Genetic findings in short Turkish children born to consanguineous parents

IntroductionThe diagnostic yield of genetic analysis in the evaluation of children with short stature depends onassociated clinical characteristics, but the additional effect of parental consanguinity has not beenwell documented.MethodsThis observational case series of 42 short children from 34 consanguineous families was collected bysix referral centres of paediatric endocrinology (inclusion criteria: short stature and parentalconsanguinity). In eighteen patients (12 families, Group 1), the clinical features suggested a specificgenetic defect in the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis, and a candidategene approach was used. In others (Group 2) a hypothesis-free approach was chosen (gene panels,microarray analysis, and whole-exome sequencing), further subdivided into 11 patients with severeshort stature (height <-3.5 SDS) and microcephaly (head circumference <-3.0 SDS) (group 2a), 10patients with syndromic short stature (group 2b) and were 3 patients with nonspecific isolated GHdeficiency (group 2c).ResultsIn all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, andSTAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1,and 17p13.3 microdeletions. In group 2c no genetic cause was found. Homozygous, compoundheterozygous and heterozygous variants were found in 21, 1 and 4 patients, respectively.ConclusionGenetic testing in short children from consanguineous parents has a high diagnostic yield, especiallyin cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature

Clinical and echocardiographic predictors of mortality in acute pulmonary embolism

Purpose: The aim of this study was to evaluate the utility of adding quantitative assessments of cardiac function from echocardiography to clinical factors in predicting the outcome of patients with acute pulmonary embolism (PE). Methods: Patients with a diagnosis of acute PE, based on a positive ventilation perfusion scan or computed tomography (CT) chest angiogram, were identified using the Duke University Hospital Database. Of these, 69 had echocardiograms within 24–48 h of the diagnosis that were suitable for offline analysis. Clinical features that were analyzed included age, gender, body mass index, vital signs and comorbidities. Echocardiographic parameters that were analyzed included left ventricular (LV) ejection fraction (EF), regional, free wall and global RV speckle-tracking strain, RV fraction area change (RVFAC), Tricuspid Annular Plane Systolic Excursion (TAPSE), pulmonary artery acceleration time (PAAT) and RV myocardial performance (Tei) index. Univariable and multivariable regression statistical analysis models were used. Results: Out of 69 patients with acute PE, the median age was 55 and 48 % were female. The median body mass 2 index (BMI) was 27 kg/m . Twenty-nine percent of the cohort had a history of cancer, with a significant increase in cancer prevalence in non-survivors (57 % vs 29 %, p = 0.02). Clinical parameters including heart rate, respiratory rate, troponin T level, active malignancy, hypertension and COPD were higher among non-survivors when compared to survivors (p ≤ 0.05). Using univariable analysis, NYHA class III symptoms, hypoxemia on presentation, tachycardia, tachypnea, elevation in Troponin T, absence of hypertension, active malignancy and chronic obstructive pulmonary disease (COPD) were increased in non-survivors compared to survivors (p ≤ 0.05). In multivariable models, RV Tei Index, global and free (lateral) wall RVLS were found to be negatively associated with survival probability after adjusting for age, gender and systolic blood pressure (p ≤ 0.05). Conclusion: The addition of echocardiographic assessment of RV function to clinical parameters improved the prediction of outcomes for patients with acute PE. Larger studies are needed to validate these findings

Postoperative pain intensity after using different instrumentation techniques: a randomized clinical study

Postoperative pain is a frequent complication associated with root canal treatment, especially during apical instrumentation of tooth with preexisting periradicular inflammation OBJECTIVES: The aim of this clinical study was to evaluate the influence of the instrumentation techniques on the incidence and intensity of postoperative pain in single-visit root canal treatment. MATERIAL AND METHODS: Ninety patients with single root/canal and non-vital pulps were included. The patients were assigned into 3 groups according to root canal instrumentation technique used; modified step-back, reciprocal, and rotational techniques. Root canal treatment was carried out in a single visit and the severity of postoperative pain was assessed via 4-point pain intensity scale. All the participants were called through the phone at 12, 24 and 48 h to obtain the pain scores. Data were analyzed through the Kruskal–Wallis test. RESULTS: There was significant difference between all groups (p<0.05). The modified step-back technique produced postoperative pain significantly lower than the rotational (p=0.018) and reciprocal (p=0.020) techniques. No difference was found between the reciprocal and rotational techniques (p=0.868). Postoperative pain in the first 12 h period (p=0.763) and in the 24 h period (p=0.147) was not significantly different between the groups. However, the difference in the 48 h period was statistically different between the groups (p=0.040). CONCLUSION: All instrumentation techniques caused postoperative pain. The modified step-back technique produced less pain compared to the rotational and reciprocal techniques

Challenges of source selection in the WoD

Federated querying, the idea to execute queries over several distributed knowledge bases, lies at the core of the semantic web vision. To accommodate this vision, SPARQL provides the SERVICE keyword that allows one to allocate sub-queries to servers. In many cases, however, data may be available from multiple sources resulting in a combinatorially growing number of alternative allocations of subqueries to sources. Running a federated query on all possible sources might not be very lucrative from a user's point of view if extensive execution times or fees are involved in accessing the sources' data. To address this shortcoming, federated join-cardinality approximation techniques have been proposed to narrow down the number of possible allocations to a few most promising (or results-yielding) ones. In this paper, we analyze the usefulness of cardinality approximation for source selection. We compare both the runtime and accuracy of Bloom Filters empirically and elaborate on their suitability and limitations for different kind of queries. As we show, the performance of cardinality approximations of federated SPARQL queries degenerates when applied to queries with multiple joins of low selectivity. We generalize our results analytically to any estimation technique exhibiting false positives. These findings argue for a renewed effort to find novel join-cardinality approximation techniques or a change of paradigm in query execution to settings, where such estimations play a less important role