First observation of 28O.

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

Rotational thromboelastometry during Cesarean section as a predictive evaluation for the progression of persistent postpartum hemorrhage in parturients with placenta previa: A prospective observational study.

Background: The rotational thromboelastogram (ROTEM) has been used in the management of massive bleeding and transfusion strategy. This study investigated ROTEM parameters measured during Cesarean section as predictors for the progression of persistent postpartum hemorrhage (PPH) in parturients with placenta previa. Methods: This prospective observational study recruited 100 women scheduled for elective Cesarean section after being diagnosed with placenta previa. Recruited women were divided into two groups according to the amount of estimated blood loss: the PPH group (PPH > 1500 ml) vs. the non-PPH group. ROTEM with laboratory tests was performed three times, preoperative, intraoperative, and postoperative time, which were compared between the two groups. Results: The PPH and non-PPH groups included 57 and 41 women, respectively. The area under the receiver-operating characteristic curve of postoperative FIBTEM A5 to detect PPH was 0.76 (95% CI = 0.64 to 0.87; P < 0.001). When postoperative FIBTEM A5 was 9.5, the sensitivity and specificity were 0.74 (95% CI = 0.55 to 0.88) and 0.73 (95% CI = 0.57 to 0.86), respectively. When subgrouping the PPH group based on the postoperative FIBTEM A5 value of 9.5, intraoperative cEBL was similar between the two subgroups; however, postoperative RBC was transfused more in the subgroup with FIBTEM A5 < 9.5 than the subgroup with FIBTEM A5 ≥ 9.5 (7.4 ± 3.0 vs 5.1 ± 2.3 units, respectively; P = 0.003). Conclusion: Postoperative FIBTEM A5, with appropriate selection of the cut-off value, can be a biomarker for more prolonged PPH and massive transfusion following Cesarean section by placenta previa.

Halo Structure of the Neutron-Dripline Nucleus

The heaviest bound isotope of boron ^{19}B has been investigated using exclusive measurements of its Coulomb dissociation, into ^{17}B and two neutrons, in collisions with Pb at 220 MeV/nucleon. Enhanced electric dipole (E1) strength is observed just above the two-neutron decay threshold with an integrated E1 strength of B(E1)=1.64±0.06(stat)±0.12(sys) e^{2} fm^{2} for relative energies below 6 MeV. This feature, known as a soft E1 excitation, provides the first firm evidence that ^{19}B has a prominent two-neutron halo. Three-body calculations that reproduce the energy spectrum indicate that the valence neutrons have a significant s-wave configuration and exhibit a dineutronlike correlation.

Extending the Southern Shore of the Island of Inversion to

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230 MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

The influence of preoperative epidural labor analgesia on postoperative pain in parturients undergoing emergency cesarean section : A retrospective analysis.

BACKGROUND: Intense noxious input from the periphery may result in central sensitization and hyperexcitability, thus accentuating subsequent postoperative pain. Parturients who undergo emergency cesarean section (C-sec) after experiencing labor pain often develop labor pain-induced sensitization. OBJECTIVE: This retrospective study evaluated whether parturients without epidural labor analgesia (ELA) who underwent emergency C­sec, experienced more severe postoperative pain and required more rescue analgesics during the postoperative period. METHODS: The institution's medical database was searched for parturients who underwent emergency C­sec under spinal anesthesia for any reason between January 2013 and December 2016. Those who underwent elective C­sec under spinal anesthesia were included as the reference arm. Parturients were divided into three groups: ELA, no-ELA and elective. Characteristics of patients and perioperative outcomes were evaluated. As primary outcomes, numerical rating scale (NRS) for postoperative pain (0-10) was recorded up to 96 h postoperatively, and use of rescue analgesics was evaluated at 6, 24, and 48 h postoperatively. RESULTS: In the ELA, no-ELA, and elective groups, 61, 73, and 88 parturients, respectively, were ultimately enrolled. The NRS for pain were similar among the three groups, except at 6 h postoperatively. Parturients in the no-ELA group demonstrated significantly higher NRS at 6 h postoperatively than those in the ELA group (P = 0.01).More patients in the no-ELA group required rescue analgesics than in the ELA (P = 0.001) and elective groups (P < 0.001) at 6-24 h postoperatively. Moreover, the proportion of patients requiring rescue analgesics ≥2 times was also significantly higher in the no-ELA group (vs. the ELA group, P = 0.004; vs. the elective group, P < 0.001). CONCLUSION: Parturients undergoing emergency C­sec without ELA management during labor experienced greater postoperative pain and a greater use of rescue analgesics during the postoperative period. The findings suggest that administration of ELA before emergency C­sec may act as pre-emptive analgesia against postoperative pain.

First Observation of

The most neutron-rich boron isotopes ^{20}B and ^{21}B have been observed for the first time following proton removal from ^{22}N and ^{22}C at energies around 230 MeV/nucleon. Both nuclei were found to exist as resonances which were detected through their decay into ^{19}B and one or two neutrons. Two-proton removal from ^{22}N populated a prominent resonancelike structure in ^{20}B at around 2.5 MeV above the one-neutron decay threshold, which is interpreted as arising from the closely spaced 1^{-},2^{-} ground-state doublet predicted by the shell model. In the case of proton removal from ^{22}C, the ^{19}B plus one- and two-neutron channels were consistent with the population of a resonance in ^{21}B 2.47±0.19 MeV above the two-neutron decay threshold, which is found to exhibit direct two-neutron decay. The ground-state mass excesses determined for ^{20,21}B are found to be in agreement with mass surface extrapolations derived within the latest atomic-mass evaluations.

The Effect of Intraoperative Nefopam Administration on Acute Postoperative Pain and Chronic Discomfort After Robotic or Endoscopic Assisted Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Acute postoperative pain and chronic discomfort are reported after robotic or endoscopic thyroidectomy. The purpose of this prospective, randomized, and double-blinded clinical trial was to investigate whether intraoperative infusion of nefopam decreases acute postoperative pain and chronic discomfort following either a robotic or endoscopic thyroidectomy via the bilateral axillo-breast approach (BABA). METHODS: Patients were randomized into two groups: The control group (n = 29) or the nefopam group (n = 29). Patients in each group were infused with the same volume of saline or nefopam (0.2 mg/kg bolus, 120 µg/kg/h continuous infusion) during surgery. Acute postoperative pain, the need for rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Chronic pain and discomfort was recorded at 3 months after surgery. RESULTS: Patients in the nefopam group reported lower pain scores in the neck, as well as the axilla and anterior chest areas at 1, 6, 24, and 48 h postoperatively, when compared with the control group (P < 0.05 at each time points). Rescue analgesics were required less in the nefopam group than in the control group (1.4 [1] vs. 2.3 [1.5]; P = 0.001). The degree of chronic pain and discomfort were relatively lower in the nefopam group (P < 0.05). CONCLUSION: We report that intravenous nefopam infusion during surgery decreased acute postoperative pain and the need for rescue analgesics, as well as chronic discomfort, following BABA robotic or endoscopic thyroidectomy without adverse events.

Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with sugammadex of high-dose rocuronium for a short procedure.

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg-1 with neostigmine (50 µg.kg-1 with glycopyrrolate 10 µg.kg-1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg-1 with neostigmine.

A prospective randomised trial comparing insertion success rate and incidence of catheterisation-related complications for subclavian venous catheterisation using a thin-walled introducer needle or a catheter-over-needle technique.

In clinical practice, both a thin-walled introducer needle and catheter-over-needle technique can be used to allow insertion of a guidewire during central venous catheterisation using the Seldinger technique. We compared the incidence of catheterisation-related complications (arterial puncture, haemothorax, pneumothorax, haematoma and catheter tip malposition) and insertion success rate for these two techniques in patients requiring right-sided subclavian central venous catheterisation. A total of 414 patients requiring infraclavicular subclavian venous catheterisation were randomly allocated to either a thin-walled introducer needle (needle group, n = 208) or catheter-over-needle technique (catheter group, n = 206). The catheterisation-related complication rate was lower in the needle group compared with the catheter group (5.8% vs. 15.5%; p = 0.001). Overall insertion success rates were similar (97.1% and 92.7% in the needle and catheter groups respectively; p = 0.046), although the first-pass success rate was higher in the needle group (62.0% vs. 35.4%; p < 0.001). We recommend the use of a thin-walled introducer needle technique for right-sided infraclavicular subclavian venous catheterisation.

Nucleus

The unbound nucleus ^{26}O has been investigated using invariant-mass spectroscopy following one-proton removal reaction from a ^{27}F beam at 201 MeV/nucleon. The decay products, ^{24}O and two neutrons, were detected in coincidence using the newly commissioned SAMURAI spectrometer at the RIKEN Radioactive Isotope Beam Factory. The ^{26}O ground-state resonance was found to lie only 18±3(stat)±4(syst) keV above threshold. In addition, a higher lying level, which is most likely the first 2^{+} state, was observed for the first time at 1.28_{-0.08}^{+0.11} MeV above threshold. Comparison with theoretical predictions suggests that three-nucleon forces, pf-shell intruder configurations, and the continuum are key elements to understanding the structure of the most neutron-rich oxygen isotopes beyond the drip line.

Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals.

Subthreshold depression (StD) is a highly prevalent condition associated with increased service utilization and social morbidity. Nevertheless, due to limitations in current diagnostic systems that set the boundary for major depressive disorder (MDD), very few brain imaging studies on the neurobiology of StD have been carried out, and its underlying neurobiological mechanism remains unclear. In recent years, accumulating evidence suggests that the disruption of the default mode network (DMN), a network involved in self-referential processing, affective cognition, and emotion regulation, is involved in major depressive disorder. Using independent component analysis, we investigated resting-state default mode network (DMN) functional connectivity (FC) changes in two cohorts of StD patients with different age ranges (young and middle-aged, n = 57) as well as matched controls (n = 79). We found significant FC increase between the DMN and ventral striatum (key region in the reward network), in both cohorts of StD patients in comparison with controls. In addition, we also found the FC between the DMN and ventral striatum was positively and significantly associated with scores on the Center for Epidemiologic Studies Depression Scale (CES-D), a measurement of depressive symptomatology. We speculate that this enhanced FC between the DMN and the ventral striatum may reflect a self-compensation to ameliorate the lowered reward function.

Novel strategy for a bispecific antibody: induction of dual target internalization and degradation.

Activation of the extensive cross-talk among the receptor tyrosine kinases (RTKs), particularly ErbB family-Met cross-talk, has emerged as a likely source of drug resistance. Notwithstanding brilliant successes were attained while using small-molecule inhibitors or antibody therapeutics against specific RTKs in multiple cancers over recent decades, a high recurrence rate remains unsolved in patients treated with these targeted inhibitors. It is well aligned with multifaceted properties of cancer and cross-talk and convergence of signaling pathways of RTKs. Thereby many therapeutic interventions have been actively developed to overcome inherent or acquired resistance. To date, no bispecific antibody (BsAb) showed complete depletion of dual RTKs from the plasma membrane and efficient dual degradation. In this manuscript, we report the first findings of a target-specific dual internalization and degradation of membrane RTKs induced by designed BsAbs based on the internalizing monoclonal antibodies and the therapeutic values of these BsAbs. Leveraging the anti-Met mAb able to internalize and degrade by a unique mechanism, we generated the BsAbs for Met/epidermal growth factor receptor (EGFR) and Met/HER2 to induce an efficient EGFR or HER2 internalization and degradation in the presence of Met that is frequently overexpressed in the invasive tumors and involved in the resistance against EGFR- or HER2-targeted therapies. We found that Met/EGFR BsAb ME22S induces dissociation of the Met-EGFR complex from Hsp90, followed by significant degradation of Met and EGFR. By employing patient-derived tumor models we demonstrate therapeutic potential of the BsAb-mediated dual degradation in various cancers.

Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium.

We examined the use of neostigmine for reversing shallow (defined as train-of-four ratio of 0.5), cisatracurium- and rocuronium-induced neuromuscular block in 112 patients, by use of 0 µg.kg(-1) , 10 µg.kg(-1) , 20 µg.kg(-1) or 40 µg.kg(-1) dose of neostigmine for reversal. The times from neostigmine administration to train-of-four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train-of-four ratio of 1.0 was significantly shorter with neostigmine 40 µg.kg(-1) compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train-of-four ratio of 0.5-1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 µg.kg(-1) was the most effective at reducing recovery time after neuromuscular blockade.

Timing of reversal with respect to three nerve stimulator end-points from cisatracurium-induced neuromuscular block.

After elective ear surgery with cisatracurium neuromuscular blockade, 48 adults were randomly assigned to receive neostigmine: (a) at appearance of the fourth twitch of a 'train-of-four'; (b) at loss of fade to train-of-four; or (c) at loss of fade to double-burst stimulation, all monitored using a TOF-Watch SX® on one arm. For each of these conditions, the recovery from train-of-four (TOF) ratio was measured in parallel objectively using a TOF-Watch SX placed on the contralateral arm. The median (IQR [range]) time from administration of reversal to a train-of-four ratio ≥ 0.9 was 11 (9-15.5 [2-28]) min, 8 (4-13.5 [1-25]) min and 7 (4-10 [2-15]) min in the three groups, respectively. This recovery time was significantly shorter when reversal was given at loss of fade to double-burst stimulation (c), than when given at the appearance of the fourth twitch (a), p = 0.046. However, the total time to extubation may be unaffected as it takes longer for fade to be lost after double-burst stimulation than for four twitches subjectively to appear.

Subthreshold depression is associated with impaired resting-state functional connectivity of the cognitive control network.

Subthreshold depression (StD) is a prevalent condition associated with social morbidity and increased service utilization, as well as a high risk of developing into a major depressive disorder (MDD). The lack of well-defined diagnostic criteria for StD has limited research on this disorder, with very few brain-imaging studies examining the neurobiology of StD. Yet, identifying the neural pathology of StD has the potential to elucidate risk factors and prognostic markers for major depression and is crucial for developing tailored treatments for patients at mild stages of depression. We investigated resting-state functional connectivity (rs-FC) of the cognitive control network (CCN), known to be dysregulated in MDD, using the bilateral dorsolateral prefrontal cortex (DLPFC) as a seed, focusing on two cohorts of StD subjects (young and middle aged) as well as matched controls. Irrespective of age, we found a significant rs-FC decrease in the CCN of the StD subjects, compared with matched controls, particularly between the DLPFC and the brain regions associated with the representation of self and other mental states (temporo-parietal junction (TPJ) and precuneus), as well as salience detection and orienting (insula). The functional connectivity between the DLPFC and the left TPJ was also associated with depressive symptom scores measured by the Center for Epidemiologic Studies Depression Scale. This finding may shed light on the neural pathology of StD, leading to better understanding of mild stages of depression, its diagnosis and the development of new treatments.

Efficacy of the APACHE II score at ICU discharge in predicting post-ICU mortality and ICU readmission in critically ill surgical patients.

In this study, we evaluated the efficacy of the discharge Acute Physiology and Chronic Health Evaluation (APACHE) II score in predicting post-intensive care unit (ICU) mortality and ICU readmission during the same hospitalisation in a surgical ICU. Of 1190 patients who were admitted to the ICU and stayed >48 hours between October 2007 and March 2010, 23 (1.9%) died and 86 (7.2%) were readmitted after initial ICU discharge, with 26 (3.0%) admitted within 48 hours. The area under the receiver operating characteristics curve of the discharge and admission APACHE II scores in predicting in-hospital mortality was 0.631 (95% confidence interval [CI] 0.603 to 0.658) and 0.669 (95% CI 0.642 to 0.696), respectively (P=0.510). The area under the receiver operating characteristics curve of discharge and admission APACHE II scores for predicting all forms of readmission was 0.606 (95% CI 0.578 to 0.634) and 0.574 (95% CI 0.545 to 0.602), respectively (P=0.316). The area under the receiver operating characteristics curve of discharge APACHE II score in predicting early ICU readmissions was, however, higher than that of admission APACHE II score (0.688 [95% CI 0.660 to 0.714] versus 0.505 [95% CI 0.476 to 0.534], P=0.001). The discharge APACHE II score (odds ratio [OR] 1.1, 95% CI 1.01 to 1.22, P=0.024), unplanned ICU readmission (OR 20.0, 95% CI 7.6 to 53.1, P=0.001), eosinopenia at ICU discharge (OR 6.0, 95% CI 1.34 to 26.9, P=0.019), and hospital length-of-stay before ICU admission (OR 1.02, 95% CI 1.01 to 1.03, P=0.021) were significant independent factors in predicting post-ICU mortality. This study suggests that the discharge APACHE II score may be useful in predicting post-ICU mortality and is superior to the admission APACHE II score in predicting early ICU readmission in surgical ICU patients.

Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia.

BACKGROUND: The antioxidant mechanism of sevoflurane post-conditioning-induced neuroprotection remains unclear. We determined whether sevoflurane post-conditioning induces nuclear factor erythroid 2-related factor (Nrf2, a master transcription factor regulating antioxidant defence genes) and haemoxygenase-1 (HO-1, an antioxidant enzyme) expression, and whether protein kinase C (PKC) is involved in Nrf2 activation, in a rat model of transient global cerebral ischaemia/reperfusion (I/R) injury. METHODS: Eighty-six rats were assigned to five groups: sham (n=6), control (n=20), sevoflurane post-conditioning (two cycles with 2 vol% sevoflurane inhalation for 10 min, n=20), chelerythrine (a PKC inhibitor; 5 mg kg(-1) i.v. administration, n=20), and sevoflurane post-conditioning plus chelerythrine (n=20). The levels of nuclear Nrf2 and cytoplasmic HO-1 were assessed 1 or 7 days after ischaemia (n=10 each, apart from the sham group, n=3). RESULTS: On day 1 but not day 7 post-ischaemia, Nrf2 and HO-1 expression were significantly higher in the sevoflurane post-conditioning group than in the control group. Chelerythrine administration reduced the elevated Nrf2 and HO-1 expression induced by sevoflurane post-conditioning. CONCLUSIONS: Sevoflurane post-conditioning increased Nrf2/HO-1 expression via PKC signalling in the early phase after transient global cerebral I/R injury, suggesting that activation of antioxidant enzymes may be responsible for sevoflurane post-conditioning-induced neuroprotection in the early phase after cerebral I/R injury.

Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer surgery, measured by rotational thromboelastometry (ROTEM® ).

We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in patients undergoing laparoscopic colorectal cancer surgery. Patients were randomly allocated to the magnesium group (n = 22) or control group (n = 22). The magnesium group received intravenous magnesium sulphate (50 mg.kg(-1) followed by a continuous infusion of 15 mg.kg(-1) .h(-1) ), whereas the control group received the same volume of isotonic saline. Mean (SD) postoperative serum magnesium levels were 1.60 (0.13) mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the control group (p < 0.001). All maximum clot firmness values of ROTEM analysis were significantly lower on the third postoperative day in the magnesium group compared with the control group (p < 0.05). We conclude that ROTEM analysis demonstrated that intra-operative administration of intravenous magnesium sulphate reduces blood hypercoagulability in patients undergoing laparoscopic colorectal cancer surgery.