| 1. |
|
|
| 2. |
- Ageron, M., et al.
(author)
-
ANTARES : The first undersea neutrino telescope
- 2011
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 656:1, s. 11-38
-
Journal article (peer-reviewed)abstract
- The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 3. |
- Delios, A., et al.
(author)
-
Examining the generalizability of research findings from archival data
- 2022
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
-
Journal article (peer-reviewed)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
|
|
| 4. |
- Tierney, W., et al.
(author)
-
A creative destruction approach to replication : Implicit work and sex morality across cultures
- 2021
-
In: Journal of Experimental Social Psychology. - : Elsevier BV. - 0022-1031 .- 1096-0465. ; 93
-
Journal article (peer-reviewed)abstract
- How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures.
|
|
| 5. |
- Perez-Nadales, Elena, et al.
(author)
-
Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
- 2020
-
In: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
-
Journal article (peer-reviewed)abstract
- Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
|
|
| 6. |
|
|
| 7. |
- Wang, I, et al.
(author)
-
Fluorescence diagnostics and kinetic studies in the head and neck region utilizing low-dose delta-aminolevulinic acid sensitization
- 1999
-
In: Cancer Letters. - 1872-7980. ; 135:1, s. 11-19
-
Journal article (peer-reviewed)abstract
- Diagnostic measurements and pharmacokinetic studies were performed in 17 patients with various kinds of malignant, premalignant and benign lesions in the head and neck region by means of point monitoring laser-induced fluorescence. For marking different types of tissue, delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was used. The ALA-induced PpIX synthesis was monitored at different time intervals after oral administration of ALA in low doses, 5 and 15 mg/kg b.w. Besides the porphyrin-related signal the tissue endogenous fluorescence was also recorded. The fluorescence spectra were evaluated at two different wavelengths corresponding to the specific drug-related fluorescence peak and the endogenous tissue fluorescence emission at 635 and 490 nm, respectively. The evaluated fluorescence data were correlated to the histopathological tissue investigation. A fall-off in the overall fluorescence intensity at 490 nm was obtained for an the malignant and premalignant areas, as well as an increased red fluorescence. A ratio between the red and the blue/green fluorescence intensity was formed for each time interval after the ALA administration. The lower drug dose seems to be sufficient to obtain a useful demarcation ratio between normal and diseased tissue with a very low PpIX fluorescence intensity in the normal tissue. A PpIX fluorescence maximum seems to occur between 3 and 4 h in normal tissues, whereas malignant tumour tissue shows a higher level for a longer period of time. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
|
|
| 8. |
- Zetterberg, P., et al.
(author)
-
Initial multi-node and antenna transmitter and receiver architectures and schemes; Deliverable D5.1
- 2016
-
Reports (other academic/artistic)abstract
- This deliverable provides the initial concepts and solutions from the technical work related to multi-antenna and multi-node transceiver schemes in millimetre wave (denoted as 6-100GHz) spectrum. It also briefly presents the use cases on which the work will be based and categorises the solutions in terms of their applicability to access, backhaul and relay deployments. Another important contribution from this report is the modelling of the hardware impairments in millimetre wave transceivers and the analysis of their impact on system performance.
|
|
| 9. |
|
|
| 10. |
- Durán Bosch, Vicente Andrés, 1977, et al.
(author)
-
Compressive imaging in scattering media
- 2015
-
In: Optics Express. - : The Optical Society. - 1094-4087 .- 1094-4087. ; 23:11, s. 14424-14433
-
Journal article (peer-reviewed)abstract
- One challenge that has long held the attention of scientists is that of clearly seeing objects hidden by turbid media, as smoke, fog or biological tissue, which has major implications in fields such as remote sensing or early diagnosis of diseases. Here, we combine structured incoherent illumination and bucket detection for imaging an absorbing object completely embedded in a scattering medium. A sequence of low-intensity microstructured light patterns is launched onto the object, whose image is accurately reconstructed through the light fluctuations measured by a single-pixel detector. Our technique is noninvasive, does not require coherent sources, raster scanning nor time-gated detection and benefits from the compressive sensing strategy. As a proof of concept, we experimentally retrieve the image of a transilluminated target both sandwiched between two holographic diffusers and embedded in a 6mm-thick sample of chicken breast.
|
|
| 11. |
- Durán Bosch, Vicente Andrés, 1977, et al.
(author)
-
Transillumination imaging through biological tissue by single-pixel detection
- 2015
-
In: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9781628417067 ; 9541, s. Artno 95410B-
-
Conference paper (peer-reviewed)abstract
- One challenge that has long held the attention of scientists is that of clearly seeing objects hidden by turbid media, as smoke, fog or biological tissue, which has major implications in fields such as remote sensing or early diagnosis of diseases. Here, we combine structured incoherent illumination and bucket detection for imaging an absorbing object completely embedded in a scattering medium. A sequence of low-intensity microstructured light patterns is launched onto the object, whose image is accurately reconstructed through the light fluctuations measured by a single-pixel detector. Our technique is noninvasive, does not require coherent sources, raster scanning nor time-gated detection and benefits from the compressive sensing strategy. As a proof of concept, we experimentally retrieve the image of a transilluminated target both sandwiched between two holographic diffusers and embedded in a 6mm-thick sample of chicken breast.
|
|
| 12. |
- Fulton, Joel, et al.
(author)
-
Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-gamma (PPAR gamma) are disrupted by retinal disease-associated mutations
- 2017
-
In: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 8
-
Journal article (peer-reviewed)abstract
- Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the nuclear receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand-binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of peroxisome proliferator-activated receptor-gamma (PPAR gamma)/NR1C3 and thyroid hormone receptor b (TRb) TR beta/NR1A2. The binding of PNR to PPAR. was specific for this paralog, as no interaction was observed with the LBDs of PPAR alpha/NR1C1 or PPAR delta/NR1C2. In support of these findings, PPAR. and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPAR. LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPAR gamma complex formation. Wild-type PNR, but not a PNR309G mutant, was able to repress PPAR gamma-mediated transcription in reporter assays. In summary, our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPAR. and TR beta that have potential importance in retinal development and disease.
|
|
| 13. |
- Fulton, Joel, et al.
(author)
-
Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-γ (PPARγ) are disrupted by retinal disease-associated mutations
- 2017
-
In: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 8:3, s. 2677-2677
-
Journal article (peer-reviewed)abstract
- Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the nuclear receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand-binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of peroxisome proliferator-activated receptor-γ (PPARγ)/NR1C3 and thyroid hormone receptor b (TRb) TRβ/NR1A2. The binding of PNR to PPARγ was specific for this paralog, as no interaction was observed with the LBDs of PPARα/NR1C1 or PPARδ/NR1C2. In support of these findings, PPARγ and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild-type PNR, but not a PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary, our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ and TRβ that have potential importance in retinal development and disease.
|
|
| 14. |
- Karmin, Monika, et al.
(author)
-
A recent bottleneck of Y chromosome diversity coincides with a global change in culture.
- 2015
-
In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:4
-
Journal article (peer-reviewed)abstract
- It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
|
|
| 15. |
|
|
| 16. |
- Magtalas, M. C., et al.
(author)
-
Ethnomedicinal plants used for the prevention and treatment of anemia in the Philippines : a systematic review
- 2023
-
In: Tropical Medicine and Health. - 1348-8945 .- 1349-4147. ; 51:1
-
Research review (peer-reviewed)abstract
- Background: Medicinal plants are still used in developing countries, including the Philippines, to treat common diseases in the community. Anemia is a common disease encountered in the community. It is characterized by a lower-than-normal level of red blood cell count. This systematic review identified the medicinal plants used for anemia treatment in the Philippines. Methods: The study was conducted based on the PRISMA flow diagram, starting with a data search on electronic databases. The collected studies were screened based on the inclusion and exclusion criteria. The necessary information was extracted from the eligible research papers, and the studies’ quality was assessed through a developed quality assessment tool. Results: A total of 20 ethnobotanical studies on medicinal plants used for anemia treatment were obtained from different provinces within the 12 regions of the Philippines. Most ethnobotanical studies were conducted in Region X (Northern Mindanao), CAR (Cordillera Administrative Region), and Region XIII (CARAGA), Philippines. The most common plant family is Convovulaceae, with nine records (21.95%), followed by Cucurbitaceae, with six records (14.63%), and Moringaceae, with five records (12.2%). The most common plant part used was the leaves. Others involved mixing different plant parts, with fruits and leaves being the most common combination. The most common route of administration utilized was drinking the decoction, followed by eating the plant. Most medicinal plants used to treat anemia in the Philippines had records of toxicologic (four species, 15.38%) or teratogenic (one species, 3.85%) properties. Eight plant species were reported as nontoxic (30.77%). In addition, ten plant species (38.46%) had no data on toxicity or teratogenicity. Conclusion: There were only 20 ethnobotanical studies that documented the use of plants in treating anemia in the Philippines. This study listed several medicinal plants used in treating anemia in the Philippines. However, pharmacological and toxicological studies are still needed to determine their safety and efficacy in treating anemia in the community.
|
|
| 17. |
|
|
| 18. |
- Beal, Jacob, et al.
(author)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Brodkorb, A., et al.
(author)
-
INFOGEST static in vitro simulation of gastrointestinal food digestion
- 2019
-
In: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 14:4, s. 991-1014
-
Journal article (peer-reviewed)abstract
- Developing a mechanistic understanding of the impact of food structure and composition on human health has increasingly involved simulating digestion in the upper gastrointestinal tract. These simulations have used a wide range of different conditions that often have very little physiological relevance, and this impedes the meaningful comparison of results. The standardized protocol presented here is based on an international consensus developed by the COST INFOGEST network. The method is designed to be used with standard laboratory equipment and requires limited experience to encourage a wide range of researchers to adopt it. It is a static digestion method that uses constant ratios of meal to digestive fluids and a constant pH for each step of digestion. This makes the method simple to use but not suitable for simulating digestion kinetics. Using this method, food samples are subjected to sequential oral, gastric and intestinal digestion while parameters such as electrolytes, enzymes, bile, dilution, pH and time of digestion are based on available physiological data. This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase. The method can be used to assess the endpoints resulting from digestion of foods by analyzing the digestion products (e.g., peptides/amino acids, fatty acids, simple sugars) and evaluating the release of micronutrients from the food matrix. The whole protocol can be completed in ~7 d, including ~5 d required for the determination of enzyme activities.
|
|
| 22. |
|
|
| 23. |
- Clemente, P, et al.
(author)
-
ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5750-
-
Journal article (peer-reviewed)abstract
- Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved. Using Drosophila and mouse models, we demonstrate that non-canonical processing results in the formation of 3′ phosphates, and that phosphatase activity by the carbon catabolite repressor 4 domain-containing family member ANGEL2 is required for their hydrolysis. Furthermore, our data suggest that members of the FAST kinase domain-containing protein family are responsible for these 3′ phosphates. Our results therefore propose a mechanism for non-canonical RNA processing in metazoan mitochondria, by identifying the role of ANGEL2.
|
|
| 24. |
- Clemente, P., et al.
(author)
-
Single-pixel digital ghost holography
- 2012
-
In: Physical Review A - Atomic, Molecular, and Optical Physics. - 2469-9926 .- 2469-9934. ; 86:4
-
Journal article (peer-reviewed)abstract
- Since its discovery, the "ghost" diffraction phenomenon has emerged as an unconventional technique for optical imaging with very promising advantages. However, extracting the intensity and phase information of a structured and realistic object remains a challenge. Here we show that a ghost hologram can be recorded with a single-pixel configuration by adapting concepts from standard digital holography. The presented homodyne scheme enables phase imaging with nanometric depth resolution and three-dimensional focusing ability and shows a high signal-to-noise ratio.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Forzieri, Giovanni, et al.
(author)
-
The Database of European Forest Insect and Disease Disturbances: DEFID2
- 2023
-
In: Global Change Biology. - 1365-2486. ; 29:21, s. 6040-6065
-
Journal article (peer-reviewed)abstract
- Insect and disease outbreaks in forests are biotic disturbances that can profoundly alter ecosystem dynamics. In many parts of the world, these disturbance regimes are intensifying as the climate changes and shifts the distribution of species and biomes. As a result, key forest ecosystem services, such as carbon sequestration, regulation of water flows, wood production, protection of soils, and the conservation of biodiversity, could be increasingly compromised. Despite the relevance of these detrimental effects, there are currently no spatially detailed databases that record insect and disease disturbances on forests at the pan-European scale. Here, we present the new Database of European Forest Insect and Disease Disturbances (DEFID2). It comprises over 650,000 harmonized georeferenced records, mapped as polygons or points, of insects and disease disturbances that occurred between 1963 and 2021 in European forests. The records currently span eight different countries and were acquired through diverse methods (e.g., ground surveys, remote sensing techniques). The records in DEFID2 are described by a set of qualitative attributes, including severity and patterns of damage symptoms, agents, host tree species, climate-driven trigger factors, silvicultural practices, and eventual sanitary interventions. They are further complemented with a satellite-based quantitative characterization of the affected forest areas based on Landsat Normalized Burn Ratio time series, and damage metrics derived from them using the LandTrendr spectral–temporal segmentation algorithm (including onset, duration, magnitude, and rate of the disturbance), and possible interactions with windthrow and wildfire events. The DEFID2 database is a novel resource for many large-scale applications dealing with biotic disturbances. It offers a unique contribution to design networks of experiments, improve our understanding of ecological processes underlying biotic forest disturbances, monitor their dynamics, and enhance their representation in land-climate models. Further data sharing is encouraged to extend and improve the DEFID2 database continuously. The database is freely available at https://jeodpp.jrc.ec.europa.eu/ftp/jrc-opendata/FOREST/DISTURBANCES/DEFID2/.
|
|
| 28. |
|
|
| 29. |
- Lundgren, S, et al.
(author)
-
Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia
- 2021
-
In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:115, s. 1365-1379
-
Journal article (peer-reviewed)abstract
- The prevalence and functional impact of somatic mutations in nonleukemic T cells is not well characterized, although clonal T-cell expansions are common. In immune-mediated aplastic anemia (AA), cytotoxic T-cell expansions are shown to participate in disease pathogenesis. We investigated the mutation profiles of T cells in AA by a custom panel of 2533 genes. We sequenced CD4+ and CD8+ T cells of 24 AA patients and compared the results to 20 healthy controls and whole-exome sequencing of 37 patients with AA. Somatic variants were common both in patients and healthy controls but enriched to AA patients’ CD8+ T cells, which accumulated most mutations on JAK-STAT and MAPK pathways. Mutation burden was associated with CD8+ T-cell clonality, assessed by T-cell receptor beta sequencing. To understand the effect of mutations, we performed single-cell sequencing of AA patients carrying STAT3 or other mutations in CD8+ T cells. STAT3 mutated clone was cytotoxic, clearly distinguishable from other CD8+ T cells, and attenuated by successful immunosuppressive treatment. Our results suggest that somatic mutations in T cells are common, associate with clonality, and can alter T-cell phenotype, warranting further investigation of their role in the pathogenesis of AA.
|
|
| 30. |
|
|
| 31. |
- Mastinu, Enzo, 1987, et al.
(author)
-
Grip control and motor coordination with implanted and surface electrodes while grasping with an osseointegrated prosthetic hand
- 2019
-
In: Journal of Neuroengineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 16:1
-
Journal article (peer-reviewed)abstract
- Background: Replacement of a lost limb by an artificial substitute is not yet ideal. Resolution and coordination of motor control approximating that of a biological limb could dramatically improve the functionality of prosthetic devices, and thus reduce the gap towards a suitable limb replacement. Methods: In this study, we investigated the control resolution and coordination exhibited by subjects with transhumeral amputation who were implanted with epimysial electrodes and an osseointegrated interface that provides bidirectional communication in addition to skeletal attachment (e-OPRA Implant System). We assessed control resolution and coordination in the context of routine and delicate grasping using the Pick and Lift and the Virtual Eggs Tests. Performance when utilizing implanted electrodes was compared with the standard-of-care technology for myoelectric prostheses, namely surface electrodes. Results: Results showed that implanted electrodes provide superior controllability over the prosthetic terminal device compared to conventional surface electrodes. Significant improvements were found in the control of the grip force and its reliability during object transfer. However, these improvements failed to increase motor coordination, and surprisingly decreased the temporal correlation between grip and load forces observed with surface electrodes. We found that despite being more functional and reliable, prosthetic control via implanted electrodes still depended highly on visual feedback. Conclusions: Our findings indicate that incidental sensory feedback (visual, auditory, and osseoperceptive in this case) is insufficient for restoring natural grasp behavior in amputees, and support the idea that supplemental tactile sensory feedback is needed to learn and maintain the motor tasks internal model, which could ultimately restore natural grasp behavior in subjects using prosthetic hands. © 2019 The Author(s).
|
|
| 32. |
|
|
| 33. |
- Nowotny, H, et al.
(author)
-
Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis
- 2021
-
In: Endocrine. - : Springer Science and Business Media LLC. - 1559-0100 .- 1355-008X. ; 7371:23, s. 586-594
-
Journal article (peer-reviewed)abstract
- Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.
|
|
| 34. |
- Olive, M, et al.
(author)
-
Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions
- 2019
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1396-
-
Journal article (peer-reviewed)abstract
- Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.
|
|
| 35. |
- Ortiz Catalan, Max Jair, 1982, et al.
(author)
-
A highly integrated bionic hand with neural control and feedback for use in daily life
- 2023
-
In: Science Robotics. - 2470-9476. ; 8:83
-
Journal article (peer-reviewed)abstract
- Restoration of sensorimotor function after amputation has remained challenging because of the lack of human-machine interfaces that provide reliable control, feedback, and attachment. Here, we present the clinical implementation of a transradial neuromusculoskeletal prosthesis-a bionic hand connected directly to the user's nervous and skeletal systems. In one person with unilateral below-elbow amputation, titanium implants were placed intramedullary in the radius and ulna bones, and electromuscular constructs were created surgically by transferring the severed nerves to free muscle grafts. The native muscles, free muscle grafts, and ulnar nerve were implanted with electrodes. Percutaneous extensions from the titanium implants provided direct skeletal attachment and bidirectional communication between the implanted electrodes and a prosthetic hand. Operation of the bionic hand in daily life resulted in improved prosthetic function, reduced postamputation, and increased quality of life. Sensations elicited via direct neural stimulation were consistently perceived on the phantom hand throughout the study. To date, the patient continues using the prosthesis in daily life. The functionality of conventional artificial limbs is hindered by discomfort and limited and unreliable control. Neuromusculoskeletal interfaces can overcome these hurdles and provide the means for the everyday use of a prosthesis with reliable neural control fixated into the skeleton.
|
|
| 36. |
|
|
| 37. |
- Pierrotti, Ligia C., et al.
(author)
-
Efficacy of beta-lactam/beta-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)
- 2021
-
In: Transplant Infectious Disease. - : John Wiley & Sons. - 1398-2273 .- 1399-3062. ; 23:3
-
Journal article (peer-reviewed)abstract
- Background Whether active therapy with beta-lactam/beta-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. Methods We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. Results Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count <= 500 cells/mu L at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. Conclusions Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
|
|
| 38. |
- Saeed, Kordo, et al.
(author)
-
The early identification of disease progression in patients with suspected infection presenting to the emergency department : A multi-centre derivation and validation study
- 2019
-
In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 23:1
-
Journal article (peer-reviewed)abstract
- Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. Methods: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. Results: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. Conclusions: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.
|
|
| 39. |
- Siibak, Triinu, et al.
(author)
-
A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma
- 2017
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:13, s. 2515-2525
-
Journal article (peer-reviewed)abstract
- Mutations in the mitochondrial DNA polymerase, POLG, are associated with a variety of clinical presentations, ranging from early onset fatal brain disease in Alpers syndrome to chronic progressive external ophthalmoplegia. The majority of mutations are linked with disturbances of mitochondrial DNA (mtDNA) integrity and maintenance. On a molecular level, depending on their location within the enzyme, mutations either lead to mtDNA depletion or the accumulation of multiple mtDNA deletions, and in some cases these molecular changes can be correlated to the clinical presentation. We identified a patient with a dominant p.Y955H mutation in POLG, presenting with a severe, early-onset multi-systemic mitochondrial disease with bilateral sensorineural hearing loss, cataract, myopathy, and liver failure. Using a combination of disease models of Drosophila melanogaster and in vitro biochemistry analysis, we compare the molecular consequences of the p.Y955H mutation to the well-documented p.Y955C mutation. We demonstrate that both mutations affect mtDNA replication and display a dominant negative effect, with the p.Y955H allele resulting in a more severe polymerase dysfunction.
|
|
| 40. |
|
|
