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Purpose: A cancer diagnosis can result in a considerable financial burden to individuals and their households. This study aimed to investigate this problem in patients treated for melanoma brain metastases. Methods: An economic evaluation was conducted as a sub-study of a randomised controlled trial of whole brain radiotherapy (WBRT) versus observation following surgery and/or stereotactic radiosurgery (SRS) for 1-3 melanoma brain metastases. Employment status and pre-tax household income were measured at baseline and every 2 months for 12 months. Outcomes included changes in employment status or household income category at 12 months. Results: Of 125 patients, 64 were included in the analysis, 31 randomised to WBRT and 33 to observation, 61 patients were excluded because they were not in the workforce at baseline (42) or were unsure about their income (19). Mean age was 61 years (range 27-88), 37 (58%) completed employment questionnaires and 61 (96%) completed income questionnaires at baseline. Prior to treatment, 39% worked full-time, 8% part-time and 53% were unemployed. At 12 months, 23%, 12% and 65% individuals were employed full-time, part-time and unemployed, respectively. Job status change and household income at 12 months were not significantly different between the two treatment groups (p=0.18 and 0.87, respectively). Conclusions: A substantial proportion of patients experienced job loss after treatment of melanoma brain metastases, however this was similar for those undergoing WBRT or observation alone. Strategies to reduce the impact for both groups (e.g., financial counselling, employment rehabilitation) could be implemented by clinicians and allied health workers.

RATIONALE: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVES: To test differing durations of intravenous antimicrobials for CF exacerbations. METHODS: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percent predicted FEV(1) (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV(1) changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. CONCLUSIONS: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Size cues are increasingly common in brand names (e.g., Xiaomi and Mini Cooper), but scant research has investigated whether and how brand name size cues influence consumers’ perceptions. This research shows that a brand name size cue can evoke gender associations, which subsequently affect consumers’ perceived warmth and competence of the target brand. A series of seven studies provide converging evidence that brands with a size cue of smallness in the name are perceived to be warmer but less competent, while those with a size cue of bigness are perceived to be less warm but more competent. A combination of measurement-of-mediation and moderation-of-process approaches provide support for the role of gender associations underlying the effect of brand name size cues on consumers’ brand perceptions. This research also shows that brand name size cues can have diverging effects on the perceived warmth of the brand versus of the product. Finally, this research rules out alternative accounts based on perceived market power and firm size.

Deceptive advertising, or advertising that intends to mislead consumers by false claims or incomplete disclosure, is ubiquitous in the marketplace. Though prior research has shown that consumers generally view companies’ deceptive communication as unethical and react to it negatively, anecdotal evidence suggests that some consumers are more accepting of such misleading tactics than others. Delving deeper into this phenomenon, this research examines the role of self-construal on consumers’ responses toward deceptive advertising. Three studies provide converging evidence that interdependent (vs. independent) consumers are more tolerant of deceptive advertising, which is mediated by their attribution styles. Moreover, we further demonstrate the self-construal effect on lie acceptability decreases as the firm becomes smaller, when it is easier for consumers to pinpoint who should be responsible for the misconduct and thus are more likely to make internal attribution.

Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75g oral glucose tolerance test, excluding pre-existing diabetes. Cord plasma were analysed using targeted liquid-chromatography tandem mass-spectrometry to determine relative concentrations of 404 lipid species across 17 lipid classes. Birthweights were standardized for sex and gestational age by local references, and regression analyses adjusted for maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2h glucose, with false discovery-corrected p

This research demonstrates that under states of certainty, consumers with a relatively stronger global (local) identity prefer global (local) brands, whereas under states of uncertainty, consumers with a relatively stronger global (local) identity prefer local (global) brands. This effect occurs because uncertainty (certainty) activates a divergent (convergent) thinking style, which results in a preference for options that are more distant from (closer to) the identity to which consumers associate more strongly. The effect holds both when individuals’ global–local citizenship identity is measured and when it is manipulated. The research further establishes an important boundary condition for the effect. The effect holds in the citizenship identity context because people normally associate themselves with both local and global citizenship identities, and situational or dispositional factors only influence the degree to which they associate with each identity. The effect does not surface when individuals construe their local–global citizenship identities as interfering, meaning they conceive that holding one identity conflicts with holding the other.

The costs and benefits of various products, such as insurance and subscription services, are recurring. Marketers can choose to frame these attributes either as a series of periodic occurrences (e.g., “$10 per month”) or aggregate them over a longer period (“$120 per year”). Five studies show that the effectiveness of such temporal framing depends on consumers’ salient regulatory goals. Compared with prevention‐focused consumers, promotion‐focused consumers are more likely to perceive benefits, costs, and losses to be larger when they are framed in aggregate (vs. periodic) terms. Mediation analyses suggest that, relative to prevention‐focused consumers’ vigilant information processing style, promotion‐focused consumers’ eagerness makes them more susceptible to temporal framing effects. The results suggest that regulatory goal is a consequential factor in determining the effectiveness of temporal framing.

How does market power affect consumer perceptions and purchase behavior? In the theoretically and pragmatically important context of price increases, we theorize that (i) consumer price fairness perceptions decline with market power when a price increase is due to costs; and (ii) this fairness difference arises due to greater perceptions of controllability and, in turn, exploitation by firms with higher market power. Consistent with our theorizing, we further argue that market power does not affect fairness (iii) when prices rise due to demand (which is perceived as equally exploitative and unfair regardless of firm power) or (iv) when price increases are clearly beyond the firm’s control (and perceived as equally fair for firms with high and low market power). We provide empirical support for these predictions in a series of behavioral experiments combined with an analysis of retail scanner data. Together, our findings shed light on how market power and pricing actions jointly drive consumer perceptions of unfairness, with implications for firms’ pricing strategies, competition in the retail marketplace, and the principle of dual entitlement as a community standard of fairness in pricing.

Asymmetric pricing is less prevalent, and perceived as less fair, in collectivist (vs. individualist) cultures because it violates communal norms (Chen et al. 2018). We replicate this cultural difference by directly measuring managers' asymmetric pricing decisions and by priming self-construal among individual consumers as well as using country as a proxy for culture. In addition, we identify tactics that managers can employ to mitigate consumer unfairness perceptions. Together, these findings replicate, generalize, and extend the results in Chen et al. (2018), thereby shedding light on the generalizability of the principle of dual entitlement (Kahneman et al. 1986a, 1986b), a cornerstone of behavioral pricing.

Background Nausea and vomiting of pregnancy (NVP) is common and underlying mechanisms are poorly understood. Longer-term offspring outcomes are also not well documented. This study aimed to determine if NVP, even in milder forms, is associated with adverse pregnancy and childhood growth outcomes. Methods In the GUSTO prospective mother-offspring cohort, women with singleton pregnancies (n = 1172) recruited in first trimester responded to interviewer-administered questions at 26–28 weeks’ gestation about earlier episodes of NVP since becoming pregnant. Pregnancy outcomes were obtained from medical records. Offspring height and weight measured at 15 time-points between birth to 72 months (m) were standardised for age and sex. Results 58.5% (n = 686) reported mild-moderate vomiting (mNVP), 10.5% (n = 123) severe vomiting (sNVP) and 5.7% (n = 67) severe vomiting with hospitalisation (shNVP). There was no difference in odds of gestational diabetes, hypertensive disorders of pregnancy, labour induction or caesarean section after adjustment for covariates. sNVP was associated with late preterm delivery [34+ 0–36+ 6 weeks’, adjusted OR = 3.04 (95% CI 1.39,6.68)], without increased odds of neonatal unit admission. Compared with no NVP, boys born to mothers with sNVP were longer at birth [adjusted β = 0.38 standard deviations (SDs) (95% CI 0.02,0.73)], remained taller [0.64 SDs (0.23,1.04) at 72 m] and heavier [0.57 SDs (0.05,1.08) at 60 m] without differences in BMI. Conversely, girls born to mothers with shNVP were lighter from 48 m [− 0.52 SDs (− 1.00, − 0.03)] onwards with lower BMI [− 0.61 SDs (− 1.12,-0.09)]. Conditional growth modelling revealed significant sex-divergence in weight-gain at birth-3 m, 6-9 m and 4–5 years. Conclusions Severe NVP was associated with late preterm delivery, and both mild-moderate and severe NVP associated with sex-dependent differences in early childhood growth. Boys whose mothers had NVP were taller and heavier from birth with faster growth in the first year, whereas, girls had poorer weight gain and were lighter by 48 m. As even milder severities of NVP could have long-term impact on offspring growth, further research is needed to determine mechanisms involved and implications on future health. Trial registration Clinicaltrials.gov identifier NCT01174875.

The unprecedented crisis of COVID-19 posed severe negative consequences for consumers, marketers, and society at large. By investigating the effect of individuals' distance from the COVID-19 epicenter (i.e., the geographical area in which COVID-19 pandemic is currently most severe) on consumers' risk perception and subsequent behaviors, this research provides novel empirical findings that can offer practical insights for marketers. While intuitively, people expect individuals closer to the COVID-19 epicenter to generate a greater risk perception of the pandemic, empirical evidence from four studies provides consistent results for the opposite effect. We find that a closer (vs. farther) distance to the epicenter associates with lower (vs. higher) perceived risk of the pandemic, leading to less (vs. more) irrational consumption behaviors. We refer to this phenomenon as the ?distance proximity effect,? which holds for both physical and psychological distances. We further demonstrated that this effect is mediated by consumers' perception of uncertainty and moderated by individuals' risk aversion tendency. The current research contributes to the literature of consumers' risk perception and irrational consumption by highlighting a novel factor of distance proximity. It also offers some timely insights into managing and intervening COVID-19 related issues inside and outside an epicenter.

This research tests the idea that a salient global identity positively affects people’s willingness to pay for environmentally friendly products. Results from a large-scale multi-nation survey ( N = 75,934) as well as two studies ( N = 322) conducted in Singapore supported this prediction. We found that participants with a more (vs. less) dominant global identity indicated greater support for environmentally friendly products and exhibited increased pro-environmental behavior. We further show that the effect is driven by a stronger feeling of personal responsibility toward the environment among individuals who possess a dominant global identity. Findings from this research suggest that the formation of stronger global identity, a psychological consequence of increasing globalization, can have an important impact on people’s pro-environmental behavior.

BackgroundSipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and/or clinical responses to this treatment.MethodsA total of 50 patients with mCRPC were enrolled into a clinical trial (NCT01804465, ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-γ (IFN-γ) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as >30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis.ResultsWe found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival.ConclusionCombining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4.

The ubiquity of promotions and price discounts has prompted much research to understand how consumers respond to deals. In this research, we present an affective perspective for why some consumers may be more deal prone than others. Specifically, we propose that for interdependents (vs. independents), chancing upon a deal leads to heightened arousal and greater purchase intention for the discounted product. We further propose that this effect arises because interdependents (vs. independents) are more likely to possess a comparative mindset. Findings from five studies provide converging evidence to support our propositions. Across the studies, we adopt different operationalizations of self-construal (via country, cultural prime, self-construal scale and prime), measures of arousal (skin conductance and self-report measures) and use different product categories. We further show that when a comparative mindset is made salient for independents and interdependents, the observed effect dissipates.

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18 to 45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N=557 censored). Women who successfully conceived (N=475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N=373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated phenotypic data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition the S-PRESTO study, draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

Background: While socioeconomic position (SEP) is consistently related to pregnancy and birth outcome disparities, relevant biological mechanisms are manifold, thus necessitating more comprehensive characterization of SEP-exposome associations during pregnancy. Objectives: We implemented an exposomic approach to systematically characterize the socioeconomic landscape of prenatal exposures in a setting where social segregation was less distinct in a hypotheses-generating manner. Methods: We described the correlation structure of 134 prenatal exogenous and endogenous sources (e.g., micronutrients, hormones, immunomodulatory metabolites, environmental pollutants) collected in a diverse, population-representative, urban, high-income longitudinal mother-offspring cohort (N = 1341; 2009–2011). We examined the associations between maternal, paternal, household, and areal level SEP indicators and 134 exposures using multiple regressions adjusted for precision variables, as well as potential effect measure modification by ethnicity and nativity. Finally, we generated summary SEP indices using Multiple Correspondence Analysis to further explore possible curved relationships. Results: Individual and household SEP were associated with anthropometric/adiposity measures, folate, omega-3 fatty acids, insulin-like growth factor-II, fasting glucose, and neopterin, an inflammatory marker. We observed paternal education was more strongly and consistently related to maternal exposures than maternal education. This was most apparent amongst couples discordant on education. Analyses revealed additional non-linear associations between areal composite SEP and particulate matter. Environmental contaminants (e.g., per- and polyfluoroalkyl substances) and micronutrients (e.g., folate and copper) showed opposing associations by ethnicity and nativity, respectively. Discussion: SEP-exposome relationships are complex, non-linear, and context specific. Our findings reinforce the potential role of paternal contributions and context-specific modifiers of associations, such as between ethnicity and maternal diet-related exposures. Despite weak presumed areal clustering of individual exposures in our context, our approach reinforces subtle non-linearities in areal-level exposures. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This research is supported by the Singapore National Research Foundation under the Translational and Clinical Research (TCR) Flagship, and Open Fund Large Collaborative Grant (OFLCG) Programmes and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore - NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014; OFLCG/MOH-000504. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore.

Background Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if fetal growth deceleration followed by rapid postnatal weight gain is associated with childhood cardiometabolic risk biomarkers in a contemporary well-nourished population. Methods We defined fetal growth deceleration (FGD) as ultrasound-measured 2nd-3rd-trimester abdominal circumference decrease by ≥0.67 standard deviation score (SDS) and rapid postnatal weight gain (RPWG) as 0–2-year-old weight increase by ≥0.67 SDS. In the GUSTO mother-offspring cohort, we grouped 797 children into four groups of FGD-only (14.2%), RPWG-only (23.3%), both (mismatch, 10.7%) or neither (reference, 51.8%). Adjusting for confounders and comparing with the reference group, we tested associations of these growth groups with childhood cardiometabolic biomarkers: magnetic resonance imaging (MRI)-measured abdominal fat (n = 262), liver fat (n = 216), intramyocellular lipids (n = 227), quantitative magnetic resonance-measured overall body fat % (BF%) (n = 310), homeostasis model assessment of insulin resistance (HOMA-IR) (n = 323), arterial wall thickness (n = 422) and stiffness (n = 443), and blood pressure trajectories (ages 3–6 years). Results Mean±SD birthweights were: FGD-only (3.11 ± 0.38 kg), RPWG-only (3.03 ± 0.37 kg), mismatch (2.87 ± 0.31 kg), reference (3.30 ± 0.36 kg). FGD-only children had elevated blood pressure trajectories without correspondingly increased BF%. RPWG-only children had altered body fat partitioning, higher BF% [BF = 4.26%, 95% confidence interval (CI) (2.34, 6.19)], HOMA-IR 0.28 units (0.11, 0.45)] and elevated blood pressure trajectories. Mismatch children did not have increased adiposity, but had elevated ectopic fat, elevated HOMA-IR [0.29 units (0.04,0.55)] and the highest blood pressure trajectories. Associations remained even after excluding small-for-gestational-age infants from analyses. Conclusions Fetal growth deceleration coupled with rapid postnatal weight gain was associated with elevated childhood cardiometabolic risk biomarkers without correspondingly increased BF%.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

We investigated whether adding anthropometric measures to HbA1c would have stronger discriminative ability over HbA1c alone in detecting dysglycemia (diabetes and prediabetes) among Asian women trying to conceive. Among 971 Singaporean women, multiple regression models and area under receiver-operating characteristic (AUROC) curves were used to analyze associations of anthropometric (weight, height, waist/hip circumferences, 4-site skinfold thicknesses) and HbA1c z-scores with dysglycemia (fasting glucose ≥6.1 mmol/L with 2-hour glucose ≥7.8 mmol/l). The prevalence of dysglycemia was 10.9%. After adjusting for sociodemographic/medical history, BMI (Odds Ratio [OR] = 1.62 [95%CI 1.32-1.99]), waist-to-height ratio (OR = 1.74 [1.39-2.17]) and total skinfolds (OR = 2.02 [1.60-2.55]) showed the strongest associations with dysglycemia but none outperformed HbA1c (OR = 4.09 [2.81-5.94]). After adjustment for history, adding BMI, waist-to-height ratio and total skinfolds (anthropometry trio) as continuous variables to HbA1c (AUROC = 0.80 [95%CI 0.75-0.85]) performed similarly to HbA1c alone (AUROC = 0.79 [0.74-0.84]). However, using clinically-defined thresholds without considering history, as in common clinical practice, BMI ≥ 23 kg/m2 + HbA1c ≥ 5.7% (AUROC = 0.70 [0.64-0.75]) and anthropometry trio + HbA1c ≥ 5.7% (AUROC = 0.71 [0.65-0.76]) both outperformed HbA1c ≥ 5.7% alone (AUROC = 0.61 [0.57-0.65]). In a two-stage strategy, incorporating BMI ≥ 23 kg/m2 alongside HbA1c ≥ 5.7% into first-stage screening to identify high risk women for subsequent oral glucose tolerance testing improves dysglycemia detection in Asian women preconception. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version The S-PRESTO study group includes Anne Eng Neo Goh, Anne Rifkin-Graboi, Anqi Qiu, Bee Wah Lee, Bobby Cheon, Christiani Jeyakumar Henry, Ciaran Gerard Forde, Claudia Chi, Doris Fok, Elaine Quah, Elizabeth Tham, Evelyn Chung Ning Law, Evelyn Xiu Ling Loo, Faidon Magkos, Falk Mueller-Riemenschneider, George Seow Heong Yeo, Helen Yu Chen, Hugo P S van Bever, Joanne Yoong, Joao N. Ferreira., Jonathan Tze Liang Choo, Kenneth Kwek, Kuan Jin Lee, Lieng Hsi Ling, Ling Wei Chen, Lourdes Mary Daniel, Marielle V. Fortier, Mary Foong-Fong Chong, Mei Chien Chua, Michael Meaney, Neerja Karnani, Oon Hoe Teoh, Queenie Ling Jun Li, Sendhil Velan, Shephali Tagore, Shirong Cai, Shu E Soh, Sok Bee Lim, Stella Tsotsi, Stephen Chin-Ying Hsu, Sue Anne Toh, Teng Hong Tan, Tong Wei Yew, Victor Samuel Rajadurai, Wee Meng Han, Wei Wei Pang, Yin Bun Cheung, and Yiong Huak Chan. We also acknowledge the efforts of the research coordinators, admin staff, study managers and participants. This work was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore - NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore.

BackgroundSelf-reported maternal active smoking has been associated with reduced offspring birth length and shorter stature in early and late childhood.ObjectiveTo use circulating cotinine as an objective biomarker to investigate the association between smoking and environmental tobacco smoke (ETS) exposure in pregnancy and longitudinal measures of offspring length/height from birth to 60 months.MethodsIn 969 maternal-offspring dyads from the GUSTO cohort, maternal plasma cotinine at 26–28 weeks’ gestation was measured by LC/MS/MS and categorized into four groups: Group 1: cotinine ResultsAdjusting for infant sex, gestational age at birth, ethnicity, maternal age, education, parity, BMI, and height, Group 4 offspring were shorter at birth [z-score β = −0.42 SD units (SDs) (95% CI = −0.77 to −0.06)] than Group 1 offspring. Group 4 offspring continued to be shorter at older ages, with similar effect sizes at 3 months [−0.57 SDs (−0.95 to −0.20)], 36 months [−0.53 SDs (−0.92 to −0.15)], 48 months [−0.43 SDs (−0.81 to −0.04)], and 60 months [−0.57 SDs (−0.96 to −0.17)]. Associations were particularly marked in boys. No significant differences in stature were observed in Groups 2 or 3 compared with Group 1.ConclusionsThis Asian longitudinal study associated high prenatal cotinine with persistently shorter stature in offspring from birth and into early childhood, whilst low prenatal cotinine levels and ETS exposure showed no such association.ImplicationsLittle is known about the long-term effects of prenatal tobacco exposure on offspring stature in Asia where passive smoking is common. This study has used an objective biomarker to reveal that the association of prenatal tobacco exposure with offspring length/height mainly occurs at a high maternal cotinine level of greater than 14 ng/mL in pregnancy, consistent with active smoking, but no significant associations were found with lower cotinine levels, consistent with passive smoking. Encouraging women to quit smoking prior to or during pregnancy may avert the long-term negative impact on their child’s height despite appreciable prenatal ETS exposure.

Phthalate exposure is related to the development of allergic diseases; however, studies regarding its effect on lung function are limited. Our study aims to identify an association between phthalate exposure at different ages and lung function in children at age 9 by conducting a cohort study. The Taiwan Birth Panel Study (TBPS) was established from April 2004 to January 2005. Urine samples were collected from children in the TBPS cohort at ages 2, 5, and 9years. Urinary phthalate metabolite concentrations were measured via ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry. Questionnaires, lung function tests and serum IgE levels were obtained from children at the age of 9. Multiple linear regressions adjusted for confounding factors were applied to investigate the associations between phthalate exposure at different ages and lung function at age 9. Our results demonstrate that in children with allergic diseases, a per log unit increase in the urinary phthalate metabolite mono-ethyl phthalate (MEP) concentration at age 9 was associated with a decreasing forced expiratory volume in 1 sec (FEV1) (β=-25.22; 95% CI: -47.53 to -2.91 per log ml/ln-μg/g cr) and forced vital capacity (FVC) (β=-32.3; 95% CI: -63.51 to -1.09 per log ml/ln-μg/g cr). For children with high serum IgE levels (>100kU/L) at age 9, the urinary MEP concentrations at the same age were negatively associated with the FEV1 (β=-30.4; 95% CI: -56.8 to -4.0 per log ml/ln-μg/g cr), FVC (β=-47.6; 95% CI: -84.2 to -11.0 per log ml/ln-μg/g cr) and peak expiratory flow (PEF) (β=-102.4; 95% CI: 180.2 to -24.7 per log ml/ln-μg/g cr). Phthalate exposure at ages 2 and 5 had little effect on lung function at age 9. Our study suggests that concurrent exposure to phthalates, such as MEP, is negatively associated with lung function in children. Further investigation is required to elaborate on this correlation.

Sun-induced chlorophyll fluorescence (SIF) from spaceborne sensors is a promising tool for global carbon cycle monitoring, but its application is constrained by insufficient understanding of the drivers underlying diurnal SIF dynamics. SIF measurements from ground-based towers can reveal diurnal SIF dynamics across biomes and environmental conditions; however, meaningful interpretation of diurnal variations requires disentangling impacts from canopy structure, plant physiology, instrument configuration and retrieval methods, which often interact with and confound each other. This study aims to unpack these drivers using 1) concurrent ground and airborne canopy-scale and leaf-scale measurements at a corn field, 2) a mechanistic SIF model that explicitly considers the dynamics of photochemistry (via the fraction of open photosystem II reaction centers, qL) and photoprotection (via nonphotochemical quenching, NPQ) as well as their interactive dependence on the sub-canopy light environment, and 3) cross-comparison of SIF instrument configurations and retrieval methods. We found that crop row orientations and sun angles can introduce a distinctive midday dip in SIF in absence of stress, due to a midday drop of absorbed photosynthetically active radiation (APAR) when crop rows are north-south oriented. Canopy structure caused distinctive responses in both qL and NPQ at different positions within the vertical canopy that collectively influenced fluorescence quantum yield (ΦF) at the leaf scale. Once integrated at the canopy scale, diurnal dynamics of both APAR and canopy escape probability (e) are critical for accurately shaping diurnal SIF variations. While leaf-level qL and NPQ exhibited strong diurnal dynamics, their influence was attenuated at the canopy scale due to opposing effects on SIF at different canopy layers. Furthermore, different system configurations (i.e., bi-hemispherical vs. hemispherical-conical) and retrieval methods can bias the SIF magnitude and distort its diurnal shapes, therefore confounding the interpretation of inherent strength and dynamics of SIF emission. Our findings demonstrate the importance of crop row structures, interactive variations in canopy structure and plant physiology, instrument configuration, and retrieval method in shaping the measured dynamics of diurnal SIF. This study highlights the necessity to account for these factors to accurately interpret satellite SIF, and informs future synthesis work with different SIF instrumentation and retrieval methods across sites.

According to the dual entitlement principle, consumers find it fair for firms to price asymmetrically to cost changes—that is, for firms to increase prices when costs increase but maintain prices when costs decrease. However, a meta-analysis reveals asymmetric pricing is less prevalent in collectivistic (vs. individualistic) countries (study 1). We propose a fairness-based explanation, demonstrating that interdependent consumers in collectivistic cultures perceive asymmetric pricing to be less fair than do independent consumers in individualistic cultures (studies 2, 4, and 5). We attribute this cultural variation to culture-specific relationship norms. Specifically, we argue that while the practice of asymmetric pricing is consistent with the exchange norms among independent consumers that emphasize self-interest pursuit, it is inconsistent with the communal norms among interdependent consumers mandating firm benevolence. Supporting this argument, we find that (a) directly manipulating communal (vs. exchange) norms yields similar differences in fairness perceptions that mimic those due to culture (study 3), (b) the cultural differences are mediated by the communal mandate for firm benevolence (study 4), and (c) the cultural differences are mitigated when a firm frames asymmetric pricing as benevolent (study 5). We conclude by discussing the theoretical and managerial implications of these findings.

Background Perfluoroalkyl substances (PFASs) are wildly distributed environmental pollutants. Laboratory mice exposed prenatally to PFASs develop smaller birth weight but are more likely to become obese in adulthood. The evidences in human studies are still inconclusive. Methods The participants were 429 mother-infant pairs from Taiwan Birth Panel Study. These children were followed serially and growth data were collected through face to face interviews and records in Child Healthcare Handbooks until 108 months of age. The age-specific z-scores for weight (WAZ), length/height (LAZ/HAZ) and BMI (BMIAZ) were calculated. PFASs in umbilical cord blood were analyzed by ultra-high-performance liquid chromatography/tandem mass spectrometry. Results At birth, perfluorooctyl sulfonate (PFOS) levels were negatively associated with weight and height [per ln unit: adjusted β (95% confidence interval, CI) = − 0.14 (− 0.26, − 0.01) for WAZ and − 0.16 (− 0.31, − 0.02) for LAZ]. However, these adverse impacts diminished as children grow up. When stratified the analysis by gender, the effects of prenatal PFOS exposure were more obvious for girls especially during the time span of 6 to 12 and 12 to 24 months of age [per ln unit: adjusted β (95% CI) = − 0.25 (− 0.47, − 0.04) and − 0.24 (− 0.41, − 0.04) for WAZ, respectively; per ln unit: adjusted β (95% CI) = − 0.33 (− 0.59, − 0.08) and − 0.25 (− 0.45, − 0.05) for BMIAZ, respectively]. Later in the period of 60 to 108 months of age, positive association between prenatal PFOS exposure and girls' BMI was observed [per ln unit: adjusted β (95% CI) = 0.34 (0.007, 0.68) for BMIAZ]. There was little evidence in these data for a consistent association of perfluorooctanoic acid (PFOA) with any of the indicators. Conclusions Our study had shown that higher prenatal PFOS exposure was associated with decreased fetal growth, but the effects were diminished as children grow up. Modest effect of gender specific manner was observed.

Numerous studies have explored the associations between environmental pollutants and pediatric health. Recent studies have investigated the issue in Asia, but no systematic review has been published to date. This study aims to elucidate the issue by summarizing relevant epidemiologic evidence for cohorts in Asia, using information from the Birth Cohort Consortium of Asia (BiCCA). Environmental pollutants include mercury, environmental tobacco smoke (ETS), polychlorinated biphenyls (PCB), perfluoroalkyl substances (PFAS) and phthalates. This study sought to classify the effects of such compounds on fetal growth and pregnancy outcomes, neurodevelopment and behavioral problems, allergic disease and immune function and the endocrine system and puberty. These evidences showed ETS has been associated with infant birth weight, children's neurodevelopment and allergy disease; mercury and PCB have been shown to affect children's neurodevelopment; phthalate has effects on endocrine function; PFAS alters children's neurodevelopment, the endocrine system, and the allergic response. However, more consistent and coordinated research is necessary to understand the whole picture of single environmental and/or co-exposure and children's health. Therefore, harmonization and international collaboration are also needed in Asia.

This research examines the impact of a salient global (or local) identity on individual's regulatory goals. Specifically, we show that when people's identity as a global citizen is salient, they are more likely to focus on promotion goals; whereas when their identity as a local citizen is salient, they are more likely to focus on prevention goals. We further show that this arises because people are likely to adopt a more abstract or higher level (vs. concrete or lower level) construal when their global (local) identity is salient. Evidence from three studies supports this central proposition.

Background: Prenatal tobacco exposure (maternal active and passive smoking) has been associated with childhood obesity. It is unclear whether this is directly attributable to in utero exposure, with a graded effect across exposure groupings, or to associated lifestyle factors. Methods: In 971 maternal-offspring pairs from the GUSTO cohort, maternal plasma cotinine at 26-28 weeks' gestation and smoking history were used to categorise mothers into prenatal tobacco exposure groups. Offspring anthropometry was obtained longitudinally from birth and at ages 3, 6, 9, 12, 15, 18, 24, 36 months (m). Multiple linear regression, mixed linear models and counterfactual-based analysis were conducted, adjusting for ethnicity, maternal age, education, 1st trimester BMI, parity and gestational age. Findings: All results were compared with unexposed offspring (undetectable maternal cotinine and no history of tobacco exposure). Infants with low maternal cotinine (0·17-13·99 ng/ml) had a similar birthweight, while those with high maternal cotinine (≥14ng/ml) had a lower birthweight [β(95%CI) -162·0g (-291·8,-32·2)]. Low maternal cotinine was associated with higher offspring weight z-score at 18m [0·24 SDs (0·01,0·47)] and 36m [0·27 SDs (0·03,0·52)], and higher BMI z-score at 6m and across 15-36m [36m: 0·45 SDs (0·20,0·70)]. Over the 36m period high maternal cotinine was associated with accelerated gain in weight zscore [0·17 SDs/year (0·03,0·31)]. There was a dose-dependent BMI z-score acceleration, with offspring of mothers with low and high cotinine showing 0·09 (0·01,0·17) SDs/year and 0·17 (0·02,0·32) SDs/year gain, respectively. The association of prenatal tobacco exposure with 36m BMI was not explained by reduced breast-feeding, poor diet and increased screen time. Interpretation: Avoiding even low levels of prenatal tobacco exposure may reduce the risk of early childhood obesity. In utero programming by tobacco exposure directly influences childhood BMI rather than through unhealthy childhood lifestyle factors. Funding Statement: Singapore's National Medical Research Council and Singapore Institute for Clinical Sciences, A*STAR. Declaration of Interests: KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10042) and the NIHR Southampton Biomedical Research Centre) and the European Union (Erasmus+ Programme Early Nutrition eAcademy Southeast Asia-573651-EPP-1-2016-1- DE-EPPKA2-CBHE-JP). KMG, Y-SC, and YSL have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG, S-YC and Y-SC are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have no financial or personal conflict of interest to declare. Ethics Approval Statement: The study was ethically-approved by the Institutional Review Boards of the KK Women’s and Children’s Hospital, and the National University Health System. Informed written consent was obtained from all participants

AIMS: Whether low physical activity levels and high sedentary behaviour impair glucose metabolism before conception remains insufficiently documented, especially in at-risk populations such as Asian women. We examined the associations of physical activity and screen time, a proxy for sedentary behaviour, with fasting and post-load glucose levels of Singaporean women enrolled in a multi-ethnic Asian preconception study. METHODS: Moderate and vigorous physical activity and screen time (television and other electronic devices) were self-reported by women enrolled in the S-PRESTO cohort. Fasting, 30-min and 120-min glucose levels before/during an oral 75-g glucose tolerance test were measured. Associations of physical activity and screen time with glucose levels were analysed using generalized estimating equations. RESULTS: 946 women aged 31.4±3.7 years were examined; 72% of Chinese, 15.5% Malay, 9.3% Indian and 3.2% of mixed ethnicities. 32% of women reported being active, 36% watching television ≥2 h/day and 26% using electronic devices ≥3 h/day. In adjusted models, vigorous, but not moderate physical activity, was associated with lower overall glucose levels, and more strongly with post-challenge than fasting glucose levels. Compared to women not engaging in vigorous physical activity, those engaging in ≥75 min/week had lower fasting (-0.14 [-0.28, -0.01] mmol/L), 30-min (0.35 [-0.68, -0.02]) and 120-min (-0.53 [-0.16, -0.90]) glucose levels (overall p-value=0.05). We found no associations of screen time with glucose levels. CONCLUSIONS: Independently of the time spent in non-vigorous physical activity and using screens, engaging in vigorous physical activity may be a modifiable factor to improve glucose regulation in women of Asian ethnicities attempting to conceive.

5045 Background: SipT is an FDA-approved autologous cellular immunotherapy targeting Prostatic Acid Phosphatase (PAP) that improves survival in patients with mCRPC. Combining immunotherapies could provide opportunities to enhance efficacy. We performed a randomized phase II trial adding CTLA-4 blockade with Ipi following SipT treatment and assessed whether timing of this sequence could modify immune and/or clinical responses to this treatment. Methods: Fifty chemotherapy-naïve mCRPC pts were randomized to receive ipi (4 doses of 3mg/kg every 3 weeks) either immediately (n = 24) or 3 weeks (n = 26) following completion of sipT. Blood was collected at various time points of the study. Immune-related adverse events (irAE) were recorded. The primary endpoint was to determine the proportion of pts who achieved an antibody titer of ³1:400 to PA2024, the targeting cassette in SipT and/or PAP. Clinical response was defined as ³30% reduction in serum prostate specific antigen (PSA) compared to pre-treatment levels. Radiographic progression-free survival (rPFS) and overall survival (OS) were defined as from the date of randomization to the date of radiographic progression and the date of death, respectively, or last follow-up date. Luminex assays for anti-PAP and anti-PA2024 specific serum IgG and ELISpot for IFN-g production against PAP and PA2024 were used to assess antigen-specific B and T cells responses, respectively. Modulation of circulating immune cells was evaluated by CyTOF. Results: SipT + Ipi did not induce any unexpected irAEs. The timing of Ipi did not significantly alter the rates of clinical response, rPFS, OS, toxicity, nor antigen-specific B and T cell responses. Clinical responses were observed in 6 of 50 (12%) pts and were often durable (median 140 days, range 55-689 days). Pts experiencing irAEs were more likely to have a PSA response (P = 0.001). The median rPFS was 5.7 months (mos). The median OS was 31.9 mos. This treatment induced antibody and T cell immune responses irrespective of treatment arm. Single cell assessment bt CyTOF demonstrated that treatment induced CD4 and CD8 T cell activation that was more pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells were associated with better clinical outcomes even at baseline. Lower frequencies of CTLA-4 positive T cells was associated with prior radiation therapy. Prior radiation treatment was associated with improved rPFS (6.5 vs. 3.9 mos, P = 0.004). Conclusions: These findings suggest that pre-existing immunity may help dictate responsiveness to Ipi and SipT combination immunotherapy in mCRPC pts. Prior radiation therapy seems to leave not only a lasting impression on the T cell compartment, but also can associate with improved clinical outcomes with subsequent immunotherapy. Clinical trial information: NCT01804465.

In the present work, waste polystyrene was successfully applied as a precursor for the synthesis of proton exchange membrane (PEM). The study also examined the membrane characteristics before and after sulfonation and the latter reaction was facilitated with the aid of acetyl sulfate. The obtained membranes were characterized for its inherent nature. The functional group analysis of the raw precursor clearly discloses the presence of sulfonic groups in the raw precursor and increase in sulfonic groups were observed for the sulfonated samples. The thermogravimetric results revealed that the raw precursor and the sulfonated membrane (SM) exhibited almost similar thermal stability. The sulfonation contributed for better water uptake and is further proven by ion exchange capacity and proton conductivity analysis where SM achieved higher IEC and proton conductivity. The IEC increased from 0.105 to 0.536 meq/L and from 4.357 × 10−7 to 1.327 × 10−6 S/cm for proton conductivity. Thus, the study has proven...

Background: The environment is an important factor which not only may influence children’s health at early life but also may lead to adverse consequences on later health. However, children in Asia are facing both traditional environmental hazards and new pediatric morbidities. A collaboration platform of Asian birth cohort studies to promote children’s environmental health is warranted.

Human beings have always coveted beautiful objects, but the desire to look good is reaching new heights worldwide. Although the pursuit of beauty appears universal, industry evidence suggests that it is particularly strong in Asia. This research examines the effect of culture on the pursuit of beauty. Three studies provide converging evidence that interdependent self-construal increases the likelihood of using appearance-enhancing products. Study 1 operationalizes culture through nationality and self-construal and shows that Easterners (more interdependent) are more likely to use appearance-enhancing products than Westerners (less interdependent). This use is driven by interdependents’ tendency to conform to societal norms, which in turn leads to heightened self-discrepancy (Study 2). The use of appearance-enhancing tools helps minimize this discrepancy. Study 3 shows that strength of norms moderates the impact of interdependence on the use of appearance-enhancing tools. When norms are loosely defined and adherence is not strictly enforced, interdependents’ appearance enhancement tendency is reduced. This research offers actionable insights into the pursuit of beauty, marketing of beauty brands, policy making, and consumer well-being.

We examine how brand-switching varies across cultures, depending on the drivers of a prior unsatisfactory consumption experience. We draw from the literature on regret, norm theory and cross-cultural psychology to predict that Westerners are more likely to switch brands when the unsatisfactory consumption experience is a consequence of their inaction relative to the inaction of a group to which they belong. In contrast, it is predicted that Easterners are more likely to switch brands when the unsatisfactory consumption experience is a consequence of inaction on the part of the group to which they belong relative to their own inaction. We discuss the relevance of our research for marketing theory, the need to account for cultural differences in consumer segments, and the implications for organizations targeting culturally distinct market segments, both domestically and internationally.

Background This study aimed to investigate the association between cord blood cotinine levels and birth outcome, and to determine whether fetal metabolic gene polymorphisms of glutathione-S-transferase (GST) modulate the effect of environmental tobacco smoke exposure during pregnancy. Methods This study included 328 maternal and neonatal pairs. Maternal and cord blood cotinine levels were measured using high performance liquid chromatography. The GST T1 ( GSTT1 ) and GST M1 ( GSTM1 ) polymorphisms were examined using the polymerase chain reaction method. The birth outcomes included birth weight, length, and head circumference, and the risks of having low birth weight and being small for gestational age (SGA). Results Cord cotinine level had a dose-dependent impact on the reduction of birth weight, length, and head circumference in newborns. Elevation of cord blood cotinine concentration increased the rate of SGA and low birth weight. The neonates who had GSTT1 or GSTM1 polymorphism were associated with an increased risk of being SGA. A combination of the GSTT1 and GSTM1 null genotype exacerbated the effect of maternal environmental tobacco smoke exposure on SGA more than the presence of either genotype alone (odds ratio=8.90, 95% confidence interval=1.00–79.5). Conclusion Cord blood cotinine adversely affects birth outcomes. GSTT1 and GSTM1 null genotype may modify the effect of cord blood cotinine on birth outcomes.

In recent years, the Government of the Hong Kong SAR has allocated considerably more attention and resources to pre-primary education. This chapter considers how these changes at the policy and pedagogy levels are shaping the learning experiences of young children in Hong Kong. It will focus on the impact of the following four broad policy changes initiated in the last decade: the implementation of the Guide to the Pre-primary curriculum; the adoption of the biliterate and trilingual language policy; the enactment of a new quality assurance process; and the introduction of the Pre-primary Education Voucher Scheme (PEVS). It was assumed that the implementation of these policies would enhance the preschool and home learning experiences of young children. However, after one decade of implementation of these measures, studies have shown that: (1) preschool teachers still encounter difficulties in implementing child-centred teaching approaches and are likely to continue to adopt teacher-directed instruction or product-oriented pedagogy; (2) there are problems associated with the implementation of the trilingual language policy; (3) there are still wide variations in preschool quality despite the new quality assurance processes; and (4) the PEVS has resulted in some middle-families using the extra disposable income to enrol their children in additional academic classes rather than more play-based extra-curricular activities. Against the background of these research findings, this chapter argues that the changing role of the State, teacher characteristics and traditional Chinese beliefs should be adequately considered for an understanding of the early learning experiences of young Chinese learners in Hong Kong. Preschool education in Hong Kong has not necessarily become more child-centred as teachers have difficulties implementing developmentally appropriate teaching. On the other hand, the government has allocated more resources in enhancing the quality of early childhood education through supporting professional development of teachers. In terms of home-based learning, the influence of traditional Chinese beliefs about academic achievement is predominant and parents continue to prioritize academic learning. Thus Chinese parental beliefs and practices moderate the efforts of the state to promote holistic early development and learning.

This research examines cross-cultural differences in brand dilution effects and the moderating role of motivation and extension typicality. Drawing from recent findings that indicate that culture affects the way people treat conflicting information, this research predicts that Easterners and Westerners react differently to failures by a brand extension. In contrast to previous findings that have suggested that failure in a typical extension leads to less brand dilution for Westerners when they are highly motivated (than when they are less motivated), this study argues that Easterners exhibit greater brand dilution when they are less motivated (than when they are highly motivated). The opposite pattern of results should emerge when the extension is atypical. Three studies provide support for these predictions and the underlying processes.

In a genetic screen for active zone defective mutants inCaenorhabditis elegans, we isolated a loss-of-function allele ofunc-7, a gene encoding an innexin/pannexin family gap junction protein. Innexin UNC-7 regulates the size and distribution of active zones atC. elegansneuromuscular junctions. Loss-of-function mutations in another innexin, UNC-9, cause similar active zone defects asunc-7mutants. In addition to presumptive gap junction localizations, both UNC-7 and UNC-9 are also localized perisynaptically throughout development and required in presynaptic neurons to regulate active zone differentiation. Our mosaic analyses, electron microscopy, as well as expression studies suggest a novel and likely nonjunctional role of specific innexins in active zone differentiation in addition to gap junction formations.

This research examines the impact of field dependency on the way people structure brand information in memory. The authors propose that a person's level of field dependency is an important determinant of the way information is stored in memory. Specifically, the authors argue that field independents are more likely to extract and integrate episodic information to form overall brand beliefs, while field dependents tend to store more detailed, episodic information in memory and are less likely to generalize information across product categories. The authors further propose that this effect is moderated by level of expertise and that such differences have important implications for how people evaluate marketing communications. The results from five studies support their propositions.

This paper characterizes early mathematics instruction in Hong Kong. The teaching of addition in three pre‐primary and three lower primary schools was observed and nine teachers were interviewed about their beliefs about early mathematics teaching. A child‐centered, play‐based approach was evident but teachers emphasized discipline, diligence and academic success. Observations also revealed practices reflective of both constructivist and instructivist pedagogies. Results from interviews suggest that teachers' traditional cultural beliefs about instruction were challenged by western ideologies introduced in continuing professional development courses and by notions promulgated by the educational reforms. Both consistencies and inconsistencies between teachers' beliefs and practices were identified. Implications of the findings are discussed. *This article is based on research conducted by the first author, in partial fulfillment of a Ph.D. degree, under the supervision of the second author. Portions of the...

CD8 + cells from healthy, asymptomatic HIV-1-infected individuals can inhibit HIV-1 replication in naturally or acutely infected CD4 + cells in the absence of cell killing. This CD8 + cell noncytotoxic anti-HIV response (CNAR) is mediated by a soluble CD8 + cell antiviral factor (CAF). CNAR/CAF inhibits HIV-1 replication by blocking viral RNA transcription. HIV transcription is regulated by a variety of cis -acting DNA sequence elements within the proviral long terminal repeat (LTR). We hypothesized that one of the HIV-1 LTR proviral DNA sequence elements that binds host cell transcriptional factors is involved in this antiviral activity. To assess this possibility, we constructed full-length infectious HIV-1 molecular clones with mutations in the LTR elements NFAT, AP-1, IL-2 homology region, and the downstream ISRE. We also tested full-length infectious molecular clones that had deletions of either the NF-κB or Sp1 sites of the LTR or lacked functional Tat and TAR elements. Viruses generated from these molecular clones were used to acutely infect CD4 + cells that subsequently were either co-cultured with CD8 + cells from individuals that exhibited strong CNAR or cultured with CAF-containing fluids. The replication of all of the mutant HIV-1 viruses tested was substantially reduced in the presence of CNAR/CAF. These findings suggest that other regions in the viral LTR or other host cell processes are involved in the transcriptional block elicited by CNAR/CAF.