2,744 research outputs found
Evaluation of a multidisciplinary Tier 3 weight management service for adults with morbid obesity, or obesity and comorbidities, based in primary care
A multidisciplinary Tier 3 weight management service in primary care recruited patients with a body mass index ≥40 kg·m−2, or 30 kg·m−2 with obesity-related co-morbidity to a 1-year programme. A cohort of 230 participants was recruited and evaluated using the National Obesity Observatory Standard Evaluation Framework. The primary outcome was weight loss of at least 5% of baseline weight at 12 months. Diet was assessed using the two-item food frequency questionnaire, activity using the General Practice Physical Activity questionnaire and quality of life using the EuroQol-5D-5L questionnaire. A focus group explored the participants' experiences. Baseline mean weight was 124.4 kg and mean body mass index was 44.1 kg·m−2. A total of 102 participants achieved 5% weight loss at 12 months. The mean weight loss was 10.2 kg among the 117 participants who completed the 12-month programme. Baseline observation carried forward analysis gave a mean weight loss of 5.9 kg at 12 months. Fruit and vegetable intake, activity level and quality of life all improved. The dropout rate was 14.3% at 6 months and 45.1% at 1 year. Focus group participants described high levels of satisfaction. It was possible to deliver a Tier 3 weight management service for obese patients with complex co-morbidity in a primary care setting with a full multidisciplinary team, which obtained good health outcomes compared with existing services
Mitochondrial aminoacyl-tRNA synthetases trigger unique compensatory mechanisms in neurons
\ua9 The Author(s) 2023. Published by Oxford University Press. Mitochondrial aminoacyl-tRNA synthetase (mt-ARS) mutations cause severe, progressive, and often lethal diseases with highly heterogeneous and tissue-specific clinical manifestations. This study investigates the molecular mechanisms triggered by three different mt-ARS defects caused by biallelic mutations in AARS2, EARS2, and RARS2, using an in vitro model of human neuronal cells. We report distinct molecular mechanisms of mitochondrial dysfunction among the mt-ARS defects studied. Our findings highlight the ability of proliferating neuronal progenitor cells (iNPCs) to compensate for mitochondrial translation defects and maintain balanced levels of oxidative phosphorylation (OXPHOS) components, which becomes more challenging in mature neurons. Mutant iNPCs exhibit unique compensatory mechanisms, involving specific branches of the integrated stress response, which may be gene-specific or related to the severity of the mitochondrial translation defect. RNA sequencing revealed distinct transcriptomic profiles showing dysregulation of neuronal differentiation and protein translation. This study provides valuable insights into the tissue-specific compensatory mechanisms potentially underlying the phenotypes of patients with mt-ARS defects. Our novel in vitro model may more accurately represent the neurological presentation of patients and offer an improved platform for future investigations and therapeutic development
Predicting consumer biomass, size-structure, production, catch potential, responses to fishing and associated uncertainties in the world's marine ecosystems
Existing estimates of fish and consumer biomass in the world’s oceans are disparate. This creates uncertainty about the roles of fish and other consumers in biogeochemical cycles and ecosystem processes, the extent of human and environmental impacts and fishery potential. We develop and use a size-based macroecological model to assess the effects of parameter uncertainty on predicted consumer biomass, production and distribution. Resulting uncertainty is large (e.g. median global biomass 4.9 billion tonnes for consumers weighing 1 g to 1000 kg; 50% uncertainty intervals of 2 to 10.4 billion tonnes; 90% uncertainty intervals of 0.3 to 26.1 billion tonnes) and driven primarily by uncertainty in trophic transfer efficiency and its relationship with predator-prey body mass ratios. Even the upper uncertainty intervals for global predictions of consumer biomass demonstrate the remarkable scarcity of marine consumers, with less than one part in 30 million by volume of the global oceans comprising tissue of macroscopic animals. Thus the apparently high densities of marine life seen in surface and coastal waters and frequently visited abundance hotspots will likely give many in society a false impression of the abundance of marine animals. Unexploited baseline biomass predictions from the simple macroecological model were used to calibrate a more complex size- and trait-based model to estimate fisheries yield and impacts. Yields are highly dependent on baseline biomass and fisheries selectivity. Predicted global sustainable fisheries yield increases ≈4 fold when smaller individuals (< 20 cm from species of maximum mass < 1kg) are targeted in all oceans, but the predicted yields would rarely be accessible in practice and this fishing strategy leads to the collapse of larger species if fishing mortality rates on different size classes cannot be decoupled. Our analyses show that models with minimal parameter demands that are based on a few established ecological principles can support equitable analysis and comparison of diverse ecosystems. The analyses provide insights into the effects of parameter uncertainty on global biomass and production estimates, which have yet to be achieved with complex models, and will therefore help to highlight priorities for future research and data collection. However, the focus on simple model structures and global processes means that non-phytoplankton primary production and several groups, structures and processes of ecological and conservation interest are not represented. Consequently, our simple models become increasingly less useful than more complex alternatives when addressing questions about food web structure and function, biodiversity, resilience and human impacts at smaller scales and for areas closer to coasts
Institutional change in the European Parliament:balancing legislative ethics and parliamentary independence
The structure of protostellar envelopes derived from submillimeter continuum images
High dynamic range imaging of submillimeter dust emission from the envelopes
of eight young protostars in the Taurus and Perseus star-forming regions has
been carried out using the SCUBA submillimeter camera on the James Clerk
Maxwell Telescope. Good correspondence between the spectral classifications of
the protostars and the spatial distributions of their dust emission is
observed, in the sense that those with cooler spectral energy distributions
also have a larger fraction of the submillimeter flux originating in an
extended envelope compared with a disk. This results from the cool sources
having more massive envelopes rather than warm sources having larger disks.
Azimuthally-averaged radial profiles of the dust emission are used to derive
the power-law index of the envelope density distributions, p (defined by rho
proportional to r^-p), and most of the sources are found to have values of p
consistent with those predicted by models of cloud collapse. However, the
youngest protostars in our sample, L1527 and HH211-mm, deviate significantly
from the theoretical predictions, exhibiting values of p somewhat lower than
can be accounted for by existing models. For L1527 heating of the envelope by
shocks where the outflow impinges on the surrounding medium may explain our
result. For HH211-mm another explanation is needed, and one possibility is that
a shallow density profile is being maintained in the outer envelope by magnetic
fields and/or turbulence. If this is the case star formation must be determined
by the rate at which the support is lost from the cloud, rather than the
hydrodynamical properties of the envelope, such as the sound speed.Comment: Accepted for publication in the Astrophysical Journa
T Cells Activated by Zwitterionic Molecules Prevent Abscesses Induced by Pathogenic Bacteria
Immunologic paradigms classify bacterial polysaccharides as T cell-independent antigens. However, these models fail to explain how zwitterionic polysaccharides (Zps) confer protection against intraabdominal abscess formation in a T cell-dependent manner. Here, we demonstrate that Zps elicit a potent CD4+ T cell response in vitro that requires available major histocompatibility complex class II molecules on antigen-presenting cells. Specific chemical modifications to Zps show that: 1) the activity is specific for carbohydrate structure, and 2) the proliferative response depends upon free amino and carboxyl groups on the repeating units of these polysaccharides. Peptides synthesized to mimic the zwitterionic charge motif associated with Zps also exhibited these biologic properties. Lysine-aspartic acid (KD) peptides with more than 15 repeating units stimulated CD4+ T cells in vitro and conferred protection against abscesses induced by bacteria such as Bacteroides fragilis and Staphylococcus aureus. Evidence for the biologic importance of T cell activation by these zwitterionic polymers was provided when human CD4+ T cells stimulated with these molecules in vitro and adoptively transferred to rats in vivo conferred protection against intraabdominal abscesses induced by viable bacterial challenge. These studies demonstrate that bacterial polysaccharides with a distinct charge motif activate T cells and that this activity confers immunity to a distinct pathologic response to bacterial infection
Activated Ion Electron Capture Dissociation (AI ECD) of proteins: synchronization of infrared and electron irradiation with ion magnetron motion.
Here, we show that to perform activated ion electron capture dissociation (AI-ECD) in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer equipped with a CO(2) laser, it is necessary to synchronize both infrared irradiation and electron capture dissociation with ion magnetron motion. This requirement is essential for instruments in which the infrared laser is angled off-axis, such as the Thermo Finnigan LTQ FT. Generally, the electron irradiation time required for proteins is much shorter (ms) than that required for peptides (tens of ms), and the modulation of ECD, AI ECD, and infrared multiphoton dissociation (IRMPD) with ion magnetron motion is more pronounced. We have optimized AI ECD for ubiquitin, cytochrome c, and myoglobin; however the results can be extended to other proteins. We demonstrate that pre-ECD and post-ECD activation are physically different and display different kinetics. We also demonstrate how, by use of appropriate AI ECD time sequences and normalization, the kinetics of protein gas-phase refolding can be deconvoluted from the diffusion of the ion cloud and measured on the time scale longer than the period of ion magnetron motion
The pion-three-nucleon problem with two-cluster connected-kernel equations
It is found that the coupled piNNN-NNN system breaks into fragments in a
nontrivial way. Assuming the particles as distinguishable, there are indeed
four modes of fragmentation into two clusters, while in the standard three-body
problem there are three possible two-cluster partitions and conversely the
four-body problem has seven different possibilities. It is shown how to
formulate the pion-three-nucleon collision problem through the
integral-equation approach by taking into account the proper fragmentation of
the system. The final result does not depend on the assumption of separability
of the two-body t-matrices. Then, the quasiparticle method a' la
Grassberger-Sandhas is applied and effective two-cluster connected-kernel
equations are obtained. The corresponding bound-state problem is also
formulated, and the resulting homogeneous equation provides a new approach
which generalizes the commonly used techniques to describe the three-nucleon
bound-state problem, where the meson degrees of freedom are usually suppressed.Comment: 20 pages, REVTeX, with 3 COLOR figures (PostScript
Finite formation time effects in quasi-elastic scattering on nuclear targets
The problem of the final state interaction in quasi-elastic
scattering at large , is investigated by exploiting the idea that the
ejected nucleon needs a finite amount of time to assume its asymptotic form. It
is shown that when the dependence of the scattering amplitude of the ejected
nucleon on its virtuality is taken into account, the final state interaction is
decreased. The developed approach is simpler to implement than the one based on
the color transparency description of the damping of the final state
interaction, and is essentially equivalent to the latter in the case of the
single rescattering term. The process on the deuteron is numerically
investigated and it is shown that, at , appreciable finite formation time
effects at of the order of 10 (GeV/c) are expected.Comment: 23 pages, 3 figure
The Relative to Suppression in Proton-Nucleus and Nucleus-Nucleus Collisions
We calculate the nuclear suppression for and production
within a coupled channel approach in the subspace of the and
states. We are able to explain, why (i) the and show the same
suppression from to in proton-nucleus collisions and why
(ii) the is absorbed more strongly than the in nucleus-nucleus
collisions at . The numerical result which includes only interactions
with nucleons acconts for half of the observed suppression in sulphur-uranium
collisions.Comment: 8 pages, LATEX, 3 uuencoded figure
- …