Harmonization of four biomarkers across nine nationally representative studies of older persons.

INTRODUCTION: A growing number of international population surveys have included measurement of biomarkers, but differ in the type of specimens collected, sample processing procedures, shipment protocols, and laboratory assay platforms. The purpose of this study is to harmonize biomarker data from nine nationally representative studies of people 50 years of age and over by adjusting for assay platforms and type of specimens for total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), glycosylated hemoglobin (HbA1c), and C-reactive protein (CRP). METHODS: Sets of 24 identical serum, plasma, whole blood, and dried blood spot harmonization samples with known analyte levels were generated at a reference laboratory, shipped at -80°C to the respective study laboratories, and subsequently assayed following the study laboratory's protocol. Both original and harmonized study data were used to calculate mean values and at-risk prevalence. RESULTS: The correlation coefficients between the biomarker values of the harmonization samples obtained by the study laboratories and the reference laboratory were 0.99 or above for all analytes and laboratories, indicating the high quality of assays at all laboratories. However, using the harmonized data from each study, there were significant differences in the mean values and country ranking of the prevalence of at-risk levels of these four biomarkers. CONCLUSIONS: While the biomarker data from the different study laboratories were highly correlated, indicating very high correlation of rank order of specimens, absolute values did vary significantly. This can have a major impact on assessment of international differences in estimates of risks for chronic morbidity and mortality.

Hypertension awareness, treatment, and control and their association with healthcare access in the middle-aged and older Indian population: A nationwide cohort study.

BACKGROUND: Hypertension is the most important cardiovascular risk factor in India, and representative studies of middle-aged and older Indian adults have been lacking. Our objectives were to estimate the proportions of hypertensive adults who had been diagnosed, took antihypertensive medication, and achieved control in the middle-aged and older Indian population and to investigate the association between access to healthcare and hypertension management. METHODS AND FINDINGS: We designed a nationally representative cohort study of the middle-aged and older Indian population, the Longitudinal Aging Study in India (LASI), and analyzed data from the 2017-2019 baseline wave (N = 72,262) and the 2010 pilot wave (N = 1,683). Hypertension was defined as self-reported physician diagnosis or elevated blood pressure (BP) on measurement, defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg. Among hypertensive individuals, awareness, treatment, and control were defined based on self-reports of having been diagnosed, taking antihypertensive medication, and not having elevated BP, respectively. The estimated prevalence of hypertension for the Indian population aged 45 years and older was 45.9% (95% CI 45.4%-46.5%). Among hypertensive individuals, 55.7% (95% CI 54.9%-56.5%) had been diagnosed, 38.9% (95% CI 38.1%-39.6%) took antihypertensive medication, and 31.7% (95% CI 31.0%-32.4%) achieved BP control. In multivariable logistic regression models, access to public healthcare was a key predictor of hypertension treatment (odds ratio [OR] = 1.35, 95% CI 1.14-1.60, p = 0.001), especially in the most economically disadvantaged group (OR of the interaction for middle economic status = 0.76, 95% CI 0.61-0.94, p = 0.013; OR of the interaction for high economic status = 0.84, 95% CI 0.68-1.05, p = 0.124). Having health insurance was not associated with improved hypertension awareness among those with low economic status (OR = 0.96, 95% CI 0.86-1.07, p = 0.437) and those with middle economic status (OR of the interaction = 1.15, 95% CI 1.00-1.33, p = 0.051), but it was among those with high economic status (OR of the interaction = 1.28, 95% CI 1.10-1.48, p = 0.001). Comparing hypertension awareness, treatment, and control rates in the 4 pilot states, we found statistically significant (p < 0.001) improvement in hypertension management from 2010 to 2017-2019. The limitations of this study include the pilot sample being relatively small and that it recruited from only 4 states. CONCLUSIONS: Although considerable variations in hypertension diagnosis, treatment, and control exist across different sociodemographic groups and geographic areas, reducing uncontrolled hypertension remains a public health priority in India. Access to healthcare is closely tied to both hypertension diagnosis and treatment.

Venous Blood-Based Biomarkers in the China Health and Retirement Longitudinal Study: Rationale, Design, and Results From the 2015 Wave.

Blood biomarkers provide critical information about the health of older populations, especially in large developing countries where self-reports of health are often inaccurate due to lack of access to health care. However, it is very difficult to collect blood samples in representative population surveys in such countries. The China Health and Retirement Longitudinal Study (CHARLS), a nationally representative study of middle-aged and older Chinese, represents one of the first efforts to include blood biomarkers in a nationally representative survey of China. In the 2015 wave of CHARLS, 13,013 respondents located in 150 counties around China donated whole blood, which was assayed on a range of indicators. Here we describe the process of the sample collection, transportation, storage, and analysis and present basic statistics.

Validation and modification of dried blood spot-based glycosylated hemoglobin assay for the longitudinal aging study in India.

OBJECTIVES: This study aims to validate a modified dried blood spot (DBS)-based glycosylated hemoglobin (HbA1c) assay protocol, after a pretest in India showed poor correlation between the original DBS-based protocol and venous results. METHODS: The original protocol was tested on different chemistry analyzers and then simplified at the University of Washington (UW). A second pretest was conducted in India to validate the modified assay protocol, using 44 quality control specimens. RESULTS: Data from UW indicated that, using the original protocol, the correlation coefficients between DBS and venous results were above 0.98 on both Bio-Rad and Olympus chemistry analyzers. The protocol worked equally well on filter paper, with or without pre-treatment, and when the recommended amount of blood spot material, or less, was used. A second pretest of the modified protocol confirmed that DBS-based levels from both Olympus and Roche chemistry analyzers were well correlated with DBS results from UW (correlation coefficients were above 0.96), as well as with venous values (correlation coefficients were above 0.94). CONCLUSIONS: The DBS-based HbA1c values are highly correlated with venous results. The pre-treatment of filter paper does not appear to be necessary. The poor results from the first pretest are probably due to factors unrelated to the protocol, such as problems with the chemistry analyzer or assay reagents.

Anemia, hemoglobin concentration and cognitive function in the Longitudinal Ageing Study in India-Harmonized Diagnostic Assessment of Dementia (LASI-DAD) and the Health and Retirement Study.

Background: In India, anemia is widely researched in children and women of reproductive age, however, studies in older populations are lacking. Given the adverse effect of anemia on cognitive function and dementia this older population group warrants further study. The Longitudinal Ageing Study in India - Harmonized Diagnostic Assessment of Dementia (LASI-DAD) dataset contains detailed measures to allow a better understanding of anaemia as a potential risk factor for dementia. Method: 2,758 respondents from the LASI-DAD cohort, aged 60 or older, had a complete blood count measured from venous blood as well as cognitive function tests including episodic memory, executive function and verbal fluency. Linear regression was used to test the associations between blood measures (including anemia and hemoglobin concentration (g/dL)) with 11 cognitive domains. All models were adjusted for age and gender with the full model containing adjustments for rural location, years of education, smoking, region, BMI and population weights.Results from LASI-DAD were validated using the USA-based Health and Retirement Study (HRS) cohort (n=5720) to replicate associations between blood cell measures and global cognition. Results: In LASI-DAD, we showed an association between anemia and poor memory (p=0.0054). We found a positive association between hemoglobin concentration and ten cognitive domains tested (ß=0.041-0.071, p<0.05). The strongest association with hemoglobin was identified for memory-based tests (immediate episodic, delayed episodic and broad domain memory, ß=0.061-0.071, p<0.005). Positive associations were also shown between the general cognitive score and the other red blood count tests including mean corpuscular hemoglobin concentration (MCHC, ß=0.06, p=0.0001) and red cell distribution width (RDW, ß =-0.11, p<0.0001). In the HRS cohort, positive associations were replicated between general cognitive score and other blood count tests (Red Blood Cell, MCHC and RDW, p<0.05). Conclusion: We have established in a large South Asian population that low hemoglobin and anaemia are associated with low cognitive function, therefore indicating that anaemia could be an important modifiable risk factor. We have validated this result in an external cohort demonstrating both the variability of this risk factor cross-nationally and its generalizable association with cognitive outcomes.

Pertussis toxoid structure: a collaboration and comparison of two-dimensional liquid chromatography-tandem mass spectrometry, ultraperformance liquid chromatography-mass spectrometryE, and capillary liquid chromatography-matrix-assisted laser desorption ionization-tandem mass spectrometry.

The overall structure of pertussis toxoid has been established by analysis of its tryptic digest using two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS), capillary liquid chromatography-matrix-assisted laser desorption ionization-tandem mass spectrometry (CapLC-MALDI-MS/MS), and ultraperformance liquid chromatography-mass spectrometry(E) (UPLC-MS(E)). In addition to oxidation and hydrolysis of amino acids losses of terminal peptides are observed. On-line UPLC-MS(E) generated a similar sequence coverage as the other two methods that involved off-line fraction collection. In light of recent favorable comparisons to data-dependent acquisition, UPLC-MS(E) should be the initial method of choice for analysis of a peptide mixture of moderate complexity.

The prevalence of frailty and its relationship with sociodemographic factors, regional healthcare disparities, and healthcare utilization in the aging population across India.

Objective: To estimate frailty prevalence and its relationship with the socio-economic and regional factors and health care outcomes. Methods: In this study, participants from the harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) were included. The frailty index (FI) was calculated using a 32-variable deficit model, with a value of ≥ 25% considered as frail. Data on demographic (including caste and religion) and socioeconomic profiles and health care utilization were obtained. The state-wise health index maintained by the government based on various health-related parameters was used to group the participants' residential states into high-, intermediate-, and low-performing states. Multivariable and zero-inflated negative binomial regression was used to assess the relationship of frailty index with sociodemographic characteristics, health index, and health care expenditure or hospitalization. Results: Among the 3953 eligible participants, the prevalence of frailty was 42.34% (men = 34.99% and women = 49.35%). Compared to high-performing states, intermediate- and low-performing states had a higher proportion of frail individuals (49.7% vs. 46.8% vs. 34.5%, P < 0.001). In the adjusted analysis, frailty was positively associated with age, female sex, rural locality, lower education level, and caste (scheduled caste and other backward classes). After adjusting for the socio-economic profile, FI was inversely associated with the composite health index of a state (P < 0.001). FI was also significantly correlated with total 1-year health care expenditure and hospitalization (P < 0.001 and 0.020, respectively). Conclusion: There is a high prevalence of frailty among older Indian adults that is associated with sociodemographic factors and regional health care performance. Furthermore, frailty is associated with increased health care utilization and expenditure.

Deep phenotyping and genomic data from a nationally representative study on dementia in India.

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.

Case study: contamination of heparin with oversulfated chondroitin sulfate.

In late 2007 and early 2008, a cluster of adverse events in patients receiving Heparin Sodium Injection occurred in the United States and in some countries in Europe. The adverse events were reported as being "allergic type" reactions, chiefly characterized by acute hypotension, nausea, and shortness of breath. The root cause of the cluster of adverse events was determined to be a contamination of the heparin by oversulfated chondroitin sulfate. The isolation and structure determination of this contaminant was accomplished by an FDA-led consortium of academic and government laboratories and independently by Baxter Healthcare, whose vial products were first identified in the USA as being associated with the adverse events. Oversulfated chondroitin sulfate was shown to produce acute hypotension in animal models, demonstrating that it was most likely the causative agent responsible for certain of the reported adverse events in patients receiving the contaminated heparin products.

Links Between Mortality and Socioeconomic Characteristics, Disease Burden, and Biological and Physical Functioning in the Aging Chinese Population.

OBJECTIVES: Determinants of mortality may depend on the time and place where they are examined. China provides an important context in which to study the determinants of mortality at older ages because of its unique social, economic, and epidemiological circumstances. This study uses a nationally representative sample of persons in China to determine how socioeconomic characteristics, early-life conditions, biological and physical functioning, and disease burden predict 4-year mortality after age 60. METHODS: We used data from the China Health and Retirement Longitudinal Study. We employed a series of Cox proportional hazard models based on exact survival time to predict 4-year all-cause mortality between the 2011 baseline interview and the 2015 interview. RESULTS: We found that rural residence, poor physical functioning ability, uncontrolled hypertension, diabetes, cancer, a high level of systemic inflammation, and poor kidney functioning are strong predictors of mortality among older Chinese. DISCUSSION: The results show that the objectively measured indicators of physical functioning and biomarkers are independent and strong predictors of mortality risk after accounting for several additional self-reported health measures, confirming the value of incorporating biological and performance measurements in population health surveys to help understand health changes and aging processes that lead to mortality. This study also highlights the importance of social and historical context in the study of old-age mortality.

Disability Incidence Rates for Men and Women in 23 Countries: Evidence on Health Effects of Gender Inequality.

BACKGROUND: Inequality in gender varies across social contexts, which may influence the health of both men and women. Based on theories of gender as a social system, we examine whether systematic gender inequality at the macro-level influences health of men and women. METHOD: Using harmonized panel data from the Gateway to Global Aging Data in 23 high- and middle-income countries (N = 168 873), we estimate disability prevalence and incidence for men and women ages 55-89 (2000-2016). Within each country or geographic region, we also investigate gender differences in age gradients of the probability of disability onset. We, then, pool data from all countries and test the hypothesis that gender inequality increases the probability of disability onset. RESULTS: We found substantial cross-country variation in disability incidence rates, and this variation is greater for women than for men. Among ages 65-69, disability incidence rates ranged from 0.4 to 5.0 for men and from 0.5 to 9.4 for women. Our within-country analysis showed significant gender differences in age gradients of the probability of disability onset in the United States, Korea, Southern Europe, Mexico, and China, but not in Northern, Central, and Eastern Europe, England, and Israel. Testing hypothesized effects of gender inequality, we find that gender inequality is significantly associated with the probability of disability onset for women, but not for men. CONCLUSIONS: Macro-level societal gender inequality is significantly associated with the probability of disability onset for women. Reducing and eliminating gender inequality is crucial to achieving good health for women.

Characterization of pertussis toxoid by two-dimensional liquid chromatography-tandem mass spectrometry.

Pertussis toxoid, an acellular pertussis vaccine prepared by hydrogen peroxide treatment in the presence of Fe(3+), has not been well characterized. Because the toxoid has been a part of the DTaP vaccine for infants, it is of interest and significance to have a clear understanding of its structure. The five subunits of pertussis toxin (PT) have a combined molecular weight of approximately 95,000Da. The peroxide treatment in toxoid formation introduces additional complexity into the protein sequence. To maximize sequence coverage, a two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) approach was used to analyze the tryptic digest of toxoid as a whole. An analytical-scale high-performance liquid chromatography (HPLC) instrument using a pentafluorophenyl (PFP) column was used as the first-dimensional LC for fraction collection. The fractions were then analyzed by nanoLC-MS/MS using a C18 column to acquire collision-activated dissociation (CAD) spectra of the tryptic peptides. It is shown that a PFP column has a different peptide retention specificity from a C18 column. A combination of a PFP column and a C18 column is a viable approach for dispersing peptides in a complex mixture. From the structures of 65 peptides that represented approximately 50% of its sequence, PT was found to have sustained heavy oxidative damages during toxoid preparation. Nearly all methionine, cysteine, and (likely) tryptophan residues were oxidized. Evidence of histidine and tyrosine oxidation was also observed. In addition, a large percentage of asparagine was found hydrolyzed to aspartic acid. These findings corrrelate well with the reduction of PT toxicity by peroxide treatment.

Living Longer, With or Without Disability? A Global and Longitudinal Perspective.

BACKGROUND: Significant gains in life expectancy have been achieved, but living longer does not necessarily mean the years gained are productive and healthy. Different theories predict different patterns of time trends in old-age disability prevalence. METHODS: Using the Gateway to Global Aging Data, which provides internationally harmonized longitudinal data from the Health and Retirement Study and its sister surveys, we compare time trends (from 2004 to 2014) in disability prevalence across countries. RESULTS: Disability prevalence varies greatly across countries, and divergent time trends are observed across countries. For countries such as Belgium, Czechia, and Mexico, we observe an increase of disability prevalence, whereas in countries such as Denmark, England, Greece, Korea, Poland, and Sweden, we observe a substantial decrease in disability prevalence. Looking further into the severity of disability, we often observe differential trends in prevalence, but there is no evidence supporting the dynamic equilibrium hypothesis that predicts increased prevalence of modest disability but a decrease in severe disability prevalence. CONCLUSIONS: Significant gains in life expectancy have translated into different gains in healthy years of life across different countries. Diverse time trends in disability prevalence across countries reaffirm that the expansion of late-life disability is not inevitable.

Cognitive Function and Cardiometabolic-Inflammatory Risk Factors Among Older Indians and Americans.

OBJECTIVES: To investigate how cardiometabolic-inflammatory risk factors are related to cognition among older adults in India and the United States. DESIGN: The Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) and the Harmonized Cognitive Assessment Protocol of the Health and Retirement Study (HRS-HCAP) in the United States conducted an in-depth assessment of cognition, using protocols designed for international comparison. SETTING: Cognitive tests were conducted in hospital or household settings in India and in household settings in the United States. PARTICIPANTS: Respondents aged 60 years and older from LASI-DAD (N = 1,865) and respondents aged 65 years and older from HRS-HCAP (N = 2,111) who provided venous blood specimen. MEASUREMENTS: We used total composite scores from the common cognitive tests administered. Cardiovascular risk was indicated by systolic and diastolic blood pressure, pulse rate, pro-B-type natriuretic peptide (proBNP), and homocysteine. Metabolic risk was measured by body mass index, glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol, and lipoprotein (a) (only in India). Inflammatory risk was indicted by white blood cell count, C-reactive protein, albumin, and uric acid (only in India). RESULTS: The distribution of both total cognition scores and of cardiometabolic risk factors differed significantly between India and the United States. In both countries, lower cognition was associated with older age, lower education, elevated homocysteine, elevated proBNP, and lower albumin levels. The associations between HbA1c levels and cognitive measures were statistically significant in both countries, but in the opposite direction, with a coefficient of 1.5 (P < .001) in India and -2.4 (P < .001) in the United States for one percentage increase in absolute HbA1c value. CONCLUSION: Cardiometabolic-inflammatory biomarkers are associated with cognitive functional levels in each country, but the relationships may vary across countries. J Am Geriatr Soc 68:S36-S44, 2020.

Ascertaining cause of mortality among middle-aged and older persons using computer-coded and expert review verbal autopsies in the China Health and Retirement Longitudinal Study.

BACKGROUND: Verbal autopsy is designed to ascertain causes of death that are not registered or certified. Verbal autopsy has been validated in multiple settings but has not been as widely evaluated for older populations as for younger age groups. OBJECTIVE: This study aims to provide empirical evidence of the value of verbal autopsy interviews in the context of population-based surveys of older adults by comparing the cause-of-death assignments derived from two methods of interpreting verbal autopsy data. METHODS: Data used in this study come from the China Health and Retirement Longitudinal Study, a nationally representative longitudinal survey of older Chinese. We compared 407 causes of death determined using InterVA, which is a computer-coded method, and causes of death as assigned by experts; then evaluated factors that affect the results of the two approaches. RESULTS: Among the 407 deaths, neoplasms, cardiac disease, and stroke are the leading causes of death according to both approaches. The consistency of the two approaches is about 45% at the individual level. The primary reason for the mismatch is that no cause of death could be assigned for more than 25% of the sample based on expert review. A higher likelihood of mismatch is associated with advanced age and a long period between death and verbal autopsy interview. CONCLUSION: Both approaches identify the same leading causes of death at the aggregate level, but consistency is relatively low at the individual level. InterVA works well when causes of death are characterized by distinctive signs and symptoms. Grouping the various causes of death with shared etiology or common risk factors may help improve the quality of the ascertainment of causes of death. Open-ended narratives are helpful because they provide information about the circumstances surrounding the death that are not available in the structured verbal autopsy interviews.

Methodological considerations in designing and implementing the harmonized diagnostic assessment of dementia for longitudinal aging study in India (LASI-DAD).

The Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI-DAD) is a population-representative, prospective cohort study of late-life cognition and dementia. It is part of an ongoing international research collaboration that aims to measure and understand cognitive impairment and dementia risk by collecting a set of cognitive and neuropsychological assessments and informant reports, referred to as the Harmonized Cognitive Assessment Protocol (HCAP). LASI-DAD provides nationally representative data drawn from a subsample of the ongoing Longitudinal Aging Study in India (LASI). One of LASI-DAD's distinctive features is its rich geriatric assessment, including the collection of venous blood samples and brain imaging data for a subsample of respondents. In this paper, we discuss the methodological considerations of developing and implementing the HCAP protocol in India. The lessons we learned from translating and applying the HCAP protocol in an environment where illiteracy and innumeracy are high will provide important insights to researchers interested in measuring and collecting data on late-life cognition and dementia in developing countries. We further developed an innovative blood management system that enables us to follow the collection, transportation, assay, and storage of samples. Such innovation can benefit other population surveys collecting biomarker data.

Source-induced fragmentation of heparin, heparan, and galactosaminoglycans and application.

Sulfated glycosaminoglycans (GAGs) are difficult molecules for analysis by mass spectrometry due to their complexity in saccharide composition, polydispersity, and sequence heterogeneity. Structural information is typically derived from their enzymatic or chemical digests. Many analytical studies focused on the determination of disaccharide compositions. In this study a direct electrospray mass spectrometry method is described for the analysis of intact heparin, heparan sulfate, dermatan sulfate, and chondroitin sulfates. The GAGs were desalted by membrane filtration and analyzed in dilute formic acid (0.5%) in negative ion mode. At the dissociation cone voltage (defined as minimum cone voltage to dissociate all polymeric molecules), heparin, heparan sulfate, dermatan sulfate, and chondroitin sulfates produced simple mass spectra consisting primarily of monosaccharide and disaccharide ions derived from glycosidic bond cleavages. The type and abundance of the ions in the dissociation of each molecule were a good reflection of their saccharide compositions. The major ions of heparin were the hexuronic acid ion (m/z 175), glucosamine ion (m/z 240), and the disaccharide ion (m/z 416). Heparan sulfate produced the same set of fragments as heparin since they shared the same compositional saccharides. However, the formation of the m/z 175 ion dominated the source induced fragmentation process for heparan sulfate reflecting its high content of the nonsulfated disaccharide D-glucuronic acid-acetylated glucosamine (GlcA-GlcNAc). Chondroitin/dermatan sulfates contained only acetylated amino sugar (acetylated galactosamine (GalNAc). Consequently, the principle mono/disaccharide ions were all acetylated with m/z values of 282 and 458, respectively. The contrast among the dissociation features of the three types of molecules were sufficient to allow their ready differentiation. Additionally, sensitive detection of chondroitin/dermatan sulfate and heparan sulfate in heparin was made possible by the same differences in the dissociation chemistry of the three types of molecules. As low as 0.5% chondroitin/dermatan sulfate and 5% heparan sulfate in heparin can be reliably detected. This method was successfully used for the detection of oversulfated chondroitin sulfate in heparin as a contaminant following reports of increased adverse events associated with heparin injections from the end of 2007 to early 2008. Heparin is an important, widely prescribed anticoagulant. In light of this contamination event, quality assurance beyond standard activity assays proves to be important. This method provides a simple and fast way for the detection of low level chondroitin, dermatan, and heparan sulfates and their oversulfated derivatives in heparin raw material or formulation.

Famine, death, and madness: schizophrenia in early adulthood after prenatal exposure to the Chinese Great Leap Forward Famine.

Using data from large scale, nationally representative sample surveys, we tested the hypothesis that prenatal exposure to famine increases schizophrenia risk at adulthood by studying the Great Leap Forward Famine in China (1959-1961). Our results show that, in the urban population, being conceived and born during the famine increased the risk of developing schizophrenia at early adulthood as compared to both the pre-famine and post-famine cohorts. In the rural population, however, the post-famine cohort had the highest risk of developing schizophrenia, and there was virtually no difference in schizophrenia risk between the pre-famine and the famine cohort. This finding contrasts sharply with previous studies on the Dutch Hunger Winter as well as with smaller scale local studies in China based on hospital records. We offer an explanation for the urban-rural difference in the schizophrenia-famine relationship based on population selection by differential excess mortality and provide supportive evidence through province- and cohort-level ecological analysis.

Development and evaluation of a questionnaire for measuring suboptimal health status in urban Chinese.

BACKGROUND: Suboptimal health status (SHS) is characterized by ambiguous health complaints, general weakness, and lack of vitality, and has become a new public health challenge in China. It is believed to be a subclinical, reversible stage of chronic disease. Studies of intervention and prognosis for SHS are expected to become increasingly important. Consequently, a reliable and valid instrument to assess SHS is essential. We developed and evaluated a questionnaire for measuring SHS in urban Chinese. METHODS: Focus group discussions and a literature review provided the basis for the development of the questionnaire. Questionnaire validity and reliability were evaluated in a small pilot study and in a larger cross-sectional study of 3000 individuals. Analyses included tests for reliability and internal consistency, exploratory and confirmatory factor analysis, and tests for discriminative ability and convergent validity. RESULTS: The final questionnaire included 25 items on SHS (SHSQ-25), and encompassed 5 subscales: fatigue, the cardiovascular system, the digestive tract, the immune system, and mental status. Overall, 2799 of 3000 participants completed the questionnaire (93.3%). Test-retest reliability coefficients of individual items ranged from 0.89 to 0.98. Item-subscale correlations ranged from 0.51 to 0.72, and Cronbach's alpha was 0.70 or higher for all subscales. Factor analysis established 5 distinct domains, as conceptualized in our model. One-way ANOVA showed statistically significant differences in scale scores between 3 occupation groups; these included total scores and subscores (P<0.01). The correlation between the SHS scores and experienced stress was statistically significant (r=0.57, P<0.001). CONCLUSIONS: The SHSQ-25 is a reliable and valid instrument for measuring sub-health status in urban Chinese.

Routine Absorption Mode FTMS Data Display with an Ethoxylated Anionic Detergent as a Dual-Role (Mass and Phase) Calibrant.

Absorption mode display of Fourier transform mass spectrometry (FTMS) data is known to improve both peak shape and resolution. Most FTMS data, however, are shown in magnitude mode due to the lack of a routine for determining the phase of ions that are necessary for absorption mode display. Despite the recent development of phase calibration methods, the use of absorption mode processing as a routine has been inhibited by the lack of a good phase calibration standard, particularly a standard that can be used as both a mass and a phase calibrant. A dual-role calibrant will enable the consolidation of mass and phase calibration into a single step making phase calibration as accessible as mass calibration without any incremental increase in complexity in the calibration procedure. We tested a series of detergents and found Triton QS-15, an anionic detergent, suitable as a dual-role calibrant. Additionally, Triton QS-15 produces both positive and negative ion series and thus can be used as a calibrant in both ionization modes. The establishment of a phase calibration routine helps to enable the application of FTMS in areas that require extreme mass resolution. One of the areas is the separation of the fine isotopic peaks of molecules with a large molecular mass (e.g., > 500 u). For data acquired using an ion cyclotron resonance instrument with a small magnet (e.g., 7 Tesla), there may not be adequate mass resolution to establish a useful isotopic fine structure if the data is displayed in the historical magnitude mode. A mere switch to the absorption mode display makes the isotopic fine structure (IFS) readily available for molecular formula determination. Graphical Abstract x.