Unusual Near-Horizon Cosmic-Ray-like Events Observed by ANITA-IV.

ANITA's fourth long-duration balloon flight in 2016 detected 29 cosmic-ray (CR)-like events on a background of 0.37_{-0.17}^{+0.27} anthropogenic events. CRs are mainly seen in reflection off the Antarctic ice sheets, creating a phase-inverted waveform polarity. However, four of the below-horizon CR-like events show anomalous noninverted polarity, a p=5.3×10^{-4} chance if due to background. All anomalous events are from locations near the horizon; ANITA-IV observed no steeply upcoming anomalous events similar to the two such events seen in prior flights.

Randomized trial of oral versus enteral feeding for patients with postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Whether continued oral feeding may have a negative impact on healing of postoperative pancreatic fistula (POPF) is unclear. The aim was to test the hypothesis that oral feeding is non-inferior to enteral feeding in closure of POPF after pancreatoduodenectomy, and to clarify the effects of oral feeding on the duration and grade of POPF. METHODS: This multicentre, non-inferiority randomized trial of oral or enteral feeding of patients with POPF after pancreatoduodenectomy recruited patients between August 2013 and September 2016. The primary efficacy outcome was the 30-day fistula closure rate. The prespecified non-inferiority margin was 15 per cent. Other efficacy outcomes included grade of fistula, and hospital stay and costs. RESULTS: A total of 114 patients were included, and received oral (57) or enteral (57) feeding. The two groups were balanced in baseline characteristics and no patient was lost to follow-up. In intention-to-treat analysis, oral feeding was non-inferior to enteral feeding in terms of 30-day fistula closure rate (88 versus 89 per cent respectively; difference -1·8 per cent, lower limit of 95 per cent c.i. -14·4 per cent; P = 0·020 for non-inferiority). Compared with enteral feeding, oral feeding significantly reduced hospital costs and duration of stay. No significant differences were noted in the number of patients whose POPF evolved into grade B/C, or other outcomes. CONCLUSION: Oral feeding in patients with POPF after pancreatoduodenectomy did not increase the duration or grade of POPF, and was associated with reduced duration of stay and hospital costs. Registration number: NCT01755260 (http://www.clinicaltrials.gov).

Hepatitis B virus infection in Taiwan: The role of NTCP rs2296651 variant in relation to sex.

Sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV) infection. NTCP rs2296651 is believed to be an Asian-specific variant responsible for HBV susceptibility. We investigated the relationship between rs2296651 and HBV infection in Taiwan based on stratification by gender and menopausal status. We recruited 10 017 Taiwan Biobank participants aged 30-70 years with complete genetic data and sociodemographic information. Gender-stratified multivariate logistic regression models were used to determine the relationship between NTCP variant and HBV infection. Among individuals with HBV infection, the genotype frequencies of GG, AG and AA in women were 0.85, 0.15 and 0 while those in men were 0.82, 0.18 and 0, respectively. The multivariate-adjusted odds ratios (OR) of HBV infection were 0.77 (95% CI 0.59-0.99) in women and 0.98 (95% CI 0.79-1.20) in men. The adjusted OR was 0.87 (CI 0.63-1.19) in premenopausal and 0.59 (0.36-0.97) in postmenopausal women. We found that genetic variation in the HBV receptor gene (NTCP) was significantly associated with a decreased risk of HBV infection in Taiwanese women.

Effect of Bidens pilosa on infection and drug resistance of Eimeria in chickens.

Extensive use of current anti-coccidial drugs together with drug resistance and residue has raised concerns about public health and poultry development. Here, we studied the anti-coccidial properties of Bidens pilosa. A phytochemical approach was developed for analysis of B. pilosa utilized as a feed additive. The protective effects of B. pilosa supplemented chicken diet were evaluated chickens infected with Eimeria tenella. B. pilosa, at doses of 0.5%, 1% and 5% of the chicken diet, significantly protected against E.tenella as measured by reduction in mortality, weight loss, fecal oocyst excretion and gut pathology in chickens. Finally, drug resistance of E. tenella to B. pilosa was assessed in chickens using the anti-coccidial index. This index showed that B. pilosa induced little, if any, drug resistance to Eimeria in chickens. Collectively, this work suggests that B. pilosa may serve as a novel, natural remedy for coccidiosis with low drug resistance in chickens.

Auditory efferent dysfunction in normal-hearing chronic idiopathic tinnitus.

OBJECTIVE: To investigate the function of the auditory efferent system in patients with chronic idiopathic tinnitus, but normal pure-tone audiograms. METHODS: We studied 15 subjects with normal hearing that had experienced either unilateral or bilateral persistent tinnitus for at least 3 months. The ears of the 15 subjects were classified into tinnitus-positive-ear (TPE) and tinnitus-negative-ear (TNE) groups. The control-ear group (CE) comprised the ears of 15 subjects with normal hearing and no tinnitus. We measured different types of otoacoustic emissions (OAEs), including spontaneous (SOAEs), transient evoked (TEOAEs), and distortion product (DPOAEs). We also analyzed contralateral suppression of OAEs and auditory brainstem responses (ABRs). Data were compared among TPE, TNE, and CE groups. RESULTS: The data associated with cochlear mechanics, including the prevalence of SOAEs, the number of SOAE peaks, and the overall TEOAE responses in the absence of a contralateral stimulus, were not significantly different among the TPE, TNE, and CE groups. In the TPE group, contralateral stimuli failed to significantly suppress overall TEOAEs, and contralateral suppression of DPOAEs was significantly reduced over a limited frequency range. Furthermore, the TPE group showed prolonged latencies in waves III and V of ABRs. CONCLUSION: This study demonstrated that abnormal contralateral suppression of OAEs and ABRs indicated a dysfunction in the ipsilateral efferent medial olivocochlear system; this might play a role in normal-hearing tinnitus.

Diffusion of co-sputtered metals as bonding materials for 3D interconnects during thermal treatments.

Diffusion behaviors of co-sputtered metals during thermal treatments were investigated, where these co-sputtered metals can be used as bonding materials for 3D Interconnects. In this paper, we report the diffusion behaviors and discuss the diffusion mechanisms of co-sputtered metals before and after annealing. Atom and vacancy volume, vacancy formation energy, and activation energy are proposed to explain the diffusion direction and diffusion rate among different co-sputtered metals. Based on the excellent bonding performance of this method, Cu/metal co-sputtering bonding is considered as a potential candidate for advanced bonding technology.

Successful treatment of erlotinib-induced acute hepatitis and acute interstitial pneumonitis with high-dose corticosteroid: a case report and literature review.

Erlotinib, a kind of epidermal growth factor receptor tyrosine kinase inhibitor, is a target therapy and approved for the treatment of metastatic non-small cell lung cancer (NSCLC) and advanced pancreatic cancer. Among these EGFR-TKI agents, including gefitinib and erlotinib, the common dose-limiting toxicities are diarrhea, mucositis and skin rash (Acneform eruptions). In addition to the above adverse effects, infrequent but potentially fatal and lethal entity complications include acute interstitial lung disease (ILD) and acute hepatitis. The incidence of EGFR-TKI agents (gefitinib and erlotinib) induced acute hepatitis is rare and hepatotoxicity of EGFR-TKI agent was rarely discussed. The treatment of EGFR-TKI agents induced acute hepatitis remains uncertain and cessation medication is current policy. Here we reported a case of erlotinib induced interstitial pneumonitis and acute hepatitis with clinical appearance of hypoxemia and general weakness, treated with high dose pulse therapy and showed good recovery.

Successful treatment of gallbladder neuroendocrine carcinoma with combined chemo-radiotherapy: a case report and literature review.

Neuroendocrine tumors (NETs) occur in the bronchopulmonary system. Extrapulmonary NETs are rare and are considered to ac count for 2.5 - 5% of all NETs, with more than 60% of these tumors occurring along the gastro intestinal tract, including primary NET of the gall bladder. Pri mary NETs of the gall bladder have been classified as carcinoid, neuroendocrine carcinoma or heterogeneous carcinoma. Currently, the main treatment of neuroendocrine car ci noma re mains surgery. The role of radiotherapy and chemotherapy is undefined be cause of the paucity of data. In advanced cases, chemotherapy has been prescribed with such effective agents as cisplatin, carboplatin, etoposide and paclitaxel. Here we re port a case of a 64-year-old Taiwanese male patient with neuroendocrine carcinoma of the gall bladder who received combined chemoradiotherapy (CCRT) with cisplatin, 5- fluorouracil and leucovorin (PFL) from June 2009 un til now, and whose disease is stable. CCRT with PFL may be a possible reg i men for high-grade neuroendocrine carcinoma of the gall bladder.

Color variation in periodic Ag line arrays patterned by using electron-beam lithography.

Periodic Ag line arrays with different line pitches from 500 nm to 950 nm on ITO coated glass substrates have been fabricated by using electron-beam lithography (EBL) technique for studying the color light guide in a display system. The patterned Ag line array is used as a light outcoupling and color-selection component due to the emission wavelength changed by the Ag line arrays with different periodic distances that could achieve color variation. We have demonstrated that the ITO coated glass substrates containing periodic Ag line arrays with varied line pitches can be used as a color filter in a display device. This means that with a proper metallic nanostructure layer, the red, green, and blue colors in a display system can be obtained without a traditional color filter for modern multi-applications of optoelectronic display devices.

Effect of impurity scattering on the linear and nonlinear conductances of quasi-one-dimensional disordered quantum wires by asymmetrically lateral confinement.

We have studied the linear conductance and source-drain bias spectroscopies of clean and disordered quantum wires (QWs) against thermal cycling and lateral shifting, which change the impurity configuration. Conductance quantization and the zero bias anomaly (ZBA) are robust in clean QWs. In contrast, disordered QWs show complexities in the ways of conductance resonance, peak splitting and trace crossing in source-drain bias spectroscopies. The experimental results and theoretical predictions are in congruence. Moreover, the resonant state arising from the impurities results in either a single peak or double-splitting peaks in the spectroscopies from the detailed impurity configurations. The resonant splitting peaks are found to influence the ZBA, indicating that a clean QW is crucial for investigating the intrinsic characteristics of the ZBA of QWs.

Comparisons of intraocular pressure measurements: Goldmann applanation tonometry, noncontact tonometry, Tono-Pen tonometry, and dynamic contour tonometry.

AIMS: To compare intraocular pressure (IOP) readings between Tono-Pen tonometry and GAT, between noncontact tonometry (NCT) and GAT, and between dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT). The correlation between IOP reading and possible confounder was identified. METHODS: This observational cross-sectional study enrolled sixty-two healthy subjects. All IOP and ocular pulse amplitude (OPA) measurements were taken by a single ophthalmologist; mean keratometric power (MK), central corneal thickness (CCT), and lens thickness (LT) were measured by a single experienced technician. RESULTS: Stepwise multiple regression analysis indicated that GAT (P=0.017) and DCT (P=0.002) readings correlated positively with MK; GAT, NCT, and Tono-Pen readings correlated positively with CCT (P<0.05); NCT (P=0.035), and DCT (P=0.016) readings correlated negatively with LT; GAT (P=0.006) and Tono-Pen (P=0.009) readings correlated positively with OPA. CONCLUSIONS: The K, CCT, LT, and OPA are confounders in tonometry readings.

Accuracy of corneal flap thickness achieved by two different age MK-2000 microkeratomes.

AIMS: To investigate the accuracy of corneal flap thickness (FT) using two different age MK-2000 microkeratomes. METHODS: The prospective cohort study enroled 260 patients with refractive error. Flaps were created using two microkeratomes A and B (new and aged, respectively) with 130-mum heads in two patient groups and two times the same blade in both treated eyes of each patient. The variations in FTs were compared between two groups and between both operated eyes of each patient. The correlations were analysed between FT and CCT or keratometric power. RESULTS: In the A and B groups, the average FTs were 123.3+/-18.7 and 147.5+/-19.1 mum respectively. Difference in measurements between the actual FTs of first eye operations in the A group and intended 130 mum of FTs was not significant (P=0.462), but those of second operated eyes in the A group and both treated eyes in the B group were significant (P<0.001). Second cut achieved a thinner flap and increased the variability in FT, and an aged microkeratome achieved a thicker flap than a new microkeratome and than that claimed by the manufacturer. Positive correlations were observed between preoperative CCT and FT (P<0.05). CONCLUSIONS: The first eye operation by a new MK-2000 microkeratome achieves the accuracy of the intended FT. FTs varied between first and second cuts of each patient and between two different age MK-2000 microkeratomes. LASIK surgeons should compare FT when using an aged MK-2000 microkeratome, and frequent and periodic comparison of FT achieved by all microkeratomes may be also recommended.

Aortic valve sclerosis is an echocardiographic indicator of significant coronary disease in patients undergoing diagnostic coronary angiography.

Aortic valve sclerosis (AVS) is considered to be a manifestation of generalised atherosclerosis that involves the aortic valve. It has been associated with higher cardiovascular morbidity and mortality in a population-based study. This investigation used transthoracic echocardiography (TTE) to evaluate the prevalence and significance of AVS in 357 Chinese patients with suspected coronary artery disease (CAD). This work reveals that AVS is an independent echocardiographic predictor of significant CAD in such clinical setting (O.R.=3.18; 95% confidence interval 1.52-6.7; p=0.002). Other independent predictors include male gender, diabetes mellitus and hypertriglyceridemia. The predictive value of AVS for the presence of CAD is more prominent in females and in subjects aged <65 years. The recognition of AVS on TTE should alert the physicians to the possibility of underlying significant CAD, and further evaluation with aggressive management is indicated, even though no angiographic documentation is available.

Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes.

Urocortin (UCN), a member of the Corticotropin-Releasing Factor (CRF) family of peptides is a well described cardioprotective agent. UCN is able to bind to two types of G-protein coupled receptors: CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2), whereas, two homologues of UCN, stresscopin (SCP) or also known as urocortin III (UCNIII) and stresscopin related peptide (SRP), or urocortin II (UCNII), bind exclusively and with high affinity to CRFR2, we hypothesised that they will exhibit more pronounced cardioprotective effects than UCN. We show for the first time that SCP is expressed in rat cardiomyocytes and that the levels of SRP and SCP are increased by hypoxic stress. All three peptides have potent cardioprotective effects in cells exposed to hypoxia/reoxygenation. When used at 10(-8) M they increased the amount of live cells by 25% when added prior to hypoxia, and by 20% when UCN and SCP were added at the onset of reoxygenation. In addition, the peptides are equally are more potent antiapoptotic factors than UCN. The antiapoptotic effects of SCP were more pronounced than SRP and UCN at a concentration of 10(-10) M. Furthermore, SCP and SRP protect cardiomyocytes better than UCN at concentrations up to and including 10(-10) M and reduced the amount of TUNEL positive cells almost by half at concentrations of 10(-12) to 10(-10) M. More importantly, we demonstrate that SCP and SRP are able to protect cardiomyocytes even if they are administered after the hypoxic insult and prior to reoxygenation. In this case SCP was more potent than UCN and SRP at 10(-12) M and both SCP and SRP exhibited higher protection at 10(-8) M compared to UCN. Cardioprotection of cardiomyocytes by 10(-8) M of peptides was abolished when treated with 50 microM LY294002 or 100 microM PD98059, but not by 10 microM SB203580 prior to the hypoxic insult. Transfection of dominant negative Akt and MEK1 also blocked protection by the peptides, whereas dominant negative MEKK6 had no effects, demonstrating that SCP and SRP, like UCN, require activation of p42/44 Mitogen activated protein kinase and Akt/Protein Kinase B in order to produce their cardioprotective effects. In addition, we showed that SCP and UCN are potent activators of the p42/44 MAPK pathway, with SRP able to induce phosphorylation of p42/44 MAPK as well, albeit not as pronounced.

Impairment of spermatogenesis in transgenic mice with selective overexpression of Bcl-2 in the somatic cells of the testis.

To explore the functional role of Bcl-2 in germ cell development, transgenic mice carrying 6 kilobases of the inhibin-alpha promoter were generated to express human bcl-2 gene product in the gonads. Although female transgenic mice demonstrated decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis, the adult males exhibited variable impairment of spermatogenesis. The degree of damage ranged from tubules with intraepithelial vacuoles of varying sizes to near atrophied tubules consisting of Sertoli cells and a few spermatogonia. Although there was no significant change in body weight, an approximately 34% decrease in testicular weights was noted in transgenic animals compared with wild-type mice. Gamete maturation, assessed by determining the percentage of tubules with advanced (steps 13-16) spermatids, was decreased to 44.4% of the values measured in the wild-type animals. The incidence of germ cell apoptosis increased 3.8-fold in the transgenic animals and was associated with a marked loss of germ cells. Electron microscopy of the testes further revealed large vacuoles in the Sertoli cell cytoplasm and dilations of the intracellular spaces between adjacent Sertoli cells, spermatid malformations, and increased germ cell apoptosis in the transgenic animals. There was no evidence of Sertoli cell death either by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay or electron microscopy. Leydig cell ultrastructure, cell size and numbers, and plasma levels of testosterone were not different between normal and the transgenic animals. Collectively, these results support the critical role of Bcl-2 in male germ cell development and are consistent with the gender-specific role of the Bcl-2 family members in reproduction.

Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis.

Survival factors activate kinases which, in turn, phosphorylate the proapoptotic Bcl-xl/Bcl-2-associated death promoter homolog (BAD) protein at key serine residues. Phosphorylated BAD interacts with 14-3-3 proteins, and overexpression of 14-3-3 attenuates BAD-mediated apoptosis. Although BAD is known to interact with Bcl-2, Bcl-w, and Bcl-xL, the exact relationship between BAD and anti- or proapoptotic Bcl-2 proteins has not been analyzed systematically. Using the yeast two-hybrid protein interaction assay, we found that BAD interacted negligibly with proapoptotic Bcl-2 proteins. Even though wild type BAD only interacted with selected numbers of antiapoptotic proteins, underphosphorylated mutant BAD interacted with all antiapoptotic Bcl-2 proteins tested (Bcl-2, Bcl-w, Bcl-xL, Bfl-1/A1, Mcl-1, Ced-9, and BHRF-1). Using nonphosphorylated recombinant BAD expressed in bacteria, direct interactions between BAD and diverse antiapoptotic Bcl-2 members were also observed. Furthermore, apoptosis induced by BAD was blocked by coexpression with Bcl-2, Bcl-w, and Bfl-1. Comparison of BAD orthologs from zebrafish to human indicated the conservation of a 14-3-3 binding site and the BH3 domain during evolution. Thus, highly conserved BAD interacts with diverse antiapoptotic Bcl-2 members to regulate apoptosis.

Cataract formation after pars plana vitrectomy.

To investigate the duration and pattern of cataract formation after pars plana vitrectomy, thirty-three eyes from 33 patients with complete data from March 1995 to January 2000 were collected in this study. The time and pattern of cataract formation was analyzed according to Lens Opacities Classification System III (LOCS III). The correlation between the mean cataract progression and follow-up time was determined by simple regression and correlation analysis. Diabetes mellitus and hypertension were the main causes of patients with vitreoretinopathy who underwent pars plana vitrectomy procedure. Twenty-one patients (63.6%) had diabetes mellitus and 11 patients (33.3%) had hypertension. Four eyes (13.8%) received intravitreal gas injection after pars plana vitrectomy. The correlation between cataract progression and follow-up time was clinically significant (p < 0.05). Thirty-one patients (94%) were nuclear cataract, the mean time of cataract formation being 9.1 months; 15 patients (46.9%) were cortical cataract, the mean time of formation being 8 months; and 24 patients (72.7%) were posterior subcapsular cataract, the mean time of formation being 13.3 months. Cataract formation after pars plana vitrectomy is not infrequent. Nuclear cataract is the most common type in this study. Vitreous microenvironmental changes, post-vitrectomy uveitis, intravitreal gas, and patient age may be the key points of cataract formation after surgery. The mechanism of longer-term effect of pars plana vitrectomy on lens status is still unknown and merits further study.

Evolution and classification of cystine knot-containing hormones and related extracellular signaling molecules.

The cystine knot three-dimensional structure is found in many extracellular molecules and is conserved among divergent species. The identification of proteins with a cystine knot structure is difficult by commonly used pairwise alignments because the sequence homology among these proteins is low. Taking advantage of complete genome sequences in diverse organisms, we used a complementary approach of pattern searches and pairwise alignments to screen the predicted protein sequences of five model species (human, fly, worm, slime mold, and yeast) and retrieved proteins with low sequence homology but containing a typical cystine knot signature. Sequence comparison between proteins known to have a cystine knot three-dimensional structure (transforming growth factor-beta, glycoprotein hormone, and platelet-derived growth factor subfamily members) identified new crucial amino acid residues (two hydrophilic amino acid residues flanking cysteine 5 of the cystine knot). In addition to the well known members of the cystine knot superfamily, novel subfamilies of proteins (mucins, norrie disease protein, von Willebrand factor, bone morphogenetic protein antagonists, and slit-like proteins) were identified as putative cystine knot-containing proteins. Phylogenetic analysis revealed the ancient evolution of these proteins and the relationship between hormones [e.g. transforming growth factor-beta (TGFbeta)] and extracellular matrix proteins (e.g. mucins). They are absent in the unicellular yeast genome but present in nematode, fly, and higher species, indicating that the cystine knot structure evolved in extracellular signaling molecules of multicellular organisms. All data retrieved by this study can be viewed at http://hormone.stanford.edu/.

Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor.

Adaptive stress responses mediated by the endocrine, autonomic, cardiovascular and immune systems are essential for the survival of the individual. Initial stress-induced responses provide a vital short-term metabolic lift, but prolonged or inappropriate exposure to stress can compromise homeostasis thereby leading to disease. This 'fight-or-flight' response is characterized by the activation of the corticotropin-releasing hormone (CRH)-adrenocorticotropin-glucocorticoid axis, mediated by the type 1 CRH receptor. In contrast, the type 2 CRH receptor mediates the stress-coping responses during the recovery phase of stress. We identified human stresscopin (SCP) and stresscopin-related peptide (SRP) as specific ligands for the type 2 CRH receptor. The genes encoding these peptides were expressed in diverse peripheral tissues as well as in the central nervous system. Treatment with SCP or SRP suppressed food intake, delayed gastric emptying and decreased heat-induced edema. Thus SCP and SRP might represent endogenous ligands for maintaining homeostasis after stress, and could allow the design of drugs to ameliorate stress-related diseases.