Modelling stochastic bivariate mortality

Stochastic mortality, i.e. modelling death arrival via a jump process with stochastic intensity, is gaining increasing reputation as a way to represent mortality risk. This paper represents a first attempt to model the mortality risk of couples of individuals, according to the stochastic intensity approach. On the theoretical side, we extend to couples the Cox processes set up, i.e. the idea that mortality is driven by a jump process whose intensity is itself a stochastic process, proper of a particular generation within each gender. Dependence between the survival times of the members of a couple is captured by an Archimedean copula. On the calibration side, we fit the joint survival function by calibrating separately the (analytical) copula and the (analytical) margins. First, we select the best fit copula according to the methodology of Wang and Wells (2000) for censored data. Then, we provide a sample-based calibration for the intensity, using a time-homogeneous, non mean-reverting, affine process: this gives the analytical marginal survival functions. Coupling the best fit copula with the calibrated margins we obtain, on a sample generation, a joint survival function which incorporates the stochastic nature of mortality improvements and is far from representing independency.On the contrary, since the best fit copula turns out to be a Nelsen one, dependency is increasing with age and long-term dependence exists

Effect of the dual endothelin receptor antagonist bosentan on untreatable skin ulcers in a patient with diabetes: a case report

<p>Abstract</p> <p>Introduction</p> <p>Refractory skin ulcers are a major burden in patients with diabetes. Their pathogenesis is multifactorial, and data increasingly implicate endothelin as a mediator of diabetic macro- and microvasculopathy. Here we describe the first reported case of an endothelin receptor antagonist being used to successfully treat refractory skin ulcers in a patient with diabetes.</p> <p>Case presentation</p> <p>An 85-year-old Caucasian man with a 30-year history of type 2 diabetes developed multiple skin ulcerations, including a right heel ulcer. Despite appropriate treatment, the ulcer showed little improvement and the risk of amputation was high. The patient was treated with the dual endothelin receptor antagonist bosentan. After three weeks of treatment, major improvements were observed, and after 21 weeks, all ulcers had healed. No abnormalities were observed during monitoring of blood pressure, erythrocyte sedimentation rate or serum aminotransferase levels.</p> <p>Conclusion</p> <p>In patients with refractory ulceration associated with diabetes, bosentan may be of real benefit, especially in terms of amputation prevention. This case supports the proposed role for endothelin in the pathogenesis of skin ulceration in diabetes and is suggestive of a potential benefit of bosentan in this patient type. This case report is of interest to diabetologists and dermatologists.</p

Measurement of the e+e−→K+K−π+π−e^+e^- \to K^+K^-\pi^+\pi^- cross section with the CMD-3 detector at the VEPP-2000 collider

The process $e^+e^- \to K^+K^-\pi^+\pi^-$ has been studied in the center-of-mass energy range from 1500 to 2000\,MeV using a data sample of 23 pb$^{-1}$ collected with the CMD-3 detector at the VEPP-2000 $e^+e^-$ collider. Using about 24000 selected events, the $e^+e^- \to K^+K^-\pi^+\pi^-$ cross section has been measured with a systematic uncertainty decreasing from 11.7\% at 1500-1600\,MeV to 6.1\% above 1800\,MeV. A preliminary study of $K^+K^-\pi^+\pi^-$ production dynamics has been performed

Study of the process e+e−→ppˉe^+e^-\to p\bar{p} in the c.m. energy range from threshold to 2 GeV with the CMD-3 detector

Using a data sample of 6.8 pb$^{-1}$ collected with the CMD-3 detector at the VEPP-2000 $e^+e^-$ collider we select about 2700 events of the $e^+e^- \to p\bar{p}$ process and measure its cross section at 12 energy ponts with about 6\% systematic uncertainty. From the angular distribution of produced nucleons we obtain the ratio $|G_{E}/G_{M}| = 1.49 \pm 0.23 \pm 0.30$

Structural Dynamic of a Self-Assembling Peptide d-EAK16 Made of Only D-Amino Acids

We here report systematic study of structural dynamics of a 16-residue self-assembling peptide d-EAK16 made of only D-amino acids. We compare these results with its chiral counterpart L-form, l-EAK16. Circular dichroism was used to follow the structural dynamics under various temperature and pH conditions. At 25°C the d-EAK16 peptide displayed a typical beta-sheet spectrum. Upon increasing the temperature above 70°C, there was a spectrum shift as the 218 nm valley widens toward 210 nm. Above 80°C, the d-EAK16 peptide transformed into a typical alpha-helix CD spectrum without going through a detectable random-coil intermediate. When increasing the temperature from 4°C to 110°C then cooling back from 110°C to 4°C, there was a hysteresis: the secondary structure from beta-sheet to alpha-helix and then from alpha-helix to beta-sheet occurred. d-EAK16 formed an alpha-helical conformation at pH0.76 and pH12 but formed a beta-sheet at neutral pH. The effects of various pH conditions, ionic strength and denaturing agents were also noted. Since D-form peptides are resistant to natural enzyme degradation, such drastic structural changes may be exploited for fabricating molecular sensors to detect minute environmental changes. This provides insight into the behaviors of self-assembling peptides made of D-amino acids and points the way to designing new peptide materials for biomedical engineering and nanobiotechnology

The photochemistry of N-p-toluenesulfonyl peptides: the peptide bond as an electron donor

The scope of photobiological processes that involve absorbers within a protein matrix may be limited by the vulnerability of the peptide group to attack by highly reactive redox centers consequent upon electronic excitation. We have explored the nature of this vulnerability by undertaking comprehensive product analyses of aqueous photolysates of 12 N-p-toluene-sulfonyl peptides with systematically selected structures. The results indicate that degradation includes a major pathway that is initiated by intramolecular electron transfer in which the peptide bond serves as electron donor, and the data support the likelihood of a relay process in dipeptide derivatives