Wpływ starzenia się i zakażenia wirusem HIV na związek pomiędzy stanem spoczynkowym mózgu a funkcjonowaniem poznawczym

Rationale and objective: The aging HIV seropositive (HIV+) population struggles with the brain functional and structural abnormalities. Consequently, HIV+ individuals can experience decline in neurocognitive performance. The current state of knowledge informs on the neuroinfectious actions of the HIV virus to a limited extent. However, with the new methods of brain imaging, such as resting state functional magnetic resonance imaging (RS-fMRI), we can now better understand the functional brain bases of the clinical neurocognitive portrait in this specific patient population. Up to date, few scientific reports addressed the effects of age and HIV infection on the resting state (RS) of the brain and cognitive functioning. Due to previous inconsistent findings, the issue remains unclear. This study aimed to examine the effects of aging and HIV infection on the RS of the brain in relationship to the cognitive functioning. Methods: This study analyzed data from a final number of 108 participants between 25 and 75 years of age, including 54 HIV+ individuals (age M=41; SD=12 years) and 54 demographically matched HIV-seronegative controls (age M=43; SD=12 years), with the mean of 16 years of education. All HIV+ participants were receiving HAART. The data retained for the current analyses included neuroimaging data of resting state functional magnetic resonance imaging (RS-fMRI), and neurocognitive data from a comprehensive battery of tests assessing attention, executive functions, memory, psychomotor functions, and semantic skills. RS data was analyzed using Regions of Interest-based approach, Independent Component Analysis, and Voxel-based analysis. Cognitive tests outcome T-scores were comprised into Neurocognitive Factor Scores. Between group differences in RS and neurocognitive data was assessed with T-unpaired test. Bivariate correlations examined relationships between age, RS measures, and neurocognitive factors. Multiple Linear Regression Analysis were performed in order to investigate the effects of age and HIV infection on the relationship between RS brain activity and neurocognitive performance. Results: Control group revealed patterns of aging in RS functional connectivity (FC) and neurocognitive decline comparable to the general population. HIV infection was related to decreases and increases in RS-FC and deterioration in attention and sematic skills as compared to controls. Interaction effects of age and HIV infection were exposed in terms of intra- and internetwork remote FC, which was weakening with age in HIV+ group, while strengthening with age in healthy comparators. No age-HIV interaction effects were observed on cognitive factors. Significant relationships were distinguished between RS-FC measures sensitive to age-HIV interaction effects and neurocognitive factors. Age had no significant moderator effects on majority of the revealed relationships in controls. HIV significantly moderated relationship between RS-FC and neurocognitive factors. Age in HIV+ group did not reveal significant moderator effects on the relationship between RS-FC and neurocognitive factors. Conclusions: Current study provides evidence that RS-fMRI is a sensitive technique to reveal not only additive but also interaction effects of age and HIV infection on the functioning of the brain. The results confirm that age and HIV infection lead to brain reorganization and decline in neurocognitive performance. Importantly, the study finds evidence for the employment of brain compensatory mechanisms in aging HIV+ patient population. The current findings support the hypothesis of rather accentuated than accelerated aging in the individuals aging with HIV.Uzasadnienie i cel: Osoby starzejące się z infekcją HIV (HIV+) zmagają sią z zaburzeniami w strukturze jak i funkcjonowaniu mózgu. W wyniku tego, osoby HIV+ mogą doświadczać deterioracji w funkcjonowaniu neuropoznawczym. Obecny stan wiedzy jest ograniczony na temat neuroinfekcyjnych działań wirusa HIV. Jednak przy użyciu nowych metod neuroobrazowania mózgu, takich jak badanie spoczynkowej aktywności mózgu w funkcjonalnym rezonansie magnetycznym (ang. resting state functional magnetic resonance imaging) możemy coraz lepiej opisać funkcjonalne podstawy mózgu przyczyniających się do klinicznego portretu zaburzeń neuropoznawczych w tej szczególnej grupie pacjentów. Do tej pory niewiele doniesień naukowych skierowanych było na badanie wpływu wieku i zakażenia wirusem HIV na stan spoczynkowy mózgu w odniesieniu do funkcji poznawczych. W związku z niespójnościami dotychczasowych doniesień, zagadnienie to pozostaje niewyjaśnione. To badanie miało na celu zbadanie efektów starzenia się i zakażenia wirusem HIV na stan spoczynkowy mózgu (RS) w stosunku do funkcjonowania poznawczego. Metoda: W badaniu przeanalizowano dane z ostatecznej liczby 108 uczestników między 25 a 75 rokiem życia, w tym 54 osoby HIV+ (średnia wieku = 41 lat; SD = 12 lat) oraz 54 demograficznie dopasowane osoby kontrolne HIV-seronegatywne (średnia wieku = 43 lata; SD = 12 lat), ze średnią 16 lat edukacji. Wszyscy uczestnicy HIV + byli na terapii HAART. Dane przeanalizowane w tym badaniu obejmowały dane spoczynkowego neuroobrazowania stanu mózgu (RS-fMRI) i dane neuropoznawcze z kompleksowego zestawu testów oceniających funkcje uwagi, funkcje wykonawcze, pamięć, funkcje psychomotoryczne i umiejętności semantyczne. Dane analizowano stosując podejście oparte na mózgowych regionach zainteresowania badawczego (ang. Regions of Interest-based analysis), analizy niezależnych komponentów (ang. Independent Component Analysis), i analizy opartej na wokselach (ang. Voxel-based analysis). Na podstawie wyników przekształconych (T) z testów poznawczych zostały skomponowane czynniki neuropoznawcze. Różnice pomiędzy grupami w RS i funkcjonowaniu poznawczym oceniano testem t. Dwuwymiarowe korelacje były użyte do zbadania relacji między wiekiem, RS, a czynnikami neuropoznawczymi. Wielokrotna analiza regresji liniowej przeprowadzona została w celu zbadania wpływu wieku i zakażenia wirusem HIV na relacje między spoczynkowa aktywnością mózgu (RS) a neuropoznawczą wydajnością. Wyniki: Grupa kontrolna, w zakresie połączeń funkcjonalnych (FC) w spoczynkowej aktywności mózgu oraz deterioracji funkcji neuropoznawczych, wykazała wzorce starzenia się porównywalne do ogólnej zdrowej populacji. Zakażenie wirusem HIV związane było z obniżeniem jak i z podwyższeniem RS-FC oraz pogorszeniem uwagi i umiejętności semantycznych w porównaniu z grupą kontrolną. Efekty interakcji wieku i zakażenia HIV były wykazane dla FC wewnątrz-sieciowych oraz między-sieciowych, które słabły wraz z wiekiem w grupie HIV+, a wzmacniały się wraz z wiekiem u zdrowych niezakażonych. Brak efektów interakcji wieku i wirusa HIV był wykazany dla czynników poznawczych. Wykazane zostały istotne relacje pomiędzy mocą połączeń RS-FC, które wykazały wrażliwość na skutki interakcji wieku i wirusa HIV, a wartością czynników neuropoznawczych. Wiek nie miał znaczącego wpływu jako moderator dla większości wykazanych relacji w grupie kontrolnej. Zakażenie wirusem HIV znacznie wpływało na związek między RS-FC a czynniki neuropoznawcze. Natomiast wiek w grupie HIV+ nie miał znaczących skutków jako moderator na relacje między RS-FC a czynnikami neuropoznawczymi. Wnioski: Obecne badanie dostarcza dowodów na to, że RS-fMRI jest czułą techniką mogącą ujawnić nie tylko efekty niezależne, ale również efekty interakcji wieku i zakażenia wirusem HIV na funkcjonowanie mózgu podczas braku jawnych procesów poznawczych. Wyniki tego badania dalej potwierdzają, że wiek i zakażenie wirusem HIV prowadzą do reorganizacji funkcjonalnej mózgu i spadku wydajności funkcji neuropoznawczych. Co ważne, badania to donosi o dowodach na wdrożenie kompensacyjnych mechanizmów mózgowych w populacji pacjentów starzejących się z wirusem HIV. Wyniki tego badania dowodzą o przeważającej słuszności hipotezy natężonego/skoncentrowanego (ang. accentuated) nad hipotezą przyspieszonego (ang. accelerated) starzenia się u osób żyjących z infekcją HIV

Towards a strategy for workplace learning: Report to HEFCE by CHERI and KPMG

The study, undertaken between March and November 2005 aimed to inform HEFCE thinking on developing a strategy for workplace learning by: exploring the nature, purposes and outcomes of workplace learning; considering workplace learning within the broader relationships between the worlds of work and learning; exploring emerging changes in higher education which may impact on workplace learning in the future; identifying structural issues that currently enable or inhibit workplace learning, and identify future opportunities

Constraints on the resistivity of the oceanic lithosphere and asthenosphere from seafloor ocean tidal electromagnetic measurements

Author Posting. © The Author(s), 2019. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Geophysical Journal International, 219(1), (2019): 464-478, doi:10.1093/gji/ggz315.The electromagnetic (EM) field generated by ocean tidal flow is readily detectable in both satellite magnetic field data, and in ocean-bottom measurements of electric and magnetic fields. The availability of accurate charts of tidal currents, constrained by assimilation of modern satellite altimetry data, opens the possibility of using tidal EM fields as a source to image mantle electrical resistivity beneath the ocean basins, as highlighted by the recent success in defining the globally averaged lithosphere–asthenosphere boundary (LAB) with satellite data. In fact, seafloor EM data would be expected to provide better constraints on the structure of resistive oceanic lithosphere, since the toroidal magnetic mode, which can constrain resistive features, is a significant component of the tidal EM field within the ocean, but is absent above the surface (in particular in satellite data). Here we consider this issue in more detail, using a combination of simplified theoretical analysis and 1-D and 3-D numerical modelling to provide a thorough discussion of the sensitivity of satellite and seafloor data to subsurface electrical structure. As part of this effort, and as a step toward 3-D inversion of seafloor tidal data, we have developed a new flexible 3-D spherical-coordinate finite difference scheme for both global and regional scale modelling, with higher resolution models nested in larger scale solutions. We use the new 3-D model, together with Monte Carlo simulations of errors in tidal current estimates, to provide a quantitative assessment of errors in the computed tidal EM signal caused by uncertainty in the tidal source. Over the open ocean this component of error is below 0.01 nT in Bz at satellite height and 0.05 nT in Bx on the seafloor, well below typical signal levels. However, as coastlines are approached error levels can increase substantially. Both analytical and 3-D modelling demonstrate that the seafloor magnetic field is most sensitive to the lithospheric resistance (the product of resistivity and thickness), and is more weakly influenced (primarily in the phase) by resistivity of the underlying asthenosphere. Satellite data, which contain only the poloidal magnetic mode, are more sensitive to the conductive asthenosphere, but have little sensitivity to lithospheric resistance. For both seafloor and satellite data’s changes due to plausible variations in Earth parameters are well above error levels associated with source uncertainty, at least in the ocean interior. Although the 3-D modelling results are qualitatively consistent with theoretical analysis, the presence of coastlines and bathymetric variations generates a complex response, confirming that quantitative interpretation of ocean tidal EM fields will require a 3-D treatment. As an illustration of the nested 3-D scheme, seafloor data at five magnetic and seven electric stations in the northeastern Pacific (41○N, 165○W) are fit with trial-and-error forward modelling of a local domain. The simulation results indicate that the lithospheric resistance is roughly 7 × 108 Ωm2. The phase of the seafloor data in this region are inconsistent with a sharp transition between the resistive lithosphere and conductive asthenosphere.This work has been supported by National Natural Science Foundation of China grants 41804072 and 41574104, and NSF grant EAR-1447109. Special thanks to Dr Benjamin Murphy who provided the conductivity-depth profile for 1-D earth model, Dr Min Ding who provided valuable discussion about the oceanic lithosphere and Dr Jeffery Love who provided comments on the stylistics of the manuscript

Assessment of Neurocognitive Functions, Olfaction, Taste, Mental, and Psychosocial Health in COVID-19 in Adults: Recommendations for Harmonization of Research and Implications for Clinical Practice

Assessment; COVID-19; Guidelines; Neuropsychological functions.Avaluació; COVID 19; Directrius; Funcions neuropsicològiques.Evaluación; COVID-19; Pautas; Funciones neuropsicológicasObjective: To propose a set of internationally harmonized procedures and methods for assessing neurocognitive functions, smell, taste, mental, and psychosocial health, and other factors in adults formally diagnosed with COVID-19 (confirmed as SARS-CoV-2 + WHO definition). Methods: We formed an international and cross-disciplinary NeuroCOVID Neuropsychology Taskforce in April 2020. Seven criteria were used to guide the selection of the recommendations' methods and procedures: (i) Relevance to all COVID-19 illness stages and longitudinal study design; (ii) Standard, cross-culturally valid or widely available instruments; (iii) Coverage of both direct and indirect causes of COVID-19-associated neurological and psychiatric symptoms; (iv) Control of factors specifically pertinent to COVID-19 that may affect neuropsychological performance; (v) Flexibility of administration (telehealth, computerized, remote/online, face to face); (vi) Harmonization for facilitating international research; (vii) Ease of translation to clinical practice. Results: The three proposed levels of harmonization include a screening strategy with telehealth option, a medium-size computerized assessment with an online/remote option, and a comprehensive evaluation with flexible administration. The context in which each harmonization level might be used is described. Issues of assessment timelines, guidance for home/remote assessment to support data fidelity and telehealth considerations, cross-cultural adequacy, norms, and impairment definitions are also described. Conclusions: The proposed recommendations provide rationale and methodological guidance for neuropsychological research studies and clinical assessment in adults with COVID-19. We expect that the use of the recommendations will facilitate data harmonization and global research. Research implementing the recommendations will be crucial to determine their acceptability, usability, and validity

Absence of Erythrocyte Sequestration and Lack of Multicopy Gene Family Expression in Plasmodium falciparum from a Splenectomized Malaria Patient

BACKGROUND:To avoid spleen-dependent killing mechanisms parasite-infected erythrocytes (IE) of Plasmodium falciparum malaria patients have the capacity to bind to endothelial receptors. This binding also known as sequestration, is mediated by parasite proteins, which are targeted to the erythrocyte surface. Candidate proteins are those encoded by P. falciparum multicopy gene families, such as var, rif, stevor or PfMC-2TM. However, a direct in vivo proof of IE sequestration and expression of multicopy gene families is still lacking. Here, we report on the analysis of IE from a black African immigrant, who received the diagnosis of a malignant lymphoproliferative disorder and subsequently underwent splenectomy. Three weeks after surgery, the patient experienced clinical falciparum malaria with high parasitemia and circulating developmental parasite stages usually sequestered to the vascular endothelium such as late trophozoites, schizonts or immature gametocytes. METHODOLOGY/PRINCIPAL FINDINGS:Initially, when isolated from the patient, the infected erythrocytes were incapable to bind to various endothelial receptors in vitro. Moreover, the parasites failed to express the multicopy gene families var, A-type rif and stevor but expression of B-type rif and PfMC-2TM genes were detected. In the course of in vitro cultivation, the parasites started to express all investigated multicopy gene families and concomitantly developed the ability to adhere to endothelial receptors such as CD36 and ICAM-1, respectively. CONCLUSION/SIGNIFICANCE:This case strongly supports the hypothesis that parasite surface proteins such as PfEMP1, A-type RIFIN or STEVOR are involved in interactions of infected erythrocytes with endothelial receptors mediating sequestration of mature asexual and immature sexual stages of P. falciparum. In contrast, multicopy gene families coding for B-type RIFIN and PfMC-2TM proteins may not be involved in sequestration, as these genes were transcribed in infected but not sequestered erythrocytes

Bats and Wind Farms : The Role and Importance of the Baltic Sea Countries in the European Context of Power Transition and Biodiversity Conservation

Although labeled as environmentally friendly, wind power can have negative impacts on the environment, such as habitat destruction or wildlife fatalities. Considering the distribution and migratory characteristics of European bats, the negative effects of wind power should be addressed on an appropriate scale. This review summarizes the current state of knowledge on interactions between wind farms and bats in Europe, and compares it with the situation in the countries of the European boreal biogeographic region. We analyzed data from papers published in international and national scientific journals, focusing on studies conducted in Europe. The issue of the impacts wind power has on bats is clearly overlooked in most of the countries of the European boreal region, with low volumes of research available on the topic. This is probably due to fewer wind farms in the area, making this recent issue a less-prioritized topic. However, the Baltic Sea, and the countries surrounding it, are of extreme importance with regards to bat migration, especially for the Pipistrellus nathusii. Therefore, more research on wind power and bats is needed in this region, as well as more cooperation between all the stakeholders.Although labeled as environmentally friendly, wind power can have negative impacts on the environment, such as habitat destruction or wildlife fatalities. Considering the distribution and migratory characteristics of European bats, the negative effects of wind power should be addressed on an appropriate scale. This review summarizes the current state of knowledge on interactions between wind farms and bats in Europe, and compares it with the situation in the countries of the European boreal biogeographic region. We analyzed data from papers published in international and national scientific journals, focusing on studies conducted in Europe. The issue of the impacts wind power has on bats is clearly overlooked in most of the countries of the European boreal region, with low volumes of research available on the topic. This is probably due to fewer wind farms in the area, making this recent issue a less-prioritized topic. However, the Baltic Sea, and the countries surrounding it, are of extreme importance with regards to bat migration, especially for the Pipistrellus nathusii. Therefore, more research on wind power and bats is needed in this region, as well as more cooperation between all the stakeholders.Peer reviewe

Bats and Wind Farms : The Role and Importance of the Baltic Sea Countries in the European Context of Power Transition and Biodiversity Conservation

Although labeled as environmentally friendly, wind power can have negative impacts on the environment, such as habitat destruction or wildlife fatalities. Considering the distribution and migratory characteristics of European bats, the negative effects of wind power should be addressed on an appropriate scale. This review summarizes the current state of knowledge on interactions between wind farms and bats in Europe, and compares it with the situation in the countries of the European boreal biogeographic region. We analyzed data from papers published in international and national scientific journals, focusing on studies conducted in Europe. The issue of the impacts wind power has on bats is clearly overlooked in most of the countries of the European boreal region, with low volumes of research available on the topic. This is probably due to fewer wind farms in the area, making this recent issue a less-prioritized topic. However, the Baltic Sea, and the countries surrounding it, are of extreme importance with regards to bat migration, especially for the Pipistrellus nathusii. Therefore, more research on wind power and bats is needed in this region, as well as more cooperation between all the stakeholders.Although labeled as environmentally friendly, wind power can have negative impacts on the environment, such as habitat destruction or wildlife fatalities. Considering the distribution and migratory characteristics of European bats, the negative effects of wind power should be addressed on an appropriate scale. This review summarizes the current state of knowledge on interactions between wind farms and bats in Europe, and compares it with the situation in the countries of the European boreal biogeographic region. We analyzed data from papers published in international and national scientific journals, focusing on studies conducted in Europe. The issue of the impacts wind power has on bats is clearly overlooked in most of the countries of the European boreal region, with low volumes of research available on the topic. This is probably due to fewer wind farms in the area, making this recent issue a less-prioritized topic. However, the Baltic Sea, and the countries surrounding it, are of extreme importance with regards to bat migration, especially for the Pipistrellus nathusii. Therefore, more research on wind power and bats is needed in this region, as well as more cooperation between all the stakeholders.Peer reviewe