339 research outputs found
Intracochlear Pressure Changes due to Round Window Opening: A Model Experiment
To preserve residual hearing in cochlea implantation, the electrode design has been refined and an atraumatic insertion of the cochlea electrode has become one aspect of cochlea implant research. The opening of the round window can be assumed to be a contributing factor in an atraumatic concept. The aim of our study was to observe intracochlear pressure changes due to different opening conditions of an artificial round window membrane. The experiments were performed in an artificial cochlea model. A round window was simulated with a polythene foil and a pressure sensor was placed in the helicotrema area to monitor intraluminal pressure changes. Openings of the artificial round window membrane were performed using different ways. Opening the artificial round window mechanically showed a biphasic behaviour of pressure change. Laser openings showed a unidirectional pressure change. The lowest pressure changes were observed when opening the artificial round window membrane using a diode laser. The highest pressure changes were seen when using a needle. The openings with the CO2 laser showed a negative intracochlear pressure and a loss of fluid. In our model experiments, we could prove that the opening of the artificial round window membrane causes various intracochlear pressure changes
Unveiling the double-well energy landscape in a ferroelectric layer
The properties of ferroelectric materials, which were discovered almost a century agoĀ¹ , have led to a huge range of applications, such as digital information storageĀ² , pyroelectric energy conversionĀ³ and neuromorphic computingā“ā»āµ . Recently, it was shown that ferroelectrics can have negative capacitanceā¶ā»Ā¹Ā¹, which could improve the energy efficiency of conventional electronics beyond fundamental limitsĀ¹Ā²ā»Ā¹ā“. In LandauāGinzburgāDevonshire theoryĀ¹āµā»Ā¹ā·, this negative capacitance is directly related to the doublewell shape of the ferroelectric polarizationāenergy landscape, which was thought for more than 70 years to be inaccessible to experimentsĀ¹āø. Here we report electrical measurements of the intrinsic double-well energy landscape in a thin layer of ferroelectric Hfā.ā
Zrā.ā
Oā. To achieve this, we integrated the ferroelectric into a heterostructure capacitor with a second dielectric layer to prevent immediate screening of polarization charges during switching. These results show that negative capacitance has its origin in the energy barrier in a double-well landscape. Furthermore, we demonstrate that ferroelectric negative capacitance can be fast and hysteresis-free, which is important for prospective applicationsĀ¹ā¹. In addition, the Hfā.ā
Zrā.ā
Oā used in this work is currently the most industry-relevant ferroelectric material, because both HfOā and ZrOā thin films are already used in everyday electronicsĀ²ā°. This could lead to fast adoption of negative capacitance effects in future products with markedly improved energy efficiency
Cost-Effectiveness of Adding Cetuximab to Platinum-Based Chemotherapy for First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer
To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) from the perspective of the Canadian public healthcare system.We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%.In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of 386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab.The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy
Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria
The similarity in the genetic regulation of
arthropod and vertebrate appendage formation has been
interpreted as the product of a plesiomorphic gene
network that was primitively involved in bilaterian
appendage development and co-opted to build appendages
(in modern phyla) that are not historically related
as structures. Data from lophotrochozoans are needed to
clarify the pervasiveness of plesiomorphic appendage forming
mechanisms. We assayed the expression of three
arthropod and vertebrate limb gene orthologs, Distal-less
(Dll), dachshund (dac), and optomotor blind (omb), in
direct-developing juveniles of the polychaete Neanthes
arenaceodentata. Parapodial Dll expression marks premorphogenetic
notopodia and neuropodia, becoming restricted
to the bases of notopodial cirri and to ventral
portions of neuropodia. In outgrowing cephalic appendages,
Dll activity is primarily restricted to proximal
domains. Dll expression is also prominent in the brain. dac
expression occurs in the brain, nerve cord ganglia, a pair
of pharyngeal ganglia, presumed interneurons linking a
pair of segmental nerves, and in newly differentiating
mesoderm. Domains of omb expression include the brain,
nerve cord ganglia, one pair of anterior cirri, presumed
precursors of dorsal musculature, and the same pharyngeal
ganglia and presumed interneurons that express dac.
Contrary to their roles in outgrowing arthropod and
vertebrate appendages, Dll, dac, and omb lack comparable
expression in Neanthes appendages, implying independent
evolution of annelid appendage development. We infer
that parapodia and arthropodia are not structurally or
mechanistically homologous (but their primordia might
be), that Dllās ancestral bilaterian function was in sensory
and central nervous system differentiation, and that
locomotory appendages possibly evolved from sensory
outgrowths
Molecularābeam sampling of a hollowācathode discharge in argon as a plasma diagnostic and a source for fast neutrals
Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials
<p>Abstract</p> <p>Background</p> <p>Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.</p> <p>Methods</p> <p>In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ā„20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ā„4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures.</p> <p>Results</p> <p>Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3.</p> <p>Conclusions</p> <p>These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.</p
Examining the impact of 11 long-standing health conditions on health-related quality of life using the EQ-5D in a general population sample
Objectives
Health-related quality of life (HRQoL) measures have been increasingly used in economic evaluations for policy guidance. We investigate the impact of 11 self-reported long-standing health conditions on HRQoL using the EQ-5D in a UK sample.
Methods
We used data from 13,955 patients in the South Yorkshire Cohort study collected between 2010 and 2012 containing the EQ-5D, a preference-based measure. Ordinary least squares (OLS), Tobit and two-part regression analyses were undertaken to estimate the impact of 11 long-standing health conditions on HRQoL at the individual level.
Results
The results varied significantly with the regression models employed. In the OLS and Tobit models, pain had the largest negative impact on HRQoL, followed by depression, osteoarthritis and anxiety/nerves, after controlling for all other conditions and sociodemographic characteristics. The magnitude of coefficients was higher in the Tobit model than in the OLS model. In the two-part model, these four long-standing health conditions were statistically significant, but the magnitude of coefficients decreased significantly compared to that in the OLS and Tobit models and was ranked from pain followed by depression, anxiety/nerves and osteoarthritis.
Conclusions
Pain, depression, osteoarthritis and anxiety/nerves are associated with the greatest losses of HRQoL in the UK population. The estimates presented in this article should be used to inform economic evaluations when assessing health care interventions, though improvements can be made in terms of diagnostic information and obtaining longitudinal data
Health status utilities and the impact of pressure ulcers in long-term care residents in Ontario
Quantitative Organization of GABAergic Synapses in the Molecular Layer of the Mouse Cerebellar Cortex
In the cerebellar cortex, interneurons of the molecular layer (stellate and basket cells) provide GABAergic input to Purkinje cells, as well as to each other and possibly to other interneurons. GABAergic inhibition in the molecular layer has mainly been investigated at the interneuron to Purkinje cell synapse. In this study, we used complementary subtractive strategies to quantitatively assess the ratio of GABAergic synapses on Purkinje cell dendrites versus those on interneurons. We generated a mouse model in which the GABAA receptor Ī±1 subunit (GABAARĪ±1) was selectively removed from Purkinje cells using the Cre/loxP system. Deletion of the Ī±1 subunit resulted in a complete loss of GABAAR aggregates from Purkinje cells, allowing us to determine the density of GABAAR clusters in interneurons. In a complementary approach, we determined the density of GABA synapses impinging on Purkinje cells using Ī±-dystroglycan as a specific marker of inhibitory postsynaptic sites. Combining these inverse approaches, we found that synapses received by interneurons represent approximately 40% of all GABAergic synapses in the molecular layer. Notably, this proportion was stable during postnatal development, indicating synchronized synaptogenesis. Based on the pure quantity of GABAergic synapses onto interneurons, we propose that mutual inhibition must play an important, yet largely neglected, computational role in the cerebellar cortex
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