EEG correlates of spatial orientation in the human retrosplenial complex

© 2015 Elsevier Inc. Studies on spatial navigation reliably demonstrate that the retrosplenial complex (RSC) plays a pivotal role for allocentric spatial information processing by transforming egocentric and allocentric spatial information into the respective other spatial reference frame (SRF). While more and more imaging studies investigate the role of the RSC in spatial tasks, high temporal resolution measures such as electroencephalography (EEG) are missing. To investigate the function of the RSC in spatial navigation with high temporal resolution we used EEG to analyze spectral perturbations during navigation based on allocentric and egocentric SRF. Participants performed a path integration task in a clearly structured virtual environment providing allothetic information. Continuous EEG recordings were decomposed by independent component analysis (ICA) with subsequent source reconstruction of independent time source series using equivalent dipole modeling. Time-frequency transformation was used to investigate reference frame-specific orientation processes during navigation as compared to a control condition with identical visual input but no orientation task. Our results demonstrate that navigation based on an egocentric reference frame recruited a network including the parietal, motor, and occipital cortices with dominant perturbations in the alpha band and theta modulation in frontal cortex. Allocentric navigation was accompanied by performance-related desynchronization of the 8-13. Hz frequency band and synchronization in the 12-14. Hz band in the RSC. The results support the claim that the retrosplenial complex is central to translating egocentric spatial information into allocentric reference frames. Modulations in different frequencies with different time courses in the RSC further provide first evidence of two distinct neural processes reflecting translation of spatial information based on distinct reference frames and the computation of heading changes

The role of transesophageal echocardiography in the diagnosis and management of children and young adults with valvar diseases of the left heart

Summary The role of transesophageal echocardiography in the diagnosis and management of left-sided cardiac valvar disease in children and young adults was assessed in terms of whether additional information (over transthoracic echocardiography) could be obtained, and whether the added information contributed to the better management of the patients. Between January 1991 to August 1992, 27 consecutive patients were studied. Their age ranged from 2.5 to 20 years (mean 12.7), with body weights ranging between 12 and 60 kg (mean 35.6). Twelve of the children suffered from atrioventricular valvar disease, 13 had predominant aortic valvar lesions and two had mixed valvar pathologies. Additional information was obtained by transesophageal over that of transthoracic echocardiography in 18 children (67%). Transesophageal echocardiography clarified the etiologies or mechanism of valvar regurgitation in eight and seven children with atrioventricular and aortic pathologies, respectively. The technique correctly diagnosed severe mitral regurgitation underestimated by conventional technique, detected a missed eccentric aortic regurgitant jet and convincingly excluded bacterial vegetations in one case each. The investigation contributed to the better management of three children (11%) by providing information that allowed the appropriate choice of therapy. Transesophageal echocardiography, therefore, is a useful technique for the diagnosis and management of valvar disease of the left heart in children and young adults.published_or_final_versio

Germline CRISPR/Cas9-mediated gene editing prevents vision loss in a novel mousemodel of Aniridia.

Aniridia is a rare eye disorder, which is caused by mutations in the paired box 6 (PAX6) gene and results in vision loss due to the lack of a long-term vision-saving therapy. One potential approach to treating aniridia is targeted CRISPR-based genome editing. To enable the Pax6 small eye (Sey) mouse model of aniridia, which carries the same mutation found in patients, for preclinical testing of CRISPR-based therapeutic approaches, we endogenously tagged the Sey allele, allowing for the differential detection of protein from each allele. We optimized a correction strategy in vitro then tested it in vivo in the germline of our new mouse to validate the causality of the Sey mutation. The genomic manipulations were analyzed by PCR, as well as by Sanger and next-generation sequencing. The mice were studied by slit lamp imaging, immunohistochemistry, and western blot analyses. We successfully achieved both in vitro and in vivo germline correction of the Sey mutation, with the former resulting in an average 34.8% ± 4.6% SD correction, and the latter in restoration of 3xFLAG-tagged PAX6 expression and normal eyes. Hence, in this study we have created a novel mouse model for aniridia, demonstrated that germline correction of the Sey mutation alone rescues the mutant phenotype, and developed an allele-distinguishing CRISPR-based strategy for aniridia

Haemophagocytic lymphohistiocytosis: An uncommon clinical presentation of tuberculosis

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Dementia and risk of visual impairment in Chinese older adults

We had previously identified visual impairment increasing risk of incident dementia. While a bi-directional vision-cognition association has subsequently been proposed, no study has specifically examined the longitudinal association between dementia and incidence of clinically defined visual impairment. In this territory-wide community cohort study of 10,806 visually unimpaired older adults, we examined their visual acuity annually for 6 years and tested if dementia at baseline was independently associated with higher risk of incident visual impairment (LogMAR ≥ 0.50 in the better eye despite best correction, which is equivalent to moderate visual impairment according to the World Health Organization definition). By the end of Year 6, a total of 3151 (29.2%) participants developed visual impairment. However, we did not find baseline dementia associating with higher risk of incident visual impairment, after controlling for baseline visual acuity, cataract, glaucoma, diabetes, hypertension, hypercholesterolemia, heart diseases, stroke, Parkinson's disease, depression, hearing and physical impairments, physical, intellectual and social activities, diet, smoking, age, sex, educational level, and socioeconomic status. Among different covariables, baseline visual acuity appears to be more important than dementia in contributing to the development of visual impairment. Our present findings highlight the need for re-evaluating whether dementia is indeed a risk factor for visual impairment

The Challenge Non-Typhoidal Salmonella (CHANTS) Consortium: Development of a non-typhoidal Salmonella controlled human infection model: Report from a consultation group workshop, 05 July 2022, London, UK [version 2; peer review: 2 approved]

Invasive non-typhoidal Salmonella disease (iNTS) is a major cause of morbidity and mortality globally, particularly as a cause of bloodstream infection in children and immunocompromised adults in sub-Saharan Africa. Vaccines to prevent non-typhoidal Salmonella (NTS) would represent a valuable public health tool in this setting to avert cases and prevent expansion of antimicrobial resistance. Several NTS and combination typhoidal-NTS vaccine candidates are in early-stage development, although the pathway to licensure is unclear due to challenges in conducting large phase III field trials. Controlled human infection models (CHIM) present an opportunity to accelerate vaccine development for a range of enteric pathogens. Several recent typhoidal Salmonella CHIMs have been conducted safely and have played pivotal roles in progressing vaccine candidates to pre-qualification and licensure. The Challenge Non-Typhoidal Salmonella (CHANTS) consortium has been formed with funding from the Wellcome Trust, to deliver the first NTS CHIM, which can act as a platform for future vaccine evaluation. This paper reports the conclusions of a consultation group workshop convened with key stakeholders. The aims of this meeting were to: (1) define the rationale for an NTS CHIM (2) map the NTS vaccine pipeline (3) refine study design and (4) establish potential future use cases

Consolidating emerging evidence surrounding HIVST and HIVSS: A rapid systematic mapping protocol

BACKGROUND: HIV self-testing (HIVST) is becoming popular with policy makers and commissioners globally, with a key aim of expanding access through reducing barriers to testing for individuals at risk of HIV infection. HIV self-sampling (HIVSS) was available previously to self-testing but was confined mainly to the USA and the UK. It remains to be seen whether the momentum behind HIVST will also energise efforts to expand HIVSS. Recent years have seen a rapid growth in the type of evidence related to these interventions as well as several systematic reviews. The vast majority of this evidence relates to acceptability as well as values and preferences, although new types of evidence are emerging. This systematic map aims to consolidate all emerging evidence related to HIVST and HIVSS to respond to this rapidly changing area. METHODS: We will systematically search databases and the abstracts of five conferences from 2006 to the present date, with monthly-automated database searches. Searches will combine key terms relating to HIV (e.g. HIV, AIDS, human immune-deficiency syndrome) with terms related to self-testing (e.g. home-test, self-test, mail-test, home dried blood spot test). Abstracts will be reviewed against inclusion criteria in duplicate. Data will be manually extracted through a standard form and then entered to an open access relational map (HIVST.org). When new and sufficient evidence emerges which addresses existing knowledge gaps, we will complete a review on a relevant topic. DISCUSSION: This innovative approach will allow rapid cataloguing, documenting and dissemination of new evidence and key findings as they emerge into the public domain. SYSTEMATIC REVIEW REGISTRATION: This protocol has not been registered with PROSPERO as they do not register systematic maps

Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions.

The PHENIX collaboration presents first measurements of low-momentum (0.41  GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (>5  GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield

Production of π0 and η mesons in Cu+Au collisions at sNN =200 GeV

Production of π0 and η mesons has been measured at midrapidity in Cu+Au collisions at sNN=200GeV. Measurements were performed in π0(η)→γγ decay channel in the 1(2)-20GeV/c transverse momentum range. A strong suppression is observed for π0 and η meson production at high transverse momentum in central Cu+Au collisions relative to the p+p results scaled by the number of nucleon-nucleon collisions. In central collisions the suppression is similar to Au+Au with comparable nuclear overlap. The η/π0 ratio measured as a function of transverse momentum is consistent with mT-scaling parametrization down to pT=2GeV/c, its asymptotic value is constant and consistent with Au+Au and p+p and does not show any significant dependence on collision centrality. Similar results were obtained in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions as well as in e+e- collisions in a range of collision energies sNN=3-1800 GeV. This suggests that the quark-gluon-plasma medium produced in Cu+Cu collisions either does not affect the jet fragmentation into light mesons or it affects the π0 and η the same way

Household out-of-pocket medical expenditures and national health insurance in Taiwan: income and regional inequality

BACKGROUND: Unequal geographical distribution of medical care resources and insufficient healthcare coverage have been two long-standing problems with Taiwan's public health system. The implementation of National Health Insurance (NHI) attempted to mitigate the inequality in health care use. This study examines the degree to which Taiwan's National Health Insurance (NHI) has reduced out-of-pocket medical expenditures in households in different regions and varying levels of income. METHODS: Data used in this study were drawn from the 1994 and 1996 Surveys of Family Income and Expenditure. We pooled the data from 1994 and 1996 and included a year dummy variable (NHI), equal to 1 if the household data came from 1996 in order to assess the impact of NHI on household out-of-pocket medical care expenditures shortly after its implementation in 1995. RESULTS: An individual who was older, female, married, unemployed, better educated, richer, head of a larger family household, or living in the central and eastern areas was more likely to have greater household out-of-pocket medical expenditures. NHI was found to have effectively reduced household out-of-pocket medical expenditures by 23.08%, particularly for more affluent households. With the implementation of NHI, lower and middle income quintiles had smaller decreases in out-of-pocket medical expenditure. NHI was also found to have reduced household out-of-pocket medical expenditures more for households in eastern Taiwan. CONCLUSION: Although NHI was established to create free medical care for all, further effort is needed to reduce the medical costs for certain disadvantaged groups, particularly the poor and aborigines, if equality is to be achieved