Onset of word form recognition in English, Welsh, and English-Welsh bilingual infants

Children raised in the home as English or Welsh monolinguals or English–Welsh bilinguals were tested on untrained word form recognition using both behavioral and neurophysiological procedures. Behavioral measures confirmed the onset of a familiarity effect at 11 months in English but failed to identify it in monolingual Welsh infants between 9 and 12 months. In the neurophysiological procedure the familiarity effect was detected as early as 10 months in English but did not reach significance in monolingual Welsh. Bilingual children showed word form familiarity effects by 11 months in both languages and also revealed an online time course for word recognition that combined effects found for monolingual English and Welsh. To account for the findings, accentual, grammatical, and sociolinguistic differences between English and Welsh are considered.

Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice

Introduction
Angiotensin II (Ang II) is known to induce cardiac growth and modulate myocardial contractility. It has been reported that elevated levels of endogenous Ang II contribute to the development of cardiac hypertrophy in hypertensives. However, the long-term functional effects of cardiac exposure to Ang II in normotensives is unclear.

A recently developed transgenic mouse (TG1306/1R), in which cardiac-specific overproduction of Ang II produces primary hypertrophy, provides a new experimental model for investigation of this phenotype. The aim of the present study was to use this model to investigate whether there is a functional deficit in primary hypertrophy that may predispose to cardiac failure and sudden death. We hypothesised that primary cardiac hypertrophy is associated with mechanical dysfunction in the basal state.

Methods
Normotensive heterozygous TG1306/1R mice harbouring multiple copies of a cardiac-specific rat angiotensinogen gene were studied at age 30—40 weeks and compared with age-matched wild-type littermates. Left ventricular function was measured ex vivo in bicarbonate buffer-perfused, Langendorffmounted hearts ( at a perfusion pressure of 80 mmHg, 37°C) using a fluid-filled PVC balloon interfaced to a pressure transducer and digital data acquisition system.

Results
There was no difference in the mean (±SEM) intrinsic heart rate of TG1306/1R and wild-type control mice (357.4±11.8 vs. 367.5±20.9 bpm, n=9 & 7). Under standardised end-diastolic pressure conditions, TG1306/1R hearts exhibited a significant reduction in peak developed pressure (132.2±9.4 vs. 161.5±3.1 mmHg, n=9 & 7, p<0.05) and maximum rate of pressure development (3566.7±323.7 vs. 4486.3±109.4 mmHg, n=9 & 7, p<0.05). TG1306/1R mice show a significant correlation between incidence of arrhythmia and increasing heart size (Spearman's correlation coefficient 0.61).

Conclusion
These data demonstrate that chronic in vivo exposure to elevated levels of intra-cardiac Ang II is associated with significant contractile abnormalities evident in the ex vivo intact heart. Our findings suggest that endogenous overproduction of cardiac Ang II, independent of changes in blood pressure, is sufficient to induce ventricular remodelling that culminates in impaired cardiac function which may precede failure.

Elevated dietary sodium intake exacerbates myocardial hypertrophy associated with cardiac-specific overproduction of angiotensin II

Introduction/hypothesis
Cardiac hypertrophy is an independent risk factor predictive of cardiovascular disease and is significantly associated with morbidity and mortality. The mechanism by which angiotensin II (Ang II) and dietary sodium exert additive effects on the development of cardiac hypertrophy is unclear. The goal of this study was to evaluate the hypothesis that, where there is a genetic predisposition to Ang II-dependent hypertrophy, there is also an increased susceptibility to sodium-induced hypertrophy mediated by AT₁-receptor expression.

Methods
Diets of low sodium (LS, 0.3% w:w) and high sodium (HS, 4.0% w:w) content were fed to adult (age 25 weeks) control wild-type mice (WT) and to weeks) control wild-type mice (WT) and to transgenic mice exhibiting cardiac specific overexpression of angiotensinogen (TG). At the conclusion of a 40-day dietary treatment period, cardiac tissue weights were compared and the relative expression levels of Ang II receptor subtypes (AT_1A and AT₂) were evaluated using RT-PCR.

Results
WT and TG mice fed HS and LS diets maintained comparable weight gains during the treatment period. The normalised heart weights of TG mice were elevated compared to WT, and the extent of the increase was greater for mice maintained on the HS diet treatments (WT 12% vs. TG 41% increase in cardiac weight index). While a similar pattern of growth was observed for ventricular tissues, the atrial weight parameters demonstrated an additional significant effect of dietary sodium intake on tissue weight, independent of animal genetic type. No differences in the relative (GAPDH normalised) expression levels of AT_1A- and AT₂-receptor mRNA were observed between diet or animal genetic groups.

Conclusion
This study demonstrates that, where there is a pre-existing genetic condition of Ang II-dependent cardiac hypertrophy, the pro-growth effect of elevated dietary sodium intake is selectively augmented. In TG and WT mice, this effect was evident with a relatively short dietary treatment intervention (40 days). Evaluation of the levels of Ang II receptor mRNA further demonstrated that this differential growth response was not associated with an altered relative expression of either AT_1A- or AT₂-receptor subtypes. The cellular mechanistic bases for this specific Ang II-dietary sodium interaction remain to be elucidated.

Training improves interobserver reliability for the diagnosis of scaphoid fracture displacement

Background The diagnosis of displacement in scaphoid fractures is notorious for poor interobserver reliability.

Questions/purposes We tested whether training can improve interobserver reliability and sensitivity, specificity, and accuracy for the diagnosis of scaphoid fracture displacement on radiographs and CT scans.

Methods Sixty-four orthopaedic surgeons rated a set of radiographs and CT scans of 10 displaced and 10 nondisplaced scaphoid fractures for the presence of displacement, using a web-based rating application. Before rating, observers were randomized to a training group (34 observers) and a nontraining group (30 observers). The training group received an online training module before the rating session, and the nontraining group did not. Interobserver reliability for training and nontraining was assessed by Siegel’s multirater kappa and the Z-test was used to test for significance.

Results There was a small, but significant difference in the interobserver reliability for displacement ratings in favor of the training group compared with the nontraining group. Ratings of radiographs and CT scans combined resulted in moderate agreement for both groups. The average sensitivity, specificity, and accuracy of diagnosing displacement of scaphoid fractures were, respectively, 83%, 85%, and 84% for the nontraining group and 87%, 86%, and 87% for the training group. Assuming a 5% prevalence of fracture displacement, the positive predictive value was 0.23 in the nontraining group and 0.25 in the training group. The negative predictive value was 0.99 in both groups.

Conclusions Our results suggest training can improve interobserver reliability and sensitivity, specificity and accuracy for the diagnosis of scaphoid fracture displacement, but the improvements are slight. These findings are encouraging for future research regarding interobserver variation and how to reduce it further.

Interobserver reliability of computed tomography to diagnose scaphoid waist fracture union

Purpose : To determine the interobserver agreement and diagnostic performance characteristics of computed tomography (CT) for determining union of scaphoid waist fractures.

Methods : A total of 59 orthopedic and trauma surgeons rated for union a set of 30 sagittal CT scans of 30 scaphoid waist fractures. Of these fractures, 20 were treated nonoperatively, were imaged between 6 and 10 weeks after injury, and were known to have eventually achieved union. Ten were operatively confirmed to be ununited. We rated each scan as united or ununited using a Web-based rating application. We assessed interobserver reliability using Siegel's multirater Kappa. We calculated diagnostic performance characteristics using Bayesian formulas.

Results : The interobserver agreement among 59 raters was substantial. The average sensitivity, specificity, and accuracy of diagnosing union of scaphoid waist fractures on sagittal CT scans were 78%, 96%, and 84%, respectively. Assuming a 90% prevalence of fracture union of the scaphoid, the positive predictive value of a diagnosis of union on sagittal CT scan was 0.99 and the negative predictive value was 0.41.

Conclusions : Our results suggest that CT scans are accurate and reliable for diagnosis of union but inadequate for ruling out nonunion of scaphoid waist fractures between 6 and 10 weeks after injury.

Interobserver reliability of radial head fracture classification : two-dimensional compared with three-dimensional CT

Background: The Broberg and Morrey modification of the Mason classification of radial head fractures has substantial interobserver variation. This study used a large web-based collaborative of experienced orthopaedic surgeons to test the hypothesis that three-dimensional reconstructions of computed tomography (CT) scans improve the interobserver reliability of the classification of radial head fractures according to the Broberg and Morrey modification of the Mason classification.

Methods: Eighty-five orthopaedic surgeons evaluated twelve radial head fractures. They were randomly assigned to review either radiographs and two-dimensional CT scans or radiographs and three-dimensional CT images to determine the fracture classification, fracture characteristics, and treatment recommendations. The kappa multirater measure (κ) was calculated to estimate agreement between observers.

Results: Three-dimensional CT had moderate agreement and two-dimensional CT had fair agreement among observers for the Broberg and Morrey modification of the Mason classification, a difference that was significant. Observers assessed seven fracture characteristics, including fracture line, comminution, articular surface involvement, articular step or gap of ≥2 mm, central impaction, recognition of more than three fracture fragments, and fracture fragments too small to repair. There was a significant difference in kappa values between three-dimensional CT and two-dimensional CT for fracture fragments too small to repair, recognition of three fracture fragments, and central impaction. The difference between the other four fracture characteristics was not significant. Among treatment recommendations, there was fair agreement for both three-dimensional CT and two-dimensional CT.

Conclusions: Although three-dimensional CT led to some small but significant decreases in interobserver variation, there is still considerable disagreement regarding classification and characterization of radial head fractures. Three-dimensional CT may be insufficient to optimize interobserver agreement.

Interobserver reliability of classification and characterization of proximal humeral fractures: a comparison of two and three-dimensional CT

Interobserver reliability for the classification of proximal humeral fractures is limited. The aim of this study was to test the null hypothesis that interobserver reliability of the AO classification of proximal humeral fractures, the preferred treatment, and fracture characteristics is the same for two-dimensional (2-D) and three-dimensional (3-D) computed tomography (CT). Members of the Science of Variation Group--fully trained practicing orthopaedic and trauma surgeons from around the world--were randomized to evaluate radiographs and either 2-D CT or 3-D CT images of fifteen proximal humeral fractures via a web-based survey and respond to the following four questions: (1) Is the greater tuberosity displaced? (2) Is the humeral head split? (3) Is the arterial supply compromised? (4) Is the glenohumeral joint dislocated? They also classified the fracture according to the AO system and indicated their preferred treatment of the fracture (operative or nonoperative). Agreement among observers was assessed with use of the multirater kappa (κ) measure. Interobserver reliability of the AO classification, fracture characteristics, and preferred treatment generally ranged from "slight" to "fair." A few small but statistically significant differences were found. Observers randomized to the 2-D CT group had slightly but significantly better agreement on displacement of the greater tuberosity (κ = 0.35 compared with 0.30, p < 0.001) and on the AO classification (κ = 0.18 compared with 0.17, p = 0.018). A subgroup analysis of the AO classification results revealed that shoulder and elbow surgeons, orthopaedic trauma surgeons, and surgeons in the United States had slightly greater reliability on 2-D CT, whereas surgeons in practice for ten years or less and surgeons from other subspecialties had slightly greater reliability on 3-D CT. Proximal humeral fracture classifications may be helpful conceptually, but they have poor interobserver reliability even when 3-D rather than 2-D CT is utilized. This may contribute to the similarly poor interobserver reliability that was observed for selection of the treatment for proximal humeral fractures. The lack of a reliable classification confounds efforts to compare the outcomes of treatment methods among different clinical trials and reports.

Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders

Mutations in the leucine-rich, glioma-inactivated 1 gene, LGI1, cause autosomal-dominant lateral temporal lobe epilepsy via unknown mechanisms. LGI1 belongs to a subfamily of leucine-rich repeat genes comprising four members (LGI1–LGI4) in mammals. In this study, both comparative developmental as well as molecular evolutionary methods were applied to investigate the evolution of the LGI gene family and, subsequently, of the functional importance of its different gene members. Our phylogenetic studies suggest that LGI genes evolved early in the vertebrate lineage. Genetic and expression analyses of all five zebrafish lgi genes revealed duplications of lgi1 and lgi2, each resulting in two paralogous gene copies with mostly nonoverlapping expression patterns. Furthermore, all vertebrate LGI1 orthologs experience high levels of purifying selection that argue for an essential role of this gene in neural development or function. The approach of combining expression and selection data used here exemplarily demonstrates that in poorly characterized gene families a framework of evolutionary and expression analyses can identify those genes that are functionally most important and are therefore prime candidates for human disorders.

Synthesis and modification of a functionalized 3D open-framework structure with MIL-53 topology

Amino-functionalized MIL-53(Al) was synthesized, activated, and modified in a postsynthetic modification step using formic acid. All reaction products were characterized in detail. Solid-state NMR spectroscopy unequivocally demonstrates the presence of the different guest species as well as the successful post-synthetic functionalization.

[Al4(OH)2(OCH3)4(H2N-bdc)3]⋅x H2O: A 12-connected porous metal–organic framework with an unprecedented aluminum-containing brick

A new stable aluminum aminoterephthalate system contains octameric building blocks that are connected by organic linkers to form a 12-connected net (see picture). The structure adopts a cubic centered packing motive in which octameric units replace individual atoms, thus forming distorted octahedral (red sphere) and tetrahedral cages (green spheres) with effective accessible diameters of 1 and 0.45 nm, respectively

Sharing questions and initiatives, the professional organizations' point of view

The Book Designer: Careers and Professionalisation features contrubutions from 62 International design educators and professionals.  These leaders in their field provide analysis and expert commontary on the skill and epertise now required for sucessful career in design.

Do surgeons treat their patients like they would treat themselves?

Background - There is substantial unexplained geographical and surgeon-to-surgeon variation in rates of surgery. One would expect surgeons to treat patients and themselves similarly based on best evidence and accounting for patient preferences.

Questions/purposes - (1) Are surgeons more likely to recommend surgery when choosing for a patient than for themselves? (2) Are surgeons less confident in deciding for patients than for themselves?

Methods - Two hundred fifty-four (32%) of 790 Science of Variation Group (SOVG) members reviewed 21 fictional upper extremity cases (eg, distal radius fracture, De Quervain tendinopathy) for which surgery is optional answering two questions: (1) What treatment would you choose/recommend: operative or nonoperative? (2) On a scale from 0 to 10, how confident are you about this decision? Confidence is the degree that one believes that his or her decision is the right one (ie, most appropriate). Participants were orthopaedic, trauma, and plastic surgeons, all with an interest in treating upper extremity conditions. Half of the participants were randomized to choose for themselves if they had this injury or illness. The other half was randomized to make treatment recommendations for a patient of their age and gender. For the choice of operative or nonoperative, the overall recommendation for treatment was expressed as a surgery score per surgeon by dividing the number of cases they would operate on by the total number of cases (n = 21), where 100% is when every surgeon recommended surgery for every case. For confidence, we calculated the mean confidence for all 21 cases per surgeon; overall score ranges from 0 to 10 with a higher score indicating more confidence in the decision for treatment.

Results - Surgeons were more likely to recommend surgery for a patient (44.2% ± 14.0%) than they were to choose surgery for themselves (38.5% ± 15.4%) with a mean difference of 6% (95% confidence interval [CI], 2.1%–9.4%; p = 0.002). Surgeons were more confident in deciding for themselves than they were for a patient of similar age and gender (self: 7.9 ± 1.0, patient: 7.5 ± 1.2, mean difference: 0.35 [CI, 0.075–0.62], p = 0.012).

Conclusions - Surgeons are slightly more likely to recommend surgery for a patient than they are to choose surgery for themselves and they choose for themselves with a little more confidence. Different perspectives, preferences, circumstantial information, and cognitive biases might explain the observed differences. This emphasizes the importance of (1) understanding patients’ preferences and their considerations for treatment; (2) being aware that surgeons and patients might weigh various factors differently; (3) giving patients more autonomy by letting them balance risks and benefits themselves (ie, shared decision-making); and (4) assessing how dispassionate evidence-based decision aids help inform the patient and influences their decisional conflict.

Level of Evidence - Level III, diagnostic study.