Physiographic Environment Classification: a Controlling Factor Classification of Landscape Susceptibility to Waterborne Contaminant Loss.

Spatial variation in the landscape factors climate, geomorphology, and lithology cause significant differences in water quality issues even when land use pressures are similar. The Physiographic Environment Classification (PEC) classifies landscapes based on their susceptibility to the loss of water quality contaminants. The classification is informed by a conceptual model of the landscape factors that control the hydrochemical maturity of water discharged to streams. In New Zealand, a case study using climatic, topographic, and geological data classified the country into six, 36, and 320 classes at Levels 1 (Climate), 1-2 (Climate + Geomorphology), and 1-3 (Climate + Geomorphology + Lithology), respectively. Variance partitioning analysis applied to New Zealand's national surface water monitoring network (n = 810 stations) assessed the contributions of PEC classes and land use on the spatial variation of water quality contaminants. Compared to land use, PEC explained 0.6× the variation in Nitrate Nitrite Nitrogen (NNN), 1.0× in Total Kjeldahl Nitrogen (TKN), 1.8× in Dissolved Reactive Phosphorus (DRP), 2.3× in Particulate Phosphorus (PP), 2.6× in E. coli, and 4.3× in Turbidity (TURB). Land use explained more variation in riverine NNN, while landscape factors explained more variation in DRP, PP, E. coli, and TURB. Overall, PEC accounted for 2.1× more variation in riverine contaminant concentrations than land use. The differences in contaminant concentrations between PEC classes (p < 0.05), after adjusting for land use, were consistent with the conceptual model of hydrochemical maturation. PEC elucidates underlying causes of contaminant loss susceptibility and can inform targeted land management across multiple scales.

Meeting the Growing Need for Land-Water System Modelling to Assess Land Management Actions.

Elevated contaminant levels and hydrological alterations resulting from land use are degrading aquatic ecosystems on a global scale. A range of land management actions may be used to reduce or prevent this degradation. To select among alternative management actions, decision makers require predictions of their effectiveness, their economic impacts, estimated uncertainty in the predictions, and estimated time lags between management actions and environmental responses. There are multiple methods for generating these predictions, but the most rigorous and transparent methods involve quantitative modelling. The challenge for modellers is two-fold. First, they must employ models that represent complex land-water systems, including the causal chains linking land use to contaminant loss and water use, catchment processes that alter contaminant loads and flow regimes, and ecological responses in aquatic environments. Second, they must ensure that these models meet the needs of endusers in terms of reliability, usefulness, feasibility and transparency. Integrated modelling using coupled models to represent the land-water system can meet both challenges and has advantages over alternative approaches. The need for integrated land-water system modelling is growing as the extent and intensity of human land use increases, and regulatory agencies seek more effective land management actions to counter the adverse effects. Here we present recommendations for modelling teams, to help them improve current practices and meet the growing need for land-water system models. The recommendations address several aspects of integrated modelling: (1) assembling modelling teams; (2) problem framing and conceptual modelling; (3) developing spatial frameworks; (4) integrating economic and biophysical models; (5) selecting and coupling models.

Ovarian and spawning reference, size at first maturity and fecundity of Glossogobius giuris caught along Vietnamese Mekong Delta.

This study investigates the ovarian development, spawning patterns, maturity size and fecundity of the goby Glossogobius giuris-a commercial fish in the Vietnamese Mekong Delta-based on the data analysis of 659 individuals. Specimens were caught using trawl nets from four sites representing freshwater (Cai Rang, Can Tho) to salinized regions in the dry season (Long Phu, Soc Trang), and brackish water regions (Hoa Binh, Bac Lieu and Dam Doi, Ca Mau) over the 12 months of 2020. Histological analysis showed that it was a multi-spawner as different stages of oocytes appeared in mature ovaries. The fish could spawn throughout the year, with a peak in April at the freshwater region and in September at salinized and brackish areas as mature ovaries appeared monthly during the studied period and gonadosomatic index displayed the highest value in April and in September, respectively. This goby's primary egg releasing time tended to be regulated by salinity changes over the four sampling sites. Likewise, size at first maturity of this species could be related to the salinity variation as this value was the longest in freshwater (6.14 ± 0.17) and the shortest in the salinization region (4.82 ± 0.66). Batch fecundity is measured at 5,118-100,003 eggs/female and related to fish length and weight (r2  > 0.76). Findings can be useful for the development of fish conservation strategies and artificial reproducing studies.

The mismatch between morphological and molecular attribution of three Glossogobius species in the Mekong Delta.

BACKGROUND: The Vietnamese Mekong Delta (VMD) is the granary for the whole country, providing animal and plant resources, especially fish. Among the fish species, the genus Glossogobius are the majority. Until now, research for this species has been solely relied on fish morphology for identification. Hence, the present study aimed to describe the morphological variations of the morphologically identified gobies and to validate them at the molecular level through the sequencing of the barcode region, the mitochondrial cytochrome C oxidase subunit I (COI) gene to preliminary provide fundamental information for conservation. RESULTS: The mitochondrial cytochrome C oxidase subunit I genes were amplified successfully with an approximate size of 650-680 bp. Their morphometries were quite different, and the genetic distance (p-value) among groups and within groups ranged from 0.00 to 0.12. The similarity of the COI gene sequences between the analyzed samples and in the NCBI database was from 87.01 to 100%. The specimens of G. aureus, G. giuris and G. sparsipapillus were interspersed in small branches of the phylogenetic tree with a low genetic distance highlighting that the genetic diversity of COI gene was low among species. Therefore, it is recommended that a combination of morphological method and mtCOI DNA barcoding is required for accurate classification. CONCLUSION: This study helps determine three distinct lineages of Glossogobius species, so an appropriate strategy can be proposed for exploitation and conservation.

Estimation of policy-relevant reference conditions throughout national river networks.

A method for objectively estimating reference states for suspended fine sediment (turbidity) is presented. To be fit for water policy development and implementation the method had to satisfy four requirements: (1) the method must not be dependent on data from minimally-disturbed reference sites; (2) the method must facilitate characterization of reference states throughout heterogeneous river networks, given patchy data; (3) the classification of reference states must be relevant and legitimate to end-users; (4) the method should provide several classifications of reference states at different spatial resolutions allowing selection of the resolution yielding the most parsimonious classification of reference states throughout the network. Implementing the method involves two stages: (1) Development of a river classification based on sediment supply and retention regimes (defining 'turbidity classes') at multiple spatial resolutions. (2) At each resolution, for each turbidity class, estimation of a reference state based on relationships between turbidity and anthropogenic stressors, then objective selection of the resolution yielding the most parsimonious classification of reference states throughout the network. Implementing the method requires a river network GIS and turbidity data within classes, preferably from monitoring sites spanning the domains of the anthropogenic stressor variables used for model-based estimation of reference states.•A method is presented for estimating reference states for suspended fine sediment (turbidity) throughout spatially heterogeneous river networks.•Development of the method was guided by the requirements of policy analysts during reform of water policy in New Zealand.•The method presented was used to develop fine sediment regulatory thresholds of national water policy.

First reference on reproductive biology of Butis koilomatodon in Mekong Delta, Vietnam.

BACKGROUND: The key to fishery management is knowing the appropriate reproductive strategies of the targeted fish. For most gobiid species, the iteroparous pattern is dominant compared to semelparity. Albeit Butis koilomatodon plays an important role in the Mekong Delta's food supply, its reproductive biological data have not been known. Hence, this study was conducted to provide new fundamental knowledge of reproductive traits of Butis koilomatodon in the Mekong Delta. RESULTS: A total of 1314 individuals (903 males and 411 females) were monthly collected by bottom gill nets from July 2019 to June 2020 at six sampling sites along estuarial and coastal regions, from Tra Vinh to Ca Mau provinces, southern of Vietnam. pH and salinity of these six sampling sites are 7.72-7.93 pH and 11.17-26.17‰, respectively. The pH varies with sites, but not seasons; whereas a reverse case is found in salinity. Different types of oocytes are found in histological specimens of ovaries prove that B. koilomatodon is a multi-spawner. The gonadosomatic index value, together with the monthly presence of mature ovaries reveal that this species spawns throughout the year. The length at first mature male Butis koilomatodon (5.1-8.6 cm) is higher than that of females (4.8-6.7 cm), except in Hoa Binh and Dong Hai. Batch fecundity (3085 to 32,087 eggs/female) increases with fish weight (1.48-12.30 g) and length (4.8-9.0 cm) due to high determination values (r2 > 0.6). CONCLUSION: Knowledge of reproductive traits gained from this study was a reference source for future studies and helped manage this species' resources.

A Heuristic Method for Determining Changes of Source Loads to Comply with Water Quality Limits in Catchments.

A common land and water management task is to determine where and by how much source loadings need to change to meet water quality limits in receiving environments. This paper addresses the problem of quantifying changes in loading when limits are specified in many locations in a large and spatially heterogeneous catchment, accounting for cumulative downstream impacts. Current approaches to this problem tend to use either scenario analysis or optimization, which suffer from difficulties of generating scenarios that meet the limits, or high complexity of optimization approaches. In contrast, we present a novel method in which simple catchment models, load limits, upstream/downstream spatial relationships and spatial allocation rules are combined to arrive at source load changes. The process iteratively establishes the critical location (river segment or lake) where the limits are most constraining, and then adjusts sources upstream of the critical location to meet the limit at that location. The method is demonstrated with application to New Zealand (268,000 km2) for nutrients and the microbial indicator E. coli, which was conducted to support policy development regarding water quality limits. The model provided useful insights, such as a source load excess (the need for source load reduction) even after mitigation measures are introduced in order to comply with E. coli limits. On the other hand, there was headroom (ability to increase source loading) for nutrients. The method enables assessment of the necessary source load reductions to achieve water quality limits over broad areas such as large catchments or whole regions.

Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients.

Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).1 It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.2 The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.

Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia.

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 µg) and folic acid (400 µg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514.

Prediction of fruit and vegetable intake from biomarkers using individual participant data of diet-controlled intervention studies.

Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258.0 g, the correlation between observed and predicted intake was 0.78 and the mean difference between observed and predicted intake was - 1.7 g (limits of agreement: - 466.3, 462.8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201.1 g, the correlation was 0.65 and the mean bias was 2.4 g (limits of agreement: -368.2, 373.0 g). The prediction models which include the biomarkers and subject characteristics may be used to estimate average intake at the group level and to investigate the ranking of individuals with regard to their intake of fruit and vegetables when validating questionnaires that measure intake.

A review of vitamin A equivalency of ß-carotene in various food matrices for human consumption.

Vitamin A equivalency of ß-carotene (VEB) is defined as the amount of ingested ß-carotene in µg that is absorbed and converted into 1 µg retinol (vitamin A) in the human body. The objective of the present review was to discuss the different estimates for VEB in various types of dietary food matrices. Different methods are discussed such as mass balance, dose-response and isotopic labelling. The VEB is currently estimated by the US Institute of Medicine (IOM) as 12:1 in a mixed diet and 2:1 in oil. For humans consuming ß-carotene dissolved in oil, a VEB between 2:1 and 4:1 is feasible. A VEB of approximately 4:1 is applicable for biofortified cassava, yellow maize and Golden Rice, which are specially bred for human consumption in developing countries. We propose a range of 9:1-16:1 for VEB in a mixed diet that encompasses the IOM VEB of 12:1 and is realistic for a Western diet under Western conditions. For a 'prudent' (i.e. non-Western) diet including a variety of commonly consumed vegetables, a VEB could range from 9:1 to 28:1 in a mixed diet.

Food matrix effects on bioaccessibility of ß-carotene can be measured in an in vitro gastrointestinal model.

Since the food matrix determines ß-carotene availability for intestinal absorption, food matrix effects on the bioaccessibility of ß-carotene from two diets were investigated in vitro and compared with in vivo data. The "mixed diet" consisted of ß-carotene-rich vegetables, and the "oil diet" contained ß-carotene-low vegetables with supplemental ß-carotene. The application of extrinsically labeled ß-carotene was also investigated. The bioaccessibility of ß-carotene was 28 µg/100 µg ß-carotene from the mixed diet and 53 µg/100 µg ß-carotene from the oil diet. This ratio of 1.9:1 was consistent with in vivo data, where the apparent absorption was 1.9-fold higher in the oil diet than in the mixed diet. The labeled ß-carotene was not equally distributed over time. In conclusion, the food matrix effects on bioaccessibility of ß-carotene could be measured using an in vitro model and were consistent with in vivo data. The application of extrinsically labeled ß-carotene was not confirmed.

Dam design can impede adaptive management of environmental flows: a case study from the Opuha Dam, New Zealand.

The Opuha Dam was designed for water storage, hydropower, and to augment summer low flows. Following its commissioning in 1999, algal blooms (dominated first by Phormidium and later Didymosphenia geminata) downstream of the dam were attributed to the reduced frequency and magnitude of high-flow events. In this study, we used a 20-year monitoring dataset to quantify changes associated with the dam. We also studied the effectiveness of flushing flows to remove periphyton from the river bed. Following the completion of the dam, daily maximum flows downstream have exceeded 100 m(3) s(-1) only three times; two of these floods exceeded the pre-dam mean annual flood of 203 m(3) s(-1) (compared to 19 times >100 m(3) s(-1) and 6 times >203 m(3) s(-1) in the 8 years of record before the dam). Other changes downstream included increases in water temperature, bed armoring, frequency of algal blooms, and changes to the aquatic invertebrate community. Seven experimental flushing flows resulted in limited periphyton reductions. Flood wave attenuation, bed armoring, and a shortage of surface sand and gravel, likely limited the effectiveness of these moderate floods. Floods similar to pre-dam levels may be effective for control of periphyton downstream; however, flushing flows of that magnitude are not possible with the existing dam infrastructure. These results highlight the need for dams to be planned and built with the capacity to provide the natural range of flows for adaptive management, particularly high flows.

The role of antibiotic prophylaxis in endoscopic retrograde cholangiopancreatography; a retrospective single-center evaluation.

OBJECTIVE: Endoscopic retrograde cholangiopancreaticography (ERCP) can be complicated by post-ERCP cholangitis even when performed by experienced endoscopists. Therefore, antibiotic prophylaxis is recommended for certain patients, but controversy exists as to which patient groups really benefit from this strategy. We retrospectively evaluated the use of antibiotics in a primary teaching hospital in the Netherlands with regard to the incidence of post-ERCP cholangitis and cholecystitis. MATERIAL AND METHODS: Retrospective single-center evaluation in a primary teaching hospital. All consecutive ERCPs between 2000 and 2006 were studied. Primary end point was the incidence of post-ERCP cholangitis and cholecystitis, divided into four categories: definite, likely, possible and unlikely. Additionally, occurrence of complications such as pneumonia, post-ERCP pancreatitis, perforation of the duodenum, substantial bleeding and the need for re-ERCP within 5 days was scored. RESULTS: Five hundred forty ERCPs in 327 patients were screened. Of these, 292 ERCPs performed in 193 patients were included. Eight ERCPs (2.7%) of all ERCPs were followed by definite cholangitis and two ERCPs (0.7%) by likely cholangitis. The occurrence rate of ERCP-related complications remained low. CONCLUSIONS: This study shows that with our current policy of restricted use of antibiotic prophylaxis the overall incidence of biliary tract infections is low.

Vitamin A equivalency and apparent absorption of beta-carotene in ileostomy subjects using a dual-isotope dilution technique.

The objective was to quantify the vitamin A equivalency of beta-carotene in two diets using a dual-isotope dilution technique and the apparent beta-carotene absorption as measured by the oral-faecal balance technique. Seventeen healthy adults with an ileostomy completed the 4-week diet-controlled, cross-over intervention study. Each subject followed both diets for 2 weeks: a diet containing vegetables low in beta-carotene content with supplemental beta-carotene in salad dressing oil ('oil diet'; mean beta-carotene intake 3.1 mg/d) and a diet containing vegetables and fruits high in beta-carotene content ('mixed diet'; mean beta-carotene intake 7.6 mg/d). Daily each subject consumed a mean of 190 microg [13C10]beta-carotene and 195 microg [13C10]retinyl palmitate in oil capsules. The vitamin A equivalency of beta-carotene was calculated as the dose-corrected ratio of [13C5]retinol to [13C10]retinol in serum. Apparent absorption of beta-carotene was determined with oral-faecal balance. Isotopic data quantified a vitamin A equivalency of [13C10]beta-carotene in oil of 3.6:1 (95 % CI 2.8, 4.6) regardless of dietary matrices differences. The apparent absorption of (labelled and dietary) beta-carotene from the 'oil diet' (30 %) was 1.9-fold higher than from the 'mixed diet' (16 %). This extrinsic labelling technique can measure precisely the vitamin A equivalency of beta-carotene in oil capsules, but it does not represent the effect of different dietary matrices.

Vitamin A equivalency of beta-carotene in healthy adults: limitation of the extrinsic dual-isotope dilution technique to measure matrix effect.

Data on the vitamin A equivalency of beta-carotene in food are inconsistent. We quantified the vitamin A equivalency (microg) of beta-carotene in two diets using the dual-isotope dilution technique and the oral-faecal balance technique. A diet-controlled, cross-over intervention study was conducted in twenty-four healthy adults. Each subject followed two diets for 3 weeks each: a diet containing vegetables low in beta-carotene with supplemental beta-carotene in salad dressing oil ('oil diet') and a diet containing vegetables and fruits high in beta-carotene ('mixed diet'). During all 6 weeks, each subject daily consumed a mean of 55 (sd 0.5) microg [13C10]beta-carotene and 55 (sd 0.5) microg [13C10]retinyl palmitate in oil capsules. The vitamin A equivalency of beta-carotene was calculated as the dose-corrected ratio of [13C5]retinol to [13C10]retinol in serum and from apparent absorption by oral-faecal balance. Isotopic data quantified a vitamin A equivalency of [13C10]beta-carotene in oil of 3.4 microg (95 % CI 2.8, 3.9), thus the bio-efficacy of the beta-carotene in oil was 28 % in the presence of both diets. However, data from oral-faecal balance estimated vitamin A equivalency as 6:1 microg (95 % CI 4, 7) for beta-carotene in the 'oil diet'. beta-Carotene in the 'oil diet' had 2.9-fold higher vitamin A equivalency than beta-carotene in the 'mixed diet'. In conclusion, this extrinsic labelling technique cannot measure effects of mixed vegetables and fruits matrices, but can measure precisely the vitamin A equivalency of the beta-carotene in oil capsules.

Definition procedures have little effect on performance of environmental classifications of streams and rivers.

Mapped environmental classifications are defined using various procedures, but there has been little evaluation of the differences in their ability to discriminate variation in independent ecological characteristics. We tested the performance of environmental classifications of the streams and rivers of France that had been defined from the same environmental data using geographic regionalization and numerical classification of individual river valley segments. Test data comprised invertebrate assemblages, water chemistry, and hydrological indexes obtained from sites throughout France. Classification performance was measured by analysis of similarity (ANOSIM). Geometric regions defined by a regular grid and without regard to environmental variables and a posteriori classifications based on clustering the test datasets defined lower and upper bounds of performance for a given number of classes. Differences in classification performances were generally small. The ANOSIM statistics for the a posteriori classifications were around twice that of all environmental classifications, including geometrically defined regions. The hydro-ecoregions performed slightly better for the invertebrate data and the network classification performed slightly better for the chemistry and hydrological data. Our results indicate that environmental classifications that are defined using different procedures can be comparable in terms of their ability to discriminate variation of ecological characteristics and that alleged differences in performance arising from different classification procedures can be small relative to unexplained variation. We conclude that definition procedures might have little effect on the performance of large-scale environmental classifications and decisions over which procedures to use should be based primarily on pragmatic considerations.

Murine TNF(DeltaARE) Crohn's disease model displays diminished expression of intestinal Ca2+ transporters.

BACKGROUND: Patients suffering from Crohn's disease (CD) show increased incidence of low bone mineral density. Investigating this complication is difficult because the exact etiology of CD remains elusive. Mice carrying a deletion in the tumor necrosis factor (TNF) AU-rich elements (ARE) are reported as a model for human CD and are characterized by elevated TNF-alpha levels and inflammations in the terminal ileum. To evaluate whether these mice have a Ca(2+) handling problem, this study analyzed the Ca(2+) homeostasis in heterozygous TNF(DeltaARE) mice (TNF(DeltaARE/+)) in comparison to wildtype littermates. METHODS: Beside serum Ca(2+) and vitamin D levels, the expression of Ca(2+) transporters was analyzed in intestine, kidney and bone using quantitative real-time PCR, Western blot and immunohistochemistry. Bone scans were performed to measure bone parameters. RESULTS: Ca(2+) transporters in duodenum (TRPV6, calbindin-D(9K), PMCA1b) and kidney (TRPV5, calbindin-D(28K), NCX1) showed significantly reduced mRNA expression levels in TNP(DeltaARE/+) mice, except for renal TRPV5. In bone, only calbindin-D(9K) mRNA displayed a significant down-regulation. These findings were supported by declined duodenal calbindin-D(9K) and renal calbindin-D(28K) protein values. Likely, this down-regulation of Ca(2+) transporters in TNP(DeltaARE/+) mice is mediated by the 58 +/- 9% reduction in serum 1,25(OH)(2)D(3) levels. Diminished expression of Ca(2+) transporters combined with unchanged serum Ca(2+) levels assumes Ca(2+) loss from bone to compensate for the body's overall Ca(2+) shortage. Indeed, microcomputed tomography scanning demonstrated reduced trabecular and corticol bone thickness and volume in TNF(DeltaARE/+) mice. This finding is further supported by increased total deoxypyridinoline in serum. CONCLUSIONS: Our results imply that TNF(DeltaARE/+) mice have a disturbed Ca(2+) homeostasis characterized by reduced duodenal and renal Ca(2+) transporters, diminished 1,25(OH)(2)D(3) levels, and increased bone resorption associated with profound bone abnormalities.