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Dietary calcium deficiency is considered to be widespread globally, with published estimates suggesting that approximately half of the world's population has inadequate access to dietary calcium. Calcium is essential for bone health, but inadequate intakes have also been linked to other health outcomes, including pregnancy complications, cancers, and cardiovascular disease. Populations in low‐ and middle‐income countries (LMICs) are at greatest risk of low calcium intakes, although many individuals in high‐income countries (HICs) also do not meet recommendations. Paradoxically, many LMICs with lower calcium intakes show lower rates of osteoporotic fracture as compared with HICs, though data are sparse. Calcium intake recommendations vary across agencies and may need to be customized based on other dietary factors, health‐related behaviors, or the risk of calcium‐related health outcomes. The lack of standard methods to assess the calcium status of an individual or population has challenged efforts to estimate the prevalence of calcium deficiency and the global burden of related adverse health consequences. This paper aims to consolidate available evidence related to the global prevalence of inadequate calcium intakes and associated health outcomes, with the goal of providing a foundation for developing policies and population‐level interventions to safely improve calcium intake and status where necessary. [ABSTRACT FROM AUTHOR]

Calcium intake remains inadequate in many low‐ and middle‐income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food‐based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium‐deficiency rickets). Specifically, some animal‐source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple‐food fortification with calcium can also be a cost‐effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high‐calcium varieties or through the application of calcium‐rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population. [ABSTRACT FROM AUTHOR]

Censoring due to a limit of detection or limit of quantification happens quite often in many medical studies. Conventional approaches to deal with censoring when analyzing these data include, for example, the substitution method and the complete case (CC) analysis. More recently, maximum likelihood estimation (MLE) has been increasingly used. While the CC analysis and the substitution method usually lead to biased estimates, the MLE approach appears to perform well in many situations. This article proposes an MLE approach to estimate the association between two measurements in the presence of censoring in one or both quantities. The central idea is to use a copula function to join the marginal distributions of the two measurements. In various simulation studies, we show that our approach outperforms existing conventional methods (CC and substitution analyses). In addition, rank-based measures of global association such as Kendall's tau or Spearman's rho can be studied, hence, attention is not only confined to Pearson's product-moment correlation coefficient capturing solely linear association. We have shown in our simulations that our approach is robust to misspecification of the copula function or marginal distributions given a small association. Furthermore, we propose a straightforward MLE method to fit a (multiple) linear regression model in the presence of censoring in a covariate or both the covariate and the response. Given the marginal distribution of the censored covariate, our method outperforms conventional approaches. We also compare and discuss the performance of our method with multiple imputation and missing indicator model approaches. [ABSTRACT FROM AUTHOR]

The analysis of multivariate time-to-event (TTE) data can become complicated due to the presence of clustering, leading to dependence between multiple event times. For a long time, (conditional) frailty models and (marginal) copula models have been used to analyze clustered TTE data. In this article, we propose a general frailty model employing a copula function between the frailty terms to construct flexible (bivariate) frailty distributions with the application to current status data. The model has the advantage to impose a less restrictive correlation structure among latent frailty variables as compared to traditional frailty models. Specifically, our model uses a copula function to join the marginal distributions of the frailty vector. In this article, we considered different copula functions, and we relied on marginal gamma distributions due to their mathematical convenience. Based on a simulation study, our novel model outperformed the commonly used additive correlated gamma frailty model, especially in the case of a negative association between the frailties. At the end of the article, the new methodology is illustrated on real-life data applications entailing bivariate serological survey data. [ABSTRACT FROM AUTHOR]

Skeletal mineralization is initiated in utero and continues throughout childhood and adolescence. During these key periods of the life cycle, calcium retention must increase significantly to provide sufficient mineral for bone deposition and skeletal growth. Stable calcium isotopes have served as a fundamental tool to non‐invasively characterize the dynamic changes in calcium physiology that occur from infancy through adolescence. These approaches have helped define the dynamics of calcium absorption and utilization in healthy children and in children with chronic diseases. As data in this area have accumulated, new areas of emphasis are beginning to characterize the determinants of variability in mineral retention, the genetic determinants of bone turnover and calcium flux and the impact of the gut microbiome on whole body and niche specific calcium dynamics. Advances in these areas will help define calcium utilization in paediatric populations and provide information that may be useful in maximizing bone acquisition across this critical phase of the life cycle. Stable calcium isotopes can be utilized to characterize normal calcium absorption and utilization in healthy children and evaluate possible alterations in calcium dynamics that occur in children with chronic diseases. Using the dual stable isotope approach, one stable isotope of calcium is ingested orally and a second stable isotope of calcium is given intravenously. The cumulative excretion of the oral to the intravenous calcium tracer in a 24 h urine pool provides a measure of fractional calcium absorption. Rates of bone calcium deposition can be determined by following the clearance of the intravenous tracer in serum and urine for 120 h or more post‐dosing. The amount of calcium secreted into the gastrointestinal tract daily (endogenous faecal calcium secretion) can be quantified with this approach and has been found to roughly equal the amount of calcium lost per day in urine (∼1.5 mg kg−1 day−1). Paediatric diseases that impair gut integrity can increase endogenous faecal calcium secretion, as has been shown for children with cystic fibrosis. Urinary calcium losses may increase when renal function is compromised (as occurs in children with renal disease) or may increase due to interactions with other dietary factors (such as sodium intake) or be associated with other metabolic abnormalities (glycosylated haemoglobin is correlated to urinary calcium excretion in children with juvenile diabetes). Evaluating overall calcium balance provides an estimation of the net amount of calcium available for bone calcium accretion in children and the degree to which calcium is gained or lost by the paediatric skeleton. [ABSTRACT FROM AUTHOR]

Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25‐hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency–related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low‐ and middle‐income countries have been hampered by limited availability of population‐representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D < 30 nmol/L) or the risk for vitamin D deficiency is determined to be high based on proxy indicators (e.g., prevalence of rickets >1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency–related conditions in vulnerable populations. Here we report the outcome of a working group convened in January and March 2017 by the Sackler Institute for Nutrition Science at the New York Academy of Sciences and the Bill & Melinda Gates Foundation to assess the global prevalence and disease burden of vitamin D deficiency, and population‐based strategies to improve vitamin D status, particularly in low‐ and middle‐income countries. The working group aimed to examine definitions of vitamin D deficiency based on biomarkers and correlations with disease or health outcomes. [ABSTRACT FROM AUTHOR]

Aims: To psychometrically evaluate the Impact of Nighttime Urination (INTU) questionnaire, a new patient‐reported outcome measure developed to assess the impact of nocturia on health and functioning in a multicenter, behavioral modification (fluid restriction) study. Methods: Participants aged 50‐95 years with at least two voiding episodes/night for ≥6 months completed voiding diaries and the INTU on 3 consecutive days during weeks 1 and 2 (same day recall) and completed the Pittsburgh Sleep Quality Index (PSQI) and Nocturia Quality of Life Questionnaire (N‐QOL) at baseline and days 8 and 15. Psychometric evaluations of the INTU were conducted. Results: Rasch analysis showed the INTU to be a unidimensional construct, with most items located on the severe end of the symptom severity continuum. In addition to an Overall Impact Score (10 items), exploratory factor analysis affirmed by confirmatory factor analysis identified two domains: Daytime (six items) and Nighttime (four items) Impact Scores (comparative fit index = 0.968; root mean square error of approximation = 0.08). Concurrent validity met prespecified hypotheses, indicating similarity of concepts with the PSQI (correlation [r] = 0.627) and N‐QOL (r = −0.784) total scores. The INTU differentiated among patients with different nocturic episode frequencies (P < 0.05 for all three summary scores). Statistically significant decreases were observed in mean Overall and Nighttime Impact Scores at week 2 versus week 1 in responders, indicating that the instrument can detect changes in response to symptom improvements. Conclusions: The INTU questionnaire demonstrated robust measurement properties and is a suitable tool for assessing the patient‐reported impact of nocturia on health and functioning. [ABSTRACT FROM AUTHOR]

Aims: This study describes development of the Impact of Nighttime Urination (INTU) questionnaire to assess nocturia impacts on health and functioning. Methods: Development of the questionnaire followed an iterative patient‐directed process as recommended by current guidance for patient‐reported outcome (PRO) measures. An initial 15‐item questionnaire was devised based on reviewing the published literature, and then modified through four rounds of semi‐structured interviews of 28 individuals with nocturia. In each round, open‐ended concept elicitation, followed by cognitive debriefing, was used to assess the questionnaire. Items were modified based on participants’ responses and incorporated into the next round of interviews. Results: In all rounds, participants reported that their experiences were easy to recall and report on a daily basis and that the burden of completing the questionnaire was low. The final questionnaire has a same‐day recall period. It includes six daytime impact items—having limited concentration, a sense of feeling tired, difficulty getting things done, irritability, not feeling rested, and drowsiness—and four items that measure the nighttime impact of nocturia—patient concern, waking up too early, difficulty getting enough sleep, and feeling bothered by having to get up at night to void. Responses follow a 5‐ or 4‐point scale. The final INTU captures the key concepts associated with nocturia as confirmed by cognitive debriefing. Conclusions: Development of the 10‐item INTU, a nocturia‐specific PRO measure, was based on direct input and feedback from patients and has demonstrated that it captures the patient‐reported impacts of nocturia. [ABSTRACT FROM AUTHOR]

ABSTRACT Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC ( p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Magnesium (Mg) is a key factor in bone health, but few studies have evaluated Mg intake or absorption and their relationship with bone mineral content (BMC) or bone mineral density (BMD) in children. We measured Mg intake, absorption, and urinary excretion in a group of children 4 to 8 years of age. Mg absorption was determined using a dual-tracer stable isotope technique, with 25Mg given intravenously and 26Mg given orally. We found a small, but significantly greater Mg absorption efficiency (percentage absorption) in males than females (67% ± 12% versus 60% ± 8%, p = 0.02) but no difference in estimated net Mg retention (average of 37 mg/d in both males and females). Relating dietary Mg intake to estimated Mg retention showed that an intake of 133 mg/d, slightly above the current estimated average requirement (EAR) of 110 mg/d, led to a net average retention of 10 mg/d, the likely minimum growth-related need for this age group. Covariate analysis showed that Mg intake and total Mg absorption, but not calcium intake or total absorption were significantly associated with both total body BMC and BMD. These results suggest that usual Mg intakes in small children in the United States meet dietary requirements in most but not all children. Within the usual range of children's diets in the United States, dietary Mg intake and absorption may be important, relatively unrecognized factors in bone health. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Excessive absorption and subsequent storage of dietary iron has been found in a variety of captively held birds and mammals, including fruit bats. It is thought that feeding a diet that is low in iron can prevent the onset of this disease; however, manufacturing a diet with commonly available foodstuffs that contains a sufficiently low iron concentration is difficult. An alternative is to feed captive animals that may be susceptible to this disease potential iron chelators such as tannins that may bind to iron and block its absorption. Using stable isotope methods established in humans, we measured iron bioavailability in straw-colored fruit bats ( Eidolon helvum) and tested whether tannic acid significantly reduced the extent of iron absorption. Regardless of dose, tannic acid significantly reduced iron absorption (by 40%) and in the absence of tannic acid, iron absorption was extensive in this species (up to 30%), more so than in humans. Species susceptible to iron storage disease may efficiently absorb iron in the gut regardless of iron status, and supplementing these species with tannic acid in captivity may provide an alternative or additional means of preventing the development of this disease. Zoo Biol 29:335-343, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective Calcium absorption is an important determinant of calcium retention and bone metabolism. However, most methods of measuring calcium absorption, including the well-established dual stable isotope method, are costly and cumbersome to implement. We evaluated whether an oral calcium tolerance test (OCTT), which involves measuring calcium excretion in a fasting 2-h urine collection and two 2-h collections following an oral calcium dose, may be a useful index of calcium absorption in older adults consuming a fixed calcium intake of 30 mmol/day. Design After a 10-day metabolic diet containing 30 mmol/day of calcium, subjects had calcium absorption measured using the dual stable isotope method and the OCTT. Participants Eleven healthy subjects aged 54–74 years. Measurements Fractional calcium absorption (FCA), calcium excretion in a fasting 2-h urine collection and two 2-h collections in response to a 10-mmol calcium dose (total intake 30 mmol/day). Results Calcium excretion from several combinations of the urine collections was examined in relation to FCA. The most predictive of FCA was calcium excretion 4 h following the calcium dose. This measure was significantly correlated with FCA ( r = 0·735, P = 0·010), fitting 54% of the variability in FCA. Conclusion Urinary calcium excretion during the 4 h after a 10-mmol calcium dose is a useful index of calcium absorption among older adults consuming recommended calcium intakes. This test is inexpensive, easy to implement and potentially useful in large clinical studies. [ABSTRACT FROM AUTHOR]

The swept volume problem is practical, difficult and interesting enough to have received a great deal of attention over the years, and the literature contains much discussion of methods for computing swept volumes in many situations. The method presented here permits an arbitrary polyhedral object (given in a typical boundary representation) to be swept through an arbitrary trajectory. A polyhedral approximation to the volume swept by this moving object is computed and output in a typical boundary representation. A number of examples are presented demonstrating the practicality of this method. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The author explores the advantages and disadvantages of vitamin D supplementation during pregnancy based on a study by Hollis and coworkers published in the issue. He notes on the finding of the study that increases in both vitamin D supplementation and serum 25(OH)D level were associated with higher serum 1,25-dihydroxyvitamin D3[1,25(OH)D3] levels. He believes that the study provides novel data about vitamin D in pregnancy.

Background: Calcium absorption efficiency and bone mineral mass are increased in adolescents who receive inulin-type fructans (ITF). The mechanism of action is unknown but in animal models appears to be related to increased colonic calcium absorption. Methods: We conducted a calcium kinetic study in young adults after dosing 42Ca orally and also giving 46Ca IV. Kinetic measurements were performed before and after 6 weeks of supplementation with 8 g/d of a mixed short and long degree of polymerization (DP) ITF. Blood samples were collected over 26 hours and a 48-hour urine collection obtained. The area under the curve of the oral tracer in the blood was calculated and relative increased absorption throughout the sampling period determined. Results: Eight young adults (of 13 studied), with average calcium intake about 900 mg/d responded to the ITF with an increased calcium absorption of at least 3%. The average increase in absorption was 8.3% (72 mg/d). Colonic absorption, defined as absorption that occurred more than 7 hours after oral dosing, represented 60-67% of the increase, or about 45 mg/d calcium absorption in the colon. Discussion: These findings suggest that multiple mechanisms account for the increased calcium absorption associated with the ingestion of a mixed long and short DP ITF. These likely include increased solubility and increased absorptive surface area throughout the intestine. [ABSTRACT FROM AUTHOR]

Background: Panama continues to have a substantial incidence of malnutrition. Among the most affected populations are children in rural areas and in indigenous populations. Methods: We evaluated nutritional status of preschool (PS) and school-aged (SA) children in two high-risk areas in Panama to determine the prevalence of growth-failure, anemia, Fe and Zn deficiency. Results: (data are Mean ± SEM) Discussion: These data demonstrate a high rate of malnutrition in this population. Although weight recovery occurs in SA children, longitudinal growth failure does not improve during this time. Iron and Zn deficiency are more common in PS than SA children. Intervention programs should focus on PS age groups. Anemia in PS children is primarily Fe deficient; in SA children it is likely associated with other issues such as parasite infection. [ABSTRACT FROM AUTHOR]