Shear stress has been recognized as an important parameter in controlling particle back-transport from membrane surfaces. However, little is known of the relationship between transient shear ...conditions induced by air sparging and fouling control near membrane surfaces. In this paper, the different types of surface shear stress profiles that had beneficial effects on minimizing reversible surface fouling were examined. The relationship between different statistical shear parameters (e.g. time-averaged shear, standard deviation of shear and amplitude of shear) and fouling control that have been used by others were examined as well. It was found that the fouling rate for membranes subjected to transient shear conditions was lower than for membranes subjected to constant shear conditions. The magnitude, duration and frequency of the shear conditions were found to have an impact on the fouling rate of membranes. It was also found that although some statistical shear parameters could generally be used to relate shear and fouling, they were inadequate to relate surface shear stress to fouling, for all transient shear conditions examined.
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► Shear stress profiles with beneficial effects on minimizing fouling were examined. ► Transient shear profiles yielded less fouling, compared to constant shear profiles. ► Magnitude, duration and frequency of the shear profiles affected fouling rate. ► Some statistical shear parameters were inadequate in relating shear to fouling.
ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended ...Phase 2 dose (RP2D).
Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement.
80 patients were enrolled, 61 in dose-escalation/food-effect cohorts and 19 with pre-defined tumour types in the expansion cohort. The most common ARQ 087-related adverse events were fatigue (49%), nausea (46%), aspartate aminotransferase (AST) increase (30%), and diarrhoea (23%). Four patients (5%) experienced grade 1 treatment-related hyperphosphataemia. Dose-limiting toxicity was reversible grade 3 AST increase. The RP2D was 300 mg QD. Pharmacokinetics were linear and dose-proportional from 25 to 325 mg QD, and were unaffected by food. Statistically significant changes (P-value<0.05) suggest phosphate and FGF19 levels as markers of target engagement. In 18 evaluable patients with FGFR genetic alterations, 3 confirmed partial responses (two intrahepatic cholangiocarcinomas (iCCA) with FGFR2 fusions and one urothelial cancer with FGFR2 and FGF19 amplification) and two durable stable disease at ⩾16 weeks with tumour reduction (FGFR2 fusion-positive iCCA and adrenocortical carcinoma with FGFR1 amplification) were observed.
ARQ 087 had manageable toxicity at the RP2D of 300 mg QD, showed pharmacodynamics effects, and achieved objective responses, notably in patients with FGFR2 genetic alterations.
Increasing anthropogenic CO
2
emissions to the atmosphere are causing a rise in
p
CO
2
concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve ...our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO
2
levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO
2
gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO
2
concentrations increased. CO
2
enrichment caused significant increases in chlorophyll
a
concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO
2
levels increased. The responses of benthic microalgae to rising anthropogenic CO
2
emissions are likely to have significant ecological ramifications for coastal systems.
The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an ...outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0–∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.
The measurement of OH reactivity, the inverse of the OH lifetime, provides a powerful tool to investigate atmospheric photochemistry. A new airborne OH reactivity instrument was designed and deployed ...for the first time on the NASA DC-8 aircraft during the second phase of Intercontinental Chemical Transport Experiment-B (INTEX-B) campaign, which was focused on the Asian pollution outflow over Pacific Ocean and was based in Hawaii and Alaska. The OH reactivity was measured by adding OH, generated by photolyzing water vapor with 185 nm UV light in a moveable wand, to the flow of ambient air in a flow tube and measuring the OH signal with laser induced fluorescence. As the wand was pulled back away from the OH detector, the OH signal decay was recorded; the slope of −Δln(signal)/Δ time was the OH reactivity. The overall absolute uncertainty at the 2σ confidence levels is about 1 s−1 at low altitudes (for decay about 6 s−1), and 0.7 s−1 at high altitudes (for decay about 2 s−1). From the median vertical profile obtained in the second phase of INTEX-B, the measured OH reactivity (4.0±1.0 s−1) is higher than the OH reactivity calculated from assuming that OH was in steady state (3.3±0.8 s−1), and even higher than the OH reactivity that was calculated from the total measurements of all OH reactants (1.6±0.4 s−1). Model calculations show that the missing OH reactivity is consistent with the over-predicted OH and under-predicted HCHO in the boundary layer and lower troposphere. The over-predicted OH and under-predicted HCHO suggest that the missing OH sinks are most likely related to some highly reactive VOCs that have HCHO as an oxidation product.
The noncoding genome is pervasively transcribed. Noncoding RNAs (ncRNAs) generated from enhancers have been proposed as a general facet of enhancer function and some have been shown to be required ...for enhancer activity. Here we examine the transcription-factor-(TF)-dependence of ncRNA expression to define enhancers and enhancer-associated ncRNAs that are involved in a TF-dependent regulatory network. TBX5, a cardiac TF, regulates a network of cardiac channel genes to maintain cardiac rhythm. We deep sequenced wildtype and
-mutant mouse atria, identifying ~2600 novel
-dependent ncRNAs. Tbx5-dependent ncRNAs were enriched for tissue-specific marks of active enhancers genome-wide. Tbx5-dependent ncRNAs emanated from regions that are enriched for TBX5-binding and that demonstrated Tbx5-dependent enhancer activity.
-dependent ncRNA transcription provided a quantitative metric of
-dependent enhancer activity, correlating with target gene expression. We identified
, a novel
-dependent long noncoding RNA (lncRNA) required for the expression of the calcium-handling gene
. We illustrate that TF-dependent enhancer transcription can illuminate components of TF-dependent gene regulatory networks.
Increased BMI may increase the body's capacity to store potent inhaled anaesthetics, more so with more soluble agents. Accordingly, we asked whether increased BMI and longer anaesthesia prolonged ...airway reflex recovery.
We measured time from anaesthetic discontinuation until first response to command (T1); from response to command until ability to swallow (T2); and from anaesthetic discontinuation to recovery of ability to swallow (T3) in 120 patients within three BMI ranges (18–24, 25–29, and ≥30 kg m−2). All received sevoflurane or desflurane, delivered via an LMA.
T1 and T3 after sevoflurane exceeded T1 and T3 after desflurane: 6.6 (sd 4.2) vs 4.0 (1.9) min (P<0.001), and 14.1 (sd 8.3) vs 6.1 (2.0) min (P<0.0001). T3 correlated more strongly with BMI after sevoflurane (28 s per kg m−2, P=0.02) than desflurane (7 s per kg m−2, P=0.03). Regarding T2, patients receiving sevoflurane with BMI ≥30 kg m−2 were less often able to swallow 2 min after response to command than were those with BMI 18–24 or 25–29 kg m−2 (3/20 vs 10/20 or 9/20, P<0.05). Each sevoflurane MAC-hour delayed T3 by 4.5 min (268 s) (R=0.46, P<0.001) whereas each desflurane MAC-hour delayed T3 by 0.2 min (16 s) (R=0.10, P=0.44).
Prolonged sevoflurane administration and greater BMI delay airway reflex recovery. The contribution of BMI to this delay is more pronounced after sevoflurane than desflurane.
Highlights • We evaluated gravimetric measurement of blood loss at postpartum haemorrhage. • We compared measured blood loss with fall in haemoglobin after postpartum haemorrhage. • We used ...simulation to compare gravimetric measurement with visual estimation. • A good correlation exists between gravimetrically measured blood loss and fall in haemoglobin. • Gravimetric measurement was more accurate than visual estimation in simulated postpartum haemorrhage.
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