Penetrance and predictive value of genetic screening in acute porphyria

Objective: Penetrance, predictive value and female patients' perspectives on genetic testing were evaluated among Finnish patients with acute porphyria. We conducted a retrospective study to evaluate prognosis among at-risk female family members depending on the primary method of diagnosis. Methods: The penetrance was calculated among 23 genetically heterogeneous families selected from the Finnish porphyria registry (n = 515, AIP 333; VP 182). We included kindreds with >= 9 patients in a family (range 9-23 patients, total 216 AIP; 129 VP). In 2015, the registry included 164 living female subjects between 14 and 85 years of age. A questionnaire was sent to 143 women, of whom 107 (75%, AIP 67; VP 40) replied. Female at-risk relatives (AIP 54; VP 30) were divided into two groups based on the primary method of diagnosis: mutation analysis (Group A, n = 40) or biochemical analysis (Group B, n = 44). Results: Mean penetrance for all acute symptoms was 35% among AIP and 40% among VP families. In both study groups, the penetrance was higher among female (AIP 50%; VP 44%) than male patients (AIP 17%; VP 33%). Penetrance for hospitalized attacks was 30% among AIP families (range 10-80%, for women 41%) and 25% in VP (range 0-50%, for women 27%) demonstrating wide variations among families even with the similar genotype. Acute porphyria was diagnosed at the median age of 26 years (range 0-76 years) among female patients, commonly after the onset of acute symptoms. Diagnostic delay was an average of 7.4 years (range 1-30 years). Acute symptoms occurred at the median age of 24 years (range 10-57 years) and the first hospitalization at the median age of 26.5 years (range 15-57 years). At the onset of symptoms, 38% of the women were Conclusions: Among female at-risk relatives the annual risk for hospitalization due to an acute attack is <1% and for acute symptoms <2% during the fertile years. Genetic testing of relatives diminishes the risk of acute attacks. Diagnosis before symptom onset is key for subjects to remain asymptomatic during follow-up, and genetic screening should be done earlier than currently.Peer reviewe

Aerodynamics Of Soccer Balls And Volleyballs

The purpose of this study was to investigate range, flight time, speed and trajectory of selected official soccer balls and volleyballs in a constant release angle (18 degree) shot by a ball gun with a hydraulic shooting steel leg mechanism in an indoor soccer hall. Five soccer balls (m=0.422 ± 0.010 kg, d=0.108 + 0.002 rn, p=(0.69 + 0.01) x 105 Nm-2) and five volleyballs (m=0.278 ± 0.006 kg, d=0.105 + 0.002 rn, p=(0.69 ±0.01) x 105 Nm-2) were used. Three speeds of the kicking steel leg were applied to the stationary and rotating balls with two constant angular velocities (45.6 and 65.0 radls). All shots of the balls were recorded with two JVC 707 5-VHS camcorders (50 Hz) for kinematic and kinetic motion analysis. An APAS performance analysis system was used for detailed 3D analysis of the release phase of the shot. The range of the ball was measured in x-z coordinates on the Astroturf ground. A Panasonic camcorder with timer was used to measure the flight time of the ball. A 3- way ANOVA was applied in order to study the differences of the balls and their behaviour in the placid air. The release velocities of the stationary soccer balls with three speed categories .were 18.8 + 0.1 ms·1, 23.1 ± 0.1 msand 26.5 ± 0.1 ms-1 and in volleyballs 20.5 ± 0.2 ms-I, 25.6 ± 0.2 ms-1 and 29.4 ± 0.2 ms-1, respectively. The range of the fastest shot off the soccer balls was on average 44.8 m with the lateral deviation of 3.3 degrees. The average range of the volleyballs in the fastest shots without spin was 45.2 m with the lateral deviation of 4.8 degrees. The average ground speeds in the fastest shots of the soccer ball and volleyball were 20.6 ms-1 and 24.7 ms-1, respectively. With the fastest spin and shot the range and deviation of soccer balls and volleyballs were 34.4 m and 38.6 m and 19.7 and 21.4 degrees, respectively. The main effects of the ball type, shot speed and spin were significant (

Strain-Rate Frequency Superposition in Large-Amplitude Oscillatory Shear

In a recent work, Wyss, {\it et.al.} [Phys. Rev. Lett., {\bf 98}, 238303 (2007)] have noted a property of `soft solids' under oscillatory shear, the so-called strain-rate frequency superposition (SRFS). We extend this study to the case of soft solids under large-amplitude oscillatory shear (LAOS). We show results from LAOS studies in a monodisperse hydrogel suspension, an aqueous gel, and a biopolymer suspension, and show that constant strain-rate frequency sweep measurements with soft solids can be superimposed onto master curves for higher harmonic moduli, with the {\it same} shift factors as for the linear viscoelastic moduli. We show that the behavior of higher harmonic moduli at low frequencies in constant strain-rate frequency sweep measurements is similar to that at large strain amplitudes in strain-amplitude sweep tests. We show surface plots of the harmonic moduli and the energy dissipation rate per unit volume in LAOS for soft solids, and show experimentally that the energy dissipated per unit volume depends on the first harmonic loss modulus alone, in both the linear and the nonlinear viscoelastic regime.Comment: 10 pages, 25 figures, accepted for publication in Physical Review E. Incorporates referee comment

Integrated optics sensors for multi-sensing platforms

An overview is presented of research projects on optical sensing, in the Integrated Optical MicroSystems group of the MESA+ Institute for Nanotechnology at the University of Twente

Rationality as the Rule of Reason

The demands of rationality are linked both to our subjective normative perspective (given that rationality is a person-level concept) and to objective reasons or favoring relations (given that rationality is non-contingently authoritative for us). In this paper, I propose a new way of reconciling the tension between these two aspects: roughly, what rationality requires of us is having the attitudes that correspond to our take on reasons in the light of our evidence, but only if it is competent. I show how this view can account for structural rationality on the assumption that intentions and beliefs as such involve competent perceptions of downstream reasons, and explore various implications of the account

An update of clinical management of acute intermittent porphyria

Peer reviewe