bluuebunny/crossref_metadata_2025 huggingface dataset:
VIRTUAL REALITY AND OLDER ADULTS: A USABILITY STUDY
Authors: Brown Julie A
Published: November 2019

Within the past two years there has been a very small but growing number of scholarly articles that highlight the potential benefit of mobile Virtual Reality (VR) platforms among older adult populations. Yet, it is critical to assess older adult user needs and preferences, as well as ethical considerations, before utilizing VR in applied contexts. This pilot study investigated perceptions of VR use and its potential application by individually interviewing ten community-dwelling older adults (ages 63 to 89) both before and after trying the Samsung Gear VR and followed with two focus group discussions. Themes identified from the transcripts include 1) usability, 2) video subject matter preferences, and 3) implications with use. These themes highlighted both the challenges and opportunities of VR use among a wide range of older populations, and provided greater insight with its exploration and application in future studies, particularly with individuals with functional limitations.
ADDRESSING THE SUCCESSFUL TRANSITION OF COMMUNITY COLLEGE GERONTOLOGY STUDENTS TO UNIVERSITY SETTINGS
Authors: Manoogian Margaret M
Published: November 2019

Developed in 2012, our gerontology program has tracked enrollment, learning outcomes, student competency development, and career paths post-graduation. Enrolled students tend to be older, transferring from community colleges, reentering college due to work and family commitments, and retooling career paths. Our efforts have focused on career integration across all courses culminating in a two-term practicum program. Additionally, through discussions with community college faculty and students, alumni, and community partners, we have adapted our curriculum to address student needs for work, family care, and academic engagement through flexible course delivery, syllabus construction, applied project development, and direct contact with professionals in and outside the classroom. Developing strategies to ensure transfer student success is critical, as well as offering strong career preparation for older students entering the workforce. Comprehensive placement data and an overview of the needs and challenges for university programs to partner with community college programs will be highlighted.
DEMENTIA CAREGIVER EMBRACE OF HOME VIDEO TELEHEALTH VISITS
Authors: Moo Lauren
Published: November 2019

Bringing people with dementia to in-person medical visits can be logistically challenging for family caregivers, especially when they themselves are older adults with their own health or mobility challenges, when they live far from the clinic, or when they have to combat inclement weather. Our dementia management clinic has successfully trialed video visits into the home. Video sessions have been welcomed by many dementia caregivers citing reduced travel and less disruption of daily routine as the primary benefits of participating. Caregivers report equivalent visit satisfaction compared to in-person visits. While technical issues have been common, most were just brief audio or video lags. Expansion of HIPAA compliant telemedicine software options across devices is increasing the population of caregivers who are able to participate in home video visits. (127 words)
IMPLEMENTING HOME SAFETY TOOLKIT TO CAREGIVERS OF VETERANS WITH DEMENTIA
Authors: Trudeau Scott A
Published: November 2019

The purpose of this project was to study the processes necessary to make a Home Safety Toolkit (HST) for Veterans with dementia accessible to veterans and their caregivers. This Type 3 Implementation–Effectiveness Hybrid Research Design, included diagnostic analyses of the current processes by which Veterans receive home safety items, and identification of modifications necessary in order to provide the HST to Veterans with dementia. Two Veterans Health Administration Networks, one in the Northeast and one in the Mid-Atlantic region, participated. A formative evaluation used semi-structured interviews with key staff informants and caregivers identified facilitators and barriers to successful acquisition and use of home safety items. Qualitative data analysis reveals key barriers of time and cost, selection of best items, and caregiver reluctance to change. There was resounding support from caregivers regarding the potential benefits of self-paced toolkit including education and home safety items to implement for their veteran.
WE CAN’T AVOID IT. IT’S THERE! AGEISM EXPERIENCED BY DIVERSE CULTURAL GROUPS IN OTTAWA, CANADA
Authors: Bergeron Caroline D , Lagacé Martine
Published: November 2019

Introduction: Discrimination based on age is pervasive across Canada. Little is known about the experiences of ageism among diverse cultural groups. The purpose of this pilot study was to explore the perceptions of ageism among culturally diverse older adults in Ottawa, Canada. Methods: Three focus groups were conducted with Chinese, Arab, and Indian older adults in Ottawa in June 2016. An 8-item protocol was developed to guide the discussions. Qualitative data were analyzed using open, axial, and selective coding. Results: Twenty-five culturally diverse older adults (9 Chinese, 6 Arab, and 10 Indian) participated in the focus groups. All described personal positive and negative examples of discrimination based on their age without being familiar with the term “ageism”. Several described their experiences with the intersection of age, race, and gender, although these interpretations varied by cultural group. Ageism in the media was also easily recognized. Participants recommended using specific content, communication channels, and organizations to counteract ageism. Discussion: This pilot study helped to illustrate that ageism is a societal problem that requires a societal solution. As Canada’s population becomes older and more diverse, important efforts are needed to raise awareness of ageism.
ETHNIC DISPARITY IN NUTRITIONAL STATUS: EVIDENCE FROM ECUADOR’S NATIONAL SURVEY OF HEALTH, WELFARE AND AGING (SABE)
Authors: Amano Takashi , Gallegos Carlos Andres
Published: November 2019

Providing effective public services to improve the nutritional status among older adults is pivotal in countries experiencing population aging. Public investment and social policy in Ecuador have focused mainly on standard food-based interventions and cash transference programs. These efforts, however, may be not effective enough to reach those populations that need the most. This study aims to identify those populations that should be targeted by specific interventions. Data were drawn from Ecuador’s Survey of Health, Welfare and Aging (SABE) – 2009, a probability sample of households with at least one person who were 60 years or older in Ecuador. The final sample consisted of 5,235 people who were 60 years or older. Ethnic identity was categorized into four categories: Indigenous People, Mestizo (Mixed of Spanish and Indigenous People), Afro-Ecuadorian/Mulato, and Other. Nutritional status was measured using Mini Nutritional Assessment (MNA). Ordered logistic regression analysis was utilized to assess the association between ethnic identity and nutritional status. Results revealed that the Indigenous ethnicity was significantly associated with worse nutritional status compared to Mestizo and Other even after controlling for a range of covariates including socio-economic status, health related factors, and social support. These findings suggest the existence of underlaying factors hindering the nutritional status of among indigenous older adults in Ecuador. Considering the information revealed by SABE, interventions and other strategies should be targeted and designed specifically accounting for the needs, preferences, and culture of the most vulnerable population.
DISTANCE FROM APARTMENT TO ACTIVITY AS A BARRIER TO PARTICIPATION IN GROUP ACTIVITIES FOR ASSISTED LIVING RESIDENTS
Authors: Mauldin Rebecca L , Fernandez Jason
Published: November 2019

Participating in group activities is potentially also beneficial for residents of assisted living facilities, who have decreased independence due to physical or cognitive limitations. However, their impaired abilities can make attending group activities difficult. One potential barrier is the physical distance from residents’ apartments to the activity location. This study analyzed resident (N=30) attendance at group activities in an assisted living facility. Attendance records for 822 group activities over the course of six months and the distance between residents’ apartments and activity location were analyzed. Exponential random graph models were used to estimate the effect of individual-level, activity-level, and social network factors on the likelihood that a resident attends an activity. On average, residents attended 128 events (SD = 151) during the six month study period. The average size of activities was 4.6 residents (SD = 2.9). The closest distance between a resident’s apartment and an activity was 7.7 feet; however, some residents had to travel up to 382 feet to attend an activity (M=153 ft.; SD=52). After controlling for individual-, activity-, and social network-level factors, distance to the activity was significantly and negatively associated with the likelihood a resident attended the activity. In spite of the fact that assisted living facilities offer supports and services to help residents overcome their physical limitations, it appears that distances within the building can be barriers to participation in group activities. This should be taken into account in designing facilities, locating group activities, and devising strategies to increase participation in group activities.
IDENTIFYING SALIENT TRAINING AND SUPPORT NEEDS WITHIN A STATEWIDE LIFELONG COMMUNITIES NETWORK
Authors: Crittenden Jennifer , Oh Patricia A , Lee Laura
Published: November 2019

As the older adult population grows in the United States, the need for community planning approaches that respond to the needs of older adults is of increasing importance. As a result, lifelong community movements, encompassing models such as Age-Friendly Communities, Livable Communities, and “Aging-in-Place” initiatives are proliferating. Maine, the oldest state by median age, currently hosts the largest number of AARP designated Age-Friendly Communities efforts. Given the size of this network, the purpose of this study was to collect descriptive information about the status of existing lifelong communities initiatives, their training and support needs, and the desired format and configuration of future training programming. An electronic survey was distributed to community representatives from 76 lifelong communities initiatives throughout Maine. A total of 38 communities responded to the survey representing a response rate of 50%. The majority of respondents (80.4%) reported having a committee or other coordinating group guiding their work. A large portion have completed planning phase activities including hosting focus groups (79.5%), carrying out a survey (66.7%), and identifying a list of local assets (59%). Fewer have completed the plan drafting phase (17.9%). A majority reported receiving assistance from AARP (66%) and a regional educational consortium (66%). The areas with highest self-reported training needs (based on mean ratings) are: Volunteer recruitment and retention, specialized trainings on Age-Friendly Community topics, Dementia-Friendly Communities topics, and outreach and community engagement strategies. Implications will be discussed including optimal configuration of training and support for similar such networks.
GLUTATHIONE, MITOCHONDRIAL DEFECTS, AND A UNIQUE METABOLIC CYCLE IN OLDER HUMANS: IMPLICATIONS FOR SARCOPENIA
Authors: Sekhar Rajagopal V , Hsu Jean , Jahoor Farook , Chacko Shaji , Kumar Premranjan , Liu Chun
Published: November 2019

Sarcopenia in aging leads to decreased muscle mass and physical-function (muscle strength and exercise capacity), but underlying mechanisms are not well understood and effective interventions are limited. We hypothesized that deficiency of the intracellular antioxidant protein Glutathione initiates a unique self-perpetuating metabolic cycle linking impaired fasted mitochondrial fuel-oxidation (fMFO) to protein catabolism and contributes to sarcopenia. We also hypothesized that supplementing the Glutathione precursor amino-acids glycine and N-acetylcysteine (GlyNAC) to correct Glutathione deficiency in older humans could reverse these defects. We tested our hypothesis in a 24-week open-label clinical-trial in 8 older-humans (74y) studied before and 24-weeks after GlyNAC supplementation, compared to 8 gender-matched unsupplemented young-controls (25y), and measured intracellular Glutathione concentrations, fMFO, physical-function, muscle-protein breakdown-rate (MPBR), gluconeogenesis, and urine nitrogen-excretion (UNE). GlyNAC supplementation in older humans corrected Glutathione deficiency and restored impaired fMFO (to levels in young controls), lowered MPBR and UNE, and increased physical-function, but did not affect gluconeogenesis or increase lean-mass, and suggest that muscle amino-acids are utilized for energy needs rather than glucose production. The absence of an increase in lean-mass suggests that GlyNAC should be combined with anabolic agents for potential benefits in combating sarcopenia. Overall, these results indicate the presence of a unique reversible metabolic cycle in older humans initiated by Glutathione deficiency which results in impaired mitochondrial fatty-acid and glucose oxidation, muscle-protein breakdown, UNE, and leads to deficiency of glycine and cysteine which re-initiate the cycle. These data have implications for improving physical-function and muscle mass in age-associated sarcopenia, and warrants further investigation.
NOVEL STAIN SEPARATION METHOD FOR AUTOMATIC STEREOLOGY OF IMMUNOSTAINED TISSUE SECTIONS
Authors: Dave Palak , Goldgof Dmitry , Hall Lawrence O , Alahmari Saeed , Mouton Peter R
Published: November 2019

Many studies of brain aging and neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases require rapid counts of high signal: noise (S:N) stained brain cells such as neurons and neuroglial (microglia cells) on tissue sections. To increase throughput efficiency of this work, we have combined deep learned (DL) neural networks and computerized stereology (DL-stereology) for automatic cell counts with low error (<10%) compared to time-intensive manual counts. To date, however, this approach has been limited to sections with a single high S:N immunostain for neurons (NeuN) or microglial cells (Iba-1). The present study expands this approach to protocols that combine immunostains with counterstains, e.g., cresyl violet (CV). In our method, a stain separation technique called Sparse Non-negative Matrix Factorization (SNMF) converts a dual-stained color image to a single gray image showing only the principal immunostain. Validation testing was done using semi- and automatic stereology-based counts of sections immunostained for neurons or microglia with CV counterstaining from the neocortex of a transgenic mouse model of tauopathy (Tg4510 mouse) and controls. Cell count results with principal stain gray images show an average error rate of 16.78% and 28.47% for the semi-automatic approach and 8.51% and 9.36% for the fully-automatic DL-stereology approach for neurons and microglia, respectively, as compared to manual cell counts (ground truth). This work indicates that stain separation by SNMF can support high throughput, fully automatic DL-stereology based counts of neurons and microglia on counterstained tissue sections.
SOLUBLE INTERCELLULAR ADHESION MOLECULE (SICAM-1) AS A BIOMARKER OF VASCULAR COGNITIVE IMPAIRMENT IN OLDER ADULTS
Authors: Arenas Rosalinda Sanchez , Gregory Michael A , Manuel-Apolinar Leticia
Published: November 2019

Background: Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal. Objective: To determine whether sICAM-1 contributes to the prediction of VCI. Methods: Community-dwelling older adults (n=172) from the “Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults” (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI. Results: 31 VCI cases were identified. sICAM-1 was higher in VCI [VCI: 450.7 (241.6) ng/ml vs. Control: 296.9 (140.9) ng/ml]. sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) was associated with VCI group membership in all models [OR = 6.9 (95% CI: 1.1- 42.2)]. The final saturated model explained 64% of the variance in VCI group membership. Conclusion: High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.
PAIN EXPERIENCES IN OLDER ADULTS WITH HEART FAILURE IN THE HOME HEALTHCARE SETTING AFTER HOSPITAL DISCHARGE
Authors: Kang Youjeong , Reid Cary
Published: November 2019

Pain symptoms are underreported in older adults (i.e., those ages ≥65), because many consider it a part of aging. Pain is highly prevalent in patients with heart failure (HF). HF is increasing in incidence with the aging population. Pain is also an important risk factor for rehospitalization among home healthcare patients with HF. However, little is known about the pain experiences of older adults with HF after hospital discharge. Accordingly, this study sought to describe pain and other symptoms among older adults with HF in the home healthcare setting using a mixed-methods approach. We conducted semi-structured interviews. We used the Edmonton Symptom Assessment Scale and Brief Pain Instrument on older adults (N=17) with HF in the home healthcare setting within 10 days of hospital discharge. The mean age was 76±9.25 years, nearly 50% were female, and most (90%) were White. The majority of participants managed pain with medications. Loss of appetite had the highest mean severity score (3.88±2.50) of symptoms measured. The mean score for pain at its worst was 4.94±3.07. Pain interfering with sleep had the highest mean score (4.24±3.36). Using content analysis we identified 4 distinct themes regarding the pain experience: (1) differences in the pain experiences before and after being diagnosed of HF, (2) symptoms accompanied with pain, (3) health care providers’ pain assessment, and (4) knowledge about pain management. These findings will contribute to the development and evaluation of a pain assessment and management protocol targeting older adults with HF in the home healthcare setting.
COGNITION, SELF-RATED COGNITIVE HEALTH, AND CONCERNS ABOUT ALZHEIMER’S DISEASE IN OLDER KOREAN AMERICANS
Authors: Jang Yuri , Park Nan Sook , Chiriboga David , Yoon Hyunwoo , Rhee Min-Kyoung
Published: November 2019

Responding to the dearth of research on cognitive health in older ethnic minorities, the present study explored the associations among cognitive performance, self-rated cognitive health, and concerns about Alzheimer’s Disease (AD) in older Korean Americans. We hypothesized that (1) cognitive performance and self-rated cognitive health would be moderately associated; (2) both cognitive performance and self-rated cognitive health would be associated with concerns about AD; and (3) the effect of cognitive performance on concerns about AD would be mediated by self-rated cognitive health. Analyses of the survey data of 2,150 older Korean Americans (mean age = 73.2) residing in five states provided support for the hypotheses. Cognitive performance, measured with a Korean version of the Mini-Mental State Exam (MMSE), and a single item asking respondents to rate their overall cognitive status on a 5-point scale (excellent/very good/good/fair/poor) were moderately associated. Both poor performance in the MMSE and negative ratings of cognitive health status were associated with increased concerns about AD. Mediation analyses using the macro PROCESS showed that the indirect effect of cognitive performance on the concerns about AD through self-rated cognitive health (−.01 [.002]) was significant (bias corrected 95% confidence interval for the indirect effect = −.02, −.01). That is, the effect of cognitive performance on the concerns about AD was mediated by individuals’ subjective evaluations of their cognitive health. Findings not only help better understand the psychological mechanisms that underlie cognitive health and AD concerns but also suggest avenues for interventions.
A Hostile Environment for Children? The Rights and Best Interests of the Refugee Child in the United Kingdom’s Asylum Law
Authors: Brittle Ruth
Published: November 2019

Children experiencing persecution, torture, ill-treatment, exploitation and violence are compelled to flee across international borders to seek protection in another state. When a child seeks international protection, the framework of rights under the Convention on the Rights of the Child and the Convention Relating to the Status of Refugees should guide a state to determine the child’s status and protection needs. However, a child’s best interests and right to protection may clash with a state’s interest in immigration control. Increasingly, states are implementing strict laws to discourage irregular migration and to encourage those without leave to remain to return to their countries of origin. Such laws or policies have an impact on people seeking international protection, including children. The UK government’s ‘hostile environment’ policy is an example of this and applies to all adults and children who enter the UK irregularly and have no right to remain. I argue that the UK’s approach violates its international obligations under the Convention on the Rights of the Child. This article analyses how the children’s rights framework, in particular the ‘best interests’ principle, is able to challenge the UK’s ‘hostile environment’ policy.
Toward efficient energy consumption in middle income housing buildings in Egypt
Authors: Hegazy Ibrahim Rizk
Published: November 2019

Current research pays special attention to the application of approaches that promote sustainable design in a built environment and ensure energy efficiency. In this context, the form of housing buildings is an important parameter that has a meaningful impact on the use of energy in housing buildings. Hence, this research attempts to study the impact of the form of housing buildings on energy efficiency taking into account the mid-hot weather conditions in one of the middle-income housing buildings in new communities in Egypt. To achieve the research aim, a comparative analysis is carried out using parametric numerical analysis—DesignBuilder energy analysis—to compare the various hypothetical proposals for different building configurations. The study determines that the efficiency of energy use in buildings depends to a large extent on their forms that will help urban designers and planners to propose the best energy performance in the form of housing buildings in the stage of conceptual design suitable for other environmental, social and economic urban planning issues. These results should be incorporated into the building codes adopted in Egypt’s new cities in order to reach more energy-efficient housing buildings in Egypt.
Human Immunodeficiency Virus Infection Is Associated With Preterm Delivery Independent of Vaginal Microbiota in Pregnant African Women
Authors: Gudza-Mugabe Muchaneta , Havyarimana Enock , Jaumdally Shameem , Garson Kirsty Lee , Lennard Katie , Tarupiwa Andrew , Mugabe Fortunate , Marere Tarisai , Mavenyengwa Rooyen T , Masson Lindi , Jaspan Heather B
Published: November 2019

Background

During pregnancy, the vaginal microbiota is relatively stable. However, African women have more diverse vaginal microbiota than their European counterparts, in addition to high human immunodeficiency virus (HIV) prevalence and risk of adverse birth outcomes. Although HIV is associated with alterations in vaginal microbiota and inflammation in nonpregnant women, these relationships are underexplored in pregnant women.

Methods

In this study, we characterize the vaginal microbiota and immune factors in pregnant African women who were HIV-uninfected (n = 314) versus HIV-infected (n = 42). Mucosal samples were collected once at the enrollment visit (between 15 and 35 weeks of gestation) and women were followed until delivery.

Results

Vaginal microbial communities of pregnant women with HIV were significantly more diverse than women without HIV (P = .004), with community structure also differing by HIV status (P = .002, R2 = 0.02). Human immunodeficiency virus infection was also associated with increased risk of preterm birth (PTB) (31% versus 15.3%; P = .066). In a multivariate analysis, HIV infection was independently associated with diverse vaginal community state type (CST)-IVA (P = .005) and CST-IVB (P = .018) as well as PTB (P = .049). No association between HIV status and cytokine concentrations was found.

Conclusions

Longitudinal studies with accurate gestational age assessment would be important to confirm these relationships.
Overall assessment of fermented feed for pigs: a series of meta-analyses
Authors: Xu Bocheng , Zhu Luoyi , Fu Jie , Li Zhi , Wang Yizhen , Jin Mingliang
Published: November 2019

As an alternative to antimicrobial growth promoters, fermented feed (FF) has been continuously developed for two decades; however, its effects on feed, performance, digestibility, and meat quality of pigs have yet to be systematically and comprehensively evaluated. This study aimed to (i) quantitatively evaluate the effects of fermentation on nutritional components of feed stuffs; (ii) quantitatively evaluate the effects of FF on pig growth performance, digestibility, and meat quality; and (iii) explore the dose–effect relationship. From PubMed and Web of Science (searched range from January 1, 2000 to April 4, 2019), we collected 3,271 articles, of which 30 articles (3,562 pigs) were included in our meta-analysis. Our analysis revealed that fermentation significantly increased the CP content in feed (P < 0.05). For weaned piglets and growing pigs, FF significantly improved ADG, G:F, DM digestibility, N digestibility, and energy digestibility (P < 0.05). However, compared with the basal diet, FF had no significant effects on growth performance and nutrient digestibility in finishing pigs (P > 0.05). In the subgroup analyses, fermented ingredients increased the growth performance of weaned piglets and growing pigs, and fermented additives promoted the growth of pigs at all stages. The dose–effect analysis confirmed that the optimal doses of fermented ingredients and additives were 8% and 0.15%, respectively. Furthermore, FF had beneficial impacts on meat quality through increased lightness, redness, marbling and flavor and reduced drip loss (P < 0.05). In conclusions, FF improved growth performance and meat quality primarily due to its positive effects on nutritive value and utilization.
Wild Bee Visitation Rates Exceed Pollination Thresholds in Commercial Cucurbita Agroecosystems
Authors: McGrady C M , Troyer R , Fleischer S J
Published: November 2019

Wild bees supply sufficient pollination in Cucurbita agroecosystems in certain settings; however, some growers continue to stock fields with managed pollinators due to uncertainties of temporal and spatial variation on pollination services supplied by wild bees. Here, we evaluate wild bee pollination activity in wholesale, commercial pumpkin fields over 3 yr. We identified 37 species of bees foraging in commercial pumpkin fields. Honey bees (Apis mellifera L. [Hymenoptera: Apidae]), squash bees (Eucera (Peponapis) Say, Dorchin [Hymenoptera: Apidae]), and bumble bees (Bombus spp., primarily B. impatiens Cresson [Hymenoptera: Apidae]) were the most active pollinator taxa, responsible for over 95% of all pollination visits. Preference for female flowers decreased as distance from field edge increased for several bee taxa. Visitation rates from one key pollinator was negatively affected by field size. Visitation rates for multiple taxa exhibited a curvilinear response as the growing season progressed and responded positively to increasing floral density. We synthesized existing literature to estimate minimum ‘pollination thresholds’ per taxa and determined that each of the most active pollinator taxa exceeded these thresholds independently. Under current conditions, renting honey bee hives may be superfluous in this system. These results can aid growers when executing pollination management strategies and further highlights the importance of monitoring and conserving wild pollinator populations.
Indications for hip arthroscopy in pediatric patients a systematic review
Authors: Awad Moayd Abdullah H , Bajwa Arpun K , Slaunwhite Erin , Logan Karl J , Wong Ivan H
Published: November 2019

The purpose of this study was to evaluate the current available literature on hip arthroscopy and determine the clinical indications in the pediatric patient population (age ≤ 18). In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), a comprehensive literature search was performed on the 23 October 2018 using PubMed, Cochrane Library, Embase and e-books to identify research surrounding the use of hip arthroscopy in the pediatrics. Exclusion criteria were studies that described joints other than the hip, animal studies, systematic reviews, open procedures and those that reported solely on patients aged 19-year-old and older. From 232 studies, 57 were reviewed in detail; 17 articles were removed as their indication fell into a category of ‘diagnostic hip arthroscopy for pain’ or no clear separation between the data on the adult and pediatric population could be made in a full text review of the paper. Eleven categories were identified as indications for hip arthroscopy in the pediatric population. At best a Grade C recommendation can be made to support the use of hip arthroscopy in the pediatric population. Our results support our hypothesis. Despite the exponential increase in hip arthroscopy over the last decade, limited evidence exists in support of its use in the pediatric (≤18) population. Our findings support the need for further research in delineating the indications for its use, as clearly arthroscopy may be advantageous in many situations, particularly in light of the alternatives.
Targeted delivery and enhanced gene-silencing activity of centrally modified folic acid–siRNA conjugates
Authors: Salim Lidya , Islam Golam , Desaulniers Jean-Paul
Published: November 2019

One of the major hurdles in RNAi research has been the development of safe and effective delivery systems for siRNAs. Although various chemical modifications have been proposed to improve their pharmacokinetic behaviour, their delivery to target cells and tissues presents many challenges. In this work, we implemented a receptor-targeting strategy to selectively deliver siRNAs to cancer cells using folic acid as a ligand. Folic acid is capable of binding to cell-surface folate receptors with high affinity. These receptors have become important molecular targets for cancer research as they are overexpressed in numerous cancers despite being expressed at low levels in normal tissues. Employing a post-column copper-catalyzed alkyne–azide cycloaddition (CuAAC), we report the synthesis of siRNAs bearing folic acid modifications at different positions within the sense strand. In the absence of a transfection carrier, these siRNAs were selectively taken up by cancer cells expressing folate receptors. We show that centrally modified folic acid–siRNAs display enhanced gene-silencing activity against an exogenous gene target (∼80% knockdown after 0.75 μM treatment) and low cytotoxicity. In addition, these siRNAs achieved potent dose-dependent knockdown of endogenous Bcl-2, an important anti-apoptotic gene.
ATIM-01. NIVOLUMAB AND BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA; A TRANSLATIONAL TRIAL IN PROGRESS
Authors: Eibye Simone , Hasselbalch Benedikte , Marie Svane Inge , Reker Hadrup Sine , Rønn Olsen Lars , Skjoeth-Rasmussen Jane , Scheie David , Østrup Olga , Skovgaard Poulsen Hans , Lassen Ulrik
Published: November 2019

Glioblastoma multiforme (GBM) is an aggressive brain tumor with a poor prognosis. Standard of care at diagnosis is surgical resection, followed by radiation and temozolomide. Receiving this therapy, the median survival is 14.6 months [1]. We have no standard treatment for relapse and known options have limited effect. There is an urgent need for novel treatment interventions to improve clinical outcomes and quality of life. Recently, improved overall survival has been achieved with immune therapeutics in melanoma and renal cell carcinoma. Accordingly, it has been posited that immunotherapy may offer promise in other difficult cancers such as GBM [2]. We present our translational study; a phase II open label, two-armed translational study of Nivolumab and Bevacizumab for recurrent GBM, who have failed Stupp’s regime [1]. Patients are included in two arms depending on possibly salvage neurosurgical resection. Both arms receive Nivolumab and Bevacizumab administrated every second weekend, but the surgical arm also receive Nivolumab 7 days prior surgery. We expect 40 patients; 20 in each arm. Enrollment period is expected to 20 months, started October 2018. Our primary objective is to make preliminary assessment of immune related biomarkers, including PD-L1; therefore, we perform full genome sequencing on tumor biopsies from the surgical arm and on blood samples from both arms. We evaluate changes in the transcriptomic landscape caused by the check-point inhibition and relation to response as compared with baseline sequencing data, as well as the impact of tumor mutation burden and neoepitope load. We investigate the tumor microenvironment by harvesting tumor infiltrating lymphocytes and study the composition by flow-cytometry. The patients are evaluated by blood samples, FET-PET as wells as clinical examinations to evaluate PFS and OS. Overall the study will provide us with a unique possibility to investigate and thereof predict which patients will profit from the treatment.
ATIM-07. EFFICACY AND SAFETY OF NIVOLUMAB IN PATIENTS WITH FIRST RECURRENCE OF GLIOBLASTOMA: A MULTICENTER, OPEN-LABEL, NON-COMPARATIVE STUDY (ONO-4538-19)
Authors: Kagawa Naoki , Aoki Tomokazu , Sugiyama Kazuhiko , Wakabayashi Toshihiko , Arakawa Yoshiki , Yamaguchi Shigeru , Tanaka Shota , Nishikawa Ryo
Published: November 2019

BACKGROUND

The anti-programmed cell death protein 1 (PD-1) immune checkpoint antibody, nivolumab, may be beneficial in patients with recurrent glioblastoma.

OBJECTIVE

This open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma.

METHODS

Patients with a first recurrence of histologically confirmed World Health Organization (WHO) Grade IV glioma, after treatment with temozolomide plus radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression based on Response Assessment in Neuro-Oncology (RANO) criteria or development of toxicity. The primary endpoint was 1-year overall survival rate (1y-OS) assessed using a Bayesian approach. The prespecified efficacy criteria were that the Bayesian posterior mean 1y-OS with nivolumab would be 49%, and the Bayesian posterior probability threshold for exceeding the 1y-OS of bevacizumab (34.5%) from the Japanese Phase II study (JO22506) would be 93%.

RESULTS

Of the 50 patients enrolled, 44 (93.5%) had recurrent malignant glioma (glioblastoma and gliosarcoma), 26 (59.1%) had measurable disease, and 4 (9.1%) received corticosteroids at baseline. The posterior mean (90% Bayesian credible intervals) 1y-OS with nivolumab was 54.35% (42.27–66.21), and the observed posterior probability of exceeding the 1y-OS of bevacizumab (34.5%, JO22506) was 99.7%. The median (90% confidence interval) overall and progression-free survival (PFS) was 13.09 months (10.38, 17.68) and 1.45 months (1.41, 1.54), respectively. One partial response was observed (objective response rate [ORR] 1/26 evaluable patients [3.8%]). The grade 3–5 treatment-related adverse event rate was 16.0%; most adverse events resolved and were manageable.

CONCLUSION

The 1y-OS with nivolumab monotherapy in Japanese patients was higher than that in the bevacizumab group in the JO22506 study. However, PFS and ORR were not improved compared with JO22506. The safety profile of nivolumab was consistent with that observed in other tumor types.
ATIM-13. MULTIMODAL IMMUNOTHERAPY WITH IO-VAC® FOR PATIENTS WITH GBM: A SINGLE INSTITUTION EXPERIENCE
Authors: Van Gool Stefaan , Makalowski Jennifer , Stuecker Wilfried
Published: November 2019

Multimodal immunotherapy (Newcastle Disease Virus (NDV) + modulated electrohyperthermia + IO-VAC® + immunomodulatory strategies) is an innovative treatment for primary GBM and might prolong overall survival (OS). IO-VAC® consists of DCs loaded with autologous tumor antigens and matured with cytokine cocktail and NDV. We retrospectively reviewed 132 cases of primary GBM. Multimodal immunotherapy was integrated as individualized treatment approach and following different scenario’s in combination with standard treatment in the first line treatment in 71 patients, used at time of first or subsequent relapse as treatment with or without chemotherapy in 61 cases. Median ages were resp. 55 and 53 y. Median KPI at start of immunotherapy was 90 and 80. Median OS for the patients treated with immunotherapy as part of first-line treatment was 20 months with 2-y OS of 40% (CI95%: -13,+13). Median OS for patients treated at time of relapse was 7 months with but still with 18-m OS of 16% (CI95%: -12,+9). Two resp. 1 patients were lost of follow up. A subgroup of 34 GBM patients (10 females) with median age 58y (20–67) was detected, who received NDV + modulated electrohyperthermia during Temozolomide maintenance cycles followed by two IO-VAC® DC vaccinations, and further NDV + modulated electrohyperthermia courses. Median KPI was 70 (60–100). MGMT status was methylated (12), unmethylated (13), unknown (9). Median OS for this subgroup was 23.4 months with 2-year OS of 48% (CI95%: -18,+20). Immunotherapy was feasible without immunotherapy-related side effects of grade III or more. The data suggest that multimodal immunotherapy with IO-VAC® already during and after maintenance chemotherapy, at time of achieved minimal residual disease with local therapy, might help in prolongation of OS. Prolongation of OS in a small group of patients at time of relapse was also demonstrated. IO-VAC® is an approved advanced therapy medicinal product (DE-NW-04-GMP-2015-0030).
ATIM-15. SUSTAINED COMPLETE RADIOGRAPHIC RESPONSE AND PROLONGED SYSTEMIC IMMUNE ACTIVATION IN A PATIENT WITH MGMT UNMETHYLATED MIDLINE GLIOBLASTOMA RECEIVING CMV pp65-LAMP RNA-PULSED DENDRITIC CELL VACCINES
Authors: Rahman Maryam , Ghiaseddin Ashley , Yegorov Oleg , Yang Changlin , Dechkovskaia Anjelika , Tran David , Massini Tara , Kresak Jesse , Mitchell Duane
Published: November 2019

BACKGROUND

We initiated a Phase 2, randomized, placebo-controlled, clinical trial evaluating the efficacy of autologous CMV pp65-LAMP RNA pulsed dendritic cell vaccines mixed with GM-CSF and administered during cycles of adjuvant dose-intensified temozolomide (ATTAC II, NCT02465268).

STUDY OBJECTIVE

A patient with partially resected GBM experienced a sustained complete radiographic response after receiving five DC vaccines. Peripheral blood responses were characterized to examine possible immunologic biomarkers concordant with a sustained clinical response.

METHODS

Patients with newly diagnosed glioblastoma undergoing surgical resection are eligible and randomized 2:1 to DC vaccine arms vs placebo (PBMCs in saline). DC vaccines consist of CMV pp65 RNA conjugated either to the full-length lysosomal associated membrane protein (LAMP) or to the short LAMP signal sequence. Patients undergo leukapheresis for DC generation prior to standard chemoradiation and receive cycle 1 of dose-intensified temozolomide (100 mg/m^2 x 21 days) before first three biweekly intradermal DC vaccines admixed with GM-CSF. Subsequent DC vaccines (total of 10) are given monthly with each diTMZ cycle with an intradermal tetanus-diphtheria booster given 6-24hrs before the third, fifth, seventh, and ninth DC vaccines. PBMCs and serum are collected for immune monitoring.

RESULTS

A 58-year old white male with partially-resected, MGMT-unmethlyated, p53 mutant, H3.3 mutant, midline glioblastoma was enrolled on the ATTAC II study and experienced a complete radiographic response after the fifth DC vaccine that has been sustained > 10 months. Immune monitoring by Elispot, cytokine array, and single-cell RNA sequencing have revealed significant expansion of CMV pp65-specific immune responses, increased circulating IFNg, and marked systemic expansion of cytotoxic T cells and iNKT cells during vaccination. These responses were sustained through cycles of diTMZ despite profound lymphopenia.

CONCLUSIONS

CMV pp65-LAMP RNA-pulsed DC vaccination was associated with profound immunologic and clinical response in a patient with MGMT unmethylated midline glioblastoma.
ATIM-27. TUMOR MUTATIONAL BURDEN PREDICTS RESPONSE TO ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN MALIGNANT GLIOMA PATIENTS: ASSESSMENT OF TRANSCRIPTIONAL AND IMMUNOLOGICAL CORRELATES
Authors: Gromeier Matthias , Brown Michael , Beuabier Nike , Yan Hai , He Yiping , Zhang Gao , Desjardins Annick , Herndon James , Bolognesi Dani , Friedman Allan , Friedman Henry , McSherry Frances , Lin Xiang , Wei Zhi , Nair Smita , Peters Katherine , Randazzo Dina , Sampson John , McLendon Roger , Bigner Darell , Ashley David
Published: November 2019

BACKGROUND

The live attenuated oral poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We have previously reported that deep sequencing of biopsy material obtained prior to PVSRIPO infusion confirmed that a very low mutational load is associated with longer survival.

METHODS

Patient tumor material from both phase I and 2 clinical trials was collected pre PVSRIPO. When available, post-treatment tissue from longitudinal samples were also collected. Tissue was subjected to RNA sequencing, histological analysis, and flow cytometry analysis. RNAseq analyses were performed comparing pre- and post- treatment expression profiles and computational predictions of tumor immune composition deciphered changes after PVSRIPO therapy. Histology and flow cytometry quantitated myeloid, CD8/4/regulatory T cell densities, and other immune cell types after treatment and compared to baseline tissue similarly analyzed to detect changes.

RESULTS

To date, analysis of phase 1 trial data has demonstrated a correlation between low TMB and increased markers of immunological gene expression profiles. This trend was not observed in TCGA samples that were almost exclusively primary GBM suggesting and interplay with prior therapy or evolution with recurrence.

CONCLUSION

Our findings presented here suggest that response to PVSRIPO therapy, and possibly that of other modalities engaging innate antiviral signatures in situ, may be dependent upon prevailing tumor microenvironment composition/status at the time of treatment.
ATIM-28. PHASE II TRIAL OF AV-GBM-1 (AUTOLOGOUS DENDRITIC CELLS LOADED WITH TUMOR ASSOCIATED ANTIGENS) AS ADJUNCTIVE THERAPY FOLLOWING SURGERY PLUS CONCURRENT CHEMORADIATION IN NEWLY DIAGNOSED GBM PATIENTS
Authors: Bota Daniela , Taylor Thomas , Picconi David , Duma Christopher , Aiken Robert , LaRocca Renato , Xiao-Tang Kong , Fu Beverly , Alsharif Mohamad , Hsieh Candace , Nistor Gabriel , Dillman Robert
Published: November 2019

Newly-diagnosed glioblastoma (GBM) patients have a limited survival (18–24 months). In the last decade immunotherapy has improved survival for patients with other malignancies, but not GBM. Herein we present the design and initial enrollment results for the AV-GBM-1 single-arm phase 2 trial. The study enrolls patients with primary GBM who have undergone craniotomy, have a tumor cell culture established, and complete satisfactory leukapheresis prior to planned concurrent chemotherapy and radiation. Patients are scheduled to receive up to 8 vaccine injections at weeks 1, 2, 3, 8, 12, 16, 20 and 24. Blood samples are collected just prior to each injection. The primary endpoint is overall survival from date of enrollment for intent-to-treat with AV-GBM-1. The study has fully enrolled 26 of planned 55 patients. The cell line success rate is 30/32, with 6 in progress; successful completion of leukapheresis is 28/29. Two patients have completed all 8 doses, two discontinued after dose 3 and dose 6 because of progressive disease; 15 are currently in treatment, and 6 are about to start treatment. There have been seven SAE, all for hospitalizations related to GBM. For the first 8 treated patients, plasma samples from baseline and weeks 2, 3, and 8 have been analyzed for immune markers by RayBiotech Life Inc. using quantitative multiplex ELISA array. Markers reflecting Th1, Th2, Th17 pathways and B-cells, natural killer cells and cytotoxic T-lymphocytes increased in 7/8 patients. Principal component analysis demonstrates correlative marker groupings with early dominance of Th1/Th17 (weeks 1 and 2) followed by Th2/immunoglobulins at week 8. These findings show that these patient-specific dendritic cell vaccines are inducing pro-inflammatory responses similar to what was observed in a previous trial in melanoma. The study is progressing efficiently. Full enrollment data may be available for presentation at the time of the annual meeting.
ATIM-32. PREDICTORS OF IMPROVED SURVIVAL FOLLOWING ONCOLYTIC VIRUS TREATMENT IN PATIENTS WITH RECURRENT GLIOBLASTOMA: GENE EXPRESSION ANALYSIS FROM THE PHASE IB G207 CLINICAL TRIAL
Authors: Cassady Kevin , Miller Katherine , Prasad Nripesh , Maric Dragan , Bernstock Josh , Roth Justin , Barker Naomi , Coleman Jennifer , Schieffer Kathleen , Leraas Kristen , Miller Anthony , Leavenworth Jianmei , Cutter Gary , Whitley Richard , Roizman Bernard , Yancey Gillespie G , Mardis Elaine , Markert James
Published: November 2019

Our Phase I trials of experimental virotherapy for recurrent glioblastoma (GBM) have shown that inoculation with a conditionally replication-competent early generation oncolytic herpes simplex virus (oHSV), G207, is safe. However, while 17 of 37 subjects experienced objective clinical responses, the highly attenuated oHSV did not uniformly improve survival. We sought to identify predictors that would identify mechanisms contributing to survival and improve future trial design, by studying accrued samples. We analyzed pre-treatment biopsy and post-G207-treatment tumor samples (collected D2-5 post injection) banked from the patients enrolled in the phase IB G207 trial. The key findings from these patients suggest that productive G207 infection and G207-induced changes in gene expression were predictive of oHSV therapeutic success. RNAseq-based transcriptome analysis of these samples revealed that both the intrinsic IFN mediated antiviral response and adaptive immune functional response in patients correlated significantly with improved survival following G207 inoculation. Further, GBM tissue stained using multiplex fluorescent immunohistochemistry supported differences in the tumor microenvironments that were identified from RNAseq data analysis. Our data indicate that both viral gene expression and the resulting intrinsic anti-viral and recruited adaptive response were critical for survival after G207 inoculation and predict survival with this early generation oHSV in patients with recurrent malignant glioma.