Due to the competitive edge it confers on students, educational institutions, and non-English speaking nations in a globalized economy, English as a medium of instruction (EMI) has been gaining ...popularity in tertiary education in non-native English-speaking (NNES) countries. Institute-wide EMI implementation has often been imposed by top-down decisions, in combination with the optimistic view that the horse should always be placed before the cart. However, emerging evidence suggests that the delivery of such programs to NNES students has led to new pedagogical challenges and learning problems that go beyond the scope of language learning and teaching and deserve immediate attention. For example, how would an instructor respond to situations in which students’ learning of content is compromised by their limited language proficiency? This book draws on the current practice of EMI in diverse disciplines and university settings and examines how these new pedagogical and learning issues can be addressed. The discussion also involves a reflection on the essence of EMI in relation to the use of the first language (L1) as the medium of instruction in tertiary education. In addition, the book includes discussion about how to ensure and maintain the quality of EMI programs and assess the readiness of stakeholders for such programs, which include administrators, teachers, and students. The discussion is led by exemplars in Hong Kong and Taiwan, where the majority of students are native Chinese speakers, in the hope of developing critical perspectives and practical guidelines as references for EMI in other NNES settings.
Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants ...with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.
In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 normal to 5 most impaired), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.
Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval CI, 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57).
The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).
Purpose An essential aspect of patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) is the integration of patient perspectives and experiences with clinical data to ...evaluate interventions. Thus, PCOR and CER require capturing patient-reported outcome (PRO) data appropriately to inform research, healthcare delivery, and policy. This initiative’s goal was to identify minimum standards for the design and selection of a PRO measure for use in PCOR and CER. Methods We performed a literature review to find existing guidelines for the selection of PRO measures. We also conducted an online survey of the International Society for Quality of Life Research (ISOQOL) membership to solicit input on PRO standards. A standard was designated as “recommended” when >50 % respondents endorsed it as “required as a minimum standard.” Results The literature review identified 387 articles. Survey response rate was 120 of 506 ISOQOL members. The respondents had an average of 15 years experience in PRO research, and 89 % felt competent or very competent providing feedback. Final recommendations for PRO measure standards included: documentation of the conceptual and measurement model; evidence for reliability, validity (content validity, construct validity, responsiveness); interpretability of scores; quality translation, and acceptable patient and investigator burden. Conclusion The development of these minimum measurement standards is intended to promote the appropriate use of PRO measures to inform PCOR and CER, which in turn can improve the effectiveness and efficiency of healthcare delivery. A next step is to expand these minimum standards to identify best practices for selecting decision-relevant PRO measures.
A peer-support program called Resilience In Stressful Events (RISE) was designed to help hospital staff cope with stressful patient-related events. The aim of this study was to evaluate the impact of ...the RISE program by conducting an economic evaluation of its cost benefit.
A Markov model with a 1-year time horizon was developed to compare the cost benefit with and without the RISE program from a provider (hospital) perspective. Nursing staff who used the RISE program between 2015 and 2016 at a 1000-bed, private hospital in the United States were included in the analysis. The cost of running the RISE program, nurse turnover, and nurse time off were modeled. Data on costs were obtained from literature review and hospital data. Probabilities of quitting or taking time off with or without the RISE program were estimated using survey data. Net monetary benefit (NMB) and budget impact of having the RISE program were computed to determine cost benefit to the hospital.
Expected model results of the RISE program found a net monetary benefit savings of US $22,576.05 per nurse who initiated a RISE call. These savings were determined to be 99.9% consistent on the basis of a probabilistic sensitivity analysis. The budget impact analysis revealed that a hospital could save US $1.81 million each year because of the RISE program.
The RISE program resulted in substantial cost savings to the hospital. Hospitals should be encouraged by these findings to implement institution-wide support programs for medical staff, based on a high demand for this type of service and the potential for cost savings.
Metastatic breast cancers (mBCs) are largely resistant to immune checkpoint blockade, but the mechanisms remain unclear. Primary breast cancers are characterized by a dense fibrotic stroma, which is ...considered immunosuppressive in multiple malignancies, but the stromal composition of breast cancer metastases and its role in immunosuppression are largely unknown. Here we show that liver and lung metastases of human breast cancers tend to be highly fibrotic, and unlike primary breast tumors, they exclude cytotoxic T lymphocytes (CTLs). Unbiased analysis of the The Cancer Genome Atlas database of human breast tumors revealed a set of genes that are associated with stromal T-lymphocyte exclusion. Among these, we focused on CXCL12 as a relevant target based on its known roles in immunosuppression in other cancer types. We found that the CXCL12 receptor CXCR4 is highly expressed in both human primary tumors and metastases. To gain insight into the role of the CXCL12/CXCR4 axis, we inhibited CXCR4 signaling pharmacologically and found that plerixafor decreases fibrosis, alleviates solid stress, decompresses blood vessels, increases CTL infiltration, and decreases immunosuppression in murine mBC models. By deleting CXCR4 in αSMA⁺ cells, we confirmed that these immunosuppressive effects are dependent on CXCR4 signaling in αSMA⁺ cells, which include cancer-associated fibroblasts as well as other cells such as pericytes. Accordingly, CXCR4 inhibition more than doubles the response to immune checkpoint blockers in mice bearing mBCs. These findings demonstrate that CXCL12/CXCR4-mediated desmoplasia in mBC promotes immunosuppression and is a potential target for overcoming therapeutic resistance to immune checkpoint blockade in mBC patients.
To report the frequency and severity of optical coherence tomography (OCT) retinal thickness measurement errors and to describe parameters that predict these errors.
Observational case series.
Two ...hundred consecutive patients undergoing OCT imaging.
One eye (primary) from each of 200 consecutive patients undergoing Stratus OCT imaging (Carl Zeiss Meditec, Dublin, CA) with radial lines or fast macular thickness-based acquisition protocols was selected for review by 2 graders. On each of the line scans, graders evaluated the position of the automated retinal boundary lines (inner retinal surface and retinal pigment epithelium band) used by the OCT machine for thickness calculations and graded the positioning on a 6-point subjective, categorical error scale to generate an error score. The presence of thickness errors was correlated with various parameters, including the analysis confidence assessment reported by the OCT software, disease diagnosis, retinal morphologic features, the foveal center thickness standard deviation (FCTSD), and the FCTSD-to-foveal center thickness (FCT) ratio.
Average OCT retinal thickness error score.
Errors of retinal boundary detection and thickness measurement were observed in 92% of eyes, but were severe in only 13.5% of eyes. The identification of an error or low analysis confidence by the OCT software was strongly associated with the severity of the retinal thickness errors. A higher FCTSD-to-FCT ratio and presence of subretinal fluid also were associated with more severe errors. Retinal cysts and a diagnosis of retinal vascular disease such as diabetic macular edema were less likely to be associated with significant errors.
Retinal thickness measurement errors occur frequently with current OCT segmentation and analysis algorithms. Severe errors are more frequent in eyes with subretinal pathologic features, but generally are detected by the OCT software. A high FCTSD-to-FCT ratio (>0.1) also may alert the clinician to the possibility of thickness errors. Clinical studies, particularly those pertaining to subretinal diseases, should consider these errors when incorporating OCT imaging in the study design.
The General English Proficiency Test (GEPT) is a 5-level, criterion-referenced English as a Foreign Language (EFL) testing system implemented in Taiwan to assess the general English proficiency of ...EFL learners. In 1999, with the aim of encouraging the general study of English and to result in beneficial washback effects on the teaching and learning of English, the Ministry of Education lent its support to the Language Training and Testing Center in the development of the GEPT. Throughout a decade of efforts, the GEPT has won popular recognition in Taiwan. To date, more than 4.3 million Taiwanese have taken the test. This article first documents the evolution of the GEPT from the perspectives of test development and validation. The article then provides an overview of how GEPT scores are used in both educational and professional domains and discusses several key issues and problems that have emerged due to the new context introduced by the GEPT. Finally, the article outlines how the GEPT will address the challenges it faces in the years to come.
To identify modifying factors that preserve functional independence among individuals at high dementia risk.
Health and Retirement Study participants aged 65 years or older without baseline ...activities of daily living (ADL) limitations (n = 4,922) were interviewed biennially for up to 12 years. Dementia probability, estimated from direct and proxy cognitive assessments, was categorized as low (i.e., normal cognitive function), mild, moderate, or high risk (i.e., very impaired) and used to predict incident ADL limitations (censoring after limitation onset). We assessed multiplicative and additive interactions of dementia category with modifiers (previously self-reported physical activity, smoking, alcohol consumption, depression, and income) in predicting incident limitations.
Smoking, not drinking, and income predicted incident ADL limitations and had larger absolute effects on ADL onset among individuals with high dementia probability than among cognitively normal individuals. Smoking increased the 2-year risk of ADL limitations onset from 9.9% to 14.9% among the lowest dementia probability category and from 32.6% to 42.7% among the highest dementia probability category. Not drinking increased the 2-year risk of ADL limitations onset by 2.1 percentage points among the lowest dementia probability category and 13.2 percentage points among the highest dementia probability category. Low income increased the 2-year risk of ADL limitations onset by 0.4% among the lowest dementia probability category and 12.9% among the highest dementia probability category.
Smoking, not drinking, and low income predict incident dependence even in the context of cognitive impairment. Regardless of cognitive status, reducing these risk factors may improve functional outcomes and delay institutionalization.
CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome ...single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.696_698del p.Lys232del) in exon 7 of NAD(P) dependent steroid dehydrogenase-like (
NSDHL), a gene that encodes an enzyme in the cholesterol biosynthesis pathway. We also found that males with intellectual disability in another reported family with an NSDHL mutation (c.1098 dup p.Arg367SerfsX33) have CKS. These two mutations, which alter protein folding, show temperature-sensitive protein stability and complementation in Erg26-deficient yeast. As described for the allelic disorder CHILD syndrome, cells and cerebrospinal fluid from CKS patients have increased methyl sterol levels. We hypothesize that methyl sterol accumulation, not only cholesterol deficiency, causes CKS, given that cerebrospinal fluid cholesterol, plasma cholesterol, and plasma 24S-hydroxycholesterol levels are normal in males with CKS. In summary, CKS expands the spectrum of cholesterol-related disorders and insight into the role of cholesterol in human development.
Interleukin-12 (IL-12) has been described as a pivotal molecule in the immune response based in part on its ability to influence the differentiation of T helper (Th) cells into a type 1 (Th1) ...phenotype. This event is crucial in that appropriate differentiation of naive T cells can determine susceptibility or resistance to given pathogens by influencing the balance between cellular and humoral immunity. In order to further delineate the role of IL-12 in the immune response, we generated mice deficient for this cytokine. IL-12 knockout mice were viable, fully fertile, and displayed no obvious developmental abnormalities. Upon immunological analysis, these mice demonstrated an impaired ability to effect a Th1 response as well as an impaired ability to produce interferon-gamma in response to endotoxin in vivo. These data establish an essential role for IL-12 in the generation of optimal Th1 responses in vivo, but weak responses can occur independently of IL-12.