Hyperthermia and maximal oxygen uptake in men and women.

To compare the effect of hyperthermia on maximal oxygen uptake (VO2max) in men and women, VO2max was measured in 11 male and 11 female runners under seven conditions involving various ambient temperatures (Ta at 50% RH) and preheating designed to manipulate the esophageal (Tes) and mean skin (Tsk) temperatures at VO2max. The conditions were: 25 degrees C, no preheating (control); 25, 35, 40, and 45 degrees C, with exercise-induced preheating by a 20-min walk at approximately 33% of control VO2max; 45 degrees C, no preheating; and 45 degrees C, with passive preheating during which Tes and Tsk were increased to the same degree as at the end of the 20-min walk at 45 degrees C. Compared to VO2max (l x min(-1)) in the control condition (4.52+/-0.46 in men, 3.01+/-0.45 in women), VO2max in men and women was reduced with exercise-induced or passive preheating and increased Ta, approximately 4% at 35 degrees C, approximately 9% at 40 degrees C and approximately 18% at 45 degrees C. Percentage reductions (7-36%) in physical performance (treadmill test time to exhaustion) were strongly related to reductions in VO2max (r=0.82-0.84). The effects of hyperthermia on VO2max and physical performance in men and women were almost identical. We conclude that men and women do not differ in their thermal responses to maximal exercise, or in the relationship of hyperthermia to reductions in VO2max and physical performance at high temperature. Data are reported as mean (SD) unless otherwise stated.

Right-left digit ratio (2D:4D) and maximal oxygen uptake.

A low digit ratio (2D:4D) and low 2D:4D in the right compared with the left hand (right-left 2D:4D) are thought to be determined by high in utero concentrations of testosterone, and are related to "masculine" traits such as aggression and performance in sports like running and rugby. Low right-left 2D:4D is also related to sensitivity to testosterone as measured by the number of cytosine-adenine-guanine triplet repeats in exon 1 of the androgen receptor gene. Here we show that low right-left 2D:4D is associated with high maximal oxygen uptake (VO2(max)), high velocity at VO2(max), and high maximum lactate concentration in a sample of teenage boys. We suggest that low right-left 2D:4D is linked to performance in some sports because it is a proxy of high sensitivity to prenatal and maybe also circulating testosterone and high VO2(max).

Counterexamples to some pointwise estimates of the maximal Cauchy transform in terms of the Cauchy transform

Motivated by the work of Mateu, Orobitg, Pérez and Verdera, who proved inequalities of the form $T_*f\lesssim M(Tf)$ or $T_*f\lesssim M^2(Tf)$ for certain singular integral operators $T$, such as the Hilbert or the Beurling transforms, we study the possibility of establishing this type of control for the Cauchy transform along a Lipschitz graph. We show that this is not possible in general, and we give a partial positive result when the graph is substituted by a Jordan curve.

Preinfarction angina prior to first myocardial infarction does not influence long-term prognosis: a retrospective study with subgroup analysis in elderly and diabetic patients.

BACKGROUND AND HYPOTHESIS Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against in-hospital complications, this effect has not been well documented after initial hospitalization, especially in older or diabetic patients. We examined whether angina 1 week before a first MI provides protection in these patients. METHODS A total of 290 consecutive patients, 143 elderly (>64 years of age) and 147 adults (<65 years of age), 68 of whom were diabetic (23.4%) and 222 nondiabetic (76.6%), were examined to assess the effect of preceding angina on long-term prognosis (56 months) after initial hospitalization for a first MI. RESULTS No significant differences were found in long-term complications after initial hospitalization in these adult and elderly patients according to whether or not they had prodromal angina (44.4% with angina vs 45.4% without in adults; 45.5% vs 58% in elderly, P < 0.2). Nor were differences found according to their diabetic status (61.5% with angina vs 72.7% without in diabetics; 37.3% vs 38.3% in nondiabetics; P = 0.4). CONCLUSION The occurrence of angina 1 week before a first MI does not confer long-term protection against cardiovascular complications after initial hospitalization in adult or elderly patients, whether or not they have diabetes.

Low rates of X-Y recombination, not turnovers, account for homomorphic sex chromosomes in several diploid species of Palearctic green toads (Bufo viridis subgroup).

Contrasting with birds and mammals, most ectothermic vertebrates present homomorphic sex chromosomes, which might be due either to a high turnover rate or to occasional X-Y recombination. We tested these two hypotheses in a group of Palearctic green toads that diverged some 3.3 million years ago. Using sibship analyses of sex-linked markers, we show that all four species investigated share the same pair of sex chromosomes and a pattern of male heterogamety with drastically reduced X-Y recombination in males. Phylogenetic analyses of sex-linked sequences show that X and Y alleles cluster by species, not by gametolog. We conclude that X-Y homomorphy and fine-scale sequence similarity in these species do not stem from recent sex-chromosome turnovers, but from occasional X-Y recombination.

Strong reproductive barriers in a narrow hybrid zone of West-Mediterranean green toads (Bufo viridis subgroup) with Plio-Pleistocene divergence

Background One key question in evolutionary biology deals with the mode and rate at which reproductive isolation accumulates during allopatric speciation. Little is known about secondary contacts of recently diverged anuran species. Here we conduct a multi-locus field study to investigate a contact zone between two lineages of green toads with an estimated divergence time of 2.7 My, and report results from preliminary experimental crosses. Results The Sicilian endemic Bufo siculus and the Italian mainland-origin B. balearicus form a narrow hybrid zone east of Mt. Etna. Despite bidirectional mtDNA introgression over a ca. 40 km North-South cline, no F1 hybrids could be found, and nuclear genomes display almost no admixture. Populations from each side of the contact zone showed depressed genetic diversity and very strong differentiation (FST = 0.52). Preliminary experimental crosses point to a slightly reduced fitness in F1 hybrids, a strong hybrid breakdown in backcrossed offspring (F1 x parental, with very few reaching metamorphosis) and a complete and early mortality in F2 (F1 x F1). Conclusion Genetic patterns at the contact zone are molded by drift and selection. Local effective sizes are reduced by the geography and history of the contact zone, B. balearicus populations being at the front wave of a recent expansion (late Pleistocene). Selection against hybrids likely results from intrinsic genomic causes (disruption of coadapted sets of genes in backcrosses and F2-hybrids), possibly reinforced by local adaptation (the ranges of the two taxa roughly coincide with the borders of semiarid and arid climates). The absence of F1 in the field might be due to premating isolation mechanisms. Our results, show that these lineages have evolved almost complete reproductive isolation after some 2.7 My of divergence, contrasting sharply with evidence from laboratory experiments that some anuran species may still produce viable F1 offspring after > 20 My of divergence.

Implementació de la cerca d'un subgraf comú maximal a dos grafs mitjançant colles

La memòria que ací es presenta s'emmarca dins de l'àrea de teoria de grafs. En concret es treballa la implementació d'un algorisme per trobar el subgraf comú maximal (SCM) de dos grafs mitjançant la cerca de colles maximals (CM). L'aportació principal del projecte consisteix en, donats dos grafs qualsevol, trobar el seu graf associat per tal de poder cercar la seva colla maximal (CM). I així, utilitzant funcions existents en el llenguatge de programació, poder trobar el seu subgraf comú maximal (SCM), necessari per calcular la distància entre grafs i així determinar quan d'isomorfs són.

The equity core and the Lorenz-maximal allocations in the equal division core

In this paper, we characterize the non-emptiness of the equity core (Selten, 1978) and provide a method, easy to implement, for computing the Lorenz-maximal allocations in the equal division core (Dutta-Ray, 1991). Both results are based on a geometrical decomposition of the equity core as a finite union of polyhedrons. Keywords: Cooperative game, equity core, equal division core, Lorenz domination. JEL classification: C71

Hierachy-based methodology for producing educational contents with maximal reutilization

Computer based training or distance education are facing dramatic changes withthe advent of standardization efforts, some of them concentrating in maximal reuse.This is of paramount importance for a sustainable -cost affordable- production ofeducational materials. Reuse in itself should not be a goal, though, since manymethodological aspects might be lost. In this paper we propose two contentproduction approaches for the InterMediActor platform under a competence-basedmethodology: either a bottom-up approach where content is designed from scratchor a top-down methodology where existing material can be gradually adapted tofulfil requisites to be used with maximal flexibility into InterMediActor.

Extent of resection in glioblastoma - variation between molecular risk groups in rtog-0525

Whether maximal surgical resection of glioblastoma improves patient survival has been controversial, as it is difficult to perform an unbiased assessment of extent of resection (EOR) independent of other patient-specific prognostic factors. Recently, glioblastoma has been sub-classified into 4 distinct molecular risk groups (RGs), which have been validated as prognostic biomarkers in the randomized clinical trial of temozolomide dosing in glioblastoma: the Radiation Therapy Oncology Group 0525 (RTOG-0525) trial. We sought to perform exploratory analyses examining gross total resection (GTR) versus sub-total resection (STR) within these RGs in RTOG-0525 patients. Across all randomized patients, n ¼ 354 had STR and n ¼ 450 had GTR as determined by neurosurgeon operative report. GTR was not significantly associated with survival across the overall study group. A total of 725 patients had sufficient tissue for determination of molecular RG. There were no significant differences in percentage of GTR between each of the 4 RGs (P ¼ 0.64). In exploratory subgroup analyses, GTR was associated with improved survival only for patients with tumors from RG4. Hazard ratios (95% confidence intervals) were 0.52 (0.08-2.07) for RG1 (n ¼ 28, 68% GTR), 1.74 (0.75-4.05) for RG2 (n ¼ 39, 56% GTR), 1.09 (0.84-1.42) for RG3 (n ¼ 284, 56% GTR), and 1.26 (1.01-1.56) for RG4 (n ¼ 374, 55% GTR). In univariate analysis within RG4, GTR was associated with a median survival of 14.6 months vs 12.7 months for STR (P ¼ 0.0352. In a Cox model adjusting for age, KPS, and neurologic function (NF), surgery remained an independent factor within RG4: GTR (P ¼ 0.0331), age (P ¼ 0.0014), KPS (P ¼ .3289), and NF (P ¼ 0.3804). There are important cautions in the interpretation of these data, including lack of MRI confirmation of EOR, and inclusion of a range of STR (from biopsy to near-total resection). However, these exploratory results raise the possibility that upfront characterization of tumor molecular profile may allow for personalized therapeutic strategies to improve outcomes for patients with glioblastoma.

Inferring the degree of incipient speciation in secondary contact zones of closely related lineages of Palearctic green toads (Bufo viridis subgroup).

Reproductive isolation between lineages is expected to accumulate with divergence time, but the time taken to speciate may strongly vary between different groups of organisms. In anuran amphibians, laboratory crosses can still produce viable hybrid offspring >20 My after separation, but the speed of speciation in closely related anuran lineages under natural conditions is poorly studied. Palearctic green toads (Bufo viridis subgroup) offer an excellent system to address this question, comprising several lineages that arose at different times and form secondary contact zones. Using mitochondrial and nuclear markers, we previously demonstrated that in Sicily, B. siculus and B. balearicus developed advanced reproductive isolation after Plio-Pleistocene divergence (2.6 My, 3.3-1.9), with limited historic mtDNA introgression, scarce nuclear admixture, but low, if any, current gene flow. Here, we study genetic interactions between younger lineages of early Pleistocene divergence (1.9 My, 2.5-1.3) in northeastern Italy (B. balearicus, B. viridis). We find significantly more, asymmetric nuclear and wider, differential mtDNA introgression. The population structure seems to be molded by geographic distance and barriers (rivers), much more than by intrinsic genomic incompatibilities. These differences of hybridization between zones may be partly explained by differences in the duration of previous isolation. Scattered research on other anurans suggests that wide hybrid zones with strong introgression may develop when secondary contacts occur <2 My after divergence, whereas narrower zones with restricted gene flow form when divergence exceeds 3 My. Our study strengthens support for this rule of thumb by comparing lineages with different divergence times within the same radiation.

Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial.

Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a pathogenetically heterogeneous group, significantly enriched for IDH1 mutations (19 vs. 3%, p = 0.003) and EGFR amplifications (71 vs. 48%, p = 0.04) compared with other GBM, while co-deletion of 1p/19q was found in only one case and the MGMT methylation frequency was alike (47 vs. 46%). Expression profiles classified most of the GBM-O into two subtypes, 36% (5/14 evaluable) as proneural and 43% as classical GBM. The detection of pseudo-palisading necrosis (PPN) was associated with benefit from chemotherapy (p = 0.0002), while no such effect was present in the absence of PPN (p = 0.86). In the adjusted interaction model including clinical prognostic factors and MGMT status, PPN was borderline nonsignificant (p = 0.063). Taken together, recognition of an oligodendroglioma-like component in an otherwise classic GBM identifies a pathogenetically mixed group without prognostic significance. However, the presence of PPN may indicate biological features of clinical relevance for further improvement of therapy.

New polymorphic microsatellites markers and development of mitotyping primers for West-Mediterranean green toad species (Bufo viridis subgroup)

We report new polymorphic microsatellites for three species of Palearctic green toads (Bufo viridis subgroup): 10 in B. balearicus and seven each in B. siculus and B. boulengeri. Diversity at these loci, measured for 27 B. balearicus, 23 B. siculus and 11 B. boulengeri, ranged from low to high (two to 10 alleles). Mitotyping primers, specific to the control region, which allow fast screening of parapatric Sicilian endemic B. siculus and Italian mainland-origin B. balearicus, were developed.

Evidence for a TCR affinity threshold delimiting maximal CD8 T cell function.

Protective adaptive immune responses rely on TCR-mediated recognition of Ag-derived peptides presented by self-MHC molecules. However, self-Ag (tumor)-specific TCRs are often of too low affinity to achieve best functionality. To precisely assess the relationship between TCR-peptide-MHC binding parameters and T cell function, we tested a panel of sequence-optimized HLA-A(*)0201/NY-ESO-1(157-165)-specific TCR variants with affinities lying within physiological boundaries to preserve antigenic specificity and avoid cross-reactivity, as well as two outliers (i.e., a very high- and a low-affinity TCR). Primary human CD8 T cells transduced with these TCRs demonstrated robust correlations between binding measurements of TCR affinity and avidity and the biological response of the T cells, such as TCR cell-surface clustering, intracellular signaling, proliferation, and target cell lysis. Strikingly, above a defined TCR-peptide-MHC affinity threshold (K(D) < approximately 5 muM), T cell function could not be further enhanced, revealing a plateau of maximal T cell function, compatible with the notion that multiple TCRs with slightly different affinities participate equally (codominantly) in immune responses. We propose that rational design of improved self-specific TCRs may not need to be optimized beyond a given affinity threshold to achieve both optimal T cell function and avoidance of the unpredictable risk of cross-reactivity.