Artificial intelligence-assisted quantification and assessment of whole slide images for pediatric kidney disease diagnosis.

MOTIVATION: Pediatric kidney disease is a widespread, progressive condition that severely impacts growth and development of children. Chronic kidney disease is often more insidious in children than in adults, usually requiring a renal biopsy for diagnosis. Biopsy evaluation requires copious examination by trained pathologists, which can be tedious and prone to human error. In this study, we propose an artificial intelligence (AI) method to assist pathologists in accurate segmentation and classification of pediatric kidney structures, named as AI-based Pediatric Kidney Diagnosis (APKD). RESULTS: We collected 2935 pediatric patients diagnosed with kidney disease for the development of APKD. The dataset comprised 93 932 histological structures annotated manually by three skilled nephropathologists. APKD scored an average accuracy of 94% for each kidney structure category, including 99% in the glomerulus. We found strong correlation between the model and manual detection in detected glomeruli (Spearman correlation coefficient r = 0.98, P < .001; intraclass correlation coefficient ICC = 0.98, 95% CI = 0.96-0.98). Compared to manual detection, APKD was approximately 5.5 times faster in segmenting glomeruli. Finally, we show how the pathological features extracted by APKD can identify focal abnormalities of the glomerular capillary wall to aid in the early diagnosis of pediatric kidney disease. AVAILABILITY AND IMPLEMENTATION: https://github.com/ChunyueFeng/Kidney-DataSet.

Machine learning for abdominal aortic calcification assessment from bone density machine-derived lateral spine images.

BACKGROUND: Lateral spine images for vertebral fracture assessment can be easily obtained on modern bone density machines. Abdominal aortic calcification (AAC) can be scored on these images by trained imaging specialists to assess cardiovascular disease risk. However, this process is laborious and requires careful training. METHODS: Training and testing of model performance of the convolutional neural network (CNN) algorithm for automated AAC-24 scoring utilised 5012 lateral spine images (2 manufacturers, 4 models of bone density machines), with trained imaging specialist AAC scores. Validation occurred in a registry-based cohort study of 8565 older men and women with images captured as part of routine clinical practice for fracture risk assessment. Cox proportional hazards models were used to estimate the association between machine-learning AAC (ML-AAC-24) scores with future incident Major Adverse Cardiovascular Events (MACE) that including death, hospitalised acute myocardial infarction or ischemic cerebrovascular disease ascertained from linked healthcare data. FINDINGS: The average intraclass correlation coefficient between imaging specialist and ML-AAC-24 scores for 5012 images was 0.84 (95% CI 0.83, 0.84) with classification accuracy of 80% for established AAC groups. During a mean follow-up 4 years in the registry-based cohort, MACE outcomes were reported in 1177 people (13.7%). With increasing ML-AAC-24 scores there was an increasing proportion of people with MACE (low 7.9%, moderate 14.5%, high 21.2%), as well as individual MACE components (all p-trend <0.001). After multivariable adjustment, moderate and high ML-AAC-24 groups remained significantly associated with MACE (HR 1.54, 95% CI 1.31-1.80 & HR 2.06, 95% CI 1.75-2.42, respectively), compared to those with low ML-AAC-24. INTERPRETATION: The ML-AAC-24 scores had substantial levels of agreement with trained imaging specialists, and was associated with a substantial gradient of risk for cardiovascular events in a real-world setting. This approach could be readily implemented into these clinical settings to improve identification of people at high CVD risk. FUNDING: The study was supported by a National Health and Medical Research Council of Australia Ideas grant and the Rady Innovation Fund, Rady Faculty of Health Sciences, University of Manitoba.

Nanoscale Calculation of Proton-Induced DNA Damage Using a Chromatin Geometry Model with Geant4-DNA.

Monte Carlo simulations can quantify various types of DNA damage to evaluate the biological effects of ionizing radiation at the nanometer scale. This work presents a study simulating the DNA target response after proton irradiation. A chromatin fiber model and new physics constructors with the ELastic Scattering of Electrons and Positrons by neutral Atoms (ELSEPA) model were used to describe the DNA geometry and the physical stage of water radiolysis with the Geant4-DNA toolkit, respectively. Three key parameters (the energy threshold model for strand breaks, the physics model and the maximum distance to distinguish DSB clusters) of scoring DNA damage were studied to investigate the impact on the uncertainties of DNA damage. On the basis of comparison of our results with experimental data and published findings, we were able to accurately predict the yield of various types of DNA damage. Our results indicated that the difference in physics constructor can cause up to 56.4% in the DNA double-strand break (DSB) yields. The DSB yields were quite sensitive to the energy threshold for strand breaks (SB) and the maximum distance to classify the DSB clusters, which were even more than 100 times and four times than the default configurations, respectively.

Physical activity estimated by osteogenic potential and energy expenditure has differing associations with bone mass in young adults: the raine study.

Ground impacts during physical activity may be important for peak bone mass. We found differences in how energy expenditure and impact scores estimated from a physical activity questionnaire related to bone health in young adults. Using both estimate types can improve our understanding of the skeletal benefits of physical activity. PURPOSE: It is unclear whether mechanical loading during physical activity, estimated from physical activity questionnaires which assess metabolic equivalents of task (METs), is associated with skeletal health. This longitudinal study investigated how physical activity loading scores, assessed at ages 17 and 20 years, (a) compares with physical activity measured in METs, and (b) is associated with bone mass at age 20 years. METHODS: A total of 826 participants from the Raine Study Gen2 were assessed for physical activity energy expenditure via the International Physical Activity Questionnaire (IPAQ) at age 17 and 20 years. Loading scores (the product of peak force and application rate) per week were subsequently estimated from the IPAQ. Whole-body and appendicular bone mineral density (BMD) at age 20 years were assessed by dual-energy X-ray absorptiometry. RESULTS: Bland-Altman minimal detectable difference for physical activity Z- scores at age 17 and 20 years were 1.59 standard deviations (SDs) and 1.33 SDs, respectively, greater than the a priori minimal clinically important change of 0.5 SDs. Loading score, but not IPAQ score, had significant positive associations with whole-body and leg BMD after adjustment for covariates (ß = 0.008 and 0.012 g/cm2, respectively, for age 17 and 20 years loading scores). IPAQ score at age 20 years, but not loading score, had a significant positive association with arm BMD (ß = 0.007 g/cm2). CONCLUSION: This study revealed disagreement in associations of self-reported METs and loading score estimates with bone health in young adults. Coupling traditional energy expenditure questionnaire outcomes with bone-loading estimates may improve understanding of the location-specific skeletal benefits of physical activity in young adults.

"The biggest reform to China's health system": did the zero-markup drug policy achieve its goal at traditional Chinese medicines county hospitals?

The zero-markup drug policy (ZMDP) was heralded as the biggest reform to China's modern health system. However, there have been a very limited number of investigations of the ZMDP at county hospital level, and those limited county hospital studies have several limitations in terms of sample representativeness and study design. We investigated the overall and dynamic effects of ZMDP at traditional Chinese medicine (TCM) county hospitals. We obtained longitudinal data from all TCM county hospitals in 2004-16 and the implementation year of ZMDP for each hospital. We used differences-in-difference methods to identify the overall and dynamic effects of ZMDP. On average, the ZMDP reform was associated with the reduction in the share of revenue from drug sales (3.1%), revenue from western medicines sales (12.7%), revenue from medical care services (3.6%) and gross hospital revenue (3.4%), as well as increased government subsidies (24.4%). The ZMDP reform was not significantly associated with the number of annual outpatient and inpatient visits. In terms of dynamic effects, the share of revenue from drug sales decreased by 2.5% in the implementation year and by about 5% in the subsequent years. Revenue from western medicine sales fell substantially in the short term and continued to drop in the long term. Government subsidies went up strikingly in the short term and long term, and revenue from medical care services and gross revenue decreased only in the implementation year. The ZMDP achieved its stated goal through reducing the share of revenue from drug sales without disrupting the availability of healthcare services at TCM county hospitals. The success of ZMDP was mainly due to the huge growth in the government's financial investment in TCM hospitals.

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Health financing and integration of urban and rural residents' basic medical insurance systems in China.

BACKGROUND: China is in the process of integrating the new cooperative medical scheme (NCMS) and the urban residents' basic medical insurance system (URBMI) into the urban and rural residents' basic medical insurance system (URRBMI). However, how to integrate the financing policies of NCMS and URBMI has not been described in detail. This paper attempts to illustrate the differences between the financing mechanisms of NCMS and URBMI, to analyze financing inequity between urban and rural residents and to identify financing mechanisms for integrating urban and rural residents' medical insurance systems. METHODS: Financing data for NCMS and URBMI (from 2008 to 2015) was collected from the China health statistics yearbook, the China health and family planning statistics yearbook, the National Handbook of NCMS Information, the China human resources and social security statistics yearbook, and the China social security yearbook. "Ability to pay" was introduced to measure inequity in health financing. Individual contributions to NCMS and URBMI as a function of per capita disposable income was used to analyze equity in health financing between rural and urban residents. RESULTS: URBMI had a financing mechanism that was similar to that used by NCMS in that public finance accounted for more than three quarters of the pooling funds. The scale of financing for NCMS was less than 5% of the per capita net income of rural residents and less than 2% of the per capita disposable income of urban residents for URBMI. Individual contributions to the NCMS and URBMI funds were less than 1% of their disposable and net incomes. Inequity in health financing between urban and rural residents in China was not improved as expected with the introduction of NCMS and URBMI. The role of the central government and local governments in financing NCMS and URBMI was oscillating in the past decade. CONCLUSIONS: The scale of financing for URRBMI is insufficient for the increasing demands for medical services from the insured. The pooling fund should be increased so that it can better adjust to China's rapidly aging population and epidemiological transitions as well as protect the insured from poverty due to illness. Individual contributions to the URBMI and NCMS funds were small in terms of contributors' incomes. The role of the central government and local governments in financing URRBMI was not clearly identified. Individual contributions to the URRBMI fund should be increased to ensure the sustainable development of URRBMI. Compulsory enrollment should be required so that URRBMI improves the social medical insurance system in China.

Essential Public Health Services' Accessibility and its Determinants among Adults with Chronic Diseases in China.

BACKGROUND: Along with three years implementation of health reform in China, this study aimed at providing the up-to-date evidence about the accessibility of essential public health services (EPHS) among adults with chronic diseases (CDs) in both urban and rural areas, as well as determinants in access to EPHS. METHODS: The data were collected from a cross-sectional survey conducted in 2013, which used a multistage stratified random sampling method to select 54 urban communities and 54 rural villages. Hypertension patients and diabetes patients were the target population who are the main beneficiaries of EPHS. Single factor analysis of influencing factors on difference access to EPHS was performed by Chi-Square analysis. Logistic regression analysis was used to determine the predictors of effective management and effective control. RESULTS: Patients with hypertension or diabetes were predominantly middle-aged or older persons and had a mean age of 65.26 year. People with CDs in China have a higher basic accessibility rate in EPHS with more than 90% of them having experience in receiving EPHS. And those who are willing to receive services from doctors have the most positive influence on effective management and control in blood pressure or blood glucose. But unsatisfied quality and equity of EPHS still exist in primary health system. 90% of participants could receive EPHS, but just 44% of them could control their diseases effectively. And participants from cities had the higher rates in effective management (urban: rural = 57%: 50.6%) and effective control (urban: rural = 39.5%: 27.8%). CONCLUSION: People with CDs have a high level in geography and economic accessibility to EPHS, but the effectiveness of health management also needs to be improved, especially for those living in rural areas. Our study highlights the continuing need for improving ability to provide EPHS and the equality among regions. Meanwhile, strengthen health education and promotion for patients with CDs to improve their willingness to receive EPHS is also highlighted.

A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus.

BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. AIM: To identify CNVs associated with osteoporotic bone fracture risk. METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p = 8.69 × 10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p = 0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

[Current status and urban-rural comparison of clinical agency of detection, management, and health insurance for hypertensive patients in communities of five provinces in China in 2010].

OBJECTIVE: To investigate the status of the clinical agency of detection, management, and health insurance for hypertensive patients in urban and rural communities of five provinces in China in 2010, in order to provide fundamental data for implementation and evaluation of community health management of hypertensive patients in basic public health service. METHODS: From Jiangsu, Shandong, Hebei, Sichuan and Gansu provinces, cities and districts (counties) were selected according to economic development level and 10 survey sites were finally determined. In each survey site, 3-4 communities or townships were selected by cluster sampling methods in 2010. A total of 8326 eligible hypertensive patients (4363 in urban and 3963 in rural) were included. The urban-rural difference of clinical agency and health insurance was compared for hypertensive patients. RESULTS: In urban areas, 43.74% (1867/4268) hypertensive patients were first diagnosed at hospitals of district level or above, 25.07% (1070/4268) at community health service centers (CHSC), and 20.20% (862/4268) at community health service stations (CHSS), respectively; 30.72% (1274/4147) and 31.11% (1290/4147) patients chose CHSC and CHSS for their follow-up visiting, respectively; 60.23% (3073/5102) antihypertensive medication was obtained from pharmacies. In rural areas, 54.58% (2133/3908) hypertensive patients were first diagnosed at village clinics, 22.36% (874/3908) at township hospitals, and 18.86% (737/3908) at hospitals of county level or above; 70.49% (2695/3823) patients chose village clinics for their follow-up visiting; 46.23% (2116/4577) antihypertensive medication was obtained from village clinics, and 36.29% (1661/4577) from pharmacies. The main reasons for choosing clinical agency for both urban and rural patients were convenience (45.79%, 6276/13 706) and low cost (11.78%, 1614/13 706). The proportions of reimbursements for hospitalization expenses and total medical expenses for hypertensive patients in urban in the past year were 66.67% and 34.78%, respectively, which were much higher than those in rural (35.71% and 9.50%) (Z value was -12.13 and -17.56, P < 0.01). CONCLUSION: Community-based hypertension detection and routine blood pressure measurement during clinical visiting should be further strengthened to improve early diagnosis of hypertension. The development of community-based clinical agency should be able to provide convenient and low cost health service for hypertensive patients to improve treatment, follow-up and control of hypertension.

Assessment of gene-by-sex interaction effect on bone mineral density.

Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.

Combining metabolic engineering and adaptive evolution to enhance the production of dihydroxyacetone from glycerol by Gluconobacter oxydans in a low-cost way.

Gluconobacter oxydans can rapidly and effectively transform glycerol to dihydroxyacetone (DHA) by membrane-bound quinoprotein sorbitol dehydrogenase (mSLDH). Two mutant strains of GDHE Δadh pBBR-PtufBsldAB and GDHE Δadh pBBR-sldAB derived from the GDHE strain were constructed for the enhancement of DHA production. Growth performances of both strains were largely improved after adaptively growing in the medium with glucose as the sole carbon source. The resulting GAT and GAN strains exhibited better catalytic property than the GDHE strain in the presence of a high concentration of glycerol. All strains of GDHE, GAT and GAN cultivated on glucose showed enhanced catalytic capacity than those grown on sorbitol, indicating a favorable prospect of using glucose as carbon source to reduce the cost in industrial production. It was also the first time to reveal that the expression level of the sldAB gene in glucose-growing strains were higher than that of the strains cultivated on sorbitol.

[The analysis of drug cost and direct medical expense in community health management of hypertensive patients].

OBJECTIVE: To investigate the current situation of drug cost, hospitalization cost and direct medical expense in community health management of hypertensive patients, in order to lay foundation for evaluating whether the community health management in basic public health service has cost-effect in Health Economics. METHODS: A total of 8326 hypertensive patients from 10 survey pilots in 5 provinces were selected by cluster sampling methods, including 3967 patients who took part in community health management for over 1 year as management group and 4359 cases who have never taken part in community health management as control group. The essential information of research objects were collected by questionnaire; and the medical cost information in the last year (from November 2009 to November 2010) were collected retrospectively. The different annual medical treatment cost, hospitalization cost and direct medical expense in the two groups were compared and analyzed. RESULTS: The average annual drug cost in hypertension was (621.50 ± 1337.78) yuan per patient; while the cost was (616.13 ± 1248.40) yuan in management group and (626.44 ± 1414.30) yuan in control group respectively. The average annual drug cost of hypertensive patients who took medicine therapy was (702.05 ± 1401.79) yuan per person, while the cost in the management group ((688.50 ± 1300.70) yuan) was much lower than it in control group ((714.64 ± 1489.60) yuan). The annual average drug cost in urban was (731.88 ± 1403.31) yuan per person, which was higher than it in rural as (407.44 ± 1171.44) yuan per person. The average hospitalized rate was 12.2% (1014/8326), and the average annual cost among the hospitalized patients was (9264.47 ± 18 088.49) yuan per person; while the cost was (7583.70 ± 13 267.00) yuan in management group, which was lower than it in control group as (11 028.00 ± 21 919.00) yuan. The average annual hospitalized cost in hypertension was (1064.87 ± 6804.83) yuan per person; while the cost was (936.73 ± 5284.90) yuan in management group, which was lower than it in control group as (1181.50 ± 7937.90) yuan. The average annual direct medical expense in hypertension was (2275.08 ± 8225.66) yuan per person; while the expense was (2165.10 ± 6564.60) yuan in management group and (2375.20 ± 9487.60) yuan in control group. The average annual direct medical expense in urban ((2801.06 ± 9428.54) yuan per person) was higher than it in rural ((1254.70 ± 4990.27) yuan per person). CONCLUSION: The community health or standardized management of hypertensive patients can reduce the average annual drug cost and hospitalization cost (around 26 yuan and 245 yuan separately); and thereby save the annual direct medical expense per capita in hypertension (around 210 yuan). In the reform and development of national medical health system, we should enhance and promote the standardized community health management of hypertensive patients.

[Pb pollution on surfaces in a typical coking plant and health risk assessment].

Pb pollution on the surfaces of buildings and devices at a coking plant was studied. The objectives of this study were to determine the Pb content and its spatial variation on the surfaces, and to assess the potential health risk from this Pb. Ninety-four wipe samples were collected from 56 buildings and devices at the coking plant, and their Pb contents were determined. Surface Pb concentrations ranged from 0-538 micro x g/dm2, and concentrations in 78.7% of the samples exceeded the US Department of Housing and Urban Development (HUD) standard (2.69 microg/dm2). By area, the proportion of samples with concentrations greater than the US HUD standard were 78.9% in the office and living zone, 75.0% in the refining zone, 73.7% in the coking zone and 78.6% in the coke-gas zone. Among the various types of surfaces, the coke pusher had the highest average surface concentration of Pb. The average surface concentrations of Ph on common coking plant surface materials followed the order paints > brick > cement > glass, and the concentrations in 94.4% of the wipe samples taken from paint surfaces exceeded the US HUD standard.

Management capacity and health insurance: the case of the New Cooperative Medical Scheme in six counties in rural China.

In 2003, China launched the New Cooperative Medical Scheme (NCMS) as a form of health insurance for rural areas. Counties play an important part in the management of the system, raising issues over the capacity of local government to manage complex health insurance systems. This paper examines the extent and impact of county level managerial capacity to manage the NCMS. The paper is largely based on qualitative data but supported by quantitative data. Policy makers, NCMS administrators, health providers and residents were interviewed in May 2006 in six counties in rural China. Management capacity was defined as the capability to bring together and use resources to carry out responsibilities. The results are grouped into three areas of management capacity: staff, organizational and contextual. Respondents complained about inadequate staffing, poor organizational resources and conduct of responsibilities in areas such as premium collection and remuneration. Key problems in contextual capacity included: counties are restricted in their ability to use resources for management; counties lack support from other organizations and suffer from a conflict of responsibilities. This paper underlines the importance of effective management capacity for NCMS at the decentralized level and suggests pointers for the content and process of management capacity development.

Balancing the funds in the New Cooperative Medical Scheme in rural China: determinants and influencing factors in two provinces.

In recent years, the central government in China has been leading the re-establishment of its rural health insurance system, but local government institutions have considerable flexibility in the specific design and management of schemes. Maintaining a reasonable balance of funds is critical to ensure that the schemes are sustainable and effective in offering financial protection to members. This paper explores the financial management of the NCMS in China through a case study of the balance of funds and the factors influencing this, in six counties in two Chinese provinces. The main data source is NCMS management data from each county from 2003 to 2005, supplemented by: a household questionnaire survey, qualitative interviews and focus group discussions with all local stakeholders and policy document analysis. The study found that five out of six counties held a large fund surplus, whilst enrolees obtained only partial financial protection. However, in one county greater risk pooling for enrolees was accompanied by relatively high utilisation levels, resulting in a fund deficit. The opportunities to sustainably increase the financial protection offered to NCMS enrolees are limited by the financial pressures on local government, specific political incentives and low technical capacities at the county level and below. Our analysis suggests that in the short term, efforts should be made to improve the management of the current NCMS design, which should be supported through capacity building for NCMS offices. However, further medium-term initiatives may be required including changes to the design of the schemes.

Effects of school milk intervention on cortical bone accretion and indicators relevant to bone metabolism in Chinese girls aged 10-12 y in Beijing.

BACKGROUND: We previously reported that increased milk consumption enhances growth and bone mineral accretion in Chinese girls aged 10-12 y. OBJECTIVE: Our objective was to evaluate the effects of milk supplementation on cortical bone accretion and to study the physiologic mechanisms underlying the observed changes in bone. DESIGN: Chinese girls aged 10 y were randomly assigned into calcium-fortified milk (Ca milk), calcium and vitamin D-fortified milk (CaD milk), and control groups according to their schools in a 24-mo school milk intervention trial. Periosteal and medullary diameters of metacarpal bone were measured at baseline and 24 mo in the Ca milk (n = 177), CaD milk (n = 210), and control (n = 219) groups. Insulin-like growth factor I (IGF-I), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), osteocalcin, and deoxypyridinoline concentrations were measured at baseline and at 12 and 24 mo in the Ca milk (n = 43), CaD milk (n = 44), and control (n = 41) groups. RESULTS: After adjustment for pubertal status and clustering by school, 24-mo supplementation led to greater increases in periosteal diameter (1.2%) and cortical thickness (5.7%) and to smaller gains in medullary diameter (6.7%) than did the control (P < 0.05). The CaD milk group had lower serum BAP at 12 mo (19.9%) and lower serum PTH at 12 (46.2%) and 24 (16.4%) mo than did the control group (P < 0.05). The effect of milk supplementation on increasing IGF-I concentrations at 24 mo (16.7-23.3%) was significant in individual analyses but not after adjustment for clustering by school. CONCLUSIONS: Milk supplementation showed positive effects on periosteal and endosteal apposition of cortical bone.