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Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis
Hydroxyurea is the standard treatment in high risk patients with polycythemia vera. Yet, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematological transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in contemporary patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using WHO diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow-ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on follow-up duration. Thrombosis rates were 1.9, 3.6 and 6.8% persons/year at median ages 60, 70 and 80 respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at 5 year and 33.7% at 10 years; overall mortality was 12.6% and 56.2% at 5 and 10 years respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using hard endpoints for efficacy, such as major thrombosis
Stability analysis and quasinormal modes of Reissner Nordstr{\o}m Space-time via Lyapunov exponent
We explicitly derive the proper time principal Lyapunov exponent
() and coordinate time () principal Lyapunov exponent
() for Reissner Nordstr{\o}m (RN) black hole (BH) . We also
compute their ratio. For RN space-time, it is shown that the ratio is
for
time-like circular geodesics and for Schwarzschild BH it is
. We
further show that their ratio may vary from
orbit to orbit. For instance, Schwarzschild BH at innermost stable circular
orbit(ISCO), the ratio is
and at marginally
bound circular orbit (MBCO) the ratio is calculated to be
. Similarly, for extremal RN
BH the ratio at ISCO is
.
We also further analyse the geodesic stability via this exponent. By evaluating
the Lyapunov exponent, it is shown that in the eikonal limit , the real and
imaginary parts of the quasi-normal modes of RN BH is given by the frequency
and instability time scale of the unstable null circular geodesics.Comment: Accepted in Pramana, 07/09/201
Recognizing Speech in a Novel Accent: The Motor Theory of Speech Perception Reframed
The motor theory of speech perception holds that we perceive the speech of
another in terms of a motor representation of that speech. However, when we
have learned to recognize a foreign accent, it seems plausible that recognition
of a word rarely involves reconstruction of the speech gestures of the speaker
rather than the listener. To better assess the motor theory and this
observation, we proceed in three stages. Part 1 places the motor theory of
speech perception in a larger framework based on our earlier models of the
adaptive formation of mirror neurons for grasping, and for viewing extensions
of that mirror system as part of a larger system for neuro-linguistic
processing, augmented by the present consideration of recognizing speech in a
novel accent. Part 2 then offers a novel computational model of how a listener
comes to understand the speech of someone speaking the listener's native
language with a foreign accent. The core tenet of the model is that the
listener uses hypotheses about the word the speaker is currently uttering to
update probabilities linking the sound produced by the speaker to phonemes in
the native language repertoire of the listener. This, on average, improves the
recognition of later words. This model is neutral regarding the nature of the
representations it uses (motor vs. auditory). It serve as a reference point for
the discussion in Part 3, which proposes a dual-stream neuro-linguistic
architecture to revisits claims for and against the motor theory of speech
perception and the relevance of mirror neurons, and extracts some implications
for the reframing of the motor theory
The foot posture index, ankle lunge test, Beighton scale and the lower limb assessment score in healthy children: a reliability study
<p>Abstract</p> <p>Background</p> <p>Outcome measures are important when evaluating treatments and physiological progress in paediatric populations. Reliable, relevant measures of foot posture are important for such assessments to be accurate over time. The aim of the study was to assess the intra- and inter-rater reliability of common outcome measures for paediatric foot conditions.</p> <p>Methods</p> <p>A repeated measures, same-subject design assessed the intra- and inter-rater reliability of measures of foot posture, joint hypermobility and ankle range: the Foot Posture Index (FPI-6), the ankle lunge test, the Beighton scale and the lower limb assessment scale (LLAS), used by two examiners in 30 healthy children (aged 7 to 15 years). The Oxford Ankle Foot Questionnaire (OxAFQ-C) was completed by participants and a parent, to assess the extent of foot and ankle problems.</p> <p>Results</p> <p>The OxAFQ-C demonstrated a mean (SD) score of 6 (6) in adults and 7(5) for children, showing good agreement between parents and children, and which indicates mid-range (transient) disability. Intra-rater reliability was good for the FPI-6 (ICC = 0.93 - 0.94), ankle lunge test (ICC = 0.85-0.95), Beighton scale (ICC = 0.96-0.98) and LLAS (ICC = 0.90-0.98). Inter-rater reliability was largely good for each of the: FPI-6 (ICC = 0.79), ankle lunge test (ICC = 0.83), Beighton scale (ICC = 0.73) and LLAS (ICC = 0.78).</p> <p>Conclusion</p> <p>The four measures investigated demonstrated adequate intra-rater and inter-rater reliability in this paediatric sample, which further justifies their use in clinical practice.</p
Listening to the patient as a possible route to cost-effective rehabilitation: a case report
<p>Abstract</p> <p>Introduction</p> <p>Adolescents with cerebral palsy often do not need a specific rehabilitative treatment; however, when specific needs are expressed, clinicians should listen and try to answer them.</p> <p>Case presentation</p> <p>We present the case of a 17-year-old Italian male patient with hemiplegia who had received standard physiotherapy and, ultimately, after a period of adapted physical activity performed in a group, was under consideration for discharge. However, due to unsatisfactory hand control, he asked for help to reach a personal goal, the ability to drive a motorbike, without surgery. Functional taping showed efficacy, but was neither cost-effective nor practical for the patient and his family; by contrast, a dynamic orthosis associated with training in a real-life environment was instead successful.</p> <p>Conclusion</p> <p>The present case underlines the importance of considering solutions involving the motivation and compliance of the patient in order to improve his activity and participation.</p
Frovatriptan versus zolmitriptan for the acute treatment of migraine: a double-blind, randomized, multicenter, Italian study
The objective of this study is to assess patientsâ satisfaction with migraine treatment with frovatriptan (F) or zolmitriptan (Z), by preference questionnaire. 133 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or Z 2.5 mg. The study had a multicenter, randomized, double-blind, cross-over design, with each of the two treatment periods lasting no more than 3 months. At the end of the study, patients were asked to assign preference to one of the treatments (primary endpoint). The number of pain-free (PF) and pain-relief (PR) episodes at 2 h, and number of recurrent and sustained pain-free (SPF) episodes within 48 h were the secondary study endpoints. Seventy-seven percent of patients expressed a preference. Average score of preference was 2.9 ± 1.3 (F) versus 3.0 ± 1.3 (Z; p = NS). Rate of PF episodes at 2 h was 26% with F and 31% with Z (p = NS). PR episodes at 2 h were 57% for F and 58% for Z (p = NS). Rate of recurrence was 21 (F) and 24% (Z; p = NS). Time to recurrence within 48 h was better for F especially between 4 and 16 h (p < 0.05). SPF episodes were 18 (F) versus 22% (Z; p = NS). Drug-related adverse events were significantly (p < 0.05) less under F (3 vs. 10). In conclusion, our study suggests that F has a similar efficacy of Z, with some advantage as regards tolerability and recurrence
Temperature Evolution in Nanoscale Carbon-Based Memory Devices Due to Local Joule Heating
© 2002-2012 IEEE. Tetrahedral amorphous (ta-C) carbon-based memory devices have recently gained traction due to their good scalability and promising properties like nanosecond switching speeds. However, cycling endurance is still a key challenge. In this paper, we present a model that takes local fluctuations in sp 2 and sp 3 content into account when describing the conductivity of ta-C memory devices. We present a detailed study of the conductivity of ta-C memory devices ranging from ohmic behavior at low electric fields to dielectric breakdown. The study consists of pulsed switching experiments and device-scale simulations, which allows us for the first time to provide insights into the local temperature distribution at the onset of memory switching
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