In this study, patients treated in ICUs were at high risk for new cognitive impairment during 12 months of follow-up, with 24% of patients having deficits similar in severity to those in Alzheimer's ...disease. A longer duration of delirium was associated with worse cognitive scores.
Survivors of critical illness frequently have a prolonged and poorly understood form of cognitive dysfunction,
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which is characterized by new deficits (or exacerbations of preexisting mild deficits) in global cognition or executive function. This long-term cognitive impairment after critical illness may be a growing public health problem, given the large number of acutely ill patients being treated in intensive care units (ICUs) globally.
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Among older adults, cognitive decline is associated with institutionalization,
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hospitalization,
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and considerable annual societal costs.
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Yet little is known about the epidemiology of long-term cognitive impairment after critical illness.
Delirium, a form of acute brain . . .
We statistically evaluated the relative orientation between gas column density structures, inferred from Herschel submillimetre observations, and the magnetic field projected on the plane of sky, ...inferred from polarized thermal emission of Galactic dust observed by the Balloon-borne Large-Aperture Submillimetre Telescope for Polarimetry (BLASTPol) at 250, 350, and 500 μm, towards the Vela C molecular complex. First, we find very good agreement between the polarization orientations in the three wavelength-bands, suggesting that, at the considered common angular resolution of 3.́0 that corresponds to a physical scale of approximately 0.61 pc, the inferred magnetic field orientation is not significantly affected by temperature or dust grain alignment effects. Second, we find that the relative orientation between gas column density structures and the magnetic field changes progressively with increasing gas column density, from mostly parallel or having no preferred orientation at low column densities to mostly perpendicular at the highest column densities. This observation is in agreement with previous studies by the Planck collaboration towards more nearby molecular clouds. Finally, we find a correspondencebetween (a) the trends in relative orientation between the column density structures and the projected magnetic field; and (b) the shape of the column density probability distribution functions (PDFs). In the sub-regions of Vela C dominated by one clear filamentary structure, or “ridges”, where the high-column density tails of the PDFs are flatter, we find a sharp transition from preferentially parallel or having no preferred relative orientation at low column densities to preferentially perpendicular at highest column densities. In the sub-regions of Vela C dominated by several filamentary structures with multiple orientations, or “nests”, where the maximum values of the column density are smaller than in the ridge-like sub-regions and the high-column density tails of the PDFs are steeper, such a transition is also present, but it is clearly less sharp than in the ridge-like sub-regions. Both of these results suggest that the magnetic field is dynamically important for the formation of density structures in this region.
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We use regional air quality modeling to evaluate the impact of model resolution on uncertainty associated with the human health benefits resulting from proposed air quality regulations. Using a ...regional photochemical model (CAMx), we ran a modeling episode with meteorological inputs simulating conditions as they occurred during August through September 2006 (a period representative of conditions leading to high ozone), and two emissions inventories (a 2006 base case and a 2018 proposed control scenario, both for Houston, Texas) at 36, 12, 4 and 2 km resolution. The base case model performance was evaluated for each resolution against daily maximum 8-h averaged ozone measured at monitoring stations. Results from each resolution were more similar to each other than they were to measured values. Population-weighted ozone concentrations were calculated for each resolution and applied to concentration response functions (with 95% confidence intervals) to estimate the health impacts of modeled ozone reduction from the base case to the control scenario. We found that estimated avoided mortalities were not significantly different between the 2, 4 and 12 km resolution runs, but the 36 km resolution may over-predict some potential health impacts. Given the cost/benefit analysis requirements motivated by Executive Order 12866 as it applies to the Clean Air Act, the uncertainty associated with human health impacts and therefore the results reported in this study, we conclude that health impacts calculated from population weighted ozone concentrations obtained using regional photochemical models at 36 km resolution fall within the range of values obtained using fine (12 km or finer) resolution modeling. However, in some cases, 36 km resolution may not be fine enough to statistically replicate the results achieved using 2, 4 or 12 km resolution. On average, when modeling at 36 km resolution, an estimated 5 deaths per week during the May through September ozone season are avoided because of ozone reductions resulting from the proposed emissions reductions (95% confidence interval was 2-8). When modeling at 2, 4 or 12 km finer scale resolution, on average 4 deaths are avoided due to the same reductions (95% confidence interval was 1-7). Study results show that ozone modeling at a resolution finer than 12 km is unlikely to reduce uncertainty in benefits analysis for this specific region. We suggest that 12 km resolution may be appropriate for uncertainty analyses of health impacts due to ozone control scenarios, in areas with similar chemistry, meteorology and population density, but that resolution requirements should be assessed on a case-by-case basis and revised as confidence intervals for concentration-response functions are updated.
The Enquiring About Tolerance (EAT) study was a randomized trial of the early introduction of allergenic solids into the infant diet from 3 months of age. The intervention effect did not reach ...statistical significance in the intention-to-treat analysis of the primary outcome.
We sought to determine whether infants at high risk of developing a food allergy benefited from early introduction.
A secondary intention-to-treat analysis was performed of 3 groups: nonwhite infants; infants with visible eczema at enrollment, with severity determined by SCORAD; and infants with enrollment food sensitization (specific IgE ≥0.1 kU/L).
Among infants with sensitization to 1 or more foods at enrollment (≥0.1 kU/L), early introduction group (EIG) infants developed significantly less food allergy to 1 or more foods than standard introduction group (SIG) infants (SIG, 34.2%; EIG, 19.2%; P = .03), and among infants with sensitization to egg at enrollment, EIG infants developed less egg allergy (SIG, 48.6%; EIG, 20.0%; P = .01). Similarly, among infants with moderate SCORAD (15-<40) at enrollment, EIG infants developed significantly less food allergy to 1 or more foods (SIG, 46.7%; EIG, 22.6%; P = .048) and less egg allergy (SIG, 43.3%; EIG, 16.1%; P = .02).
Early introduction was effective in preventing the development of food allergy in specific groups of infants at high risk of developing food allergy: those sensitized to egg or to any food at enrollment and those with eczema of increasing severity at enrollment. This efficacy occurred despite low adherence to the early introduction regimen. This has significant implications for the new national infant feeding recommendations that are emerging around the world.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Relaxin-3 (INSL-7) is a recently discovered member of the insulin superfamily. Relaxin-3 mRNA is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus. ...Relaxin-3 binds with high affinity to the LGR7 receptor and to the previously orphan G protein-coupled receptor GPCR135. GPCR135 mRNA is expressed predominantly in the central nervous system, particularly in the paraventricular nucleus (PVN). The presence of relaxin-3 and these receptors in the PVN led us to investigate the effect of central administration of relaxin-3 on food intake in male Wistar rats. The receptor involved in mediating these effects was also investigated. Intracerebroventricular injections of human relaxin-3 (H3) to satiated rats significantly increased food intake 1 h post administration in the early light phase 0.96 ± 0.16 g (vehicle) vs. 1.81 ± 0.21 g (180 pmol H3), P < 0.05 and the early dark phase 2.95 ± 0.45 g (vehicle) vs. 4.39 ± 0.39 g (180 pmol H3), P < 0.05. Intra-PVN H3 administration significantly increased 1-h food intake in satiated rats in the early light phase 0.34 ± 0.16 g (vehicle) vs. 1.23 ± 0.30 g (18 pmol H3), P < 0.05 and the early dark phase 4.43 ± 0.32 g (vehicle) vs. 6.57 ± 0.42 g (18 pmol H3), P < 0.05. Feeding behavior increased after intra-PVN H3. Equimolar doses of human relaxin-2, which binds the LGR7 receptor but not GPCR135, did not increase feeding. Hypothalamic neuropeptide Y, proopiomelanocortin, or agouti-related peptide mRNA expression did not change after acute intracerebroventricular H3. These results suggest a novel role for relaxin-3 in appetite regulation.
Summary
Background
Guidelines for follow‐up of patients with melanoma are based on limited evidence.
Objectives
To guide skin surveillance, we developed a risk prediction model for subsequent primary ...melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors.
Methods
Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population‐based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years’ follow‐up via the cancer registry. Discrimination and calibration were assessed.
Results
The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C‐statistic was 0·73 95% confidence interval (CI) 0·68–0·77, 0·65 (95% CI 0·62–0·68) and 0·65 (95% CI 0·61–0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87–5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score.
Conclusions
The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education.
What's already known about this topic?
Current guidelines for the frequency and length of follow‐up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence.
People with one or more primary melanomas have, on average, a higher risk of developing another primary invasive melanoma, compared with the general population, but an accurate way of estimating individual risk is needed.
What does this study add?
We provide a comprehensive risk prediction model for subsequent primary melanomas, using data from 1266 participants with melanoma (2613 primary melanomas), over a median 14 years’ follow‐up.
The model includes 12 risk factors comprising demographic, phenotypical, histopathological and genomic factors, and sun exposure.
It enables estimation of the absolute risk of subsequent primary melanomas, and can be used to tailor surveillance intensity, communicate individual risk and provide patient education.
Linked Comment: Robinson. Br J Dermatol 2020; 182:1081.
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ABSTRACT
Membrane type 1 metalloprotease (MT1‐MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components ...and indirectly by activating pro‐MMP 2. We investigated the effects of MT1‐MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1‐MMP or MMP‐2. MT1‐MMP and MMP‐2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1‐MMP 1) were able to activate endogenous or exogenous pro‐MMP‐2, 2) displayed an enhanced in vitro invasiveness through matrigel‐coated filters independent of MMP‐2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutanously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1‐MMP regardless of MMP‐2 expression levels, suggesting that the production of MMP‐2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1‐MMP‐producing cells was associated with an up‐regulation of VEGF expression. These results emphasize the importance of MT1‐MMP during tumor angiogenesis and open new opportunities for the development of anti‐angiogenic strategies combining inhibitors of MT1‐MMP and VEGF antagonists.—Sounni, N. E., Devy, L., Hajitou, A., Frankenne, F., Munaut, C., Gilles, C., Deroanne, C., Thompson, E. W., Foidart, J. M., Noel, A. MT1‐MMP expression promotes tumor growth and angiogenesis through an up‐regulation of vascular en‐dothelial growth factor expression. FASEB J. 16, 555–564 (2002)
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The Met Office Global and Regional Ensemble Prediction System–Global (MOGREPS‐G) used an ensemble transform Kalman filter (ETKF) to perturb its initial conditions from its operational implementation ...in September 2008 until December 2019. In 2019, MOGREPS‐G became the first operational atmospheric ensemble to apply hybrid four‐dimensional ensemble variational data assimilation (En‐4DEnVar) to each of the 44 perturbed ensemble members. Other enhancements have also been added, including to the inflation used to improve ensemble spread. The combined impact of these changes on ensemble forecasts is overwhelmingly positive but initially more neutral for deterministic forecasts, which also use the ensemble to represent flow‐dependent forecast errors in their hybrid data assimilation updates. The latter result is not a surprise, because the deterministic forecast's hybrid data assimilation was initially weighted more strongly to the modelled stationary covariance component and not optimised to take full advantage of the upgraded ensemble. A subsequent operational upgrade in December 2020 has introduced shifting in addition to lagging to exploit the ensemble better in the deterministic forecast's hybrid data assimilation by including ensemble members from a previous cycle and also from adjacent forecast lead times to augment the ensemble without having to run additional forecasts. More weight has since been given to the ensemble in the deterministic forecast's hybrid data assimilation in May 2022. A key motive for adopting hybrid 4DEnVar in MOGREPS‐G is to reduce maintenance overheads by virtue of sharing much of the deterministic forecast system's data assimilation code. This also enables the ensemble to assimilate almost all observation types used by the deterministic forecast. The updated system also exploits parallelism better so as to be fast enough for operational use, despite assimilating more observations and being more computationally expensive than the Met Office's ETKF.
In December 2019, the Met Office MOGREPS‐G global atmospheric ensemble introduced an ensemble of data assimilations, applying four‐dimensional ensemble variational data assimilation to each member. The upgrade also includes additive inflation and ensemble relaxation techniques. Ensemble spread, in particular, has improved, shown by comparing the ratio of averaged root‐mean‐square error of the ensemble mean with the averaged ensemble spread for 250‐hPa temperature six hours after the cycle time for the original (top) and upgraded systems (bottom).
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Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms. The Multicentre Aneurysm Screening Study was designed to assess whether or not such ...screening is beneficial.
A population-based sample of men (n=67 800) aged 65–74 years was enrolled, and each individual randomly allocated to either receive an invitation for an abdominal ultrasound scan (invited group, n=33 839) or not (control group, n=33 961). Men in whom abdominal aortic aneurysms (⩾3 cm in diameter) were detected were followed-up with repeat ultrasound scans for a mean of 4·1 years. Surgery was considered on specific criteria (diameter ⩾5·5 cm, expansion ⩾1 cm per year, symptoms). Mortality data were obtained from the Office of National Statistics, and an intention-to-treat analysis was based on cause of death. Quality of life was assessed with four standardised scales. The primary outcome measure was mortality related to abdominal aortic aneurysm.
27 147 of 33 839 (80%) men in the invited group accepted the invitation to screening, and 1333 aneurysms were detected. There were 65 aneurysm-related deaths (absolute risk 0·19%) in the invited group, and 113 (0·33%) in the control group (risk reduction 42%, 95% CI 22–58; p=0·0002), with a 53% reduction (95% CI 30–64) in those who attended screening. 30-day mortality was 6% (24 of 414) after elective surgery for an aneurysm, and 37% (30 of 81) after emergency surgery.
Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SIK, UILJ, UKNU, UL, UM, UPCLJ, UPUK, VSZLJ
The COVID‐19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While ...several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies’ preparedness for future pandemics. On June 1–4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium “Progress in Vaccine Development for Infectious Diseases” to discuss state‐of‐the‐art technologies, recent advancements in understanding vaccine‐mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
On June 1–4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium “Progress in Vaccine Development for Infectious Diseases” to discuss state‐of‐the‐art technologies, recent advancements in understanding vaccine‐mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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