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The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species' geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Research question: The purpose of this study was to evaluate the test-retest reliability of lower extremity kinematics during squat, hip abduction and lunge exercises captured by the Kinect and to evaluate the agreement to a reference 3D camera-based motion system. Methods: Twenty-one healthy individuals performed five repetitions of each lower limb exercise on two different days. Movements were simultaneously assessed by the Kinect and the reference 3D motion system. Joint angles and positions of the lower limb were calculated for sagittal and frontal plane. For the inter-session reliability and the agreement between the two systems standard error of measurement (SEM), bias with limits of agreement (LoA) and Pearson Correlation Coefficient (r) were calculated. Results: Parameters indicated varying reliability for the assessed joint angles and positions and decreasing reliability with increasing task complexity. Across all exercises, measurement deviations were shown especially for small movement amplitudes. Variability was acceptable for joint angles and positions during the squat, partially acceptable during the hip abduction and predominately inacceptable during the lunge. The agreement between systems was characterized by systematic errors. Overestimations by the Kinect were apparent for hip flexion during the squat and hip abduction/adduction during the hip abduction exercise as well as for the knee positions during the lunge. Knee and hip flexion during hip abduction and lunge were underestimated by the Kinect. Significance: The Kinect system can reliably assess lower limb joint angles and positions during simple exercises. The validity of the system is however restricted. An application in the field of early orthopedic rehabilitation without further development of post-processing techniques seems so far limited.
Background: Telerehabilitation can contribute to the maintenance of successful rehabilitation regardless of location and time. The aim of this study was to investigate a specific three-month interactive telerehabilitation routine regarding its effectiveness in assisting patients with physical functionality and with returning to work compared to typical aftercare.
Objective: The aim of the study was to investigate a specific three-month interactive telerehabilitation with regard to effectiveness in functioning and return to work compared to usual aftercare.
Methods: From August 2016 to December 2017, 111 patients (mean 54.9 years old; SD 6.8; 54.3% female) with hip or knee replacement were enrolled in the randomized controlled trial. At discharge from inpatient rehabilitation and after three months, their distance in the 6-minute walk test was assessed as the primary endpoint. Other functional parameters, including health related quality of life, pain, and time to return to work, were secondary endpoints.
Results: Patients in the intervention group performed telerehabilitation for an average of 55.0 minutes (SD 9.2) per week. Adherence was high, at over 75%, until the 7th week of the three-month intervention phase. Almost all the patients and therapists used the communication options. Both the intervention group (average difference 88.3 m; SD 57.7; P=.95) and the control group (average difference 79.6 m; SD 48.7; P=.95) increased their distance in the 6-minute-walk-test. Improvements in other functional parameters, as well as in quality of life and pain, were achieved in both groups. The higher proportion of working patients in the intervention group (64.6%; P=.01) versus the control group (46.2%) is of note.
Conclusions: The effect of the investigated telerehabilitation therapy in patients following knee or hip replacement was equivalent to the usual aftercare in terms of functional testing, quality of life, and pain. Since a significantly higher return-to-work rate could be achieved, this therapy might be a promising supplement to established aftercare.
Lanthanide-doped upconverting nanoparticles (UCNP) are being extensively studied for bioapplications due to their unique photoluminescence properties and low toxicity. Interest in RET applications involving UCNP is also increasing, but due to factors such as large sizes, ion emission distributions within the particles, and complicated energy transfer processes within the UCNP, there are still many questions to be answered. In this study, four types of core and core-shell NaYF4-based UCNP co-doped with Yb3+ and Tm3+ as sensitizer and activator, respectively, were investigated as donors for the Methyl 5-(8-decanoylbenzo[1,2-d:4,5-d ']bis([1,3]dioxole)-4-yl)-5-oxopentanoate (DBD-6) dye. The possibility of resonance energy transfer (RET) between UCNP and the DBD-6 attached to their surface was demonstrated based on the comparison of luminescence intensities, band ratios, and decay kinetics. The architecture of UCNP influenced both the luminescence properties and the energy transfer to the dye: UCNP with an inert shell were the brightest, but their RET efficiency was the lowest (17%). Nanoparticles with Tm3+ only in the shell have revealed the highest RET efficiencies (up to 51%) despite the compromised luminescence due to surface quenching.
Background: Telerehabilitation can contribute to the maintenance of successful rehabilitation regardless of location and time. The aim of this study was to investigate a specific three-month interactive telerehabilitation routine regarding its effectiveness in assisting patients with physical functionality and with returning to work compared to typical aftercare.
Objective: The aim of the study was to investigate a specific three-month interactive telerehabilitation with regard to effectiveness in functioning and return to work compared to usual aftercare.
Methods: From August 2016 to December 2017, 111 patients (mean 54.9 years old; SD 6.8; 54.3% female) with hip or knee replacement were enrolled in the randomized controlled trial. At discharge from inpatient rehabilitation and after three months, their distance in the 6-minute walk test was assessed as the primary endpoint. Other functional parameters, including health related quality of life, pain, and time to return to work, were secondary endpoints.
Results: Patients in the intervention group performed telerehabilitation for an average of 55.0 minutes (SD 9.2) per week. Adherence was high, at over 75%, until the 7th week of the three-month intervention phase. Almost all the patients and therapists used the communication options. Both the intervention group (average difference 88.3 m; SD 57.7; P=.95) and the control group (average difference 79.6 m; SD 48.7; P=.95) increased their distance in the 6-minute-walk-test. Improvements in other functional parameters, as well as in quality of life and pain, were achieved in both groups. The higher proportion of working patients in the intervention group (64.6%; P=.01) versus the control group (46.2%) is of note.
Conclusions: The effect of the investigated telerehabilitation therapy in patients following knee or hip replacement was equivalent to the usual aftercare in terms of functional testing, quality of life, and pain. Since a significantly higher return-to-work rate could be achieved, this therapy might be a promising supplement to established aftercare.
Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
Lanthanide-doped upconverting nanoparticles (UCNP) are being extensively studied for bioapplications due to their unique photoluminescence properties and low toxicity. Interest in RET applications involving UCNP is also increasing, but due to factors such as large sizes, ion emission distributions within the particles, and complicated energy transfer processes within the UCNP, there are still many questions to be answered. In this study, four types of core and core-shell NaYF4-based UCNP co-doped with Yb3+ and Tm3+ as sensitizer and activator, respectively, were investigated as donors for the Methyl 5-(8-decanoylbenzo[1,2-d:4,5-d ']bis([1,3]dioxole)-4-yl)-5-oxopentanoate (DBD-6) dye. The possibility of resonance energy transfer (RET) between UCNP and the DBD-6 attached to their surface was demonstrated based on the comparison of luminescence intensities, band ratios, and decay kinetics. The architecture of UCNP influenced both the luminescence properties and the energy transfer to the dye: UCNP with an inert shell were the brightest, but their RET efficiency was the lowest (17%). Nanoparticles with Tm3+ only in the shell have revealed the highest RET efficiencies (up to 51%) despite the compromised luminescence due to surface quenching.
A new generation of wavelength-tunable, fluorescent dyes, so-called DBD ([1,3]dioxolo[4,5-f][1,3]benzodioxole) dyes, were developed a few years ago, and they showed great potential as probes, for example, for fluorescence microscopy. However, their photophysics is not fully explored and leaves open questions regarding their large fluorescence Stokes shifts and sensitivity to solvent conditions of differently substituted DBD dyes. To improve the understanding of the influence of the substitution pattern of the DBD dyes on their respective photophysics, transient absorption spectroscopy (TAS) was used, that is, a pump-probe experiment on the femtosecond timescale. TAS allows measurements of excited states, ground state recovery, solvent relaxation, and fluorescence properties on time scales of up to several nanoseconds. Two different DBD dye samples were investigated: aryl- and ester-substituted DBD dyes. Experiments were carried out in solvents with different polarities using different excitation energies and at different viscosities. Based on the experimental data and theoretical calculations, we were able to determine the conformational changes of the molecule due to electronic excitation and were able to investigate solvent relaxation processes for both types of DBD dyes. By generalizing the theory for quadrupole-induced solvent relaxation developed by Togashi et al., we derived quadrupole moments of both molecules in the ground and excited state. Our data showed differences in the binding of polar solvent molecules to the dyes depending on the substituent on the DBD dye. In the case of water as the solvent, an additional efficient quenching process in the electronically excited state was revealed, which was indicated by the observation of solvated electrons in the TAS signals.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.