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Background Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. Methods We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. Results Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. Conclusions Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

The interest in HER2-low breast cancer (BC) has increased in recent years with the development of novel anti-HER2 antibody-drug conjugates. Here, we investigated the clinical outcomes and relapse patterns of patients with HER2-low or -zero BCs in an Asian population.We retrospectively identified HER2-low or -zero BC patients with stage I-III tumours who were treated with neoadjuvant chemotherapy and underwent curative surgery, between 2014 and 2018 at Asan Medical Center, Seoul, Korea.A total of 818 and 754 HER2-zero and HER2-low BC patients, respectively, were consecutively included in this analysis. The HER2-low group had more hormone receptor [HR]-positive patients (81% versus 56%, P 0.001). The HER2-zero group had a higher proportion of patients who achieved pathological complete response (pCR) (14.7% versus 9.8%, P = 0.003); however, no significant differences of pCR rate by HER2 status were identified in the HR-positive (P = 0.4) and HR-negative groups (P = 0.3) when analysed separately. The HER2-low BC cases had higher 5-year overall survival (OS) and disease-free survival (DFS) rates (P 0.001 for OS; P = 0.002 for DFS); however, no differences were observed in terms of OS and DFS by HER2 status in the HR-positive group (P = 0.21 for OS and P = 0.66 for DFS).Our current findings do not support that HER2-low BC had different biology and clinical features compared to HER2-zero BC in patients who treated with neoadjuvant chemotherapy. However, the prognostic impact of HER2-low status in BC remains controversial; thus warranting further research.

Tissue homeostasis and regeneration rely on resident stem cells (SCs), whose behaviour is regulated through niche-dependent crosstalk. The mechanisms underlying SC identity are still unfolding. Here, using spatiotemporal gene ablation in murine hair follicles, we uncover a critical role for the transcription factors (TFs) nuclear factor IB (NFIB) and IX (NFIX) in maintaining SC identity. Without NFI TFs, SCs lose their hair-regenerating capability, and produce skin bearing striking resemblance to irreversible human alopecia, which also displays reduced NFIs. Through single-cell transcriptomics, ATAC-Seq and ChIP-Seq profiling, we expose a key role for NFIB and NFIX in governing super-enhancer maintenance of the key hair follicle SC-specific TF genes. When NFIB and NFIX are genetically removed, the stemness epigenetic landscape is lost. Super-enhancers driving SC identity are decommissioned, while unwanted lineages are de-repressed ectopically. Together, our findings expose NFIB and NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration. Adam, Yang et al. show that the transcription factors NFIB and NFIX promote stemness by establishing chromatin accessibility and regulating the super-enhancers that govern bulge stem cell identity.

Background. Heterogeneity in HIV microepidemics across US cities necessitates locally oriented, combination implementation strategies to prioritize resources. We calibrated and validated a dynamic, compartmental HIV transmission model to establish a status quo treatment scenario, holding constant current levels of care for 6 US cities. Methods. Built off a comprehensive evidence synthesis, we adapted and extended a previously published model to replicate the transmission, progression, and clinical care for each microepidemic. We identified a common set of 17 calibration targets between 2012 and 2015 and used the Morris method to select the most influential parameters for calibration. We then applied the Nelder-Mead algorithm to iteratively calibrate the model to generate 2000 best-fitting parameter sets. Finally, model projections were internally validated with a series of robustness checks and externally validated against published estimates of HIV incidence, while the face validity of 25-year projections was assessed by a Scientific Advisory Committee (SAC). Results. We documented our process for model development, calibration, and validation to maximize its transparency and reproducibility. The projected outcomes demonstrated a good fit to calibration targets, with a mean goodness-of-fit ranging from 0.0174 (New York City [NYC]) to 0.0861 (Atlanta). Most of the incidence predictions were within the uncertainty range for 5 of the 6 cities (ranging from 21% [Miami] to 100% [NYC]), demonstrating good external validity. The face validity of the long-term projections was confirmed by our SAC, showing that the incidence would decrease or remain stable in Atlanta, Los Angeles, NYC, and Seattle while increasing in Baltimore and Miami. Discussion. This exercise provides a basis for assessing the incremental value of further investments in HIV combination implementation strategies tailored to urban HIV microepidemics.

ObjectiveCombination strategies generate health benefits through improved health outcomes among people living with HIV (PLHIV) and prevention of new infections. We aimed to determine health benefits attributable to improved health among PLHIV versus HIV prevention for a set of combination strategies in six US cities.DesignA dynamic HIV transmission model.MethodsUsing a model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City (NYC) and Seattle, we assessed the health benefits of city-specific optimal combinations of evidence-based interventions implemented at publicly documented levels and at ideal (90% coverage) scale-up (2020-2030 implementation, 20-year study period). We calculated the proportion of health benefit gains (measured as quality-adjusted life-years) resulting from averted and delayed HIV infections; improved health outcomes among PLHIV; and improved health outcomes due to medication for opioid use disorder (MOUD).ResultsThe HIV-specific proportion of total benefits ranged from 68.3% (95% credible interval: 55.3-80.0) in Seattle to 98.5% (97.5-99.3) in Miami, with the rest attributable to MOUD. The majority of HIV-specific health benefits in five of six cities were attributable HIV prevention, and ranged from 33.1% (26.1-41.1) in NYC to 83.1% (79.6-86.6) in Atlanta. Scaling up to ideal service levels resulted in three to seven-fold increases in additional health benefits, mostly from MOUD, with HIV-specific health gains primarily driven by HIV prevention.ConclusionOptimal combination strategies generated a larger proportion of health benefits attributable to HIV prevention in five of six cities, underlining the substantial benefits of antiretroviral therapy engagement for the prevention of HIV transmission through viral suppression. Understanding to whom benefits accrue may be important in assessing the equity and impact of HIV investments.

Summary Background Accurately estimating HIV disease progression and retention on antiretroviral therapy (ART) can help inform interventions to control HIV microepidemics and mathematical models used to inform health-resource allocation decisions. Our objective was to estimate the monthly probabilities of on-ART CD4 T-cell count progression, mortality, ART dropout, and ART reinitiation using a continuous-time multistate Markov model. We also aimed to validate health-state transition probability estimates to ensure they accurately reproduced the regional HIV microepidemics across the USA. Methods In our modelling study, we considered a cohort of patients from the HIV Research Network, a consortium of 17 adult and paediatric HIV-care providers located in the northeastern (n=8), southern (n=5), and western (n=4) regions of the USA. Individuals aged 15 years or older who were in HIV care (defined as one CD4 test and one HIV-care visit in a calendar year period) with at least one ART prescription between Jan 1, 2010, and Dec 31, 2015, were included in the analysis. We used continuous-time multistate Markov models to estimate transitions between CD4 strata and between on-ART and off-ART states. We examined and adjusted for differences in probability of transition by region, race or ethnicity, sex, HIV risk group, and other baseline clinical indicators. Findings The median age of the 32 242 individuals included in the analysis was 44 years (interquartile range 35–51). Over a median follow-up of 4·9 years (2·6–6·0), 8614 (26·7%) of 32 242 people interrupted ART and 1325 (4·1%) of 32 242 people died. Women, men who have sex with men, and individuals with no previous ART experience had greater increases in CD4 cell counts, whereas black people and people who inject drugs had increased probabilities of ART dropout and faster disease progression. Regardless of CD4 strata, individuals had increased hazard for ART dropout if they were from the south (adjusted hazard ratio [aHR] range from 1·91, 95% CI 1·71–2·13, to 2·45, 2·29–2·62) or the west (aHR range from 1·29, 1·10–1·51, to 1·66, 1·51–1·82) of the USA, compared with individuals from the northeast USA. Interpretation Our results show heterogeneities in disease progression during ART and probability of ART retention across race and ethnicity, HIV risk groups, and regions. These differences should be viewed as targets for intervention and should be incorporated in mathematical models of regional HIV microepidemics in the USA. Funding US National Institutes of Health, Agency for Healthcare Research and Quality, and Health Resources and Services Administration.

BackgroundThe COVID-19 pandemic was preceded by an ongoing overdose crisis and linked to escalating drug overdose deaths in British Columbia (BC). At the outset of these dual public health emergencies, the BC government announced interim Risk Mitigation Guidance (RMG) that permitted prescribing medication alternatives to substances, including opioids, alcohol, stimulants, and benzodiazepines, an intervention sometimes referred to as ‘Safe Supply’. This protocol outlines the approach for a study of the implementation of RMG and its impacts on COVID-19 infection, drug-related and systemic harms, continuity of care for people with substance use disorder, as well as their behavioural, psychosocial, and well-being outcomes.MethodsWe conduct a parallel mixed-method study that involves both analysis of population-level administrative health data and primary data collection, including a 10-week longitudinal observational study (target n=200), a cross-sectional survey (target n=200), and qualitative interviews (target n=60). We have implemented a participatory approach to this evaluation, partnering with people with lived or living experience of substance use, as well as researchers and public health decision-makers across the province. Linked population-level administrative databases will analyze data from a cohort of BC residents with an indication of substance use disorder between 1996 and 2000. We will conduct a high-dimensional propensity score matching and marginal structural modeling to construct a control group and assess the impact of RMG dispensation receipt on a collaboratively-determined set of primary and secondary outcomes.DiscussionThis study constitutes the first formal evaluation of a province-wide program providing regulated pharmaceutical alternatives to the toxic drug supply. The study features an integrated knowledge translation approach, including communications with people with lived/living experience of substance use and consortium meetings with various stakeholders. Supported by the unique research context in BC, our selected mixed method study design will provide an exceptionally strong evidence base to judge not only the impact of the initial implementation of RMG, but also critical evidence on the implementation of the program, which can be used to adapt its future iterations if deemed successful.

We estimated human immunodeficiency virus incidence and incidence rate ratios (IRRs) for black and Hispanic vs white populations in 6 cities in the United States (2020-2030). Large reductions in incidence are possible, but without elimination of disparities in healthcare access, we found that wide disparities persisted for black compared with white populations in particular (lowest IRR, 1.69 [95% credible interval, 1.19-2.30]).

BackgroundPersons who inject drugs (PWID) are at a disproportionately high risk of HIV infection. We aimed to determine the highest-valued combination implementation strategies to reduce the burden of HIV among PWID in 6 US cities.MethodsUsing a dynamic HIV transmission model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City, and Seattle, we assessed the value of implementing combinations of evidence-based interventions at optimistic (drawn from best available evidence) or ideal (90% coverage) scale-up. We estimated reduction in HIV incidence among PWID, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) for each city (10-year implementation; 20-year horizon; 2018 $ US).ResultsCombinations that maximized health benefits contained between 6 (Atlanta and Seattle) and 12 (Miami) interventions with ICER values ranging from $94 069/QALY in Los Angeles to $146 256/QALY in Miami. These strategies reduced HIV incidence by 8.1% (credible interval [CI], 2.8%-13.2%) in Seattle and 54.4% (CI, 37.6%-73.9%) in Miami. Incidence reduction reached 16.1%-75.5% at ideal scale.ConclusionsEvidence-based interventions targeted to PWID can deliver considerable value; however, ending the HIV epidemic among PWID will require innovative implementation strategies and supporting programs to reduce social and structural barriers to care.

BackgroundThe HIV epidemic in the USA is a collection of diverse local microepidemics. We aimed to identify optimal combination implementation strategies of evidence-based interventions to reach 90% reduction of incidence in 10 years, in six US cities that comprise 24·1% of people living with HIV in the USA.MethodsIn this economic modelling study, we used a dynamic HIV transmission model calibrated with the best available evidence on epidemiological and structural conditions for six US cities: Atlanta (GA), Baltimore (MD), Los Angeles (CA), Miami (FL), New York City (NY), and Seattle (WA). We assessed 23 040 combinations of 16 evidence-based interventions (ie, HIV prevention, testing, treatment, engagement, and re-engagement) to identify combination strategies providing the greatest health benefit while remaining cost-effective. Main outcomes included averted HIV infections, quality-adjusted life-years (QALYs), total cost (in 2018 US$), and incremental cost-effectiveness ratio (ICER; from the health-care sector perspective, 3% annual discount rate). Interventions were implemented at previously documented and ideal (90% coverage or adoption) scale-up, and sustained from 2020 to 2030, with outcomes evaluated until 2040.FindingsOptimal combination strategies providing health benefit and cost-effectiveness contained between nine (Seattle) and 13 (Miami) individual interventions. If implemented at previously documented scale-up, these strategies could reduce incidence by between 30·7% (95% credible interval 19·1-43·7; Seattle) and 50·1% (41·5-58·0; New York City) by 2030, at ICERs ranging from cost-saving in Atlanta, Baltimore, and Miami, to $95 416 per QALY in Seattle. Incidence reductions reached between 39·5% (26·3-53·8) in Seattle and 83·6% (70·8-87·0) in Baltimore at ideal implementation. Total costs of implementing strategies across the cities at previously documented scale-up reached $559 million per year in 2024; however, costs were offset by long-term reductions in new infections and delayed disease progression, with Atlanta, Baltimore, and Miami projecting cost savings over the 20 year study period.InterpretationEvidence-based interventions can deliver substantial public health and economic value; however, complementary strategies to overcome social and structural barriers to HIV care will be required to reach national targets of the ending the HIV epidemic initiative by 2030.FundingNational Institutes of Health.

Tissue homeostasis and regeneration rely on resident stem cells (SCs), whose behaviour is regulated through niche-dependent crosstalk. The mechanisms underlying SC identity are still unfolding. Here, using spatiotemporal gene ablation in murine hair follicles, we uncover a critical role for the transcription factors (TFs) nuclear factor IB (NFIB) and IX (NFIX) in maintaining SC identity. Without NFI TFs, SCs lose their hair-regenerating capability, and produce skin bearing striking resemblance to irreversible human alopecia, which also displays reduced NFIs. Through single-cell transcriptomics, ATAC-Seq and ChIP-Seq profiling, we expose a key role for NFIB and NFIX in governing super-enhancer maintenance of the key hair follicle SC-specific TF genes. When NFIB and NFIX are genetically removed, the stemness epigenetic landscape is lost. Super-enhancers driving SC identity are decommissioned, while unwanted lineages are de-repressed ectopically. Together, our findings expose NFIB and NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.

ObjectiveEffective interventions to reduce the public health burden of HIV/AIDS can vary in their ability to deliver value at different levels of scale and in different epidemiological contexts. Our objective was to determine the cost-effectiveness of HIV treatment and prevention interventions implemented at previously documented scales of delivery in six US cities with diverse HIV microepidemics.DesignDynamic HIV transmission model-based cost-effectiveness analysis.MethodsWe identified and estimated previously documented scale of delivery and costs for 16 evidence-based interventions from the US CDC's Compendium of Evidence-Based Interventions and Best Practices for HIV Prevention. Using a model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City and Seattle, we estimated averted HIV infections, quality-adjusted life years (QALY) gained and incremental cost-effectiveness ratios (healthcare perspective; 3% discount rate, 2018$US), for each intervention and city (10-year implementation) compared with the status quo over a 20-year time horizon.ResultsIncreased HIV testing was cost-saving or cost-effective across cities. Targeted preexposure prophylaxis for high-risk MSM was cost-saving in Miami and cost-effective in Atlanta ($6123/QALY), Baltimore ($18 333/QALY) and Los Angeles ($86 117/QALY). Interventions designed to improve antiretroviral therapy initiation provided greater value than other treatment engagement interventions. No single intervention was projected to reduce HIV incidence by more than 10.1% in any city.ConclusionCombination implementation strategies should be tailored to local epidemiological contexts to provide the most value. Complementary strategies addressing factors hindering access to HIV care will be necessary to meet targets for HIV elimination in the United States.

Background. Heterogeneity in HIV microepidemics across US cities necessitates locally oriented, combination implementation strategies to prioritize resources. We calibrated and validated a dynamic, compartmental HIV transmission model to establish a status quo treatment scenario, holding constant current levels of care for 6 US cities. Methods. Built off a comprehensive evidence synthesis, we adapted and extended a previously published model to replicate the transmission, progression, and clinical care for each microepidemic. We identified a common set of 17 calibration targets between 2012 and 2015 and used the Morris method to select the most influential parameters for calibration. We then applied the Nelder-Mead algorithm to iteratively calibrate the model to generate 2000 best-fitting parameter sets. Finally, model projections were internally validated with a series of robustness checks and externally validated against published estimates of HIV incidence, while the face validity of 25-year projections was assessed by a Scientific Advisory Committee (SAC). Results. We documented our process for model development, calibration, and validation to maximize its transparency and reproducibility. The projected outcomes demonstrated a good fit to calibration targets, with a mean goodness-of-fit ranging from 0.0174 (New York City [NYC]) to 0.0861 (Atlanta). Most of the incidence predictions were within the uncertainty range for 5 of the 6 cities (ranging from 21% [Miami] to 100% [NYC]), demonstrating good external validity. The face validity of the long-term projections was confirmed by our SAC, showing that the incidence would decrease or remain stable in Atlanta, Los Angeles, NYC, and Seattle while increasing in Baltimore and Miami. Discussion. This exercise provides a basis for assessing the incremental value of further investments in HIV combination implementation strategies tailored to urban HIV microepidemics.

Summary Background The HIV epidemic in the USA is a collection of diverse local microepidemics. We aimed to identify optimal combination implementation strategies of evidence-based interventions to reach 90% reduction of incidence in 10 years, in six US cities that comprise 24·1% of people living with HIV in the USA. Methods In this economic modelling study, we used a dynamic HIV transmission model calibrated with the best available evidence on epidemiological and structural conditions for six US cities: Atlanta (GA), Baltimore (MD), Los Angeles (CA), Miami (FL), New York City (NY), and Seattle (WA). We assessed 23 040 combinations of 16 evidence-based interventions (ie, HIV prevention, testing, treatment, engagement, and re-engagement) to identify combination strategies providing the greatest health benefit while remaining cost-effective. Main outcomes included averted HIV infections, quality-adjusted life-years (QALYs), total cost (in 2018 US$), and incremental cost-effectiveness ratio (ICER; from the health-care sector perspective, 3% annual discount rate). Interventions were implemented at previously documented and ideal (90% coverage or adoption) scale-up, and sustained from 2020 to 2030, with outcomes evaluated until 2040. Findings Optimal combination strategies providing health benefit and cost-effectiveness contained between nine (Seattle) and 13 (Miami) individual interventions. If implemented at previously documented scale-up, these strategies could reduce incidence by between 30·7% (95% credible interval 19·1–43·7; Seattle) and 50·1% (41·5–58·0; New York City) by 2030, at ICERs ranging from cost-saving in Atlanta, Baltimore, and Miami, to $95 416 per QALY in Seattle. Incidence reductions reached between 39·5% (26·3–53·8) in Seattle and 83·6% (70·8–87·0) in Baltimore at ideal implementation. Total costs of implementing strategies across the cities at previously documented scale-up reached $559 million per year in 2024; however, costs were offset by long-term reductions in new infections and delayed disease progression, with Atlanta, Baltimore, and Miami projecting cost savings over the 20 year study period. Interpretation Evidence-based interventions can deliver substantial public health and economic value; however, complementary strategies to overcome social and structural barriers to HIV care will be required to reach national targets of the ending the HIV epidemic initiative by 2030. Funding National Institutes of Health.

BackgroundAccurately estimating HIV disease progression and retention on antiretroviral therapy (ART) can help inform interventions to control HIV microepidemics and mathematical models used to inform health-resource allocation decisions. Our objective was to estimate the monthly probabilities of on-ART CD4 T-cell count progression, mortality, ART dropout, and ART reinitiation using a continuous-time multistate Markov model. We also aimed to validate health-state transition probability estimates to ensure they accurately reproduced the regional HIV microepidemics across the USA.MethodsIn our modelling study, we considered a cohort of patients from the HIV Research Network, a consortium of 17 adult and paediatric HIV-care providers located in the northeastern (n=8), southern (n=5), and western (n=4) regions of the USA. Individuals aged 15 years or older who were in HIV care (defined as one CD4 test and one HIV-care visit in a calendar year period) with at least one ART prescription between Jan 1, 2010, and Dec 31, 2015, were included in the analysis. We used continuous-time multistate Markov models to estimate transitions between CD4 strata and between on-ART and off-ART states. We examined and adjusted for differences in probability of transition by region, race or ethnicity, sex, HIV risk group, and other baseline clinical indicators.FindingsThe median age of the 32 242 individuals included in the analysis was 44 years (interquartile range 35-51). Over a median follow-up of 4·9 years (2·6-6·0), 8614 (26·7%) of 32 242 people interrupted ART and 1325 (4·1%) of 32 242 people died. Women, men who have sex with men, and individuals with no previous ART experience had greater increases in CD4 cell counts, whereas black people and people who inject drugs had increased probabilities of ART dropout and faster disease progression. Regardless of CD4 strata, individuals had increased hazard for ART dropout if they were from the south (adjusted hazard ratio [aHR] range from 1·91, 95% CI 1·71-2·13, to 2·45, 2·29-2·62) or the west (aHR range from 1·29, 1·10-1·51, to 1·66, 1·51-1·82) of the USA, compared with individuals from the northeast USA.InterpretationOur results show heterogeneities in disease progression during ART and probability of ART retention across race and ethnicity, HIV risk groups, and regions. These differences should be viewed as targets for intervention and should be incorporated in mathematical models of regional HIV microepidemics in the USA.FundingUS National Institutes of Health, Agency for Healthcare Research and Quality, and Health Resources and Services Administration.

Supplemental material, CascadeCEA_calibration_Appendix-revision.rjf_online_supp for Development and Calibration of a Dynamic HIV Transmission Model for 6 US Cities by Xiao Zang, Emanuel Krebs, Jeong E. Min, Ankur Pandya, Brandon D. L. Marshall, Bruce R. Schackman, Czarina N. Behrends, Daniel J. Feaster, Bohdan Nosyk, Czarina N. Behrends, Carlos Del Rio, Julia Dombrowski, Daniel J Feaster, Kelly Gebo, Matthew Golden, Reuben Granich, Thomas Kerr, Gregory Kirk, Brandon D. L. Marshall, Shruti H. Mehta, Lisa Metsch, Julio Montaner, Bohdan Nosyk, Bruce R. Schackman, Steven Shoptaw, William Small and Steffanie A. Strathdee in Medical Decision Making

Background: The AquaPonic system is an eco-friendly recycling method that can save energy and reduce the impact of environmental pollution from fish manure by utilizing it as a nutrient for plant growth. The aquaponic system is required to measure and control the suitability and efficiency of the circulation system depending on the concentration of the ammonium ion and the nitrate ion. For the measurement of nitrate and ammonium ions, ISE (Ion Selective Electrodes) were fabricated and applied to the designed system. Methods: ISE were prepared for the measurement and analysis of ammonium and nitrate ions, which are the most important components of nitrogen circulation in the fish excrement of the designed aquaponic-system. The temperature, humidity, light composition and light intensity of plant growing area were controlled to collect meaningful information about growth of the plant. Lettuce was cultivated in a total of 60 ports and cultivated in a hydroponic cultivation method using fish excrement as a nutrient. Nitrate and ammonium ions were measured at 24 hour intervals for 1 month of growth of tilapia and lettuce. In order to investigate the growth of lettuce, weights and length were collected and the images of tilapia were obtained at feeding to determine the growth of tilapia. Results: The analysis of the weight, length, and nutrients of the lettuce grown in the designed aqua phonics system showed that the designed aquaponic-system is an efficient system. Discussions: In order to design an aquaponic-system for various crops and species, it is considered necessary to conduct experiments on aquaponic-system which combines various crops and species. Further research on the algorithm that can control the system in optimum environment is needed by collecting information about growth of plant and fish in controlled environment. Conclusion: It is expected that further research on the development of algorithms that can determine the optimum growth environment by acquiring the growth information as changing the growth environment through the controllable system.

Background: Subcortical vascular dementia (SVaD) is a common form of dementia, attributed to ischemic small-vessel disease. Blood viscosity (BV) may contribute to the pathophysiology of SVaD. However, SVaD patients with coexisting amyloid deposition may not show differences in BV because their small-vessel disease may result from amyloid angiopathy independently of BV. We, therefore, hypothesized that BV might show different changes compared with control subjects in subcortical vascular mild cognitive impairment (svMCI) that refers to the prodromal stage of SVaD according to cerebral amyloid burden detected by the [ 11 C] Pittsburgh compound B (PiB) PET (positron emission tomography), and apolipoprotein 4 (ApoE4) genotype (a known risk factor for vascular and parenchymal amyloid). Methods: Our subjects consisted of 33 healthy normal controls (NC), 28 patients with PiB(2) svMCI, and 12 with PiB(1) svMCI. They underwent scanning capillary tube viscometer measuring BV during systolic and diastolic phases. Results: ComparedwiththeNCgroup,thePiB(2)svMCIgroupshowed increaseddiastolicblood viscosity (DBV) but no difference in systolic blood viscosity (SBV). By contrast, there was no significant difference in SBV and DBV between the NC and PiB(1) svMCI groups. Within the PiB(1) svMCI group, ApoE4(2) subgroup showed increased DBV compared with the ApoE4(1) subgroup. Conclusions: Increased DBVis an important contributor to the development of ‘‘pure’’ svMCI (ie, without cerebral amyloid deposition). The relationship between BVand PiB(1) svMCI differed according to ApoE genotype, suggesting that the pathogenesis of PiB(1) svMCI might also be

Background— Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. Methods and Results— We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene ( ALMS1 ) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. Conclusions— The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.

Jeong E, Lee J-Y, Kim S-J, Choi J. Predominant immunoreactivity of Porphyromonas gingivalis heat shock protein in autoimmune diseases. J Periodont Res 2012; 47: 811–816. © 2012 John Wiley & Sons A/S Background and Objective: Autoimmune diseases, including atherosclerosis, diabetes mellitus and rheumatoid arthritis, can be triggered and aggravated by the pathogen-driven antigenic peptide from Porphyromonas gingivalis HSP60. P. gingivalis is the major pathogen of chronic periodontitis, which is a global epidemic prevalent in two-thirds of the adult population. The monoclonal antibody raised against peptide 19 (Pep19: TLVVNRLRGSLKICAVKAPG) from P. gingivalis HSP60 was polyreactive to the human homolog. The aim of this study was to determine if Pep19 from P. gingivalis HSP60 manifests itself as a predominant antigen in infection-triggered autoimmune diseases. Material and Methods: Pep19 from P. gingivalis HSP60, Mycobacterium tuberculosis HSP60 and Chlamydia pneumoniae HSP60 was synthesized for comparative recognition by the sera from patients with atherosclerosis, type 2 diabetes and rheumatoid arthritis, all with ongoing periodontal disease, and by the sera of a control group of patients with periodontal disease but with no history of atherosclerosis, type 2 diabetes or rheumatoid arthritis. Results: Of the Pep19 peptides from P. gingivalis HSP60, M. tuberculosis HSP60 and C. pneumoniae HSP60, Pep19 from P. gingivalis HSP60 was the peptide epitope predominantly and most consistently recognized by the serum samples of the four disease groups (chronic periodontitis, atherosclerosis, type 2 diabetes mellitus and rheumatoid arthritis). Conclusion: Seroreactivity to Pep19 of P. gingivalis HSP60, an oral pathogen, was predominant in patients with autoimmune disease with ongoing periodontal disease.

We have developed a mutant strain derived from Agrobacterium sp. ATCC 31750, which produces a water-soluble polysaccharide having potential utility to the food, feed, pharmaceutical and cosmetic industries. A high concentration of product (15 g/L) is obtained by 48 h cultivation of the mutant strain under optimized fermentation conditions. The water-soluble polysaccharide obtained from cultures of the mutant strain beta82 has Glc:Man:Gal in approximate molar ratios of 5.8:6.7:1.0. The molecular weight of the polysaccharide was determined to be approximately 1000 kDa by HPSEC analysis. Linkage analysis contained 3-Glc p , 3-Man p , terminal Glc p and terminal Man p , as well as a small proportion of 3- and 3,4-Gal p , and 4,6-Man p residues. Based on analyses using FT-IR and 13 C NMR spectrometers, most glycosidic bonds joining these sugar residues are of the α-type, and acetyl groups are apparently attached to the polymer chain at random.

A trisaccharide, 6d-Altro-Hepp (13) GlcNAc (13) Gal (1, as an O-antigenic repeating unit of Campylobacter jejuni serotypes O:23 and O:36, was synthesized. Coupling of the 6d-altro-Hepp (13) GlcNAc (1SEt donor with Gal (1 acceptor in the presence of NIS-TfOH promoter afforded the trisaccharide having the (13) Gal linkage. -Stereospecificity and the desired regioselectivity for the 3-OH Gal are obtained. Subsequent hydrogenation, acetylation, azide displacement, hydrazinolysis, Nacetylation, and finally deacetylation furnished the title trisaccharide hapten for further glycoconjugation.

Summary Background Widespread HIV screening and access to highly active antiretroviral treatment (ART) were cost effective in mathematical models, but population-level implementation has led to questions about cost, value, and feasibility. In 1996, British Columbia, Canada, introduced universal coverage of drug and other health-care costs for people with HIV/AIDS and and began extensive scale-up in access to ART. We aimed to assess the cost-effectiveness of ART scale-up in British Columbia compared with hypothetical scenarios of constrained treatment access. Methods Using comprehensive linked population-level data, we populated a dynamic, compartmental transmission model to simulate the HIV/AIDS epidemic in British Columbia from 1997 to 2010. We estimated HIV incidence, prevalence, mortality, costs (in 2010 CAN$), and quality-adjusted life-years (QALYs) for the study period, which was 1997–2010. We calculated incremental cost-effectiveness ratios from societal and third-party-payer perspectives to compare actual practice (true numbers of individuals accessing ART) to scenarios of constrained expansion (75% and 50% probability of accessing ART). We also investigated structural and parameter uncertainty. Findings Actual practice resulted in 263 averted incident cases compared with 75% of observed access and 676 averted cases compared with 50% of observed access to ART. From a third-party-payer perspective, actual practice resulted in incremental cost-effectiveness ratios of $23 679 per QALY versus 75% access and $24 250 per QALY versus 50% access. From a societal perspective, actual practice was cost saving within the study period. When the model was extended to 2035, current observed access resulted in cumulative savings of $25·1 million compared with the 75% access scenario and $65·5 million compared with the 50% access scenario. Interpretation ART scale-up in British Columbia has decreased HIV-related morbidity, mortality, and transmission. Resulting incremental cost-effectiveness ratios for actual practice, derived within a limited timeframe, were within established cost-effectiveness thresholds and were cost saving from a societal perspective. Funding BC Ministry of Health, National Institute of Drug Abuse at the US National Institutes of Health.

Simultaneous ground-based measurements of aerosol chemical composition and atmospheric aerosol optical depth (AOD) in the UV and visible regions were carried out at Gwangju (35.13°N, 126.50°E), Korea during a biomass burning period, October 4–November 12, 2002. An Asian dust event and biomass burning events were observed during the study period. The correlation coefficients (R) between AOD and PM2.5 and PM10 mass concentration during the study period are 0.58±0.15 and 0.52±0.14, respectively. Aerosol optical properties (AOD and Angstrom exponent) and chemical characteristics were presented for selected days and their impacts on aerosol loading were examined. Both fine and coarse mode particle mass concentrations increased on biomass burning day resulting in high AOD values. The simultaneous occurrence of Asian dust and biomass burning resulted in the highest AOD of 1.20 at 311 nm and the lowest Angstrom exponent of 0.42 in the visible range. When both transported urban pollutants and land dust aerosols affected the air quality over the study area, AOD and surface PM mass concentration increased 18–60% and 230–890%, respectively.

The 'C-mycosidic' glycopeptidolipid typing antigens from all serovars in the Mycobacterium avium/M. intracellulare/M. scrofulaceum complex have been examined to varying extents. Detailed analysis of those from serovars 8, 9, 16 and 25 show that the antigens consist of short acetylated oligosaccharides linked to a common fattyacyl-peptidyl-O-(3,4-di-O-methylrhamnose) 'core'. The oligosaccharide units, in a form suitable for chemical studies, were liberated as oligosaccharide alditols on treatment of the glycopeptidolipids with alkaline borohydride solution. The alditol in the reduced oligosaccharides from all sources is 6-deoxytalitol. Moreover rhamnose is also always present, indicating that a 'basal' disaccharide, rhamnosyl-6-deoxytalosyl, is always linked to the allo-threonine in the acylpeptide. In addition the oligosaccharides from the glycopeptidolipids of each serovar are distinguished by their own individualistic sugars: 3-O-methylglucose in serovar 8; 2,3-di-O-methylfucose in serovar 9; 2-O-methylfucose in serovar 25; 4-O-methylrhamnose in the oligosaccharide from one of the two glycopeptidolipids in serovar 16 and apparently another rhamnosyl substituent in the other oligosaccharide. The glycopeptidolipid antigens in their structural principals, cellular location and physiological role bear a striking miniscule resemblance to cell wall components of other bacteria such as the O-antigenic and R-antigenic lipopolysaccharides.

Extensive forest fire activities occurred in May 2003 across Siberia, Russia, particularly in the area between the Amur and Lena rivers east of Lake Baikal. These forest fires released large amounts of particulates and gases into the atmosphere, resulting in adverse effects on regional air quality and radiation budget. On certain occasions, a smoke pollution plume from these forest fires was transported through Mongolia and eastern China, down to the Korean peninsula. In this study, satellite data and ground-based radiation measurement data were analyzed to estimate the smoke aerosol's impact on the local atmospheric environment over Korea. Aerosol optical depth (AOD) values retrieved using the Bremen Aerosol Retrieval method from Moderate Resolution Imaging Spectroradiometer data were compared with those derived from ground-based radiation measurements. Large AOD values in the range 2.0–4.0 were observed on 20 May 2003 over Korea due to the influence of the long-range transported smoke aerosol plume from the Russian fires, resulting in a surface-observed short-wavelength direct aerosol radiative forcing efficiency of −90 to −200 W m −2 . This smoke aerosol plume also resulted in a decrease in the solar visible irradiance of up to 57%, and increased the surface PM10 concentration by up to 258 μg m −3 .

The main objective of this study was to investigate the chemical characteristics of post-harvest biomass burning aerosols from field burning of barley straw in late spring and rice straw in late fall in rural areas of Korea. A 12-hr integrated intensive sampling of particulate matter (PM) with an aerodynamic diameter less than or equal to 10 microm (PM10) and PM with an aerodynamic diameter less than or equal to 2.5 microm (PM2.5) biomass burning aerosols had been conducted continuously in Gwangju, Korea, during two biomass burning periods: June 4--15, 2001, and October 8--November 14, 2002. The fine and coarse particles of biomass burning aerosols were analyzed for mass and ionic, elemental, and carbonaceous species. The average fine and coarse mass concentrations of biomass burning aerosols were, respectively, 129.6 and 24.2 microg/m3 in June 2001 and 47.1 and 33.2 microg/m3 in October--November 2002. An exceptionally high PM2.5 concentration of 157.8 microg/m3 was observed during biomass burning events under stagnant atmospheric conditions. In the fine mode, chlorine and potassium were unusually rich because of the high content of semi-arid vegetation. Both organic carbon (OC) and elemental carbon increased during the biomass burning periods, with the former exhibiting a higher abundance. PM from the open field burning of agricultural waste has an adverse impact on local air quality and regional climate.

A trisaccharide, GlcNAcp-β-(1→3)-Galp-a-(1→2)-6-deoxy-altroHepp-α-(1→O-propyl, as an O-antigenic repeating unit of C. jejuni serotype 0:23 and 0:36 was synthesized. Coupling of the GlcNPhth-(1→3)-Gal disaccharide donor with allyl 6-deoxy-altroHep acceptor in the presence of iodonium dicollidine perchlorate (IDCP) promoter afforded the α-galactosidic trisaccharide with high stereoselectivities. Subsequent deacetalation, dephthaloylation, N-acetylation, and hydrogenolytic debenzylation furnished the title compound.

A trisaccharide, the O-antigenic repeating unit ofC. jejuni serotype 0:23 and 0:36, was synthesized as a 2′-azidoethyl glycoside by block addition of perbenzylated thiogalactoside donors to α-altroHepp-(1→3)-GlcNPhth disaccharide acceptor in presence of IDCP promoter. The αlinkedaltro heptopyranoside moiety in the glycosyl acceptor was effectively prepared bySwern oxidation of α-mannohepp-(1→3)-GlcNPhth disaccharide followed by mild reduction with NaCNBH3.

Objective and importance: Stereotactic biopsy for brain lesion is usually a safe procedure and the reported rate of complication is minimal. Moreover, local seeding along the trajectory of the stereotactic biopsy is a rare complication. The authors report a case of metastatic implantation along the trajectory of the stereotactic biopsy in anaplastic astrocytoma.

Transcription factors are central constituents of gene regulatory networks that control diverse aspects of plant development and environmental adaptability. Therefore they have been explored for decades as primary targets for agricultural biotechnology. A gene of interest can readily be introduced into many crop plants, whereas targeted gene inactivation is practically difficult in many cases. Here, we developed an artificial small interfering peptide (a‐siPEP) approach, which is based on overexpression of specific protein domains, and evaluated its application for the targeted inactivation of transcription factors in the dicot model, Arabidopsis, and monocot model, Brachypodium. We designed potential a‐siPEPs of two representative MADS box transcription factors, SUPPRESSOR OF OVEREXPRESSOR OF CONSTANS 1 (SOC1) and AGAMOUS (AG), and a MYB transcription factor, LATE ELONGATED HYPOCOTYL (LHY). Transgenic plants overproducing the a‐siPEPs displayed phenotypes comparable to those of gene‐deficient mutants. The a‐siPEPs attenuate nuclear import and DNA‐binding of target transcription factors. Our data demonstrate that the a‐siPEP tool is an efficient genetic means of inactivating specific transcription factors in plants.

Although l -DOPA represents the standard of care in Parkinson's disease, long-term treatment may be compromised by l -DOPA-induced dyskinesia (LID), with adverse fluctuations in motor responsiveness and progressive loss of control. Here we show that in rats with 6-hydroxydopamine-induced lesions of the median forebrain bundle, LID correlates with 5-HT levels. Rats were treated with l -DOPA (6 mg/kg) and benserazide (15 mg/kg) daily for 3 weeks to induce the development of abnormal involuntary movements (AIMs). After this chronic l -DOPA treatment, the lesion side of the rats displayed significant changes in striatal dopamine (DA) and 5-HT levels. Striatal DA and 5-hydroxytryptamine (5-HT) levels were inversely correlated, and AIMs were strongly positively correlated with DA levels and negatively correlated with 5-HT levels. Axial AIMs were more strongly correlated with DA and 5-HT levels than were the other AIMs subtypes, while locomotive AIMs showed no significant correlation at all. In addition, striatal 5-HT was more strongly (negatively) correlated with the AIMs than striatal DA levels. These results demonstrate that 5-HT contributes to LID and that both striatal DA (positively) and 5-HT (negatively) affect the severity of LID. We suggest that by strategic modification of the serotonin system it may be possible to attenuate the adverse effects of chronic l -DOPA therapy.

Sulfonamide is one of the most stable nitrogen protective group, and various sulfonamides have been developed and applied for organic synthesis. However, deprotection of most sulfonamides has drawbacks due to harsh reaction conditions. Benzothiazole-2-sulfonyl (Bts) was first reported as an amine protective group in amino acid synthesis. Compared to other sulfonyl groups, Bts is an attractive choice because it requires milder deprotection conditions. Initially, Bts chloride, the reagent for Bts protection for simple amines, was prepared using Cl2 gas, which is toxic and inconvenient. Recently, an improved methodology using aqueous sodium hypochlorite instead of toxic Cl2 was reported and making Bts protection much easier. The Bts group is known to have an electron withdrawing property, and Bts protected amide shows a different reactivity compared to other N-protected amide derivatives. Although usual amide bond is strong enough not to be easily hydrolyzed or aminolized, N-Bts amide linkage can be broken by attack of simple amine nucleophiles. This is another benefit of Bts protection, and the ring opening reaction of 1-Bts piperazin-2-one derivative as a peptide nucleic acid (PNA) monomer with a PNA oligomer anchored on solid phase has been usefully applied for solid phase PNA synthesis. In this paper, a facile cyclization reaction of N-Bts amino alcohol with chloroacetyl chloride is described. We speculated that if the Bts group could effectively withdraw electrons from nitrogen, nucleophilicity of Bts attached amine would be reduced, and a different reactivity toward electrophiles would be observed compared to normal amine derivatives. These subtle reactivity differences could be an effective means of obtaining different regioselectivity. Detailed data pertaining to change of nucleophilicity due to Bts protection has not been reported thus far. To investigate this hypothesis, Bts, Ts (toluensulfonyl), and Boc (t-butyl carbamate) protected amino alcohols were prepared, and reactions with chloroacetyl chloride were performed (Scheme 1). Between two chlorides in chloroacetyl chloride, acyl chloride is known to be more reactive toward usual nucleophiles. In the case of unprotected amino alcohol, the amine should react with acyl chloride prior to OH, and OH can subsequently attack α-carbon to produce a morpholine-3-one. However, for N-protected amino alcohol, OH should be acylated prior to the acylation of Nprotected amine. If the N-protected amine has sufficient reactivity to perform intramolecular cyclization to attack αcarbon, a morpholine-2-one derivative can be prepared. In the reaction of N-Bts amino alcohol (2a, b), The OH group reacted with acyl chloride to form ester 3a, b. After workup to remove remaining chloroacetyl chloride, and stirring in DMF with K2CO3, it was found that N-Bts amine could substitute a chloride at α-carbon, and morpholine-2one (4a) or 1,4-oxazepan-2-one (4b) derivative was produced. When N-Ts amino ethanol (5a) was reacted with chloroacetyl chloride dropwise, a different outcome was obtained. A mixture of O-acylated (6a) and diacylated compound 8 was produced in 1:4 ratios. The production of diacylated compound 8 as a major product means that N-Ts amine has enough nucleophilicity to react with acyl chloride, and its reactivity is higher than N-Bts amine. When O-acylated product (6a) was separated and stirred with K2CO3, morpholine-2-one derivative (7a) was obtained.

The aim of the present study was to evaluate the clinical characteristics, prognoses and predictors of mortality of patients with pulmonary tuberculosis (TB) with acute respiratory failure (ARF), and to investigate the adjunctive use of corticosteroids in such cases. TB patients with ARF requiring mechanical ventilation (n = 90) were enrolled retrospectively during 1989-2006. The patients were divided into two groups: tuberculous pneumonia (TBP; n = 66), and miliary TB (MTB; n = 24). The TBP patients were older than the MTB patients (mean age 68.0 versus 54.5 yrs), and the mean+/-SD interval from hospital admission to start of anti-TB treatment was longer for the TBP than for the MTB group (5.0+/-7.0 versus 2.8+/-2.5 days). However, there was no difference in in-hospital mortality rate between the two groups (68.2 versus 58.3%). In the TBP patients, multivariate analysis showed that advanced age and shock unrelated to sepsis were associated with poor outcomes. Even though corticosteroid use was a predictor of survival in TBP patients, it was difficult to conclusively determine the efficacy of corticosteroids in TBP with ARF because of the retrospective study design. The present study reveals the need for randomised controlled trials to clarify the role of corticosteroids as adjunctive therapy in the management of tuberculous pneumonia with acute respiratory failure.

We analyze WMAP 3 year data using the one-point distribution functions to probe the non-Gaussianity in the Cosmic Microwave Background (CMB) Anisotropy data. Computer simulations are performed to determine the uncertainties of the results. We report the non-Gaussianity parameter f_NL is constrained to 26, Comment: 4 pages, 2 figures in postscripts, some typos corrected

A trisaccharide, GlcNAcp-β-(1→3)-Galp-a-(1→2)-6-deoxy-altroHepp-α-(1→O-propyl, as an O-antigenic repeating unit of C. jejuni serotype 0:23 and 0:36 was synthesized. Coupling of the GlcNPhth-(1→3)-Gal disaccharide donor with allyl 6-deoxy-altroHep acceptor in the presence of iodonium dicollidine perchlorate (IDCP) promoter afforded the α-galactosidic trisaccharide with high stereoselectivities. Subsequent deacetalation, dephthaloylation, N-acetylation, and hydrogenolytic debenzylation furnished the title compound.

A trisaccharide, the O-antigenic repeating unit of C. jejuni serotype O:23 and O:36, was synthesized as a 2'-azidoethyl glycoside by block addition of perbenzylated thiogalactoside donors to alpha-altroHepp-(1--3)-GlcNPhth disaccharide acceptor in presence of IDCP promoter. The alpha-linked altroheptopyranoside moiety in the glycosyl acceptor was effectively prepared by Swern oxidation of alpha-mannohepp-(1--3)-GlcNPhth disaccharide followed by mild reduction with NaCNBH3.

Stereotactic biopsy for brain lesion is usually a safe procedure and the reported rate of complication is minimal. Moreover, local seeding along the trajectory of the stereotactic biopsy is arare complication. The authors report a case of metastatic implantation along the trajectory of the stereotactic biopsy in anaplastic astrocytoma.A 64-year-old man who presented with a one-month history of speech and memory disturbance underwent magnetic resonance (MR) imaging that disclosed a large mass in the left basal ganglia and medial temporal region.Under the impression of high-grade glioma, computed tomography guided stereotactic biopsy was performed using the Riechert-Mundinger system. The histologic diagnosis was anaplastic astrocytoma. MR images after two cycles of chemotherapy showed a small enhancing portion in the middle of the biopsy tract, which was considered a surgical artifact and not included in the field of the following conventional fractionated radiation therapy. MR images three months after the completion of radiation therapy revealed that the enhancing portion had become a larger mass irrespective of good control of the primary tumor.Our findings suggest that tumor seeding along the stereotactic biopsy trajectory must be considered if an enhancing lesion appears in the MR image following the stereotactic biopsy. The cause and the prevention of implantation metastasis along the stereotactic biopsy tract are also discussed.

Health and Welfare Training Center of Korean National Institute of Health (KNIH) has developed various education curricula for officials who are involved in the public health or welfare sectors. Still almost all education programmes are off-line based. In off-line settings, both the lecturers and the students should come to NIH from their counties to join the education programmes, and it is impossible for the students to review or to re-practice the education contents. We developed a prototype on-line setting education programmes to provide a more convenient and more effective service to the officials. This web-based interactive education programme consisted of the specific objectives on vaccination for the public health officials who were working for the national immunization programmes. It became a prototype of web-based education and was evaluated by the participants in April, 2001. From the evaluation, we improved the contents and tried to develop more subjects for the officials' training.