Non‐biaryl atropisomers are valuable in medicine, materials, and catalysis, but their enantioselective synthesis remains a challenge. Herein, a counterion‐mediated O‐alkylation method for the ...generation of atropisomeric amides with an er up to 99:1 is outlined. This dynamic kinetic resolution is enabled by the observation that the rate of racemization of atropisomeric naphthamides is significantly increased by the presence of an intramolecular O−H⋅⋅⋅NCO hydrogen bond. Upon O‐alkylation of the H‐bond donor, the barrier to rotation is significantly increased. Quantum calculations demonstrate that the intramolecular H‐bond reduces the rotational barrier about the aryl–amide bond, stabilizing the planar transition state for racemization by approximately 40 kJ mol−1, thereby facilitating the observed dynamic kinetic resolution.
Non‐biaryl atropisomers are valuable in medicine, materials, and catalysis, but their enantioselective synthesis remains a challenge. A counterion‐mediated O‐alkylation method for the generation of atropisomeric amides with an er up to 99:1 is outlined.
Upgraded electronics, improved water system dynamics, better calibration and analysis techniques allowed Super-Kamiokande-IV to clearly observe very low-energy B8 solar neutrino interactions, with ...recoil electron kinetic energies as low as ∼3.5 MeV. Super-Kamiokande-IV data-taking began in September of 2008; this paper includes data until February 2014, a total livetime of 1664 days. The measured solar neutrino flux is (2.308±0.020(stat)−0.040+0.039(syst))×106/(cm2 sec) assuming no oscillations. The observed recoil electron energy spectrum is consistent with no distortions due to neutrino oscillations. An extended maximum likelihood fit to the amplitude of the expected solar zenith angle variation of the neutrino-electron elastic scattering rate in SK-IV results in a day/night asymmetry of (−3.6±1.6(stat)±0.6(syst))%. The SK-IV solar neutrino data determine the solar mixing angle as sin2θ12=0.327−0.031+0.026, all SK solar data (SK-I, SK-II, SK III and SK-IV) measures this angle to be sin2θ12=0.334−0.023+0.027, the determined mass-squared splitting is Δm212=4.8−0.8+1.5×10−5 eV2.
We present the results from a search for gravitational-wave transients associated with core-collapse supernovae observed within a source distance of approximately 20 Mpc during the first and second ...observing runs of Advanced LIGO and Advanced Virgo. No significant gravitational-wave candidate was detected. We report the detection efficiencies as a function of the distance for waveforms derived from multidimensional numerical simulations and phenomenological extreme emission models. The sources with neutrino-driven explosions are detectable at the distances approaching 5 kpc, and for magnetorotationally driven explosions the distances are up to 54 kpc. However, waveforms for extreme emission models are detectable up to 28 Mpc. For the first time, the gravitational-wave data enabled us to exclude part of the parameter spaces of two extreme emission models with confidence up to 83%, limited by coincident data coverage. Besides, using ad hoc harmonic signals windowed with Gaussian envelopes, we constrained the gravitational-wave energy emitted during core collapse at the levels of 4.27 × 10^(−4) Mꙩc^(2) and 1.28 × 10^(−1) Mꙩc^(2) for emissions at 235 and 1304 Hz, respectively. These constraints are 2 orders of magnitude more stringent than previously derived in the corresponding analysis using initial LIGO, initial Virgo, and GEO 600 data.
Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical ...distribution, with lineage B predominating in Asia (89.0% vs 0%-5.5%; Pcorrected< .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name "Asian lineage" be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B.
In this study, we examined the impact of goal-directed processing on the response to emotional pictures and the impact of emotional pictures on goal-directed processing. Subjects (N=22) viewed ...neutral or emotional pictures in the presence or absence of a demanding cognitive task. Goal-directed processing disrupted the BOLD response to emotional pictures. In particular, the BOLD response within bilateral amygdala and inferior frontal gyrus decreased during concurrent task performance. Moreover, the presence of both positive and negative distractors disrupted task performance, with reaction times increasing for emotional relative to neutral distractors. Moreover, in line with the suggestion of the importance of lateral frontal regions in emotional regulation Ochsner, K. N., Ray, R. D., Cooper, J. C., Robertson, E. R., Chopra, S., Gabrieli, J. D., et al. (2004). For better or for worse: neural systems supporting the cognitive down-and up-regulation of negative emotion. NeuroImage, 23(2), 483–499, connectivity analysis revealed positive connectivity between lateral superior frontal cortex and regions of middle frontal cortex previously implicated in emotional suppression Beauregard, M., Levesque, J., and Bourgouin, P. (2001). Neural correlates of conscious self-regulation of emotion. J. Neurosci., 21 (18), RC165.; Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., et al. (2003). Neural circuitry underlying voluntary suppression of sadness. Biol. Psychiatry, 53 (6), 502–510.; Ohira, H., Nomura, M., Ichikawa, N., Isowa, T., Iidaka, T., Sato, A., et al. (2006). Association of neural and physiological responses during voluntary emotion suppression. NeuroImage, 29 (3), 721–733 and negative connectivity with bilateral amygdala. These data suggest that processes involved in emotional regulation are recruited during task performance in the context of emotional distractors.
We present a search for transient and highly variable sources at low radio frequencies (150-200 MHz) that explores long time-scales of 1-3 yr. We conducted this search by comparing the TIFR GMRT Sky ...Survey Alternative Data Release 1 (TGSS ADR1) and the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey catalogues. To account for the different completeness thresholds in the individual surveys, we searched for compact GLEAM sources above a flux density limit of 100 mJy that were not present in the TGSS ADR1; and also for compact TGSS ADR1 sources above a flux density limit of 200 mJy that had no counterpart in GLEAM. From a total sample of 234 333 GLEAM sources and 275 612 TGSS ADR1 sources in the overlap region between the two surveys, there were 99 658 GLEAM sources and 38 978 TGSS ADR sources that passed our flux density cut-off and compactness criteria. Analysis of these sources resulted in three candidate transient sources. Further analysis ruled out two candidates as imaging artefacts. We analyse the third candidate and show it is likely to be real, with a flux density of 182 plus or minus 26 mJy at 147.5 MHz. This gives a transient surface density of p = (6.2 plus or minus 6) x 10 super( -5) deg super( -2). We present initial follow-up observations and discuss possible causes for this candidate. The small number of spurious sources from this search demonstrates the high reliability of these two new low-frequency radio catalogues.
Purpose
To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of ...lower or higher 90-day mortality according to age, and other identified clusters.
Methods
Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation.
Results
HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio OR, 0.83 95% credible interval CrI 0.68–1.00, with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 95% CrI 1.02–1.56. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 95% CrI 0.65–1.14) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2.
Conclusion
In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.
•Organic farming improved the pollination success of field bean.•High use of conventionally managed leys in crop rotations did not improve field bean pollination.•Increasing landscape complexity ...increased field bean pollination on organic farms.•Semi-natural habitats enhanced pollination services for a bumblebee-pollinated crop.
Organic farming has the potential to enhance ecosystem services such as crop pollination. However, it is not known if a similar effect can be generated on conventional farms, without reducing external inputs such as inorganic fertilizers and pesticides, by using more complex crop rotations including ley for animal fodder production. In two separate designs, both located in southern Sweden, we tested if local organic farming and the landscape proportion of conventionally managed leys, along a landscape heterogeneity gradient, affected the pollination success of field bean. The number of developed pods was higher on organic farms compared to conventional ones. Development of beans, which demands high pollination efficiency, increased with increasing landscape heterogeneity, but only on organic farms. Increasing proportion of ley on conventional farms did not significantly influence the development of beans. The number of developed pods was not affected by the proportion of ley in the landscape. Our results demonstrate that in order to maximize pollination success it is important to improve both field management and preserve semi-natural habitats in the agricultural landscape. Reducing farming intensity with conventionally managed leys does not seem to be as effective as organic farming for delivering crop pollination services.
Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical ...predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type‐specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6‐367A (D86E) but significantly less isolates with E6‐203G, ‐245G, ‐367C (prototype‐like) than other regions (p ≤ 0.003). E7‐632T, ‐760A (T20I, G63S) was more frequently found in Asia, and E7‐793G (T74A) was more frequent in Africa (p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas.
What's new?
For unknown reasons, human papillomavirus (HPV) 58 accounts for a significant proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. In this study, the authors analyzed the E6 and E7 genes from HPV58 samples from around the world. They found that patients with an HPV58 variant containing T20I and G63S substitutions in E7 had a greater risk of developing cancer. This variant was also more prevalent in Asia than in other regions, and may therefore help to explain the higher disease burden observed in this region.
Symptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the ...optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH.
Data on management and outcomes for patients with CSDH referred to UK and Ireland NSUs were collected prospectively over an 8-month period and audited against criteria predefined from the literature: NSU mortality < 5%, NSU morbidity < 10%, symptomatic recurrence within 60 days requiring repeat surgery < 20%, and unfavorable functional status (modified Rankin Scale score of 4-6) at NSU discharge < 30%.
Data from 1205 patients in 26 NSUs were collected. Bur-hole craniostomy was the most common procedure (89%), and symptomatic recurrence requiring repeat surgery within 60 days was observed in 9% of patients. Criteria on mortality (2%), rate of recurrence (9%), and unfavorable functional outcome (22%) were met, but morbidity was greater than expected (14%). Multivariate analysis demonstrated that failure to insert a drain intraoperatively independently predicted recurrence and unfavorable functional outcome (p = 0.011 and p = 0.048, respectively). Increasing patient age (p < 0.00001), postoperative bed rest (p = 0.019), and use of a single bur hole (p = 0.020) independently predicted unfavorable functional outcomes, but prescription of high-flow oxygen or preoperative use of antiplatelet medications did not.
This is the largest prospective CSDH study and helps establish national standards. It has confirmed in a real-world setting the effectiveness of placing a subdural drain. This study identified a number of modifiable prognostic factors but questions the necessity of some common aspects of CSDH management, such as enforced postoperative bed rest. Future studies should seek to establish how practitioners can optimize perioperative care of patients with CSDH to reduce morbidity as well as minimize CSDH recurrence. The BNTRC is unique worldwide, conducting multicenter trainee-led research and audits. This study demonstrates that collaborative research networks are powerful tools to interrogate clinical research questions.
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