Objective
To examine oral complications 6 months after modern radiation therapy (RT) for head and neck cancer (HNC).
Methods
Prospective multicenter cohort study of patients with HNC receiving ...intensity‐modulated radiation therapy or more advanced RT. Stimulated whole salivary flow, maximal mouth opening, oral mucositis, oral pain, oral health‐related quality of life (OH‐QOL), and oral hygiene practices were measured in 372 subjects pre‐RT and 216 subjects at 6 months from the start of RT.
Results
Mean stimulated whole salivary flow declined from 1.09 to 0.47 ml/min at 6 months (p < .0001). Mean maximal mouth opening reduced from 45.58 to 42.53 mm at 6 months (p < .0001). 8.1% of subjects had some oral mucositis at 6 months, including 3.8% with oral ulceration. Mean overall pain score was unchanged. OH‐QOL was reduced at 6 months, with changes related to dry mouth, sticky saliva, swallowing solid foods, and sense of taste (p ≤ .0001). At 6 months, there was greater frequency of using dental floss and greater proportion using supplemental fluoride (p < .0001).
Conclusions
Despite advances in RT techniques, patients with HNC experience oral complications 6 months after RT, with resulting negative impacts on oral function and quality of life.
LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. ...Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10−48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5 σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020.
Background
Until recently, investigations of the normal patterns of motility of the healthy human colon have been limited by the resolution of in vivo recording techniques.
Methods
We have used a ...new, high‐resolution fiber‐optic manometry system (72 sensors at 1‐cm intervals) to record motor activity from colon in 10 healthy human subjects.
Key Results
In the fasted colon, on the basis of rate and extent of propagation, four types of propagating motor pattern could be identified: (i) cyclic motor patterns (at 2–6/min); (ii) short single motor patterns; (iii) long single motor patterns; and (iv) occasional retrograde, slow motor patterns. For the most part, the cyclic and short single motor patterns propagated in a retrograde direction. Following a 700 kCal meal, a fifth motor pattern appeared; high‐amplitude propagating sequences (HAPS) and there was large increase in retrograde cyclic motor patterns (5.6 ± 5.4/2 h vs 34.7 + 19.8/2 h; p < 0.001). The duration and amplitude of individual pressure events were significantly correlated. Discriminant and multivariate analysis of duration, gradient, and amplitude of the pressure events that made up propagating motor patterns distinguished clearly two types of pressure events: those belonging to HAPS and those belonging to all other propagating motor patterns.
Conclusions & Inferences
This work provides the first comprehensive description of colonic motor patterns recorded by high‐resolution manometry and demonstrates an abundance of retrograde propagating motor patterns. The propagating motor patterns appear to be generated by two independent sources, potentially indicating their neurogenic or myogenic origin.
This work provides the first comprehensive description of colonic motor patterns recorded by high‐resolution manometry and demonstrates an abundance of retrograde propagating motor patterns. The propagating motor patterns appear to be generated by two independent sources, potentially indicating their neurogenic or myogenic origin.
Subcutaneously injected therapeutics must pass through the interstitial matrix of the skin in order to reach their intended targets. This complex, three-dimensional structure limits the type and ...quantity of drugs that can be administered by local injection. Here we found that depolymerization of the viscoelastic component of the interstitial matrix in animal models with a highly purified recombinant human hyaluronidase enzyme (rHuPH20) increased the dispersion of locally injected drugs, across a broad range of molecular weights without tissue distortion. rHuPH20 increased infusion rates and the pattern and extent of appearance of locally injected drugs in systemic blood. In particular, rHuPH20 changed the pharmacokinetic profiles and significantly augmented the absolute bioavailability of locally injected large protein therapeutics. Importantly, within 24 h of injection, the interstitial viscoelastic barriers were restored without histologic alterations or signs of inflammation. rHuPH20 may function as an interstitial delivery enhancing agent capable of increasing the dispersion and bioavailability of coinjected drugs that may enable subcutaneous administration of therapeutics and replace intravenous delivery.
The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in <48 h from a stable ...value within 3 months. The baseline SCr may influence AKI risk and patient outcomes. The objective of this study is to determine in cirrhosis whether the baseline SCr has any effect on the in-hospital AKI course and patient survival.
North American Consortium for the Study of End-Stage Liver Disease is a consortium of tertiary-care hepatology centers prospectively enroling non-elective cirrhotic inpatients. Patients with different baseline SCr levels (≤0.5, 0.51-1.0, 1.01-1.5, >1.5 mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes and 30-day survival.
653 hospitalized cirrhotics (56.7±10years, 64% men, 30% with infection) were included. The incidence of AKI was 47% of enrolled patients. Patients with higher baseline SCr were more likely to develop AKI, with significantly higher delta and peak SCr (P<0.001) than the other groups, more likely to have a progressive AKI course (P<0.0001), associated with a significantly reduced 30-day survival (P<0.0001). Multivariate logistic regression showed that the delta SCr during an AKI episode to be the strongest factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70 mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day mortality.
Admitted cirrhotic patients with higher baseline SCr are at higher risk for in-hospital development of AKI, and more likely to have AKI progression with reduced survival. Therefore, such patients should be closely monitored and treated promptly for their AKI.
We have previously described critical and nonredundant roles for the phosphoinositide 3-kinase p110δ during the activation and differentiation of naive T cells, and p110δ inhibitors are currently ...being developed for clinical use. However, to effectively treat established inflammatory or autoimmune diseases, it is important to be able to inhibit previously activated or memory T cells. In this study, using the isoform-selective inhibitor IC87114, we show that sustained p110δ activity is required for interferon-γ production. Moreover, acute inhibition of p110δ inhibits cytokine production and reduces hypersensitivity responses in mice. Whether p110δ played a similar role in human T cells was unknown. Here we show that IC87114 potently blocked T-cell receptor–induced phosphoinositide 3-kinase signaling by both naive and effector/memory human T cells. Importantly, IC87114 reduced cytokine production by memory T cells from healthy and allergic donors and from inflammatory arthritis patients. These studies establish that previously activated memory T cells are at least as sensitive to p110δ inhibition as naive T cells and show that mouse models accurately predict p110δ function in human T cells. There is therefore a strong rationale for p110δ inhibitors to be considered for therapeutic use in T-cell–mediated autoimmune and inflammatory diseases.
Abstract
Turbulent flow in a weakly convective marine atmospheric boundary layer (MABL) driven by geostrophic winds
U
g
= 10 m s
−1
and heterogeneous sea surface temperature (SST) is examined using ...fine-mesh large-eddy simulation (LES). The imposed SST heterogeneity is a single-sided warm or cold front with temperature jumps Δ
θ
= (2, −1.5) K varying over a horizontal distance between 0.1, −6 km characteristic of an upper-ocean mesoscale or submesoscale regime. A Fourier-fringe technique is implemented in the LES to overcome the assumptions of horizontally homogeneous periodic flow. Grid meshes of 2.2 × 10
9
points with fine-resolution (horizontal, vertical) spacing (
δx
=
δy
,
δz
) = (4.4, 2) m are used. Geostrophic winds blowing across SST isotherms generate secondary circulations that vary with the sign of the front. Warm fronts feature overshoots in the temperature field, nonlinear temperature and momentum fluxes, a local maximum in the vertical velocity variance, and an extended spatial evolution of the boundary layer with increasing distance from the SST front. Cold fronts collapse the incoming turbulence but leave behind residual motions above the boundary layer. In the case of a warm front, the internal boundary layer grows with downstream distance conveying the surface changes aloft and downwind. SST fronts modify entrainment fluxes and generate persistent horizontal advection at large distances from the front.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: The purpose of this study was to assess the wear experience of silicone hydrogel daily disposable contact lenses with water surface technology over a long day of lens wear. Methods: ...Thirty-five soft contact lens wearers were refit with the daily disposable study lenses and participants scored their initial impressions of comfort, vision and satisfaction using a visual analog scale (VAS). Participants used their smart phones to complete surveys of comfort and vision on a scale of 1-10 at 10, 12, 14, and 16 hours of lens wear on 5 weeknights. A participant score for each time point was calculated by averaging the evening responses. End of study VAS surveys of symptoms were also completed. Results: Median (Interquartile Range) VAS initial impression scores were 99.00 (12.00) for quality of vision, 98.00 (16.00) for comfort, and 100.00 (13.00) for satisfaction. The end of study surveys found end of day median VAS scores of 87.00 (19.00) for end of day quality of vision and 75.00 (24.50) for end of day comfort. The median score for overall quality of vision was 93.00 (14.00) and for overall comfort was 93.00 (16.50). The median score for end of day dryness was 37.00 (55.00) and overall dryness was 13.00 (34.00). Conclusion: The daily disposable lenses with water surface treatment used in this study maintained high median scores for comfort and quality of vision for up to 16 hours of wear. Keywords: daily disposable contact lenses, water surface contact lenses, comfort, end of day comfort, long wear time
Objective: The purpose of this study was to assess the wear experience of participants while wearing a toric daily disposable contact lens with water surface technology over long days of lens wear. ...Methods: Existing soft toric contact lens wearers were fit with the daily disposable study lenses. Participants assessed their initial comfort, vision, and satisfaction with the lenses by visual analog scale (VAS) survey. After a successful 1-week follow-up visit, participants were scheduled for 5 survey days, in which surveys were deployed to their smartphones for immediate assessments of comfort and quality of vision on a 1-10 scale at 10, 12, 14, and 16 hours of lens wear on 5 subsequent weeknights. The final study visit assessed visual acuity, and overall lens wear experience surveys were completed with VAS surveys. The overall median and interquartile (IQR) range of all surveys were calculated. Results: Thirty bilateral toric lens wearers completed the study. Median (IQR) initial impression VAS scores were 97(12) for quality of vision, 100(9) for comfort, and 96(10) for satisfaction. Median evening surveys resulted in comfort scores of 10(1) at 10 hours, 9(2) at 12 hours, 9(2) at 14 hours, and 8(2) at 16 hours of wear. Median evening surveys resulted in quality of vision scores of 10(1) at 10 hours, 10(2) at 12 hours, 9(2) at 14 hours, and 9(3) at 16 hours of wear. VAS scores for overall experience were 97(9) for comfort, 95(13) for vision, and 8(31) for dryness. End-of-day VAS scores were 93(21) for comfort, 90(15) for vision, and 21(38) for dryness. Mean (+ or - standard deviation) OU LogMAR visual acuity with the study lenses was -0.19(0.06). Conclusion: Surveys of wear experience resulted in high scores for comfort and vision over the course of a long day of wear with the daily disposable study lenses in this population of patients with astigmatism. Keywords: soft contact lenses, daily disposable, end-of-day, comfort, vision
Abstract
Turbulent flow in a weakly convective marine atmospheric boundary layer (MABL) driven by geostrophic winds
V
g
= 10 m s
−1
and heterogeneous sea surface temperature (SST) is examined using ...fine-mesh large-eddy simulation (LES). The imposed SST heterogeneity is a single-sided warm or cold front with jumps Δ
θ
= (2, −1.5) K varying over a horizontal
x
distance of 1 km characteristic of an upper-ocean mesoscale or submesoscale front. The geostrophic winds are oriented parallel to the SST isotherms (i.e., the winds are alongfront). Previously, Sullivan et al. examined a similar flow configuration but with geostrophic winds oriented perpendicular to the imposed SST isotherms (i.e., the winds were across-front). Results with alongfront and across-front winds differ in important ways. With alongfront winds, the ageostrophic surface wind is weak, about 5 times smaller than the geostrophic wind, and horizontal pressure gradients couple the SST front and the atmosphere in the momentum budget. With across-front winds, horizontal pressure gradients are weak and mean horizontal advection primarily balances vertical flux divergence. Alongfront winds generate persistent secondary circulations (SC) that modify the surface fluxes as well as turbulent fluxes in the MABL interior depending on the sign of Δ
θ
. Warm and cold filaments develop opposing pairs of SC with a central upwelling or downwelling region between the cells. Cold filaments reduce the entrainment near the boundary layer top that can potentially impact cloud initiation. The surface-wind–SST-isotherm orientation is an important component of atmosphere–ocean coupling. The results also show frontogenetic tendencies in the MABL.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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