The <i>Ink4a/Arf</i> Locus Is a Barrier to Direct Neuronal Transdifferentiation

Price, James D.,Park, Ki-Youb,Chen, Jiadong,Salinas, Ryan D.,Cho, Mathew J.,Kriegstein, Arnold R.,Lim, Daniel A. Society for Neuroscience 2014 The Journal of neuroscience Vol.34 No.37

<P>Non-neurogenic cell types, such as cortical astroglia and fibroblasts, can be directly converted into neurons by the overexpression of defined transcription factors. Normally, the cellular phenotype of such differentiated cells is remarkably stable and resists direct cell transdifferentiation. Here we show that the <I>Ink4a/Arf</I> (also known as <I>Cdkn2a</I>) locus is a developmental barrier to direct neuronal transdifferentiation induced by transcription factor overexpression. With serial passage <I>in vitro</I>, wild-type postnatal cortical astroglia become progressively resistant to <I>Dlx2</I>-induced neuronal transdifferentiation. In contrast, the neurogenic competence of <I>Ink4a/Arf</I>-deficient astroglia is both greatly increased and does not diminish through serial cell culture passage. Electrophysiological analysis further demonstrates the neuronal identity of cells induced from <I>Ink4a/Arf-</I>null astroglia, and short hairpin RNA-mediated acute knockdown of p16Ink4a and p19Arf p16<SUP>Ink4a</SUP> and p19<SUP>Arf</SUP> indicates that these gene products function postnatally as a barrier to cellular transdifferentiation. Finally, we found that mouse fibroblasts deficient for <I>Ink4a/Arf</I> also exhibit greatly enhanced transcription factor-induced neuronal induction. These data indicate that <I>Ink4a/Arf</I> is a potent barrier to direct neuronal transdifferentiation and further suggest that this locus functions normally in the progressive developmental restriction of postnatal astrocytes.</P>

Development and Validation of an Attitudinal-Profiling Tool for Patients With Asthma

Aileen David-Wang,David Price,조상헌,James Chung-Man Ho,Chong-Kin Liam,Glenn Neira,Pei-Li Teh,REcognise Asthma and LInk to Symptoms and Experience 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.1

Purpose: To develop a profiling tool which accurately assigns a patient to the appropriate attitudinal cluster for the management of asthma. Methods: Attitudinal data from an online survey of 2,467 patients with asthma from 8 Asian countries/region, aged 18-50 years, having had ≥2 prescriptions in the previous 2 years and access to social media was used in a discriminant function analysis to identify a minimal set of questions for the Profiling Tool. A split-sample procedure based on 100 sets of randomly selected estimation and validation sub-samples from the original sample was used to cross-validate the Tool and assess the robustness of its predictive accuracy. Results: Our Profiling Tool contained 10 attitudinal questions for the patient and 1 GINA-based level of asthma control question for the physician. It achieved a predictive accuracy of 76.2%. The estimation and validation sub-sample accuracies of 76.7% and 75.3%, respectively, were consistent with the tool’s predictive accuracy at 95% confidence level; and their 1.4 percentage-points difference set upper-bound estimate for the degree of over-fitting. Conclusions: The Profiling Tool is highly predictive (>75%) of the attitudinal clusters that best describe patients with asthma in the Asian population. By identifying the attitudinal profile of the patient, the physician can make the appropriate asthma management decisions in practice. The challenge is to integrate its use into the consultation workflow and apply to areas where Internet resources are not available or patients who are not comfortable with the use of such technology.

Sun Protection Counseling by Pediatricians

Easton, Alyssa N.,Price, James H.,Boehm, Kathryn,Telljohann, Susan MediMedia Korea 1998 JAMA-Korea Vol.13 No.2

Molecular Volume Effects on the Dynamics of Polymerized Ionic Liquids and their Monomers

Choi, U Hyeok,Mittal, Anuj,Price Jr., Terry L.,Lee Jr., Minjae,Gibson Jr., Harry W.,Runt Jr., James,Colby Jr., Ralph H. Elsevier 2015 ELECTROCHIMICA ACTA Vol.175 No.-

<P><B>Abstract</B></P> <P>The dependences of the glass transition temperature and the dielectric constant on molecular volume of the repeat unit for polymerized ionic liquids, the monomers they were polymerized from and simple ionic liquids, are reviewed and compared. The ionic conductivities of these materials and the frequencies at which ionic rearrangements occur are shown to be controlled by their glass transition temperatures. The ionic conductivity is proportional to the product of dielectric constant and ionic rearrangement frequency, with the proportionality constant determined by the molecular volume of the repeat unit.</P>

Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia over three Decades

Roder, David,Karapetis, Christos S,Wattchow, David,Moore, James,Singhal, Nimit,Joshi, Rohit,Keefe, Dorothy,Fusco, Kellie,Powell, Kate,Eckert, Marion,Price, Timothy J Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. Materials and Methods: Kaplan-Meier productlimit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. Results: Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. Conclusions: We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres.

Metastatic Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia Over Three Decades

Roder, David,Karapetis, Christos S,Wattchow, David,Moore, James,Singhal, Nimit,Joshi, Rohit,Keefe, Dorothy,Fusco, Kellie,Buranyi-Trevarton, Dianne,Sharplin, Greg,Price, Timothy J Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

Estimating a Causal Model of Job Satisfaction in a Korean Hospital

서영준 ( Young Joon Seo ),고종욱 ( Jong Wook Ko ),( James L Price ) 한국보건행정학회 1995 보건행정학회지 Vol.5 No.1