The Vitamin D Metabolite Diagnostic Ratio Associates With Phenotypic Traits of Idiopathic Hypercalciuria.

Introduction: Underlying mechanisms for hypercalciuria remain unknown in most cases; thus, the designation "idiopathic." We hypothesized that the vitamin D-inactivating enzyme, CYP24A1 contributes to the pathogenesis of hypercalciuria in kidney stone formers. Methods: We conducted association analyses between CYP24A1 activity, estimated by the vitamin D metabolite diagnostic ratio (25(OH) vitamin D3/total 24,25 (OH)2 vitamin D ratio; VMDR), and the phenotype of participants in 2 observational cohorts of kidney stone formers, the Swiss Kidney Stone Cohort (SKSC) and the Bern Kidney Stone Registry (BKSR). Circulating 25(OH)- and 24,25 (OH)2 vitamin D were quantified using a validated liquid chromatography tandem mass spectrometry assay. Results: A total of 974 participants were included in the analysis. We found a positive association of VMDR (and hence negative association of CYP24A1 activity) with total (ß 0.009 mmol/l; 95% confidence interval [CI]: 0.002, 0.016; P = 0.02) and ionized plasma calcium (ß 0.005 mmol/l; 95% CI: 0.002, 0.008; P < 0.01), absolute and fractional excretion of urinary calcium (ß 0.054 mmol/24h; 95% CI: 0.010, 0.097; P = 0.02 and ß 0.046%; 95% CI: 0.018, 0.074; P < 0.01, respectively). Further, VMDR was associated with an increased likelihood of forming calcium oxalate dihydrate stones (Odds ratio [OR] 1.64; 95% CI: 1.22, 2.35; P < 0.01) and reduced bone mineral density (BMD) at the femoral neck (ß -0.005 g/cm2; 95% CI: -0.010, -0.001; P = 0.04). The described associations became stronger when the analysis was confined to idiopathic calcium stone formers. Conclusion: Our study reveals that CYP24A1 activity, estimated by VMDR, is associated with clinical traits previously linked to idiopathic hypercalciuria.

Lexical competition influences correct and incorrect visual word recognition.

A growing body of research suggests that visual word recognition is error-prone, and that errors may contribute to inhibitory neighbour frequency effects in word identification and reading. The present study used the neighbourhood frequency effect to examine the relationship between lexical competition and error making during visual word recognition. A novel adaptation of the visual world paradigm (VWP) was used, in which participants selected a briefly presented printed target word from an array containing the target, its higher- or lower-frequency neighbour, an orthographic onset competitor, and an orthographically unrelated distractor word. Analyses of the visual inspection of the arrays suggested that lexical competition occurred when words were correctly identified, as competitors were preferentially viewed as a function of their orthographic similarity with the target, and higher-frequency neighbours were preferentially viewed over lower-frequency neighbours. Orthographic similarity and neighbour frequency also influenced error making. Targets were often mistaken for their neighbours, and these errors were more common for targets with higher-frequency neighbours. The time course of target and neighbour viewing for error trials also provided preliminary evidence for two kinds of errors: early-occurring, perceptual errors and later-occurring selection errors that resulted from unsuccessfully resolved lexical competition. Together, these findings suggest that neighbour frequency effects reflect the contribution of both general lexical competition and occasional errors.

Zinc isotopic evidence for recycled carbonate in the deep mantle.

Carbonate, the major carbon reservoir on Earth's surface, can enter into the mantle by subduction. However, evidence for recycled surficial carbonates in the deep mantle is still scarce. Ocean island basalts from Cook-Austral islands and St. Helena Island, widely called HIMU basalts because of their high µ = 238U/204Pb sources, are thought to be fed by mantle plumes originating in the lower mantle. Here we report exceptionally high δ66Zn values (δ66Zn = 0.38 ± 0.03‰) of these HIMU lavas relative to most published data for oceanic basalts (δ66Zn = 0.31 ± 0.10‰), which requires a source contributed by isotopically heavy recycled surficial carbonates. During subduction of the oceanic lithosphere, melting of mixed surficial carbonates and basaltic crust in the deep mantle generates carbonatite melts, which metasomatizes the nearby mantle and the resultant carbonated mantle ultimately evolves into a high-δ66Zn HIMU source. High-δ66Zn signatures of HIMU basalts, therefore, demonstrate that carbonates can be transported into Earth's deep mantle.

Archean cratonic mantle recycled at a mid-ocean ridge.

Basalts and mantle peridotites of mid-ocean ridges are thought to sample Earth's upper mantle. Osmium isotopes of abyssal peridotites uniquely preserve melt extraction events throughout Earth history, but existing records only indicate ages up to ~2 billion years (Ga) ago. Thus, the memory of the suspected large volumes of mantle lithosphere that existed in Archean time (>2.5 Ga) has apparently been lost somehow. We report abyssal peridotites with melt-depletion ages up to 2.8 Ga, documented by extremely unradiogenic 187Os/188Os ratios (to as low as 0.1095) and refractory major elements that compositionally resemble the deep keels of Archean cratons. These oceanic rocks were thus derived from the once-extensive Archean continental keels that have been dislodged and recycled back into the mantle, the feasibility of which we confirm with numerical modeling. This unexpected connection between young oceanic and ancient continental lithosphere indicates an underappreciated degree of compositional recycling over time.

Predictors of Bone Mineral Density in Kidney Stone Formers.

Introduction: Nephrolithiasis is associated with an increased fracture risk, but predictors of bone mineral density (BMD) in stone formers (SFs) remain poorly defined. Methods: We conducted a retrospective analysis in the Bern Kidney Stone Registry (BKSR), an observational cohort of kidney SFs. Inclusion criteria were age ≥18 years and ≥1 past stone episode. Participants with non-calcium (Ca)-containing kidney stones, a history of primary hyperparathyroidism or antiresorptive or anabolic bone treatment were excluded. Multivariable linear regression analyses were used to assess the association of blood and 24-hours urine parameters and stone composition with BMD at the lumbar spine and femoral neck. Results: In the analysis, 504 participants were included, mean age was 46 years, and 76% were male. In multivariable analyses, fasting (ß: -0.031; P = 0.042), postload (ß: -0.059; P = 0.0028) and Δ postload - fasting (ß: -0.053; P = 0.0029) urine Ca-to-creatinine ratios after 1 week of a sodium- and Ca- restricted diet and Ca oxalate dihydrate stone content (ß: -0.042; P = 0.011) were negatively associated with z scores at the lumbar spine. At the femoral neck, alkaline phosphatase (ß: -0.035; P = 0.0034) and parathyroid hormone (PTH) (ß: -0.035; P = 0.0026) were negatively associated with z scores, whereas 24-hours urine Ca (ß: 0.033; P = 0.0085), magnesium (ß: 0.043; P = 3.5 × 10-4), and potassium (ß: 0.032; P = 0.012) correlated positively with z scores at the femoral neck. Conclusion: Our study reveals distinct predictors of BMD in SFs. Commonly available clinical parameters, such as kidney stone composition results, can be used to identify SFs at risk for low BMD.

The perceptual span in Tibetan reading.

Tibetan script differs from other alphabetic writing systems in that word forms can be composed of horizontally and vertically arrayed characters. To examine information extraction during the reading of this script, eye movements of native readers were recorded and used to control the size of a window of legible text that moved in synchrony with the eyes. Letters outside the window were masked, and no viewing constraints were imposed in a control condition. Comparisons of window conditions with the control condition showed that reading speed and oculomotor activity matched the control condition, when windows revealed three letters to the left and seven to eight letters to the right of a fixated letter location. Cross-script comparisons indicate that this perceptual span is smaller than for English and larger than for Chinese script. We suggest that the information density of a writing system influences the perceptual span during reading.

Attention shifting during the reading of Chinese sentences.

An eye-movement-contingent probe detection task was used to determine the allocation of visual attention during Chinese reading. On a subset of trials, a to-be-detected visual probe replaced visual text when the eyes crossed and landed to the right of an invisible interword boundary. The probe was either near the fixated location or at a more distant location in the right or left visual field. Probe detection latencies were shorter for probes that were closer to fixation, and they were shorter when the probes were shown in the right rather than the left visual field when word order progressed from left to right. A right visual field advantage also emerged when word order was reversed and progressed from right to left. These results indicate that the direction of shifts of attention is preset and progresses with a script-specific word order. This directional bias can account for asymmetric extensions of the perceptual span toward upcoming words during normal reading. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Regressions during Reading.

Readers occasionally move their eyes to prior text. We distinguish two types of these movements (regressions). One type consists of relatively large regressions that seek to re-process prior text and to revise represented linguistic content to improve comprehension. The other consists of relatively small regressions that seek to correct inaccurate or premature oculomotor programming to improve visual word recognition. Large regressions are guided by spatial and linguistic knowledge, while small regressions appear to be exclusively guided by knowledge of spatial location. There are substantial individual differences in the use of regressions, and college-level readers often do not regress even when this would improve sentence comprehension.

Re-reconsidering the role of temporal order in spoken word recognition.

Spoken word recognition models incorporate the temporal unfolding of word information by assuming that positional match constrains lexical activation. Recent findings challenge the linearity constraint. In the visual world paradigm, Toscano, Anderson, and McMurray observed that listeners preferentially viewed a picture of a target word's anadrome competitor (e.g., competitor bus for target sub) compared with phonologically unrelated distractors (e.g., well) or competitors sharing an overlapping vowel (e.g., sun). Toscano et al. concluded that spoken word recognition relies on coarse grain spectral similarity for mapping spoken input to a lexical representation. Our experiments aimed to replicate the anadrome effect and to test the coarse grain similarity account using competitors without vowel position overlap (e.g., competitor leaf for target flea). The results confirmed the original effect: anadrome competitor fixation curves diverged from unrelated distractors approximately 275 ms after the onset of the target word. In contrast, the no vowel position overlap competitor did not show an increase in fixations compared with the unrelated distractors. The contrasting results for the anadrome and no vowel position overlap items are discussed in terms of theoretical implications of sequential match versus coarse grain similarity accounts of spoken word recognition. We also discuss design issues (repetition of stimulus materials and display parameters) concerning the use of the visual world paradigm in making inferences about online spoken word recognition.

Recycled ancient ghost carbonate in the Pitcairn mantle plume.

The extreme Sr, Nd, Hf, and Pb isotopic compositions found in Pitcairn Island basalts have been labeled enriched mantle 1 (EM1), characterizing them as one of the isotopic mantle end members. The EM1 origin has been vigorously debated for over 25 years, with interpretations ranging from delaminated subcontinental lithosphere, to recycled lower continental crust, to recycled oceanic crust carrying ancient pelagic sediments, all of which may potentially generate the requisite radiogenic isotopic composition. Here we find that δ26Mg ratios in Pitcairn EM1 basalts are significantly lower than in normal mantle and are the lowest values so far recorded in oceanic basalts. A global survey of Mg isotopic compositions of potentially recycled components shows that marine carbonates constitute the most common and typical reservoir invariably characterized by extremely low δ26Mg values. We therefore infer that the subnormal δ26Mg of the Pitcairn EM1 component originates from subducted marine carbonates. This, combined with previously published evidence showing exceptionally unradiogenic Pb as well as sulfur isotopes affected by mass-independent fractionation, suggests that the Pitcairn EM1 component is most likely derived from late Archean subducted carbonate-bearing sediments. However, the low Ca/Al ratios of Pitcairn lavas are inconsistent with experimental evidence showing high Ca/Al ratios in melts derived from carbonate-bearing mantle sources. We suggest that carbonate-silicate reactions in the late Archean subducted sediments exhausted the carbonates, but the isotopically light magnesium of the carbonate was incorporated in the silicates, which then entered the lower mantle and ultimately became the Pitcairn plume source.

The effect of a previous created distal arteriovenous-fistula on radial bone DXA measurements in prevalent renal transplant recipients.

BACKGROUND: Accelerated bone loss occurs rapidly following renal transplantation due to intensive immunosuppression and persistent hyperparathyroidism. In renal transplant recipients (RTRs) due to the hyperparathyroidism the non-dominant forearm is often utilized as a peripheral measurement site for dual-energy x-ray absorptiometry (DXA) measurements. The forearm is also the site of previous created distal arteriovenous fistulas (AVF). Although AVF remain patent long after successful transplantation, there are no data available concerning their impact on radial bone DXA measurements. METHODS: In this cross-sectional study we performed DXA in 40 RTRs with preexisting distal AVF (RTRs-AVF) to assess areal bone mineral density (aBMD) differences between both forearms (three areas) and compared our findings to patients with chronic kidney disease (CKD, n = 40), pre-emptive RTRs (RTRs-pre, n = 15) and healthy volunteers (n = 20). In addition, we assessed relevant demographic, biochemical and clinical aspects. RESULTS: We found a marked radial asymmetry between the forearms in RTRs with preexisting AVF. The radial aBMD at the distal AVF forearm was lower compared to the contralateral forearm, resulting in significant differences for all three areas analyzed: the Rad-1/3: median (interquartile range) in g/cm2, Rad-1/3: 0.760 (0.641-0.804) vs. 0.742 (0.642, 0.794), p = 0.016; ultradistal radius, Rad-UD: 0.433 (0.392-0.507) vs. 0.420 (0.356, 0.475), p = 0.004; and total radius, Rad-total: 0.603 (0.518, 0.655) vs. 0.599 (0.504, 0.642), p = 0.001). No such asymmetries were observed in any other groups. Lower aBMD in AVF forearm subregions resulted in misclassification of osteoporosis. CONCLUSIONS: In renal transplant recipients, a previously created distal fistula may exert a negative impact on the radial bone leading to significant site-to-site aBMD differences, which can result in diagnostic misclassifications.

Eye movement programming and reading accuracy.

Eye movements were measured during the silent reading of sentences to extract several oculomotor measures. Rather than each measure being examined independently, oculomotor responses were grouped into two types, the assumption being that the grouping would project onto underlying constructs. Properties of forward-directed movements were assumed to reflect the success with which linguistic information was acquired (acquisition), and corrective responses were assumed to reveal readers' responding to difficulties (correction). These two types of oculomotor responses were linked to indexes of reading accuracy (accuracy), which were obtained from separate materials so that eye movements with one set of materials could be used to predict reading accuracy for another set of materials. Path analyses indicated that correction, but not acquisition, was linked to accuracy. The additional clustering of acquisition, correction, and accuracy scores identified a group of readers with relatively low accuracy scores. These readers were typical in their acquisition of linguistic information but under-used corrective responding.

Bone Mass Distribution of the Distal Tibia in Normal, Osteopenic, and Osteoporotic Conditions: An Ex Vivo Assessment Using HR-pQCT, DXA, and Computational Modelling.

Osteoporosis leads to bone loss and structural deterioration, which increase the risk of fractures. The aim of this study was to characterize the three-dimensional (3D) bone mass distributions of the distal tibia in normal, osteopenic, and osteoporotic conditions. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the 33 % of the distal tibia and local dual-energy X-ray absorptiometry were applied to 53 intact, fresh-frozen tibiae. The HR-pQCTs were graded to assign local T-scores and merged into three equally sized average normal, osteopenic, and osteoporotic surface models. Volumetric bone mineral density (vBMD) was determined using categorized T-scores, volumetric visualization, and virtual bore probes at the dia-, meta-, and epiphyseal sites (T-DIA, T-META, and T-EPI). We observed a distinct 3D bone mass distribution that was gradually uninfluenced by T-score categories. T-DIA was characterized by the lowest bone mass located in the medullary cavity and a wide homogenous cortex containing the maximum vBMD. The T-META showed decreased cortical thickness and maximal vBMD. At the T-EPI, the relatively low vBMD of the mostly trabecular bone was similar to the maximal cortical vBMD in this sub-region. Four trabecular regions of low bone mass were identified in the recesses. The bone content gradually decreased at all sites, whereas the pattern of bone mass distribution remained essentially unchanged, with the exception of disproportionate losses at T-DIA, T-META, and T-EPI that consistently showed increased endocortical, intracortical, and trabecular bone loss. Extra information can be obtained from the specific pattern of bone mass distribution, potential disproportionate bone losses, and method used.

Misperception of orthographic neighbors during silent and oral reading.

The study examined whether words are misperceived during natural fluent reading and the extent to which contextual and lexical properties bias perception. Target words were pairs of orthographic neighbors that differed in frequency. Pretarget context was neutral (Experiment 1) or biased toward the higher frequency member of the pair (Experiments 2 and 3), and posttarget context was neutral, congruent, or incongruent. Critically, incongruent context was constructed so that it was congruent with the target's neighbor. First-pass viewing showed only effects of target frequency. During silent reading (Experiments 1 and 2), rereading measures showed that the target frequency effect was smaller in the incongruent posttarget context condition than in the neutral and congruent conditions, and this occurred irrespective of prior context. Presumably, lower frequency words were less impeded by incongruent context because they were often misperceived as a congruent higher frequency neighbor. An oral reading task (Experiment 3) showed that the lower frequency target was more often misread than the higher frequency neighbor, and this proneness to error was influenced by posttarget context. Although target frequency influenced proneness to error, biased prior sentence context appeared to influence the construal of sentence meaning to accommodate incongruent targets and posttarget context. (PsycINFO Database Record

Syllabic tone articulation influences the identification and use of words during Chinese sentence reading: Evidence from ERP and eye movement recordings.

In two experiments, we examined the contribution of articulation-specific features to visual word recognition during the reading of Chinese. In spoken Standard Chinese, a syllable with a full tone can be tone-neutralized through sound weakening and pitch contour change, and there are two types of two-character compound words with respect to their articulation variation. One type requires articulation of a full tone for each constituent character, and the other requires a full- and a neutral-tone articulation for the first and second characters, respectively. Words of these two types with identical first characters were selected and embedded in sentences. Native speakers of Standard Chinese were recruited to read the sentences. In Experiment 1, the individual words of a sentence were presented serially at a fixed pace while event-related potentials were recorded. This resulted in less-negative N100 and anterior N250 amplitudes and in more-negative N400 amplitudes when targets contained a neutral tone. Complete sentences were visible in Experiment 2, and eye movements were recorded while participants read. Analyses of oculomotor activity revealed shorter viewing durations and fewer refixations on-and fewer regressive saccades to-target words when their second syllable was articulated with a neutral rather than a full tone. Together, the results indicate that readers represent articulation-specific word properties, that these representations are routinely activated early during the silent reading of Chinese sentences, and that the representations are also used during later stages of word processing.

Bone mineral density (BMD) and vertebral trabecular bone score (TBS) for the identification of elderly women at high risk for fracture: the SEMOF cohort study.

PURPOSE: To determine the predictive value of the vertebral trabecular bone score (TBS) alone or in addition to bone mineral density (BMD) with regard to fracture risk. METHODS: Retrospective analysis of the relative contribution of BMD [measured at the femoral neck (FN), total hip (TH), and lumbar spine (LS)] and TBS with regard to the risk of incident clinical fractures in a representative cohort of elderly post-menopausal women previously participating in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk study. RESULTS: Complete datasets were available for 556 of 701 women (79 %). Mean age 76.1 years, LS BMD 0.863 g/cm2, and TBS 1.195. LS BMD and LS TBS were moderately correlated (r 2 = 0.25). After a mean of 2.7 ± 0.8 years of follow-up, the incidence of fragility fractures was 9.4 %. Age- and BMI-adjusted hazard ratios per standard deviation decrease (95 % confidence intervals) were 1.58 (1.16-2.16), 1.77 (1.31-2.39), and 1.59 (1.21-2.09) for LS, FN, and TH BMD, respectively, and 2.01 (1.54-2.63) for TBS. Whereas 58 and 60 % of fragility fractures occurred in women with BMD T score ≤-2.5 and a TBS <1.150, respectively, combining these two thresholds identified 77 % of all women with an osteoporotic fracture. CONCLUSIONS: Lumbar spine TBS alone or in combination with BMD predicted incident clinical fracture risk in a representative population-based sample of elderly post-menopausal women.

Revisiting the Single-Case Approach to Studying Reading Disorders.

Oscar Marin was a neurologist with a remarkably broad interest in the brain and its function. He was passionate about understanding how the brain processes language and about helping people with acquired language disorders through his science-based practice. Here we honor his memory by presenting a review and commentary charting the cycle of neuroscientific approaches to studying reading disorders over the past century. During this time, "best practices" have changed from individual case studies to group studies and mega-studies and back again to individual studies. We show how, across decades and almost unimaginable advances in neuroimaging technology, the individual approach taken by Oscar Marin has retained its importance.

Microstructural parameters of bone evaluated using HR-pQCT correlate with the DXA-derived cortical index and the trabecular bone score in a cohort of randomly selected premenopausal women.

BACKGROUND: Areal bone mineral density is predictive for fracture risk. Microstructural bone parameters evaluated at the appendicular skeleton by high-resolution peripheral quantitative computed tomography (HR-pQCT) display differences between healthy patients and fracture patients. With the simple geometry of the cortex at the distal tibial diaphysis, a cortical index of the tibia combining material and mechanical properties correlated highly with bone strength ex vivo. The trabecular bone score derived from the scan of the lumbar spine by dual-energy X-ray absorptiometry (DXA) correlated ex vivo with the micro architectural parameters. It is unknown if these microstructural correlations could be made in healthy premenopausal women. METHODS: Randomly selected women between 20-40 years of age were examined by DXA and HR-pQCT at the standard regions of interest and at customized sub regions to focus on cortical and trabecular parameters of strength separately. For cortical strength, at the distal tibia the volumetric cortical index was calculated directly from HR-pQCT and the areal cortical index was derived from the DXA scan using a Canny threshold-based tool. For trabecular strength, the trabecular bone score was calculated based on the DXA scan of the lumbar spine and was compared with the corresponding parameters derived from the HR-pQCT measurements at radius and tibia. RESULTS: Seventy-two healthy women were included (average age 33.8 years, average BMI 23.2 kg/m(2)). The areal cortical index correlated highly with the volumetric cortical index at the distal tibia (R  =  0.798). The trabecular bone score correlated moderately with the microstructural parameters of the trabecular bone. CONCLUSION: This study in randomly selected premenopausal women demonstrated that microstructural parameters of the bone evaluated by HR-pQCT correlated with the DXA derived parameters of skeletal regions containing predominantly cortical or cancellous bone. Whether these indexes are suitable for better predictions of the fracture risk deserves further investigation.

Real-life results of balloon kyphoplasty for vertebral compression fractures from the SWISSspine registry.

BACKGROUND CONTEXT: The Swiss Federal Office of Public Health mandated a nationwide health technology assessment-registry for balloon kyphoplasty (BKP) for decision making on reimbursement of these interventions. The early results of the registry led to a permanent coverage of BKP by basic health insurance. The documentation was continued for further evidence generation. PURPOSE: This analysis reports on the 1 year results of patients after BKP treatment. STUDY DESIGN: Prospective multicenter observational case series. PATIENT SAMPLE: The data on 625 cases with 819 treated vertebrae were documented from March 2005 to May 2012. OUTCOME MEASURES: Surgeon-administered outcome instruments were primary intervention form for BKP and the follow-up form; patient self-reported measures were EuroQol-5D questionnaire, North American Spine Society outcome instrument /Core Outcome Measures Index (including visual analog scale), and a comorbidity questionnaire. Outcome measures were back pain, medication, quality of life (QoL), cement extrusions, and new fractures within the first postoperative year. METHODS: Data were recorded preoperatively and at 3 to 6-month and 1-year follow-ups. Wilcoxon signed-rank test was used for comparison of pre- with postoperative measurements. Multivariate logistic regression was used to identify factors with a significant influence on the outcome. RESULTS: Seventy percent of patients were women with mean age of 71 years (range, 18-91 years); mean age of men was 65 years (range, 15-93 years). Significant and clinically relevant reduction of back pain, improvement of QoL, and reduction of pain killer consumption was seen within the first postoperative year. Preoperative back pain decreased from 69.3 to 29.0 at 3 to 6-month and remained unchanged at 1-year follow-ups. Consequently, QoL improved from 0.23 to 0.71 and 0.75 at the same follow-up intervals. The overall vertebra-based cement extrusion rates with and without extrusions into intervertebral discs were 22.1% and 15.3%, respectively. Symptomatic cement extrusions with radiculopathy were five (0.8%). A new vertebral fracture within a year from the BKP surgery was observed in 18.4% of the patients. CONCLUSIONS: The results of the largest observational study for BKP so far are consistent with published randomized trials and systematic reviews. In this routine health care setting, BKP is safe and effective in reducing pain, improving QoL, and lowering pain_killer consumption and has an acceptable rate of cement extrusions. Postoperative outcome results show clear and significant clinical improvement at early follow-up that remain stable during the first postoperative year.