The ability to acquire and use several languages selectively is a unique and essential human capacity. Here we investigate the fundamental question of how multiple languages are represented in a human brain. We applied functional magnetic resonance imaging (fMRI) to determine the spatial relationship between native and second languages in the human cortex, and show that within the frontal-lobe language-sensitive regions (Broca's area), second languages acquired in adulthood ('late' bilingual subjects) are spatially separated from native languages. However, when acquired during the early language acquisition stage of development ('early' bilingual subjects), native and second languages tend to be represented in common frontal cortical areas. In both late and early bilingual subjects, the temporal-lobe language-sensitive regions (Wernicke's area) also show effectively little or no separation of activity based on the age of language acquisition. This discovery of language-specific regions in Broca's area advances our understanding of the cortical representation that underlies multiple language functions.

Naviculocuboid overlap, anteroposterior talonavicular coverage angle, and anteroposterior talus-first metatarsal angle are reliable and valid measures for the evaluation of hindfoot valgus and varus deformities.

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Background Intra-class correlation coefficients (ICCs) provide a statistical means of testing the reliability. However, their interpretation is not well documented in the orthopedic field. The purpose of this study was to investigate the use of ICCs in the orthopedic literature and to demonstrate pitfalls regarding their use. Methods First, orthopedic articles that used ICCs were retrieved from the Pubmed database, and journal demography, ICC models and concurrent statistics used were evaluated. Second, reliability test was performed on three common physical examinations in cerebral palsy, namely, the Thomas test, the Staheli test, and popliteal angle measurement. Thirty patients were assessed by three orthopedic surgeons to explore the statistical methods testing reliability. Third, the factors affecting the ICC values were examined by simulating the data sets based on the physical examination data where the ranges, slopes, and interobserver variability were modified. Results Of the 92 orthopedic articles identified, 58 articles (63%) did not clarify the ICC model used, and only 5 articles (5%) described all models, types, and measures. In reliability testing, although the popliteal angle showed a larger mean absolute difference than the Thomas test and the Staheli test, the ICC of popliteal angle was higher, which was believed to be contrary to the context of measurement. In addition, the ICC values were affected by the model, type, and measures used. In simulated data sets, the ICC showed higher values when the range of data sets were larger, the slopes of the data sets were parallel, and the interobserver variability was smaller. Conclusions Care should be taken when interpreting the absolute ICC values, i.e., a higher ICC does not necessarily mean less variability because the ICC values can also be affected by various factors. The authors recommend that researchers clarify ICC models used and ICC values are interpreted in the context of measurement.

PURPOSE. The purpose of this study was to investigate the topographic relationship between the decreased parapapillary retinal microvasculature as assessed by optical coherence tomography angiography (OCTA) and retinal nerve fiber layer (RNFL) defect in eyes with primary open-angle glaucoma (POAG) and a localized RNFL defect.METHODS. The peripapillary retinal circulation was evaluated using the OCTA centered on the optic nerve head in 98 POAG eyes having a localized RNFL defect and 45 healthy control eyes. A vascular impairment (VI) was identified in OCTA by the presence of a sign indicating decreased microvasculature. The frequencies of VI were compared between the POAG and control groups, and the topographic correlation between the VI and the RNFL defect identified in red-free fundus photographs was determined in the POAG group.RESULTS. The VI was observed as an area of decreased density of the microvascular network of the retina in 100% of the POAG eyes. The VI exactly coincided with the RNFL defect evident in red-free fundus photographs in terms of both the location and extent (Pearson's correlation coefficient ¼ 0.997 and 0.988, respectively, all P < 0.001). None of the control eyes exhibited VI in OCTA.CONCLUSIONS. Decreased parapapillary microvasculature of the retina determined by OCTA was found at the location of RNFL defect in POAG patients. This finding suggests that the decreased retinal microvasculature is likely secondary loss or closure of capillaries at the area of glaucomatous RNFL atrophy.Keywords: primary open-angle glaucoma, optical coherence tomography angiography, retinal microvasculature S tudies have shown that peripapillary retinal blood flow 1,2 and retinal vessel caliber 3,4 are reduced in glaucoma patients compared with healthy subjects, using laser Doppler flowmetry, 1 Doppler optical coherence tomography (OCT), 2 and measurements of retinal vessel caliber. [3][4][5][6] Decreased retinal perfusion has also been demonstrated angiographically in glaucoma patients using fluorescein angiography.7-10 These findings has raised the interest in the potential role of decreased ocular perfusion as an etiopathogenic factor for the glaucomatous optic neuropathy (GON), together with epidemiologic or clinical data that demonstrated the association of low blood pressure [11][12][13] or nocturnal blood pressure dips 14-16 with glaucoma. In contrast, Quigley et al. 17 demonstrated that the density of capillaries remained constant across a wide range of neural tissue losses within the optic nerve head (ONH) in both experimental and human glaucoma eyes. In addition, Cull et al. 18 showed that the ONH blood flow measured by laser speckle flowgraphy increased during the earliest stage of glaucoma followed by a linear decline that was strongly correlated with thickness reduction of the retinal nerve fiber layer (RNFL) thickness. These findings suggest that the reduced retinal perfusion could simply result from ONH degeneration and a consequently diminished metabolic demand.1,2,4-6 It therefore remains unc...

IntroductionFever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.MethodsWe designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality.ResultsWe recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU 36.5°C to 37.4°C), MAXICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).ConclusionsIn non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.Trial registrationClinicalTrials.gov: NCT00940654

Researchers need to consider statistical independence when performing statistical analysis, particularly in studies involving bilateral cases. If data dependency within a subject is not considered, studies involving bilateral cases can bias results, depending on the context of those studies.