Absorption of Nasal and Bronchial Fluids: Precision Sampling of the Human Respiratory Mucosa and Laboratory Processing of Samples.

The methods of nasal absorption (NA) and bronchial absorption (BA) use synthetic absorptive matrices (SAM) to absorb the mucosal lining fluid (MLF) of the human respiratory tract. NA is a non-invasive technique which absorbs fluid from the inferior turbinate, and causes minimal discomfort. NA has yielded reproducible results with the ability to frequently repeat sampling of the upper airway. By comparison, alternative methods of sampling the respiratory mucosa, such as nasopharyngeal aspiration (NPA) and conventional swabbing, are more invasive and may result in greater data variability. Other methods have limitations, for instance, biopsies and bronchial procedures are invasive, sputum contains many dead and dying cells and requires liquefaction, exhaled breath condensate (EBC) contains water and saliva, and lavage samples are dilute and variable. BA can be performed through the working channel of a bronchoscope in clinic. Sampling is well tolerated and can be conducted at multiple sites in the airway. BA results in MLF samples being less dilute than bronchoalveolar lavage (BAL) samples. This article demonstrates the techniques of NA and BA, as well as the laboratory processing of the resulting samples, which can be tailored to the desired downstream biomarker being measured. These absorption techniques are useful alternatives to the conventional sampling techniques used in clinical respiratory research

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Epigenetic age acceleration in adolescence associates with BMI, inflammation and risk score for middle age cardiovascular disease

BACKGROUND: 'Accelerated ageing', assessed by adult DNA methylation predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age 17-years) associated with adiposity/CVD-risk measured (ages 17, 20, 22-years), and projected CVD by middle-age. METHODS: DNA methylation measured in peripheral blood provided 2 estimates of epigenetic age acceleration; intrinsic (IEAA, (preserved across cell types) and extrinsic (EEAA, dependent on cell admixture and methylation levels within each cell type).Adiposity was assessed by anthropometry, ultrasound and DEXA (ages 17, 20, 22 years). CVD-risk factors (lipids, HOMA-IR, blood pressure, inflammatory markers) were assessed at age 17-years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients/5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD-risk factors and CVD development. RESULTS: In 995 participants (49.6% female, age 17.3+/-0.6 years), EEAA (/5-years) was associated with increased BMI of 2.4% (95%CI 1.2-3.6%) and 2.4% (0.8-3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3-33%) in hsCRP, 10% (4-17%) in interferon-gamma induced protein (IP-10) and 4% (2-6%) in tumour necrosis factor receptor 2 (sTNFR2), adjusted for BMI and HOMA-IR. EEAA(/5-years) results in a 4% increase in hard endpoints of CVD by 47 years old and a 3% increase, after adjustment for conventional risk factors. CONCLUSIONS: Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle-age CVD. Irrespective whether this is cause or effect, assessing epigenetic age might refine disease prediction

A reference time scale for Site U1385 (Shackleton Site) on the SW Iberian Margin

We produced a composite depth scale and chronology for Site U1385 on the SW Iberian Margin. Using log(Ca/Ti) measured by core scanning XRF at 1-cm resolution in all holes, a composite section was constructed to 166.5 meters composite depth (mcd) that corrects for stretching and squeezing in each core. Oxygen isotopes of benthic foraminifera were correlated to a stacked δ^18O reference signal (LR04) to produce an oxygen isotope stratigraphy and age model. Variations in sediment color contain very strong precession signals at Site U1385, and the amplitude modulation of these cycles provides a powerful tool for developing an orbitally-tuned age model. We tuned the U1385 record by correlating peaks in L* to the local summer insolation maxima at 37^oN. The benthic δ^18O record of Site U1385, when placed on the tuned age model, generally agrees with other time scales within their respective chronologic uncertainties. The age model is transferred to down-core data to produce a continuous time series of log(Ca/Ti) that reflect relative changes of biogenic carbonate and detrital sediment. Biogenic carbonate increases during interglacial and interstadial climate states and decreases during glacial and stadial periods. Much of the variance in the log(Ca/Ti) is explained by a linear combination of orbital frequencies (precession, tilt and eccentricity), whereas the residual signal reflects suborbital climate variability. The strong correlation between suborbital log(Ca/Ti) variability and Greenland temperature over the last glacial cycle at Site U1385 suggests that this signal can be used as a proxy for millennial-scale climate variability over the past 1.5 Ma. Millennial climate variability, as expressed by log(Ca/Ti) at Site U1385, was a persistent feature of glacial climates over the past 1.5 Ma, including glacial periods of the early Pleistocene (‘41-kyr world’) when boundary conditions differed significantly from those of the late Pleistocene (‘100-kyr world’). Suborbital variability was suppressed during interglacial stages and enhanced during glacial periods, especially when benthic δ^18O surpassed ~ 3.3-3.5‰. Each glacial inception was marked by appearance of strong millennial variability and each deglaciation was preceded by a terminal stadial event. Suborbital variability may be a symptomatic feature of glacial climate or, alternatively, may play a more active role in the inception and/or termination of glacial cycles.This research was supported by the Natural Environmental Research Council Grant NE/K005804/1 to DH and LS and NE/J017922/1 to DH.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.gloplacha.2015.07.00

Kombinasi Format Factory, U-lead dan Microsoft Office Powerpoint dalam Upaya Meningkatkan Kualitas Media Pembelajaran

Peserta didik mempunyai gaya belajar yang berbeda-beda. Gaya belajar tersebut meliputi auditori, visual dan kinestetik (VAK). Seorang guru harus mampu memenuhi kebutuhan masing-masing gaya belajar peserta didik tersebut. Salah satu cara yang dapat dilakukan adalah dengan menggunakan media pembelajaran berbasis VAK. Media pembelajaran berbasis VAK dapat dipenuhi dengan menyisipkan file video di dalamnya. Selain itu, penggunaan file video sebagai media pembelajaran mendukung implementasi pembelajaran saintifik pada kurikulum 2013. Namun, belum semua guru memiliki kemampuan untuk mengemas file video tersebut dalam bentuk media pembelajaran. Tujuan penelitian ini adalah untuk meningkatkan kemampuan guru-guru di SMA Negeri 1 Teras dan SMA Negeri 1 Boyolali dalam membuat media pembelajaran berbasis VAK dengan kombinasi software Format Factory, U-Lead dan PowerPoint. Hasil penelitian menunjukkan bahwa terjadi peningkatan kemampuan para guru di SMA Negeri 1 Teras dan SMA Negeri 1 Boyolali dalam membuat media pembelajaran. Peningkatan kemampuan guru-guru tersebut berada di atas target yang direncanakan. Rerata peningkatan kemampuan guru-guru di SMA Negeri 1 Teras 7,87% di atas target, sedangkan di SMA Negeri 1 Boyolali 9,58% di atas target. Kata kunci: Media Pembelajaran, Format Factory, U-Lead, PowerPoint Students have different learning styles. Learning styles include visual learners, auditory learners, and kinesthetic learners. A teacher must be able to fulfill the needs of individual students\u27 learning styles. One way that can be applied is using Visual, Audio and Kinesthetic (VAK) learning media based. VAK-learning media based can be created by inserting video files on it. In addition, using video file as a learning media can support the implementation of scientific learning on the 2013 curriculum. However, not all teachers have the ability to use video files into a learning media. The purpose of this study is to improve the teachers\u27 ability at SMA Negeri 1 Teras and SMAN 1 Boyolali on making VAK-learning media based with a combination of Format Factory, U-Lead and PowerPoint software. The results showed that the teachers\u27 ability on making VAK-learning media based was increased. Increased the teachers\u27 ability was above planned target score. The mean score of the teachers\u27 ability at SMA Negeri 1 Teras 7.87% above the target, while at SMAN 1 Boyolali 9.58% above the target

Epidural Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Comprehensive Evidence-Based Guidelines.

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations

A reference time scale for Site U1385 (Shackleton Site) on the SW Iberian Margin

Variations in sediment color contain very strong precession signals at Site U1385, and the amplitude modulation of these cycles provides a powerful tool for developing an orbitally-tuned age model. We tuned the U1385 record by correlating peaks in L* to the local summer insolation maxima at 37°N. The benthic δ18O record of Site U1385, when placed on the tuned age model, generally agrees with other time scales within their respective chronologic uncertainties. The age model is transferred to down-core data to produce a continuous time series of log(Ca/Ti) that reflect relative changes of biogenic carbonate and detrital sediment. Biogenic carbonate increases during interglacial and interstadial climate states and decreases during glacial and stadial periods. Much of the variance in the log(Ca/Ti) is explained by a linear combination of orbital frequencies (precession, tilt and eccentricity), whereas the residual signal reflects suborbital climate variability. The strong correlation between suborbital log(Ca/Ti) variability and Greenland temperature over the last glacial cycle at Site U1385 suggests that this signal can be used as a proxy for millennial-scale climate variability over the past 1.5 Ma. Millennial climate variability, as expressed by log(Ca/Ti) at Site U1385, was a persistent feature of glacial climates over the past 1.5 Ma, including glacial periods of the early Pleistocene (‘41-kyr world’) when boundary conditions differed significantly from those of the late Pleistocene (‘100-kyr world’). Suborbital variability was suppressed during interglacial stages and enhanced during glacial periods, especially when benthic δ18O surpassed ~ 3.3–3.5‰. Each glacial inception was marked by appearance of strong millennial variability and each deglaciation was preceded by a terminal stadial event. Suborbital variability may be a symptomatic feature of glacial climate or, alternatively, may play a more active role in the inception and/or termination of glacial cycles

First measurement of muon-neutrino disappearance in NOvA

This paper reports the first measurement using the NOvA detectors of νμ disappearance in a νμ beam. The analysis uses a 14 kton-equivalent exposure of 2.74×1020 protons-on-target from the Fermilab NuMI beam. Assuming the normal neutrino mass hierarchy, we measure Δm232=(2.52+0.20−0.18)×10−3  eV2 and sin2θ23 in the range 0.38–0.65, both at the 68% confidence level, with two statistically degenerate best-fit points at sin2θ23=0.43 and 0.60. Results for the inverted mass hierarchy are also presented

First measurement of electron neutrino appearance in NOvA

We report results from the first search for νμ→νe transitions by the NOvA experiment. In an exposure equivalent to 2.74×1020 protons on target in the upgraded NuMI beam at Fermilab, we observe 6 events in the Far Detector, compared to a background expectation of 0.99±0.11(syst) events based on the Near Detector measurement. A secondary analysis observes 11 events with a background of 1.07±0.14(syst). The 3.3σ excess of events observed in the primary analysis disfavors 0.1π<δCP<0.5π in the inverted mass hierarchy at the 90% C.L