Parent clinical trial priorities for fragile X syndrome: a best-worst scaling.

An expansion in the availability of clinical drug trials for genetic neurodevelopmental conditions is underway. Delineating patient priorities is key to the success of drug development and clinical trial design. There is a lack of evidence about parent decision-making in the context of clinical drug trials for genetic neurodevelopmental conditions. We assessed parents' priorities when making a decision whether to enroll their child with fragile X syndrome (FXS) in a clinical drug trial. An online survey included a best-worst scaling method for parents to prioritize motivating and discouraging factors for child enrollment. Parents were recruited through the National Fragile X Foundation and FRAXA. Sequential best-worst with conditional logit analysis was used to determine how parents prioritize motivating and discouraging factors about trial enrollment decisions. Respondents (N = 354) were largely biological mothers (83%) of an individual with FXS who ranged in age from under 5 to over 21 years. The highest motivating factor was a trial to test a drug targeting the underlying FXS mechanism (coeff = 3.28, p < 0.001), followed by the potential of the drug to help many people (coeff = 3.03, p < 0.001). Respondents rated requirement of blood draws (coeff = -3.09, p < 0.001), loss of access to the drug post trial (coeff = -3.01, p < 0.001), and drug side effects (coeff = -2.96, p < 0.001) as most discouraging. The priorities defined by parents can be incorporated into evidence-based trial design and execution to enhance the enrollment process

On the implications of aerosol liquid water and phase separation for modeled organic aerosol mass

Water is an important component of PM2.5 Many traditional SOA species are highly soluble and thus can be considered extractable Water can influence the partitioning of compounds traditionally considered insoluble in models Organic aerosol takes up water according to RH Organic aerosol interacts with inorganic water Deviations in ideality (solubility) must be considered

Outbreak of Aeromonas hydrophila wound infections association with mud football

On 16 February 2002, a total of 26 people presented to the emergency department of the local hospital in the rural town of Collie in southwest Western Australia with many infected scratches and pustules distributed over their bodies. All of the patients had participated in a “mud football” competition the previous day, in which there had been 100 participants. One patient required removal of an infected thumbnail, and another required surgical debridement of an infected toe. Aeromonas hydrophila was isolated from all 3 patients from whom swab specimens were obtained. To prepare the mud football fields, a paddock was irrigated with water that was pumped from an adjacent river during the 1-month period before the competition. A. hydrophila was subsequently isolated from a water sample obtained from the river. This is the first published report of an outbreak of A. hydrophila wound infections associated with exposure to mud.Hassan Vally, Amanda Whittle, Scott Cameron, Gary K. Dowse and Tony Watso

Doppler velocimetry of spin propagation in a two-dimensional electron gas

Controlling the flow of electrons by manipulation of their spin is a key to the development of spin-based electronics. While recent demonstrations of electrical-gate control in spin-transistor configurations show great promise, operation at room temperature remains elusive. Further progress requires a deeper understanding of the propagation of spin polarization, particularly in the high mobility semiconductors used for devices. Here we report the application of Doppler velocimetry to resolve the motion of spin-polarized electrons in GaAs quantum wells driven by a drifting Fermi sea. We find that the spin mobility tracks the high electron mobility precisely as a function of T. However, we also observe that the coherent precession of spins driven by spin-orbit interaction, which is essential for the operation of a broad class of spin logic devices, breaks down at temperatures above 150 K for reasons that are not understood theoretically

Quantum nondemolition measurement of mechanical motion quanta

The fields of opto- and electromechanics have facilitated numerous advances in the areas of precision measurement and sensing, ultimately driving the studies of mechanical systems into the quantum regime. To date, however, the quantization of the mechanical motion and the associated quantum jumps between phonon states remains elusive. For optomechanical systems, the coupling to the environment was shown to preclude the detection of the mechanical mode occupation, unless strong single photon optomechanical coupling is achieved. Here, we propose and analyse an electromechanical setup, which allows to overcome this limitation and resolve the energy levels of a mechanical oscillator. We find that the heating of the membrane, caused by the interaction with the environment and unwanted couplings, can be suppressed for carefully designed electromechanical systems. The results suggest that phonon number measurement is within reach for modern electromechanical setups.Comment: 8 pages, 5 figures plus 24 pages, 11 figures supplemental materia

Models of Star-Planet Magnetic Interaction

Magnetic interactions between a planet and its environment are known to lead to phenomena such as aurorae and shocks in the solar system. The large number of close-in exoplanets that were discovered triggered a renewed interest in magnetic interactions in star-planet systems. Multiple other magnetic effects were then unveiled, such as planet inflation or heating, planet migration, planetary material escape, and even modification of the host star properties. We review here the recent efforts in modelling and understanding magnetic interactions between stars and planets in the context of compact systems. We first provide simple estimates of the effects of magnetic interactions and then detail analytical and numerical models for different representative scenarii. We finally lay out a series of future developments that are needed today to better understand and constrain these fascinating interactions.Comment: 23 pages, 10 figures, accepted as a chapter in the Handbook of Exoplanet

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects