The presence of a
mutation is a predictor of poor outcome in leukaemia, and efficacious targeted therapies for these patients are lacking. The curaxin CBL0137 has demonstrated promising antitumour ...activities in multiple cancers such as glioblastoma, acting through p53 activation, NF‑κB inhibition and chromatin remodelling. In the present study, it was revealed using Annexin‑V/7‑AAD apoptosis assays that CBL0137 has efficacy across several human acute leukaemia cell lines with wild‑type
, but sensitivity is reduced in
‑mutated subtypes. A heterozygous
loss‑of‑function mutation in the
human RS4;11 cell line was generated, and it was demonstrated that heterozygous
loss‑of‑function is sufficient to cause a significant reduction in CBL0137 sensitivity. To the best of our knowledge, this is the first evidence to suggest a clinically significant role for functional p53 in the efficacy of CBL0137 in acute leukaemia. Future CBL0137 clinical trials should include
mutation screening, to establish the clinical relevance of
mutations in CBL0137 efficacy.
We investigated an outbreak of 396 Salmonella enterica serotype I 4,5,12:i:- infections to determine the source. After 7 weeks of extensive hypothesis-generation interviews, no refined hypothesis was ...formed. Nevertheless, a case-control study was initiated. Subsequently, an iterative hypothesis-generation approach used by a single interviewing team identified brand A not-ready-to-eat frozen pot pies as a likely vehicle. The case-control study, modified to assess this new hypothesis, along with product testing indicated that the turkey variety of pot pies was responsible. Review of product labels identified inconsistent language regarding preparation, and the cooking instructions included undefined microwave wattage categories. Surveys found that most patients did not follow the product's cooking instructions and did not know their oven's wattage. The manufacturer voluntarily recalled pot pies and improved the product's cooking instructions. This investigation highlights the value of careful hypothesis-generation and the risks posed by frozen not-ready-to-eat microwavable foods.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Ground- and space-based observations of solar flares from radio wavelengths to gamma-rays have produced considerable insights but raised several unsolved controversies. The last unexplored wavelength ...frontier for solar flares is in the range of submillimeter and infrared wavelengths. Here we report the detection of an intense impulsive burst at 30 THz using a new imaging system. The 30 THz emission exhibited remarkable time coincidence with peaks observed at microwave, mm/submm, visible, EUV, and hard X-ray wavelengths. The emission location coincides with a very weak white-light feature, and is consistent with heating below the temperature minimum in the atmosphere. However, there are problems in attributing the heating to accelerated electrons. The peak 30 THz flux is several times larger than the usual microwave peak near 9 GHz, attributed to non-thermal electrons in the corona. The 30 THz emission could be consistent with an optically thick spectrum increasing from low to high frequencies. It might be part of the same spectral component found at sub-THz frequencies whose nature remains mysterious. Further observations at these wavelengths will provide a new window for flare studies.
We present an asteroseismic study of the solar-like stars KIC 11395018, KIC 10273246, KIC 10920273, KIC 10339342, and KIC 11234888 using short-cadence time series of more than eight months from the ...Kepler satellite. For four of these stars, we derive atmospheric parameters from spectra acquired with the Nordic Optical Telescope. The global seismic quantities (average largefrequency separation and frequency of maximum power), combined with the atmospheric parameters, yield the mean density and surface gravity with precisions of 2% and ~0.03 dex, respectively. We also determine the radius, mass, and age with precisions of 2–5%, 7–11%, and ~35%, respectively, using grid-based analyses. Coupling the stellar parameters with photometric data yields an asteroseismic distance with a precision better than 10%. A vsini measurement provides a rotational period-inclination correlation, and using the rotational periods from the recent literature, we constrain the stellar inclination for three of the stars. An Li abundance analysis yields an independent estimate of the age, but this is inconsistent with the asteroseismically determined age for one of the stars. We assess the performance of five grid-based analysis methods and find them all to provide consistent values of the surface gravity to ~0.03 dex when both atmospheric and seismic constraints are at hand. The different grid-based analyses all yield fitted values of radius and mass to within 2.4σ, and taking the mean of these results reduces it to 1.5σ. The absence of a metallicity constraint when the average large frequency separation is measured with a precision of 1% biases the fitted radius and mass for the stars with non-solar metallicity (metal-rich KIC 11395018 and metal-poor KIC 10273246), while including a metallicity constraint reduces the uncertainties in both of these parameters by almost a factor of two. We found that including the average small frequency separation improves the determination of the age only for KIC 11395018 and KIC 11234888, and for the latter this improvement was due to the lack of strong atmospheric constraints.
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Background
Despite its widespread use, the beneficial effect of low‐dose fentanyl administered at induction of anesthesia on perioperative outcomes has not been studied in the ambulatory setting. ...Therefore, this study was designed to test the hypothesis that administration of small‐dose fentanyl vs. saline during induction reduces coughing and movements without adversely affecting recovery after day‐surgery.
Methods
One hundred consenting outpatients scheduled to undergo superficial surgical procedures under general anesthesia with a laryngeal mask airway (LMA) device for airway management were randomly assigned to one of two treatment groups: control (n = 50) or fentanyl (n = 50). After administration of 2 ml of the unlabelled study medication containing either fentanyl (100 μg) or saline, anesthesia was induced with lidocaine 30–50 mg and propofol 2 mg/kg IV followed by the insertion of an LMA device. General anesthesia was maintained using a propofol infusion, 75 μg/kg/min, and desflurane (2–5% end‐tidal) in 100% oxygen.
Results
Coughing was observed in six (12%) and ten (20%) in the fentanyl and control group, respectively (P = 0.41). The incidence of movements during surgery was lower in the fentanyl group (18% vs. 31%, P < 0001). There were no significant differences in early and late recovery times or pain scores between the two groups.
Conclusion
Administration of a small‐dose of fentanyl at induction of anesthesia significantly reduced purposeful movements during day‐surgery under propofol‐desflurane anesthesia. No significant difference was found in coughing or recovery times.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The recent discovery of impulsive solar burst emission in the 30 THz band is raising new interpretation challenges. One event associated with a GOES M2 class flare has been observed simultaneously in ...microwaves, Hα, EUV, and soft X-ray bands. Although these new observations confirm some features found in the two prior known events, they exhibit time profile structure discrepancies between 30 THz, microwaves, and hard X-rays (as inferred from the Neupert effect). These results suggest a more complex relationship between 30 THz emission and radiation produced at other wavelength ranges. The multiple frequency emissions in the impulsive phase are likely to be produced at a common flaring site lower in the chromosphere. The 30 THz burst emission may be either part of a nonthermal radiation mechanism or due to the rapid thermal response to a beam of high-energy particles bombarding the dense solar atmosphere.
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Logistic regression analysis was performed on data drawn from a clinical trials database for Staphylococcus aureus septicaemia treated with teicoplanin. Variables analysed were age, body weight, mean ...pre-dose and post-dose serum teicoplanin concentrations, mean dose (mg or mg/kg body weight) and combination versus monotherapy. Only two variables correlated with clinical outcome at a significance level better than 0.05: age (P = 0.012) and mean pre-dose serum concentration (P = 0.010). The probability of successful treatment declined with age and increased with mean pre-dose serum concentration.
Numerous studies have demonstrated upper-airway neuromuscular abnormalities during wakefulness in snorers and obstructive sleep apnea (OSA) patients. However, the functional role of sensorimotor ...impairment in OSA pathogenesis/disease progression and its potential effects on protective upper-airway reflexes, measures of respiratory sensory processing, and force characteristics remain unclear. This study aimed to gain physiological insight into the potential role of sensorimotor impairment in OSA pathogenesis/disease progression by comparing sensory processing properties (respiratory-related evoked potentials; RREP), functionally important protective reflexes (genioglossus and tensor palatini) across a range of negative pressures (brief pulses and entrained iron lung ventilation), and tongue force and time to task failure characteristics between 12 untreated OSA patients and 13 controls. We hypothesized that abnormalities in these measures would be present in OSA patients. Upper-airway reflexes (e.g., genioglossus onset latency, 20 ± 1 vs. 19 ± 2 ms, P = 0.82), early RREP components (e.g., P1 latency 25 ± 2 vs. 25 ± 1 ms, P = 0.78), and the slope of epiglottic pressure vs. genioglossus activity during iron lung ventilation (-0.68 ± 1.0 vs. -0.80 ± 2.0 cmH(2)O/%max, P = 0.59) were not different between patients and controls. Maximal tongue protrusion force was greater in OSA patients vs. controls (35 ± 2 vs. 27 ± 2 N, P < 0.01), but task failure occurred more rapidly (149 ± 24 vs. 254 ± 23 s, P < 0.01). Upper-airway protective reflexes across a range of negative pressures as measured by electromyography and the early P1 component of the RREP are preserved in OSA patients during wakefulness. Consistent with an adaptive training effect, tongue protrusion force is increased, not decreased, in untreated OSA patients. However, OSA patients may be vulnerable to fatigue of upper-airway dilator muscles, which could contribute to disease progression.
Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway ...pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep.
Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at "CPAP lung volume", with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2).
The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001).
An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.
Novel species of microfungi described in the present study include the following from Australia: Bagadiella victoriae and Bagadiella koalae on Eucalyptus spp., Catenulostroma eucalyptorum on ...Eucalyptus laevopinea, Cercospora eremochloae on Eremochloa
bimaculata, Devriesia queenslandica on Scaevola taccada, Diaporthe musigena on Musa sp., Diaporthe acaciigena on Acacia retinodes, Leptoxyphium kurandae on Eucalyptus sp., Neofusicoccum grevilleae on Grevillea aurea, Phytophthora
fluvialis from water in native bushland, Pseudocercospora cyathicola on Cyathea australis, and Teratosphaeria mareebensis on Eucalyptus sp. Other species include Passalora leptophlebiae on Eucalyptus leptophlebia (Brazil), Exophiala tremulae
on Populus tremuloides and Dictyosporium stellatum from submerged wood (Canada), Mycosphaerella valgourgensis on Yucca sp. (France), Sclerostagonospora cycadis on Cycas revoluta (Japan), Rachicladosporium pini on Pinus monophylla (Netherlands),
Mycosphaerella wachendorfiae on Wachendorfia thyrsifolia and Diaporthe rhusicola on Rhus pendulina (South Africa). Novel genera of hyphomycetes include Noosia banksiae on Banksia aemula (Australia), Utrechtiana cibiessia on Phragmites australis
(Netherlands), and Funbolia dimorpha on blackened stem bark of an unidentified tree (USA). Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.
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