Genetic and Environmental Influences on Chinese Language and Reading Abilities

This study investigated the etiology of individual differences in Chinese language and reading skills in 312 typically developing Chinese twin pairs aged from 3 to 11 years (228 pairs of monozygotic twins and 84 pairs of dizygotic twins; 166 male pairs and 146 female pairs). Children were individually given tasks of Chinese word reading, receptive vocabulary, phonological memory, tone awareness, syllable and rhyme awareness, rapid automatized naming, morphological awareness and orthographic skills, and Raven's Coloured Progressive Matrices. All analyses controlled for the effects of age. There were moderate to substantial genetic influences on word reading, tone awareness, phonological memory, morphological awareness and rapid automatized naming (estimates ranged from .42 to .73), while shared environment exerted moderate to strong effects on receptive vocabulary, syllable and rhyme awareness and orthographic skills (estimates ranged from .35 to .63). Results were largely unchanged when scores were adjusted for nonverbal reasoning as well as age. Findings of this study are mostly similar to those found for English, a language with very different characteristics, and suggest the universality of genetic and environmental influences across languages

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

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 Web-Based Stratified Stepped Care Mental Health Platform (TourHeart): Semistructured Interviews With Stakeholders

BackgroundTourHeart, a web-based stratified stepped care mental health platform, is a one-stop solution that integrates psychoeducation and other well-being promotional tools for mental health promotion and mental illness prevention and evidence-based, low-intensity psychological interventions for the treatment of people with anxiety and depressive symptoms. Instead of focusing only on symptom reduction, the platform aims to be person-centered and recovery-oriented, and continual feedback from stakeholders is sought. Understanding the perspectives of users and service providers enables platform developers to fine-tune both the design and content of the services for enhanced service personalization and personal recovery. ObjectiveThis qualitative study evaluated a web-based mental health platform by incorporating the perspectives of both users and service providers who administered the platform and provided coaching services. The platform included both web-based and offline services targeting adults along the mental health spectrum based on the two-continua model of mental health and mental illness. MethodsInterview questions were designed based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework (RE-AIM). Views on offline services, the design of the web-based platform, user experience, and the contents of the platform were explored using semistructured interviews. A total of 27 service users and 22 service providers were recruited using purposive criterion sampling. A hybrid thematic analysis was performed to identify salient aspects of users’ and providers’ experiences with and views of the platform. ResultsTotally, 3 broad themes (namely, the quality of the platform, drivers for platform use, and coaching services) emerged from the interview data that highlighted users’ views of and experiences with the web-based platform. The platform’s general esthetics, operations, and contents were found to be critical features and drivers for continued use. Although coaching services were indispensable, participants preferred the autonomy and anonymity associated with web-based mental health services. ConclusionsThis study highlights the importance of web-based mental health services being easy to navigate and understand, being user-centric, and providing adequate guidance in self-help. It also confirms existing design standards and recommendations and suggests that more rigorous, iterative user experience research and robust evaluation should be conducted in the future adaptation of web-based stratified stepped care services, so that they can be more personalized and better promote personal recovery

The Genetic and Environmental Foundation of the Simple View of Reading in Chinese.

The Simple View of Reading (SVR) in Chinese was examined in a genetically sensitive design. A total of 270 pairs of Chinese twins (190 pairs of monozygotic twins and 80 pairs of same-sex dizygotic twins) were tested on Chinese vocabulary and word reading at the mean age 7.8 years and reading comprehension of sentences and passages one year later. Results of behavior-genetic analyses showed that both vocabulary and word reading had significant independent genetic influences on reading comprehension, and the two factors together accounted for most but not all of the genetic influences on reading comprehension. In addition, sentence comprehension had a stronger genetic correlation with word reading while passage comprehension showed a trend of stronger genetic overlap with vocabulary. These findings suggest that the genetic foundation of the SVR in Chinese is largely supported in that language comprehension and decoding are two core skills for reading comprehension in nonalphabetic as well as alphabetic written languages

A qualitative exploration of the experiences of school nurses during COVID-19 pandemic as the frontline primary health care professionals

Background: It is widely acknowledged that the experiences of frontline primary health care professionals during COVID-19 are important to understand how they respond and act under situations of pandemic as the gatekeepers in primary health care system. School nurses are primary health care professionals who lead health care in schools and practice in a holistic manner to address the needs of schoolchildren and school personnel. There are rising mental health concerns of frontline health care professionals with anxiety and panic disorders, somatic symptoms, and feeling isolated. No studies use a qualitative study approach to document community frontline school nursing professionals’ experiences and challenges during the COVID-19 pandemic. Hence, understanding the school nurses’ experiences and challenges to fight against COVID-19 in the communities is important. Purpose: This study aims to explore the experiences of school nurses during the COVID-19 pandemic in Hong Kong. Methods: A qualitative study design adopted the principles of thematic analysis. Nineteen school nurses were recruited to participate in individual semistructured interviews and shared their roles and responsibilities during the COVID-19 pandemic. Findings: Three themes indicated the school nurses’ expand professional responsibilities to fight against COVID-19 emerged from the data analysis. These were “Managing Stress,” “Navigating the School Through the Pandemic,” and “Raising the Profile of the School Nurse Professional,” Discussion: Findings reveal the important role of school nursing professionals in minimizing the community-wide risk posed by pandemics and the need to integrate them into planning and implementation of school health policies and guidelines in the primary health care system. This essential role in schools is necessary to assess, implement, monitor, prevent, and reduce the spread of virus in school communities and to minimize the burden to and extra health care resources utilized in the acute care setting during COVID-19 pandemic