention was therapeutic in that symptoms reduced after engagement with our transmedia storytelling intervention. Our 6-week intervention led to a statistically significant improvement of the debilitating symptoms of depression and anxiety. This drop in symptom levels over the 6-week intervention illustrates how a digital storytelling intervention using the Internet can make a measurable difference in an individual’s life. This is even more important because of our sample’s vulnerability; 75% (21/28) of our Latina participants reported co-occurring depression and anxiety, which is commensurate with the literature . Co-occuEast Los High resource Web page associated with the show provided a hyperlink to Planned Parenthood, which was used 26,414 times during the first season and another 30,868 times in the 6 weeks after the season ended [Compelling, story-based content that individuals find appropriate, desirable, and easily accessible via the Internet provides a way to reach thousands of people about topics that are often considered taboo. For example, the on ended ,58. InteIt is key for story-based edutainment to have realistic stories set in a believable world that is socioculturally relevant with a main character that viewers can relate to ,60 and iIn conjunction with symptom reduction, transmedia storytelling interventions may also serve as catalysts that help women take action to seek mental health services. For our sample, both perceived confidence (self-efficacy) and importance were associated with increased actions taken to get help 1 and 6 weeks after viewing the media. On the basis of Bandura’s social cognitive theory, self-efficacy is a psychological determinant of behavior change commonly targeted in health promotion interventions . Other rThis was a feasibility study with a one-group pretest posttest design. Thus, results cannot be generalized beyond this sample until an attention control and usual care are added to the research, as necessary, to verify the efficacy for this transmedia intervention. With the surveys and the qualitative interview administered by the RA, a psychiatric mental health nurse practitioner, the possibility of a therapeutic effect exists.East Los High [Because telenovelas have long been enjoyed by Latina audiences and because of the success of Los High , compellFuture implications of this study include advancements in the use of transmedia, such as further development of more interactive Web-based activities to access other evidence-based therapeutic help for women to make strides in managing their symptoms. This research and development may provide insight into how to refine and tailor future evidence-based Web-based treatment programs for Latinas. A recent review of Internet-based cognitive behavioral therapy (iCBT) supports the efficacy of iCBT to successfully treat depression and anxiety and particularly in overcoming the barriers that often preclude treatment . Due to


Three-dimensional (3D) printing is opening new opportunities in biomedicine by enabling creative problem solving, faster prototyping of ideas, advances in tissue engineering, and customized patient solutions. The National Institutes of Health (NIH) Library purchased a Makerbot Replicator 2 3D printer to give scientists a chance to try out this technology. To launch the service, the library offered training, conducted a survey on service model preferences, and tracked usage and class attendance. 3D printing was very popular, with new lab equipment prototypes being the most common model type. Most survey respondents indicated they would use the service again and be willing to pay for models. There was high interest in training for 3D modeling, which has a steep learning curve. 3D printers also require significant care and repairs. NIH scientists are using 3D printing to improve their research, and it is opening new avenues for problem solving in labs. Several scientists found the 3D printer so helpful they bought one for their labs. Having a printer in a central and open location like a library can help scientists, doctors, and students learn how to use this technology in their work. Three-dimensional (3D) printing applications in biomedical fields are only limited by the imagination and a few technical issues. Although transplantable 3D organs are years away, progress is being made, as demonstrated in 2016 when scientists announced they used a 3D printer to create an ovarian implant for a mouse that produced healthy offspring –9. AnothHoy states that it is possible for doctors and medical students to learn the basic skills for 3D printing and modeling in a library with a consumer-grade printer, which is the type commonly purchased by libraries . These sAcademic Library Use of 3D Printing surveyed twenty-five colleges about their experiences and provided valuable information for librarians considering implementing a printing service [Four previously published articles provide advice for planning and implementing a 3D printing service in an academic library that can be applied to a medical library setting –20. Libr service . The surHealth sciences librarians are beginning to take notice of 3D printing with discussion at conferences –24. In 2The National Institutes of Health (NIH) Library ran a 3D-printing pilot to provide NIH staff with an opportunity to try out 3D-printing technology and to gauge their interest in a permanent 3D-printing service. An additional goal of the pilot was to build partnerships among NIH scientists, fellows, students, engineers, and administrators who were interested in 3D printing, so that the library could serve as an information hub connecting individuals who have 3D printing needs to experts in 3D modeling and printing.website.After consulting with librarians at other institutions and reading product reviews of consumer-grade 3D printers, the NIH Library purchased a single-nozzle Makerbot Replicator 2 printer that uses a type of plastic known as polylactic acid (PLA). The print size limitations for this model are 11×6×6 inches. Makerbot provides a free proprietary 3D model slicing program, Makerbot Desktop, on its Beginning in June 2014, use of the 3D printer was freely offered to NIH scientists, fellows, and students, and library policy restricted projects to NIH-related work. Due to long print times (average eight to twelve hours), the printer was available on a first-come, first-served basis. To decrease the upheaval to library staff and to provide users with a maximum learning opportunity, the library implemented a self-service model. Users were required to attend a biweekly librarian-led 3D printing orientation on how to prepare models, safely operate the printer, and start print jobs.the library, and a Twitter account (@NIHL3D) was established for those who wished to follow new developments in biomedical 3D printing. Users of the 3D printer were asked to fill out a survey (on paper or via SurveyMonkey) including questions about future service model preferences. In addition, library staff reached out to other people at NIH who were interested in or had experience with 3D printers and set up an email discussion list to share expertise and hardware.A librarian provided continuing assistance by appointment or walk-in, including troubleshooting failed prints and advising on model design and issues. A website was created to help users find information on modeling software and 3D printing at Knowledge about the availability of the 3D printer mainly spread by word of mouth. The first user was a research fellow who needed to print a prototype of a drosophila container for drug testing in her lab. Soon, the library was nearly overwhelmed by people interested in the new technology. When the printer broke down and was sent to the manufacturer for repairs, one of the library’s network partners lent his personal Makerbot Replicator 2x to the library in June 2014 so that the pilot could continue. Both printers remain in the library today.At the end of the pilot period in December 2014, 213 people from 21 different institutes had attended an orientation, with the highest attendance from members of the National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute of Neurological Disorders and Stroke. Based on personal records kept by the librarian, approximately 173 successful print jobs were completed, although many failed the first time. As the printers were available on nights and weekends, the actual number of prints was probably higher. During the pilot period, replacement parts and repairs included:nozzle clearing (regularly)Z axis chipthermocouple (3 times)XYZ cable (2 times)misaligned gantrythermal insulation (3 times)loose beltmotherboard (2 times)X axis motor3D printing and replacement of the broken air duct (2 times)Based on the high usage of the 3D printers during the pilot period, the service became permanent in 2015, and changes were made to the service model to improve its sustainability. A small group of librarians and reference assistants learned to operate and repair the printers so that a greater number of staff could assist with minor problems; orientations were reduced to monthly; hours of printer operation were recorded on a monthly basis; and a voluntary sign-in log was set up to track the number of separate printing jobs. In 2015, 182 people attended orientations, and at least 196 models were produced. Replacement parts and repairs needed for 2015 were:nozzle clearing (regularly)thermocouple (2 times)thermal insulation motherboard (1 times)LCD display (2 times)extruder (2 times)3D printing and replacement of the broken air duct Although attendance at the 3D-printing orientations was initially very high, it dropped off after August 2014 , possiblThe number of print jobs per month was erratic , with a I have been building custom pieces needed for electrophysiological recordings. These pieces included a holder for electronic valves, holders for switches and other electronic equipment and micro manipulators. Similar pieces can be bought for several hundreds of dollars but not with the degree of customization required.I printed an adapter to hold a red filter over a lamp used for dissection. This filter is needed to prevent the bleaching of pigment in retinal tissues during tissue handling so that the responses of these cells to light can later be measured. I might have been able to find a commercially-available adapter, but this way, I was able to get exactly what I needed in a timely manner, and the only cost was my time.We are using 3D printing to fabricate custom parts for an open-source operant chamber that can be used to measure how willing mice are to work for rewards like sucrose. While multiple commercial operant chambers exist, they cost several thousand dollars. We have developed one from open-source and off the shelf parts that costs around $100 in total... While we have been able to repurpose many household objects for our operant chamber, we turned to 3D printing for parts that were not possible to find. We are currently printing custom covers for the sensors, and a drinking well that we can combine with the photo interrupter switch to track when the mouse drinks the sucrose. All of our models will be available online for others to use. We hope that our open source operant chamber will make behavioral research more affordable for scientists across disciplines.Most (75%) respondents were willing to pay to print 3D models after the free pilot, although we continued to provide our 3D printing service for free after it became permanent. There was high interest in 3D scanning (76%), modeling (72%), and training (62%). Half of the respondents heard about the pilot via word of mouth (50%). People reported being very satisfied with the service (average 4.75 out of 5) and very likely to recommend it to their colleagues (average 4.88 out of 5). Respondents also reported a high likelihood of printing on a monthly basis (63%).Catalyst and NIH Record newsletters and other publications: The library’s first 3D printer customer is getting a patent for her design, and a paper was published about the mouse operant chamber [Even with printer breakdowns and prints that did not always come out correctly the first time, the 3D printers had a definite “coolness” factor, especially among younger researchers. The service garnered positive NIH campus media attention for the library in the form of articles in the  chamber . FurtherConsumer-level 3D printing is a new technology that can break down and require repairs, but most repairs are not difficult. It is highly recommended that libraries choose a printer with an extensive online community, as most common problems and their solutions have been encountered before by others who have documented them on YouTube, which is an invaluable resource in this field . ExtendeOnly a tiny minority of orientation participants knew anything about how to model or print in 3D. They had seen news stories about 3D printing and were excited about the new technology, but the modeling software learning curve is steep and requires time and motivation to master. Only an estimated 40% of orientation attendees printed models. If modeling classes had been concurrently available, more users may have followed through with print jobs. Of those who did print models, many needed advice to make their models printable. Consequently, in 2016, the library again tapped into the rich resources of the NIH community and found volunteers to teach various beginner-level 3D-modeling tools—including Blender, Solidworks, OpenSCAD, and Maya—and molecular modeling tools such as Chimera.When the library decided to offer 3D printing on a long-term basis, a more reliable printer, a Stratasys uPrint, was purchased at the end of 2015. It is hoped that there will be less down time, and scientists have been particularly interested in the uPrint’s dissolvable supports, especially when printing delicate protein ribbon structures. The uPrint utilizes a chemical bath to soak away supports, because manually picking away supports is tedious work that can break delicate models. The uPrint also has a sealed, heated chamber that reduces curling and cracking of models, which can be issues with consumer-grade printers.3D printing is a rapidly growing area that currently touches nearly every area of medicine: custom implants, dentistry, surgical guides, prosthetics, facial reconstruction, and tissue engineering for drug testing. The demand for 3D-printing skills will continue to grow as there are new developments in microprinting and tissue engineering. Health sciences libraries can position themselves as training centers where doctors and medical students, as well as basic scientists, can learn about the scope of this technology and how to leverage it in their work to improve patient care. Those libraries lacking the staff or funding for a 3D printer could offer 3D modeling training. Many software packages are free, and the number of commercial print services where patrons can send their models is growing.


Population breast screening has been implemented in the UK for over 25 years, but the size of benefit attributable to such programmes remains controversial. We have conducted the first individual-based cohort evaluation of population breast screening in the UK, to estimate the impact of the NHS breast screening programme (NHSBSP) on breast cancer mortality.We followed 988 090 women aged 49–64 years in 1991 resident in England and Wales, who because of the staggered implementation of the NHSBSP, included both invited subjects and an uninvited control group. Individual-level breast screening histories were linked to individual-level mortality and breast cancer incidence data from national registers. Risk of death from breast cancer was investigated by incidence-based mortality analyses in relation to intention to screen and first round attendance. Overdiagnosis of breast cancer following a single screening round was also investigated.P<0·001) after adjustment for age, socioeconomic status and lead-time. Breast cancer deaths among first invitation attenders were 46% lower than among non-attenders  and 32% lower following adjustment for age, socioeconomic status and self-selection bias . There was little evidence of overdiagnosis associated with invitation to first screen.Invitation to NHSBSP screening was associated with a reduction in breast cancer mortality in 1991–2005 of 21% (RR=0.79, 95% CI: 0.73–0.84, The results indicate a substantial, statistically significant reduction in breast cancer mortality between 1991 and 2005 associated with NHSBSP activity. This is important in public health terms. Population breast screening was introduced in a number of countries from the late 1980s after randomised controlled trials reported that mammographic screening could reduce breast cancer mortality by an average of 23% in invited women aged 50–69 years . This, cWith the exception of Finland, population-based breast screening has been introduced without intrinsic provision for evaluation, making identification of an uninvited comparison population difficult. The use of individual-level data to take into account the screening history of each woman and to identify breast cancers diagnosed before invitation has been strongly recommended (The UK NHS Breast Screening Programme (NHSBSP) is one of the largest nationally organised programmes in the world, currently inviting nearly three million women each year . The NHSTo evaluate the impact of the NHSBSP in England and Wales on breast cancer mortality we conducted a retrospective cohort analysis using individual-level screening exposure and mortality outcome data. The staggered implementation period of the programme was used to provide an uninvited control group. This paper presents an analysis of the impact of NHSBSP activity on breast cancer mortality between 1991 and 2005.We describe our methods briefly below, with additional details provided in in situ disease, were collected from the national cancer registration system. Socioeconomic status (SES) was estimated based on postcode of residence at study entry using the Townsend Index  and exemption from individual informed consent was approved by the then Patient Information Advisory Group (PIAG 3-07(g)/2002).Women entered the study on 1 January 1991 and exited at date of death, date lost to follow-up or 31 December 2005, whichever was earliest . Primary analysis was conducted on an ‘intention-to-screen' basis . In the NHSBSP, women were scheduled for invitation on the basis of demographic information and their further eligibility was checked by their GP practice before being invited. This process of checking suitability for screening with GPs on the basis of health status (a process that has now ceased) meant that ill-health could result in a scheduled woman not being invited at that episode. Under these circumstances, use of invitation as the measure of exposure in an intention to screen analysis could have led to an estimate that was biased in favour of screening because of a healthy invitee effect . To avoiLead-time bias consequent on screening advancing the date of diagnosis can bias results against a positive effect of screening in IBM analysis by including breast cancer deaths in women who would otherwise have been diagnosed beyond the accrual period  assumingA conventional mortality analysis of intention to screen was also conducted in which deaths were allocated to exposure groups at the date of death and breast cancer mortality in women living in the earliest and latest areas to start screening was compared. We designated as early-starting postcode districts those where ⩾95% of women were first invited before December 1991 and late-starting areas where ⩾95% of women were first invited after July 1993. Follow-up continued until the end of 2005.We conducted an analysis based on screening attendance, dividing women at entry according to whether or not they had attended within 6 months of their first screening invitation. In the NHSBSP, if a woman does not attend within 6 months of her invitation, the episode is closed. The limit of 6 months therefore ensures that in our analysis any attendance relates directly to the correct invitation. In this analysis, only women who had been sent an invitation were included. Estimates were adjusted to take account of the increased mortality risk in women who do not accept screening  was conducted. Some of these women, due to their age and the staggered introduction of screening, were never invited by the NHSBSP. Those who were invited would have had only a single invitation (women were not invited above age 64 years at that time), giving at least 12 years of follow-up for lead-time to dissipate so that any remaining excess incidence in the invited group can be attributed to screening. Excess incidence has been expressed both as a proportion of observed incidence in uninvited women and of that in invited women, methods A and B advocated by the To investigate overdiagnosis of breast cancer due to screening, a cumulative incidence analysis , adjusted by age and calendar year were used to compare non-breast cancer mortality between exposure groups .The number of women needed to be invited to save one breast cancer death was calculated as the reciprocal of the number of lives saved per woman invited . The numP-values. Age and socioeconomic status were included as covariates in the model.Poisson regression, conducted in STATA V10·0 , was used to calculate rate ratios and associated 95% confidence intervals and Data on a total of 1 426 379 women aged 49–64 years on 1 January 1991 were extracted from 28 screening call/recall databases. Of these, we excluded from analyses women who were not traced at NSTS (14 157), women with breast cancer diagnosed before 1 January 1991 (28 870) and women invited before 1 January 1991 (395 262). This resulted in an analysis population of 988 090 women.n=101) were flagged at the NHS central register to determine an underlying cause. None was found to have died of breast cancer. A total of 39 134 women (4%) were lost to follow-up for reasons other than death before 31 December 2005, and a further 8014 who left the study area before being scheduled for NHSBSP invitation were lost to follow-up in the IBM analysis.Between 1 January 1991 and 31 December 2005, there were 41 120 cases of breast cancer diagnosed and 146 539 deaths in the cohort, including 8002 deaths from breast cancer. Linkage failed to produce an underlying cause of death for 2% of deaths (3032/146 539). To determine whether any of the missing causes of death were due to breast cancer, all women whom we knew from cancer registration had been diagnosed with breast cancer but whose cause of death was not known . After adjusting for lead-time bias of 3 years, the mortality reduction increased to 21% . The absolute difference was 0.31 per 1000 person-years and the number needed to be invited to save one death from breast cancer was 1436 (based on inviting women for 2 years and 9 years of follow-up). Non-breast cancer SMRs in the invited and uninvited groups were 0.96 (0.95–0.97) and 0.98 (0.96–1.00), respectively, SMR ratio 0.98.Breast cancer mortality was 17% lower in women invited for screening than in uninvited women  and this estimate was unaffected when adjusted for age and SES (P<0.001).A total of 790 946 women were invited to their first screen between ages 49 and 64 years, and 587 809 (74%) attended within 6 months. The breast cancer mortality reduction in women who attended their first screen compared with those who did not attend was 46% . This equates to 0.3% overdiagnosis after one invitation and 12 years of follow-up as a percentage of the observed incidence in either invited or uninvited women.A total of 162 502 women aged 62–64 years at entry contributed 2 033 325 person-years of follow-up during which 6108 breast cancers were diagnosed. Lead-time effects were apparent when follow-up was censored at the end of 1995 or the end of 2000, but had disappeared by 2005. At the end of follow-up, the cumulative incidence rates of breast cancer adjusted for SES in the invited and uninvited groups were 3.01 (95% CI: 2.89–3.13) and 3.00 (95% CI: 2.90–3.10) cases per 1000 person-years, respectively ; As a consequence of breast screening, some early-stage tumours are diagnosed which would never progress to become clinically apparent during a woman's lifetime. This represents overdiagnosis. Whilst our study was primarily designed to estimate the impact of NHS breast screening on breast cancer mortality, the oldest birth cohorts offered an opportunity to investigate overdiagnosis of breast cancer in relation to screening activity. By 2005, lead-time effects in the invited group had dissipated, so that unlike previously published estimates of overdiagnosis in the NHSBSP , our anaThis study uses individual-level data for both screening and outcome data. The failure to accurately measure exposure to screening and to adopt an incidence-based mortality approach is a key limitation of studies that have examined population trends for the purpose of evaluating breast screening (We were unable to ascertain dates of breast cancer diagnosis for 5% of breast cancer deaths. Sensitivity analyses excluding such cases had no impact on the estimates of the effect of screening on mortality. Findings were also unaffected when analyses were conducted excluding the 2% of deaths with unknown cause.Findings from analyses comparing mortality in screening attenders with that in non-attenders are highly dependent on the magnitude of the correction factor used to adjust for self-selection bias. We applied a population-specific correction factor of 1.19, derived from the UK cohort study data, that was similar in magnitude to the correction factors 1.11 and 1.17 derived from Italian and Icelandic evaluation study data, respectively  resultedThere were concerns that screening exposure data collected from the breast screening call/recall system might not accurately reflect screening prior to 1995. Validation by checking detailed screening histories of over 100 000 individuals indicated a high level of accuracy and completeness overall, but there was evidence of some missing screening information in some areas before 1995. The effect of this would be to dilute a positive effect of screening.Temporal differences between exposure groups in our intention to screen IBM analyses mean they are potentially confounded by changes in non-screening factors over time. Falling UK breast cancer mortality rates since 1990 are likely to be due to a combination of factors, including improvements in treatment and the direct effect of screening through earlier detection and treatment. In addition, there are likely to be indirect screening effects which include increased breast awareness associated with promotion of the NHSBSP  so that Findings from this large evaluation of the NHSBSP are similar to those reported by cohort evaluations of organised screening in other countries (The wide variety of approaches that have been used to estimate the impact of population breast screening reflects the difficulty of evaluating programmes that were introduced without provision of a suitable comparison population. Cohort studies using individual-level data and observed mortality represent a robust approach to evaluation and this study is the first evaluation of the NHS breast screening programme to adopt such a strategy. This cohort study adds considerably to the body of evidence indicating that population-based mammographic screening leads to a reduction in breast cancer mortality.


The role of immunization in the production of antibodies directed against immunogens is widely appreciated in laboratory animals and in humans. However, the role of immunization in the development of “natural antibodies” has not been investigated. Natural antibodies are those antibodies present without known history of infection or immunization, and react to a wide range of targets, including “cryptic” self-antigens that are exposed upon cell death. In this study, the ability of immunization to elicit the production of natural antibodies in laboratory rats was evaluated. Laboratory rats were immunized with a series of injections using peanut extracts , a high molecular weight protein conjugated to hapten (FITC-KLH), and a carbohydrate conjugated to hapten . Significantly greater binding of antibodies from immunized animals compared to controls was observed to numerous autologous organ extracts  for both IgM and IgG, although the effect was more pronounced for IgM. These studies suggest that immunization may have at least one unforeseen benefit, enhancing networks of natural antibodies that may be important in such processes as wound repair and tumor surveillance. Such enhancement of natural antibody function may be particularly important in Western society, where decreased exposure to the environment may be associated with a weakened natural antibody repertoire. The term 'natural antibodies' describes immunoglobulin molecules produced against antigens without known history of immunization or infection . NaturaCurrent research suggests that the natural antibody repertoire is inherently linked to the host biome. For example, one of the differences between wild rodents and laboratory rodents is that the wild animals have much higher natural antibody levels compared to their laboratory counterparts . RecentThis study examines the effect of vaccination on the natural IgM and IgG antibody repertoire. Sprague Dawley laboratory rats were given an immunization protocol designed to broadly stimulate the humoral immune system. The immunization cocktail included hapten conjugates with protein and carbohydrate carriers to provoke T-cell-dependent and -independent responses, respectively, as well as peanut extracts. The binding of natural antibodies from the sera of immunized and non-immunized rats to antigens extracted from rat organs was then quantitatively assessed.Male (n=4) and female (n=8) Sprague Dawley rats were purchased from Harlan Sprague Dawley . The rats were acclimatized in standard animal housing at Duke University for 62 days. Once acclimatized, the rats were bred. The 31 female rats that resulted from the breeding were utilized for the experiments in this study. All animal housing and procedures were approved by the Duke University Medical Center Institutional Animal Care and Use committee.2 inhalation at 71 days of age. Blood was collected from the posterior vena cava and centrifuged, and sera were stored at -80 °C until use.In order to evaluate the effect of immunization on the natural antibody repertoire, 20 of the 31 female rats were immunized with a cocktail containing peanut extract, fluorescein isothiocyanate labelled keyhole limpet hemocyanin (FITC-KLH) and 2,4-dinitrophenyl conjugated to AminoEthylCarboxyMethyl-FICOLL . The peanut extract was used to promote an IgE response, whilst FITC-KLH and DNP-Ficoll were used for T-cell-dependent and T-cell-independent stimulation, respectively. The remaining 11 rats acted as controls and did not receive any immunization. All rats were euthanized by COThe peanut extract was prepared as previously described by Pi et al. (2015). Raw pe3 buffer at pH 9.3, in dialysis tubing . The mixture was kept at 4 °C for 24 hours and the dialysis solution was changed once during this process. FITC  and KLH were then combined at a 20 µg:1 mg ratio, and incubated for 1.5 hours at room temperature. Next, the FITC-KLH conjugate was dialyzed in 500 mL saline solution overnight at 4 °C. The buffer was changed, and the sample was dialyzed for 2 hrs at room temperature. The absorbance of purified FITC-KLH was read at 280 nm and 495 nm, and the labeling ratio (FITC:Protein) was determined based on the ratio of those absorbancies. Two batches, with labeling ratios 2.4 and 5.3, were made and pooled. Labeled FITC-KLH was stored at -80 °C, in a manner that ensured each aliquot was only thawed once before use.Conjugation and purification of FITC-KLH was conducted as previously described . To begAn immunization cocktail was mixed to provide broad antigenic stimulation with a single injection. Previously frozen aliquots of peanut extract, FITC-KLH and DNP-Ficoll were thawed and mixed in PBS, to concentrations of 2 mg/ml, 1 mg/ml and 2 mg/ml respectively. The resulting mixture was aliquoted and frozen to -80 °C until use.Table 1The immunization protocol consisted of 6 intraperitoneal injections over 14 days and is summarized in Tissue extracts were prepared by a method similar to that previously described . These TM Gel). The standard wells of each gel were loaded with 5 µL of a molecular weight standard (PageRuler Plus). Once loaded, protein electrophoresis with SDS PAGE was used to separate the antigen mixture. Brain and liver extracts were run at 45 V for 4 hr 50 min; kidney extract was run at 55 V for 4 hr; lung and prostate extracts were run at 65 V for 3 hr 15 min, and spleen extract was run at 70 V for 3 hr.Once collected, washed and homogenized, organ extracts were loaded onto PVDF membranes for immunoblotting. For this purpose, 280 µL of each organ extract  was mixed with 108 µL SDS sample buffer (4x) , and 43 µL sample reducing agent (10x) (Novex NuPAGE®). Each mixture was vortexed, boiled for 7 minutes at 100 °C, vortexed again and centrifuged for 7 minutes at 15,996 x g. Subsequently, a 200 µL volume of each antigen mixture was loaded into the large well of each of two 4-12 % acrylamide gradient preparation gels . PVDF membranes were blocked for 70 minutes at room temperature using 1.0 bovine serum albumin, 0.1 % Tween 20, and 1x sodium azide in Tris buffered saline (blocking buffer). Each membrane was then cut into 16 strips (excluding the standard strip), each 4 mm wide.Once separated, antigens were transferred to PVDF membranes for 7 minutes at 20 V using an iBlotTM NBT-BCIP  was used to develop the strips. Strips incubated in goat anti-rat IgG were developed for 28 minutes with fresh developer added after 14 minutes. Alternatively, strips incubated with goat anti-rat IgM were developed for 7 minutes. To conclude the process, all strips were washed with distilled water twice for 6 minutes each and air dried.Sera were randomly selected from 8 of the 20 immunized rats and 8 of the 11 non-immunized rats. Membrane strips were incubated overnight at 4 °C with specific rat sera diluted 1/400 in blocking buffer. A control strip was incubated overnight in blocking buffer to account for anti-IgG and anti-IgM conjugate binding directly to organ-derived antigens. The next morning, the strips were washed 3 times for 10 minutes each with Tris buffered saline. Strips were then incubated for 1 hour at room temperature in alkaline-phosphatase conjugated, affinity purified goat antibody diluted at 1/1000 in blocking buffer. Goat antibody specific for the Fc region of rat IgG (Sigma-Aldrich) was used to detect natural IgG binding. Meanwhile, goat antibody specific for rat µ-chain (Sigma-Alrich) was used to detect natural IgM binding. After 1 hour, strips were washed another 3 times for 10 minutes each in Tris buffered saline. Once washed, 1-StepDried blots were scanned and Quantity One software v. 4.6.6 (Bio-Rad Laboratories) was utilized to quantify the substrate development on each image, corresponding to the amount of natural antibody binding to antigens. For each blot, the image intensity was manually adjusted to eliminate background noise, and the sensitivity was manually configured to maximize the congruency between the computer detected bands and the bands detectable to the investigator upon visual inspection. Similarly, the noise filter was adjusted to account for artifacts, typically small, that did not correspond to protein bands on the gel.Natural antibody binding was quantified by several measures. The size of a single band was calculated by plotting a curve of the average intensity of all pixels in each row of the band against the band length. The area under this curve was taken as the size (Intensity x mm) of that band. Once all bands were identified, the size of the bands on the control strip was subtracted from the corresponding bands on all other strips. If the band size on the control strip was greater than the band size on an experimental strip, then this band was excluded from all analysis. The average band size associated with the serum of a given animal was defined as the average of all band sizes in a single strip, and the average band size for the group was calculated using the mean band size of all the blots in that group. The number of bands detected was taken as a measure of the number of antigens recognized by the natural antibody repertoire. Subsequently, the total natural antibody binding for a particular organ extract was taken as the sum intensity of all bands. Both total binding and band size were measured in arbitrary units of intensity that depend on developing time and exposure among other factors such as the nature of the enzyme conjugate. With that in mind, both measures were normalised to the mean of the non-immunized group. All calculations were performed for IgM and IgG antibody isotypes.The natural antibody binding characteristics of the sera from non-immunized and immunized rats were compared with unpaired, two tailed t-tests. All calculations were performed with Graphpad Prism Software .A typical blot pattern using sera from immunized and unimmunized animals is shown in Figure 1Natural IgM from immunized rats, on average, recognized significantly more antigens than the natural IgM from non-immunized rats, regardless of which organ the antigens were from Figure 2. NaturalNatural IgG from the sera of immunized rats recognized an average of 14 % more antigens per organ than the natural IgG from the sera of non-immunized rats. Subsequently, the range of immunization-associated difference in IgG repertoire was also smaller than that of IgM. The IgG from immunized rats recognized 18 % more liver antigens than the IgG from non-immunized rats, and this was the largest difference observed. Meanwhile, the immunization-associated difference in the average number of lung antigens recognized by IgG was less than 1 % and not statistically significant. Furthermore, the immunization- associated differences in the number of antigens recognized by IgG were only statistically significant with respect to antigens from the brain and the liver.The average band size was quantified using Bio-Rad quantity one software as described in the 'Methods' section. It was then normalized to the average band size produced by the sera of non-immunized rats. This average band size was calculated for IgM and IgG binding in all organ extracts. Whilst band length is included, pixel intensity is the primary variable contributing to band size. The pixel intensity demonstrates how much antibody is bound to the antigen in that specific band. Therefore, average band size can be taken as the strength with which the antibodies bind to antigens. In this case, it represents the average strength of natural antibody binding to antigens extracted from particular organs.Taking the mean of the average band size seen with all organ extracts, the mean average band size produced by IgM recognition of antigens was 19 % greater with the sera of immunized rats compared to non-immunized rats Figure 3. The aveMeanwhile, the average band size produced by natural IgG binding in each organ extract was on average 18 % greater with the natural IgG from immunized rats as opposed to non-immunized rats Figure 3. HoweverThe total binding for each lane was calculated as the sum of all band sizes. The mean total binding for each group was assessed for IgM and IgG natural antibodies and normalized to the mean of the non-immunized group. The quantification of total binding reflects both the range of the natural antibody repertoire (number of bands) and the intensity of natural antibody binding (average band size). That is, the total binding can be approximated as by multiplying the number of bands by the average band size. Thus, an increase in either antibody repertoire or antibody binding strength can increase total binding.Compared to natural IgM from non-immunized rats, the total binding produced by natural IgM from immunized rats was significantly greater with all organ extracts except the spleen Figure 4. The aveIt was noted above that total binding reflects the number of bands and the average band size. With antigens from the kidney, prostate and spleen, the relative immunization-associated changes in the mean number of bands recognized by natural IgM binding were larger than the relative differences in the average band size. Thus, the immunization- associated differences in total binding seen with self-antigens from these organs were more dependent on the expansion of the natural IgM repertoire as opposed to alterations in antibody binding intensity. In contrast, with liver and brain antigens it appears that the immunization-associated difference in total IgM binding was due in greater part to differences in the average band size and thus the intensity of antibody binding, although this finding was not statistically significant.The immunization-associated differences in total binding of natural IgG to organ extracts were not as notable as the differences associated with IgM binding Figure 4. The meaThis study examined how a series of 6 immunizations over 14 days with a variety of antigens affected the natural IgM and IgG antibody repertoires of Sprague Dawley rats. On average, the natural antibodies from the sera of immunized rats produced a greater number of bands, larger average band sizes and greater total binding compared to natural antibodies from the sera of non-immunized rats. This indicates that in laboratory rats, immunization is associated with a larger natural antibody repertoire and stronger antibody binding, both of which contribute to greater total natural antibody binding.Larger immunization-associated differences in natural antibody binding were seen with IgM antibodies compared to IgG antibodies. This fits with the current understanding of immunoglobulin class switching, where the acute phase of primary antigen exposure is characterized by a large IgM response. The short time scale of this experiment (28 days) may explain the isotype-dependent difference since the study was likely terminated before the completion of B-cell class switching. It might be expected that IgM levels would subside during the isotype switching process, coinciding with an increase IgG levels.In vitro and in vivo evidence has shown that DNP-Ficoll induces IgM and IgG responses.Whilst not as large, immunization-associated differences in IgG binding were observed. These changes may be a result of early isotype switching. Alternatively, IgG may have been expressed by B-cells previously primed to environmental exposure to antigens that cross react with the immunization antigens. The immunization-associated differences in IgG binding may also be due to T-cell-independent stimulation. DNP-Ficoll is the prototypical antigen for eliciting Type-2 thymus independent B-cell responses. The time scale of this experiment may also explain disparities in the magnitude of immunization-associated differences in the number of antigens recognized, compared to the differences in the average band size. Looking specifically at IgM, immunization was associated with a 28 % difference in the number of antigens recognized per organ extract, yet only a 19 % difference in the average band size per organ extract. Furthermore, the IgM from immunized rats recognized significantly more antigens in all organ extracts compared to IgM from non-immunized rats; whilst the immunization-associated difference in the average band size was only significant with antigens from 2 organ extracts. These observations suggest that in this experiment, immunization influenced the diversity of the natural antibody repertoire to a greater extent than it influenced increases in antibody binding to specific antigens. It is likely that the acute immune exposure used in this model led to polyclonal B-cell proliferation and an increase in the number of different antibodies produced. However, the acute nature of the exposure may not have allowed sufficient time for B-cell selection, somatic hyper mutation and the resulting affinity maturation that would have increased the strength of antibody binding. On the other hand, any affinity maturation that did occur may have been directed toward the antigens used for immunization without directly affecting the degree of binding toward unrelated targets. Future studies aimed at evaluating the effect of long term immunostimulation on the diversity of the natural IgG repertoire and on the binding strength of natural IgM and IgG antibodies may help further elucidate the processes involved.Neisseria meningitides, Streptococcus pneumoniae and Haemophilus influenza  is a copper containing, oxygen transporting molecule derived from molluscs . Th). Th18])al., 1995[18]). Keal., 2014). It is al., 2014). These The findings of this experiment have several implications for future research and potentially for clinical practice. The results indicate that it is possible to manipulate the natural antibody repertoire of laboratory rats by selective immunization. This can be accomplished relatively quickly (14 days) and without exposing the rats to any pathogens or live organisms. Whilst the immunization protocol did contain highly immunogenic compounds and an adjuvant, it nonetheless successfully influenced the natural antibody repertoire without the need for infection or exposure to potentially infectious organisms. Therefore, it may be possible to utilize immunization to manipulate the natural antibody repertoire in humans for the purpose of preventing or even treating disease.As previously discussed, natural antibodies are important in innate immune defence as well as in cell surveillance and subsequently, cancer prevention. Indeed, non-specific effects of vaccination have been characterized in both animals and humans. These effects seem to have both positive and negative outcomes depending on such factors as gender and the specific nature of the vaccine schedule. Most studies have examined associations between immunization schedules and rates of illness across populations of children in low-income countries. For example, a randomized trial in children recruited through the Bandim Health Project suggested that, based on mortality rates by age 3, there may be a beneficial nonspecific effect of a two dose vaccination for measles at 4.5 months and 9 months, as opposed to the current approach of vaccinating against measles once at 9 months only . ThusIn the future, the Western world will likely turn to artificial stimulation of immune function for health. Vaccination is only one form of such stimulation. Indeed, “helminthic therapy” is already being used by many (Cheng et al., 2015; Liu et As Western society continues to make progress toward the eradication of infectious diseases, the possibility exists that immunization will transition from a tool to prevent infectious disease into a means of promoting healthy immune function and development. This study suggests that immunization may in fact be helpful in order to develop a natural antibody repertoire that is necessary for efficient surveillance of cancer, and that this function of immunization may be most critical in a hypothetical environment of the future which lacks infectious disease.


Predictive factors including risk perception for mid-term mental health after a nuclear disaster remain unknown. The purpose of this study was to examine the association between perceived radiation risk and other factors at baseline and mid-term mental health after the Fukushima Daiichi nuclear disaster of 2011 in Japan. A mail-based questionnaire survey was conducted in January 2012 and January 2013. Mental health status was assessed using the K6 scale. Psychological distress over the 2-year period was categorized into the following four groups: chronic, recovered, resistant, or worsened. Most participants (80.3%) were resistant to the disaster. A positive association was found between the radiation risk perception regarding immediate effects and the worsened group in women. Baseline post-traumatic stress disorder (PTSD) or a history of psychiatric disease predicted being in the chronic or worsened group in mid-term course. These results suggest that evacuees who believed that their health was substantially affected by the nuclear disaster were at an increased risk of having poor mid-term mental health in women. Careful assessment of risk perception after a nuclear disaster, including the presence of PTSD or a history of psychiatric disease, is needed for appropriate interventions. Although post-traumatic stress disorder (PTSD) is the most common psychiatric reaction to disaster, depression, which often coexists with PTSD , is alsoMany studies have reported risk factors for mental health after disasters, suggesting that disaster exposure ,6,7, genAfter the Chernobyl nuclear power plant accident in 1986, exposure to a nuclear disaster , female The Fukushima Health Management Survey is a mail-based questionnaire survey focusing on lifestyle and mental health among adult residents (aged ≥15 years on 11 March 2011) of the evacuation zone designated by the Japanese government  ,28 that The outcome of this study was scores on the K6 scale , which iOnly the participants who responded to the K6 scale in both FY2011 and FY2012 were included in the analysis. Based on K6 scores from both years, we divided mental health status over the 2-year period into the following four groups: chronic group (K6 score ≥ 13 in both FY2011 and FY2012); recovered group (K6 score ≥ 13 in FY2011 and <13 in FY2012); resistant group (K6 score < 13 in both FY2011 and FY2012); and worsened group (K6 score < 13 in FY2011 and ≥13 in FY2012). To investigate predictive factors for mid-term mental health status, we focused the changes in psychological distress (K6) from baseline. We used logistic regression analysis to investigate the predictive factors at baseline associated with: (1) worsened group  and (2) recovered group . Multivariate logistic regression analysis adjusting all predictors ) were used. We analyzed males and females separately because gender may have effects on mental health status after disaster ,37. All The baseline characteristics of the four groups are shown in The prevalence of being at high risk for psychological distress (K6 score ≥ 13) was 14.3% in FY2011 and 11.7% in FY2012, which are relatively high compared with the data of non-disaster settings in Japan  . In thosResults from univariate and multivariate analyses of potential factors for the recovered group compared with the chronic group are shown in Among women, the perceived risk that immediate effects were likely  or very likely  was negatively associated with the recovered group . In multTo the best of our knowledge, this is the first longitudinal study conducted to investigate the association between perceived radiation risk at baseline and mid-term mental health after a nuclear accident in a large sample. In this study, most (80.3%) of the 36,056 evacuees were resistant to the disaster. This is consistent with a previous finding that few people develop chronic mental disorders after traumatic events . Our resWe also found that the degree of perceived radiation risk predicted the degree of worsening mental health status after the disaster, although multivariate analysis revealed that the association between perceived radiation risk regarding immediate effects and the worsened group remained significant among only women after controlling for individual and disaster-related factors. This finding was consistent with that from a recent cross-sectional study demonstrating that perceived radiation risk was associated with psychological distress after the Fukushima disaster . PreviouHaving PTSD symptoms related to the nuclear disaster at baseline was significantly associated with mental health status during the 2-year period of this study; this finding was consistent with those from previous study  reportinOur results regarding the positive association between the worsened group and not living in one’s own home are consistent with those from a previous systematic review  reportinThis study did have several limitations. First, a relatively low proportion of the target population was included in the analysis, which might have affected the interpretation of the results. Previous studies ,47 showeIn summary, we found a significant association between perceived radiation risk regarding immediate effects and mid-term mental health after a nuclear accident in women, indicating that female evacuees who believe that their health is highly affected by a nuclear accident are at an increased risk of poor mid-term mental health. Although it is difficult to generalize these findings to other disasters, the assessment of perceived risk and other predictors such as PTSD symptoms or a history of psychiatric disease is needed in order to promote careful intervention for affected populations.


Developing multiple soft tissue sarcomas (STSs) is a rare process, sparsely reported in the literature to date. Little is known about the pattern of disease development or outcomes in these patients. Patients were identified from three tertiary orthopaedic oncology centres in Canada and the UK. Patients who developed multiple extremity STSs were collated retrospectively from prospective oncology databases. A literature review using MEDLINE was also performed. Six patients were identified in the case series from these three institutions, and five studies were identified from the literature review. Overall, 17 patients were identified with a median age of 51 years (range: 19 to 77). The prevalence of this manifestation in STS patients is 1 in 1225. The median disease-free interval between diagnoses was 2.3 years (range: 0 to 19 years). Most patients developed the secondary STS in a metachronous pattern, the remaining, synchronously. The median survival after the first sarcoma was 6 years, and it was 1.6 years after the second sarcoma. The 5-year overall survival rate was 83.3% and 50% following the first and second STS diagnoses, respectively. A diagnosis of two STSs does not confer a worse prognosis than the diagnosis of a single STS. Developing a second STS is a rare event with no identifiable histological pattern of occurrence. Presentation in a metachronous pattern is more common. A high degree of vigilance is required in patients with a previous STS both to detect both local recurrence and to identify new masses remote from the previous STS site. Acquiring an early histological diagnosis should be attempted. Soft tissue sarcoma (STS) is a general term assigned to a group of rare malignant tumours arising from a mesenchymal stem cell. The term “sarcoma” encompasses approximately 100 different histological subtypes of tumour as per the latest World Health Organization Classification of Tumours of Soft Tissue and Bone (4th edition) . PrognosCommonly, the primary complaint of a patient presenting with a suspected soft tissue sarcoma is the presence of an enlarging, painless mass. Detailed evaluation of the mass and its association with surrounding structures is crucial . CertainAlthough uncommon, patients with STS have an increased risk of developing a second primary neoplasm (carcinoma), even when excluding known syndromic associations such as Li–Fraumeni syndrome and neurofibromatosis , 9. OutsTwo tertiary sarcoma centres in Canada and one in the United Kingdom collaborated in this study. A retrospective review from 1997 to July 2017 was conducted using the prospectively collated oncology databases at each centre. Electronic notes were searched using a combination of the following terms: “sarcoma,” “multiple,” “new,” “different,” “synchronous,” and “metachronous.” A list of patients was generated when the database notes indicated the possibility of a second primary soft tissue sarcoma. Patients with two or more histologically confirmed extremity STSs were manually identified. Clinical information including the patient demographics, pathologic diagnosis, tumour site, operation, and survival outcomes were gathered from clinical notes. Diagnoses were made by specialized musculoskeletal pathologists at the three centres. No minimum follow-up criteria were assigned in order to maximize inclusion.In most cases, access to both STS specimens was available to allow direct comparison for accurate histological diagnosis and to distinguish this from a distant soft tissue metastasis of the original primary sarcoma or a radiation-induced sarcoma. Cahan's criteria were used to discern a second primary sarcoma from an iatrogenic sarcoma secondary to radiation, which are a latency period of at least 2 years, the tumour must arise in the direct region of previous radiation, and the sarcoma must be histologically different from the previously radiated lesion .A search was conducted using the MEDLINE OVID interface from 1946 to July 2017. The search strategy used was [Sarcoma OR ST neoplasm] AND [synchronous OR metachronous]. Inclusion criteria included English, human studies with one or more of the subjects with multiple sarcomas. This yielded 157 results, of which five papers were identified that met the inclusion criteria . Manual Patients identified in our case series and in the literature review with desmoid tumours, Kaposi sarcoma, and gastrointestinal stromal tumours (GISTs) were excluded from the study due to their unique disease pattern which differs from that of other STSs.n=7351), this amounted to a prevalence of 0.08%. The median age of the patients in our series was 54.5 years (range: 28 to 67). Five (83.3%) of the patients were male, and the other was female. The median interval between the diagnosis of the primary and secondary sarcomas was 2.7 years (range: 0.1 to 4.6 years).Six patients were identified to meet the study inclusion criteria after detailed interrogation of the databases from the three tertiary orthopaedic oncology centres. Amongst all patients with STS at these centres (Four (66.7%) patients developed sarcomas in a metachronous pattern. The diagnosis interval for the remaining two patients was 1 and 5 months. Although both primary tumours were not diagnosed at the same time, the interval is short enough to be considered a synchronous pattern. Four patients developed their second STS on the ipsilateral side to the first, three of which occurred in different areas of the same limb, while the fourth patient's first STS occurred in the hand followed by one in the lower limb. Liposarcoma was the most common diagnosis, followed by undifferentiated pleomorphic sarcoma .The median time from first sarcoma diagnosis to last follow-up was 7.7 years (range: 0.8 to 12.9). Five (83.3%) patients were alive with no evidence of disease at last follow-up. One patient developed a local recurrence 33 months after resection of their second sarcoma; however, this was resected, and the patient remained free of disease before dying 7 years later with no evidence of sarcoma recurrence. Two patients developed metastasis amenable to complete metastasectomy at 2 and 60 months after the first and second STS excision, respectively. Following metastasectomy, these patients had no evidence of disease at 10.1 and 3.2 years of follow-up.All patients were managed under the care of a sarcoma multidisciplinary team (MDT), with treatment following international guidelines active at the time. One patient was treated with radiotherapy for both sarcomas, while five patients received radiation for only one of their two sarcomas. Of the patients who underwent radiotherapy for only one sarcoma, two received it for the first sarcoma and three for the second sarcoma. No patients received adjuvant chemotherapy treatment.Postoperative surveillance comprised clinical examination for evidence of local and regional recurrence with subsequent magnetic resonance imaging (MRI) based on concerning clinical findings and chest radiography with subsequent computerized tomography (CT) to confirm metastasis based on abnormal radiographs. Follow-up occurred at 3-month intervals for the first 2 years, 6-month intervals until 5 years, and annually until 10 years following resection as per international guidelines .Five patient series were identified that included patients with multiple different histologically confirmed STSs , 12–14. n=8, 23.5%) followed by liposarcoma  and leiomyosarcoma . From available data, 7 (53.8%) patients' second tumours arose on the contralateral side and 6 (46.2%) on the ipsilateral side. Overall, tumours presented as high grade (grade 3) in 57.1% of cases, intermediate grade (grade 2) in 28.6% of cases, and low grade (grade 1) in 14.3% of cases  including 9 males and 6 females (two patients' sex were not reported). The median interval between the first and second STS diagnoses was 2.3 years (range: 0 to 19). This included 6 (35.3%) synchronous manifestations of multiple sarcomas and 11 patients (64.7%) that developed distinct tumours in a metachronous pattern. The most common diagnosis was undifferentiated pleomorphic sarcoma (The median time from first tumour diagnosis to death or last follow-up was 6 years (range: 0.2 to 26). The 5-year overall survival rate was 83.3%. Median survival time from the second sarcoma diagnosis was 1.6 years (range: 0 to 19) with a 5-year disease-free survival rate of 50%. Overall, six patients were deceased, and 11 were alive with no evidence of disease at last follow-up.One series which included four patients did not report information on adjuvant therapy . From thA case series of 6 patients and literature review of 11 patients were conducted on multiple primary STSs occurring in individual patients. The aim of the study was to determine the impact developing a second primary STS had on overall survival and whether there are any predictable histological or chronological patterns to disease presentation. We hoped to better enable clinicians to provide a prognosis when faced with these patients as well as to advise on routine STS follow-up. The prognosis in these patients was found to be poor relative to patients with one STS diagnosis, and no predictable patterns of disease presentation were identified.There are many possible explanations for the development of multiple sarcomas in a single patient. One possibility is that these patients may have a genetic predisposition to malignant mesenchymal disease that is currently not described. Alternatively, general risk factors for malignancy may have been the underlying cause such as immunocompromise or exposure to carcinogens, either environmental or iatrogenic. These factors have been associated with the formation of cancers –17, althThe median survival time from the first STS diagnosis was 6 years; however, it was only 1.6 years after the second STS diagnosis. The 5-year disease-free survival was 83.3% and 50%, after the first and second STS diagnoses, respectively. The American Cancer Society reported the mean 5-year survival rate of STS as 64% in 2017 . IsolatiThe prevalence of a patient with one STS developing a second STS is low, 0.082% or 1 in 1225. Grobmyer et al. were also able to determine the incidence of developing two STSs. They reported that, in a patient previously diagnosed with STS, the incidence of a second primary sarcoma was 1 per 2500 population, or 12.5 times greater than the standard incidence of STS , 19.No identifiable patterns were identified in terms of distinct STS subtypes presenting together in the same patient. The type of sarcoma that arises secondarily appears to be random, independent of the first sarcoma diagnosis. The time used to define synchronous development was 6 months or less between diagnoses. This cutoff time was chosen as it would be too narrow of an interval to develop two individual primaries meaning that the second tumour likely went unrecognized previously. The median time between sarcoma diagnoses was 2.3 years. Approximately one-third of patients developed the second sarcoma in a synchronous pattern, while in two-thirds, the second sarcoma developed metachronously. Therefore, more attention should be paid to identifying a second STS in patients during the postoperative follow-up period. Over recent years, there has been an increase in the use of whole-body staging studies, such as fluorodeoxyglucose positron emission tomography (FDG-PET) or whole body MRI. This may lead to an earlier detection of a second primary tumour in those patients who are undergoing staging at the initial diagnosis but also have a synchronous second primary STS. However, the cost and availability associated with the routine use of these tests need to be considered in light of the rarity of a diagnosis of a second soft tissue sarcoma.The occurrence of a second STS in the same patient is very rare, and therefore, no change to the management of new patients or patient follow-up is recommended. During follow-up visits for a primary STS, a short screening phrase such as “Have you noticed any new lumps or bumps?” is recommended to raise attention to any newly developing masses. Any second mass a patient develops should not be presumed to be the same disease, and new histological diagnosis should be made. Therefore, we recommend reimaging, restaging, and a biopsy to help diagnose new disease, including radiation-induced tumours, from recurrence or metastasis . In factUnfortunately, several limitations to interpreting these figures exist including the short follow-up period of many patients. Only 12 of the 17 patients had follow-up to five years after diagnosis of their first sarcoma. As well, all patients from one series had very short survival after the second STS diagnosis, which may have skewed the results . AnotherFurther research is recommended as current available evidence is limited. Larger series of other orthopaedic oncology centres' experience and more case reports are encouraged to increase the amount of described information. This will hopefully help to uncover any patterns of disease occurrence which may lead to identifying risk factors or certain genetic predispositions.In conclusion, this study aimed to help define the pattern of disease and outcomes in patients with nonsyndromic, non-radiation-induced multiple extremity STSs. The incidence of this scenario is very low, and more reports are encouraged. This study was unable to definitively demonstrate that patient prognosis with multiple STSs is poor relative to those diagnosed with a single sarcoma. A high index of suspicion should be maintained to detect a second STS in patients with a current or previous primary STS as they are at an increased risk compared to the general population. Our results demonstrate that majority of patients with multiple STSs present in a metachronous pattern of disease and require routine long-term screening. Management of the second sarcoma should continue in line with internationally recognized guidelines. The recommendations for practice include thorough screening for any new symptoms as well as ensuring a second histological diagnosis is made in the setting of a new mass.