This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive ...assessment (Photochemical and Photobiological Sciences, 2019, 18, 595–828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.
This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an ...update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595-828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases.
The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the ...stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth’s surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1–67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.
The standard of care for the definitive treatment of locoregionally advanced cervical cancer is external beam radiation therapy (EBRT) with concurrent chemotherapy followed by a brachytherapy boost. ...Historically, EBRT was delivered via a two-dimensional technique based primarily on bony landmarks. This gave way to three-dimensional conformal radiation therapy, which allows for dose calculation and adjustment based on individual tumour and patient anatomy. Further technological advances have established intensity-modulated radiation therapy (IMRT) as a standard treatment modality, given the ability to maintain tumoricidal doses to target volumes while reducing unwanted radiation dose to nearby critical structures, thereby reducing toxicity. Routine image guidance allows for increased confidence in patient alignment prior to treatment, and the ability to visualise the daily position of the targets and organs at risk has been instrumental in allowing safe reductions in treated volumes. Additional EBRT technologies, including proton therapy and stereotactic body radiation therapy, may further improve the therapeutic index. In the realm of brachytherapy, a shift from point-based dose planning to image-guided brachytherapy has been associated with improved local control and reduced toxicity, with additional refinement ongoing. Here we will discuss these advances, the supporting data and future directions.
Intrahepatic cholestasis of pregnancy (ICP) has a complex aetiology with a significant genetic component. ABCB11 encodes the bile salt export pump (BSEP); mutations cause a spectrum of cholestatic ...disease, and are implicated in the aetiology of ICP.
ABCB11 variation in ICP was investigated by screening for five mutant alleles (E297G, D482G, N591S, D676Y and G855R) and the V444A polymorphism (c.1331T>C, rs2287622) in two ICP cohorts (n = 333 UK, n = 158 continental Europe), and controls (n = 261) for V444A. PCR primers were used to amplify and sequence patient and control DNA. The molecular basis for the observed phenotypes was investigated in silico by analysing the equivalent residues in the structure of the homologous bacterial transporter Sav1866.
E297G was observed four times and D482G once. N591S was present in two patients; D676Y and G855R were not observed. The V444A polymorphism was associated with ICP (allelic analysis for C vs T: OR 1.7 (95% CI 1.4 to 2.1, p<0.001)). In addition, CC homozygotes were more likely to have ICP than TT homozygotes: OR 2.8 (95% CI 1.7 to 4.4 p<0.0001). Structural analyses suggest that E297G and D482G destabilize the protein fold of BSEP. The molecular basis of V444A and N591S was not apparent from the Sav1866 structure.
Heterozygosity for the common ABCB11 mutations accounts for 1% of European ICP cases; these two mutants probably reduce the folding efficiency of BSEP. N591S is a recurrent mutation; however, the mechanism may be independent of protein stability or function. The V444A polymorphism is a significant risk factor for ICP in this population.
This experiment compared Holstein-Friesian (HF) cows of New Zealand (NZ) origin representative of genetics present in the 1970s (NZ70; n=45) and 1990s (NZ90; n=60), and a group of HF cows of North ...American origin with 1990s genetics (NA90; n=60), which were managed in grazing systems with a range of feeding allowances (4.5 to 7.0 t/cow per yr) over 3 yr. The NZ70 cows had the lowest Breeding Worth genetic index and the lowest breeding values for yields of fat, protein, and milk volume; the NZ90 and NA90 cows were selected to have similar breeding values for milk traits and were representative of cows of high genetic merit in the 1990s. The NZ90 cows had a higher milk protein concentration (3.71%) than either the NA90 (3.43%) or the NZ70 cows (3.41%), and a higher milk fat concentration (4.86%) than the NA90 cows (4.26%) with a level similar to the NZ70 cows (4.65%). The NZ90 cows produced significantly greater yields of fat, protein, and lactose than the NA90 and NZ70 cows. The NZ70 cows had the lowest mean annual body weight (473kg) but the highest body condition score (BCS; 5.06). Days in milk were the same for the 2 NZ strains (286 d in milk), both of which were greater than the NA90 cows (252 d in milk). There was no genotype × environment interaction for combined milk fat and protein yield (milksolids), with NZ90 producing 52 kg/cow more than the NA90 at all feeding levels. The NZ70 strain had the highest seasonal average BCS (5.06), followed by the NZ90 (4.51) and the NA90 (4.13) strains on a 1 to 10 scale. Body condition score increased with higher feeding levels in the 2 NZ strains, but not in the NA strain. The first-parity cows commenced luteal activity 11 d later than older cows (parities 2 and 3), and the NA90 cows commenced luteal activity 4 and 10 d earlier than the NZ70 and NZ90 cows. Earlier estrus activity did not result in a higher in-calf rate. The NZ70 and NZ90 cows had similar in-calf rates (pregnancy diagnosed to 6 wk; 69%), which were higher than those achieved by NA90 cows (54%). Results showed that the NA90 strain used in this experiment was not suitable for traditional NZ grazing systems. Grazing systems need to be modified if the NA90 strain is to be successfully farmed in NZ. The data reported here show that the NA90 cows require large amounts of feed, but this will not prevent them from having a lower BCS than the NZ strains. Combined with poor reproductive performance, this means that NA90 cows are less productive than NZ HF in pasture-based seasonal calving systems with low levels of supplementation.
Models of synaptic plasticity have been used to better understand neural development as well as learning and memory. One prominent classic model is the Bienenstock-Cooper-Munro (BCM) model that has ...been particularly successful in explaining plasticity of the visual cortex. Here, in an effort to include more biophysical detail in the BCM model, we incorporate 1) feedforward inhibition, and 2) the experimental observation that large synapses are relatively harder to potentiate than weak ones, while synaptic depression is proportional to the synaptic strength. These modifications change the outcome of unsupervised plasticity under the BCM model. The amount of feed-forward inhibition adds a parameter to BCM that turns out to determine the strength of competition. In the limit of strong inhibition the learning outcome is identical to standard BCM and the neuron becomes selective to one stimulus only (winner-take-all). For smaller values of inhibition, competition is weaker and the receptive fields are less selective. However, both BCM variants can yield realistic receptive fields.
To examine how common patient factors affect screening mammographic sensitivity and cancer stage at diagnosis.
The authors used a population-based database of 183,134 screening mammograms and a ...statewide tumor registry to identify 807 breast cancers detected at screening mammography.
Sensitivity varied significantly with ethnicity, use of estrogen replacement therapy, mammographic breast density, and age. Sensitivity was 54% (13 of 24) in women younger than 40 years, 77% (121 of 157) in women aged 40-49 years, 78% (224 of 286) in women aged 50-64 years, and 81% (277 of 340) in women older than 64 years. Sensitivity was 68% (162 of 237) for dense breasts and 85% (302 of 356) for nondense breasts and 74% (180 of 244) in estrogen replacement therapy users and 81% (417 of 513) in nonusers. Sensitivity was most markedly reduced with the combination of dense breasts and estrogen replacement therapy use; there was little difference when only one factor was present. Median cancer size and the percentage of early cancers showed little change with any factors.
Age is a minor determinant of mammographic sensitivity in women aged 40 years or older. Sensitivity is substantially decreased with the combination of higher breast density and estrogen replacement therapy use. There was not a notable shift in cancer outcomes in the groups with lower mammographic sensitivity. These data do not support different screening recommendations in women aged 40-49 years or in estrogen replacement therapy users.
ABSTRACT We present the results of SPT-GMOS, a spectroscopic survey with the Gemini Multi-Object Spectrograph (GMOS) on Gemini South. The targets of SPT-GMOS are galaxy clusters identified in the ...SPT-SZ survey, a millimeter-wave survey of 2500 deg2 of the southern sky using the South Pole Telescope (SPT). Multi-object spectroscopic observations of 62 SPT-selected galaxy clusters were performed between 2011 January and 2015 December, yielding spectra with radial velocity measurements for 2595 sources. We identify 2243 of these sources as galaxies, and 352 as stars. Of the galaxies, we identify 1579 as members of SPT-SZ galaxy clusters. The primary goal of these observations was to obtain spectra of cluster member galaxies to estimate cluster redshifts and velocity dispersions. We describe the full spectroscopic data set and resulting data products, including galaxy redshifts, cluster redshifts, and velocity dispersions, and measurements of several well-known spectral indices for each galaxy: the equivalent width, W, of O ii λλ3727, 3729 and H-δ, and the 4000 break strength, D4000. We use the spectral indices to classify galaxies by spectral type (i.e., passive, post-starburst, star-forming), and we match the spectra against photometric catalogs to characterize spectroscopically observed cluster members as a function of brightness (relative to m ). Finally, we report several new measurements of redshifts for ten bright, strongly lensed background galaxies in the cores of eight galaxy clusters. Combining the SPT-GMOS data set with previous spectroscopic follow-up of SPT-SZ galaxy clusters results in spectroscopic measurements for >100 clusters, or ∼20% of the full SPT-SZ sample.
Pregnancy alters bile acid homeostasis and can unmask cholestatic disease in genetically predisposed but otherwise asymptomatic individuals. In this report, we show that normal pregnant mice have ...raised hepatic bile acid levels in the presence of procholestatic gene expression. The nuclear receptor farnesoid X receptor (FXR) regulates the transcription of the majority of these genes, and we show that both ablation and activation of Fxr prevent the accumulation of hepatic bile acids during pregnancy. These observations suggest that the function of Fxr may be perturbed during gestation. In subsequent in vitro experiments, serum from pregnant mice and humans was found to repress expression of the Fxr target gene, small heterodimer partner (Shp), in liver‐derived Fao cells. Estradiol or estradiol metabolites may contribute to this effect because coincubation with the estrogen receptor (ER) antagonist fulvestrant (ICI 182780) abolished the repressive effects on Shp expression. Finally, we report that ERα interacts with FXR in an estradiol‐dependent manner and represses its function in vitro. Conclusion: Ligand‐activated ERα may inhibit FXR function during pregnancy and result in procholestatic gene expression and raised hepatic bile acid levels. We propose that this could cause intrahepatic cholestasis of pregnancy in genetically predisposed individuals. HEPATOLOGY 2010
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