Late Quaternary separation of Britain from mainland Europe is considered to be a consequence of spillover of a large proglacial lake in the Southern North Sea basin. Lake spillover is inferred to ...have caused breaching of a rock ridge at the Dover Strait, although this hypothesis remains untested. Here we show that opening of the Strait involved at least two major episodes of erosion. Sub-bottom records reveal a remarkable set of sediment-infilled depressions that are deeply incised into bedrock that we interpret as giant plunge pools. These support a model of initial erosion of the Dover Strait by lake overspill, plunge pool erosion by waterfalls and subsequent dam breaching. Cross-cutting of these landforms by a prominent bedrock-eroded valley that is characterized by features associated with catastrophic flooding indicates final breaching of the Strait by high-magnitude flows. These events set-up conditions for island Britain during sea-level highstands and caused large-scale re-routing of NW European drainage.
Energy expenditure in rock/pop drumming De La Rue, S E; Draper, S B; Potter, C R ...
International journal of sports medicine,
10/2013, Letnik:
34, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Despite the vigorous nature of rock/pop drumming, there are no precise data on the energy expenditure of this activity. The aim of this study was to quantify the energy cost of rock/pop drumming. ...Fourteen male drummers (mean±SD; age 27±8 yrs.) completed an incremental drumming test to establish the relationship between energy expenditure and heart rate for this activity and a ramped cycle ergometer test to exhaustion as a criterion measure for peak values (oxygen uptake and heart rate). During live concert performance heart rate was continuously measured and used to estimate energy expenditure (from the energy expenditure vs. heart rate data derived from the drumming test). During concert performance, estimated energy expenditure (mean±SD) was 623±168 kcal.h⁻¹ (8.1±2.2 METs) during performances of 38.6±15.6 min, and drummers achieved a peak heart rate of 186±16 b.min⁻¹. During the drumming test participants attained 78.7±8.3% of the cycle ergometer peak oxygen uptake. Rock/pop drumming represents a relatively high-intensity form of physical activity and as such involves significant energy expenditure. Rock/pop drumming should be considered as a viable alternative to more traditional forms of physical activity.
Alzheimer's disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in ...the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma ...(EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Euclid preparation Pocino, A.; Tutusaus, I.; Fosalba, P. ...
Astronomy and astrophysics (Berlin),
11/2021, Letnik:
655
Journal Article
Recenzirano
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Photometric redshifts (photo-
z
s) are one of the main ingredients in the analysis of cosmological probes. Their accuracy particularly affects the results of the analyses of galaxy clustering with ...photometrically selected galaxies (GC
ph
) and weak lensing. In the next decade, space missions such as
Euclid
will collect precise and accurate photometric measurements for millions of galaxies. These data should be complemented with upcoming ground-based observations to derive precise and accurate photo-
z
s. In this article we explore how the tomographic redshift binning and depth of ground-based observations will affect the cosmological constraints expected from the
Euclid
mission. We focus on GC
ph
and extend the study to include galaxy-galaxy lensing (GGL). We add a layer of complexity to the analysis by simulating several realistic photo-
z
distributions based on the
Euclid
Consortium Flagship simulation and using a machine learning photo-
z
algorithm. We then use the Fisher matrix formalism together with these galaxy samples to study the cosmological constraining power as a function of redshift binning, survey depth, and photo-
z
accuracy. We find that bins with an equal width in redshift provide a higher figure of merit (FoM) than equipopulated bins and that increasing the number of redshift bins from ten to 13 improves the FoM by 35% and 15% for GC
ph
and its combination with GGL, respectively. For GC
ph
, an increase in the survey depth provides a higher FoM. However, when we include faint galaxies beyond the limit of the spectroscopic training data, the resulting FoM decreases because of the spurious photo-
z
s. When combining GC
ph
and GGL, the number density of the sample, which is set by the survey depth, is the main factor driving the variations in the FoM. Adding galaxies at faint magnitudes and high redshift increases the FoM, even when they are beyond the spectroscopic limit, since the number density increase compensates for the photo-
z
degradation in this case. We conclude that there is more information that can be extracted beyond the nominal ten tomographic redshift bins of
Euclid
and that we should be cautious when adding faint galaxies into our sample since they can degrade the cosmological constraints.
Background and Methods: In Paget's disease of the breast, the epidermis of the nipple is infiltrated by large neoplastic cells of glandular origin. It has been hypothesized that the spread of Paget ...cells through the nipple epidermis is induced by a motility factor that acts via the HER2/NEU receptor. To test this hypothesis, we characterized and purified a motility factor released by keratinocytes and identified its target receptors in specimens from patients with Paget's disease and in SK-BR-3 breast adenocarcinoma cells, which overexpress HER2/NEU. Results: We isolated the motility factor from keratinocyte-conditioned medium and sequenced tryptic peptides. These sequences were used to identify the motility factor as heregulin-α, which is released by skin keratinocytes. Heregulin-α induces spreading, motility, and chemotaxis of SK-BR-3 cells, as does motility factor. Motility factor activities of heregulin-α are inhibited by monoclonal antibody AB2, directed against the extracellular domain of HER2/NEU, which blocks the binding of heregulin-α. We used in situ hybridization to show that normal epidermal cells produce heregulin-α messenger RNA and that heregulin receptors, HER3 and/or HER4, as well as their coreceptor HER2/NEU, are expressed by Paget cells. Conclusions: Heregulin-α is a motility factor that is produced and released by normal epidermal keratinocytes and thus plays a key role in the pathogenesis of Paget's disease. Paget cells express heregulin receptors HER2/NEU, as well as HER3 and/or HER4, both of which function as a co-receptor of HER2/NEU. Binding of heregulin-α to the receptor complex on Paget cells results in the chemotaxis of these breast cancer cells, which eventually migrate into the overlying nipple epidermis.
In the white population, an association between oculo(dermal) melanocytosis (ODM) and uveal melanoma is well recognized. However, the lifetime prevalence of uveal melanoma in the ODM population is ...not known. This study was designed to determine the lifetime prevalence of uveal melanoma among patients with ocular melanocytosis.
Fifty-six white patients manifesting ODM with uveal melanoma formed the basis of the study.
Published prevalence rates of ODM and uveal melanoma were used for calculations using Bayes' theorem.
The lifetime prevalence of uveal melanoma in white patients with ODM is estimated to be 2.6 × 10
−3. The median age at diagnosis of uveal melanoma in the ODM population was similar to a randomly selected population (60.5 years and 62.5 years, respectively). In the vast majority of patients (90%) with ODM-associated uveal melanoma, the uveal melanoma was diagnosed between the ages of 31 years and 80 years.
One of about 400 patients with ODM followed for life is estimated to develop uveal melanoma. Excessive melanocytes in the uveal tract in ODM may provide the biologic basis for susceptibility to the development of uveal melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of uveal melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing uveal melanoma.
Two different receptors which bind angiotensin II specifically have been identified in humans and were designated angiotensin II type-1 receptor (AT1) and angiotensin II type-2 receptor (AT2). They ...only have 34% sequence homology and act through different signalling pathways. AT1 stimulation has been implicated in hypertrophy and hyperplasia in various tissues. In order to study the involvement of AT1 in tissues from controls (n=10) and patients with hyperplasia (n=33), ductal carcinoma in situ (DCIS) (n=23) and invasive carcinoma of the breast (n=25), we tested biopsies and breast-derived cell lines using immunocytochemistry, in situ hybridisation and cell proliferation techniques. The results show specific overexpression of AT1 receptor on the cytoplasmic membrane of cells of hyperplastic lesions with and without atypia and on DCIS of the breast. Evidence for growth stimulation is provided by in vitro experiments showing growth induction by angiotensin II of T47D cells which express the AT1 but not the AT2 receptor. The expression of AT1 on the cell membrane disappears in invasive breast cancer cells suggesting a regulatory pathway which is no longer needed in invasive carcinoma. The specific AT1 expression upregulation might well be an important step in the pathogenesis of hyperplasia of the breast, which is regarded as a precursor lesion for breast cancer.
Background: Most reports on intraocular medulloepithelioma have been single case descriptions. The authors reviewed ten patients with intraocular medulloepithelioma, discuss some little known ...clinical features of this entity, and make diagnostic and therapeutic recommendations.
Patients and Methods: The records of the authors' patients with histopathologically confirmed medulloepithelioma were reviewed, and the clinical features, diagnostic problems, management, histopathology, and prognosis were assessed.
Results: Of the ten patients, nine were children, ranging in age from 2 months to 10 years, and one patient was 58 years of age at the time of clinical presentation. In seven patients, there was a delay in diagnosis, ranging from 3 to 28 months, and four patients underwent surgery for cataract, glaucoma, or other secondary conditions while the tumor was unsuspected. All patients had a nonpigmented ciliary body mass and a notched or subluxated lens, and six had neovascular glaucoma and evident cysts in the mass. The authors' initial management was enucleation in four patients and local resection in six. Of the six patients managed by local resection, five eventually required enucleation, four because of local tumor recurrence and one because of ocular inflammation and discomfort. Pathologically, nine tumors were classified as malignant (5 teratoid, 4 nonteratoid) and one as benign. In one patient (the adult), metastasis to the parotid gland developed.
Conclusion: Intraocular medulloepithelioma generally occurs in the first decade of life as a nonpigmented ciliary body mass. It has a tendency to cause secondary neovascular glaucoma, a characteristic lens notch and subluxation, and a neoplastic cyclitic membrane. Enucleation is the best treatment for advanced cases. For smaller circumscribed lesions, local resection may be attempted, but such treatment is followed frequently by local recurrence. Although most medulloepitheliomas are cytologically malignant, distant metastasis is uncommon.
Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for ...intraocular tumors previously has not been clarified.
Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique.
Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use of a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed.
Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures.
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