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of Pride
Funders &
Board of
Facilitating Action
Leading with Data
Patient-Centered Care
Systems Transformation
Voices of Communities
Supporting Families of Children and Youth with Special Health Care Needs
Risk, Resiliency, and Coping in National Guard Families
Working Collaboratively for Social Justice: "Michigan Power to Thrive"
Spirit of Community Health: Exploring Characteristics of Tribal Public Health System Organization and Performance
Helping Children with Genetic Conditions Gain Access to Optimal Services
© 2015 MPHI | www.mphi.org
MPHI received funding from the federal Health Resources and Services Administration (HRSA) in 2013 to house and manage the "Michigan Family-to-Family Health Information Center" (F2F). The center provides information, education, technical assistance, and peer support to families of children and youth with special health care needs (CYSHCN) and the professionals who serve them. To date, MPHI has accomplished the following. To date, MPHI has accomplished the following:
Provided educational opportunities for families of CYSHCN
Provided educational opportunities for professionals to build family/professional partnerships and promote a family-centered, community-based, and culturally competent system of care
Collaborated with state committees and councils to address barriers and participate in opportunities to improve systems of care through the six national 2010 objectives for CYSHCN
Provided technical assistance, information and resources to families and CYSHCN
Launched a statewide information repository on the F2F website and developed a "Tell Your Story" feature to collect family stories and trends
Providing educational opportunities for families of CYSHCN
Purchased "Parents Partnering for Change" training to help parents develop skills and knowledge that enable them to be active participants in their communities
Partnered with Region 4 Midwest Genetics Collaborative to offer "Care Coordination: Empowering Families" training, which provides parents with skills, knowledge, and resources to enable them to coordinate care for children who have complex needs, in partnership with a culturally competent medical home ‒ 78 parents have participated in the one-day training to date
Partnered with Michigan Consumers for Healthcare to provide a webinar on the Affordable Care Act and how it impacts families of CYSHCN ‒ 71 people participated in the live webinar and there have been 117 views via the website to date
Providing educational opportunities for professionals to build family-professional partnerships and promote a family-centered, community-based, and culturally competent system of care
Attended the Developmental Disabilities Conference and interacted with 100 families and 200 professionals, promoting F2F
Conducted outreach to provider professional organizations
Developed and launched the F2F website, providing resources to health care professionals
Participated in a regional community resource mapping meeting with disability-related organizations
Partnered with the Michigan Primary Care Transformation project to provide a webinar on parent-professional partnerships and how to engage families in building a family-centered practice; the webinar targeted care coordinators in primary care practices
Presented "Caring for the Caregiver" to professionals and parents at the Parenting Awareness Michigan Conference
Collaborating with state committees and councils to address barriers and participate in opportunities to improve systems of care through the six national 2010 objectives for CYSHCN
Established 27-member F2F Advisory Board
Represented families as a member of Children's Special Health Care Services' Advisory Board and the State of Michigan Newborn Screening Quality Assurance Advisory Committee
Providing technical assistance, information and resources to families and CYSHCN
Partnered with Michigan's Children's Special Health Care Services' Family Center and Family Phone Line to coordinate activities and resources
Developed and launched the F2F website to provide resources for families and caregivers
Established F2F Facebook page to share information and connect parents
Published six electronic newsletters
Partnered with Newborn Screening to provide educational materials on navigating insurance coverage for metabolic formulas
HRSA recently awarded MPHI a second grant, which extends the project to 2018. For more information visit https://f2fmichigan.org/ .
In 2012, MPHI received its first grant from the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health Traumatic Brain Injury Research Program to conduct a longitudinal study of "Risk, Resiliency, and Coping in National Guard Families." This three-year study followed a battalion of soldiers that deployed from the Michigan National Guard, collecting data from the soldiers and their spouses/significant others and parents. Quantitative and qualitative methods were used to expand our understanding of stress and adaptation associated with war-time deployments for National Guard families.
The quantitative portion of the study used a survey method to collect individual and family outcomes and process measures 90 days, one year, and two years following the battalion's return from Afghanistan. Outcome data were then linked to data collected by university partners before deployment; more than 650 families were represented in the data set.
The qualitative portion of the study included three in-depth, 90-minute interviews with a sub-sample of 30 families. The interviews were conducted in the family home approximately six, 18, and 30 months following the soldier's return from Afghanistan.
MPHI provided project management, study design, online data collection, data management and warehousing, and analysis and dissemination of findings. Project partners included the Michigan National Guard, Michigan State University, the University of Michigan, Virginia Polytechnic Institute & State University, and Ann Arbor Veterans Administration Healthcare.
The project has led to improved understanding of deployment processes for military families. Community partners will use the findings to inform development and adaptation of evidence-based family and community-resilience programs, and to enhance methods that build and sustain strong relationships within military families.
Findings have been presented at the following conferences.
2014 Military Health System Research Symposium, Ft. Lauderdale, FL
34th Congress of the International Academy of Law and Mental Health, Vienna, Austria
2015 American Association for Marriage and Family Therapy Annual Conference, Austin, TX
2015 International Society for Traumatic Stress Studies Annual Meeting, New Orleans, LA
2015 National Council on Family Relations Annual Conference, Vancouver, BC, Canada
Study team members will continue to analyze data and disseminate results through peer-reviewed journals.
"Michigan Power to Thrive" (MPTT) is a network of eight local health departments and six local affiliates of GAMALIEL of Michigan, all working cooperatively for social justice since 2013. MPTT is part of a larger movement within public health to adopt community-organizing practices in order to advance a health equity framework. The network's first two years were spent building relationships between the two disciplines and cross-training. Early efforts to mount a multi-county campaign focused on adoption of a "Health in All Policies" decision-making strategy by city and county governments.
MPHI coordinates this network as part of its "Center for Health Equity Practice," with funding from ISAIAH, Inc., a faith-based organizing group based in Minnesota, and the National Association for City and County Health Officials.
In August 2015, MPTT held an issues convention exploring eight possible issue targets to pursue collectively. The two issues of most interest were mass incarceration/mass deportation and early childhood development. Work teams met again in October and November after engaging in one-to-one interactions with people knowledgeable about the current policy landscape for both issues. The mass incarceration/mass deportation workgroup is focusing on employment supports for formerly incarcerated people and driver cards for undocumented residents. The early childhood development workgroup is focusing on alternatives to expulsion from preschool for 3- and 4-year olds.
To mobilize communities around the issue of early childhood development, local MPTT partners worked together on community screenings of episodes from the documentary series, The Raising of America. These episodes make clear the importance of attending to a child's development in the first years of life from multiple perspectives, including health, social stability, economics, and recovery from trauma. They also advance a larger narrative to counter what has been called the "school-to-prison" pipeline ̶ the early traumatization and stigmatization of black and brown children, limiting their access to the opportunities and resources needed to achieve well-being.
The principal organizations involved in Michigan Power to Thrive are local health departments in Calhoun, Genesee, Ingham, Kalamazoo, Kent, Saginaw, Washtenaw, and Wayne Counties, and the local faith-based organizing affiliates of GAMALIEL of Michigan: MOSES (Detroit), WeROC (Ypsilanti), ACTION of Greater Lansing, ISAAC (Kalamazoo), The Ezekiel Project (Saginaw), and JONAH (Battle Creek).
National health data reveal that American Indian/Alaska Native (AI/AN) people experience poorer health outcomes and have shorter average life expectancy than the overall U.S. population. Addressing the causes of poor health and early death requires interventions outside of a medical office ‒ preventive services, chronic care management, community-based services ‒ which are inherent to public health. Yet, Native American tribes often face challenges to improving public health, such as social inequities, cross-cultural and jurisdictional barriers, limited access to health care, and lack of parity in financial resources. It is imperative that Tribal health agencies are able to determine how they can improve tribal members' health through the delivery of essential public health services.
The Robert Wood Johnson Foundation's "Public Health Services and Systems Research" grant program funded MPHI to conduct a study to help build an evidence base around how tribes organize and partner to deliver public health services. MPHI conducted an examination of a single tribal public health system, exploring how and through what relationships it delivered public health services, and assessing the key characteristics that addressed health disparities. Data sources included interviews and ecomaps with public health system partners, focus groups with community members, secondary data, and document review. The study followed the principles of tribal community-based participatory research and involved participants in creating and disseminating knowledge.
Findings suggested many future directions for research and practice, including the following.
A great need for additional resources to support development of tribal public health laws and policies
The importance of sustainable and flexible financing for tribal public health services
The potential value of practice-based evidence that emphasizes community wisdom and culture
Opportunities that exist for the public health field to learn from Tribes about the potential benefits and pitfalls of the integration of public health and health care
Valuable insight that can be gained by having a research agenda for tribal public health systems and services
A full report of the results, a policy brief, and practitioners' toolkit can be found here: https://www.mphi.org/tribalhealth/ .
Since 2004, the "Region 4 Midwest Genetics Collaborative" (Region 4) has been funded by the federal Health Resources and Services Administration to facilitate partnerships to ensure children who are born with rare genetic conditions receive optimal genetic services. Region 4 is housed at and managed by MPHI, which provides fiscal management, strategic direction, project coordination, and facilitation. Partners include genetic experts, health care providers, state newborn screening laboratory and follow-up programs, and families. Stakeholders from seven states ̶ Illinois, Indiana, Kentucky, Michigan, Minnesota, Ohio, and Wisconsin ̶ participate in Region 4.
Current Efforts
Work is accomplished by engaging stakeholders in workgroups and/or stakeholder forums, which address the following goals.
Facilitate collaboration
Improve effective follow-up for children
Improve access to genetic services
Increase the number of children who receive quality genetic services
Improve the adoption and implementation of recommendations from the Advisory Committee on Heritable Disorders in Newborns and Children
An example of Region 4's work is the "Care Coordination: Empowering Families" training, which provides parents with the skills, knowledge, and resources they need to coordinate their children's complex health care needs in partnership with a medical home. More than 270 caregivers of children with genetic conditions have been trained; 144 of them were trained through partnerships with the Michigan Department of Health and Human Services' Children's Special Health Care Services and the Michigan Family-to-Family Health Information Center (also housed at MPHI). With support from the Genetic Alliance, 40 facilitators have been trained; facilitators are now available in 12 states.
At Region 4's 2015 Annual Meeting, staff utilized the HRSA-funded Heartland Genetic Services Collaborative's "Genetic Service Assessment" quality measurement tool to collect data on genetic services in the region. The information will be used in a regional needs assessment to identify strengths and gaps in genetic services. Another component to the needs assessment is the access-to-genetic-service-providers mapping project, which will examine the number of birth defects in the region by county and provide information on the spatial distribution of genetic services providers. Region 4 plans to expand this assessment by using partnerships with state public health programs to obtain newborn screening data. Further measures to be examined include distance-to-care metrics and a genetic condition trend analysis by county.
Additional Priorities
Region 4 will continue to address the following needs the collaborative identified as priorities for the 2012-2017 grant cycle.
Cross-state technical assistance and resources to advance implementation of lysosomal storage disorders (50 rare inherited metabolic disorders that result from defects in lysosomal function)
Education and long-term follow-up resources for congenital hypothyroidism
Implementation and evaluation of sickle cell trait short-term follow-up recommendations, developed through facilitated consensus methods with regional experts
For more information, please visit http://region4genetics.org .


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Every Batman Movie Ranked, From Worst to Best
We ranked 75 years of Batman movies in one list.
Fire up the Batcomputer for Some 'Batman Begins' Facts
If you've seen Christopher Nolan's Batman Begins, you probably remember the great scene where Bruce Wayne (Christian Bale) and Ducard (Liam Neeson) fight on a frozen lake. But did you know that all throughout the day Bale and Neeson shot this scene, they could hear cracks in the ice beneath their feet? When the crew returned to the lake the next day, the entire thing had thawed. Yikes. That's just one of the facts featured in the newest episode of You Think You Know Movies!
Joseph Gordon-Levitt Says The Dark Knight Trilogy Had the Perfect Ending
In today's superhero movies there's no such thing as a finite ending. Everything feeds into a sequel, spin-off or remake within Marvel and DC's larger cinematic universes. Superhero franchises have become giant movie making machines where endings become teases for the next installment. But the one outlier of that cyclical trend was Christopher Nolan's The Dark Knight trilogy, which began before Marvel dominated movie screens.
A Brief History of Movies Compared to Chris Nolan's Batman
This week, an interview with Bryan Cranston made the rounds in which the actor compared the new Power Rangers movie to Christopher Nolan's The Dark Knight. Baffling as that analogy may seem, it's far from the first time that we've heard an actor, filmmaker or producer compare a forthcoming project to Nolan's Batman films — something that's become shorthand for "gritty reboot." Here, we've collected a brief history of the many, many, MANY times that people have compared their films to Nolan's Batman. As you can imagine, most — if not all — of these things were nothing like those Batman films.
Britt Hayes
Christopher Nolan's Contribution to 'Batman vs. Superman'
Though Christopher Nolan executive produced Batman v. Superman, he didn't have much involvement in the film and took a backseat after being highly active as a producer on Man of Steel. But the Dark Knight director did have some input on the newest Batman movie, including one of the film's most crucial scenes...
Zack Snyder Says He Received Christopher Nolan's Blessing
Christopher Nolan delivered a solid trilogy of Batman films (okay, two really good Batman movies and a competent sequel we begrudgingly accept) and inspired a wave of gritty blockbuster imitators. His Dark Knight trilogy gave us the best Batman movies since Tim Burton's time with the iconic superhero, which made fans feel a little skeptical about Zack Snyder and Ben Affleck's plans for the character. In an attempt to soothe your fears — however reasonable and totally justified they may be — Snyder has revealed that he received Nolan's blessing for Batman v Superman: Dawn of Justice. So that's something, right?
Christopher Nolan Reportedly Producing an 'Akira' Trilogy
A live action remake of the beloved 1988 anime Akira, based on Katsuhiro Otomo's hugely popular manga of the same name, has been floating around Hollywood for over a decade, attracting and dropping actors and directors at a shocking rate (at one point, Garrett Hedlund and Kristen Stewart were set to star). For whatever reason, this film doesn't want to get made. But Warner Bros. isn't giving up on this project and if a new rumor is to be believed, they've officially reached out to one of the most powerful and popular filmmakers in their regular employ to make it happen. So, how do you feel about not one, but three Akira films produced by Christopher Nolan?
Jacob Hall
15 Facts You May Not Have Known About 'The Dark Knight Rises'
Anne Hathaway memorably played Catwoman in The Dark Knight Rises, but she very nearly played another catty superhero. The Oscar-winning actress was set to play Black Cat in Sam Raimi's Spider-Man 4, which would have also featured John Malkovich as Vulture. That film was canceled shortly before filming and Sony eventually decided to reboot the whole franchise. That's just one of the facts packed into the latest episode of You Think You Know Movies, which goes completely batty with The Dark Knight Rises!
'Kick-Ass' Director Matthew Vaughn Says Audiences "Have Had Enough" of Dark Superhero Movies
As 'Batman' goes, so goes comic-book movies. When Tim Burton turned the Dark Knight into a retro-gothic hero, Hollywood followed suit with a slew of heavily stylized pulp throwbacks. (See: 'Dick Tracy,' 'The Phantom,' 'The Shadow,' etc.) And when Christopher Nolan turned the Dark Knight into, well, 'The Dark Knight,' it sparked a wave of "grim and gritty" movies, with serious superheroes doing and saying serious things in outrageous spandex costumes that had been reimagined as biker gear or body armor. (See: 'Man of Steel' [Or maybe don't.]) There's been some pushback, but we're really only now coming out of the trend toward ultra-serious, uber-dark comic-book movies.
Read the 'Interstellar' Prequel Written By Christopher Nolan
Like so many major films released these days, 'Interstellar' has a comic book tie-in. But unlike most comic book tie-ins, this one is actually written by the original film's director and is premiering online. And yes, you can read the whole thing right now, free of charge. We're going to jump straight into spoilers right at the end of this sentence, so if you haven't had a chance to see Christopher Nolan's science fiction adventure yet, you may want to consider turning around.

redpajama_set_name: RedPajamaCommonCrawl


Your Say: What is your favourite tinted lip balm for soft lips and barely there lip colour?
Every year when Summer rolls around, thoughts turn to light makeup. For a few months in a year, most of the world knows what it feels like to live in Malaysia – hot, humid, and sweaty. Not a very conducive environment to wear heavy makeup! LOL!
It's no wonder then that thoughts also turn to light, tinted lips in place of opaque, bold lip colours.
With this in mind, a reader asked me on Instagram, how I'd compare some of my favourite tinted lip balms, in particular, with the introduction of the Chanel Les Beiges Healthy Glow Lip Balm earlier this year.
I thought this was an interesting question. I was also curious to know if you have any favourite tinted lip balms for that barely there, transparent tint of colour on lips, on days when you're just not arsed to wear lipstick. Do share!
The Chanel Les Beiges 2018 collection expands and I think that's great!
In what has quickly become a favourite capsule makeup collection release of mine, the Chanel Les Beiges 2018 grabbed my fancy quite quickly. I previewed the items in the inaugural Beauty hors d'oeuvres segment, and I've finally had a go at some of the key releases.
As a range, the Les Beiges collection focuses on light makeup, laying emphasis on beautiful, healthy glowing skin, barely there makeup and a very natural vibe. It is no surprise therefore, that I fell for it. That is the sort of makeup I wear, and the sort of makeup I gravitate towards.
Those who prefer stronger, bolder colours may find the collection insipid. But this year, the Les Beiges takes on more colour, and that for me, is both a good and bad thing. Good, because it may appeal to a wider cross-section of the public. Bad, because it isn't as fool-proof as it used to be.
After last week's marathon blog content, I think you're about as wiped as I am LOL! I haven't blogged daily for a couple of years now, and I'd forgotten how much it really takes out of a person. I take my hats off to all the bloggers who are still churning out daily content, because guys, you deserve all the accolades you get. I can't go there again. It's too draining – physically and mentally.
With this in mind, I thought it would be nice to kick back with some little beauty hors d'oeuvres, or bite-sized appetizers in the beauty world. These are little snack-bites of some upcoming new releases that you can keep an eye out for, if it catches your fancy.
If there's one thing I try to refrain from saying is "This is a must-have!" Truthfully, very few things are, especially when it's something from the luxury designer houses. Ok, perhaps a Chanel Classic Flap is a must have in a bag collection. If you don't have to rob a bank to get it LOL!
That said, I am going to go out on a limb today, to tell you that there is one, just ONE item, from the Chanel Neapolis Spring-Summer 2018 makeup collection that I think is a must-have. I say this loosely of course. If you are in the market for something nice, that is really good quality, you could do worse.
The only problem is that it's a limited edition product, and because I received these only very recently, I don't know if they are still available in store or at counters. But if you do decide to hop along and take a look, then look at these.
Where makeup collections released for Spring tend to be rather insipid, pink, pastel things, I love how Chanel has taken the bold approach to bring colour into the still dreary days of winter. For us here in the tropics, it's always sunny so this is a collection that is right up our alley! Inspired by creative director Lucia Pica's hometown, Naples, Chanel Neapolis is a burst of colour, combining interesting textures and lifting the spirits.


Lyuska Hulliger's practice focuses on various aspects of criminal law, particularly on criminal economic law, criminal procedure and international mutual assistance in criminal matters. She has extensive experience in family and contract law and regularly advises and assists clients in litigation proceedings before Swiss courts. She joined Fontanet & Associés as an associate in 2015 from Poncet Turrettini Amaudruz Neyroud & Associés where she also completed her internship. She is a member of the Geneva Bar Association and passed her Bar exam in 2011. Lyuska Hulliger graduated in Law from the Universities of Geneva and Sydney (Bachelor in 2007, Master in civil and criminal law in 2009).
Pascal de Preux/Lyuska Hulliger, commentaire de l'art. 138 CP (abus de confiance), in Macaluso/Moreillon/Queloz (éd.), Commentaire romand, Code pénal II, Bâle 2017.


Correspondence: Benjamin J. Frankfort, 6565 Fannin Street, NC-205, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030; benjamin.frankfort@bcm.edu.
Michelle R. Butler, Claudia M. Prospero Ponce, Y. Etan Weinstock, Silvia Orengo-Nania, Patricia Chevez-Barrios, Benjamin J. Frankfort; Topical Silver Nanoparticles Result in Improved Bleb Function by Increasing Filtration and Reducing Fibrosis in a Rabbit Model of Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2013;54(7):4982-4990. doi: 10.1167/iovs.13-12047.
Purpose.: To compare the effects of silver nanoparticles (AgNPs) and mitomycin C (MMC) on intraocular pressure (IOP) and external, histologic, and immunohistochemical bleb characteristics in a rabbit model of filtration surgery.
Methods.: Filtration surgery with concurrent topical application of either AgNPs or MMC was performed on 14 pigmented Dutch Belted rabbits. IOP and bleb characteristics were compared on postoperative day 1 and at weeks 1 through 6. Hematoxylin and eosin staining and smooth muscle actin (SMA) immunohistochemistry were performed at postoperative week 6.
Results.: Average IOP across all time points was reduced 5.8 and 3.8 mm Hg in AgNP- and MMC-treated eyes, respectively. At week 6, IOP was reduced 4.1 and 0.2 mm Hg in AgNP- and MMC-treated eyes, respectively. Blebs were smaller, thicker, and less ischemic in AgNP-treated eyes. AgNP-treated eyes showed less fibrosis and more stromal edema, suggesting increased filtration, and also had fewer SMA-positive myofibroblasts, suggesting reduced bleb contraction. AgNP-treated eyes showed more lymphocytes than MMC-treated eyes. There were few complications in both groups.
Conclusions.: In a rabbit model of filtration surgery, AgNPs are a reasonable alternative to MMC as adjunctive therapy. Compared to MMC, AgNPs result in an improved and sustained reduction of IOP and promote blebs with decreased fibrosis and ischemia as well as increased filtration despite a smaller overall size. This combination may offer an opportunity to promote long-term surgical IOP reduction with an improved complication profile.
The potential combination of decreased scarring, reduced inflammation, fibroblast inhibition, infection prophylaxis, and high tolerability suggests that AgNPs would be beneficial during trabeculectomy surgery. In particular, AgNPs may allow healing to occur without aggressive scar tissue formation or subconjunctival fibrosis, thereby promoting bleb survival. To test this hypothesis, we compared the effects of AgNPs and MMC in an established rabbit model of filtration surgery. 45 We report that AgNP-treated rabbits had lower IOP, as well as thicker, smaller, and less ischemic blebs. Histologically, AgNP-treated rabbits had reduced fibrosis and myofibroblast proliferation. AgNP-treated animals also had increased lymphocytic infiltrate and increased edematous intrastromal fluid-filled spaces within the surgical bleb, likely representing increased filtration. AgNPs show potential as a novel adjuvant during filtration surgery.
4-minute application of AgNPs, 10 nm average diameter, 0.1 mg/mL colloidal solution in water (Plasmachem, Berlin, Germany), which was not irrigated.
The surgeon was aware of the adjuvant because of the difference in color of liquid MMC (clear) and AgNPs (ochre). A 22-gauge intravenous catheter was then inserted into the anterior chamber through a 3 mm scleral tunnel to ensure patency of the sclerostomy. The posterior edge of the catheter was trimmed and fixed to the sclera with a single 10-0 nylon suture. The peritomy was closed with three 10-0 nylon sutures (one central mattress at 12 o'clock and one suture at each limbal wound edge). Rabbits then received a weight-based intramuscular injection of buprenorphrine 0.3 mg/mL and were allowed to recover on a warming blanket.
Rabbits were evaluated on postoperative day 1 (POD1) and at postoperative weeks 1 through 6 (POW1–POW6) by two investigators (MRB and BJF). At all time points, topical anesthetic was placed in the operative eye, and recordings were made of IOP with a Tonopen (Reichert Technologies). We recorded the following bleb characteristics: thickness (the thickness of the surface of the bleb tissue; 3-point scale where 0 = thin, 1 = moderate, and 2 = thick); height (vertical extent of the bleb from the limbus to the superior bleb edge in millimeters); width (horizontal extent of the bleb along the limbus in millimeters; diffuseness (measure of how much of the treated area the bleb involved); vascularity of the bleb, bleb edge, and surrounding nonbleb tissue (all evaluated on a 3-point scale where 0 = minimal, 1 = moderate, and 2 = prominent); anterior chamber depth (0 = flat, 1 = shallow, 2 = deep); and complications. 46 For each characteristic, the same two investigators made separate and independent measurements, and the average was recorded. Since the surgeon was involved the measurements (BJF), one reading was not masked. Animals were assessed for pain and distress at all time points. After the POW6 examination, all animals were euthanized with a lethal dose of beuthanasia D administered to the ear vein. Operative eyes were promptly enucleated and placed in 10% formalin.
Enucleated eyes were labeled by the pathologist in a masked fashion so that the treatment group could not be determined from the slide label. Fourteen eyes were grossly examined to include sections of the bleb and adjacent tissues for histologic examination. The selected areas of the eye were then processed for routine paraffin-embedded tissue. Three levels of each block were obtained and stained with standard hematoxylin–eosin (H&E) stain. Unstained slides in between levels were then used for immunohistochemistry. Slides were deparaffinized, rinsed with deionized water, and placed in Dako Wash Buffer (Carpinteria, CA). Antigen retrieval was performed using Dako Target Retrieval Solution. Endogenous peroxidase activity was blocked with 3% H2O2, and endogenous biotin was blocked using Vector Avidin/Biotin Blocking Kit (Burlingame, CA). Nonspecific protein binding was blocked with Dako Serum Free Protein Block, and the slides were incubated with mouse ready-to-use antismooth muscle actin, clone 1A4 (Biogenex, Fremont, CA) for 30 minutes at room temperature. Slides were washed and incubated for 30 minutes with Vector biotinylated anti-mouse IgG diluted 1:150 in Dako Antibody Diluent. Slides were then washed and incubated for 30 minutes with Vector VECTASTAIN Elite Standard ABC Kit prepared in Dako Wash Buffer according to manufacturer's directions. Slides were washed in wash buffer and incubated for 5 minutes with Dako 3,3′ Diaminobenzidine (DAB)+ Substrate Chromogen System prepared according to manufacturer's directions. Slides were rinsed in deionized water, placed in wash buffer, counterstained with Hematoxylin 2 (Richard-Allan Scientific, Kalamazoo, MI), dehydrated, and coverslipped.
Fibrosis (defined as the presence of collagen deposition within the tissue) and edema (defined as fluid-filled spaces within the tissue stroma that appears as cleared stroma when seen histologically) were evaluated through the middle of the bleb over the sclera in all eyes to allow for direct comparison of tissue. Fibrosis and edema were graded as 0 when absent, 1+ when involving less than 50% of tissue, 2+ when involving between 50% and 80% of tissue, and 3+ when involving ≥80% of the tissue. Fibroblasts were easily identified by H&E staining and were scored according to the same scale. Lymphocytes, eosinophils, and vessels, which were less abundant, were graded 0 when absent, 1+ when present in 0 cells to 1 cell per high-power field in 5 fields, 2+ when present in 2 to 4 cells per high-power field in 5 fields, and 3+ when present in >5 cells per high-power field in 5 fields. For these measurements a high-power field was defined as a single area at ×40 magnification. Myofibroblasts were identified by immunostaining with SMA and graded according to the same scale as lymphocytes, eosinophils, and vessels.
Photographs were obtained with a Nikon D3 camera (Nikon, Tokyo, Japan) with an AF Micro-NIKKOR 60 mm f/2.8D lens (Nikon) at focal distances between 0.25 and 0.50 m. Bright ambient lighting without a flash was used for all photos. Aperture, shutter speed, and ISO were adjusted for depth of field and exposure optimization.
Statistical analysis was performed using parametric and nonparametric statistics in SPSS version 20 (IBM, Armonk, NY). To measure the effect of surgery on IOP, a paired t-test with a cutoff of P < 0.05 was used. For analysis of continuous data of repeated measures, ANOVA with a cutoff of P < 0.05 was used. For analysis of ordinal data, nonparametric statistics at multiple time points (Mann-Whitney test) with a cutoff of P < 0.05 were used.
Since IOP is a critical risk factor for glaucoma development and progression, we first sought to compare the reduction in IOP achieved with AgNPs to that obtained with MMC. IOP after filtration surgery was significantly lower than baseline at multiple time points in both groups (Fig. 1, Table 1), suggestive of successful surgery. Interestingly, the IOP reduction seen in the AgNP-treated group was greater than that in the MMC-treated group (repeated measures ANOVA, P = 0.02), and the average reduction of IOP across all time points was 5.8 mm Hg in AgNP-treated eyes and 3.8 mm Hg in MMC-treated eyes. In both groups, there was a trend toward higher IOPs beginning at week 5. However, whereas the IOP of MMC-treated eyes returned essentially to baseline by week 6 (average IOP reduction = 0.2 mm Hg), the IOP of AgNP-treated eyes remained reduced (average IOP reduction = 4.1 mm Hg). This trend in IOP elevation in MMC-treated eyes is suggestive of gradual bleb failure.
Intraocular pressure (IOP) after filtration surgery is lower in eyes treated with AgNPs. IOP (mm Hg) was measured with a Tonopen preoperatively (POD 0) and at each postoperative examination (POD 1, POW 1–POW 6; see Methods). MMC- and AgNP-treated eyes are presented in black and gray, respectively; n = 7 for both groups. Preoperative mean IOPs were similar between the two groups. After filtration surgery, IOP was reduced when treated with either AgNPs or MMC at multiple time points (asterisks, paired t-test compared to baseline IOP, P < 0.05). Overall, IOP reduction in AgNP-treated eyes was greater than in MMC-treated eyes (repeated measures ANOVA, P = 0.02). At later time points (POW 5, POW 6), the IOP of MMC-treated eyes increased, suggesting late surgical failure of MMC-treated eyes. Error bars represent one SEM.
Mean, minimum (Min), and maximum (Max) IOP (mm Hg) with standard deviation (Std. dev.) for both MMC- and AgNP-treated eyes at all time points after surgery (POD 1 and POW 1–6). POD 0 represents the day of surgery; n = 7 for both groups. Both MMC- and AgNP-treated eyes had a statistically significant reduction in IOP at multiple time points, suggestive of successful filtration surgery, but the reduction in AgNP-treated eyes was greater (repeated measures ANOVA [rmANOVA], P = 0.020; see Fig. 1). IOP was lower in AgNP-treated eyes than MMC-treated eyes at every time point. IOP levels were maintained in AgNP-treated eyes but tended to rise at later time points in MMC-treated eyes. By week 6, the average reduction of IOP in MMC-treated eyes had decreased to 0.2 mm Hg, suggesting bleb failure.
In order to compare the morphologic appearance of the blebs of both groups, we recorded multiple metrics of the bleb appearance at each time point (see Methods section). Overall, bleb characteristics were quite different between the two groups. In general, AgNP-treated eyes had blebs that were smaller, thicker, more vascular, and more focal, whereas MMC-treated eyes had blebs that were larger, more diffuse, and more ischemic. The area surrounding the bleb was more vascular in the MMC-treated group. Both groups showed a gradual reduction in bleb size over time (Table 2). In general, AgNP-treated tissue appeared healthier than MMC-treated tissue and did not have areas of thin, ischemic, translucent tissue (Fig. 2).
External appearance of AgNP- and MMC-treated eyes. Eyes treated with AgNPs (A–C) and MMC (D–F) were photographed at POW 1 (A, D), POW 2 (B, E), and POW 4 (C, F). The animals shown are representative of the time course of healing for both groups. At all time points, AgNP blebs had coloring and vascularity similar to those of surrounding tissues. With time, these blebs gradually became more focal (less diffuse) in appearance (outline). MMC blebs (outline) were larger and increasingly ischemic (translucent appearance at POW 4, asterisk). Note the position of the intravenous catheter in the superior aspect of the anterior chamber in all parts of the figure.
Mean results are reported for each characteristic. Bleb height was similar between the two groups, but bleb width was significantly greater in the MMC-treated group (repeated measures ANOVA, P = 0.035), with smaller blebs in the AgNP-treated group. Blebs were also less diffuse in the AgNP-treated group (ANOVA, P = 0.049), and both groups showed a gradual reduction with time. AgNP-treated blebs were of stable, intermediate thickness at all time points while MMC-treated blebs became thin by POW 2 (Mann-Whitney test, P < 0.05, for each time point from POW 2 through POW 6). At all time points, AgNP-treated eyes were less vascular than MMC-treated eyes at the bleb edge and at nonbleb tissue. At all time points subsequent to POD 1, the bleb tissue was more vascular in the AgNP-treated group, suggesting fewer ischemic changes. Anterior chamber depth was deep for all eyes at all time points.
Surgical complications in both groups were low. Three animals treated with MMC had a mild chemical conjunctivitis that resolved spontaneously in two animals. In the third, a mild blebitis without endophthalmitis developed that resolved with topical antibiotic therapy. One AgNP-treated animal had a tube dislocation in which the tube partially migrated into the anterior chamber. There were no instances of shallowing or flattening of the anterior chamber.
Histologic analysis of enucleated eyes revealed multiple differences between AgNP- and MMC-treated eyes (Fig. 3). Most strikingly, the subconjunctival space of AgNP-treated eyes had less fibrosis (less organized collagen deposition) and more stromal edema or intrableb fluid-filled spaces than MMC-treated eyes. This edema was uniform throughout the bleb, whereas MMC-treated eyes showed abrupt fibrotic borders with large cystic spaces and contractile myofibroblasts in the wall (Figs. 4A–D). The presence of uniform stromal edema is suggestive of increased filtration throughout the bleb with transconjunctival diffusion of filtered aqueous. Thus, despite a smaller overall appearance, it is possible that AgNP-treated eyes had improved overall filtration, which may explain how the smaller blebs seen in AgNP-treated eyes could also produce a lower IOP. Interestingly, as there was no difference between the two groups with regard to the amount of total fibroblasts, this difference in healing is unlikely to result from a simple reduction of fibroblasts and is more likely due to a change in fibroblast properties, terminal differentiation, or the surrounding tissue environment. To further assess this, we quantified the number of fibroblasts that had transformed into myofibroblasts through immunostaining with smooth muscle actin (SMA). We detected smooth muscle–positive myofibroblasts primarily at the bleb edges in MMC-treated eyes, often surrounding large fluid-filled spaces, which is suggestive of encysted and contractile blebs. In AgNP-treated eyes, there was a reduced number of smooth muscle–positive myofibroblasts, which suggests reduced or altered fibroblast transformation (Figs. 4E, 4F). Since myofibroblasts have contractile properties, this reduced number of myofibroblasts most likely reduced both contraction of the bleb edges and remodeling of the bleb wall. This altered healing environment is also suggested by the finding that AgNP-treated eyes had slightly more lymphocytes than MMC-treated eyes, which were more likely to show an eosinophilic infiltrate (Figs. 4G, 4H).
Histologic summary of AgNP- and MMC-treated eyes. A scoring system was used to evaluate the bleb areas of seven MMC-treated and seven AgNP-treated eyes. Collagen deposition (Fibrosis), interstitial edema (Edema), total fibroblasts (Fibroblasts), total lymphocytes (Lymphocytes), total eosinophils (Eosinophils), blood vessels (Vessels), smooth muscle actin–positive vessels (Actin_Vessels), and smooth muscle actin–positive myofibroblasts (Actin_Myofibros) were evaluated (see Methods). (A) Mean values with standard deviation. (B) Median values. (A, B) Black bars represent MMC-treated eyes, and gray bars represent AgNP-treated eyes. Reduced fibrosis and increased lymphocyte proliferation were seen in AgNP-treated eyes compared to MMC-treated eyes (Mann-Whitney test, P = 0.025, 0.045, respectively). There were trends toward increased interstitial edema and decreased actin myofibroblasts in AgNP-treated eyes.
Histologic and immunohistochemical findings for AgNP- and MMC-treated eyes. AgNP- and MMC-treated eyes are presented in the left and right columns, respectively. (A–D, G, H) Hematoxylin and eosin staining at ×10 magnification (A, B) and ×40 magnification (C, D, G, H). (E, F) Immunohistochemistry using smooth muscle actin (SMA) antibody and DAB chromogen at ×20 magnification. Scale bars are indicated for each part of the figure. The bleb area over the sclera (asterisk) in a typical AgNP-treated eye (A) showing uniform edema and no cyst formation, and in a typical MMC-treated eye (B) showing packed collagen and a cystic bleb. A representative AgNP-treated eye (C) showing moderately edematous stroma and a representative MMC-treated eye (D) showing a densely packed, collagenous, cellular background without edematous stroma. In a typical AgNP-treated eye (E), SMA is present in smooth muscle in open vessels surrounding the edematous bleb, but no myofibroblastic proliferation is seen. In a typical MMC-treated eye (F), SMA-positive myofibroblasts are seen in the fibrous stroma at the edge of the bleb, suggesting an encysted bleb. Inflammation associated with the edges of the bleb area in a representative AgNP-treated eye (G) showed predominance of lymphocytes with a rare eosinophil. In a representative MMC-treated eye (H), less lymphocytic infiltrate and more eosinophils were seen.
Any improved surgical alternative to MMC should result in at least similar IOP lowering following filtration surgery with reduced complications. In our model of rabbit filtration surgery, MMC-treated animals had IOP that was lower than baseline at all time points, although IOP was essentially the same as baseline by postoperative week 6. Strikingly, AgNP-treated animals also had IOP lower than baseline at all time points. Furthermore, when compared to MMC-treated animals, AgNP-treated animals had a statistically lower IOP. Thus, IOP lowering with AgNPs was superior overall (Fig. 1, Table 1).
We report an increase in IOP at the later time points among MMC-treated eyes, which implies surgical failure. Another extensive study also reported a relatively high failure rate of MMC-treated blebs in rabbits at 1 month after surgery, which is consistent with our findings. 45 Thus, the maintenance of low IOP at 6 weeks in most AgNP-treated eyes is promising, and has the potential for long-term IOP reduction.
AgNP-treated blebs were thicker, less ischemic, and less hypervascular at their borders than MMC-treated blebs (Fig. 2, Table 2). Histologically, 6 weeks after surgery, AgNP-treated eyes also had markedly less fibrosis and collagen deposition than MMC-treated eyes, almost no myofibroblastic transformation, accounting for minimal bleb contraction, and increased interstitial edema suggestive of improved filtration. This combination of findings is consistent with the possibility that AgNPs promote healthier, better-functioning blebs with decreased contractile scar tissue formation. In this context, improved filtration may occur as well, resulting in decreased IOP. In a mouse model of wound healing after thermal injury, wounds treated with topical AgNPs closely resembled normal skin and had reduced hypertrophic scarring in a dose-dependent manner. 37 Therefore, it is possible that a more "normal" healing process is occurring in our filtration surgery model as well. Since we did not titrate the dose of AgNPs and since increased AgNP concentration is associated with increasing levels of both effect and toxicity, it is possible that different concentrations of AgNPs would produce different results. 40–42 Interestingly, we found that AgNP-treated blebs were smaller than MMC-treated blebs, yet had improved survival and lower IOP. This suggests that the quality of filtration may not correlate simply with bleb size, and that smaller but more efficient blebs may be possible with AgNPs. Such blebs are potentially less likely to cause symptoms of bleb dysesthesia and ocular discomfort. Lastly, the blebs of AgNP-treated eyes were thicker, more vascular, and less ischemic than those in MMC-treated eyes. This distinction is critical, as thin and ischemic blebs are thought to represent a significant risk factor for some of the devastating complications of glaucoma surgery, such as bleb leak, hypotony, and endophthalmitis. Thus, AgNP treatment may also result in fewer long-term complications following filtration surgery.
Histologic evaluation of AgNP- and MMC-treated eyes showed similar numbers of total fibroblasts. Previous work has implicated both AgNPs and MMC as inhibitors of fibroblast proliferation. 10,12,38 However, we observed very different patterns of fibrosis (dense collagen deposition in MMC-treated eyes and loose deposition with intersitial edema in AgNP-treated eyes) despite similar numbers of fibroblasts. One possible explanation is that while both AgNPs and MMC reduce fibroblast proliferation, AgNPs have additional effects on the cytokine microenvironment that result in decreased relative fibrosis. Indeed, AgNPs have been implicated as inhibitors of both IL-6 and TGF-B1, which are potent proinflammatory cytokines. 37 Similarly, AgNPs decrease peritoneal adhesions in a surgical model in mice. 39 It is possible that an analogous process occurs after filtration surgery, with less fibrosis and fewer fibrotic adhesions. Nevertheless, the relative abundance of lymphocytes in AgNP-treated eyes suggests that there is still some degree of chronic inflammation present. We also observed reduced myofibroblast transformation in AgNP-treated eyes, which contrasts with a previous study suggesting that AgNPs promote myofibroblast transformation. 38 That study was conducted on skin tissue, which has more cell types and complexity than conjunctiva. Furthermore, the authors of that report were looking at healing in sites such as skin, which require wound remodeling through myofibroblastic transformation. Thus, the differences in tissue makeup and endpoint objectives may explain the differences between the two studies, and could be further explained by the inflammatory microenvironment, the anatomic difference, or the lubrication of the tissue. Further studies to differentiate the timing and quality of the cytokine environment during the postoperative period may also explain these discrepancies. Since AgNP-treated eyes had smaller blebs that filtered more efficiently, it is possible that this altered inflammatory microenvironment resulted in decreased myofibroblastic transformation, which in turn led to decreased bleb contraction and secondary prolongation of stromal edema with improved bleb filtration capacity.
Overall, AgNPs represent a potential alternative to MMC as adjunctive therapy during filtration surgery and may be superior to MMC. While there is a mild increase in lymphocyte proliferation associated with AgNPs, they also lead to a sustained reduction of IOP and promote blebs with decreased fibrosis and ischemia as well as increased filtration. This combination of effects is ideal in filtration surgery, and may offer an opportunity to promote long-term surgical IOP reduction with an improved complication profile. Further study of the mechanisms governing the action of AgNPs on ocular tissue, the ideal delivery system for AgNPs, and long-term toxicity is warranted.
We thank Ronald L. Gross and Derek Nusbaum for critical reading of the manuscript. We thank Rebecca Penland (The Methodist Hospital Research Institute [TMHRI] Ocular Pathology Research Laboratory) for preparing and immunostaining the slides.
Supported by two Milton Boniuk, MD, Ophthalmology Resident Research Grants (MRB), the Endowment Fund of the Lions Eye Bank Foundation (MRB), an unrestricted grant from Jamil Azzam, MD (SO-N), Research to Prevent Blindness, Inc. (BJF), National Institutes of Health (NIH) Grant K08 EY021479 (BJF), and NIH Grant P30 EY002520 (Baylor College of Medicine). The authors alone are responsible for the content and writing of the paper.
Wilkins M Indar A Wormald R. Intra-operative mitomycin C for glaucoma surgery. Cochrane Database Syst Rev . 2005; 4: CD002897.


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Home Nigeria National Team Thomas Dennerby: Sports Minister Dare Intervenes To Forestall Swede's Shock Resignation
Thomas Dennerby: Sports Minister Dare Intervenes To Forestall Swede's Shock Resignation
Azu Umeh
Minister of Sports Sunday Dare has waded into the controversy surrounding Thomas Dennerby's shocking resignation as head coach of the Super Falcons.
Unconfirmed reports had suggested that the 60-year old Swede had threatened to resign his position as head coach of Nigeria's senior women's team over several issues that have boiled over in recent weeks.
The former head coach of Sweden's women's team was reportedly fed up of unfulfilled promises by the Nigeria Football Federation and alleged interference in his team's selection.
A particular sore point in his time as head coach of the nine-time African champions was his relationship with NFF head of women football Ruth David which has allegedly reached a breaking point and precipitated his decision to hand in his resignation.
However, in a message on microblogging site Twitter, Minister of Sports Sunday Dare revealed that he will intervene to ensure Dennerby who was appointed to his role in 2018 continues as head coach of the Super Falcons.
"I have personally stepped into the matter of Thomas Dennerby, the Coach of Super Falcons. I received a brief this morning and will proceed to seek a quick resolution to ensure he continues to Coach Nigeria's female team," Dare tweeted on Monday.
I have personally stepped into the matter of Thomas Dennerby, the Coach of Super Falcons. I received a brief this morning and will proceed to seek a quick resolution to ensure he continues to Coach Nigeria's female team.
— Sunday Dare (@SundayDareSD) September 16, 2019
However, in an interview with noted journalist Mitchell Obi on his radio programme, Sports Salsa, monitored in Lagos, 2nd-Vice President of the NFF Shehu Dikko confirmed that the Federation's lawyers were in conversation with the Swede's representatives in a bid to resolve their differences.
Dikko told the programme that in the event their differences proved irreconcilable, a provision exists in Dennerby's contract allowing for a mutual termination of the deal could be activated.
Dare later indicated in a follow up tweet that he had spoken with both Dennerby and the leadership of the NFF and was working to ensure an amicable resolution to the current standoff.
An hour ago I had a constructive conversation on the telephone with Super Falcons Coach Dennerby in Sweden. I have also spoken with the NFF leadership. We are working to resolve the issues in the interest of football development.
Dennerby joined the Super Falcons in 2018 and won the 2018 Women's Africa Cup of Nations and led the team to a place in the knockout round of the 2019 FIFA Women's World Cup for the first time since 1999.
His last match in charge of the Super Falcons was a 1-0 win over Algeria in a Tokyo 2020 Qualifier at the Agege Stadium in Lagos.
Sunday Dare
Thomas Dennerby
Women Football
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Victoria resident and ultra-marathoner Veronique Bourbeau wants to use her gift for running to give back. She hopes to provide safe drinking water to villages throughout Africa during her fundraising the length of the continent. (Jane Skrypnek/News Staff)
B.C. resident aims to provide safe water, become first woman to run across Africa
Veronique Bourbeau plans to run 13,000 kilometres over the course of a year
Every morning during her meditation, Veronique Bourbeau pictures herself in Cape Town, South Africa. She allows the exhaustion and exhilaration of the moment to wash through her as if she is really there.
Programming herself like this is the only way the Victoria resident can push through the impossibility of running more than 13,000 kilometres from the tip to the tail of Africa in one year and instead focus on her goal – to provide safe drinking water for people in need along the way.
"I'm a true believer that what you put in your mind can empower you or destroy you," she says.
Indeed, mental fortitude is what has allowed Bourbeau to go from being a non-runner 14 years ago to planning to become the first woman and second person ever to run the length of Africa.
When she first tried running in 2007, she hated it. It was winter in Quebec City and she was too self-conscious to go outside with the "professional" runners, so Bourbeau bought an old treadmill and began an alternating regimen of walking then running one kilometre.
It was awful, she admits, but Bourbeau loves a challenge and pushed herself to stick with it. Within seven months, she ran her first marathon. She considered quitting after that but thought it would be a shame to waste all her hard work. So Bourbeau ran another marathon and cut 40 minutes off her original time.
"It was where I really started to love running," she says.
READ ALSO: Kilted Scotsman launches walking trek across Canada in B.C.
Suddenly, Bourbeau was completing two marathons a week. She and her husband began travelling around the world for work with their two children, and everywhere they went she took on bigger and bigger challenges.
Pursuing the sport of ultramarathon, in the United Arab Emirates she ran her first 100-mile (161 km) race, then in Japan she took on 250 km and in Malaysia tackled 444 km. Each time, finishing seemed impossible, but Bourbeau pushed through and came out the other side craving more.
"When you reach this point that you didn't even know existed, you go beyond what you thought you could achieve as a person. You reach an energy so big, you are yourself but it's something more than you," she says.
Eventually Bourbeau started to think about how she could use her running to give back. She remembered a trip to Senegal, Africa years ago and the women and girls she met who spent their days lugging water instead of attending school.
"People would welcome us in for food even when they didn't know if they'd have food for the next day," she says.
Over her planned year-long run, Bourbeau plans to visit villages in 19 countries from Alexandria, Egypt to Cape Town, South Africa, raising money for clean water infrastructure along the way.
"It's about water, but it's also about humanity," she says. She believes deeply in a world where generosity and understanding govern people's actions.
For her, running is about more than a personal challenge now, it's about using her ability to make the world a better place. "We are all here for a reason. I think this is what I'm here for."
She's living in Victoria for the time being to be close to her children, who attend school here, and to secure the funding and partnerships necessary to make her trans-African trek successful. If all goes to plan, Bourbeau hopes to start her journey within the year.
More information on her goal and where to donate can be found at veroniquerun.com.
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Do you have a story tip? Email: jane.skrypnek@blackpress.ca.
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FBI: Dayton Mass Shooter Connor Betts Fantasized About Killing For Years Before 2019 Attack
Connor Betts was killed by police half a minute after he opened fire in Dayton's crowded Oregon District entertainment area. November 29, 2021 at 8:14 pm
Filed Under:Connor Betts, Dayton, dayton mass shooting, Ohio, Ohio News
COLUMBUS, Ohio (AP) — The man who gunned down nine people in Dayton, Ohio, two years ago had fantasized about mass shootings, serial killings and murder-suicide for at least a decade before carrying out the Aug. 4, 2019, attack, the FBI said Monday as it announced the conclusion of its investigation.
Shooter Connor Betts didn't share specific details with friends or family members about his fantasies, underscoring the importance of people being attuned to subtle changes in an individual, the agency said.
A phenomenon known as "bystander fatigue" may account why no one reported Betts to authorities before the shooting, according to a two-page FBI summary of its report.
That term is used "to describe the passivity, inaction, or inattention to concerning behaviors observed by individuals who have a close, interpersonal relationship to a person of concern due to their prolonged exposure to the person's erratic or otherwise troubling behavior over time," the FBI said.
Betts, 24, was killed by police half a minute after he opened fire in Dayton's crowded Oregon District entertainment area. Armed with an AR-15 style rifle and an extended ammunition magazine, Betts killed nine people, including his sister, and wounded dozens more.
The FBI's summary of its investigation did not address whether Betts intended to kill his sister, Megan, or if her death was inadvertent.
After the shooting, high school classmates said Betts was suspended years ago for compiling a "hit list" of fellow students he wanted to harm. Two of the classmates said Betts had also been suspended after he came to school with a list of female students he wanted to sexually assault.
Early on, police investigators said Betts had a "history of obsession with violent ideations with mass shootings and expressed a desire to commit a mass shooting." The FBI said it uncovered evidence Betts "looked into violent ideologies."
A friend of Connor Betts told investigators he bought body armor, a 100-round magazine and a part for Betts' gun. However, they concluded there was no indication he knew of Betts' plans.
The friend, Ethan Kollie, pleaded guilty to unrelated federal firearms charges and was sentenced to 2 1/2 years in prison.
In August, family members of four victims sued the magazine maker, Kyung Chang Industry USA Inc., saying the device serves no purpose other than allowing for the killing of as many people as possible. The magazine allowed Betts to fire 41 rounds in 32 seconds.
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