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Thyroglobulin (Tg) has been considered a measure of iodine status, but there is no global guidance. This analysis examines the relationship between serum Tg and spot urinary iodine concentration (UIC) data to identify Tg concentrations that correspond to current WHO thresholds for population iodine status. We analysed data from 730 non-pregnant Guatemalan women aged 15–49 years who had both UIC and Tg measurements. Correlations were examined. Bootstrap stratified finite sampling with replacement was used to generate cluster k-medians of UIC (mUIC) and Tg (mTg) that served as the population unit of analyses. Non-linear restricted cubic spline regression dose–response curve functions and ordinary differential equations were then used to derive the Tg threshold corresponding to WHO definitions for UIC. Mean age was 30·2 (sd 9·3) years. mTg was 10·4 ng/ml (9·9, 10·8), and mUIC was 148·7 μg/l (139·1, 161·0). Correlations between spot UIC and Tg were NS at the individual level, but correlations based on population k-medians were significant (Spearman r = −0·21 to −0·06, each P < 0·0001) and demonstrated a U-shaped relationship according to WHO categories. Derived mTg cutoffs were 14·2 ng/ml predictive of UIC insufficiency, 10·2 ng/ml for UIC adequacy, 8·5 ng/ml for UIC above adequate and 10·8 ng/ml for UIC excess. The significant and graded mUIC–mTg correlations suggest that Tg concentrations predictive of UIC categories are obtainable for non-pregnant Guatemalan women aged 15–49 years. The newly derived mTg cutoff may be more discriminant at a lower spectrum of UIC in terms of identifying iodine-deficient women, more so than in the UIC excess category.
The use of Duddingtonia flagrans in the control of goat nematodes was investigated. Initially, the time of passage of chlamydospores through the digestive tract of goats was evaluated. Two groups of seven parasite-free kids were formed. Group A received a single dose of 3.5×106D. flagrans chlamydospores (FTHO-8 strain) per kg of live weight. Group B did not receive any chlamydospores. Faeces were obtained from each kid daily from day 4 prior to inoculation until day 5 post-inoculation (PI) and were placed in Petri dishes containing water agar. Gastrointestinal nematode infective larvae were added to each Petri dish and incubated at 25°C for 7 days. Petri dishes were examined to detect the fungus and trapped nematodes. A second trial evaluated the effect of D. flagrans on the number of gastrointestinal nematode larvae harvested from goat faecal cultures in naturally infected goats. Two groups of seven goats were formed. The treated group received a single dose of 3.5×106D. flagrans chlamydospores per kg of liveweight. The control group did not receive any chlamydospores. Faeces were obtained twice daily from each kid. Two faecal cultures were made for each kid. One was incubated for 7 days and the other for 14 days. Gastrointestinal nematode larvae were recovered from each culture and counted. Percentage of larval development reduction was determined using a ratio of larvae/eggs deposited in the control and treated groups. Duddingtonia flagrans survived the digestive process of goats, and maintained its predatory activity, being observed from 21 to 81 h PI (3 to 4 days). A reduction in the infective larvae population in the treated group compared to the non-treated group was observed in both incubation periods (7 days: 5.3–36.0%; 14 days: 0–52.8%, P>0.05). Although a single inoculation of D. flagrans can induce a reduction of infective larvae collected from faeces, a different scheme of dosing may be needed to enhance the efficacy of D. flagrans in goats.
Patients suspected of having a rare genetic disease often experience lengthy and costly diagnostic odysseys. The timing of whole exome sequencing (WES) in the testing sequence, its diagnostic yield and test costs in the sequence all factor into estimates of cost-effectiveness analysis for health technology assessment.
Methods
We modeled the diagnostic pathway using a discrete event simulation model, starting with the first test result. We defined and populated the simulation based on data from the electronic medical records of n=307 from the Care-for-Rare SOLVE multi-center Canadian observational cohort. Five alternative diagnostic pathways were modeled based on the observed data: no WES, and WES as the first, second, third or fourth test in the sequence. WES as the second test in the sequence is considered standard of care in medical genetic centers in Canada. We assessed effectiveness of WES in terms of diagnostic yield, time to diagnosis, and costs as patient-level overall test costs (2020 CAD/USD) across the diagnostic pathway.
Results
Compared to molecular and specialized diagnostic tests only (i.e., no WES), WES increased diagnostic yield from 5 percent to 40 percent. The shortest time to diagnosis for those with a diagnosis was 1.82 years in the diagnostic pathway with WES as the second test. Test costs for each pathway were CAD2,800 (USD2,087, no WES), CAD2,700 (USD2,013, WES as first test), CAD3,500 (USD2,609, WES as second test), CAD4,500 (USD3,354, WES as third test), and CAD5,300 (USD3,951, WES as fourth test).
Conclusions
Placing WES earlier in the diagnostic pathway for patients suspected of having a rare disease is associated with an increased diagnostic yield, reduced time to diagnosis and lower overall test costs with the benefits being greater the earlier in the pathway that WES is implemented.
This study investigated the comprehension of plural morphosyntactic markers and its relationship with numerical comparison abilities in children with Down syndrome (DS). It evaluated 16 Spanish-speaking children with DS (mean verbal mental age = 3;6) and 16 typically developing children with similar receptive vocabulary (mean chronological age = 3;5). Children participated in two preferential looking tasks assessing their abilities to map singular and plural markers to their visual referents and to distinguish one object from more than one. Results showed that both groups of children correctly mapped plural markers to their referents but failed to map singular ones. Furthermore, results also indicated that both groups also looked at collections of more than one object with four objects but not at those with two. The eye movement patterns of children who looked at collections of more than one object suggest a counting-like strategy. These results indicate that comprehension of plural markers of children with DS is similar to that of their typically developing peers; however, it is not related to their numerical abilities.
Although gains in generational intelligence test scores have been widely demonstrated around the world, researchers still do not know what has caused them. The cognitive stimulation and nutritional hypotheses summarize the several diverse potential causes that have been considered. This article analyses data for a sample of 499 children tested in 1930 and one equivalent sample of 710 children tested 72 years later, the largest gap ever considered. Both samples comprised children aged between 7 and 11 who were assessed by the Draw-a-Man test in the city of Belo Horizonte, Brazil. Further, one additional sample of 132 children was assessed in 2004 in a rural area very similar in several diverse factors to the 1930 urban sample. The results are consistent with both the cognitive stimulation and the nutritional hypotheses.
Vitellogenin (VTG) was isolated from the haemolymph of Penaeus vannamei by a three stepprocedure including ultracentrifugation, gel filtration and ion exchange chromatography. VTG wasused to raise polyclonal antibodies that were purified by ion exchange chromatography. A two stepcompetitive assay was developed in which VTG could be quantitated by its capacity to inhibit thebinding of antibody to the VTG previously adsorbed onto a solid phase. Sensitivity from equilibriumand from non-equilibrium assays was 41 and 2.3 ng/ml respectively. Estimates of within-assay andbetween-assay variabilities of standard curves were 4.2 and 9.6% respectively. The inhibition curves for dilutions of haemolymph from vitellogenic females, egg yolk extracts and purified vitellin (VTL) were parallel to the standard VTG curve, haemolymph from immature females and males showed no cross-reactivity. The antibodies directed against VTG recognize but partially VTL as shown by displacement curves. Recovery tests were near 100%. Thus the procedure was considered to be suitable for the measurement of haemolymphatic VTG. The VTG enzyme-linked immunosorbent assay (ELISA) developed in this study was validated by detecting physiological VTG changes in female shrimps after being fed squid extracts.
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