Vowels production by Cantonese-speaking children with cochlear implant

"A dissertation submitted in partial fulfillment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, 30th June, 2010."Includes bibliographical references (p. 28-32).Thesis (B.Sc)--University of Hong Kong, 2010.This study investigated vowels production by Cantonese-speaking children with cochlear implant. Nineteen subjects with cochlear implant age ranged 2;05 to 6;01 years old were compared to 19 hearing children. All participants were required to produce 51 words, covering seven Cantonese monophthongs /a, i, E, O, u, y, J/ and ten Cantonese diphthongs /ui, Oi, ai, iu, Ey, Ai, ou, ei, au, Au/. The production accuracy was compared. Error patterns were investigated by phonological process and acoustic analysis. The production accuracy from cochlear implant subjects with hearing experience less than two years was significantly different than that of hearing children with similar hearing experience. A developmental and universal phonological acquisition process was observed. Developmental phonological rules were found in erroneous production. Articulatory complexity played an important role in vowels acquisition in CI groups. The result demonstrated a positive influence of cochlear implant on vowels production in Cantonese-speaking children.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Predictive Associations Between Prenatal and Postnatal Risk Factors and Developmental and Temperamental Outcomes Among Infants in Foster Care

Infants detained for maltreatment present with a number of prenatal and perinatal risk factors, including prenatal exposure to substances, prematurity, low birth weight, birth complications, and prolonged hospital stay. These factors pose significant risk for a broad range of infant outcomes critically linked to later functioning, including cognitive, language, motor, socio-emotional, and temperamental development (Del Giudice, 2012; Singer et al., 2008). However, many infants exposed to prenatal risk also develop normatively, highlighting the need to better understand how the postnatal environment influences individual differences in response to prenatal risk. Importantly, prior to adoptive placement, infants placed in foster care often face unique stressors, including multiple foster placements and trial stays with birth families. Exposure to these pre-placement postnatal factors vary substantially across individuals, and they likely have unique and cumulative effects on developmental outcomes (Fisher et al., 2005; Waterman et al., 2013). Emerging evidence from normative samples suggests that prenatal and postnatal factors may interact to influence developmental outcomes, potentially through prenatal programming of infant responses to postnatal environments (Pluess & Belsky, 2011). These theoretical models have yet to be tested among infants in foster care, despite a need to better understand which prenatal and postnatal risk factors influence outcomes for these high-risk children. Thus, the present study aims to disentangle prenatal and postnatal risk factors to examine their unique and interactive associations with differentiated developmental outcomes (cognitive, language, motor, socioemotional) and early temperament among high-risk infants transitioning from foster care to adoption. Participants include 68 infants aged 0-28 months (race-ethnicity: 26% Hispanic, 14% African-American, 11% Caucasian, 1% Asian/Pacific Islander, 26% Mixed, 22% Unknown) referred for developmental assessment within two months of placement in adoptive homes. Prenatal/perinatal risk factors (prematurity, substance exposure, birth weight, birth complications, hospital stay) and postnatal risk factors (birth parent stay, age detained, number of placements, age at adoption) were coded from previous medical, DCFS, and court records. Infants were assessed using the Bayley Scales of Infant Development (BSID-III) to evaluate cognitive, motor (fine and gross), language (receptive and expressive), and socioemotional development. In addition, the primary adoptive parent completed the Infant/Toddler Temperament Questionnaire to measure temperament domains (e.g., sensitivity, reactivity, regularity). Preliminary correlations revealed that cognitive and motor development were most robustly associated with prenatal risk (i.e., prematurity, birth weight) and perinatal risk factors (i.e., birth complications, duration of hospital stay), whereas infant temperament domains were additionally linked to postnatal risk factors (i.e., birth parent placement, age detained, age of adoption, number of placements). Furthermore, differential associations between individual risk factors and outcomes were observed, suggesting there are likely unique risk factors predictive of different infant outcomes. Next, stepwise regressions will be employed to examine the independent, cumulative, and interactive associations between prenatal and postnatal risk factors on each developmental and temperamental outcome. Results will provide insight into the individual and cumulative effects of prenatal and preplacement postnatal risk factors for infants transitioning from foster care to adoption. Implications for key prevention and intervention targets among high-risk infants will be discussed

RNA-seq: impact of RNA degradation on transcript quantification

Background The use of low quality RNA samples in whole-genome gene expression profiling remains controversial. It is unclear if transcript degradation in low quality RNA samples occurs uniformly, in which case the effects of degradation can be corrected via data normalization, or whether different transcripts are degraded at different rates, potentially biasing measurements of expression levels. This concern has rendered the use of low quality RNA samples in whole-genome expression profiling problematic. Yet, low quality samples (for example, samples collected in the course of fieldwork) are at times the sole means of addressing specific questions. Results We sought to quantify the impact of variation in RNA quality on estimates of gene expression levels based on RNA-seq data. To do so, we collected expression data from tissue samples that were allowed to decay for varying amounts of time prior to RNA extraction. The RNA samples we collected spanned the entire range of RNA Integrity Number (RIN) values (a metric commonly used to assess RNA quality). We observed widespread effects of RNA quality on measurements of gene expression levels, as well as a slight but significant loss of library complexity in more degraded samples. Conclusions While standard normalizations failed to account for the effects of degradation, we found that by explicitly controlling for the effects of RIN using a linear model framework we can correct for the majority of these effects. We conclude that in instances in which RIN and the effect of interest are not associated, this approach can help recover biologically meaningful signals in data from degraded RNA samples.American Heart Association (Predoctoral Fellowship

Prediction Accuracy of Serial Lung Ultrasound in COVID-19 Hospitalized Patients (Pred-Echovid Study)

The value of serial lung ultrasound (LUS) in patients with COVID-19 is not well defined. In this multicenter prospective observational study, we aimed to assess the prognostic accuracy of serial LUS in patients admitted to hospital due to COVID-19. The serial LUS protocol included two examinations (0–48 h and 72–96 h after admission) using a 10-zones sequence, and a 0 to 5 severity score. Primary combined endpoint was death or the need for invasive mechanical ventilation. Calibration (Hosmer–Lemeshow test and calibration curves), and discrimination power (area under the ROC curve) of both ultrasound exams (SCORE1 and 2), and their difference (DIFFERENTIAL-SCORE) were performed. A total of 469 patients (54.2% women, median age 60 years) were included. The primary endpoint occurred in 51 patients (10.9%). Probability risk tertiles of SCORE1 and SCORE2 (0–11 points, 12–24 points, and ≥25 points) obtained a high calibration. SCORE-2 showed a higher discrimination power than SCORE-1 (AUC 0.72 (0.58–0.85) vs. 0.61 (0.52–0.7)). The DIFFERENTIAL-SCORE showed a higher discrimination power than SCORE-1 and SCORE-2 (AUC 0.78 (0.66–0.9)). An algorithm for clinical decision-making is proposed. Serial lung ultrasound performing two examinations during the first days of hospitalization is an accurate strategy for predicting clinical deterioration of patients with COVID-19

The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma

We have previously characterized transcription factor LZIP to be a growth suppressor targeted by hepatitis C virus oncoprotein. In search of proteins closely related to LZIP, we have identified a liver-enriched transcription factor CREB-H. LZIP and CREB-H represent a new subfamily of bZIP factors. CREB-H activates transcription by binding to cAMP responsive element, box B, and ATF6-binding element. Interestingly, CREB-H has a putative transmembrane (TM) domain and it localizes ambiently to the endoplasmic reticulum. Proteolytic cleavage that removes the TM domain leads to nuclear translocation and activation of CREB-H. CREB-H activates the promoter of hepatic gluconeogenic enzyme phosphoenolpyruvate carboxykinase. This activation can be further stimulated by cAMP and protein kinase A. CREB-H transcript is exclusively abundant in adult liver. In contrast, the expression of CREB-H mRNA is aberrantly reduced in hepatoma tissues and cells. The enforced expression of CREB-H suppresses the proliferation of cultured hepatoma cells. Taken together, our findings suggest that the liver-enriched bZIP transcription factor CREB-H is a growth suppressor that plays a role in hepatic physiology and pathology

Genome-Wide Association Study of Hepatocellular Carcinoma in Southern Chinese Patients with Chronic Hepatitis B Virus Infection

One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (ORcombined = 1.31–1.39; pcombined = 2.71×10−5–5.19×10−4; PARcombined = 26–31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations