Ferroelectric thin film acoustic devices with electrical multiband switching ability

Design principles of a new class of microwave thin film bulk acoustic resonators with multiband resonance frequency switching ability are presented. The theory of the excitation of acoustic eigenmodes in multilayer ferroelectric structures is considered, and the principle of selectivity for resonator with an arbitrary number of ferroelectric layers is formulated. A so called “criterion function” is suggested that allows to determine the conditions for effective excitation at one selected resonance mode with suppression of other modes. The proposed theoretical approach is verifiedusing thepreexisting experimental data published elsewhere. Finally, the possible application of the two ferroelectric layers structures for switchable microwave overtone resonators, binary and quadrature phase-shift keying modulators are discussed. These devices could play a pivotal role in the miniaturization of microwave front-end antenna circuits

New-physics contributions to the forward-backward asymmetry in B -> K* mu+ mu-

We study the forward-backward asymmetry (AFB) and the differential branching ratio (DBR) in B -> K* mu+ mu- in the presence of new physics (NP) with different Lorentz structures. We consider NP contributions from vector-axial vector (VA), scalar-pseudoscalar (SP), and tensor (T) operators, as well as their combinations. We calculate the effects of these new Lorentz structures in the low-q^2 and high-q^2 regions, and explain their features through analytic approximations. We find two mechanisms that can give a significant deviation from the standard-model predictions, in the direction indicated by the recent measurement of AFB by the Belle experiment. They involve the addition of the following NP operators: (i) VA, or (ii) a combination of SP and T (slightly better than T alone). These two mechanisms can be distinguished through measurements of DBR in B -> K* mu+ mu- and AFB in B -> K mu+ mu-.Comment: 33 pages, revtex, 9 figures. Paper originally submitted with the wrong figures. This is corrected in the replacement. An incorrect factor of 2 found in a formula. This is corrected and figures modified. Conclusions unchanged. Typos correcte

Prospective mental imagery as its link with anxiety and depression in prisoners

Mental imagery is known to play a key role in the development and maintenance of depression and anxiety. Prisoners commonly experience psychological distress, but interventions to address this are currently lacking. We aimed to examine the link between prospective mental imagery and anxiety and depression among prisoners. One hundred twenty-three male prisoners from a Category C prison in southwest England participated in the study. They completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the General Anxiety Disorder Scale (GAD-7) to measure whether they experience depression and/or anxiety symptoms. Furthermore, they completed additional questionnaires to evaluate their prospective mental imagery. Results showed that 67.5% of prisoners presented with more depression symptoms and 27.7% with more anxiety symptoms. Supporting earlier findings, our data revealed that some dimensions of prospective mental imagery were significantly related with increased anxiety and depression symptoms in prisoners. Namely, intrusive negative personally relevant imagery was a positive predictor and likelihood of positive events a negative predictor of both anxiety and depression symptoms. The perceived likelihood of negative events was a positive predictor of depression. Intrusive verbal thought was a positive predictor of anxiety. The obtained results suggest the need to develop interventions not only targeting the reduction of prospective negative imagery but also the enhancement of positive mental imagery

Future oriented group training for suicidal patients: a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>In routine psychiatric treatment most clinicians inquire about indicators of suicide risk, but once the risk is assessed not many clinicians systematically focus on suicidal thoughts. This may reflect a commonly held opinion that once the depressive or anxious symptoms are effectively treated the suicidal symptoms will wane. Consequently, many clients with suicidal thoughts do not receive systematic treatment of their suicidal thinking. There are many indications that specific attention to suicidal thinking is necessary to effectively decrease the intensity and recurrence of suicidal thinking. We therefore developed a group training for patients with suicidal thoughts that is easy to apply in clinical settings as an addition to regular treatment and that explicitly focuses on suicidal thinking. We hypothesize that such an additional training will decrease the frequency and intensity of suicidal thinking.</p> <p>We based the training on cognitive behavioural approaches of hopelessness, worrying, and future perspectives, given the theories of Beck, McLeod and others, concerning the lack of positive expectations characteristic for many suicidal patients. In collaboration with each participant in the training individual positive future possibilities and goals were challenged.</p> <p>Methods/Design</p> <p>We evaluate the effects of our program on suicide ideation (primary outcome measure). The study is conducted in a regular treatment setting with regular inpatients and outpatients representative for Dutch psychiatric treatment settings. The design is a RCT with two arms: TAU (Treatment as Usual) versus TAU plus the training. Follow up measurements are taken 12 months after the first assessment.</p> <p>Discussion</p> <p>There is a need for research on the effectiveness of interventions in suicidology, especially RCT's. In our treatment program we combine aspects and interventions that have been proven to be useful in the treatment of suicidal thinking and behavior.</p> <p>Trial registration</p> <p>ISRCTN56421759</p

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors.

Purpose To evaluate MK-8242 in patients with wild-type TP53 advanced solid tumors. Patients and Methods MK-8242 was administered orally twice a day on days 1 to 7 in 21-day cycles. The recommended phase II dose (RP2D) was determined on the basis of safety, tolerability, pharmacokinetics (PK), and by mRNA expression of the p53 target gene pleckstrin homology-like domain, family A, member 3 ( PHLDA3). Other objectives were to characterize the PK/pharmacodynamic (PD) relationship, correlate biomarkers with response, and assess tumor response. Results Forty-seven patients received MK-8242 across eight doses that ranged from 60 to 500 mg. Initially, six patients developed dose-limiting toxicities (DLTs): grade (G) 2 nausea at 120 mg; G3 fatigue at 250 mg; G2 nausea and G4 thrombocytopenia at 350 mg; and G3 vomiting and G3 diarrhea at 500 mg. DLT criteria were revised to permit management of GI toxicities. Dosing was resumed at 400 mg, and four additional DLTs were observed: G4 neutropenia and G4 thrombocytopenia at 400 mg and G4 thrombocytopenia (two patients) at 500 mg. Other drug-related G3 and G4 events included anemia, leukopenia, pancytopenia, nausea, hyperbilirubinemia, hypophosphatemia, and anorexia. On the basis of safety, tolerability, PK, and PD, the RP2D was established at 400 mg (15 evaluable patients experienced two DLTs). PK for 400 mg (day 7) showed Cmax 3.07 μM, Tmax 3.0 hours, t1/2 (half-life) 6.6 hours, CL/F (apparent clearance) 28.9 L/h, and Vd/F (apparent volume) 274 L. Blood PHLDA3 mRNA expression correlated with drug exposure ( R(2) = 0.68; P < .001). In 41 patients with postbaseline scans, three patients with liposarcoma achieved a partial response (at 250, 400, and 500 mg), 31 showed stable disease, and eight had progressive disease. In total, 27 patients with liposarcoma had a median progression-free survival of 237 days. Conclusion At the RP2D of 400 mg twice a day, MK-8242 activated the p53 pathway with an acceptable safety and tolerability profile. The observed clinical activity (partial response and prolonged progression-free survival) provides an impetus for further study of HDM2 inhibitors in liposarcoma

Colloids as Mobile Substrates for the Implantation and Integration of Differentiated Neurons into the Mammalian Brain

Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76% cell survival rate one week post-surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons

Childhood febrile illness and the risk of myopia in UK Biobank participants

Purpose Historical reports suggest febrile illness during childhood is a risk factor for myopia. The establishment of the UK Biobank provided a unique opportunity to investigate this relationship. Patients and methods We studied a sample of UK Biobank participants of White ethnicity aged 40–69 years old who underwent autorefraction (N=91 592) and were classified as myopic (≤−0.75 Dioptres (D)), highly myopic (≤−6.00 D), or non-myopic (>−0.75 D). Self-reported age at diagnosis of past medical conditions was ascertained during an interview with a nurse at a Biobank assessment centre. Logistic regression analysis was used to calculate the odds ratio (OR) for myopia or high myopia associated with a diagnosis before age 17 years of each of nine febrile illnesses, after adjusting for potential confounders (age, sex, highest educational qualification, and birth order). Results Rubella, mumps, and pertussis were associated with myopia: rubella, OR=1.38, 95% CI: 1.03–1.85, P=0.030; mumps, OR=1.32, 95% CI: 1.07–1.64, P=0.010; and pertussis, OR=1.39, 95% CI 1.03–1.87, P=0.029. Measles, rubella, and pertussis were associated with high myopia: measles, OR=1.48, 95% CI: 1.07–2.07, P=0.019; rubella, OR=1.94, 95% CI: 1.12–3.35, P=0.017; and pertussis, OR=2.15, 95% CI: 1.24–3.71, P=0.006. The evidence did not support an interaction between education and febrile illness in explaining the above risks. Conclusion A history of childhood measles, rubella, or pertussis was associated with high myopia, whereas a history of childhood rubella, mumps, or pertussis was associated with any myopia. The reasons for these associations are unclear

Nanotechnology in Head and Neck Cancer: The Race Is On

Rapid advances in the ability to produce nanoparticles of uniform size, shape, and composition have started a revolution in the sciences. Nano-sized structures herald innovative technology with a wide range of potential therapeutic and diagnostic applications. More than 1000 nanostructures have been reported, many with potential medical applications, such as metallic-, dielectric-, magnetic-, liposomal-, and carbon-based structures. Of these, noble metallic nanoparticles are generating significant interest because of their multifunctional capacity for novel methods of laboratory-based diagnostics, in vivo clinical diagnostic imaging, and therapeutic treatments. This review focuses on recent advances in the applications of nanotechnology in head and neck cancer, with special emphasis on the particularly promising plasmonic gold nanotechnology