Quantification of collagen organization in the peripheral human cornea at micron-scale resolution

The collagen microstructure of the peripheral cornea is important in stabilizing corneal curvature and refractive status. However, the manner in which the predominantly orthogonal collagen fibrils of the central cornea integrate with the circumferential limbal collagen is unknown. We used microfocus wide-angle x-ray scattering to quantify the relative proportion and orientation of collagen fibrils over the human corneolimbal interface at intervals of 50 μm. Orthogonal fibrils changed direction 1–1.5 mm before the limbus to integrate with the circumferential limbal fibrils. Outside the central 6 mm, additional preferentially aligned collagen was found to reinforce the cornea and limbus. The manner of integration and degree of reinforcement varied significantly depending on the direction along which the limbus was approached. We also employed small-angle x-ray scattering to measure the average collagen fibril diameter from central cornea to limbus at 0.5 mm intervals. Fibril diameter was constant across the central 6 mm. More peripherally, fibril diameter increased, indicative of a merging of corneal and scleral collagen. The point of increase varied with direction, consistent with a scheme in which the oblique corneal periphery is reinforced by chords of scleral collagen. The results have implications for the cornea's biomechanical response to ocular surgeries involving peripheral incision

Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study

BACKGROUND: The association of fitness with cancer risk is not clear. METHODS: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. RESULTS: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min-1⋅kg-1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min-1⋅kg-1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. DISCUSSION: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention

Patterns of at-sea behaviour at a hybrid zone between two threatened seabirds

Patterns of behavioural variation and migratory connectivity are important characteristics of populations, particularly at the edges of species distributions, where processes involved in influencing evolutionary trajectories, such as divergence, mutual persistence, and natural hybridization, can occur. Here, we focused on two closely related seabird species that breed in the Mediterranean: Balearic shearwaters (Puffinus mauretanicus) and Yelkouan shearwaters (Puffinus yelkouan). Genetic and phenotypic evidence of hybridization between the two species on Menorca (the eastern and westernmost island in the breeding ranges of the two shearwaters, respectively) has provided important insights into relationships between these recently diverged species. Nevertheless, levels of behavioural and ecological differentiation amongst these populations remain largely unknown. Using geolocation and stable isotopes, we compared the at-sea movement behaviour of birds from the Menorcan ‘hybrid’ population with the nearest neighbouring populations of Balearic and Yelkouan shearwaters. The Menorcan population displayed a suite of behavioural features intermediate to those seen in the two species (including migration strategies, breeding season movements and limited data on phenology). Our findings provide new evidence to support suggestions that the Menorcan population is admixed, and indicate a role of non-breeding behaviours in the evolutionary trajectories of Puffinus shearwaters in the Mediterranean

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies

The Centrality of Mathematics in the History of Western Thought

This article explores the interplay of mathematics and philosophy in Western thought as well as applications to other fields

Honores y renuncias: la escultora argentina Lola Mora y la fuente de los debates

Lola Mora (1867-1936) fue la más halagada y discutida escultora argentina de\ud los últimos años del siglo XIX y comienzos del siglo XX. La prensa escrita de Buenos Aires\ud sigue el desarrollo de su carrera artística desde la llegada del viaje de estudios en 1900 y\ud la convierte en protagonista principal monopolizando así la atención de los cronistas. El tema\ud de este trabajo de investigación es una de sus obras más conocidas: la Fuente de las Nereidas\ud o denominada popularmente Fuente de Lola Mora, conjunto escultórico de mármol de Carrara\ud que se inaugura el 21 de mayo de 1903 en el Paseo de Julio. Esta investigación abordará\ud las cuestiones que se debatieron en torno a este conjunto escultórico en relación al\ud emplazamiento original en 1903, que lo transforma en un proceso particular ya que hasta\ud ese momento nunca se habían producido discusiones de tales características en torno a una\ud obra decorativa para la ciudad