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Mitigation of hearing loss from semi-circular canal transection in pseudomonas otitis media with ciprofloxacin-dexamethasone irrigation.

HYPOTHESIS: Irrigation of the mastoid with a quinolone antibiotic-steroid solution may mitigate hearing loss caused by iatrogenic semicircular canal injury in the presence of Pseudomonas aeruginosa (PA) otitis media (OM). BACKGROUND: Studies have shown the cochlea to be more vulnerable to semicircular canal transection (SCT)-related hearing loss in the presence of PA OM. Prophylactic systemic antibiotics and steroids may decrease this hearing loss, but SCT is usually not planned. The aim of this study was to determine if irrigation with ciprofloxacin-dexamethasone (cipro-dex) could improve hearing outcomes following SCT in PA OM. METHODS: PA OM was induced in 28 animals. After three to five days, unilateral SCT was performed in each animal, with sham SCT on the contralateral ear. At surgery, half of the animals (n = 14) underwent irrigation of the both mastoid bullae with cipro-dex; the second group of animals (n = 14) underwent irrigation of the bullae with sterile saline. Auditory thresholds were obtained immediately prior to SCT and 7-10 days after SCT. RESULTS: SCT ears treated with cipro-dex showed a mean click threshold improvement of 4.6 dB from pre-transection to 7-10 days post-transection, whereas thresholds in the SCT ears treated with saline worsened by 7.5 dB (p = 0.15). CONCLUSION: Irrigation of the guinea pig bulla with cipro-dex following SCT in the setting of PA OM appears safe and may yield beneficial effects on hearing.

Animals↗

Mendelian randomization underscores the importance of clinical nursing in mitigating anxiety and panic attack risks among low-educated populations.

Considering the complex and underexplored interplay between educational attainment (EA) and the prevalence of anxiety and panic attacks, which carries significant societal implications, we have designed a two-sample Mendelian randomization (MR) study. The primary objective of this research is to elucidate the causal relationship between education level and the risk of anxiety and panic attacks, thereby providing novel insights for clinical and nursing strategies. Our study adheres to the STROBE-MR guidelines and employs a classical two-sample MR analysis to investigate the causal relationship between EA (exposure) and the occurrence of anxiety/panic attacks (outcome). The data for 8 education-related phenotypes, along with anxiety and panic attack outcomes, were sourced from European population-based Genome-wide association studies databases. To ensure robustness, we applied 5 distinct MR analytical methods, supplemented by comprehensive sensitivity analyses, heterogeneity assessments, and evaluations of reverse causality bias to uphold rigorous quality control standards. Our findings, robust across various MR methods and consistent after inverse variance-weighted and false discovery rate (FDR) corrections, indicate a significant association between lower EA and an increased risk of anxiety or panic attacks. Specifically, individuals with no formal qualifications exhibited a higher risk (P-value&#x2005;=&#x2005;.005, OR&#x2005;=&#x2005;1.017, 95% CI&#x2005;=&#x2005;1.005-1.029, FDR&#x2005;=&#x2005;0.011). In contrast, higher levels of education were associated with a reduced risk: College or University degree (P-value&#x2005;<&#x2005;.01, OR&#x2005;=&#x2005;0.989, 95% CI&#x2005;=&#x2005;0.984-0.995, FDR&#x2005;=&#x2005;0.0007), EA (P-value&#x2005;<&#x2005;.01, OR&#x2005;=&#x2005;0.999, 95% CI&#x2005;=&#x2005;0.998-0.9995, FDR&#x2005;=&#x2005;0.0009), and A levels/AS levels or equivalent (P-value&#x2005;=&#x2005;.011, OR&#x2005;=&#x2005;0.988, 95% CI&#x2005;=&#x2005;0.978-0.997, FDR&#x2005;=&#x2005;0.019). These conclusions were consistently supported by at least 4 MR methods and successfully passed all quality control checks. Our study demonstrates a negative correlation between years of education and the risk of anxiety and panic attacks, suggesting that clinical nursing and patient education efforts should prioritize tailored psychological support and patient communication for individuals with lower EA. This population warrants enhanced attention and more compassionate care to mitigate their elevated risk of anxiety-related disorders.

Humans↗

Policy considerations for using forests to mitigate carbon dioxide emissions.

A recent article in Nature, "Soil Fertility Limits Carbon Sequestration by Forest Ecosystems in a CO2-Enriched Atmosphere" by Oren and colleagues, has been widely reported on, and often misinterpreted, by the press. The article dampens enthusiasm for accelerated forest growth due to CO2 fertilization and puts in question the fringe theory that the world"s forests can provide an automatic mitigation feedback. We agree that these results increase our understanding of the global carbon cycle. At the same time, their relevance in the context of the international climate change negotiations is much more complicated than portrayed by newspapers such as the New York Times ("Role of Trees in Curbing Greenhouse Gases is Challenged", May 24, 2001) and the Christian Science Monitor ("Trees No Savior for Global Warming", May 25, 2001).

Atmospheric Pressure↗

Moderated designs can balance between batch-effect mitigation and cell loss due to hashtag-assisted pooling in single-cell experiments.

Minimizing experimental noise is integral to robust data generation in single-cell omics. The current standard for avoiding batch effects during sample processing is barcode- or hashtag-assisted combining of different experimental treatments into one pool, allowing all samples to be subject to the technical protocols uniformly. The final data points for each treatment group are then computationally separated based on the original hashtag labels. Clearly, whereas hashtagging all groups and pooling them in a single well is expected to minimize batch effects, the procedure can also lead to a loss of cells that cannot be confidently decoded during the computational demultiplexing step. Here, we examine four alternate experimental designs, namely, compound, reference, chain, and confounded, that could be used instead of a single-pool approach and quantify the batch effects as well as cell loss in each case. We find a linear relationship-the percentage of cells lost is double the number of hashtags used in the experiment. We use these analyses to identify experimental designs that can successfully mitigate batch effects while minimizing multiplexing, hence the cell loss, in each well. Although a reference design offers the best overall performance, this study can help individual investigators choose particular approaches that are best suited for their biological questions.

Journal Article↗

Experimental evidence of shock mitigation in a Hertzian tapered chain.

We present an experimental study of the mechanical impulse propagation through a horizontal alignment of elastic spheres of progressively decreasing diameter phi(n): namely, a tapered chain. Experimentally, the diameters of spheres which interact via the Hertz potential are selected to keep as close as possible to an exponential decrease, phi(n+1) = (1-q)phi(n), where the experimental tapering factor is either q(1) approximately equal to 5.60% or q(2) approximately equal to 8.27%. In agreement with recent numerical results, an impulse initiated in a monodisperse chain (a chain of identical beads) propagates without shape changes and progressively transfers its energy and momentum to a propagating tail when it further travels in a tapered chain. As a result, the front pulse of this wave decreases in amplitude and accelerates. Both effects are satisfactorily described by the hard-sphere approximation, and basically, the shock mitigation is due to partial transmissions, from one bead to the next, of momentum and energy of the front pulse. In addition when small dissipation is included, better agreement with experiments is found. A close analysis of the loading part of the experimental pulses demonstrates that the front wave adopts a self-similar solution as it propagates in the tapered chain. Finally, our results corroborate the capability of these chains to thermalize propagating impulses and thereby act as shock absorbing devices.

Journal Article↗

Mitigation of tokamak disruptions using high-pressure gas injection.

High-pressure gas-jet injection of neon and argon is shown to be a simple and robust method to mitigate the deleterious effects of disruptions on the DIII-D tokamak. The gas jet penetrates to the central plasma at its sonic velocity. The deposited species dissipates >95% of the plasma by radiation and substantially reduces mechanical stresses on the vessel caused by poloidal halo currents. The gas-jet species-charge distribution can include >50% fraction neutral species which inhibits runaway electrons. The favorable scaling of this technique to burning fusion plasmas is discussed.

Journal Article↗

Deconvolution methods for mitigation of transverse blurring in optical coherence tomography.

Imaging resolution in optical coherence tomography (OCT) is a key determinant for acquiring clinically useful optical biopsies of tissues. In contrast to light or confocal microscopy, the axial and transverse resolutions in OCT are independent and each can be analyzed individually. A method for mitigating transverse blurring and the apparent loss of transverse resolution in OCT by means of Gaussian beam deconvolution is presented. Such a method provides better representation of a specimen by using known physical parameters of a lens. To implement this method, deconvolution algorithms based on a focal-dependent kernel are investigated. First, the direct inverse problem is investigated using two types of regularization, truncated singular value decomposition, and Tikhonov. Second, an iterative expectation maximization algorithm, the Richardson-Lucy algorithm, with a beam-width-dependent iteration scheme is developed. A dynamically iterative Richardson-Lucy algorithm can reduce transverse blurring by providing an improvement in the transverse point-spread-function for sparse scattering samples in regions up to two times larger than the confocal region of the lens. These deblurring improvements inside and outside of the confocal region, which are validated experimentally, are possible without introducing new optical imaging hardware or acquiring multiple images of the same specimen. Implementation of this method in sparse scattering specimens, such as engineered tissues, has the potential to improve cellular detection and categorization.

Algorithms↗

Role of histidine interruption in mitigating the pathological effects of long polyglutamine stretches in SCA1: A molecular approach.

Polyglutamine expansions, leading to aggregation, have been implicated in various neurodegenerative disorders. The range of repeats observed in normal individuals in most of these diseases is 19-36, whereas mutant proteins carry 40-81 repeats. In one such disorder, spinocerebellar ataxia (SCA1), it has been reported that certain individuals with expanded polyglutamine repeats in the disease range (Q(12)HQHQ(12)HQHQ(14/15)) but with histidine interruptions were found to be phenotypically normal. To establish the role of histidine, a comparative study of conformational properties of model peptide sequences with (Q(12)HQHQ(12)HQHQ(12)) and without (Q(42)) interruptions is presented here. Q(12)HQHQ(12)HQHQ(12) displays greater solubility and lesser aggregation propensity compared to uninterrupted Q(42) as well as much shorter Q(22). The solvent and temperature-driven conformational transitions (beta structure <--> random coil --> alpha helix) displayed by these model polyQ stretches is also discussed in the present report. The study strengthens our earlier hypothesis of the importance of histidine interruptions in mitigating the pathogenicity of expanded polyglutamine tract at the SCA1 locus. The relatively lower propensity for aggregation observed in case of histidine interrupted stretches even in the disease range suggests that at a very low concentration, the protein aggregation in normal cells, is possibly not initiated at all or the disease onset is significantly delayed. Our present study also reveals that besides histidine interruption, proline interruption in polyglutamine stretches can lower their aggregation propensity.

Amino Acid Sequence↗

Mitigation and benefits measures as policy tools for siting potentially hazardous facilities: determinants of effectiveness and appropriateness.

How do mitigation and benefits measures affect public acceptance for siting different kinds of potentially hazardous facilities? What kinds of benefits measures are seen as most (or least) appropriate for different kinds of facilities? This study used a nationwide telephone survey consisting of 1,234 interviews with randomly selected respondents to test for the effects of packages of safety and benefits measures for siting a landfill, prison, incinerator and nuclear waste repository. The experimental design used in the survey permits analysis of the fractions of respondents who are willing to change their initial levels of acceptance (or opposition) when presented with a sequence of the safety and benefit measures. The measures vary significantly in their impact on levels of acceptance for the facilities, and some measures that would at face value appear to reassure residents of facility safety turn out to lack credibility and therefore diminish facility acceptance. Ordering of the benefits versus safety measures significantly affects changes in acceptance in surprising ways. The perceived appropriateness of different kinds of benefits measures varies systematically by the type of facility under consideration. It appears that successful benefits packages will directly address the underlying dimensions of concern caused by the facility. These findings point to the importance of further research on "commensurable" benefits measures.

Journal Article↗

Destocking as a drought-mitigation strategy: clarifying rationales and answering critiques.

The idea of externally assisted emergency destocking of pastoralists has gained currency in recent years: increasing the incentives for pastoralists to sell animals, or removing the constraints to selling animals in the early stages of drought. We identify two separate rationales put forward by proponents of destocking: environmental benefits and purchasing power/welfare benefits. We consider whether specific recent critiques of 'new range ecology' and specifically of 'tracking policies' do in fact provide arguments against emergency destocking in pastoralist areas. We illustrate some of these themes with a case study of a successful destocking exercise in northern Kenya where a very specific form of support was requested and received by pastoralists themselves. The sorts of destocking that work are likely to have significant effects on pastoralist purchasing power at key points of the drought cycle, but minimal effects on the environment. Clarifying these points will make it easier to promote destocking as a drought-mitigation policy.

Agriculture↗

Bud endophytes of Scots pine produce adenine derivatives and other compounds that affect morphology and mitigate browning of callus cultures.

Endophytes are found in meristematic bud tissues of Scots pine (Pinus sylvestris L.) especially prior to growth, which would suggest their involvement in growth of the bud. To test this hypothesis, production of phytohormones by two bacterial (Methylobacterium extorquens, Pseudomonas synxantha) and one fungal endophyte (Rhodotorula minuta) was studied by mass spectrometry. The most common gibberellins, auxins, or cytokinins were not detected in the fractions studied. Instead, M. extorquens and R. minuta produced adenine derivatives that may be used as precursors in cytokinin biosynthesis. A plant tissue culture medium was conditioned with the endophytes, and pine tissue cultures were started on the media. Tetracycline inhibited callus production, which was restored on the endophyte-conditioned media. In addition, conditioning mitigated browning of the Scots pine explants. However, a decrease in tissue size was observed on the endophyte-conditioned media. Addition of adenosine monophosphate in the plant culture medium restored callus production and increased growth of the tissues, but had no effect on browning. Therefore, production of adenine ribosides by endophytes may play some role in the morphological effect observed in the pine tissues.

Journal Article↗

Mitigation of beta 1- and/or beta 2-adrenoceptor function in human heart failure.

1. Patients with congestive heart failure (CHF) have an elevated activity of the sympatho-adrenal system. We have investigated several aspects of beta-adrenoceptor desensitization in such patients. 2. The positive inotropic response to isoprenaline was attenuated in CHF patients, and the pD2-values for isoprenaline's positive inotropic effect gradually decreased in more severe forms of the disease. Stimulation of adenylate cyclase by isoprenaline was also mitigated in cardiac membranes from patients with CHF. 3. We then studied the density of cardiac beta 1- and beta 2-adrenoceptors in order to understand the mechanism of beta-adrenoceptor desensitization in these patients. Our data show that cardiac beta 1-adrenoceptors are down-regulated in all forms of severe CHF, but that cardiac beta 2-adrenoceptor density decreases only in some forms of CHF including ischaemic cardiomyopathy and mitral valve disease. 4. In circulating mononuclear leucocytes (MNL) obtained from CHF patients at rest, isoprenaline- and prostaglandin E1-stimulated cAMP generation as well as cholera toxin and pertussis toxin catalyzed ADP ribosylation were similar to those in MNL from control patients. However, pretreatment of intact MNL with pertussis toxin enhanced cAMP generation in CHF patients but not in healthy control subjects, suggesting a tonic inhibitory effect of Gi in such patients. 5. We conclude that alterations of adrenoceptors and of their signal transduction might contribute to the desensitization of beta-adrenergic responses in CHF.

Heart Failure↗

Mitigating human disturbance: can protection influence trajectories of recovery in benthic assemblages?

1. Understanding whether Marine Protected Areas (MPAs) can be considered as a suitable tool for restoring the structure and function of populations and assemblages is urgently needed to achieve an effective policy of mitigation of human impact in coastal management. However, to date, the role played by MPAs in enhancing ecosystems resilience has been more advocated than unambiguously documented. 2. This study was designed to test whether full protection in marine reserves facilitates recovery of benthos impacted by the date mussel Lithophaga lithophaga fishery, one of the most harmful human activities affecting subtidal rocky habitats in the Mediterranean Sea. 3. The effects of this destructive fishery were reproduced at one fully protected location (P) and at two unprotected control locations (Cs) in the SW Mediterranean Sea. At each location, three plots (4 m2) of rocky surface at 4-6 m depth were disturbed experimentally, while another three plots served as reference. In each plot, the species composition and relative cover of the sessile benthic assemblages were sampled photographically on each of five occasions during a period of 20 months. 4. Over and above variation in habitat features among locations, multivariate and univariate analyses revealed significant differences between P-vs.-Cs in patterns of assemblage recovery and showed that, at the fully protected location, recovery was faster than at the unprotected control locations. 5. Our results suggest that MPAs have the potential to change the trajectories of recovery of disturbed assemblages by accelerating the processes of recolonization and call for further investigation to identify the specific mechanisms underlying increased resilience.

Animals↗

[31P]/[1H] nuclear magnetic resonance study of mitigating effects of GYKI 52466 on kainate-induced metabolic impairment in perfused rat cerebrocortical slices.

PURPOSE: Kainic acid (KA) has long been used in experimental animals to induce status epilepticus (SE). A mechanistic implication of this is the association between excitotoxicity and brain damage during or after SE. We evaluated KA-induced metabolic impairment and the potential mitigating effects of GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] in superfused rat cerebral cortical slices. METHODS: Interleaved [31P]/[1H] magnetic resonance spectroscopy (MRS) was used to assess energy metabolism, intracellular pH (pHi), N-acetyl-L-aspartate (NAA) level, and lactate (Lac) formation before, during, and after a 56-min exposure to 4 mM KA in freshly oxygenated artificial cerebrospinal fluid (oxy-ACSF). RESULTS: In the absence of GYKI 52466 and during the KA exposure, NAA, PCr, and ATP levels were decreased to 91.1 +/- 0.8, 62.4 +/- 3.9, and 59.1 +/- 4.3% of the control, respectively; Lac was increased to 118.2 +/- 2.1 %, and pH, was reduced from 7.27 +/- 0.02 to 7.13 +/- 0.02. During 4-h recovery with KA-free ACSF, pHi rapidly and Lac gradually recovered, NAA decreased further to 85.5 +/- 0.3%, and PCr and ATP showed little recovery. Removal of Mg2+ from ACSF during KA exposure caused a more profound Lac increase (to 147.1 +/- 4.0%) during KA exposure and a further NAA decrease (to 80.4 +/- 0.5%) during reperfusion, but did not exacerbate PCr, ATP, and pHi changes. Inclusion of 100 microM GYKI 52466 during KA exposure significantly improved energy metabolism: the PCr and ATP levels were above 76.6 +/- 2.1 and 82.0 +/- 2.9% of the control, respectively, during KA exposure and recovered to 101.4 +/- 2.4 and 95.0 +/- 2.4%, respectively, during reperfusion. NAA level remained at 99.8 +/- 0.6% during exposure and decreased only slightly at a later stage of reperfusion. CONCLUSIONS: Our finding supports the notion that KA-induced SE causes metabolic disturbance and neuronal injury mainly by overexcitation through non-N-methyl-D-aspartate (NMDA) receptor functions.

Adenosine Triphosphate↗

A method for evaluating transmission line magnetic field mitigation strategies that incorporates biological uncertainty.

A method to determine how much reduction in public exposure to power frequency magnetic fields can be obtained for different levels of investment is presented. Which if any "effects function" best describes the relationship between field exposure and biological effect is uncertain at this time. Also, in a particular context such as construction of new transmission lines there are a variety of different technologies which might be used to reduce exposure. We describe and demonstrate a method by which exposure reduction supply curves (i.e., the cost of purchasing different amounts of exposure reduction given various mitigation options) can be estimated parametrically for different exposure conditions and effects functions, and we display illustrative results.

Cost-Benefit Analysis↗

Tennis racket shock mitigation experiments.

Measured in this study was the effectiveness of two types of retrofits in mitigating shocks in tennis rackets with ideally high grip fixity. The retrofits were a cushioned grip tape and a string implant device. Three types of rackets were investigated: wood, graphite composite, and metal. For low speed ball impact, neither retrofit changed significantly the magnitude and distribution of e, the coefficient of restitution on the racket heads. For moderate ball speeds impacting the rackets along the vertical centerline, three dynamic racket responses were measured: the free vibration damping based on racket head acceleration, the root-mean-square (rms) grip reaction force, and the fast Fourier transform (FFT) of the grip force. These latter experiments showed that the string implant device had a negligible effect on the three dynamic measures of racket response. However, the cushioned grip tape increased racket damping by up to 100 percent, reduced the rms grip force by about 20 percent, and reduced the magnitude of the FFT of this force by about 40 percent.

Biomechanical Phenomena↗

Hemodynamics analysis of a stenosed carotid bifurcation and its plaque-mitigating design.

Considering transient two-dimensional laminar flow in a diseased carotid artery segment with realistic inlet and outflow conditions, detailed velocity profiles, pressure fields, wall shear stress distributions and coupled, localized plaque formations have been simulated. The type of outflow boundary condition influences to a certain degree the extent of plaque build-up, which in turn reduces "disturbed flow" phenomena such as flow separations, recirculation zones, and wavy flow patterns in the artery branches during portions of the pulse. Based on computer experiments varying key geometric factors, a plaque-mitigating design of a carotid artery bifurcation has been proposed. Elimination of the carotid bulb, a smaller bifurcation angle, lower area ratios, and smooth wall curvatures generated a design with favorable hemodynamics parameters, leading to reduced plaque build-up by factors of 10 and 2 in the internal carotid and in the external carotid, respectively.

Blood Flow Velocity↗

Mitigating thermal mechanical damage potential during two-photon dermal imaging.

Two-photon excitation fluorescence microscopy allows in vivo high-resolution imaging of human skin structure and biochemistry with a penetration depth over 100 microm. The major damage mechanism during two-photon skin imaging is associated with the formation of cavitation at the epidermal-dermal junction, which results in thermal mechanical damage of the tissue. In this report, we verify that this damage mechanism is of thermal origin and is associated with one-photon absorption of infrared excitation light by melanin granules present in the epidermal-dermal junction. The thermal mechanical damage threshold for selected Caucasian skin specimens from a skin bank as a function of laser pulse energy and repetition rate has been determined. The experimentally established thermal mechanical damage threshold is consistent with a simple heat diffusion model for skin under femtosecond pulse laser illumination. Minimizing thermal mechanical damage is vital for the potential use of two-photon imaging in noninvasive optical biopsy of human skin in vivo. We describe a technique to mitigate specimen thermal mechanical damage based on the use of a laser pulse picker that reduces the laser repetition rate by selecting a fraction of pulses from a laser pulse train. Since the laser pulse picker decreases laser average power while maintaining laser pulse peak power, thermal mechanical damage can be minimized while two-photon fluorescence excitation efficiency is maximized.

Burns↗