Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN)

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual\u27s point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of \u27sporadic\u27 AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers

Positron emission tomography and magnetic resonance imaging methods and datasets within the dominantly inherited Alzheimer network (DIAN)

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case–control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual’s point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of ‘sporadic’ AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN)

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of 'sporadic' AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A randomized trial of synthetic osmotic cervical dilator for induction of labor vs dinoprostone vaginal insert

BACKGROUND: Induction of labor is a commonly performed obstetrical intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower in achieving cervical ripening but have a lower risk of adverse effects. OBJECTIVE: This study aimed to compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with those of dinoprostone. STUDY DESIGN: This was an open-label superiority randomized controlled trial in 4 English hospitals. Eligible participants were women ≥16 years of age undergoing induction of labor for a singleton pregnancy at ≥37 weeks’ gestation with vertex presentation and intact membranes. The women were randomly assigned to receive either Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, body mass index, and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by the Bishop score. The primary outcome was failure to achieve vaginal delivery (ieor a cesarean delivery being performed). The secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible. RESULTS: Between December 19, 2017 and January 26, 2021, 674 women were randomized (337 to Dilapan-S, and 337 to dinoprostone). The trial did not reach its planned sample size of 860 participants because of restrictions on research during the COVID-19 pandemic. The primary outcome was missing for 2 women in the dinoprostone group. Failure to achieve vaginal delivery (or a cesarean delivery being performed) occurred in 126 women (37.4%) allocated to Dilapan-S and in 115 (34.3%) women allocated to dinoprostone (adjusted risk difference, 0.02; 95% confidence interval, −0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. CONCLUSION: Women undergoing induction of labor with Dilapan-S have similar rates of cesarean delivery and maternal and neonatal adverse events compared with dinoprostone

A randomized trial of synthetic osmotic cervical dilator for induction of labor vs dinoprostone vaginal insert

Background: Induction of labor is a commonly performed obstetric intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower to achieve cervical ripening but have a lower risk of adverse effects. Objective: To compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with dinoprostone. Study Design: This was an open-label, superiority randomized controlled trial in four English hospitals. Eligible participants were women ≥ 16 years of age undergoing induction of labor for a singleton pregnancy, ≥ 37 weeks’ gestation with vertex presentation and intact membranes. Women were randomly assigned to receive Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, BMI and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by Bishop score. The primary outcome was failure to achieve vaginal delivery (i.e. Cesarean delivery). Secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible. Results: Between 19 December 2017 and 26 January 2021, 674 women were randomized (337 to Dilapan-S and 337 to dinoprostone). The trial did not reach its planned sample size of 860 due to restrictions on research during the Covid-19 pandemic. The primary outcome was missing for two women in the dinoprostone group. Failure to achieve vaginal delivery (Cesarean section) occurred in 126 women (37.4%) allocated to Dilapan-S, and 115 (34.3%) women allocated to dinoprostone (adjusted risk difference 0.02, 95% confidence interval -0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. Conclusion: Women undergoing induction of labor with Dilapan-S have similar rates of caesarean section and maternal and neonatal adverse events compared to dinoprostone

Mythologıcal elements ın transıtıon perıods of tahtacı socıety at "Taşeli" terrıtory

Araştırma sahası olan Taşeli Yöresi, Akdeniz Bölgesi’nin orta kesiminde yer alır. Taşeli Yöresi, Orta Toroslar’ da Alanya’nın doğusundan başlayarak kıyıda Gazipaşa, Anamur, Bozyazı, Aydıncık ve Silifke’nin batı kesimleri ile iç kesimlerde Gülnar, Mut ve Ermenek’i kapsayan ve arazi yapısı çok kayalık ve engebeli olan bir bölgedir. Çalışmanın sınırlılığı Anamur, Bozyazı, Silifke, Mut ilçelerinde yerleşik Yanınyatır ve Hacı Emirli Ocağına bağlı Tahtacı oymaklarıdır. Çalışmada zengin bir kültüre sahip olan Tahtacıların geçiş dönemleri olarak adlandırılan doğum, evlenme/düğün ve ölüme ilişkin inançlarındaki uygulamalar incelenecek ve bunların Türk kültürü içerisindeki yeri gösterilerek içerisindeki mitolojik unsurlar ortaya çıkarılacaktır. Araştırmamızda nitel araştırma ilkeleri çerçevesinde gözlem, görüşme ve doküman analizi yöntemleri kullanılmıştır. Bir toplumun manevi değerlerini yansıtan gerçek ve kutsal kabul edilen mitler halkın içerisinde çeşitli unsurlarıyla, farklı inanış ve uygulamalarla varlığını sürdürmektedir. Dolayısıyla Taşeli Yöresi Tahtacıları arasında, insanların korunmaya muhtaç oldukları, kutsala duydukları ihtiyaç sebebiyle bu geçiş dönemleri esnasında görülen inanış ve uygulamalarda birçok mitolojik unsura rastlanmaktadır. Sonuç olarak görülmektedir ki Tahtacılar arasında görülen geçiş dönemlerine ait inanç ve uygulamalarda Türk mitolojisine ait uygulamalar kendisini açık bir şekilde göstermektedir.The research area is “Taşeli” Territory located in the central part of Mediterranian Region. The area is located in the Central Taurus Mountains starting from east of Alanya covering Gazipaşa, Anamur, Bozyazı, Aydıncık and west part of Silifke at the Coast of Mediterranian Sea. It also covers Gülnar, Mut and Ermenek towns in the inlands. The limitation of the study is Tahtaci tribes which belong to the Yanınyatır and Hacı Emirli guilds and are settled in Anamur, Bozyazı, Silifke and Mut towns. Practices of birth, marriage/wedding and death beliefs are named as the transition periods. In this study, not only transition periods of Tahtaci Society which has a rich culture will be examined but also mythological elements will be revealed by showing their place in Turkish Culture. Observation, interview and document analysis methods were used within the framework of the qualitative research approach. Myths reflecting the moral values of a society and accepted as real and sacred are still in existence inside people with its different beliefs, elements and practices. Therefore, there are lots of mythological elements resulting from the need of protection, and sacred of the people could be seen in beliefs and practices during this transition periods among Taşeli Territory Tahtacis. As a result of applications of Turkish mythology, it shows itself clearly in the beliefs and practices that belong to the transition periods among Tahtacis

Head and Neck Cancer International Group (HNCIG) Consensus Guidelines for the Delivery of Postoperative Radiation Therapy in Complex Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

Radiation therapy (RT) consensus contouring guidelines in the postoperative setting for complex cutaneous squamous cell carcinoma of the head and neck have been developed by expert clinicians in the field of head and neck and dermato-oncology and members of the Head and Neck Cancer International Group to assist radiation oncologists involved in the management of this disease. These guidelines present a set of principles used to define postoperative RT volumes and corresponding minimum doses after resection of all macroscopic tumor with or without microscopic residual disease. It is anticipated they will promote the harmonization of postoperative RT globally and contribute to a reduction in treatment variation among clinicians, allowing for RT quality and outcomes assessment across institutions

Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network

INTRODUCTION: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD).METHODS: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross-sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (C-11-PiB PET) and structural magnetic resonance imaging (MRI).RESULTS: Female carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences.DISCUSSION: Our findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD

T1 and FLAIR signal intensities are related to tau pathology in dominantly inherited Alzheimer disease

Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (mu) and standard deviation (sigma) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-mu in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1-sigma and FLAIR-sigma) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR-mu decreased and T1-sigma and FLAIR-sigma increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity-based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients