Abyssal peridotites are ultramafic rocks collected from mid-ocean ridges that are the residues of adiabatic decompression melting. Their compositions provide information on the degree of melting and ...melt–rock interaction involved in the formation of oceanic lithosphere, as well as providing constraints on pre-existing mantle heterogeneities. This review presents a compilation of abyssal peridotite geochemical data (modes, mineral major elements, and clinopyroxene trace elements) for >1200 samples from 53 localities on 6 major ridge systems. On the basis of composition and petrography, peridotites are classified into one of five lithological groups: (1) residual peridotite, (2) dunite, (3) gabbro-veined and/or plagioclase-bearing peridotite, (4) pyroxenite-veined peridotite, and (5) other types of melt-added peridotite. Almost a third of abyssal peridotites are veined, indicating that the oceanic lithospheric mantle is more fertile, on average, than estimates based on residual peridotites alone imply. All veins appear to have formed recently during melt transport beneath the ridge, though some pyroxenites may be derived from melting of recycled oceanic crust.
A limited number of samples are available at intermediate and fast spreading rates, with samples from the East Pacific Rise indicating high degrees of melting. At slow and ultra-slow spreading rates, residual abyssal peridotites define a large (0–15% modal clinopyroxene and spinel Cr#=0.1–0.6) compositional range. These variations do not match the prediction for how degree of melting should vary as a function of spreading rate. Instead, the compositional ranges of residual peridotites are derived from a combination of melting, melt–rock interaction and pre-existing compositional variability, where melt–rock interaction is used here as a general term to refer to the wide range of processes that can occur during melt transport in the mantle. Globally, ~10% of abyssal peridotites are refractory (0% clinopyroxene, spinel Cr#>0.5, bulk Al2O3<1wt.%) and some ridge sections are dominated by harzburgites while lacking a significant basaltic crust. Abyssal ultramafic samples thus indicate that the mantle is multi-component, probably consisting of at least three components (lherzolite, harzburgite, and pyroxenite). Overall, the large compositional range among residual and melt-added peridotites implies that the oceanic lithospheric mantle is heterogeneous, which will lead to the generation of further heterogeneities upon subduction back into the mantle.
•A global database for >1200 abyssal peridotite compositions is presented.•Abyssal peridotites have large major and trace element compositional ranges.•Compositions reflect melting, melt–rock interaction and source heterogeneity.•Peridotites extend to refractory compositions at all spreading rates.•The mantle globally consists of fertile and refractory domains.
: media-1vid110.1542/5840360268001PEDS-VA_2018-1235
BACKGROUND: Childhood food allergy (FA) is a life-threatening chronic condition that substantially impairs quality of life. This large, ...population-based survey estimates childhood FA prevalence and severity of all major allergenic foods. Detailed allergen-specific information was also collected regarding FA management and health care use.
A survey was administered to US households between 2015 and 2016, obtaining parent-proxy responses for 38 408 children. Prevalence estimates were based on responses from NORC at the University of Chicago's nationally representative, probability-based AmeriSpeak Panel (51% completion rate), which were augmented by nonprobability-based responses via calibration weighting to increase precision. Prevalence was estimated via weighted proportions. Multiple logistic regression models were used to evaluate FA predictors.
Overall, estimated current FA prevalence was 7.6% (95% confidence interval: 7.1%-8.1%) after excluding 4% of children whose parent-reported FA reaction history was inconsistent with immunoglobulin E-mediated FA. The most prevalent allergens were peanut (2.2%), milk (1.9%), shellfish (1.3%), and tree nut (1.2%). Among food-allergic children, 42.3% reported ≥1 severe FA and 39.9% reported multiple FA. Furthermore, 19.0% reported ≥1 FA-related emergency department visit in the previous year and 42.0% reported ≥1 lifetime FA-related emergency department visit, whereas 40.7% had a current epinephrine autoinjector prescription. Prevalence rates were higher among African American children and children with atopic comorbidities.
FA is a major public health concern, affecting ∼8% of US children. However, >11% of children were perceived as food-allergic, suggesting that the perceived disease burden may be greater than previously acknowledged.
We review recent work on the functions of interoceptive processing, by which the nervous system anticipates, senses, and integrates signals originating from the body. We focus on several exemplar ...functions of interoception, including energy regulation (ingestion and excretion), memory, affective and emotional experience, and the psychological sense of self. We emphasize two themes across these functions. First, the anatomy of interoceptive afferents makes it difficult to manipulate or directly measure interoceptive signaling in humans. Second, recent evidence shows that multimodal integration occurs across interoceptive modalities and between interoceptive and exteroceptive modalities. Whereas exteroceptive multimodal integration has been studied relatively extensively, fundamental questions remain regarding multimodal integration that involves interoceptive modalities. Future empirical work is required to better understand how and where multimodal interoceptive integration occurs.
A key function of interoception is signaling about the body’s energy status, which then drives the behaviors needed to renew energy resources.Methodologies to manipulate and measure interoceptive signaling in humans are currently limited, which presents a challenge for the full understanding of some of the functions of interoceptive processing.Recent work suggests that the accessibility of C-tactile afferent nerve endings and their fibers in mammalian hairy skin, a pathway that mediates affective touch and shares anatomical features with classical interoceptive afferents, may provide an externally accessible experimental channel for the manipulation of interoceptive signaling in healthy humans.In real-world situations, sensations (e.g., touch) are usually multimodal, with the co-location of sense data coming from activity in both interoceptive (affective touch) and exteroceptive (tactile) afferents.
Future climate change projections for phase 5 of the Coupled Model Intercomparison Project (CMIP5) are presented for the Community Earth System Model version 1 that includes the Community Atmospheric ...Model version 5 CESM1(CAM5). These results are compared to the Community Climate System Model, version 4 (CCSM4) and include simulations using the representative concentration pathway (RCP) mitigation scenarios, and extensions for those scenarios beyond 2100 to 2300. Equilibrium climate sensitivity of CESM1 (CAM5) is 4.10°C, which is higher than the CCSM4 value of 3.20°C. The transient climate response is 2.33°C, compared to the CCSM4 value of 1.73°C. Thus, even though CESM1(CAM5) includes both the direct and indirect effects of aerosols (CCSM4 had only the direct effect), the overall climate system response including forcing and feedbacks is greater in CESM1(CAM5) compared to CCSM4. The Atlantic Ocean meridional overturning circulation (AMOC) in CESM1(CAM5) weakens considerably in the twenty-first century in all the RCP scenarios, and recovers more slowly in the lower forcing scenarios. The total aerosol optical depth (AOD) changes from ∼0.12 in 2006 to ∼0.10 in 2100, compared to a preindustrial 1850 value of 0.08, so there is less negative forcing (a net positive forcing) from that source during the twenty-first century. Consequently, the change from 2006 to 2100 in aerosol direct forcing in CESM1(CAM5) contributes to greater twenty-first century warming relative to CCSM4. There is greater Arctic warming and sea ice loss in CESM1(CAM5), with an ice-free summer Arctic occurring by about 2060 in RCP8.5 (2040s in September) as opposed to about 2100 in CCSM4 (2060s in September).
Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is ...also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.
Mammographic breast density is a strong risk factor for breast cancer. Tamoxifen, which reduces the risk of breast cancer in women at high risk, also reduces mammographic breast density. However, it ...is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug.
We conducted a nested case-control study within the first International Breast Cancer Intervention Study, a randomized prevention trial of tamoxifen vs placebo. Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5% increments. Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram, which took place 12-18 months after trial entry, and control subjects were 942 women without breast cancer. Multivariable logistic regression was used to adjust for other risk factors. All statistical tests were two-sided.
In the tamoxifen arm, 46% of women had a 10% or greater reduction in breast density at their 12- to 18-month mammogram. Compared with all women in the placebo group, women in the tamoxifen group who experienced a 10% or greater reduction in breast density had 63% reduction in breast cancer risk (odds ratio = 0.37, 95% confidence interval = 0.20 to 0.69, P = .002), whereas those who took tamoxifen but experienced less than a 10% reduction in breast density had no risk reduction (odds ratio = 1.13, 95% confidence interval = 0.72 to 1.77, P = .60). In the placebo arm, there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10% reduction in mammographic density and subjects who experienced a greater reduction.
The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting.
Transcranial magnetic stimulation (TMS) enables non-invasive modulation of brain activity with both clinical and research applications, but fundamental questions remain about the neural types and ...elements TMS activates and how stimulation parameters affect the neural response.
To develop a multi-scale computational model to quantify the effect of TMS parameters on the direct response of individual neurons.
We integrated morphologically-realistic neuronal models with TMS-induced electric fields computed in a finite element model of a human head to quantify the cortical response to TMS with several combinations of pulse waveforms and current directions.
TMS activated with lowest intensity intracortical axonal terminations in the superficial gyral crown and lip regions. Layer 5 pyramidal cells had the lowest thresholds, but layer 2/3 pyramidal cells and inhibitory basket cells were also activated at most intensities. Direct activation of layers 1 and 6 was unlikely. Neural activation was largely driven by the field magnitude, rather than the field component normal to the cortical surface. Varying the induced current direction caused a waveform-dependent shift in the activation site and provided a potential mechanism for experimentally observed differences in thresholds and latencies of muscle responses.
This biophysically-based simulation provides a novel method to elucidate mechanisms and inform parameter selection of TMS and other cortical stimulation modalities. It also serves as a foundation for more detailed network models of the response to TMS, which may include endogenous activity, synaptic connectivity, inputs from intrinsic and extrinsic axonal projections, and corticofugal axons in white matter.
•Implemented multi-scale model of TMS-induced neural activation in motor cortex.•Axon morphology varied by cell type and determined dependence of activation on spatial parameters of electric field.•TMS activated with lowest intensity layer 5 pyramidal cells at their axonal terminations.•Neural activation was driven by electric field magnitude, rather than its normal component, resulting in strongest activation of superficial gyral crown/lip region.•Model predicts monophasic A–P TMS activates more anterior region of precentral gyrus than P–A TMS.
Inhaled nitric oxide Yu, Binglan; Ichinose, Fumito; Bloch, Donald B ...
British journal of pharmacology,
January 2019, Letnik:
176, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Nitric oxide (NO) is a gas that induces relaxation of smooth muscle cells in the vasculature. Because NO reacts with oxyhaemoglobin with high affinity, the gas is rapidly scavenged by oxyhaemoglobin ...in red blood cells and the vasodilating effects of inhaled NO are limited to ventilated regions in the lung. NO therefore has the unique ability to induce pulmonary vasodilatation specifically in the portions of the lung with adequate ventilation, thereby improving oxygenation of blood and decreasing intrapulmonary right to left shunting. Inhaled NO is used to treat a spectrum of cardiopulmonary conditions, including pulmonary hypertension in children and adults. However, the widespread use of inhaled NO is limited by logistical and financial barriers. We have designed, developed and tested a simple and economic NO generation device, which uses pulsed electrical discharges in air to produce therapeutic levels of NO that can be used for inhalation therapy.
Linked Articles
This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy for the motor symptoms of Parkinson's disease (PD). However, the neural elements mediating symptom relief are ...unclear. A previous study concluded that direct optogenetic activation of STN neurons was neither necessary nor sufficient for relief of parkinsonian symptoms. However, the kinetics of the channelrhodopsin-2 (ChR2) used for cell-specific activation are too slow to follow the high rates required for effective DBS, and thus the contribution of activation of STN neurons to the therapeutic effects of DBS remains unclear. We quantified the behavioral and neuronal effects of optogenetic STN DBS in female rats following unilateral 6-hydroxydopamine (6-OHDA) lesion using an ultrafast opsin (Chronos). Optogenetic STN DBS at 130 pulses per second (pps) reduced pathologic circling and ameliorated deficits in forelimb stepping similarly to electrical DBS, while optogenetic STN DBS with ChR2 did not produce behavioral effects. As with electrical DBS, optogenetic STN DBS exhibited a strong dependence on stimulation rate; high rates produced symptom relief while low rates were ineffective. High-rate optogenetic DBS generated both increases and decreases in firing rates of single neurons in STN, globus pallidus externa (GPe), and substantia nigra pars reticular (SNr), and disrupted β band oscillatory activity in STN and SNr. High-rate optogenetic STN DBS can indeed ameliorate parkinsonian motor symptoms through reduction of abnormal oscillatory activity in the STN-associated neural circuit, and these results highlight that the kinetic properties of opsins have a strong influence on the effects of optogenetic stimulation.
Whether STN local cells contribute to the therapeutic effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) remains unclear. We re-examined the role of STN local cells in mediating the symptom-relieving effects of STN DBS using cell type-specific optogenetic stimulation with a much faster opsin, Chronos. Direct optogenetic stimulation of STN neurons was effective in treating the symptoms of parkinsonism in the 6-hydroxydopamine (6-OHDA) lesion rat. These results highlight that the kinetic properties of opsins can have a strong influence on the effects of optogenetic activation/inhibition and must be considered when employing optogenetic to study high-rate neural stimulation.
Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains poorly described.
Systematic ...PubMed, Science Direct and Scopus searches for articles reporting phenotypic (liquid culture drug susceptibility testing or pyrazinamidase activity assays) and/or genotypic (polymerase chain reaction or DNA sequencing) PZA resistance. Global and regional summary estimates were obtained from random-effects meta-analysis, stratified by presence or risk of multidrug resistant TB (MDR-TB). Regional summary estimates were combined with regional WHO TB incidence estimates to determine the annual burden of PZA resistance. Information on single nucleotide polymorphisms (SNPs) in the pncA gene was aggregated to obtain a global summary.
Pooled PZA resistance prevalence estimate was 16.2% (95% CI 11.2-21.2) among all TB cases, 41.3% (29.0-53.7) among patients at high MDR-TB risk, and 60.5% (52.3-68.6) among MDR-TB cases. The estimated global burden is 1.4 million new PZA resistant TB cases annually, about 270,000 in MDR-TB patients. Among 1,815 phenotypically resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout the pncA gene.
PZA resistance is ubiquitous, with an estimated one in six incident TB cases and more than half of all MDR-TB cases resistant to PZA globally. The diversity of SNPs across the pncA gene complicates the development of rapid molecular diagnostics. These findings caution against relying on PZA in current and future TB drug regimens, especially in MDR-TB patients.
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