Preliminary efficacy of AWARE in college health service centers: A group psychotherapy intervention for Asian American women.

ObjectiveAsian Women's Action for Resilience and Empowerment (AWARE) is a psychotherapy intervention designed to improve the mental health of Asian American women. This study documented the feasibility and preliminary efficacy of AWARE at three university health service centers in Massachusetts. Participants: 174 female Asian American college/graduate students were screened, and 48 (64%) met the eligibility criteria and enrolled in the study. Methods: This study was a non-randomized, pre-post design at three university/college health service centers in Massachusetts. Retention rates and changes in depression, anxiety, and PTSD symptoms were measured. Results: Results demonstrated high feasibility and significant preliminary efficacy of AWARE across the sites. After the completion of AWARE, participants showed statistically and clinically significant reduction of depression, anxiety, and PTSD symptoms (p-values <.001). Conclusions: This study provides strong evidence that AWARE can be successfully implemented in university settings and provides a promising model of mental health treatment for Asian American women.

Coronavirus stigmatization and psychological distress among Asians in the United States.

OBJECTIVES: Coronavirus stigmatization may be disproportionately impacting ethnoracial minority groups in the US. We test three hypotheses: [H1] Asians in the US are more likely to report experiencing coronavirus stigmatization than non-Hispanic Whites; [H2] Coronavirus stigmatization is associated with psychological distress; [H3] Magnitude of association between coronavirus stigmatization and psychological distress is more pronounced among US-born Asians, compared to non-Hispanic Whites. DESIGN: We analyzed cross-sectional survey data from the 10-31 March 2020 wave of the Understanding America Survey, a nationally representative survey of adults in the US. Psychological distress was assessed with the PHQ-4. Measures of association were estimated using multiple logistic regression and survey sampling weights. Predicted probabilities were calculated using marginal standardization ( n = 6707). RESULTS: [H1] The adjusted predicted probability of experiencing any coronavirus stigma among foreign-born Asians (11.2%, 95% CI: 5.5-17.0%; E-value = 4.52), US-born Asians (10.9%, 95% CI: 5.8-16.0%; E-value = 4.23), Blacks (8.0%, 95% CI: 5.3-10.7%; E-value = 2.92), and Hispanic Whites (7.3%, 95% CI: 4.6-9.9%; E-value = 2.58) was significantly greater than non-Hispanic Whites (4.5%, 95% CI: 3.7-5.4%). [H2] Individuals reporting any coronavirus stigma experience were significantly more likely to exhibit psychological distress (19.9%, 95% CI: 14.6-25.2% vs 10.6%, 9.6-11.6%; E-value = 3.16). [H3] The overall magnitude of association between experience of any coronavirus stigma and psychological distress was not significantly between US-born Asians and non-Hispanic Whites, though we found gender to mask this effect. US-born Asian females who experienced coronavirus stigmatization were more likely to exhibit psychological distress than non-Hispanic white females who experienced coronavirus stigmatization (relative risk (RR): 10.21, 95% CI: 2.69-38.74 vs 1.24, 95% CI: 0.76-2.01; p < 0.01). CONCLUSION: Comprehensive measures around care seeking, public awareness, and disaggregated data collection are needed to address ethnoracial coronavirus stigmatization and its impact on psychological health and well-being.

The "Let's Talk!" Conference: A Culture-Specific Community Intervention for Asian and Asian American Student Mental Health.

Asian and Asian American students face culture-specific mental health risk factors, and the current study aims to examine whether a culture-specific community intervention in the form of a conference is an effective modality for psychoeducation in the Asian American community. Participants were assessed for reported changes in knowledge, attitudes, and behavior intentions related to mental health after attending the conference. A total of 118 conference participants filled out the survey. Participants reported changes in knowledge regarding mental health issues, generational differences, and the effects of culture. Participants also reported having a more open attitude towards mental health, having greater acceptance of mental health issues in themselves and others, and realizing that mental health issues are a community issue. Lastly, participants reported changes in behavior intentions such as communicating more with friends and family, engaging in perspective-taking, participating in advocacy and activism on mental health issues, and taking care of themselves and others.

A New Golden Age? Proposal for an Innovative Global Health Funding Mechanism for Middle-Income Countries.

Despite economic growth and increased global commitment to health financing in the past decades, the health needs of some of the world's most vulnerable people remain overlooked. In particular, middle-income countries (MICs) often face the conundrum of receiving reduced development assistance for health (DAH) while still being home to most of the world's poor and the majority of the global burden. We believe that this reflects shortcomings in the global DAH system's architecture, which operate on principles that do not respond well to current realities. Hence, we propose a novel mechanism for international health financing and action that specifically addresses the newly emerged strengths and needs of MICs. The Incentives for Health (I4H) Alliance will offer MICs flexible incentives in exchange for their making and meeting health-related commitments in their countries. Countries can set their own health targets, in alignment with the existing Sustainable Development Goals' framework, and those that achieve them will be subsequently rewarded with financial or other incentives, which are not restricted to the health sector. We believe that the I4H Alliance will promote greater MIC involvement towards global health financing both as incentive providers and recipients; encourage collaboration between Ministries of Health and Finance; and provide a needed complement to traditional DAH mechanisms. We advocate for the creation of I4H at a MICs-oriented financing institution such as the New Development Bank. We intend I4H to spark new thinking around innovative health financing approaches to ensure that the "golden age" of global health remains ahead.

Lamivudine Concentration in Hair and Prediction of Virologic Failure and Drug Resistance among HIV Patients Receiving Free ART in China.

BACKGROUND: The assessment of adherence to antiretroviral therapy (ART) is important in order to predict treatment outcomes. Lamivudine (3TC) is one of the most widely used NRTIs in China, but its concentrations in hair and association with virologic failure and drug resistance have not been studied. METHODS: We conducted a cross-sectional survey to investigate 3TC concentrations in hair as a predictor of virologic failure and drug resistance among HIV patients receiving free ART. We also compared the capacity of hair 3TC concentrations with self-reported adherence in predicting virologic responses. Hair 3TC concentrations were detected through the LC-MS/MS system. RESULTS: In patients without HIV drug resistance (HIVDR), with a threshold hair 3TC concentration of 260 ng/g, the sensitivity and specificity in predicting virologic suppression were 76.9% and 89.9%, respectively. Some factors, including CD4+ cell counts, initial treatment regimens with 3TC, and current regimens with second-line drugs, influenced the association between hair 3TC concentrations and virologic suppression. In patients who experienced virologic failure with HIVDR, with a threshold of 180 ng/g, the sensitivity and specificity were 70.0% and 74.4%, respectively. Hair 3TC concentrations had higher sensitivity and specificity in predicting virologic failure and drug resistance than self-reported adherence. CONCLUSIONS: The hair 3TC concentration was a stronger indicator than self-reported adherence in predicting virologic failure and drug resistance in HIV patients receiving free ART.

Geographic origin and evolutionary history of China's two predominant HIV-1 circulating recombinant forms, CRF07_BC and CRF08_BC.

To determine the origin and evolutionary history of two predominant and closely-related circulating recombinant forms (CRF07_BC and CRF08_BC), recombinant structures and phylogenies of 7 unique recombinant forms comprised of subtypes of B' (Thai B linage) and C (designated URFs_BC) from archival specimens of injection drug users (IDUs) collected in 1996 to 1998 from western Yunnan and 4 circulating recombinant forms with B'/C recombinants recently identified (designated nCRFs_BC) in China were compared with those of CRF07_BC and CRF08_BC. The results showed that 5 of 7 URFs_BC and all the nCRFs_BC shared recombination breakpoints with CRF07_BC and/or CRF08_BC. Yunnan URFs_BC consistently occupied the basal branch positions compared with CRF07_BC, CRF08_BC, and nCRFs_BC in phylogenetic trees. The estimated most recent common ancestors (tMRCA) for Yunnan URFs_BC were from ~1987, approximately half a decade earlier than those for CRF07_BC (~1994) and CRF08_BC (~1992). Discrete phylogeographic and spatial diffusion analysis revealed that both CRF07_BC and CRF08 BC came from western Yunnan in the early 1990s. Our results provide compelling evidence for western Yunnan as the geographic origin of CRF07_BC and CRF08_BC, which emerged from a swarm of URFs_BC by a series of recombination events in western Yunnan in the early 1990s.

The sexually driven epidemic in youths in China's southwestern border region was caused by dynamic emerging multiple recombinant HIV-1 strains.

Dehong prefecture, Yunnan province on China's southwestern border was the gateway of the country's AIDS epidemic. Studies on HIV-1 molecular epidemiology will provide key information on virus transmission dynamics and help to inform HIV prevention strategies. HIV-1 infected youths (age 16-25 years) diagnosed in the continuous 3 months in 2009 to 2012 were enrolled. By means of phylogenetic and statistical analyses, It was showed that two thirds (133/205) of youths in Dehong, of which 74.1% were infected sexually, were infected by uncharacterized recombinant HIV-1 strains. Among them about 59.4% (79/131) were unique recombinant forms (URFs) and 40.6% (54/131) formed 11 transmission clusters, termed potential circulating recombinant forms (pCRFs). The emergence of recombinants was statistically significant related with people of low education, residents outside the capital city of Dehong and being Myanmar residents. It was the first report with ongoing HIV-1 recombinant strains in a sexually driven epidemic area in China. Great efforts should be put on reducing multiple risk exposures behavior in local young people, containing the spread of pCRFs to other regions, and preventing the URFs from evolving into future CRFs. Collaborative prevention across border is needed to better control the local AIDS epidemic.

Estimating HIV-1 Transmission Routes for Patients With Unknown Risk Histories by Viral Sequence Phylogenetic Analyses.

OBJECTIVE: To estimate routes of transmission among HIV-infected persons with unknown-risk histories in China. DESIGN/METHOD: All newly reported cases of HIV infection between year 1985 and 2009 were obtained from the National Databank of Chinese Center for Disease Control and Prevention (China CDC). A large number of unknown-risk HIV-positive samples were found. To estimate the transmission routes, HIV gag sequences were amplified by reverse transcription polymerase chain reaction and phylogenetically analyzed. The cases with unknown-risk history were compared with those with known-risk histories from the same local region and time period. A statistical model was developed to predict the transmission routes and was validated on known-risk samples, before testing 324 unknown-risk samples collected from 1996 to 2006. RESULTS: Newly reported cases of HIV infection in China increased steadily between 1985 and 2009, from just a handful of cases to 30,340 in 2009. Injecting drug use (IDU) was the dominant route of transmission among reported cases in the early years and decreased from 83.4% in 1985-2001 to 28.2% in 2009. Conversely, sexual transmission increased from 6.9% in 1985-2001 to 60.9% in 2009. Among the 324 unknown-risk HIV sequences collected from 1996 to 2006, our model identified 100 samples most likely transmitted by blood, 114 by IDU, and 110 by sexual transmission. Our validation samples showed that our model has 90.8%, 94.8%, and 69.6% sensitivity and 87.3%, 87.5%, and 85.5% specificity, for blood, IDU, and sexual transmission, respectively. CONCLUSIONS: We developed a model to estimate transmission route of unknown-risk HIV-positive samples and found that these unknown-risk patients could be transmitted by blood, IDU, or sex.

Reductions in virological failure and drug resistance in Chinese antiretroviral-treated patients due to lamivudine-based regimens, 2003-12.

BACKGROUND: China's National Free Antiretroviral Treatment Program (NFATP) has significantly scaled up and standardized treatment since 2008. Meanwhile, no study worldwide has examined on a large scale the effects of rapid ART programme scale-up on treatment outcomes in resource-limited settings. METHODS: We used China's national HIV drug resistance (HIVDR) surveillance database to determine virological failure, acquired drug resistance and poor adherence rates after 12-15 months of first-line ART. A total of 2252 patients were examined, with 1431 patients having initiated ART before 2008 and 821 since 2008. FINDINGS: Since 2008, virological failure at 12-15 months of treatment improved from 26.6% to 12.1%, and HIVDR rates also significantly decreased from 15.4% to 5.4%. However, these successes are strongly associated with the standardized use of lamivudine-based regimens in place of didanosine-based regimens. Patients who initiated lamivudine-based regimens before 2008 showed significant improvement in adherence [missed doses adjusted OR (AOR), 0.65; 95% CI, 0.45-0.96], virological failure (AOR, 0.29; 95% CI, 0.22-0.39) and HIVDR outcomes (AOR, 0.29; 95% CI, 0.20-0.42) compared with those who initiated didanosine-based regimens. Meanwhile, among only patients on lamivudine-based regimens, no significant changes were observed between those who initiated before 2008 and those who initiated since 2008. CONCLUSIONS: China's NFATP has been largely successful throughout the scale-up, with an overall reduction in virological failure and HIVDR. However, excluding the effect of lamivudine-based regimens, it remains crucial for the programme to improve patient adherence and quality of care, particularly in key vulnerable populations such as those infected through injecting drug or blood routes.

HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China.

OBJECTIVE: To explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China. DESIGN: A series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network. SETTING: China. PARTICIPANTS: Data were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis. RESULTS: 929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0-17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm(3) or from 0 to 199 cells/mm(3), and residence of Guangxi and Yunnan provinces. CONCLUSIONS: The proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.

HIV-infected female sex workers' high risk behavior and attitude changes in Kaiyuan City, Yunnan Province, China.

OBJECTIVE: To investigate the attitude and sexual behavior status and change among HIV positive female workers in entertainment sites in Kaiyuan city, Yunnan province, China. The key information should be applied in the integrated intervention program in future. METHODS: A cohort survey among HIV positive female workers was conducted during 12 months, between 2010 and 2012. All the risk sexual behavior and attitude were collected for assessment for the potential secondary transmission to sexual partners. RESULTS: Of 99 HIV positive women who sell sex in Kaiyuan city, 99 participated in the survey at baseline, 80, 80, 75, and 75 at 3-, 6-, 9-, and 12-month follow-ups. The percentage of participants who reported consistently used condoms in the last one month ranged between 94.5% and 95.5%. The client volume in the last one month, income per sex and age group were significant related with non-insistent condom use with their clients. CONCLUSION: It was suggested that integrated intervention program package should include 100 percent condom use promotion for the HIV positive FSW with all sexual partners, and also, include socially support involved.

High-accuracy identification of incident HIV-1 infections using a sequence clustering based diversity measure.

Accurate estimates of HIV-1 incidence are essential for monitoring epidemic trends and evaluating intervention efforts. However, the long asymptomatic stage of HIV-1 infection makes it difficult to effectively distinguish incident infections from chronic ones. Current incidence assays based on serology or viral sequence diversity are both still lacking in accuracy. In the present work, a sequence clustering based diversity (SCBD) assay was devised by utilizing the fact that viral sequences derived from each transmitted/founder (T/F) strain tend to cluster together at early stage, and that only the intra-cluster diversity is correlated with the time since HIV-1 infection. The dot-matrix pairwise alignment was used to eliminate the disproportional impact of insertion/deletions (indels) and recombination events, and so was the proportion of clusterable sequences (Pc) as an index to identify late chronic infections with declined viral genetic diversity. Tested on a dataset containing 398 incident and 163 chronic infection cases collected from the Los Alamos HIV database (last modified 2/8/2012), our SCBD method achieved 99.5% sensitivity and 98.8% specificity, with an overall accuracy of 99.3%. Further analysis and evaluation also suggested its performance was not affected by host factors such as the viral subtypes and transmission routes. The SCBD method demonstrated the potential of sequencing based techniques to become useful for identifying incident infections. Its use may be most advantageous for settings with low to moderate incidence relative to available resources. The online service is available at http://www.bioinfo.tsinghua.edu.cn:8080/SCBD/index.jsp.

Cholera toxin B subunit acts as a potent systemic adjuvant for HIV-1 DNA vaccination intramuscularly in mice.

Cholera toxin B subunit (CTB) was investigated as a classical mucosal adjuvant that can increase vaccine immunogenicity. In this study, we found out the in vitro efficacy of cholera toxin B subunit (CTB) in activating mice bone marrow-derived dendritic cells (BMDCs) through Toll-like receptor signaling pathways. In vitro RNA and transcriptional level profiling arrays revealed that CTB guides high levels of Th1 and Th2 type cytokines, inflammatory cytokines, and chemokines. Based on the robustness of these profiling results, we examined the induction of HIV Env-specific immunity by CTB co-inoculated with HIV Env DNA vaccine intramuscularly in vivo. CTB enhanced HIV-Env specific cellular immune responses in Env-specific IFN-γ ELISPOT, compared with DNA vaccine alone. Moreover, CTB induced high levels of Env specific humoral response and promoted antibody maturation after the third round of vaccination. This combination immunization strategy induced a Th2-type bias response which is indicative of a high ratio of IgG1/IgG2a. This study reports that CTB as a classical mucosal adjuvant could enhance HIV-1 DNA-based vaccine immunogenicity intramuscularly; therefore, these findings suggest that CTB could serve as an effective candidate adjuvant for DNA vaccination.

Virological outcomes and drug resistance in Chinese patients after 12 months of 3TC-based first-line antiretroviral treatment, 2011-2012.

OBJECTIVE: To determine the prevalence of virological failure and HIV drug resistance among Chinese patients one year after initiating lamivudine-based first-line antiretroviral treatment. METHODS: A prospective cohort study with follow-up at 12 months was conducted in four urban sentinel sites in China. Antiretroviral naive patients ≥18 years old were recruited. Blood samples were collected for testing CD4 cell count, viral load, and (for samples with HIV-1 RNA ≥1000 copies/ml) genotyping of drug resistance. RESULTS: A total of 513 patients were enrolled in this cohort, of whom 448 (87.3%) were retained at 12 months. The median final CD4 cell count was 313 cells/mm(3), which increased from 192 cells/mm(3) at baseline (P<0.0001). Of the 448 remaining subjects, 394 (87.9%) had successful virological suppression (HIV RNA <1000 copies/ml). Among 54 samples with viral load ≥1000 copies/ml, 40 were successfully genotyped, and 11 were found with detectable HIV drug resistance mutations. Of these, the proportions of drug resistance to NNRTIs, NRTIs and PIs were 100%, 81.8% and 0%, respectively. Injecting drug use (AOR = 0.40, 95% CI: 0.19,0.84; P = 0.0154), CD4 count at baseline ≥350 cells/mm(3) (AOR = 0.32, 95% CI: 0.14,0.72; P = 0.0056), and missed doses in the past month (AOR = 0.30, 95% CI: 0.15,0.60; P = 0.0006) were significantly negatively associated with HIV RNA <1000 copies/ml. CONCLUSIONS: Our study demonstrates effective virological and immunological outcomes at 12 months among these who initiated first-line ART treatment. However, patients infected through drug injection, who missed doses, or with higher CD4 count at baseline are at increased risk for poor virological response.

Genome sequence of a novel HIV-1 circulating recombinant form (CRF57_BC) identified from Yunnan, China.

We identified a novel HIV-1 circulating recombinant form (designated CRF57_BC) from a total of four patients with no obvious epidemiologic linkage in western Yunnan (Dehong prefecture) in China. Two strains (09CN.YNFL37 and 10CN.DHFL17) were identified in this study. An additional two strains (341 and 1439) were found among strains reported in a previous study. CRF57_BC was composed of subtype B and subtype C, with one subtype B segment inserted into the gag region of the subtype C backbone. Subregion tree analysis showed that the B regions originated from a Thai B lineage and the C regions were from an India C lineage. The emergence of CRF57_BC may reflect the continual generation of various forms of intersubtype recombinants in western Yunnan.

Genome sequence of a novel HIV-1 circulating recombinant form (CRF64_BC) identified from Yunnan, China.

We report a novel HIV-1 circulating recombinant form (CRF64_BC) that was isolated from five epidemiologically unlinked HIV-infected persons in Yunnan province. CRF64_BC was composed of subtype B and subtype C, with five short subtype B segments inserted into the subtype C backbone. Phylogenetic analysis demonstrated that the C subregion was correlated with the India C lineage, which was transmitted into China in the early 1990s. The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results. Dehong is considered the epicenter of HIV-1 in China, and recombinant strains such as CRF07_BC and CRF08_BC, which also originated from this region, have spread widely in China. The newly emerged CRF64_BC increases the complexity of the HIV epidemic in China and complicates the development of subtype-specific tools against HIV transmission.

Identification of a novel HIV Type 1 circulating recombinant form (CRF65_cpx) composed of CRF01_AE and subtypes B and C in Western Yunnan, China.

A novel HIV-1 circulating recombinant form (CRF) designated CRF65_cpx was recently characterized from three epidemiologically unlinked individuals infected through heterosexual contact in western Yunnan province of China. This is the first complex mosaic HIV-1 CRF, consisting of contributions from three or more different subtypes, identified in China. An additional full-length genome sequence with identical recombinant breakpoints was found among a previously reported recombinant strain from a man who had sex with a man in Anhui province of East Central China. The breakpoint analysis of the recombinants showed a complex genome organization composed of parental subtypes B' (Thailand variant of subtype B), C, and CRF01_AE, with 13 recombination breakpoints observed in almost all structure genes of HIV-1. The generation of complex recombinant forms is likely due to cocirculation of multiple lineages of HIV-1 strains in high-risk populations in western Yunnan.

Near full-length genome characterization of a new CRF01_AE/CRF08_BC recombinant transmitted between a heterosexual couple in Guangxi, China.

Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE is transmitted mainly by sexual activity in Guangxi, southwestern China. Other subtypes, including CRF07_BC, CRF08_BC, and subtype B, are also prevalent in this region. Cocirculation of multiple subtypes, as well as a high rate of drug use, creates favorable conditions for the emergence of recombinant viruses in Guangxi. In the present study, we identified a new HIV-1 unique recombinant form (CRF01_AE /08BC) transmitted from the infected index patient to his seronegative sexual partner. This is the first near full-length genome characterization of a CRF01_AE /08BC recombinant virus in Guangxi, and provides an important basis for future analysis on potential new recombinant transmission events.

Comparison of three intervention models for promoting circumcision among migrant workers in western China to reduce local sexual transmission of HIV.

OBJECTIVE: Three models for promoting male circumcision (MC) as a preventative intervention against HIV infection were compared among migrant worker populations in western China. METHODS: A cohort study was performed after an initial cross-sectional survey among migrant workers in three provincial level districts with high HIV prevalence in western China. A total of 1,670 HIV seronegative male migrants were cluster-randomized into three intervention models, in which the dissemination of promotional materials and expert- and volunteer-led discussions are conducted in one, two, and three stage interventions. Changes in knowledge of MC, acceptability of MC, MC surgery uptake, and the costs of implementation were analyzed at 6-month and 9-month follow-up visits. RESULTS: All three models significantly increased the participants' knowledge about MC. The three-stage model significantly increased the acceptability of MC among participants and led to greatest increase in MC uptake. At the end of follow-up, 9.2% (153/1,670) of participants underwent MC surgery; uptake among the one-, two-, and three-stage models were 4.9%, 9.3%, and 14.6%, respectively. Multivariable Cox regression analysis showed that three-stage model was the most effective method to scale up MC, with RR = 2.0 (95% CI, 1.3-3.1, P=0.002) compared to the on-site session model. The two-stage intervention model showed no significant difference with either the on-site session model (RR=1.5, 95% CI, 0.92-2.4, P=0.12) or three-stage model (P=0.10). CONCLUSIONS: A three-stage intervention with gradual introduction of knowledge led to the significantly increase in MC uptake among migrant workers in western China, and was also the most cost-effective method among the three models.

A new system for comparative functional genomics of Saccharomyces yeasts.

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene-expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting data set reveals that gene-expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In addition to regulatory changes, our approach identified gene functions that have diverged. The functions of genes in core pathways are highly conserved, but we observed many changes in which genes are involved in osmotic stress, peroxisome biogenesis, and autophagy. A surprising number of genes specific to S. bayanus respond to oxidative stress, suggesting the organism may have evolved under different selection pressures than S. cerevisiae. This work expands the scope of genome-scale evolutionary studies from sequence-based analysis to rapid experimental characterization and could be adopted for functional mapping in any lineage of interest. Furthermore, our detailed characterization of S. bayanus provides a valuable resource for comparative functional genomics studies in yeast.