S1 Intensity Research Articles

Raman parametric four-wave mixing mechanism of the first-order Stokes generated in CO2 and H2.

Without the axial component, an annular spatial profile of the first-order Stokes (S1) was observed during the SRS process in low-energy pumped CO2 gas, which is supposed to be generated by a parametric four-wave mixing process (PFWM), i.e., 2ωP = ωAS1 + ωS1. In order to verify such a mechanism, similar experiments were conducted in H2, and the annular S1 intensity distribution was also noticed. Furthermore, simulations of S1 radial intensity distributions were carried out based on the proposed PFWM phase matching geometry. The PFWM has been verified to be a process that directly annihilates two pump photons and simultaneously produces one AS1 photon and one S1 photon.

Beat-to-beat alterations of acoustic intensity and frequency at the maximum power of heart sounds are associated with NT-proBNP levels.

Auscultatory features of heart sounds (HS) in patients with heart failure (HF) have been studied intensively. Recent developments in digital and electrical devices for auscultation provided easy listening chances to recognize peculiar sounds related to diastolic HS such as S3 or S4. This study aimed to quantitatively assess HS by acoustic measures of intensity (dB) and audio frequency (Hz). Forty consecutive patients aged between 46 and 87 years (mean age, 74 years) with chronic cardiovascular disease (CVD) were enrolled in the present study after providing written informed consent during their visits to the Kitasato University Outpatient Clinic. HS were recorded at the fourth intercostal space along the left sternal border using a highly sensitive digital device. Two consecutive heartbeats were quantified on sound intensity (dB) and audio frequency (Hz) at the peak power of each spectrogram of S1-S4 using audio editing and recording application software. The participants were classified into three groups, namely, the absence of HF (n = 27), HF (n = 8), and high-risk HF (n = 5), based on the levels of NT-proBNP < 300, ≥300, and ≥900 pg/ml, respectively, and also the levels of ejection fraction (EF), such as preserved EF (n = 22), mildly reduced EF (n = 12), and reduced EF (n = 6). The intensities of four components of HS (S1-S4) decreased linearly (p < 0.02-0.001) with levels of body mass index (BMI) (range, 16.2-33.0 kg/m2). Differences in S1 intensity (ΔS1) and its frequency (ΔfS1) between two consecutive beats were non-audible level and were larger in patients with HF than those in patients without HF (ΔS1, r = 0.356, p = 0.024; ΔfS1, r = 0.356, p = 0.024). The cutoff values of ΔS1 and ΔfS1 for discriminating the presence of high-risk HF were 4.0 dB and 5.0 Hz, respectively. Despite significant attenuations of all four components of HS by BMI, beat-to-beat alterations of both intensity and frequency of S1 were associated with the severity of HF. Acoustic quantification of HS enabled analyses of sounds below the audible level, suggesting that sound analysis might provide an early sign of HF.

Nonlinear optical, optical limiting and structural properties of tetrastyryl derivatives with pyrene and bithiophene

Two tetrastyryl derivatives (S1, S2) were designed and synthesized by Schiff base reaction. The structure and properties of the compounds were characterized by FT-IR, UV–Vis, TG and Z-scan. The structure-activity relationship of S1 and S2 was studied in detail. The combination of large π conjugation and charge transfer gives the two tetrastyryl derivatives strong nonlinear optical properties. Under picosecond pulse excitation at 532 nm with 3 μJ energy, the nonlinear absorption coefficients of S1 and S2 are 6.5 × 10−12 m/W, 9 × 10−12 m/W, respectively. The third harmonic intensities of S1 and S2 are 215 and 25 times that of SiO2, respectively. S1 and S2 can be used as nonlinear optical materials and have a certain application prospect in the field of laser protection and frequency conversion.

Multi-state Markov model analysis of disease outcomes and influencing factors in HIV infected individuals receiving antiretroviral therapy in Luzhou of Sichuan province, 2010-2021

Objective: To construct a multi-state Markov model and analyze the disease outcomes and its influencing factors in HIV infected individuals receiving antiretroviral therapy. Methods: A retrospective cohort analysis was conducted in HIV infected individuals receiving antiretroviral therapy in Luzhou of Sichuan province from 2010 to 2021. The disease status was divided into CD4+T lymphocytes (CD4) counts >500 cells/μl, 350-500 cells/μl, 200-349 cells/μl, ≤199 cells/μl and death indicated by S1-S5 in turn. A reversible continuous-time discrete-state multi-state Markov model was constructed for the analysis of disease progression features. Results: A total of 7 542 HIV infected individuals receiving antiretroviral therapy were included, and the median age (Q1, Q3) was 53.4 (41.2, 64.5) years old. The transition intensity of S3→S2 was higher. During follow-up, the transition probability of S4→S5 increased gradually. Influencing factors analysis of disease outcomes in HIV infected individuals receiving antiretroviral therapy showed that compared with individuals 15-24 years old, the transition intensities of S2→S1, S3→S2 and S4→S3 were lower and the transition intensity of S3→S4 was higher in individuals ≥45 years old. Compared with single individuals, the transition intensities of S3→S2 and S4→S3 were higher and the transition intensities of S3→S4 and S4→S5 were lower in married individuals. The transition intensity of S1→S2 was higher in individuals with baseline CD4 counts ≤500 cells/μl than in individuals with baseline CD4 counts >500 cells/μl. The transition intensity of S3→S4 in individuals diagnosed during 2011-2015 was lower than that in individuals diagnosed in 2010 and before. Conclusions: HIV infected individuals receiving antiretroviral therapy tended to shift to the previous disease status, suggesting that antiretroviral therapy was conducive to immune reconstitution. Older age (≥45 years old), being married, low baseline CD4 counts and being diagnosed in 2010 and before were the risk factors for disease progression.

Impact of loss of skeletal muscle mass within 6-12months after gastrectomy and S1 adjuvant chemotherapy on the survival prognosis of elderly patients with gastric cancer.

We investigated the impact of postoperative changes in the psoas muscle mass index (PMI) after gastrectomy and S1 adjuvant chemotherapy (AC) on the long-term outcomes of elderly patients with gastric cancer. We reviewed the medical records of 228 patients aged over 75years, who underwent distal, proximal, or total gastrectomy between January, 2013 and March 2017. Among these patients, 78 with pStage IIA-IIIC who survived for at least 1year without recurrence after gastrectomy were the subjects of this analysis. The log-rank test using the cut-off value from the rate of change in PMI from 6 to 12months after gastrectomy (late rate of decrease) showed significantly poorer prognosis for the group above the cut-off value for both overall survival (OS) and recurrence-free survival (RFS) (RFS: PMI decrease ≥ 1.55%, p < 0.001; OS: PMI decrease ≥ 1.55%, p < 0.001). Patients with a relative dose intensity of S1 below 68.7% and a late rate of decrease in PMI above 1.55% were found to have a poor prognosis. It is necessary to prevent decline in the PMI of elderly patients from 6months after gastrectomy and to administer adjuvant chemotherapy with about two-thirds or more RDI of S1 to improve their survival prognosis.

Synthesis and Characterizations of 5,5'-Bibenzo[rst]pentaphene with Axial Chirality and Symmetry-Breaking Charge Transfer.

Exploration of novel biaryls consisting of two polycyclic aromatic hydrocarbon (PAH) units can be an important strategy toward further developments of organic materials with unique properties. In this study, 5,5′‐bibenzo[rst]pentaphene (BBPP) with two benzo[rst]pentaphene (BPP) units is synthesized in an efficient and versatile approach, and its structure is unambiguously elucidated by X‐ray crystallography. BBPP exhibits axial chirality, and the (M)‐ and (P)‐enantiomers are resolved by chiral high‐performance liquid chromatography and studied by circular dichroism spectroscopy. These enantiomers have a relatively high isomerization barrier of 43.6 kcal mol−1 calculated by density functional theory. The monomer BPP and dimer BBPP are characterized by UV‐vis absorption and fluorescence spectroscopy, cyclic voltammetry, and femtosecond transient absorption spectroscopy. The results indicate that both BPP and BBPP fluoresce from a formally dark S1 electronic state that is enabled by Herzberg–Teller intensity borrowing from a neighboring bright S2 state. While BPP exhibits a relatively low photoluminescence quantum yield (PLQY), BBPP exhibits a significantly enhanced PLQY due to a greater S2 intensity borrowing. Moreover, symmetry‐breaking charge transfer in BBPP is demonstrated by spectroscopic investigations in solvents of different polarity. This suggests high potential for singlet fission in such π‐extended biaryls through appropriate molecular design.

Short-interval intracortical inhibition and facilitation targeting upper and lower limb muscles

Transcranial magnetic stimulation (TMS) can be used to study excitability of corticospinal neurons in human motor cortex. It is currently not fully elucidated if corticospinal neurons in the hand vs. leg representation show the same or different regulation of their excitability by GABAAergic and glutamatergic interneuronal circuitry. Using a paired-pulse TMS protocol we tested short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) in 18 healthy participants. Motor evoked potentials were evoked in one hand (abductor digiti minimi) and one leg muscle (tibialis anterior), with systematic variation of the intensities of the first (S1) and second (S2) pulse between 60 and 140% resting motor threshold (RMT) in 10% steps, at two interstimulus intervals of 1.5 and 2.1 ms. For the hand and leg motor representations and for both interstimulus intervals, SICI occurred if the intensities of S1 < RMT and S2 > RMT, while SICF predominated if S1 = S2 ≤ RMT, or S1 > RMT and S2 < RMT. Findings confirm and extend previous evidence that the regulation of excitability of corticospinal neurons of the hand versus leg representation in human primary cortex through GABAAergic and glutamatergic interneuronal circuits is highly similar, and that corticospinal neurons of both representations are activated by TMS transsynaptically in largely identical ways.

Application of multi-state Markov model in studying transition of number of chronic complications and influencing factors in type 2 diabetes mellitus patients

Objective: To establish a multi-state Markov model of type 2 diabetes mellitus (T2DM) patients and explore the transition rule between the cumulative number of different chronic complications, estimate the transition probability and intensity between status, and explore the possible factors affecting the transition between status. Methods: A retrospective cohort study of 33 575 patients with T2DM was conducted. According to the baseline and the cumulative number of chronic complications during the follow-up period, the patients were classified based on five status: T2DM, one complication, two complications, three complications, four and above complication, indicated by S0, S1, S2, S3 and S4, respectively. A time-continuous and state-discrete multi-state irreversible Markov model was used for statistical analysis. Results: The study included 33 575 T2DM patients, and their average age was 60 years old, the median of follow-up length was 8 years. In these patients, 32 653 had no baseline complications. At the end of follow-up, the transition probabilities of S0→S1, S1→S2, S2→S3 and S3→S4 were 16.4%, 32.4%, 45.6% and 25.9%, respectively. The results of multivariate analysis showed that being female (HR=0.919), less than 60 years old (HR=0.929), higher fasting plasma glucose (HR=1.601), lower high-density lipoprotein (HR=1.087), higher total cholesterol (HR=1.090),weekly exercise (HR=0.897), vegetarian diet (HR=0.852) and heavy diet (HR=1.887) were the risk factors for S0 to S1. And being female (HR=0.768), less than 60 years old (HR=0.859) and lower high-density lipoprotein (HR=1.160) were the risk factors for S1 to S2. Conclusions: The probability of multiple complications in T2DM patients increased over time, the transition intensity of S2→S3 was largest, followed by S1→S2. Therefore, we need to conduct both early and long-term indicators monitoring and disease prevention, strengthen the health education to improve patients' daily living habits at early stage of the illness, encourage patients to have moderate exercise and balanced diet, strengthen the monitoring of fasting blood- glucose, cholesterol and high-density lipoprotein levels to prevent the deterioration of the illness.

Understanding of Light Absorption Properties of the N-Doped Graphene Oxide Quantum Dot with TD-DFT

We employed the TD-DFT method with different analyzing tools to systematically investigate the absorption properties of the C76H22 and C73H21 graphene quantum dots (GQD) with the oxygenous edge modification (oxidation with −OH and =O groups) and three types of the N-doping defect. By analyzing the change of electronic structure, transition charge localization, non-carbon atomic orbital component, charge transfer magnitude, and transition dipole moment, we found the mechanisms of the oxygenous edge modification and N-doping in modulating absorption properties of the GQD materials relevant to the bioimaging application. Both the edge =O/–OH and the doped N can make a red-shift for the absorption spectra. Only the =O group modification can turn the S1 excitation to be a charge transfer state. The edge-modified =O and doped N alone are not sufficient to generate a strong intensity for the S1 transition. Their combination can regulate the transition dipole moment distribution and enhance the intensity of S1. The edge oxidation and N-doping-induced electronic effects are also related to the deformation of the GQD planar structure. In particular, we developed a few analysis tools, including deformation maps and transition dipole moment maps, to virtualize the spatial resolution of the synergic effect of the heterogeneous atoms, O, OH, and N, as well as the edge and core carbons. These results and analysis tools can provide more detailed information to understand the mechanisms of different types of edge modifications and defects at the atomistic level. They would be very useful for synthetic chemists to design novel quantum dots with a higher photoluminescence quantum yield.

Enhancement of Chemiluminescence Intensity of S2* in Non-premixed Hydrogen Microjet Flame in the Photometric Detector for Sulfur Detection.

A transparent quartz rod (q) placed vertically on top of a non-premixed hydrogen microjet flame in a flame photometric detector (qFPD) was developed and evaluated for sulfur detection. The microjet flame burned around the quartz rod because of Coanda effect, forming an extended downstream flame zone with a relatively low temperature between 550 and 650 °C, which is favorable to the formation of S2*. The emission intensity of S2* and the signal-to-noise ratio (SNR) of sulfur response were enhanced 2.6- and 2.1-fold, respectively. It was found that the quartz rod of diameter 4 mm with a tip shape of semicircle placed 6 mm above the nozzle yielded the highest SNR. The limits of detection (LOD) for seven kinds of tested sulfur-containing compounds of qFPD were 0.3-0.5 pg S s-1, which is 5-7 times better than that of commercially available FPD detectors (LOD: 1.6-2.8 pg S s-1). The selectivity of sulfur over carbon was 105 on qFPD when the SNR for the mass flow rate of S and C atoms was ∼3 times. It was the first time that a quartz rod was used vertically on top of a microjet hydrogen-rich flame in FPD to enhance the chemiluminescence of S2* and improve the LOD down to 0.3-0.5 pg S s-1.

Electronic Spectrum of the Tropylium Cation in the Gas Phase

The structure and properties of the tropylium cation (C7H7+) have enthralled chemists since the prediction by Hückel in 1931 of the remarkable stability for cyclic, aromatic molecules containing six π-electrons. However, probing and understanding the excited electronic states of the isolated tropylium cation have proved challenging, as the accessible electronic transitions are weak, and there are difficulties in creating appreciable populations of the tropylium cation in the gas phase. Here, we present the first gas-phase S1 ←S0 electronic spectrum of the tropylium cation, recorded by resonance-enhanced photodissociation of weakly bound tropylium-Ar complexes. We demonstrate that the intensity of the symmetry-forbidden S1 ←S0 transition arises from Herzberg-Teller vibronic coupling between the S1 and S2 electronic states mediated by vibrational modes of e2' and e3' symmetry. The main geometry change upon excitation involves elongation of the C-C bonds. Multiconfigurational ab initio calculations predict that the S1 excited state is affected by the dynamical Jahn-Teller effect, which should lead to the appearance of additional weak bands that may be apparent in higher-resolution electronic spectra.

Triazole-Coupled Benzimidazole-Based Fluorescent Sensor for Silver, Bromide, and Chloride Ions in Aqueous Media.

A triazole-coupled benzimidazole-based fluorescent probe S1 with nitrogen and oxygen binding sites was synthesized and its properties as a probe for cations were investigated. Probe S1 was found to be highly selective toward Ag+ ions in aqueous media. The fluorescence intensity of S1 was quenched as a function of the concentration of Ag+ ions in the presence of potential interfering cations with a detection limit of 2.70μM. The resulting S1-Ag+ complex was subsequently studied for its anion recognition abilities and found to recognize Br- and Cl- ions, revealing the concentration-dependent fluorescence enhancement with detection limits of 22.2 and 23.0μM, respectively. Revival of the fluorescence profile of probe S1 indicated that Ag+ ion was released from the S1-Ag+ complex. Probe S1 is a sensor that can be single-handedly utilized for the qualitative and quantitative determination of Ag+, Br-, and Cl- ions in aqueous media.

Detection of Sulfur‐Related Defects in Sulfur Diffused n‐ and p‐Type Si by DLTS

Sulfur is diffused into Czochralski (CZ) and Float‐Zone (FZ) silicon wafers at 1200 °C for 30 h. After diffusion, the wafers are slowly cooled in air. Several defect levels are observed by deep level transient spectroscopy (DLTS) in n‐ and p‐type samples. All defects levels are related to sulfur defects, but none could be identified with the donor and double donor states of substitutional S or molecular S2. Additional annealing of the samples at 300 °C generates four DLTS levels in n‐type Si and no peaks in p‐type Si. The enhancement of the emission rate with the electrical field confirm their donor and double donor‐like behavior. The authors identify the four DLTS levels in the annealed n‐type Si samples with the different charge states of monoatomic S and molecular S2 (S0, S+, S20, and S2+) defects in Si. Hydrogenation of the annealed samples by wet chemical etching results in a reduction of the intensity of S0, S+, S20, and S2+ due to a passivation of these defects. The authors did not observe any electrically active SH‐complexes in the hydrogenated samples.

Understanding the Interaction Between Oligopeptide and Water in Aqueous Solution Using Temperature-Dependent Near-Infrared Spectroscopy.

Investigating the interaction between oligopeptide and water is essential for understanding the structure, dynamics and function of proteins. Temperature-dependent near-infrared (NIR) spectroscopy and independent component analysis (ICA) were employed to study the interaction between oligopeptide and water in aqueous solution. The NIR spectra of two homo-oligopeptides, penta-aspartic acid (D5) and penta-lysine (K5), in aqueous solution of different concentration were measured at different temperature (30-90 ℃). Independent component analysis was performed to extract the spectral information that changes with temperature. The independent components (ICs) representing the spectral information of NH and CH2 groups were obtained. Compared with D5, the two groups in K5 change significantly at higher temperature. The result may suggest that K5 has stronger interaction with water than D5. Moreover, three ICs that contain the spectral information of the water species with no (S0), one (S1), and two (S2) hydrogen-bonds were obtained. It was shown that the spectral intensity of S0 and S1 increases while that of S2 decreases with the temperature, and the changes of oligopeptide solutions are weaker than those of pure water. The results indicate that water structure is sensitive to temperature and the oligopeptide in aqueous solution improves the thermal stability of the water species. When oligopeptide is added, the spectral intensity of S0 and S2 decreases and that of S1 increases for D5 solution, but the intensity of all the three species decreases for K5 solution. Furthermore, the concentration effect of K5 was found to be stronger than D5. The result may reveal that D5 combines with water molecule through forming one hydrogen bond but K5 interacts with water through a different way.

Sacral neuromodulation blocks pudendal inhibition of reflex bladder activity in cats: insight into the efficacy of sacral neuromodulation in Fowler's syndrome.

This study tested the hypothesis that sacral neuromodulation, i.e., electrical stimulation of afferent axons in sacral spinal root, can block pudendal afferent inhibition of the micturition reflex. In α-chloralose-anesthetized cats, pudendal nerve stimulation (PNS) at 3-5 Hz was used to inhibit bladder reflex activity while the sacral S1 or S2 dorsal root was stimulated at 15-30 Hz to mimic sacral neuromodulation and to block the bladder inhibition induced by PNS. The intensity threshold (T) for PNS or S1/S2 dorsal root stimulation (DRS) to induce muscle twitch of anal sphincter or toe was determined. PNS at 1.5-2T intensity inhibited the micturition reflex by significantly ( P < 0.01) increasing bladder capacity to 150-170% of control capacity. S1 DRS alone at 1-1.5T intensity did not inhibit bladder activity but completely blocked PNS inhibition and restored bladder capacity to control level. At higher intensity (1.5-2T), S1 DRS alone inhibited the micturition reflex and significantly increased bladder capacity to 135.8 ± 6.6% of control capacity. However, the same higher intensity S1 DRS applied simultaneously with PNS, suppressed PNS inhibition and significantly ( P < 0.01) reduced bladder capacity to 126.8 ± 9.7% of control capacity. S2 DRS at both low (1T) and high (1.5-2T) intensity failed to significantly reduce PNS inhibition. PNS and S1 DRS did not change the amplitude and duration of micturition reflex contractions, but S2 DRS at 1.5-2T intensity doubled the duration of the contractions and increased bladder capacity. These results are important for understanding the mechanisms underlying sacral neuromodulation of nonobstructive urinary retention in Fowler's syndrome.

Cardiac Auscultation for Noncardiologists: Application in Cardiac Rehabilitation Programs: PART I: PATIENTS AFTER ACUTE CORONARY SYNDROMES AND HEART FAILURE.

During outpatient cardiac rehabilitation after an acute coronary syndrome or after an episode of congestive heart failure, a careful, periodic evaluation of patients' clinical and hemodynamic status is essential. Simple and traditional cardiac auscultation could play a role in providing useful prognostic information.Reduced intensity of the first heart sound (S1), especially when associated with prolonged apical impulse and the appearance of added sounds, may help identify left ventricular (LV) dysfunction or conduction disturbances, sometimes associated with transient myocardial ischemia. If both S1 and second heart sound (S2) are reduced in intensity, a pericardial effusion may be suspected, whereas an increased intensity of S2 may indicate increased pulmonary artery pressure. The persistence of a protodiastolic sound (S3) after an acute coronary syndrome is an indicator of severe LV dysfunction and a poor prognosis. In patients with congestive heart failure, the association of an S3 and elevated heart rate may indicate impending decompensation. A presystolic sound (S4) is often associated with S3 in patients with LV failure, although it could also be present in hypertensive patients and in patients with an LV aneurysm. Careful evaluation of apical systolic murmurs could help identifying possible LV dysfunction or mitral valve pathology, and differentiate them from a ruptured papillary muscle or ventricular septal rupture. Friction rubs after an acute myocardial infarction, due to reactive pericarditis or Dressler syndrome, are often associated with a complicated clinical course.During cardiac rehabilitation, periodic cardiac auscultation may provide useful information about the clinical-hemodynamic status of patients and allow timely detection of signs, heralding possible complications in an efficient and low-cost manner.

The influence of short-interval intracortical facilitation when assessing developmental changes in short-interval intracortical inhibition

Objective: Measures of short-interval intracortical inhibition (SICI) can be contaminated by excitatory influences of short-interval intracortical facilitation (SICF), unless examined at individually-optimized interstimulus intervals (ISIs). We hypothesized that age-related differences in SICF would explain previously reported reduced SICI in children and adolescents compared with adults. Methods: Fifty-one participants, aged 8–29years, underwent transcranial magnetic stimulation. SICF curves were constructed to determine the ISI at which SICF was minimal (i.e. the first trough). SICI curves were constructed at this individually-determined ISI with conditioning stimulus (S1) intensities of 60–110% of active motor threshold. Results: There was no effect of age on the ISI corresponding with the SICF trough. However, there was a main effect of age on the amplitude of the conditioned motor-evoked potential at the different ISIs, such that children aged 8–12years demonstrated greater SICF than those aged 16–18 and 19–21years. There was no effect of age on SICI, and no interaction between age group and S1 intensity. Conclusions: Compared with that in older adolescents and young adults, SICF is enhanced in children aged 8–12years. Surprisingly, this enhanced SICF does not appear to reduce the degree of SICI that can be evoked at the first trough in this age group. Significance: This is the first report of enhanced SICF in young children. It remains possible that enhanced SICF may have confounded earlier reports of reduced SICI in children less than 8years.

Subcortical contribution to late TMS-induced I-waves in intact humans.

Paired-pulse transcranial magnetic stimulation (TMS) of the human motor cortex results in consecutive facilitatory motor evoked potential (MEP) peaks in surface electromyography. It has been proposed that early and late MEP peaks involve different mechanisms of action; however, little is known about the characteristics of the later peaks. Using paired-pulse TMS over the hand motor cortex at different test (S1) and conditioning (S2) interstimulus intervals and intensities we examined early (first) and late (second and third) MEP peaks in a resting finger muscle. We demonstrate that the third peak had reduced amplitude and duration compared with the second, regardless of the S1 intensity. Higher S2 intensity increased the amplitude of the third but not the second peak, suggesting that the third peak had a higher threshold. The interval between the second and third peak was longer than between the first and second peak in all conditions even though all peaks had a similar latency dispersion. No differences were found in the amplitude, duration, and threshold of the first and second peaks. A threshold electrical S2 over the cervicomedullary junction facilitated the second and third but not the first peak similarly to TMS. Our results indicate that the third MEP peak is smaller and has higher threshold than the second peak and the similarities between the first and second peak suggest that this is less likely explained by a reduced effectiveness in recruitment. We argue that subcortical pathways might contribute to differences found between late TMS-induced peaks in intact humans.

Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

Spontaneous isolated pericardial tamponade associated with warfarin.

To the Editor, An 83-year-old female patient was admitted to the emergency department with progressive dyspnea and orthopnea for 3 days. She was discharged with warfarin therapy (5 mg per day) due to pulmonary embolism 5 months previously. On admission she was orthopneic and tachypneic. Her arterial blood pressure was 90/60 mmHg and heart rate was 115/min with sinus rhythm. On cardiac auscultation, S1 and S2 intensity were decreased, and pathologic murmur and pericardial friction were not observed. Other physical examination findings were unremarkable. An increased cardio-thoracic ratio was revealed on chest X-ray (Figure 1a). Decreased QRS voltage and sinus tachycardia was evaluated on electrocardiogram. The internalised normalised ratio (INR) level was 8.6 and the prothrombin time was 70 seconds. Haemoglobin was determined to be 11.1 g/dL. The other laboratory findings were normal. An emergency thoracic computed tomography (CT) scan was performed to exclude recurrent pulmonary embolism, and surprisingly showed a massive pericardial effusion (Figure 1b). However, echocardiography revealed severe pericardial effusion that was compressing the right ventricle. Therefore, vitamin K and fresh frozen plasma infusion were administered promptly. As a result, the INR was decreased to 1.4 and 800 mL haemorrhagic fluid was drained percutaneously (P/S) with the apical approach. The patient’s blood pressure, orthopnoea and dyspnoea improved dramatically. There was no other source of bleeding except haemopericardium. Consequently, the cardiac tamponade in our patient, secondary to haemopericardium, was considered to be the result of the incorrect dosage of Warfarin. On control echocardiography, there was no recurrence of pericardial fluid and the patient was discharged on the 5th day. FIG. 1. a, b. Increased cardio-thoracic ratio due to pericardial effusion on chest X-ray (a). CT scan of chest showing large pericardial effusion (see arrow) (b) Cardiac tamponade is a life-threatening emergency condition. It is an acute type of pericardial effusion in which fluid accumulates in the intrapericardial space. This creates a mechanical pressure in the cardiac chambers which disrupts cardiac filling. (1). The common causes of pericardial effusion resulting in tamponade are pericarditis, malignancy, acute myocardial infarction, congestive heart failure, collagen vascular diseases, end stage renal disease, viral and bacterial infections (1). Cardiac tamponade secondary to haemopericardium is rarely seen and occurs with traumatic and non-traumatic causes. Non-traumatic causes are less common and associated with a number of conditions such as malignancy, infection, uraemia or coagulopathy (2). Today, warfarin sodium is still the most commonly used agent for anticoagulant therapy. The risk of spontaneous bleeding in patients using warfarin is less than 10%, whereas the risk of bleeding into the pericardial space is less than 1% (3). Echocardiography, which is the diagnostic test of choice, evaluates the haemodynamic consequences and guides transcutaneous drainage; CT is useful for further workup. These methods are superior to echocardiography for anatomical information, characterisation of the effusion, and providing information about the adjacent structures (2). The primary treatment of pericardial tamponade is pericardiocentesis.. Echocardiography-guided pericardiocentesis has been shown to be a safe and effective method which can be performed at the patient’s bedside (4). Isolated haemopericardium and cardiac tamponade secondary to warfarin are seen very rare. Haemorrhagic cardiac tamponade should be excluded in patients on warfarin with unexplained hypotension and excessive anticoagulation. Close monitoring of INR level is very important in the management of patients, especially in the elderly receiving warfarin treatment (5).