Duodenal gastrointestinal stromal tumors (DGIST) are rare, and data on their management is limited. We here report the clinicopathological characteristics, different surgical treatments, and long-term prognosis of DGIST.Data of 74 consecutive patients with DGIST in a single institution from June 2000 to June 2014 were retrospectively analyzed. The overall survival (OS) and recurrence/metastasis-free survival rates of 74 cases were calculated using Kaplan–Meier method.n = 37, 50.00 %), abdominal pain , mass , and others . A total of 18 patients (24.3 %) underwent wedge resection (WR); 39 patients (52.7 %) underwent segmental resection (SR); and 17 cases (23 %) underwent pancreaticoduodenectomy (PD). The median follow-up was 56 months (1–159 months); 19 patients (25.68 %) experienced tumor recurrence or metastasis, and 14 cases (18.92 %) died. The 1-, 3-, and 5-year recurrence/metastasis-free survival rates were 93.9, 73.7, and 69 %, respectively. The 1-, 3- and 5-year OS were 100, 92.5, and 86 %, respectively. The recurrence/metastasis-free survival rate in the PD group within 5 years was lower than that in the WR group (P = 0.047), but was not different from that in the SR group (P = 0.060). No statistically significant difference was found among the three operation types (P = 0.294).Out of 74 cases, 42 cases were female (56.76 %) and 32 cases (43.24 %) were male. Approximately 22.97, 47.30, 16.22, and 13.51 % of the tumors originated in the first to fourth portion of the duodenum, respectively, with a tumor size of 5.08 ± 2.90 cm. Patients presented with gastrointestinal bleeding (DGIST patients have favorable prognosis after complete tumor removal, and surgical procedures should be determined by the DGIST tumor location and size. Nonspecific abdominal pain and gastrointestinal hemorrhage are the most frequent symptoms in GIST patients, and several emergency patients have been admitted to a hospital because of this disease [Mazur and Clark re-evaluated the histogenesis of gastrointestinal stromal tumors (GIST) in 1983, and following research has confirmed that GIST are the most common mesenchymal tumors . Althoug disease .Primary GIST is categorized into very low, low, intermediate, and high risk based on a previous study of Fletcher . HoweverCurrently, numerous studies involving DGIST have been published, but most of these studies have small samples or are retrospective case series , 14–18. KIT/PDGFRA gene mutation, confirmed by senior pathologists); (3)The tumor was located in the duodenum, as confirmed by preoperative abdominal CT scan, ultrasound endoscopy, upper gastrointestinal barium swallow radioscopy, and operation; (4)Patients with GIST synchronous with other malignancies were excluded in this study. A total of 74 DGIST patients were included and examined in this study. The Institutional Review Board and Ethics Committee of the West China Hospital of Sichuan University informed that an ethical review was not needed for this retrospective study.Medical records of DGIST patients admitted in the Department of General Surgery of West China Hospital of Sichuan University from June 2000 to June 2014 were retrospectively analyzed. Inclusion criteria are as follows: (1)Patients who underwent laparotomy; (2)Patients with DGIST, as proven by pathological, immunohistochemical, and gene mutation detection examinations , SR , and PD (operation with pancreaticogastrostomy or pancreatojejunostomy). WR with primary closure was mainly performed for small or abluminal lesions. Tumor risk categories were evaluated according to the modified National Institutes of Health (NIH) risk classification . The patData on clinical symptoms, gender, age, hospital stay, surgical procedures , operation complications , emergency admission, tumor size , tumor location , NIH risk classification, mitotic count per 50 high power fields (HPF) of the microscope, medication before and after surgery (dosage and duration), tumor recurrence/metastasis time, and postoperative follow-up information were collected. All patients were followed up by office visit, telephone call, or outpatient clinic visit after being discharged from the hospital . The censor date of the follow-up was July 2014.P < 0.05. All data analyses were performed using SPSS version 18.0 statistical software package for Microsoft Windows.Categorical variables were described in terms of frequency and percentages. The measurement data were expressed as mean ± SD. One-way ANOVA was used to compare the clinicopathological characteristics of the three surgical groups. Chi-square test was used to enumerate the data. Wilcoxon test was used to test rank the data. The recurrence/metastasis-free survival rate was measured from operation to tumor recurrence or metastasis . Overall survival (OS) time includes the period from surgery to death or until the last follow-up. Survival curves were performed using Kaplan–Meier method and compared using log-rank test. Statistical significance was defined as a two-tailed Table P = 0.005) and SR groups (P = 0.011). PDs were mainly chosen for patients with ampullary involvement or close proximity of the tumor to the second segment of the duodenum, whereas those with lesions in the other portion of the duodenum were treated with WR or SR. The hospital stay of patients in the PD group was longer than those in the WR group (P = 0.011), but was not significantly different from those in the SR group (P = 0.194). No statistically significant difference was noted regarding to gender, age, clinical manifestation, mitotic count (50HPF), and NIH risk classification among the three groups (P > 0.05). In addition, 5 patients in the SR and PD groups underwent multivisceral resection respectively; 8 patients underwent cholecystectomy; 1 patient underwent hepatic left lateral lobectomy; and 1 patient had combined right kidney and colon resection. Four patients (23.5 %) experienced postoperative complications in the PD group, such as wound infection (n = 2), delayed gastric emptying (n = 1), and anastomotic fistula (n = 1). In addition, 1 patient from the SR group had intraperitoneal infection, whereas 1 patient in the WR group had intestinal obstruction. The serious complications of reoperation and surgery-related death were not observed among the 3 groups. A total of 3 (16.7 %), 8 (20.5 %), and 4 patients (23.5 %) in the WR, SR, and PD groups, respectively, underwent perioperative blood transfusions.Table P = 0.047) but was not significantly different compared with that of the SR group . Notably, the OS among the three surgical procedures was not statistically significant (P = 0.294). The 5-year recurrence/metastasis-free survival rate of patients with tumor size of <5 cm was higher than those with tumor size of ≥5 cm (P < 0.001). The 5-year recurrence/metastasis-free survival rate of patients with mitosis count of ≤5, 6–10, and >10 were 88.5 %, 56.7 % (P = 0.012), and 33.3 % , respectively. Patients with low-, intermediate-, and high-risk, the 5-year recurrence/metastasis-free survival rates were 94.7 %, 57.1 % (P = 0.025), and 53.1 % (P = 0.001 for low risk and P = 0.364 for intermediate risk), respectively. Patients with intermediate- or high-risk who took IM adjuvant therapy revealed a trend of higher recurrence/metastasis-free survival than that of patients without taking IM (P = 0.326).With a median follow-up of 56 months (1–159 months), 7 cases were lost to follow-up. A total of 19 patients 25.68 %) had tumor recurrence or metastasis and 1 patient experienced liver and multiple bone metastases Fig. . Fourtee5.68 % haGIST has been misdiagnosed as smooth muscle or neurogenic tumor for decades because of the insufficient understanding of the GIST concept. However, GIST has been confirmed as an independently oriented differentiated mesenchymal tumor of the digestive tract along with the rapid development of immunohistochemical and molecular biological technologies. To date, most preliminary studies on DGIST are case reports or small sample studies, and only a limited number of studies have reported the operation and long-term prognosis of DGIST , 21, 22.The clinical presentations of DGIST were non-specific, which were related with the tumor size, growth location, and ulcer in the mucous layer. Alimentary tract hemorrhage is the main clinical manifestation of DGIST, as previously reported in literature . DGIST iCurrently, surgery is the only potential curative treatment of GIST if R0 is performed . But surIn the current series, the 5-year OS and recurrence/metastasis-free survival rates were 86 and 69 %, respectively, which were similar to the results of other reports , 25. By Nowadays, IM played a key role in the management of GIST when used as adjuvant therapy. The intermediate-risk subgroup of GIST Patients should take IM at least 1 year, while patients with high risk should last for at least 3 years postoperatively , 32. In In sum, patients with DGIST have a favorable prognosis after complete resection. The 5-year recurrence/metastasis-free survival and OS rates of DGIST were 69 and 86 %, respectively. The treatment of choice for DGIST should be selected according to the DGIST tumor site and size. This study showed that the PD group has a higher complication rate than the WD group, and patients of the former group experienced prolonged hospitalization. In addition, the recurrence/metastasis-free survival rate within 5 years was lower than that of the WR group, but had no significant difference with the SR group.


P < 0.05) the heart rate in groups A, B, and D. Also respiratory rate significantly (P < 0.05) decreased in groups A, B, and D but significantly (P < 0.05) increased at 20 min after induction in group C. However, temperature significantly (P < 0.05) decreased in groups A, B, and C. The induction was good and smooth in groups B and D. Surgical anaesthetic time was longer in groups B and D and shorter in group C. The quality of recovery was good in groups B and D. Side effects such as salivation and apnoea were observed in all groups. In conclusion, the multimodal therapy could be used successfully. However, group D could be the best combination considering the parameters measured.The assessment of anaesthetic and clinical indices of multimodal therapy of propofol, xylazine, and ketamine was done in West African Dwarf (WAD) goat. Sixteen healthy male WAD goats were assigned into four treatment groups, namely, control (group A) (ketamine 5 mg/kg + xylazine 0.05 mg/kg), group B (propofol 5 mg/kg + xylazine 0.05 mg/kg), group C (propofol 5 mg/kg + ketamine 5 mg/kg), and group D (propofol 2.5 mg/kg + ketamine 2.5 mg/kg + xylazine 0.05 mg/kg). All drugs were administered intravenously. The multimodal therapy decreased significantly ( Anaesthesia is an indispensible prerequisite for most surgical interventions both in humans and in animals . It is sKetamine produces stable haemodynamics during anaesthesia as a result of its stimulatory effect on the sympathetic nervous system, which counteracts the depressant effects of other drugs used during anaesthesia . It can Propofol  is a phenolic compound unrelated to any other general anesthetics. It is a nonbarbiturate, nondissociative, and noncumulative intravenous anesthetic agent . It has Xylazine is an alpha-2-adenoreceptor agonist, is nonopioid group with analgesic, sedative, and muscle relaxant effects, and is used commonly in veterinary practice . XylazinContinuous search for proper drug multimodal therapy that will offer good quality anaesthesia, analgesia, and fast recovery with mild or no side effect using drugs of known anaesthetic quality such as xylazine, ketamine, and propofol is highly imperative.The objective of this work was to evaluate the changes in common indices in multimodal therapy anaesthetic of propofol, ketamine, and xylazine in total intravenous anaesthesia in West African Dwarf (WAD) goats.The drugs used were ketamine 50 mg/mL injection , propofol 10 mg/mL injection, 20 mL vial , and xylazine 20 mg/mL injection . ad libitum with grasses and water throughout the experimental period.Sixteen healthy male WAD goats of average weight of 15 kg were used for the study. They were randomly assigned into four groups (A–D) of four goats each. The goats were fedControl (group A) goats were anaesthetized using xylazine (0.05 mg/kg body weight) and ketamine (5 mg/kg body weight) multimodal combination. Group B goats were anaesthetized using a combination of xylazine (0.05 mg/kg body weight) and propofol (5 mg/kg body weight). Group C goats were anaesthetized using ketamine (5 mg/kg body weight) and propofol (5 mg/kg body weight), while, in group D, xylazine (0.05 mg/kg body weight), ketamine (2.5 mg/kg body weight), and propofol (2.5 mg/kg body weight) were administered simultaneously. All drugs were administered intravenously through jugular vein.This was done immediately after return of pain reflexes. In the control (group A) animals, anaesthesia was maintained at 25.00 ± 5.00 min and 40.00 ± 2.00 min after induction with a total of 3 mls of ketamine (5 mg/kg body weight). Animals in group B were given repeated injection of propofol 5 mg/kg body weight at 22.00 ± 3.00 min and at 39.00 ± 2.00 min after induction with a total of 10 mls. In the group C, anaesthesia was maintained at 18.00 ± 2.00 min and at 35.00 ± 3.00 min after induction with propofol 5 mg/kg body weight with a total of 10 mls. Also anaesthesia was maintained in group D at 30.00 ± 4.00 min and 50.00 ± 3.00 min with propofol 5 mg/kg body weight with a total of 15 mls titrated to effect.The heart rate (Hr), respiratory rate (Rr), and rectal temperature (rt°) were measured at 0 min before treatment to ascertain the baseline values and subsequently every ten (10) min interval following the induction till the recovery of each animal.A modified method of determination of quality of anaesthesia according to Adetunji et al.  was usedt0) and the time of disappearance of flank twitch reflex (tz). The difference between the former and the later gave the time of the onset of flank analgesia.This was done by recording the time (in min) of the initial injections of the drugs (This was done by noting the time of disappearance of flank twitch reflex (TD) following the intravenous injection and the time of reappearance of flank twitch. Then the difference between the time of disappearance (TD) and the time of reappearance (TA) of flank twitch reflex gave the duration of flank analgesia time (DA): DA = TA − TD.This was measured by recording the time when anaesthesia induced recumbency in the goat and then the time when the goat was able to maintain standing position on its own following recovery. The difference between the two was taken as the duration of recumbency.Standing time was calculated by determining the difference between the time when the goat assumed sternal posture as sign of recovery and when the goat finally stood on its own unassisted.The quality of induction and recovery were evaluated using a modified method according to Prassinos et al. . Hence, Good. Smooth induction, rapidly assumed recumbency, no signs of excitement.Fair. Slightly prolonged induction, mild excitation, presence of swallowing reflex.Poor. Obvious excitement, jumps or attempts to stand after recumbency, full presence of swallowing reflex.Good. Smooth, easy transition to alertness, resumption of sternal position, ability to stand within a reasonable amount of time and ability to walk with minimal ataxia. Fair. Transient excitement or whole body movement, some struggles, hyperresponsiveness that disappears once the goat stands unassisted but with moderate ataxia.Poor. Stereotype behaviour, for example, circling, premature attempts to stand, prolonged struggling.Side effects like apnoea, laboured breathing and snoring, grunting, coughing, salivation, paddling movement, opened eye lid, ataxia, and urination were observed by watching the goats closely following induction of the anaesthesia, throughout the anaesthetic and postanaesthetic period.P ≤ 0.05) was considered statistical where applicable.Data were expressed as mean ± standard error of mean in each group. The means were compared using analysis of variance (ANOVA). The means were separated using least significant difference (LSD). A probability value less than or equal to 0.05 (P < 0.05) decreased in groups A, B, and D following induction when compared to group C. The heart rate was significantly (P < 0.05) lower in group A from 20 min to 40 min after induction when compared to other groups. However, the heart rate was significantly (P < 0.05) decreased in groups B and D at 60 min when compared to the control (group A). On the contrary, the heart rate significantly (P < 0.05) increased at 20 min after induction in group C (The heart rate significantly ( group C .P < 0.05) in groups A and B at 10 min after induction However, it significantly (P < 0.05) increased in groups B, C, and D at 20 min after induction when compared to group A. The multimodal therapy also significantly (P < 0.05) decreased the respiratory rate in group D at 60 min after induction when compared to control (group A) (The respiratory rate decreased significantly (group A) .P < 0.05) decrease in rectal temperature in group B from 10 min to 40 min after induction when compared to other groups. The temperature also significantly (P < 0.05) decreased in groups B, C, and D at 40 min when compared to group A. However, rectal temperature increased significantly in group D at 20 min after induction when compared to group A (There was significant ( group A .P < 0.05) shorter when compared to the control and to other groups.The onset of analgesia was 3.57 ± 0.28 min, 2.15 ± 0.10 min, 1.80 ± 0.21 min, and 1.00 ± 0.00 in groups A, B, C, and D, respectively. The onset of analgesia in group D was significantly  variation in recumbent time between group D and control. However, recumbent time in groups B and C was significantly (P < 0.05) shorter when compared to the control.The mean recumbent time following induction was 91.50 ± 3.75 min, 65.04 ± 6.45 min, 45.02 ± 5.24 min, and 91.00 ± 2.08 min in groups A, B, C, and D, respectively. There is no significant (P < 0.05) shorter when compared to control groups.The mean standing time was 7.50 ± 0.50 min, 4.58 ± 1.20 min, 1.30 ± 0.20 min, and 1.50 ± 0.40 min for groups A, B, C, and D, respectively. The mean standing time in groups B, C, and D was significantly  was used as the control in this experiment. The decrease in heart rate after induction in groups A, B, and D may be attributed to the bradycardia effect of the therapy used in these groups. Similar results have been reported following ketamine + xylazine anaesthesia , 16, 17.The multimodal therapy used in the control (group A) decreased the respiratory rate more than the multimodal therapy used in other groups at induction. However, the profound decrease in respiratory rate in group D at 60 min may be attributed to the effect of maintenance dose. It means that ketamine + xylazine combination causes respiratory depression  and addiThe decreased temperature recorded in group B is in accordance with the findings of Adetunji et al. . HoweverThe synergistic effect of propofol and other drugs used in the therapy might have resulted in the short onset of analgesia in groups B, C, and D. Propofol causes rapid induction (within 5 to 30 sec) which results in unconsciousness .Long surgical anaesthetic time was achieved in groups A, B, and D. This could be attributed to synergistic actions of the drugs used. Xylazine acts in synergism with ketamine to produce better analgesic effect .The smooth induction recorded in most of the groups may also be attributed to the combined anaesthetic and sedative actions of the drugs used. However, rapid recovery may be attributed to noncumulative effect of propofol used for maintenance in groups other than the control.Apnoea and salivation were the major side effects observed. The apnoea might have resulted from the depressive effect of the drugs on respiratory centre. Apnoea has been reported in goats after propofol administration  while keUrination was also observed in all the groups. However, it was more pronounced in groups B and D. Urination is a means of elimination of drugs by the kidney. It is a response of healthy kidney to eliminate these substances from the body. Urination following the administration of xylazine is a common occurrence in goat , 21. UriBased on the results from this study, the multimodal intravenous therapy caused smooth and uneventful induction with mild cardiopulmonary depressions and rapid recovery.Apnoea was the major side effect of the multimodal therapy more especially in propofol combinations. Therefore, care must be taken when administering these drugs by monitoring the animal closely to know when the apnoea develops. Once apnoea is noticed, drug administration should be paused until the animal regains normal regular breathing. An attempt to continue with the injection or infusion of drug once the apnoea develops may lead to respiratory arrest and possible death of the animalTherefore, the multimodal therapy used in groups A, B, and D could be used successfully in both short and long surgical procedures without untoward side effects. However, the therapy used in group D could be the best combination therapy taking into account the parameters measured.


During meditation there was an increased in oxy-hemoglobin (ΔHbO) and total hemoglobin (ΔTHC) concentration with reduced deoxy-hemoglobin (ΔHbR) concentration over the right prefrontal cortex (rPFC), whereas in random thinking there was increased ΔHbR with reduced total hemoglobin concentration on the rPFC. The mean reaction time (RT) was shorter during stroop color word task with concomitant reduction in ΔTHC after meditation, suggestive of improved performance and efficiency in task related to attention. Our findings demonstrated that meditation increased cerebral oxygenation and enhanced performance, which was associated with activation of the PFC.Recent neuroimaging studies state that meditation increases regional cerebral blood flow (rCBF) in the prefrontal cortex (PFC). The present study employed functional near infrared spectroscopy (fNIRS) to evaluate the relative hemodynamic changes in PFC during a cognitive task. Twenty-two healthy male volunteers with ages between 18 and 30 years  performed a color-word stroop task before and after 20 min of meditation and random thinking. Repeated measures ANOVA was performed followed by a  Sutras  and Bhagavad Gita (Circa 400–600 B.C.) very well describe the connection between meditation and mental modifications. Traditionally, two states of meditation have been described, viz., (i) focused meditation , and this state is supposed to lead to the next stage of effortless mental expansion i.e., (iii) meditation . When not in meditation, it is said that the mind may be in two other states ; and (ii) non-meditative focused thinking   etc.,) demonstrated that regular practice of meditation develops awareness to the contents of subjective experience, including thoughts, sensations, intentions, and emotions  would be beneficial. The neuronal activity during meditation has been reported in several electroencephalography (EEG) and magnetoencephalography (MEG) studies. Experienced meditators showed an increased EEG power in lower frequency bands   are in its infancy. In fact, there is only one study that assessed deoxyhemoglobin changes with a single wavelength probe placed over the left PFC during Qigong meditation  were recruited from S-VYASA (a Yoga University), South India. All participants had a minimum of 12-month experience in meditation  on the Sanskrit syllable “The study was approved by the Institutional Ethics Committee of S-VYASA, a Yoga University (No.-RES/IEC-S-VYASA/11/2011). The study protocol, nature of the experiments and the operating mode of the instrument was explained to the subjects before obtaining signed informed consent.cancalata) and meditation (dhyana), and eight States , Stroop_Post, and Post). Each participant was assessed for both the meditation and control session on two separate consecutive days. The sessions were randomized online with randomization software.The protocol utilized in the present study consisted of two sessions i.e., random thinking  attributes and connotations of the syllable with closed eyes. This involved combined mental chanting with effortless defocusing on syllable “OM”. This gradually allowed the participants to experience brief periods of silence, which they reported after the session.In effortless meditation session, each participant was instructed to dwell effortlessly on thoughts of “Each participant sat cross-legged with eyes closed and followed pre-recorded instructions throughout meditation and random thinking sessions. An emphasis was placed on slowly, practice with awareness of physical and mental sensations, and relaxation. The duration of each session was 20 min between 06:00 to 06:30 h conducted 5 days a week. The theoretical aspects of the meditation were detailed by the meditation teacher on the first day. Following this, the practice of each session began with pre-recorded instructions. The practice of meditation was evaluated based on their self-reporting and by consultations with the meditation teacher. The two phases—random thinking (Rand) and meditative defocusing were as follows:All Participants were assessed in a sound and light dampening Faraday cage. Participants’ were monitored using a closed circuit television outside the cabin to detect if they moved or fell asleep during a session. During the session, instructions were passed through a two-way intercom, so that participants could remain uninterrupted. The recording room temperature was maintained at 24.0 ± 1.0°C with 56 percent average humidity during the conduct of experiments. The background noise level was 26 dB of the acoustically shielded chamber. For each participant, the data acquisition session lasted 60 min.λ1 = 730 nm, λ2 = 830 nm, λ3 = 850 nm) and ten photodiodes as detectors that were symmetrically arranged in an area of 3.5 × 14 cm2, conducing to 16 nearest source—detector  at 2.5 cm separation displayed in Figure A 16-channel continuous wave fNIRS imager system  was employed to map changes in ΔHbO, ΔHbR and ΔTHC over bilateral PFC. The system consisted of a flexible probe to match contour of the human forehead . The stroop color word task consisted of red, green and blue colored boxes and the corresponding written words “RED”, “BLUE” and “GREEN”. The color was presented as color square (4.5 × 4.5 cm) boxes on a black background. The duration of the presented square boxes and words was 500 ms each. Congruent trials comprised of square color boxes followed by words describing the color of the box written in the same color ; incongruent trials comprised of words describing the color of the box written in a color other than that of the box ; neutral trials comprised words written in white . Participants were instructed to reply as speedily and accurately as possible to the name of the color word (while ignoring the color itself) consistent to the color of the Box with a button press of the response key using the thumb of their right hand. To increase the potency of the conflict stimulus, 20% of trials were congruent , 20% were incongruent  and 50% were neutral . The duration of the stimulus was 500 ms, with a variable interstimulus interval (ISI) of 1000–2500 ms the experimental steps are illustrated in Figure The participants were assessed in two separate sessions i.e., random thinking and meditation while recording hemodynamic activity on the PFC using 16-channel continuous wave fNIRS system. On the preceding day and on the day of the recording, participants were asked to avoid tea and coffee which are known to influence cognitive performance Nehlig,  and cerepost hoc analysis with Bonferroni adjustment for multiple comparisons between the mean values of different states (“During” and “Post”) and all comparisons were made with the respective “Pre” state.The hemodynamic responses of bilateral PFC were recorded and data were averaged according to the task condition . Statistical analysis has been carried out on these differential values. Filtered data were tested with Kolmogorov-Smirnov test for normality. Repeated measures analysis of variance (RM-ANOVA) was used because the same individuals were assessed in repeated sessions on two separate days . RM-ANOVA was performed with three “within subjects” factors, i.e., Factor 1: Sessions (random thinking and meditation); Factor 2: PFC (right and left). Factor 3: States , “Stroop_Post” and “Post”). The repeated measures ANOVAs were carried out for concentration changes of oxygenated and deoxygenated hemoglobin and total hemoglobin change  across the right and left PFC. This was followed by a p < 0.05. The effect size (d) defined by Cohen  of neutral, congruent and incongruent conditions and hemodynamic responses of stroop color word task before and after the sessions (random thinking and meditation). The results were averaged for each side of PFC (right and left), parameter and subject separately to compare between different conditions and sessions. A repeated measures ANOVA was carried for multiple comparisons following Bonferroni adjustment. Statistical analyses were carried out using the Statistical software SPSS version 20.0 . The alpha level was set at by Cohen , as the F = 4.862, p = 0.039, η2p = 0.188); Conditions  = 24.12, p < 0.001, η2p = 0.535); States  = 6.696, p < 0.023, η2p = 0.242), and the significant interaction between Sessions × States  = 45.36, p < 0.001, η2p = 0.684).Reaction times (RTs) were computed solely from the correctly answered trials. With respect to RT, a repeated—measures 3 way ANOVA with Sessions (random thinking and meditation) × States  × Conditions . Repeated measures ANOVA demonstrated a significant main effect for Sessions  compared to random thinking session given in Table t-test, revealed significant differences among all three conditions  in two different sessions (meditation and random thinking). In random thinking session, there were significant differences in neutral vs. congruent: t(21) = −3.86, p = 0.001; congruent vs. incongruent: t(21) = −2.31, p = 0.031; neutral vs. incongruent: t(21)= −5.92, p < 0.001 whereas in meditation session, there was a significant difference in neutral—congruent: t(21) = −4.47, p < 0.001; congruent—incongruent: t(21) = −1.85, p > 0.05 (NS); neutral—incongruent: t(21) = −6.148, p < 0.001. The mean RTs were significantly shorter in the neutral (p = 0.002), congruent (p < 001) and incongruent (p < 0.003) conditions after meditation session whereas after the random thinking session, mean RTs were delayed in the neutral (p = 0.034) and incongruent (p = 0.008) conditions. The average RTs for neutral, congruent, and incongruent trials of the stroop color word task are given in Table The RTs were compared using two-tailed paired sample gruent: t1 = −3.86In the present study, the 16 channel fNIRS device provided a set of time series recorded over the PFC. The locations of the probed regions are shown in Figure F = 9.87, p < 0.01, η2p = 0.053); Sessions × PFC × States  = 3.17, p < 0.01, η2p = 0.040).For ΔHbO, the repeated—measures ANOVA for Sessions (Random thinking and Meditation) × PFC (Left and Right) × States  revealed no significant main effect for Sessions, States and PFC. There was a significant interaction between PFC × States  = 9.99, p < 0.01, η2p = 0.054); PFC  = 4.57, p < 0.05, η2p = 0.025). Also, there was a significant interaction between Sessions × PFC ; Sessions × States  = 22.13, p < 0.001, η2p = 0.112); Sessions × PFC × States  = 9.81, p < 0.01, η2p = 0.053).For ΔHbR, the repeated—measures ANOVA demonstrated significant main effect for Sessions  = 9.71, p < 0.01, η2p = 0.053), and the significant interaction between Sessions × PFC  = 5.33, p < 0.01, η2p = 0.03); Sessions × States  = 19.87, p < 0.001, η2p = 0.102); PFC × States  = 5.96, p < 0.05, η2p = 0.033); Sessions × PFC × States  = 14.20, p < 0.001, 0.075).For total hemoglobin (ΔTHC), the repeated—measures ANOVA revealed that there was a significant main effect for PFC  and in the right PFC (p = 0.032) after random thinking session during stroop color word task, whereas, there was a significant improvement in ΔHbO in left PFC (p = 0.006) and right PFC (p = 0.046) following the meditation session.The From the above observations, it can be concluded that meditation enhances bilaterally activation of the anterior PFC and consequently, a stronger increase of oxygenation and cerebral blood flow during stroop task at the right PFC due to interference reduction.F = 5.23, p < 0.001, η2p = 0.029). There was a significant interaction between the PFC × States  = 2.42, p < 0.001, η2p = 0.014); Sessions × Hemispheres × States  = 7.32, p < 0.05, η2p = 0.040).For ΔHbO, the repeated—measures ANOVA for Sessions (Random thinking and Meditation) × PFC (Left and Right) × States  demonstrated a significant main effects for States  = 12.20, p < 0.001, η2p = 0.065); PFC  = 7.89, p < 0.01, η2p = 0.043) and States  = 3.55, p < 0.001, η2p = 0.019). There was a significant interaction between the Sessions × PFC  = 4.13, p < 0.001, η2p = 0.023); Sessions × States  = 9.99, p < 0.001, η2p = 0.054); Sessions × PFC × States  = 10.37, p < 0.001, η2p = 0.056).For ΔHbO, the repeated—measures ANOVA showed there was a significant main effect for Sessions  = 5.07, p < 0.05, η2p = 0.028); PFC  = 12.20, p < 0.001, η2p = 0.065); and States  = 2.79, p < 0.01, η2p = 0.016) and a significant interaction between the Sessions × PFC  = 6.45, p < 0.05, η2p = 0.036); Sessions × States  = 9.06, p < 0.001, η2p = 0.049); PFC × States  = 2.34, p < 0.05, η2p = 0.036]; Session × PFC × State  = 14.51, p < 0.001).For total hemoglobin change (ΔTHC), there was a significant main effect for Sessions  after random thinking session whereas there was a significant increase in the left PFC (p = 0.02) and in right PFC (p < 0.001) after meditation session. Similarly, in ΔTHC, there was a significant decrease in blood flow change in the right PFC (p < 0.001) after the random thinking session whereas there was a significant increase in blood flow change in the left (p = 0.03) and in right PFC (p < 0.001) after meditation session.In summary, as described in Table The primary goal of the present study was to ascertain whether meditation increases rCBF at bilateral PFC, measured with fNIRS, compared to random thinking. Our secondary goal was to observe the RT scores and relative changes in cerebral blood flow, and to determine if there are persistent effects following meditation session compared to random thinking session. Results as confirmed with recent studies on meditation with spectroscopy  in willful act and tasks that require intense focused and sustained attention  suggesting a contributing vascular mechanism (Jevning et al., A major strength of the present study was to examine the states of meditation and random thinking related hemodynamic responses in cerebral oxygenation during performance of the stroop color word task. It is a well established phenomenon that executive processes are facilitated by the frontal lobe and due to stroop interference brain activity may depend on increased ability to recruit frontal neural resources (Schroeter et al., There have been several neuroimaging studies evaluating the cerebral blood flow and performance of different meditation practices using behavioral, EEG and (Carter et al., In other imaging studies on meditation, there have been inconsistent results regarding the frontal cortex. A recent study showed decreased frontal activity during externally guided word generation compared to internal or volitional word generation (Cross et al., The present study reported increased oxy-hemoglobin concentration because of enhanced neural activity and cerebral blood flow in the prefrontal area during meditation compared to random thinking. In such studies, it is very important to understand the influences of systemic artifacts such as those from the heart, breathing, superficial perfusion, etc., which may be induced by the cognitive tasks related stress and autonomic responses. For example, a recent study performed on peripheral physiological measurements with temporal correlations of fNIRS and fMRI signals concluded that the physiological basis of the systemic artifact is a task-evoked sympathetic arterial vasoconstriction monitored by a decrease in venous volume and these artifacts are fairly common (Kirilina et al., In summary, the results of the present study provided first evidence that the oxygenation levels are increased in the PFC during meditation compared with random thinking in the same practitioners. Further event-related NIRS studies may apply well-tested fMRI paradigms in studies with children and patients, utilizing the advantages of the method.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


BMD showed a peak at 17 weeks . Lean mass showed an evident gain at 9  and 25 weeks , like fat mass from 13 to 17 weeks . BMI and lean mass index (LMI) reached the highest value at 21 weeks , like fat mass index (FMI) at 17 weeks (0.057 ± 0.009 g/cm2) (P < 0.01). BMI, weight, and BS showed a moderate positive correlation (0.45–0.85) with lean mass from 5 to 21 weeks. Mixed linear models provided a good prediction for lean mass, fat mass, and BMD. This study may represent a baseline reference for a future comparison of wild-type C57BL/6J mice with models of altered growth.The normal growth pattern of female C57BL/6J mice, from 5 to 30 weeks of age, has been investigated in a longitudinal study. Weight, body surface area (BS), and body mass index (BMI) were evaluated in forty mice. Lean mass and fat mass, bone mineral content (BMC), and bone mineral density (BMD) were monitored by dual energy X-ray absorptiometry (DEXA). Weight and BS increased linearly (16.15 ± 0.64–27.64 ± 1.42 g; 51.13 ± 0.74–79.57 ± 2.15 cm Growth curve models are routinely used in biomedical research to better understand the overall development of body components and for studying disorders of growth and mechanisms involved in metabolic regulation. The laboratory mouse (Mus musculus) is an excellent tool to define the physiological parameters related to growth processes and to study the effects of genetic and nongenetic factors on a variety of metabolic events. Wild type or genetically engineered C57BL/6J mice are the most widely used inbred strain in several research fields, including cardiovascular diseases and atherosclerosis, developmental and skeletal biology, or endocrine diseases like diabetes –5. In paWe performed a retrospective study involving females C57BL/6J examined by DEXA as control subjects. All experimental procedures have complied with the Italian D.L. n°116 of 1992 and associated guidelines in the European Communities Council Directive 2010/63/EU.2, each cage containing 5 animals, according to standard laboratory conditions with an ambient temperature of 24°C and 14 h of light per day. Mice had free access to water and standard chow . Chemical analysis of the diet was 20% protein and 9% fat. The general health and well-being of the mice were monitored by veterinary staff with careful observation of activity, nest building, and interaction with cage mates and by physical examination, providing an assessment of the animals' hydration, body condition, and observable abnormalities. The morphometric variables and body composition were recorded. The number of observations for each age-group is provided in Forty female C57BL/6J mice were purchased from Harlan or Charles River Laboratories and shipped to our institution 1 week before the start of experimental procedures. All mice were housed in plexiglas cages sized 365 × 207 × 140 mm, surface 530 cmIndividual weights were taken on all mice at 5, 9, 13, 17, 21, 25, and 30 weeks of age to the nearest 0.1 gram using an electronic balance. Body length was determined by measuring nasal-to-anal distance to the nearest 0.1 mm using a caliper when mice were anesthetized and immediately after DEXA scan, in order to avoid inaccuracy from movement and to confirm with X-ray images the precise positioning of mice.2), and bone mineral content  . This system employs a cone beam X-ray source generating energies of 35 and 80 keV and a flat 100 × 80 mm detector having individual pixel dimensions of 0.18 × 0.18 mm. The ratio of energy attenuation in the luminescent panel separates bone, lean tissue, and fat mass. A quality control procedure was routinely performed with a calibration phantom before imaging. Animal care and anesthesia were conducted according the guidelines that we have described elsewhere . Mice we .Body surface area was derived from the DuBois equation:2).BMI was calculated as the ratio between body weight and square surface area (g/mW2 − W1) is the weight increment in the time interval (t2 − t1).The growth rate,defined as the weight increment per unit of time, was derived from the formula:2): BMC (g)/BS;the correct projected areal bone mineral content : BMD (g/cm2)/the correct projected areal bone mineral density : Lean (g)/BS (cm2);lean mass index : Fat (g)/BS (cm2).fat mass index  and somatometric measurements, depending on the group size and in case of nonnormal distribution. A general linear mixed method, with 95% confidence intervals (CI) around the slopes and intercepts, was used to model the effects of predictor variables on changes in BMD, lean mass, and fat mass. These models incorporated a random intercept term to account for the correlation among repeated measures. The use of mixed models with in vivo studies is valid in improving the quality of the data analysis with small samples. In this way, mixed models also help to reduce the number of animals used in research , 20. Stahttp://www.jax.org/phenome). The absolute growth curve of weight against time appears U-shaped and is characterized by two phases of major increment: from 5 to 9 weeks of age (1 g/week) and from 21 to 25 weeks of age (0.69 g/week); from 9 weeks of age the gain of weight per unit of time decreases; it occurs at the age of puberty, but the mature weight, defined as the weight after which no further rise occurs, is not yet reached at 30 weeks of age. BMC described a sigmoid curve, with an initial phase of rapid increase from 0.285 ± 0.075 g (5 weeks) to 0.394 ± 0.025 g (9 weeks of age) (P < 0.001), an intermediate exponential phase from 9 to 21 weeks (P < 0.01), and a subsequent stationary phase. Correct projected areal bone mineral content  had a bell-shaped curve, with a peak and inflection point at 17 weeks of age . The peak BMD was reached at 17 weeks of age (0.0548 ± 0.0011 g/cm2∗ m), with an increase from 5 to 17 weeks of age, after which it showed a slow decline until 30 weeks of age. Correct projected areal bone mineral density  showed a peak at 17 weeks of age . Lean mass and fat mass increased progressively, with an evident gain in body protein at 9 weeks (15.8 ± 0.8 g/cm2) and 25 weeks (20.5 ± 0.3 g/cm2) of age, and a prevalence of fat mass increases from 13 (2.0 ± 0.4 g/cm2) to 17 (3.6 ± 0.7 g/cm2) weeks of age (16.92% of body weight). LMI described a flattened linear pattern that reached the maximum value at 21 weeks of age (0.284 ± 0.009 g/cm2) (2 (5 weeks) to 3.52 ± 0.11 g/cm2 (9 weeks) (P < 0.001), peaking at 21 weeks , followed by a plateau from 25 to 30 weeks (2)  . BMI inc30 weeks . FMI shoeeks (2) . Lean maeeks (2) . Since i ex vivo destructive methods. Similarly, changes in bone parameters can be evaluated in mice by invasive and/or time consuming methods including histomorphometry, biochemistry of bone tissue, and biochemical markers of skeletal turnover in blood and urine. The chemical carcass analysis is considered the “gold standard” for determining body composition [ versus relative value  or normalized value for body size . Therefore, absolute values of bone mineral content, lean and fat mass can be used to evaluate nutritional status by comparing individuals with themselves or with reference values, whereas the use of normalized indices has the advantage of compensating for interindividual differences in body size. From a methodological viewpoint, it is generally assumed in medicine that correction for interindividual body size differences is needed to avoid mistakes in the case of dimensional-dependent variables. It has been demonstrated that BMD in g/cm2 depends on bone size [2) and it has been described in rodent models of obesity using body weight and nose-to-anus length body (g/cm2) [The introduction of murine models in biomedical research has increased the need for noninvasive methods to study their phenotype. The evaluation of changes in body composition and weight with age of wild type mice gives a standard with which to compare the effects of genetic manipulation, pharmacological, and surgical treatments or nutrition . For exaposition , 29 and position , 25, 34.position . Dedicatposition . Mineralposition , 35–37. position . Like otone size  and in cone size . The forone size , 42. Nev (g/cm2) –46. To o


The crystal structure of hen egg-white lysozyme (HEWL) was analyzed under pressures of up to 950 MPa. The high pressure modified the conformation of the molecule and induced a novel phase transition in the tetragonal crystal of HEWL. P43212 to P43. Under high pressure, the crystal structure of the enzyme undergoes several local and global changes accompanied by changes in hydration structure. For example, water molecules penetrate into an internal cavity neighbouring the active site and induce an alternate conformation of one of the catalytic residues, Glu35. These phenomena have not been detected by conventional X-ray crystal structure analysis and might play an important role in the catalytic activity of HEWL.Crystal structures of hen egg-white lysozyme (HEWL) determined under pressures ranging from ambient pressure to 950 MPa are presented. From 0.1 to 710 MPa, the molecular and internal cavity volumes are monotonically compressed. However, from 710 to 890 MPa the internal cavity volume remains almost constant. Moreover, as the pressure increases to 950 MPa, the tetragonal crystal of HEWL undergoes a phase transition from  For this reason, high-pressure structural analysis has been widely used to study important characteristics of proteins such as their stability, folding and aggregation  because their higher symmetry accommodates the limitations imposed on the oscillation angle by the aperture of the DAC, which was approximately 70° for the entrance and exit apertures for the X-ray beams. Tetragonal crystals of HEWL  were obtained by the batch crystallization method from a solution consisting of 40 mg ml−1 lysozyme, 50 mM sodium acetate buffer pH 4.5, 0.8 M sodium chloride at 293 K. In order to discuss the effects of substrate binding on the behaviour of Glu35, a complex of HEWL with tetra-N-acetylchitotetraose  was also crystallized from 25 mg ml−1 lysozyme with a protein:substrate ratio of 1:1.2 and the same buffer conditions as the free enzyme. Because the solubility of tetragonal crystals of lysozyme increases with pressure , the space group changes and the crystals were merohedrally twinned. The structure solution and refinement were therefore performed on an untwinned data set using DETWIN in CCP4 (the twin fraction was 0.36). The four structures were also searched by MOLREP and refined with REFMAC5 and Coot. Water molecules were added using the solvent mode of ARP/wARP  levels less than 1.00 e Å−3 and closest contacts less than 2.30 Å or greater than 3.50 Å. The refinement statistics are compiled in Table 2The diffraction patterns were indexed, integrated and scaled using VOIDOO with a probe radius of 1.4 Å  with a 0.5 Å cutoff, and the difference-distance maps were calculated using CMView .The solvent-excluded volumes of HEWL were determined using 3.3.1.a) shows the relative variations in the unit-cell parameters and the unit-cell volume as a function of pressure. The unit-cell volume decreases from 2.38 × 106 Å3 at atmospheric pressure to 2.19 × 106 Å3 at 890 MPa. The compressibility of the unit cell is 9.4 × 10−2 GPa−1, which is almost identical to the values of 9.8 × 10−2 GPa−1 reported by Fourme et al. . Both the molecular and cavity volumes decrease approximately linearly with pressure up to 710 MPa. The compressibility of the molecular volume is 4.8 × 10−2 GPa−1, which is almost equal to the published value of 4.7 × 10−2 GPa−1 .Fig. 2P43212 to P43. The a axis of the new P43 crystal corresponds to the diagonal (a + b) of the original P43212 crystal lattice. Four molecules  are included in the asymmetric unit of the new P43 crystal, whereas these four molecules are symmetry mates in the original (low-pressure) P43212 crystal, which has one molecule in the asymmetric unit. Figs. 4b) and 4c) show the general displacement of molecules on going from 0.1 to 950 MPa. The results also indicate that when the unit-cell volume is calculated in terms of the original P43212 unit cell, its volume dramatically decreases after the phase transition . In particular, the c axis is significantly shortened. We estimate the average r.m.s.d. of the Cα-atom positions between 0.1 and 890 MPa to be 0.42 Å. However, the corresponding r.m.s.d.s for molecules A, B, C and D after the phase transition (at 950 MPa) are estimated to be 0.57, 0.70, 0.72 and 0.63 Å, respectively. One of the four molecules in the asymmetric unit, molecule C, is dramatically more distorted, and the active-site groove becomes significantly more closed . We analyzed the domain movement of molecule C between 0.1 and 950 MPa using DynDom . The former occurs between β1 and β2 and the latter occurs in the middle of α4. The degree of closure motion is 59.2%. The rotational angle and conformational translation between the α-domain and the β-domain of the high-pressure (950 MPa) molecule Cversus the ambient (0.1 MPa) structure are approximately 6.5° and 0.5 Å, respectively.Beyond this pressure range, a crystal-to-crystal phase transition occurs Fig. 4. At 950 on Fig. 1a. In pa3.3.B factors are reduced upon increasing the pressure from 0.1 to 890 MPa. In particular, the reduction between 0.1 to 190 MPa is significant. This initial decrease is also observed in the molecular and cavity volume reduction shown in Fig. 2B factor is uniform for the overall structure. At 950 MPa, despite the lower resolution than at 0.1–890 MPa, the average B factor also decreases across the molecules. However, the B factors around β2–β3 and β6 do not decrease with respect to their values at 0.1 MPa.As shown in Fig. 53.4.3.4.1.The number of water molecules observed gradually increases with pressure. For example, we assign 171 water molecules at 890 MPa compared with 100 at 0.1 MPa Fig. 7. Among t3.4.2.b and 103 at pressures of 0.1, 190, 380, 500 and 600 MPa, respectively). The cavity then swells to 44.6 Å3 at 710 MPa and is compressed again to 42.4 and 43.0 Å3 at 800 and 890 MPa, respectively. This increase in cavity volume comes from water penetrating into the cavity and from the movement of the surrounding residues. In fact, at pressures greater than 710 MPa a water molecule penetrates into the cavity . This water molecule appears to interact with Trp108 via a lone pair–π interaction . In molecule A Glu35 takes on dual conformations, as in the 890 MPa structure. In molecules B, C and D, however, the side chains have a single conformation and protrude into the cavity to hydrogen-bond to the newly present water molecules. In molecules C and D additional water molecules penetrate above the previously present water molecule that interact with Trp108 and make a hydrogen-bond network between Trp108 and the main-chain carbonyl O atom of Trp28.Above the phase-transition pressure, Glu35 of the four molecules adopts different conformations Fig. 11b. In mo4, the side chain of Glu35 is only in the outward conformation at 920 MPa and no water penetration into the cavity above Trp108 was observed, as shown in Fig. 11a). A phase transition did not take place even when the crystal was pressurized to 920 MPa.However, in the case of the complex of HEWL with (GlcNAc)4.4.1.et al., 2001A and C approach each other along the c axis. Consequently, the c axis may become shorter, as shown in Fig. 1a). After the phase transition, each structure in the asymmetric unit may embody slightly different high-energy conformations of HEWL, which are difficult to observe using the usual crystallographic methods because of their relatively low abundance at atmospheric pressure. As pointed out by Collins et al. , the unit-cell volume of tetragonal crystals of HEWL decreases monotonically upon increasing the pressure. Note, however, that the molecular volume and the internal-cavity volume are almost constant from 710 to 890 MPa . At 710 MPa, the unit-cell and molecular volumes are compressed to 93.4 and 96.4% with respect to the corresponding volumes at atmospheric pressure. This is consistent with previous reports of the unit cell exhibiting a compressibility larger than that of the molecules  theory of molecular solvation, Imai  al. 2007 reported al. 2007 subseque al. 2007 and 12 ▶a and 3a). However, a large deformation of the β-domain is detected only for molecule C at 950 MPa. In particular, molecule C undergoes a relatively large twist and closure , as detected by DynDom. This twist of the β-domain is consistent with the results of high-pressure NMR studies . The pKa of this glutamic acid is known to be 6.0–6.8, which is abnormally high . This high pKa of Glu35 is critical for it to serve as a general acid catalyst in the glycosidase activity of lysozyme under physiological conditions. The hydrophobicity of Trp108 is considered to contribute to the high pKa of Glu35. Single mutations of Trp108 to the less hydrophobic residues Tyr and Gln decrease the activity of HEWL, and the pKa of Glu35 is reduced by 0.2 and 0.6, respectively HEWL, 0.1 MPa, 4wldPDB reference: 190 MPa, 4wltPDB reference: 280 MPa, 4wlxPDB reference: 380 MPa, 4wlyPDB reference: 500 MPa, 4wm1PDB reference: 600 MPa, 4wm2PDB reference: 710 MPa, 4wm3PDB reference: 800 MPa, 4wm4PDB reference: 890 MPa, 4wm5PDB reference: 950 MPa, 4wm6PDB reference: 4, 920 MPa, 4xencomplex with (GlcNAc)PDB reference:


Childhood-to-adult persistent asthma is usually considered to be an atopic disease. However gastroesophageal reflux may also play an important role in this phenotype of asthma, especially when it is refractory to pulmonary medicine.Fifty-seven consecutive GERD patients who had decades of childhood-to-adult persistent asthmatic symptoms refractory to pulmonary medication were enrolled. GERD was assessed by a symptom questionnaire, endoscopy, reflux monitoring, and manometry, and treated by Stretta radiofrequency (SRF) or laparoscopic Nissen fundoplication (LNF). The outcomes were followed up with a questionnaire for an average of 3.3 ± 1.1 years.P < 0.001).Upper esophageal sphincter hypotonia, lower esophageal sphincter (LES) hypotonia, shortened LES, and esophageal body dyskinesia were demonstrated by esophagus manometry in 50.9%, 43.9%, 35.1%, and 45.6% of the patients, respectively. The symptom scores for heartburn, regurgitation, coughing, wheezing, and chest tightness significantly decreased from 5.8 ± 2.0, 5.6 ± 2.0, 7.3 ± 1.6, 8.4 ± 1.2, and 8.1 ± 1.5, to 1.2 ± 1.8, 1.1 ± 1.6, 2.8 ± 2.5, 3.8 ± 2.7, and 3.9 ± 2.7, respectively, after anti-reflux treatment (Esophagus dysfunction is high in childhood-to-adult persistent asthmatic patients with GERD. SRF and LNF are both effective for esophagus symptoms as well as persistent asthmatic symptoms for these patients. GER may relate with asthmatic symptoms in some patients. Evaluating asthmatic patients for possible treatment of the underlying cause, such as GERD, may improve symptoms and prevent disease persistence. Asthma is one of the most common chronic illnesses in children. In the USA, national estimates of current asthma prevalence among the children in selected minority subgroups range from 4.4% in Asian Indian children to 13.0% in American Indian/Alaska Native children . Sears eClinical data were gathered in a retrospective manner with the approval of the Ethics Committee of The Second Artillery General Hospital. Written informed consent for participation in the study was obtained from all patients.The patients enrolled in this study met the following criteria: (1) GERD evaluation treated by Stretta radiofrequency (SRF) or laparoscopic Nissen fundoplication (LNF) as described in our previous studies at Center for GERD, The Second Artillery General Hospital PLA, Beijing Normal University, People’s Republic of China;,12 (2) >Basal lung function tests were conducted on admission. The presence of acid GER was tested by ambulatory 24-hour dual pH monitoring, and a De Meester (DMS) score of >14.72 was considered to be positive for increased acid GERD ; endoscopQuestionnaires were completed before the SRF and LNF treatment and then for the follow-up. A 6-point scale ranging from 0 to 5 was applied to assess the severity and frequency of heartburn, regurgitation, coughing, wheezing, and chest tightness according to the Reflux Diagnostic Questionnaire as was applied in our previous studies -16. MediThe outcomes of anti-reflux treatment for asthmatic symptoms were as follows:(1) Cure: asymptomatic without medication;(2) Excellent: only occasionally mild, slight, or no asthmatic symptoms. Anti-asthma medication is completely ceased or reduced by more than half;(3) Good: less than weekly attacks of mild to moderate wheezing. Anti-asthma medication is still in use with various reductions;(4) Fair: the severity or frequency score is only decreased by one or two points. The patient still has weekly severe or moderate asthmatic symptoms. Drug consumption reduced by less than half or unchanged;(5) Poor: asthmatic symptoms and drug consumption is unchanged.t-test. Comparisons of the magnitude of change for the continuous variables between different groups were carried out using Mann–Whitney U-test. Correlations of non-normal variables were assessed using Spearman rank correlation coefficients. All P-values less than 0.05 were considered statistically significant.Data analysis was performed using SPSS version 13 software . Comparisons of mean values of the studied parameters before and after treatment were performed using the paired Student’s P < 0.001) and they are correlated . Patients with HH had higher heartburn score (P = 0.036) and weaker LES (P = 0.008).This study investigated consecutive asthmatic cases enrolled at our center for GERD from December 2007 to April 2011. In total, 57 cases fulfilled our inclusion criteria and were followed up in January 2013. Among these cases, SRF was carried out in 24 and LNF was performed in 33, with two of the latter having previously received SRF therapy. The mean follow-up duration was 3.3 ± 1.1 years (range 2–6 years). Patient demographics and baseline pulmonary and GER evaluation are summarized in Table P < 0.001; Table The length of stay after anti-reflux intervention ranged from 2 to 7 days for LNF with a median of 4.0 days, and from 2 to 6 days for SRF with a median of 3.2 days. By the end of an average of 3.3 years of follow-up, the symptom scores for heartburn, regurgitation, coughing, wheezing, and chest tightness significantly decreased from 5.8 ± 2.0, 5.6 ± 2.0, 7.3 ± 1.6, 8.4 ± 1.2, and 8.1 ± 1.5 to 1.2 ± 1.8, 1.1 ± 1.6, 2.8 ± 2.5, 3.8 ± 2.7, and 3.9 ± 2.7 respectively, with reduction rates of 75.1% ± 35.9%, 75.3% ± 35.8%, 58.4% ± 34.9%, 53.9% ± 32.4%, and 51.9% ± 32.7%, respectively , but not significant better for asthmatic symptoms .Esophagus symptom scores had significantly greater reductions than asthmatic symptoms (No major complications or deaths occurred during our study. Among patients receiving SRF treatment, some patients experienced several short term complications which disappeared within 1 week, such as throat discomfort in four cases, retrosternal discomfort in six cases, transient nausea/vomiting in three cases, and short-term dysphagia in three cases. As for patients receiving LNF, seven cases had mild dysphagia: three recovered within 1 month; four still had occasional symptoms when eating quickly or solid foods; three cases had prolonged bloating and two cases had increased passage of gas by anus; and three cases had reduced appetite.The association between asthma and GER has been debated for decades after Sir William Osler first observed the association between worsening asthma and distended stomachs in 1892 . The freOur study also found a high prevalence of disorders that may increase GER by endoscopy and HRM. For instance, HH was found in 35.1% of the patients by endoscopy. Furthermore, UES hypotonia, LES hypotonia, shortened LES, and esophageal body dyskinesia were demonstrated by esophagus manometry in 50.9%, 43.9%, 35.1%, and 45.6% of the patients, respectively (Table Nearly 50% of children have wheezing with respiratory illnesses in their first year of life, and 20% will have continued wheezing in later childhood, which predicts a probability of asthma . The natGER-related cough is defined as a cough that is improved or resolved by GER therapy, thus analogically GER-related asthmatic could also be defined by anti-reflux outcome. Our fundamental concern for GER-related asthmatic patients is that reflux is a risk factor for recurrent microaspiration and irritation; therefore, effective GER control is essential for the management of GER-related respiratory symptoms . Anti-acAs shown in the present study, 64.9% of the patients had good or better response to SRF or LNF therapy, while 35.1% of the patients still had less than good outcomes and 22.8% of the patients experienced different degrees of recurrence. This data suggests that the anti-reflux therapy at hand is not a panacea in these selected asthmatics as a whole. It is still difficult to define whether an a priori subset of asthmatics will improve with anti-reflux therapy. Complications, such as mild dysphagia and bloating, were evident in patients after receiving LNF; for instance, five of the seven dysphagia patents and two of the three bloating patients were found to have esophageal dyskinesia by esophagus manometry, which indicates that pre-LNF esophageal dyskinesia may represent a risk factor for complications after LNF. In this study, we showed that the outcome of asthmatic symptoms is highly related to the effectiveness of anti-reflux therapy and that their symptom scores are significantly correlated. The two patients who failed on SRF treatment in this study still had a second chance to attain a successful outcome when effective LNF is applied. Therefore, effective GER control is one of the key factors for successful GER-related asthmatic management. Although SRF treatment is less effective for esophagus symptoms, it is relatively less invasive with fewer complications. Furthermore, there has not been a perfect anti-reflux approach that can completely bring GER under control while avoiding complications and recurrence. Thus, it is still valuable to offer re-intervention for patients who failed on primary anti-reflux treatment.Another key element for GER-related asthma is persistent airway hyperactivity. In the present study, although remarkable outcomes were obtained after effective GFR control, the majority of patients still reported exacerbations of asthmatic symptoms, which could be triggered by catching a cold, exertion, and/or strong odors, such as cigarette smoke and petrol fumes. Therefore, systemic corticosteroids were discontinued after SRF or LNF, while other anti-asthma medications, such as inhaled corticosteroids, inhaled beta-agonists, and/or aminophylline with reduced dosage, were still maintained in most patients.Although the majority of asthma patients may obtain the targeted level of control with pulmonary medication, some patients will not achieve control even with the best therapy,  a group Esophagus related mortality is high in childhood-to-adult persistent asthmatic patients with GERD. SRF and LNF are both effective for treating esophagus symptoms as well as GERD-related persistent asthmatic symptoms. GER may also play an important role in this asthma phenotype. The evaluation of patients for possible treatment of the underlying causes of asthma, such as GER, can improve symptoms and prevent disease persistence. However, large-scale and controlled studies are further indicated.GER: Gastroesophageal reflux; SRF: Stretta frequency; LNF: Laparoscopic Nissen fundoplication; CT: Computed tomography; HRM: High-resolution manometry; DMS: DeMeester score; HH: Hiatal hernia; LES: Lower esophageal sphincter; PPI: Proton pump inhibitors; FVC: Forced vital capacity; FEV1: Forced expiratory volume in 1 second; FEF: Forced expiratory flow; LA: Los Angeles classification; MUESP: Mean upper esophageal sphincter pressure; MLESP: Mean lower esophageal sphincter pressure; LHPZ: Length of high pressure zone.The authors declare that they have no competing interests.ZWH studied and analyzed the data, conducted literature reviews, and drafted the manuscript. ZGW designed the study and helped draft the manuscript. ZWH, YZ, JMW, WTL, YY, SRT and AEW carried out the study, collected the data, and helped draft the manuscript. All authors read and approved the final manuscript.ZW Hu and SR Tian the attending doctor, Y Zhang, WT Liang and Y Yang the resident of Center for GERD, AE Wang the attending doctor in Department of Respiratory Medicine, The Second Artillery General Hospital.ZG Wang was a so called severe asthma patient with severe and intolerable respiratory symptoms requiring constant medication for years. After GER was confirmed and fundoplication performed, his asthma disappeared completely without taking any medication at present . He thenJM Wu is the director and chief physician of the Center for GERD of Second Artillery General Hospital.


Nutrient concentrations exhibited substantial seasonal and yearly variations. The annual fluxes of dissolved inorganic nitrogen, phosphate, and silicate in 2004 were 5.3, 2.5, and 4.2 times those in 2002, respectively, primarily due to the increase in river discharge. The relative contributions of nutrient inputs to nitrogen in the YR were: wastewater > fertilizer > atmospheric deposition > soil; while to phosphorus were: wastewater > fertilizer > soil > atmospheric deposition. The ratios of N, P and Si suggest that the YR at Lijin is strongly P-limited with respect to potential phytoplankton growth.The rapid growth of the economy in China has caused dramatic growth in the industrial and agricultural development in the Yellow River (YR) watershed. The hydrology of the YR has changed dramatically due to the climate changes and water management practices, which have resulted in a great variation in the fluxes of riverine nutrients carried by the YR. To study these changes dissolved nutrients in the YR were measured monthly at Lijin station in the downstream region of the YR from 2002 to 2004. This study provides detailed information on the nutrient status for the relevant studies in the lower YR and the Bohai Sea. The YR was enriched in nitrate (average 314 μmol·L Rivers carrying suspended and dissolved materials from the land to the ocean are the principal link in transferring nutrients between these systems ,2 and th9 mol/a in the 1980s to about 7 × 109 mol/a in 2002 [8 m3 and the minimum was 41.9 × 108 m3. The decrease of discharge was mainly due to the climate change and human activities, such as reservoir construction and water utilization [Previous studies have identified that the major sources of nitrogen and phosphate in the Yellow River (YR) were soil, fertilizer and wastewater inputs . Owing t in 2002 . Concent in 2002 ,16. Nutr in 2002 . During lization . The mailization . Since 2lization . Althouglization ,18,19,20lization .This paper reports the results of monthly monitoring at Lijin in the lower YR from the first year of water-sediment regulation in 2002 to 2004. The purposes of the investigation were to investigate the seasonal variations of the nutrients in YR, to identify and quantify the sources of nutrients to the YR, and to evaluate potential nutrient limitations in the YR.5 km2, of which 1.19 × 105 km2 or approximately 15% of total land area is farmland [11 m3) in 2002, 556 mm (4.4 × 1011 m3 ) in 2003, and 422 mm (3.4 × 1011 m3) in 2004, respectively [The YR is, after the Yangtze River, the second largest river in China in terms of both length and basin area . The YR farmland . The farfarmland . The clifarmland . The aveectively .9 tonne/a [5 km2, or ~40% of the total YR drainage basin [The YR is known for its high sediment load, with an average value of 1.6 × 10 tonne/a , approxi tonne/a . The upp tonne/a . The loege basin . The loege basin . These fge basin  with a pge basin . The lowge basin .Water samples were collected monthly at Lijin in Shandong Province from 2002 to 2004  bottles, which were thoroughly rinsed with the sample prior to collection. The samples were filtered immediately through a 0.45-μm pore-size, pre-cleaned, cellulose acetate filter. Filtrates were stored in two 100-mL acid-cleaned low density polyethylene (LDPE) bottles and preserved with CHCl−1 level. The detection limits for phosphate (PO43−-P), silicate (SiO32−-Si), nitrite (NO2−-N), nitrate (NO3−-N), and ammonia (NH4+-N) were 0.024 μmol·L−1, 0.030 μmol·L−1, 0.003 μmol·L−1, 0.015 μmol·L−1, and 0.04 μmol·L−1, respectively. The daily discharge and sediment data were monitored by the YR Conservancy Commission [Nutrient species in the filtrate were determined using an AA3 Continuous-Flow Analyzer . The quality of data was monitored by calibration with the national standards of China , and duplicate samples were determined for nutrients at μmol·Lmmission .Major sources of nitrogen and phosphate in the YR include atmospheric deposition, soil loss from land, fertilizer loss and waste-water inputs . IndividAD (g/a) is the atmospheric deposition of nutrients; r is the runoff coefficient, average 15%; W (m3) is the average basin-wide wet deposition with the values of (basin-wide precipitation volume in parentheses) 404 mm (3.21 × 1011 m3) in 2002, 556 mm (4.4 × 1011 m3 ) in 2003, and 422 mm (3.4 × 1011 m3) in 2004, respectively [A (g/mol) is the atomic mass and C (g/m3) is the nutrient concentration in the wet deposition. The respective concentrations of nitrogen and phosphate in the wet deposition varied from 0.50 to 6.80 mg/L and from 3.41 to 14.9 μg/L, respectively [Atmospheric sources include both wet and dry deposition. There is little data about dry deposition, so we did not include it. Dissolved nitrogen and phosphorus from wet deposition were estimated using the equation:ectively .4 t, while it reached 789.70 × 104 t in 1999. The fertilizer lost into the YR from farmland is the main form of non-point source pollution in the YR basin [Fertilizer loss from farmland is widely recognized as a major pathway for the increased flux of nitrogen and phosphorus into the YR ,36. SincYR basin .LF (t) is the nutrient input to the YR from the fertilizer loss; l is the percentage loss of fertilizer within the YR basin, which were 15% for nitrogen and 2.0% for phosphate [p is the fraction of the nutrients in the fertilizer, which is 0.352 for nitrogen fertilizer, 0.105 for phosphorus fertilizer [M (t) is the amount of the fertilizer used in the nine provinces  irovinces  [30,31,3rovinces .SL (t) is nutrient input to the YR from soil leaching, and S (t) is the sediment dischargedto the YR calculated from the annual suspended sediment load at Lijin. Using the suspended sediment load data from 1960 to 1985 of the middle reach of the YR (Luokou), which accounts for 90% of the basin, the relationship of suspended sediment load at Lijin with the sediment transport in the YR basin was S = 2.262x + 1.551, where x is the annual suspended sediment load (108 t) at Lijin. The annual suspended sediment load measured at Lijin was 0.5 × 108, 3.8 × 108, and 2.7 × 108 t in 2002, 2003, and 2004, respectively [NSC) was estimated to be 0.8–1.5 g/kg for N, and 1.1–1.5 g/kg for P [Pn), was 0.05 for nitrogen and 0.002 for phosphorus [As outlined previously, the Loess Plateau exhibits substantial annual soil and water loss, accounting for approximately 90% of the total sediment in the YR . This hiectively . The bacosphorus ,43.WW (g) is the DIN or DIP load of wastewater; W (m3) is the wastewater transported to the YR, which were ×108 m3 in 2002, 41.46 × 108 m3 in 2003 and 42.65 × 108 m3 in 2004, respectively [N (g/m3) is the concentration of DIN (8.0–60 mg/L) or DIP (0.76–9.0 mg/L) in the wastewater [Wastewater includes both domestic sewage and industrial wastewater. The wastewater load is described in ectively ; and N (stewater .iF (g) is the annual flux of the species i in the river water; ijC (g/m3) is the average concentration of the species i in the river water during month j; and jQ is the cumulative discharge during month j.Nutrient fluxes in the YR at Lijin were estimated using the equation:−3 to 34.2 kg·m−3. Discharge and suspended sediment load are strongly correlated , especially in summer , dissolved inorganic phosphorus (DIP—PO43−-P) and dissolved silicate (DSi—SiO32−-Si) concentrations were significant in the YR at Lijin in the period of 2002–2004. Nitrate concentration varied from 201 to 491 μmol·L−1, with an average concentration of 311 μmol·L−1 in 2002, 313 μmol·L−1 in 2003, and 317 μmol·L−1 in 2004. Nitrite concentrations varied from 0.07 to 15.1 μmol·L−1, with an average concentration of 4.0 μmol·L−1 in 2002, 1.7 μmol·L−1 in 2003, and 3.8 μmol·L−1 in 2004. Ammonia concentrations varied from below the detection limit of 0.04 μmol·L−1 to 158 μmol·L−1 from 2002 to 2004, with average concentrations of 17.5 μmol·L−1 in 2002, 41.3 μmol·L−1 in 2003, and 5.9 μmol·L−1 in 2004.Seasonal and discharge-related variations of dissolved inorganic nitrogen (DIN) species , accounting for 73%–99%, 55%–99% and 93%–99% in 2002, 2003 and 2004, respectively.Concentrations of both NOsonality  and the ischarge . NH4+-N,−1, with a mean value of 0.49 μmol·L−1 in 2002, 0.31 μmol·L−1 in 2003 and 0.23 μmol·L−1 in 2004, reflecting a substantial decrease during the study period. In most cases, DIP was within the range of 0.10–0.40 μmol·L−1 (−1), and DIP was relatively low during high discharge period (Dissolved inorganic phosphorus (DIP) concentration varied from 0.10 to 0.75 μmol·Lμmol·L−1 . The hige period .−1, with an average value of 130 μmol·L−1 in both 2002 and 2003 and 133 μmol·L−1 in 2004. Maximum concentration of DSi occurred in July 2002, September 2003 and August 2004, while the minimum concentration occurred in June 2002, April 2003 and November 2004, respectively (Dissolved silicate (DSi) concentration varied from 99 to 173 μmol·Lectively . In geneectively .As reflected by the significant, often flow-related variations of the nutrient concentrations, the molar DIN to DIP ratio in the YR water varied from 503 to 2804, with discharge-weighted averages (range in parentheses) of 576 (503–1861), 1132 (787–1848), and 1334 (769–2804) in 2002, 2003, and 2004, respectively. The increase in average molar DIN to DIP ratio from 2002 to 2004 reflects the substantial decrease of the DIP concentration during 2002 to 2004. The molar ratio of DSi to DIN ranged from 0.24 to 0.85, and, in contrast to average molar DIN to DIP ratios, similar averages of 0.67, 0.46, and 0.48 in 2002, 2003, and 2004, respectively due to the small relative changes in the concentrations of DSi and DIN.Major sources of nitrogen and phosphate in the YR include atmospheric deposition, soil loss from land, fertilizer loss and waste-water inputs . Individ5 km2, in which the area of farmland is 1.19 × 105 km2, approximately 15% of total land area [6 ton in 1981 to 8.40 × 106 ton in 2012. A recent report [The environmental changes in the YR basin are heavily impacted by the population of over 100 million. From the 1980 to the present, the population in the YR basin has continuously increased . Many stand area . The uset report  showed tThe absorption of DIP onto the suspended sediments in the YR may be the major factor resulting in the relatively low concentration compared to other world rivers . The con2 into drainage water with its abundance depending on both the lithological nature of the watershed and on the temperature [et al. [2 concentration in headwaters could be in equilibrium with quartz/chalcedony levels. One of the unique geological features of the YR basin is the wide loess, which covers about 44% of the basin. The loess in the vast YR basin has a similar grain-size distribution, being dominated by 50%–60% silt (0.01–0.05 mm) and 20%–30% clay (<0.005 mm), with very few grains greater than 0.1 mm. Mineralogically, the loess is dominated by quartz, alkali feldspar, micas, and carbonate [2.Silica is delivered to surface waters mainly by rock weathering, which releases dissolved SiOperature ,55. Neal [et al.  have poiarbonate . Waters 3−-N constituting the majority (~95%) of DIN. Increases in the fluxes of NO3−-N and SiO32−-Si paralleled discharge, which in 2004 was 4.7 times that of 2002. Fluxes of DSi, DIP and nitrate were strongly correlated with discharge, in particular for DSi, DIP and NO3−-N and to a lesser extent NH4+-N, generally increased with flow, while the flux of NO2−-N, albeit highly variable at low flow, generally decreased with increasing flow .Estimated nutrient fluxes for 2002, 2003, and 2004 are shown in Nutrient limitation diagrams using molar nutrient ratios derived from nutrient measurements from 2002 to 2004 in the YR are shown Temporal plots in molar nutrient ratios reveal features not readily observed in plots of dissolved nutrient concentrations alone . Both DIIn addition to the marked periodicity observed for both DIN/DIP and DSi/DIN, there is also an increasing underlying baseline trend for all of the nutrient ratios that is most readily observable for DSi/DIP . ExcludiIncreases in DSi concentration closely correspond to increased sediment discharge, which occurred during 2003 and 2004 and would reflect this increasing predominance of soil-derived silica. DSi mainly comes from diffuse sources. Decreasing DIP reflected a decrease in the supply or increased retention upstream of Lijin. Low flow velocities, high transparency and high nutrient levels stimulate planktonic growth within reservoirs. Increased phytoplankton production and subsequent algal sedimentation are the key processes involved in the transfer of dissolved reactive phosphorus to particulate phosphorus in several dammed rivers . Thus, p−1 was 40 times the world average for unpolluted rivers [et al., Average dissolved nutrient concentrations in the YR differ substantially from other major world rivers . The aved rivers , substan et al., ,52.In contrast to nitrate, the major constituent of DIN within the YR, the concentration of DIP in the YR was close to the world average for unpolluted rivers  and lessAverage DSi concentration of 140 μmol/L in the YR was similar to the Loire, Seine, and Po Rivers, among other world rivers ,52,65, bThe N:P molar ratio in the YR of DIN and DIP was much higher than in other world rivers, being approximately one hundred times that of the world river average and more than ten times that of polluted rivers in Europe and America. This higher N:P molar ratio is principally due to the substantially higher dissolved nitrate concentration given the similar average dissolved phosphate concentrations in the YR and world rivers. Molar N:P ratios fertilizer used in China may typically range from 22–44 or even higher , while t3−-N but relatively poor in DIP. Concentrations of DSi were similar to major world rivers. In summary, the fact that nitrogen and phosphorus is mainly influenced by fertilizer loss and wastewater, provides important evidence on control options for pollution control both for the lower YR and for nutrient input to the YR estuary and to the Bohai Sea. We should transform the agriculture into an agriculture using less fertilizer and build more powerful wastewater treatment plants. The YR is enriched with DIN and very poor in phosphate. The molar N:P ratios of riverine nutrient has very high DIN:DIP. Nutrient transport from the YR can result in phosphorus limitation for phytoplankton growth in the YR estuary and the adjacent Bohai Sea.From 2002 to 2004, the concentration of DIN  in the YR showed a strong seasonal and flow-related variation. In contrast, concentrations of DIP and DSi were less sensitive to discharge. Notably, a strong decline in DIP concentration from 2002 to 2004 is apparent. Compared to other major world rivers, the YR was relatively enriched in NO


The effects of aging on eye movements are well studied in the laboratory. Increased saccade latencies or decreased smooth-pursuit gain are well established findings. The question remains whether these findings are influenced by the rather untypical environment of a laboratory; that is, whether or not they transfer to the real world. We measured 34 healthy participants between the age of 25 and 85 during two everyday tasks in the real world: (I) walking down a hallway with free gaze, (II) visual tracking of an earth-fixed object while walking straight-ahead. Eye movements were recorded with a mobile light-weight eye tracker, the EyeSeeCam (ESC). We find that age significantly influences saccade parameters. With increasing age, saccade frequency, amplitude, peak velocity, and mean velocity are reduced and the velocity/amplitude distribution as well as the velocity profile become less skewed. In contrast to laboratory results on smooth pursuit, we did not find a significant effect of age on tracking eye-movements in the real world. Taken together, age-related eye-movement changes as measured in the laboratory only partly resemble those in the real world. It is well-conceivable that in the real world additional sensory cues, such as head-movement or vestibular signals, may partially compensate for age-related effects, which, according to this view, would be specific to early motion processing. In any case, our results highlight the importance of validity for natural situations when studying the impact of aging on real-life performance. As we are getting older, the function of the visual system appears to deteriorate. Not only does visual acuity decline in the elderly, but perception  between the age of 25 and 85 (mean = 46y ± 18.5y) were analyzed during two everyday tasks in the real world. All participants were originally recruited as healthy controls for patient studies on eye movements in natural environments , at a sampling rate of 280 Hz, a spatial resolution of 0.02° and a precision of about 0.1°  and its corresponding 95% confidence interval for each subject . In a first step, raw eye-position data was inspected for blinks or other recording artifacts due e.g., to reflections by external light sources. Blinks were classified by the absence of more than 5 samples (18 ms) and eye traces were cleaned for blink artifacts by deleting 8 samples (29 ms) before the start of a blink and 12 samples (43 ms) after a blink. Saccades were detected if eye velocity was higher than 100°/s for at least 3 consecutive samples and if the eyes moved more than 0.5° in this time period. This conservative threshold guaranteed a low false-positive rate for saccade detection, since eye movements during real-life measurements contain extensive dynamics  and are generally noisier than under controlled laboratory settings. Furthermore, a main-sequence analysis (peak velocity/amplitude) of thus defined saccades was performed by computing the power function fit  and the RMSE (root mean square error) of the retinal target velocity. The rationale for choosing the RMSE, just as for the gain, was its wide use as a global measure of pursuit performance Smyrnis,  and its In Task II the presence of specific tracking targets allowed us to determine target velocity as the temporal derivative of the target position in the head-centered scene. In addition, the GazeCam videos of the ESC could be used to calculate retinal target velocity as the temporal derivative of the target position within this retinocentric framework. The sum of all deviations from the optimal retinal target velocity (0°/s) corresponds to the RMSE. In this task, six participants  did not show a sufficient tracking of the specified target  and their data were therefore excluded from the evaluation of tracking performance . In addition the RMSE could not be evaluated precisely due to considerable frame drops in the GazeCam-videos of three other participants .n = 17) with a mean age of 30.1 ± 3.0y and an older group (n = 17) with a mean age of 61.8 ± 12.8y. There was no statistical difference in mean age of the younger or older group when comparing the tasks in which participants were excluded and the full group of participants (freeviewing-gain: younger group (n = 15): mean age 29.5 ± 2.6y; older group (n = 15): mean age 60.2 ± 14.7y; tracking-gain: younger group (n = 14): mean age 29.7 ± 3.0y; older group (n = 14): mean age 61.6 ± 13.3y; RMSE: younger group (n = 12): mean age 29.5 ± 3.2y; older group (n = 13): mean age 62.2 ± 13.6y; all p > 0.8; U-Test). Additionally the effect size of each result was computed using the “Area under the receiver operating characteristic curve” (AUC or A’)  cannot be expected to follow a normal distribution  walking through a hallway with free gaze and (II) visually tracking a stationary object on the ground while walking straight ahead.Z = 1.54; p = 0.124; U-test), nor a correlation of walking time and age (r(32) = −0.260; p = 0.138). Yet, several eye-movement parameters depended on age. The frequency of saccades showed a significantly decrease in the older participants as compared to the younger (Table r(32) = −0.484; p = 0.004; Figure r(32) = 0.313; p = 0.07; Figure When walking along a hallway with no specific instructions we neither observed a significant difference in walking time between the younger (mean: 26.5 ± 2.7 s) and the older participants  = −0.396; p = 0.02; Figure r(32) = −0.626; p < 0.001; Figure r(32) = −0.567; p < 0.001; Figure r(32) = −0.583; p < 0.001; Figure r(32) = −0.759; p < 0.001; Figure r(32) = −0.752; p < 0.001; Figure r(32) = −0.731; p < 0.001; Figure r(32) = −0.477; p = 0.004; Figure r(32) = −0.349; p = 0.043; Figure r(32) = −0.460; p = 0.006; Figure r(32) = −0.556; p < 0.001; Figure r(32) = −0.404; p = 0.018; Figure With respect to the parameters of individual saccades (amplitude and velocity measures), there was a trend towards smaller saccade amplitudes in the older participants, which however, did not reach significance Table . Yet, wer3 = −0.396r3 = −0.396r3 = −0.396r(32) = 0.04; p = 0.821; Figure r(32) = −0.476; p = 0.004; Figure Saccade amplitudes and velocities are not independent from each other, but coupled through the so-called main sequence. When fitting a power function to the main sequence (see Section Methods) for these amplitude ranges Figure , the expr(28) = 0.282; p = 0.13; Figure During the free exploration of task I, there were periods in which participants spontaneously tracked a target during walking. These tracking movements had an average gain above 1 for nearly all (29/30) participants. There was no significant linear dependency on age (r(26) = −0.169; p = 0.39; Figure r(23) = 0.064; p = 0.76; Figure For the tracking task, we did not find any significant dependence of tracking gain or tracking performance (as quantified by the RMSE) on age  as compared to instructed tracking movements (task II). Active tracking of optic flow elements in the laboratory has been reported to have a gain close to perfect, i.e., 1.0 (Niemann et al., Unlike smooth pursuit in the laboratory, which has been shown to get worse in the elderly as compared to younger adults (Moschner and Baloh, The suggested relevance of self-motion processing for oculomotor performance in the real world as compared to laboratory settings is supported by studies in schizophrenia patients. These patients show an impaired smooth pursuit in the laboratory (Holzman et al., Being aware of the numerous differences between our real-world tasks and typical laboratory measurements, our results provide a first step towards analyzing real-world oculomotor behavior in healthy aging. Furthermore, our correlation analysis together with the effect sizes allowed us to examine to what extent age influences different eye-movement parameters in real-world situations. Together with two recently published studies (Marx et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Here we show that silane, serving as a gaseous catalyst, is able to boost the graphene growth rate to ~1 μm min−1, thereby promoting graphene domains up to 20 μm in size to be synthesized via chemical vapour deposition (CVD) on hexagonal boron nitride (h-BN). Hall measurements show that the mobility of the sample reaches 20,000 cm2 V−1 s−1 at room temperature, which is among the best for CVD-grown graphene. Combining the advantages of both catalytic CVD and the ultra-flat dielectric substrate, gaseous catalyst-assisted CVD paves the way for synthesizing high-quality graphene for device applications while avoiding the transfer process.The direct growth of high-quality, large single-crystalline domains of graphene on a dielectric substrate is of vital importance for applications in electronics and optoelectronics. Traditionally, graphene domains grown on dielectrics are typically only ~1 μm with a growth rate of ~1 nm min The growth of high-quality graphene directly on to dielectric substrates is of key importance for future electronic and optoelectronic applications. Here, the authors use silane-catalysed chemical vapour deposition to fabricate large graphene sheets, up to 20 μm in size, on hexagonal boron nitride. As the first isolated atomically thin crystal34567891011121314151617(h-BN) are found to be good candidates for the substrate of graphene devicesh-BN is obviously the best one because of its insulation properties, chemical inertness and small lattice misfit. Growing graphene directly on ultra-flat h-BN can greatly preserve the pristine properties of graphene, and the mobility of the aligned graphene grown on h-BN via the CVD method reaches 20,000–30,000 cm2 V−1 s−1 at room temperature−1) and the generation of domain sizes that are mostly smaller than 1 μm. Although the fabrication of a graphene domain 11 μm in size has been achieved, it took 72 h to complete the fabricationRecently, molybdenum disulfide, tungsten disulfide and hexagonal boron nitride h-BN by almost two-order of magnitude higher than that in the absence of gaseous catalyst. The introduction of the gaseous catalyst also effectively improves the percentage of precisely aligned domains on h-BN. These results present a promising route towards very high-quality, transfer-free graphene on dielectric substrates for electronic applications.In this report, we demonstrate that silane and germane as gaseous catalysts can boost the growth rate of graphene on −1, which increases by an order of magnitude to 50 nm min−1 when germane is introduced. If silane is introduced, the growth rate further increases to 400 nm min−1 and, if the substrate is further heated to 1,350 °C, the growth rate reaches ~1,000 nm min−1, which is very close to that of graphene grown on a metal surface by CVD  calculations are performed on armchair graphene, with the results shown in catalyst , when a h-BN latticeet al. also did systematic investigations of the graphene/h-BN super-lattice with different angular rotationh-BNh-BN lattice. The ‘C’ domains exhibit the typical polycrystalline structure, with a detectable moiré pattern only on some sub-domains. h-BN shown in h-BN is very sensitive to the angular separation between the graphene and h-BN when the angular separation is less than 1° , where the integrity of the pattern gives information of graphene crystallinity and the alignment can be judged by the periodicity and the rotation of the moiré pattern with respect to the  1° ref. . Although-BN by the GCA-CVD method are very similar to those for aligned or misaligned graphene flakes on h-BN made by mechanical exfoliation−1, which is broader than that of graphene domains with a large misalignment angle. Moreover, a shoulder peak located at 1,565 cm−1 that is non-dispersive =±2,±6,±10…, where n=0, 1, 2… is the Landau level index. A further investigation to demonstrate the effects of the secondary Dirac point upon the magnetic field is still underway.In the plots of s in Rxx  and platRxx  mixture flow of 10 cm3 per min (s.c.c.m.), corresponding to 15 Pa, and annealed for 5 min, after which the Ar/H2 flow was turned off. The C2H2 flow and a mixture of silane/argon or germane/argon (5% mole ratio of silane or germane to argon) were introduced into the system for the graphene growth. The pressure was kept at 5 Pa during the growth, and the growth time was in the range of 5–40 min. After growth, both the C2H2 and gaseous catalyst flow were turned off and the system was cooled down to room temperature with the Ar/H2 mixture flowing. The samples of graphene on h-BN grown on a quartz surface were first transferred to a highly doped p-type silicon wafer with a 300-nm-thick SiO2 capping layer for electrical transport studies.Before graphene growth, k=0.05–0.5 N m−1. To obtain a high accuracy, scanners with a travel range less than 10 μm along the X and Y directions were used. Calibration for the atomic resolution was performed with newly cleaved highly ordered pyrolytic graphite (HOPG) before the measurements where, after calibration, the mean distance between the vicinal carbon atoms was measured to be 0.142 nm. The integral gain and set-point were adjusted to be as low as possible to obtain optimal images, and the scan rate was set to a value in the range of 10–60 Hz to reduce the noise from thermal drift. Several hours of pre-scanning were carried out to warm up the scanner and ensure high imaging stability. Error in this orientation measurement varies by data points and was typically ±2°, although it sometimes reached ±3°.As-grown samples were characterized by an AFM  in contact mode, and the atomic-resolution images were obtained by the AFM  under ambient conditions. The AFM images on different surfaces were recorded in contact mode using SNL-10 AFM tips from Bruker that possess a nominal tip radius of less than 10 nm, and whose cantilevers possess a force constant −1. The energy barrier of every advance step was explored by climbing nudged elastic band method. The vacuum layer inside the super-cell was kept as large as 14 Å to avoid interaction with the adjacent unit cell. The Brillion zone was sampled as 1 × 2 × 1 grid meshes for the 7 × 5 slab and 1 × 1 × 1 grid meshes for the larger 8 × 6 and 7 × 8 slabs using the Monkhorst-Pack scheme during the calculation.All of the calculations were performed within the framework of the DFT as implemented in the Vienna Ab-initio Simulation Package. The exchange-correlation potentials were treated by the gradient density approximation, and the interaction between valence electrons and ion cores was described by the projected augmented wave method. The energy cutoff for the plane wave functions was 400 eV and the force acting on each atom was less than 0.02 eV ÅRaman spectra were obtained with a WITec micro-Raman instrument possessing excitation laser lines of 488/532/633 nm. An objective lens of × 100 magnification and a 0.95 numerical aperture was used, producing a laser spot that was ~0.5 μm in diameter. The laser power was kept less than 1 mW on the sample surface to avoid laser-induced heating. The Raman images were acquired using a WITec Raman system with a 600 lines/mm grating and a piezo crystal-controlled scanning stage under a 488-nm laser excitation. The scanning step was about 200 nm.h-BN flake on the 300-nm-thick SiO2/Si substrates is about 20 nm, the effective capacitance, Cg, can be estimated as 10.5 nF cm−2. Both the electrical transport and magneto-transport measurements were carried out in a physical property measurement system  via the standard lock-in technique.The Hall bar structure of the graphene devices was defined by a standard electron beam lithographic technique. The metal contacts (60 nm Au/10 nm Ti) were deposited through electron beam evaporation, whereupon the devices were annealed in a hydrogen atmosphere at 250 °C for 3 h to remove resist residues and to reduce the contact resistance between the graphene and electrodes before the electrical measurements. Because the thickness of the M.J. and X.X. directed the research work. H.W., X.X. and S.T. conceived and designed the experiments. S.T. fabricated the graphene samples. S.T. and H.W. performed the AFM experiments. H.W., H.X. and X.L. fabricated the electronic devices. H.W., H.S.W. and Q.S. performed the transport measurements. F.D., X.Y.Z., X.C. and X.H.Z. performed the DFT calculations. C.C. and T.Y. performed the Raman measurements. H.W., X.X., S.T., F.D., C.C. and T.Y. analysed the experimental data and designed the figures. H.W., S.T., C.C., T.Y., F.D., F.H., X.X. and M.J. co-wrote the manuscript and all authors contributed to critical discussions of the manuscript.How to cite this article: Tang, S. et al. Silane-catalysed fast growth of large single-crystalline graphene on hexagonal boron nitride. Nat. Commun. 6:6499 doi: 10.1038/ncomms7499 (2015).Supplementary Figures 1-11, Supplementary Tables 1-3, Supplementary Notes 1-3, Supplementary Discussion and Supplementary References