Highlights • Auditory brainstem response (ABR) thresholds shift over 40 dB from 3 to 48 kHz in old mice compared to young adults. • DPOAE thresholds shifted over 40 dB in old mice, and their ...amplitudes were decreased or absent in the same frequency range. • Spiral ganglion neuron (SGN) density decreased with age in the whole cochlea with the largest decline in the basal turn. • A positive correlation between SGN density and ABR wave I amplitude was discovered. • mRNA and protein expression of GABAA R α1 and nAChR β2 decreased while NMDAR NR1 increased with age in SGNs of the old mice.
Point-absorbing wave energy converters (WECs) with a single-tether mooring are capable of extracting power from heave motion, but they do not utilise the full energy harvesting potential. One of the ...possible ways to increase the total power absorption is to add another controllable degree of freedom. These can be achieved by using a so-called ‘tripod’ configuration when the body is tied to three tethers attached to the power take-off systems at the sea floor. This paper investigates the optimal inclination of tethers considering two different approaches: a purely kinematic analysis, not taking into account the shape of the buoy and a dynamic analysis of spherical and cylindrical WECs, using a linear frequency-domain method. The results show that for a submerged sphere and for a submerged vertical cylinder with an aspect ratio of one, tethers should be orthogonal to each other, forming edges of the cuboidal vertex. Such a configuration of tethers provides for uniform performance of the WEC in all directions of motion. However, for the cylinders with an aspect ratio other than one, an optimal angle between the tethers depends greatly on the ratio between the cylinder height and diameter.
•A three-tether mooring configuration for the submerged point-absorbing wave energy converter is analysed.•For a submerged sphere, the tethers should be orthogonal to each other, forming edges of the cuboidal vertex.•For the cylinder the tether arrangement is highly dependent on the aspect ratio.•The higher the cylinders, the greater the angle between tethers should be.•The deeper the body is submerged, the less sensitive is the optimal angle to the wave frequency.
Extending laying cycle is a tendency in hen breeding, but egg quality declines as laying hens age. The present study was conducted to investigate the interactive effects of vitamins A and K3 on ...laying performance, egg and tibia quality, and antioxidative status of aged Roman Pink laying hens. In a 3 × 3 factorial arrangement, 1 080 87-week-old laying hens were allocated to nine groups with eight replicates in each group. Deficient, adequate and excess vitamins A (0, 7 000 and 14 000 IU/kg) and K3 (0, 2.0 and 4.0 mg/kg) were supplemented into a basal diet with 1 320 IU/kg of vitamin A and 0.5 mg/kg of vitamin K3. After 2 weeks of adaption to basal diet, hens were fed corresponding diets for 8 weeks. Vitamins A and K3 did not significantly affect the laying performance. However, they showed interactive effects on yolk ratio at week 93 as well as tibia weight and diameter (P < 0.05), and hens fed deficient vitamins A and K3 had the highest yolk ratio and tibia weight, but the lowest tibia diameter. Compared with deficient addition, adequate or excess vitamins A and K3 increased yolk color at weeks 93 and 97 (P < 0.05). Compared with hens fed deficient or excess vitamins, hens fed adequate vitamins A and K3 had higher eggshell strength at week 93 or 97 (P < 0.05). Increasing vitamin A elevated plasma total superoxide dismutase (T-SOD) activity and decreased hepatic glutathione peroxidase (GSH-Px) activity (P < 0.05). Excess vitamin K3 increased hepatic T-SOD activity (P < 0.05). Vitamins A and K3 exhibited interaction on the activities of antioxidative enzymes in eggshell gland (P < 0.05), and adequate or excess vitamins A and K3 increased the activities of GSH-Px, T-SOD and catalase (CAT). Adequate and excess vitamin A up-regulated the mRNA expression of GSH-Px1, GSH-Px3 and SOD1 in eggshell gland (P < 0.05). Vitamins A and K3 showed interactive effects on CAT mRNA expression in eggshell gland (P < 0.05) and hens fed adequate vitamins A and K3 had the highest CAT mRNA levels. In conclusion, dietary addition of vitamins A and K3 improved the eggshell quality and yolk color as well as antioxidative status in eggshell gland of aged laying hens. Adequate vitamins A and K3 showed beneficial effects and excess levels did not exhibit superior effects.
Chronic obstructive pulmonary disease (COPD) can greatly impact the quality of life by limiting patients' activities. However, data on impact of symptomatic burden on the health care resource ...utilization (HCRU) and employment in COPD are lacking. We examined the association between COPD Assessment Test (CAT) score and direct/indirect costs associated with HCRU and work productivity.
Data from >2,100 patients with COPD consulting for routine care were derived from respiratory disease-specific programs in Europe, the USA and China. Questionnaires, including CAT and Work Productivity and Activity Impairment (WPAI), were used to collect the past and current disease status data and HCRU characteristics from physicians (general practitioners/specialists) and patients. A regression approach was used to quantify the association of CAT with HCRU and WPAI variables. CAT score was modeled as a continuous independent variable (range: 0-40).
Ninety percent of patients with COPD had a CAT score ≥10. Short-acting therapy and maintenance bronchodilator monotherapy, respectively, were currently prescribed to patients with CAT scores of 10-19 (5.8% and 27.6%), 20-29 (5.1% and 13.1%) and 30-40 (2.8% and 6.6%). Prescribing of maintenance bronchodilator dual therapy was low across the CAT score groups (0-9, 7.8%; 10-19, 6.4%; 20-29, 5.9%; 30-40, 4.4%), whereas maintenance triple combination therapy was prescribed more commonly in patients with higher CAT scores (0-9, 16.1%; 10-19, 23.2%; 20-29, 25.9%; 30-40, 35.5%). Increasing CAT scores were significantly associated with a higher frequency of primary care physician visits (
<0.001), pulmonologist visits (
=0.007), exacerbations requiring hospitalization (
<0.001) and WPAI scores (
<0.001).
Most patients with COPD presented with high symptom levels, despite being treated for COPD. Increasing symptom burden was associated with increasing HCRU and had a detrimental impact on work productivity.
A maximum capture width tracking (MCWT) controller for ocean wave energy converters is presented. The MCWT controller is a maximum power point tracking (MPPT) controller modified to account for ...incoming wave conditions as well as WEC power output. The MCWT controller will be applied to latching control of an oscillating water column with Wells turbine, optimising the latching time based on sea state. The performance of the proposed MCWT latching controller will be compared to that of an MPPT latching controller in both stationary and transitioning sea states. In stationary seas, it will be shown that both controllers can optimise capture width to within the bounds of certainty that the optimal capture width can be known for a WEC in stochastic waves. In transitioning seas, it will be shown that the MCWT controller is robust to a changing environment, whereas the MPPT controller is not.
•A model independent controller for ocean wave energy converters (WECs) is presented.•WEC capture width is shown to be a Gaussian random variable.•The controller is shown to optimise WEC capture width in stationary seas.•The controller is robust to environmental changes in non-stationary sea states.•The controller is shown to be effective in bi-modal sea states.
Bone metastases represent a lethal condition that frequently occurs in solid tumors such as prostate, breast, lung, and renal cell carcinomas, and increase the risk of skeletal-related events (SREs) ...including pain, pathologic fractures, and spinal cord compression. This unique metastatic niche consists of a multicellular complex that cancer cells co-opt to engender bone remodeling, immune suppression, and stromal-mediated therapeutic resistance. This review comprehensively discusses clinical challenges of bone metastases, novel preclinical models of the bone and bone marrow microenviroment, and crucial signaling pathways active in bone homeostasis and metastatic niche. These studies establish the context to summarize the current state of investigational agents targeting BM, and approaches to improve BM-targeting therapies. Finally, we discuss opportunities to advance research in bone and bone marrow microenvironments by increasing complexity of humanized preclinical models and fostering interdisciplinary collaborations to translational research in this challenging metastatic niche.
Objectives: To understand the key characteristics of Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS) and to identify evidence gaps relating to the identification, treatment ...and management of ACOS patients.
Methods: A structured literature review and 1-hour telephone interviews with specialist respiratory physicians were conducted (n=10; China, France, Germany, Japan and the USA).
Results: All 10 physicians used the term ACOS in clinical practice. ACOS was not clearly defined in the literature. Prevalence of ACOS among adult patients with COPD or asthma ranged from 12-55%. ACOS patients had severe disease, with increased exacerbations and hospitalisations compared to some asthma and COPD patients. ACOS represented a clinical challenge due to a lack of evidence-based guidelines distinguishing between asthma, COPD and ACOS. Published data quantifying ACOS costs were limited.
Conclusions: There is a need for consensus evidence-based guidance to facilitate earlier diagnosis and to optimise the management of ACOS patients.
The study was performed to evaluate the effects of enzyme supplementation on performance and digestive parameters of broilers fed corn-soybean diets from 1 to 21 d of age. A total of 480 one-day-old ...Cobb broilers were allocated to 1 of 4 treatments, with 6 replicate pens per treatment and 20 birds per pen. The experiment consisted of a 2 × 2 factorial arrangement of treatments with 2 dietary ME levels (high ME, energy 1, 12.13 MJ/kg or low ME, energy 2, 11.92 MJ/kg) and 2 levels of supplemental enzyme (including xylanase, 1,800 IU/g, β-glucanase, 500 IU/g, and α-amylase, 800 U/g; 0 or 0.1% of diet). Enzyme supplementation had no effect on average daily weight gain, feed intake, and feed:gain. However, enzyme supplementation decreased the relative weight of the pancreas (d 7 and 21) in broilers fed the high ME diet. Low dietary ME level increased pancreatic lipase (d 7, P = 0.015), trypsin (d 14, P = 0.01; d 21, P = 0.014), amylase (d 21, P = 0.027), and pepsin (d 7, P = 0.001; d 21, P = 0.042) activity, but reduced pancreatic lipase (d 14, P = 0.03; d 21, P = 0.004) and amylase (d 14, P = 0.027) activity. Enzyme supplementation resulted in an increase in pancreatic amylase (d 7, P = 0.023), trypsin (d 7, P = 0.02; d 21, P = 0.004), lipase (d 21, P = 0.001), pepsin (d 7, P = 0.001; d 14, P = 0.004; d 21, P = 0.001), and maltase (d 14, P = 0.011, in ileum) activity. Moreover, broilers fed low dietary ME and enzyme supplementation diets had an increase in pancreatic lipase (d 21, P = 0.001) and pepsin (d 7, P = 0.001) activity. Low ME diets reduced jejunum villus height and jejunum and ileum crypt depth (d 7, 21). However, enzyme supplementation, especially enzyme supplementation in low ME diets, increased jejunum and ileum villus height and villus surface area. This suggested enzyme supplemented with low ME diet might be more effective to improve the activity of digestive enzymes and the absorptive capacity of the small intestine.
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