A key feature in intestinal immunity is the dynamic intestinal barrier, which separates the host from resident and pathogenic microbiota through a mucus gel impregnated with antimicrobial peptides. ...Using a forward genetic screen, we have found a mutation in Tvp23b, which conferred susceptibility to chemically induced and infectious colitis. Trans-Golgi apparatus membrane protein TVP23 homolog B (TVP23B) is a transmembrane protein conserved from yeast to humans. We found that TVP23B controls the homeostasis of Paneth cells and function of goblet cells, leading to a decrease in antimicrobial peptides and more penetrable mucus layer. TVP23B binds with another Golgi protein, YIPF6, which is similarly critical for intestinal homeostasis. The Golgi proteomes of YIPF6 and TVP23B-deficient colonocytes have a common deficiency of several critical glycosylation enzymes. TVP23B is necessary for the formation of the sterile mucin layer of the intestine and its absence disturbs the balance of host and microbe in vivo.
We present the results of models that were designed to study all possible water maser transitions in the frequency range 0–1.91 THz, with particular emphasis on maser transitions that may be ...generated in evolved-star envelopes and observed with the ALMA and SOFIA telescopes. We used tens of thousands of radiative transfer models of both spin-species of H2O, spanning a considerable parameter space in number density, kinetic temperature and dust temperature. Results, in the form of maser optical depths, have been summarized in a master table. Maser transitions identified in these models were grouped according to loci of inverted regions in the density/kinetic temperature plane, a property clearly related to the dominant mode of pumping. A more detailed study of the effect of dust temperature on maser optical depth enabled us to divide the maser transitions into three groups: those with both collisional and radiative pumping schemes (22, 96, 209, 321, 325, 395, 941 and 1486 GHz), a much larger set that are predominantly radiatively pumped, and another large group with a predominantly collisional pump. The effect of accelerative and decelerative velocity shifts of up to 5 km s−1 was found to be generally modest, with the primary effect of reducing computed maser optical depths. More subtle asymmetric effects, dependent on line overlap, include maximum gains offset from zero shift by >1 km s−1, but these effects were predominantly found under conditions of weak amplification. These models will allow astronomers to use multitransition water maser observations to constrain physical conditions down to the size of individual masing clouds (size of a few astronomical units).
The Rim Fire was one of the largest wildfires in California history, burning over 250,000 acres during August and September 2013 affecting air quality locally and regionally in the western U.S. ...Routine surface monitors, remotely sensed data, and aircraft based measurements were used to assess how well the Community Multiscale Air Quality (CMAQ) photochemical grid model applied at 4 and 12 km resolution represented regional plume transport and chemical evolution during this extreme wildland fire episode. Impacts were generally similar at both grid resolutions although notable differences were seen in some secondary pollutants (e.g., formaldehyde and peroxyacyl nitrate) near the Rim fire. The modeling system does well at capturing near-fire to regional scale smoke plume transport compared to remotely sensed aerosol optical depth (AOD) and aircraft transect measurements. Plume rise for the Rim fire was well characterized as the modeled plume top was consistent with remotely sensed data and the altitude of aircraft measurements, which were typically made at the top edge of the plume. Aircraft-based lidar suggests O3 downwind in the Rim fire plume was vertically stratified and tended to be higher at the plume top, while CMAQ estimated a more uniformly mixed column of O3. Predicted wildfire ozone (O3) was overestimated both at the plume top and at nearby rural and urban surface monitors. Photolysis rates were well characterized by the model compared with aircraft measurements meaning aerosol attenuation was reasonably estimated and unlikely contributing to O3 overestimates at the top of the plume. Organic carbon was underestimated close to the Rim fire compared to aircraft data, but was consistent with nearby surface measurements. Periods of elevated surface PM2.5 at rural monitors near the Rim fire were not usually coincident with elevated O3.
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•Rim fire plume well characterized by modeling system in horizontal and vertical space•Predicted wildfire O3 was overestimated at plume top and at the surface.•Predicted wildfire PM2.5 organic carbon underestimated at plume top.•Elevated PM2.5 from fire not always coincident with elevated O3 at surface
Current good practice guidelines for national greenhouse gas inventories requires that seasonal variation in emission factors from savanna fires be considered when compiling national accounts. ...African studies concluded that the emission factor for methane decreases during the dry season principally due to curing of the fuels. However, available data from Australian tropical savannas shows no effect of seasonality on emission factors, consistent with observations that the fine fuels appear to cure fully soon after the start of the fire season. To test whether the seasonality in greenhouse gas emission factors reported for Africa also occurs in Australia, methane and nitrous oxide emission factors were measured in early and in late dry season fires in Western Arnhem Land, a region typical of much of the northern Australia savanna zone. We found no significant seasonality in methane emission factors, but there was substantial variation in emission factors associated with inter‐fire differences in vegetation and fuel. This variation could be explained almost completely by combustion efficiency. Nitrous oxide emission factors were not related to combustion efficiency but showed some variation across vegetation and fuel size class. Both methane and nitrous oxide emission factors were consistent with previous work in northern Australia and with some published values from Africa. The absence of a significant seasonal trend in emission factors indicates that savanna fire emissions in northern Australia can be managed by strategic prescribed burning.
Key Points
Methane emission factors from savanna fires do not vary seasonally
Methane emission factors vary across fuel types and vegetation types
To quantify how differences in metrics characterizing physical activity and sedentary behaviour in type 2 diabetes are associated with physical function.
This analysis included participants' data ...from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) cross-sectional study. Data were stratified into two groups according to their short physical performance battery (SPPB) score (impaired physical function = SPPB < 10 and normal physical function = SPPB ≥ 10). Hand-grip strength, sit-to-stand 60 (STS-60) and the Duke Activity Status Index (DASI) score were used to assess functional capacity, while physical activity metrics were measured with a wrist-worn accelerometer. The associations between physical activity metrics and measures of functional capacity were analysed using generalized linear modelling.
Some 635 adults (median age 66 years, 34% female) were included in this analysis. Overall, 29% of the cohort scored < 10 in the SPPB test indicating impaired physical function. This group spent more time in prolonged sedentary behaviour (600.7 vs. 572.5 min) and undertook less-intense physical activity. Each sd increase in physical activity volume and intensity gradients for those with impaired physical function was associated with 17% more repetitions for STS-60 with similar associations seen for DASI score. Each sd in sedentary time was associated with 15% fewer repetitions in STS-60 and 16% lower DASI score in those with impaired physical function, whereas in normal physical function group it was 2% and 1%, respectively.
The strength of the associations for physical activity measures and functional capacity were modified by physical function status, with the strongest association seen in those with impaired physical function.
To investigate pregnancy outcomes following maternal use of pregabalin.
This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those ...of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013.
Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 6.0% vs 12/580 2.1%; odds ratio 3.0, 95% confidence interval 1.2-7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion.
This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies.
To evaluate how common radiation therapy techniques perform in the setting of the new European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) ...delineation recommendations for immediate breast reconstruction (IBR).
Seven Danish radiation therapy centres and six international European centres participated in this project. Two breast cancer cases (one left-sided and one right-sided) with a retropectoral implant were chosen for radiation therapy planning using deep-inspiration breath-hold. Target volumes were delineated according to ESTRO-ACROP delineation recommendations. The centres were asked to plan the cases using any radiation therapy technique according to the Danish Breast Cancer Group plan objectives.
In total, 35 treatment plans were collected. Half of the submitted plans, for both the left-sided and the right-sided case, used the field-in-field (FiF) technique (nine for each), a quarter used volumetric arc radiation therapy (VMAT; five for right-sided, four for left-sided) and the remaining quarter was a mix of inverse intensity-modulated radiation therapy (IMRT), helicoidal therapy and hybrid (combined open fields and VMAT) techniques. Mean clinical target volume doses were in the range 99–102% of the prescribed dose. The median FiF mean heart dose (MHD) for right-sided radiation therapy was 1 Gy (range 0.8–3.7) and 5.2 Gy for left-sided radiation therapy (range 2.2–6.5). For right-sided radiation therapy, the median VMAT MHD was 3.42 Gy, for IMRT was 2.3 Gy and for helicoidal therapy was 5.1 Gy. For left-sided radiation therapy, the median VMAT MHD was 6.3 Gy, for IMRT was 7.8 Gy and for helicoidal therapy was 7.3 Gy.
Different radiation therapy techniques could be used to plan radiation therapy in the setting of IBR. FiF provided good coverage with acceptable organ at risk doses. The best dose distribution results as a trade-off between the objectives of target volume coverage and high-dose organ at risk inclusion. The radiation therapy technique affects the interplay between these objectives.
•The study evaluated different radiation therapy techniques to plan postoperative radiation in the setting of immediate reconstruction.•All tested radiation therapy techniques could produce acceptable plans, including field-in-field (FiF) tangential plans.•IMRT offers better target coverage than FiF at the cost of a higher mean heart dose and increased low doses to distant OAR.•The ‘price’ of the low dose bath inverse radiation therapy plans should be considered when evaluating such treatments.
Objectives
Water is an essential nutrient for thermoregulation, metabolism, cognition, and overall physiological homeostatic function. However, aging adults display a blunted thirst mechanism and ...subsequently have an increased risk for dehydration or hyponatremia. Fluid consumption behaviors are modifiable and the importance of practicing adequate drinking behaviors for aging adults is amplified during exercise. Identification of aging adult’s hydration beliefs and how they attain hydration advice could provide valuable information into ways to promote better drinking habits to reduce fluid imbalances. Thus, this investigation evaluated the knowledge, beliefs and behaviors of middle-aged cyclists (MA) that were associated with hydration status and drinking behavior, before and during a 164-km mass-participation event (ambient temperature, 33.3±2.8ºC(mean±SD)). Design: This cross-sectional field study retrospectively grouped participants by their second urine specific gravity (U
sg
) measurement of the event morning prior to a mass participation cycling event. U
sg
was assessed via handheld refractometer.
Setting
The Hotter N’ Hell Hundred 164-km cycling event in Wichita Falls, Texas during the month of August.
Participants
36 male recreational cyclists (age, 53±9 y(mean±SD)).
Measurements
Participants were grouped according their urine specific gravity as either slightly hyperhydrated (SH; n=12, U
sg
≤1.014), euhydrated (EUH; n=12, U
sg
, 1.015-1.020), or slightly dehydrated (SD; n=12, U
sg
≥1.021). Exercise histories and questionnaires were recorded 24-48 h prior to the cycling event.
Results
Regardless of pre-event hydration status, all groups experienced a similar body mass loss during the 164-km event and finished with statistically similar exercise times; also, drinking behavior within all groups was influenced by multiple factors. The primary factors associated with MA cyclist drinking behavior were trial and error/personal history and thirst; further, the majority of cyclists (≥65%) in SH, EUH, and SD believed that dehydration affects performance negatively. The least important factors included rehydration recommendations from scientific and sports medicine organizations, plus information from sports drink manufacturers.
Conclusion
Considering the complexity of the present findings and the physiological changes that accompany aging such as delayed thirst perception, we recommend that MA cyclists formulate an individualized drinking plan that is based on observations during exercise.
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