[Treatment reality with ranibizumab in clinical routine use for patients with diabetic macular edema : 1­year results of the German POLARIS cohort]. / Behandlungsrealität mit Ranibizumab in der klinischen Routineanwendung bei Patienten mit diabetischem Makulaödem : 1-Jahres-Ergebnisse der deutschen POLARIS-Kohorte.

BACKGROUND: Currently only few data are available on the treatment reality with ranibizumab in patients with diabetic macular edema (DME). MATERIAL AND METHODS: POLARIS is an international observational study which included 983 patients who were treated with ranibizumab due to DME. The primary objective of the study was to investigate the influence of treatment and control intervals as well as resource utilization on the mean change in visual acuity. Secondary endpoints included the collation of disease activity monitoring in the clinical practice. This article describes the results of the German POLARIS population. The study was conducted in 8 European countries from October 2012 to January 2015. RESULTS: In Germany 220 patients were included in the study. Visual acuity improved by 4.3 letters within the first 3 months of treatment. At 12 months, visual acuity increased on average by 4.1 (SD ± 12.4) letters (approximately 1 line) for 168 patients enrolled in the efficacy analysis. Patients received an average of 4.5 (SD ± 1.9) injections, 10.3 (SD ± 6.3) visual acuity tests and 3.3 (SD ± 3.1) optical coherence tomography (OCT) examinations during the first year. Patients with ≤3 injections showed an average improvement in visual acuity by 2.7 letters which was less improvement compared to patients with >3 injections, who achieved an average improvement of 5.4 letters. There was a correlation between the number of injections and the visual acuity achieved. DISCUSSION: For Germany, the results of the POLARIS study indicate that despite a high number of visits, patients with DME are undertreated in clinical routine practice. The injection frequency in Germany was lower than in randomized clinical trials. Almost half of the patients received less than 4 injections in the first year of treatment and thus showed an undertreatment compared to the recommendations of German and international medical societies.

Contraceptive consciousness and sexual behavior in three different female age groups in Greece: a retrospective study of the evolution during the last three decades.

The aim of the study is to describe the evolution of contraceptive and sexual behavior within our Greek society. MATERIALS, MEASURES AND METHODS: We interviewed 508 females and made a statistical analysis of their answers. CONCLUSION: We tried to underline a strategy for the best promotion of the values in question. General, sexual and contraceptive education as well as the use and type of contraception are the weapons that will lead our endeavors to decreased involuntary pregnancy and towards responsible sexual behavior.

New insights into the exercise intolerance of beta-thalassemia major patients.

The purpose of our study was assessment of the relative contribution of the systems involved in blood gas exchange to the limited exercise capacity in patients with beta-thalassemia major (TM) using integrative cardiopulmonary exercise testing (CPET) with estimation of oxygen kinetics. The study consisted of 15 consecutive TM patients and 15 matched controls who performed spirometric evaluation, measurement of maximum inspiratory pressure (Pimax) and an incremental symptom-limited CPET on a cycle ergometer. Exercise capacity was markedly reduced in TM patients as assessed by peak oxygen uptake (pVO(2), mL/kg/min: 22.1+/-6.6 vs 33.8+/-8.3; P<0.001) and anaerobic threshold (mL/kg/min: 13.0+/-3.0 vs 18.7+/-4.6; P<0.001) compared with controls. No ventilatory limitation to exercise was noted in TM patients (VE/VCO(2) slope: 23.4+/-3.2 vs 27.8+/-2.6; P<0.001 and breathing reserve, %: 42.9+/-17.0 vs 29.5+/-12.0; P<0.005) and no difference in oxygen cost of work (peak VO(2)/WR, mL/min W: 12.2+/-1.7 vs 12.2+/-1.5; P=NS). Delayed recovery oxygen kinetics after exercise was observed in TM patients (VO(2)/t slope, mL/kg/min(2): 0.67+/-0.27 vs 0.93+/-0.23; P<0.05) that was significantly correlated with Pimax at rest (r: 0.81; P<0.001). The latter was also significantly correlated to pVO(2) (r: 0.84; P<0.001) and inversely correlated to ferritin levels (r: -0.6; P<0.02). Exercise capacity is markedly reduced in TM patients and this reduction is highly associated with the limited functional status of peripheral muscles.

Impaired oxygen kinetics in beta-thalassaemia major patients.

AIM: Beta-thalassaemia major (TM) affects oxygen flow and utilization and reduces patients' exercise capacity. The aim of this study was to assess phase I and phase II oxygen kinetics during submaximal exercise test in thalassaemics and make possible considerations about the pathophysiology of the energy-producing mechanisms and their expected exercise limitation. METHODS: Twelve TM patients with no clinical evidence of cardiac or respiratory disease and 10 healthy subjects performed incremental, symptom-limited cardiopulmonary exercise testing (CPET) and submaximal, constant workload CPET. Oxygen uptake (VO2), carbon dioxide output and ventilation were measured breath-by-breath. RESULTS: Peak VO2 was reduced in TM patients (22.3 +/- 7.4 vs. 28.8 +/- 4.8 mL kg(-1) min(-1), P < 0.05) as was anaerobic threshold (13.1 +/- 2.7 vs. 17.4 +/- 2.6 mL kg(-1) min(-1), P = 0.002). There was no difference in oxygen cost of work at peak exercise (11.7 +/- 1.9 vs. 12.6 +/- 1.9 mL min(-1) W(-1) for patients and controls respectively, P = ns). Phase I duration was similar in TM patients and controls (24.6 +/- 7.3 vs. 23.3 +/- 6.6 s respectively, P = ns) whereas phase II time constant in patients was significantly prolonged (42.8 +/- 12.0 vs. 32.0 +/- 9.8 s, P < 0.05). CONCLUSION: TM patients present prolonged phase II on-transient oxygen kinetics during submaximal, constant workload exercise, compared with healthy controls, possibly suggesting a slower rate of high energy phosphate production and utilization and reduced oxidative capacity of myocytes; the latter could also account for their significantly limited exercise tolerance.

Stochastic hybrid modeling of DNA replication across a complete genome.

DNA replication in eukaryotic cells initiates from hundreds of origins along their genomes, leading to complete duplication of genetic information before cell division. The large number of potential origins, coupled with system uncertainty, dictates the need for new analytical tools to capture spatial and temporal patterns of DNA replication genome-wide. We have developed a stochastic hybrid model that reproduces DNA replication throughout a complete genome. The model can capture different modes of DNA replication and is applicable to various organisms. Using genome-wide data on the location and firing efficiencies of origins in the fission yeast, we show how the DNA replication process evolves during S-phase in the presence of stochastic origin firing. Simulations reveal small regions of the genome that extend S-phase to three times its reported duration. The low levels of late replication predicted by the model are below the detection limit of techniques used to measure S-phase length. Parameter sensitivity analysis shows that increased replication fork speeds genome-wide, or additional origins are not sufficient to reduce S-phase to its reported length. We model the redistribution of a limiting initiation factor during S-phase and show that it could shorten S-phase to the reported duration. Alternatively, S-phase may be extended, and what has traditionally been defined as G2 may be occupied by low levels of DNA synthesis with the onset of mitosis delayed by activation of the G2/M checkpoint.

Black holes at the Large Hadron Collider.

If the scale of quantum gravity is near TeV, the CERN Large Hadron Collider will be producing one black hole (BH) about every second. The decays of the BHs into the final states with prompt, hard photons, electrons, or muons provide a clean signature with low background. The correlation between the BH mass and its temperature, deduced from the energy spectrum of the decay products, can test Hawking's evaporation law and determine the number of large new dimensions and the scale of quantum gravity.

Infinitely large new dimensions

We construct intersecting brane configurations in anit-de Sitter (AdS) space which localize gravity to the intersection region, generalizing the trapping of gravity to any number n of infinite extra dimensions. Since the 4D Planck scale M(Pl) is determined by the fundamental Planck scale M(*) and the AdS radius L via the familiar relation M(2)(Pl) approximately M(2+n)(*)L(n), we get two kinds of theories with TeV scale quantum gravity and submillimeter deviations from Newton's law. With M(*) approximately TeV and L approximately submillimeter, we recover the phenomenology of theories with large extra dimensions. Alternatively, if M(*) approximately L-1 approximately M(Pl), and our 3-brane is at a distance of approximately 100M(-1)(Pl) from the intersection, we obtain a theory with an exponential determination of the weak/Planck hierarchy.