Gamma-Ray Observation of the Cygnus Region in the 100-TeV Energy Region.

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

First Detection of sub-PeV Diffuse Gamma Rays from the Galactic Disk: Evidence for Ubiquitous Galactic Cosmic Rays beyond PeV Energies.

We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.

Prognosis and clinicopathologic features in patients with gastric stump cancer after curative surgery.

Background: Gastric stump ("remnant") cancer is the development of a malignancy related to previous gastric surgery. Prognosis in gastric stump cancer, compared with that in primary gastric cancer, is still controversial. Methods: From January 1988 to December 2012 at a single medical centre in Taiwan, 105 patients with gastric stump cancer, including 85 with previous peptic ulcer disease and 20 with previous gastric cancer, were analyzed for clinicopathologic characteristics and overall survival (os). Results: The 5-year os rates for patients with gastric stump cancer and with primary gastric cancer were 51.2% and 54.5% respectively (p = 0.035). Analysis of clinicopathologic characteristics indicated that, compared with patients having primary gastric cancer, those with gastric stump cancer had more lymph node metastasis (p < 0.001) and had been diagnosed at a more advanced stage (p = 0.047). Multivariate analysis with os as an endpoint showed that age [p = 0.015; hazard ratio (hr): 2.300; 95% confidence interval (ci): 1.173 to 4.509], tumour size (p = 0.037; hr: 1.700; 95% ci: 1.031 to 2.801), stromal reaction (p = 0.021; hr: 1.802; 95% ci: 1.094 to 2.969), and pathologic N category (p = 0.001; hr: 1.449; 95% ci: 1.161 to 1.807) were independent predictors in gastric stump cancer. The os rates for patients with gastric stump cancer who previously had gastric cancer or peptic ulcer disease were 72.9% and 50.0% respectively (p = 0.019). The Borrmann classification was more superficial (p = 0.005), lymph node metastases were fewer (p = 0.004), and staging was less advanced (p = 0.025) in patients with gastric stump cancer who previously had gastric cancer than in their counterparts who previously had peptic ulcer disease. Conclusions: Survival is poorer in patients with gastric stump cancer who previously had peptic ulcer disease than in those who previously had primary gastric cancer. Patients with gastric stump cancer who previously had gastric cancer and could receive curative gastrectomy tended to have a better prognosis because of a more superficial Borrmann classification. Regular follow-up in patients who have undergone gastric surgery is recommended for the early detection of gastric stump cancer.

First Detection of Photons with Energy beyond 100 TeV from an Astrophysical Source.

We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.

[Clinical observation of the relationship between the newborn hearing screening and ABO blood groups].

Objective:To analyze the relationship between ABO blood groups and otoacoustic emissions in full-term newborns, including the occurrence of SOAE and the amplitudes of DPOAE. Method:A total of eighty normal hearing female neonates were included in the study, with equal number of participants in each of the ABO blood group. Measurements of SOAE and DPOAE were collected from both ears of all participants. Result:The blood group O subjects showed significantly fewer SOAE occurrences and lower DPOAE amplitudes at 793 Hz, 1 257 Hz and 1 587 Hz than subjects with other three blood groups both in the left and right ears. Conclusion:The full-term neonates with blood group O have lower SOAE occurrence than other three blood group individual. The blood group O individuals have the lowest amplitude at 793 Hz, 1 257 Hz and 1 587 Hz of both ears.

Evaluation of the Interplanetary Magnetic Field Strength Using the Cosmic-Ray Shadow of the Sun.

We analyze the Sun's shadow observed with the Tibet-III air shower array and find that the shadow's center deviates northward (southward) from the optical solar disk center in the "away" ("toward") interplanetary magnetic field (IMF) sector. By comparing with numerical simulations based on the solar magnetic field model, we find that the average IMF strength in the away (toward) sector is 1.54±0.21_{stat}±0.20_{syst} (1.62±0.15_{stat}±0.22_{syst}) times larger than the model prediction. These demonstrate that the observed Sun's shadow is a useful tool for the quantitative evaluation of the average solar magnetic field.

Conscious sedation with midazolam and dezocine for diagnostic flexible bronchoscopy.

OBJECTIVE: This study aimed to assess the benefits and risks of conscious sedation with midazolam and dezocine in diagnostic flexible bronchoscopy (FB). PATIENTS AND METHODS: This prospective case control study enrolled 40 non-sedated and 40 sedated subjects who underwent diagnostic FB. All received the standard upper airway preparation, while sedated subjects received midazolam and dezocine for conscious sedation. Subject discomforts during FB were assessed using the verbal analogue score (VAS, 0-10 scale). Willingness to return was assessed as five scales to monitor subject's satisfaction level. Safety profiles throughout the procedures were also assessed. RESULTS: Anterograde amnesia existed in 75.0% sedated subjects. Compared to non-sedated subjects, sedated ones expressed less discomfort, with lower VAS scores regarding scope insertion (4 [0-10] vs. 0 [0-4], p < 0.001), cough (5.5 [0-10] vs. 0 [0-4], p < 0.001), dyspnea (3.5 [0-10] vs. 0 [0-4], p<0.001), pain (3 [0-10] vs. 0 [0-5], p < 0.001), and global tolerance of the procedures (5.5 [1-10] vs. 0 [0-5], p < 0.001). More sedated subjects expressed willingness to return (90.0% vs. 30.0%, p < 0.001). Sedated subjects had no more hypoxemic episodes during the procedure (7.5% vs. 5.0%, p > 0.99), which were all transient and not life-threatening. CONCLUSIONS: Conscious sedation with midazolam and dezocine reduces discomforts, improves satisfaction level, and carries no significantly risks in subjects undergoing diagnostic FB.

Clinical manifestations in patients with alpha-fetoprotein-producing gastric cancer.

BACKGROUND: Patients with alpha-fetoprotein (afp)-producing gastric cancer have a high incidence of liver metastasis and poor prognosis. There is some controversy about clinical manifestations in these patients. METHODS: Our study enrolled patients who, before surgery, had gastric cancer with serum afp exceeding 20 ng/mL [afp>20 (n = 58)] and with serum afp 20 ng/mL or less [afp≤20 (n = 1236)]. Clinical manifestations were compared between the groups. RESULTS: Early gastric cancer was more frequent (30.1% vs. 4%) and advanced gastric cancer was less frequent (69.9% vs. 96%) in the afp≤20 group than the afp>20 group (p < 0.001). Liver and lymph node metastasis occurred less frequently in the afp≤20 group (4.4% vs. 27.6%, p < 0.001, and 60.7% vs. 91.4%, p < 0.001, respectively). The 1-, 3-, 5-, and 10-year survival rates of afp≤20 patients were 75.2%, 53.4%, 45.8%, and 34.6% respectively. The 1-, 3-, 5-, and 10-year survival rates of patients with afp greater than 20 ng/mL, but 300 ng/mL or less, were 46.7%, 28.9%, 17.8%, and 13.3% respectively. The 1-, 3-, and 5-year survival rates of patients with serum afp greater than 300 ng/mL were 15.4%, 7.7%, and 0% respectively. The independent predictors for survival time were afp concentration, age, peritoneal seeding, liver metastasis, lymph node metastasis, vascular invasion, TNM stage, curative surgery, serosal invasion, and Lauren classification. CONCLUSIONS: Patients with high serum afp had a high frequency of liver and lymph node metastasis and very poor prognosis. More aggressive management with multimodal therapy (for example, chemotherapy, radiotherapy) might be needed when treating such patients.

Probe of the solar magnetic field using the "cosmic-ray shadow" of the sun.

We report on a clear solar-cycle variation of the Sun's shadow in the 10 TeV cosmic-ray flux observed by the Tibet air shower array during a full solar cycle from 1996 to 2009. In order to clarify the physical implications of the observed solar cycle variation, we develop numerical simulations of the Sun's shadow, using the potential field source surface model and the current sheet source surface (CSSS) model for the coronal magnetic field. We find that the intensity deficit in the simulated Sun's shadow is very sensitive to the coronal magnetic field structure, and the observed variation of the Sun's shadow is better reproduced by the CSSS model. This is the first successful attempt to evaluate the coronal magnetic field models by using the Sun's shadow observed in the TeV cosmic-ray flux.

A microplate-based screening assay for neuraminidase inhibitors.

Neuraminidase (NA) represents a highly promising new target for drug development in influenza virus genes. Rapid screening of enzyme inhibitors is a key method for the identification of leading compounds. In order to speed up the screening for enzyme inhibitors of natural and synthetic origin, effective and fast assays are needed. 2'-(4-Methylumbelliferyl)-α-D-N-acetylneuraminic acid (4-MUNANA) was selected as substrate for development of a microplate-based assay. The enzymatic reaction conditions were optimized as follows: in a 100 µL reaction mixture, the final concentrations were 32.5 mM sodium acetate (pH 3.5), 20 µM 4-MUNANA, 0.005% (w/v) bovine serum albumin, and 0.42 µg/mL NA. In the study, the doseresponse relationship of oseltamivir carboxylate to NA activity was observed. In addition, an overall Z' value of 0.8 proved the systems robustness and potential for screening. The assay system developed will be a valuable tool to discover new structures for the therapeutic inhibition of NA used to treat Influenza.

Significance of serum hepatocyte growth factor levels in patients with hepatocellular carcinoma undergoing hepatic resection.

BACKGROUND: Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen and may stimulate the proliferation and invasiveness of human hepatocellular carcinoma (HCC) cells through the c-met receptor. This study evaluates the significance of serum HGF levels in patients undergoing HCC resection. STUDY DESIGN: The peripheral and portal sera and HCC and non-tumorous tissues of 40 HCC patients, with tumor TNM stage I (n=12), II (n=17), and III (n=11) diseases, who underwent hepatic resection were prospectively collected. Serum HGF levels were determined by enzyme-linked immunosorbent assay. The c-met protein expressions were examined by immunohistochemistry. Median follow-up time was 69 months. RESULTS: The prehepatectomy portal HGF levels (median, 622pg/mL) were significantly higher than peripheral HGF levels (564pg/mL) (P=0.026). The posthepatectomy portal HGF levels (699pg/mL) were significantly higher than prehepatectomy portal HGF levels (P<0.001). C-met expression was detected in 87.5% HCC and in 85.0% non-tumorous liver tissues. By Cox multivariate analysis, posthepatectomy portal HGF level >699pg/mL (P<0.001), multiple tumors (P=0.042), and TNM stages II (P=0.019) and III (P=0.009) were independent factors related with survival. Patients with a posthepatectomy portal HCG level >699pg/mL and with a positive c-met expression in HCC tissue have the worst survival. CONCLUSIONS: In HCC patients, high peripheral and portal HGF serum levels related with poor prognosis after hepatic resection. Hepatocyte growth factor and c-met receptor can be targets of future HCC postoperative treatment.

Outcome of distal gastric cancer with pyloric stenosis after curative resection.

AIMS: Pyloric stenosis usually presents with symptoms, and this may lead patients to consult their physician. We evaluate whether distal gastric cancer patients with pyloric stenosis had a better outcome than those without. METHODS: A total of 551 distal gastric cancer patients who received curative subtotal gastrectomy between January 1988 and December 2003 at Taipei Veterans General Hospital were analyzed. Among them, 174 patients were sorted into the pyloric stenosis group according to obstructive symptoms. Their clinicopathological features, survival and prognostic factors were evaluated. RESULTS: The 5-year overall and disease-free survival rate of distal third gastric adenocarcinoma for the pyloric stenosis group was significantly lower than those without pyloric stenosis. Multivariate analysis revealed the pyloric stenosis group had deeper cancer invasion (relative to pT1, RR of pT2 3.1, p=0.009; pT3 6.1, p<0.001; pT4 16.5, p<0.001), and more lymph node metastasis (RR 3.6; p=0.001). The pyloric stenosis group had a tendency to lymph node metastasis toward the hepatoduodenal ligament, but this did not reach statistical difference. However, the pyloric stenosis group had significantly higher lymph node metastasis in the retropancreatic region (5.17% vs. 0.53%; p=0.001). CONCLUSIONS: Distal gastric cancers with pyloric stenosis have worse biological behavior than those without, and consequently have a poor outcome.

Topoisomerase 2alpha plays a pivotal role in the tumor biology of stage IV thymic neoplasia.

BACKGROUND: Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her-2/neu and its juxtaposed topoisomerase 2alpha (T2alpha) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients. METHODS: From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high-dose weekly 5-fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary. RESULTS: T2alpha gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her-2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (> or = 10% nuclei positive) the T2alpha protein, whereas 4 nonresponders had very low expression. T2alpha overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her-2 gene amplification (P = .0081). CONCLUSION: T2alpha and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

Anisotropy and corotation of galactic cosmic rays.

The intensity of Galactic cosmic rays is nearly isotropic because of the influence of magnetic fields in the Milky Way. Here, we present two-dimensional high-precision anisotropy measurement for energies from a few to several hundred teraelectronvolts (TeV), using the large data sample of the Tibet Air Shower Arrays. Besides revealing finer details of the known anisotropies, a new component of Galactic cosmic ray anisotropy in sidereal time is uncovered around the Cygnus region direction. For cosmic-ray energies up to a few hundred TeV, all components of anisotropies fade away, showing a corotation of Galactic cosmic rays with the local Galactic magnetic environment. These results have broad implications for a comprehensive understanding of cosmic rays, supernovae, magnetic fields, and heliospheric and Galactic dynamic environments.

Stage migration influences on stage-specific survival comparison between D1 and D3 gastric cancer surgeries.

AIMS: We evaluate the influency stage migration in a randomised trial comparing D1 (N 1 lymphadenectomy) and D3 (N 1, 2 and 3 lymphadenectomy) dissections. METHODS: Two hundred and thirteen curatively resected patients were analysed, with this TNM data. RESULTS: After applying D3 patients' data according to simulated D1 staging, D3 resections were associated with up-staging to N2-3 levels in 8% of patients according to the N stage. The likelihood of N-status migration increased with increasing depth of invasion into the gastric wall. The increases in the calculated survival rate after stage migration on known 5-year survival rates were: 2% in stage IB, 1% in stage II, 4% in stage IIIA, and 1% in stage IIIB. CONCLUSIONS: Stage migration secondary to meticulous lymph node dissection affects stage-specific survival rates. True therapeutic survival benefit of D3 resection can only be assessed in this context.

Soil quality evolution after land use change from paddy soil to vegetable land.

A survey was done in 15 typical villages, 150 soil and 86 vegetable plant samples were taken in Jiaxin prefecture of the Taihu Lake region, northern Zhejian province. Results indicate that after 15-20 years land use changed from the paddy rice-wheat (or oilseed rape) double cropping system, to a continuous vegetable land has caused soil quality dramatic change. (1) Acidification: average soil pH was 5.4; about 61% of total samples were pH < 5.5. It was 0.9 units lower than 10 years ago with same upland vegetable cultivation and was 1.2 units lower than soil pH of paddy rice-wheat (or oilseed rape) rotation. (2) Fertilizer salt accumulation: the average salt content was 0.28%, among these about 36.2% of the total samples contained more than 0.3%. (3) Nitrate N and available phosphorus (P) over accumulation: on average it was 279 mg NO3-N/kg, and 45-115 mg P/kg. Nitrate N four times higher and available P 4-10 times more than it is in present paddy rice-wheat rotation soils respectively. This has caused wide concern because of possible groundwater and well drinking water pollution by leached nitrate N and the P losses to water by runoff from vegetable lands induce surface water eutrophication.

Polymorphism of estrogen metabolism genes and cataract.

Cataract is the leading cause of visual impairment in older adults in the world. Age-related lens opacities are common and are frequent causes of loss of vision. The incidence of cataract increases significantly with increasing age in women only. The onset coincides with estrogen deficiency that occurs after menopause. Hormone replacement therapy has proven beneficial to selected postmenopausal women. Estrogen effects on biological system are modulated via the estrogen receptors (ER) and/or estrogen metabolites. Although ER have been detected in ocular tissue, whether ER polymorphism is related to cataract is not known at present. The polymorphisms of estrogen metabolizing enzymes are also related to the serum concentration and activity of estrogen. Polymorphism such as cytochrome P450c17 (A2/A2), cytochrome P450c1A (vt/vt) will result in increased formation of catechol estrogen, while people with catechol-O-methyltransferase (COMT) polymorphism COMT (L/L) will have decreased metabolism of catechol estrogen and decreased level of methoxyestradiol. COMT was also involved in tamoxifen metabolism which may further decrease the activity of COMT in breast cancer patients treated with tamoxifen. It is known that a 4-7% increase in cataract was found in tamoxifen-treated breast cancer patients than non-user. The 7.0% COMT (L/L) genotype in general population corresponded well with the 4-7% of cataract formation in tamoxifen-treated breast cancer patients. Our hypothesis is that breast cancer patients with COMT (L/L) genotype may be at increased risk of cataract formation after tamoxifen treatment.

Is submucosal epinephrine injection necessary before polypectomy? A prospective, comparative study.

BACKGROUND/AIMS: Polyps of the gastrointestinal tract are usually removed due to their link to bleeding, obstruction and malignancy. However, complications may occur following polypectomy. The aim of this study was to assess whether submucosal epinephrine injection before polypectomy could reduce the incidence of bleeding and perforation. METHODOLOGY: Between June 1997 and November 1999, patients with sessile polyps of the gastrointestinal tract found in our endoscopic unit were randomized to receive submucosal epinephrine injection (epinephrine group) or no injection (control group) before polypectomy. In the epinephrine group, epinephrine (1:10,000) was injected surrounding the stalk of the polyp until the mucosa was blanched and bulged. The patients were observed for complications in the following month. RESULTS: A total of 120 patients with 151 sessile polyps were enrolled in this study. In the epinephrine group, 75 polyps (n = 68) were randomized to receive epinephrine injection before polypectomy. In the control group, 76 polyps (n = 61) underwent polypectomy without epinephrine injection. In both groups, there was no significant difference in clinical features including the sizes of the polyps and their stalks, the location of polyps and the pathological diagnosis. There were a total of nine episodes of post-polypectomy hemorrhage, two in the epinephrine group and seven in the control group (2/75 vs. 7/76) (P = 0.07). One case in the epinephrine group experienced delayed bleeding (4 days later). Immediate hemorrhage occurred less in the epinephrine group than that in the control group (1/75 vs. 7/76, P = 0.03). There was one case of perforation in each group. CONCLUSIONS: Epinephrine injection prior to polypectomy is effective in preventing immediate bleeding.

Expression of aminopeptidase N in bile canaliculi: a predictor of clinical outcome in biliary atresia and a potential tool to implicate the mechanism of biliary atresia.

BACKGROUND: Only a few studies on extrahepatic biliary atresia (BA) have reported that the morphological changes of bile canaliculi could predict the clinical outcome after portoenterostomy and provide differential diagnosis of neonatal jaundice. Aminopeptidase N (APN) is an ectoenzyme of bile canaliculi that is involved in bile secretion. In this study, we tried to see whether APN of bile canaliculi had a significant role in BA. PATIENTS AND METHODS: We used monoclonal antibody 9B2 to compare the expression of APN in livers with BA, neonatal hepatitis, and choledochal cysts, as well as in nontumorous portions of pediatric hepatic livers with tumors. The expression of APN in fetuses, preterm babies, and term neonates was also studied. RESULTS: A high degree of 9B2 expression in BA was closely related to poor outcome. Cholestasis in choledochal cysts, rather than neonatal hepatitis, made 9B2 expression stronger. Increasing expression of 9B2 from fetuses to neonates was noted and the degree of 9B2 expression was similar between term neonates and nontumorous portions of pediatric livers with tumors. Interestingly, some cases of BA had 9B2 expression like that of preterm babies. CONCLUSIONS: APN of bile canaliculi progressively develops from fetuses to neonates and is well developed in neonates. APN can be induced to stronger expression by obstructive jaundice. The amount of expression of APN of bile canaliculi in BA is a predictor of clinical outcome and may be a tool for implicating the mechanism of BA.