New opportunities at the next-generation neutrino experiments I: BSM neutrino physics and dark matter.

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.

Comparative risk of self-harm hospitalization amongst depressive disorder patients using different antidepressants: a population-based cohort study in Taiwan.

BACKGROUND: The aim of the study was to evaluate the comparative risk of self-harm associated with the use of different antidepressants. METHOD: A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950-E958 and E980-E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment. RESULTS: There were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person-years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5-7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40-6.45], milnacipran (aHR = 2.34, 95% CI 1.24-4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06-1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30-0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline). CONCLUSIONS: The risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors.

Controlling the europium oxidation state in diopside through flux concentration.

This paper explores the connection between the H3BO3 flux concentration and the co-existence of Eu2+ and Eu3+ dopants within CaMgSi2O6 crystals (diopside). The samples were synthesised using a solid-state synthesis method under varying atmospheric conditions, including oxidative (air), neutral (N2), and reductive (H2/N2 mixture) environments. Additionally, some materials underwent chemical modification by partially substituting Si4+ with Al3+ ions acting as charge compensation defects stabilizing Eu3+ luminescence. Depending on the specific synthesis conditions, the materials predominantly displayed either the orange-red luminescence of Eu3+ (under oxidising conditions) or the blue luminescence of Eu2+; however, the comprehensive results confirmed the co-existence of Eu3+/Eu2+ luminescence in both cases. This work shows that varying flux concentrations added during synthesis significantly affect the relative strength of Eu2+ and Eu3+ emissions in a manner dependent on the synthesis atmosphere. The emission of Eu2+ increases with a higher flux concentration in materials synthesised under oxidative and neutral atmospheres independent of the chemical modification. In contrast, for materials obtained under a reductive atmosphere, the changes in the Eu3+ emission intensity depended on the presence or absence of Al3+ ions namely the increase of flux increased the Eu3+ intensity in the case of unmodified materials and decreased in the Al-modified ones. All observed effects were qualitatively explained considering the double role of the flux in the studied system, which besides facilitating the diffusion of chemical species during synthesis acts as a charge compensating agent by creating B'Si centres stabilizing Eu3+ emission.

Factors affecting the use of anti-amoebiasis protective measures among Taiwan immigrants returning to amoebiasis-endemic regions.

OBJECTIVE: To investigate the predictors of use of anti-amoebiasis protective measures (AAPMs) among Taiwan immigrants returning to their country of origin, using the Health Belief Model (HBM) to guide the investigation. DESIGN: Cross-sectional study. METHODS: Between March and May 2011, all permanent immigrants originating from amoebiasis-endemic countries who received services at the immigrant service centres in Taipei or Tainan and who reported that they had returned to their country of origin within the past five years were enrolled in the study. A structured questionnaire containing questions on sociodemographic characteristics and items related to the constructs of the HBM was used as the data collection instrument. RESULTS: Complete information was collected from 384 immigrants, with a response rate of 80% (384/480). The mean age of the subjects was 38.4 years (standard deviation 10.6 years). The majority (70%) of participants did not receive travel information through a pretravel consultation, and more than 17% reported that they did not use measures to prevent amoebiasis. Multiple regression analyses revealed that Chinese proficiency, pretravel consultation and lower barriers to using protective measures were significantly associated with the use of AAPMs during return trips to country of origin (R(2) = 0.45; F = 77.5; P < 0.001). CONCLUSION: The HBM significantly predicted the use of AAPMs in this study. A high proportion of immigrants did not use appropriate AAPMs when they returned to their country of origin. Educational approaches should be targeted at immigrants originating from amoebiasis-endemic regions who return to their country of origin.

Cardiac hemangioma located at the apex of the left ventricle: a rare case report.

We report the case of a 67-year-old man who was found to have asymptomatic murmurs during his health check-up. Echocardiography revealed a mobile spherical mass in the left ventricle (LV), whereas magnetic resonance imaging (MRI) study revealed a well-circumscribed heterogeneous mass in the LV with its base attached to the LV apex. To the best of our knowledge, such a case of hemangioma, particularly its rare location at the apex of the LV, and its asymptomatic conduction disturbance has not yet been reported in the medical literature. Because of successful surgical intervention, the patient is in good health without any further tumor recurrence at 24 months after the diagnosis.

Surgical treatment of 26 patients with necrotizing pneumonia.

BACKGROUND: This study aimed to review the outcome of patients treated with surgical resection for necrotizing lung infection with various co-morbidities and complications. METHODS: The records of 26 patients treated with pulmonary resection for necrotizing pneumonia between July 2004 and January 2010 were retrospectively reviewed. Surgical procedures included large wedge resection (n = 1), lobectomy (n = 19) and bilobectomy (n = 6). RESULTS: The study cohort consisted of 21 men and 5 women aged 35-85 years (mean 64.7 ± 15.0 years). Twenty-three (88.5%) patients had underlying risk factors. At surgical consultation, 17 patients presented with progressive respiratory distress; 6 required ventilatory support; 12 had empyema, and in 5 patients the conditions were complicated by bronchopleural fistula. Four patients had septic shock requiring vasopressor support. Three patients developed hemoptysis. Two patients had bilateral diffuse pneumonia. Klebsiella pneumoniaeand Streptococcusviridans were the most common pathogens. The right lower (n = 13) and right middle lobes (n = 10) were the most frequently affected. Four deaths (15.4%) occurred: 3 due to perioperative progressing pulmonary infection/inflammation and 1 due to hepatorenal failure. Postoperative empyema occurred in 3 patients. One patient became ventilator dependent. CONCLUSION: Pulmonaryresection for necrotizing pneumonia is a feasible treatment option in patients with progressive pulmonary sepsis.

Successful treatment for a large renal cell carcinoma with tumour thrombus.

We report the case of a 41-year-old man with symptoms of exertional dyspnoea and easy fatigue. Physical examination revealed a palpable mass with knocking pain over the right flank region and a cardiac murmur with jugular vein engorgement. Transoesophageal echocardiography revealed a right atrial mass that caused tricuspid inflow obstruction. Computed tomography revealed a giant mass (approximately 15 x 15 cm2) in the right kidney; this finding was consistent with renal cell carcinoma. Despite the metastatic status, right nephrectomy was performed and the intra-atrial tumour thrombus (TT) was resected under a cardiopulmonary bypass in order to relieve the tricuspid obstruction. Histological examination confirmed renal cell carcinoma with TT. The patient is healthy with satisfactory systolic function at 1-year follow-up.

Protamine-associated hypotension in patients on hemodialysis: retrospective study and prevalence of antiprotamine antibodies.

AIMS: Protamine, when administered to neutralize heparin in cardiovascular surgery, is associated with occasionally severe antigen-antibody reactions associated with substantial morbidity and mortality. The objective of this study is to investigate whether patients on hemodialysis are more susceptible to the protamine adverse effects. METHOD: First, a retrospective analysis of a protamine-associated hypotension episode (PAHE) in 239 patients undergoing coronary artery bypass grafting surgery was performed for the incidence study in the period of 1999 to 2005. Second, an ELISA determination of serum anti-protamine IgG antibody in 255 serum samples from individuals without previous surgical histories was conducted for prevalence survey. In both studies, patients on HD were matched for age with non HD patients. RESULTS: The highest incidence (57%) of PAHE occurred in patients on hemodialysis using of M-insulin (a mixed type of insulin aspart 30%, insulin aspart protamine 70%) formulation, and this group also exhibited a high anti-protamine IgG antibody titer in serum (odds ratio: 18.31). CONCLUSIONS: A substantial proportion of patients on hemodialysis are at high risk of acquiring protamine adverse effects, but definite conclusion about the association between uremia and PAHE, however, still needs to be made with caution.

Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation.

Etk (also called Bmx) is a member of the Btk tyrosine kinase family and is expressed in a variety of hematopoietic, epithelial, and endothelial cells. We have explored biological functions, regulators, and effectors of Etk. Coexpression of v-Src and Etk led to a transphosphorylation on tyrosine 566 of Etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of Etk. STAT3, which was previously shown to be activated by Etk, associated with Etk in vivo. To investigate whether Etk could mediate v-Src-induced activation of STAT3 and cell transformation, we overexpressed a dominant-negative mutant of Etk in an immortalized, untransformed rat liver epithelial cell line, WB, which contains endogenous Etk. Dominant-negative inactivation of Etk not only blocked v-Src-induced tyrosine phosphorylation and activation of STAT3 but also caused a great reduction in the transforming activity of v-Src. In NIH3T3 cells, although Etk did not itself induce transformation, it effectively enhanced the transforming ability of a partially active c-Src mutant (c-Src378G). Furthermore, Etk activated STAT3-mediated gene expression in synergy with this Src mutant. Our findings thus indicate that Etk is a critical mediator of Src-induced cell transformation and STAT3 activation. The role of STAT3 in Etk-mediated transformation was also examined. Expression of Etk in a human hepatoma cell line Hep3B resulted in a significant increase in its transforming ability, and this effect was abrogated by dominant-negative inhibition of STAT3. These data strongly suggest that Etk links Src to STAT3 activation. Furthermore, Src-Etk-STAT3 is an important pathway in cellular transformation.

Prolonged postprocedural outbreak of Mycobacterium massiliense infections associated with ultrasound transmission gel.

Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case-control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case-control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p <0.05) with acquiring the outbreak strain. Isolates from the cases and unopened bottles of ultrasound transmission gel were all of strain ST48 and indistinguishable or closely related by pulsed-field gel electrophoresis. After replacement of contaminated gel, no new cases were detected during 18 months' follow-up. This investigation identified the use of contaminated gel as the common source causing an outbreak on a larger scale than had been recognized. Our findings halted production by the manufacturer and prompted revision of hospital guidelines.

Extreme Hyperlactatemia After Heart Transplantation: One Center's Experience.

INTRODUCTION: Hyperlactatemia may occur early after cardiac surgery and is correlated with prognosis. This study was conducted to analyze the perioperative variables and postoperative outcomes among heart transplant recipients with extremely high lactate levels (>15 mmol/L). METHODS: The single-center medical records of heart transplantation from June 2006 to May 2013 were retrospectively reviewed for patient characteristics, perioperative hemodynamic variables, arterial blood gas analysis data, and postoperative mortality. RESULTS: Among 58 consecutive heart transplant recipients, lactate levels over the detectable upper limit (>15 mmol/L) were identified in 12 patients after intensive care unit admission, with peak time at 1.9 ± 2.0 (range 0-6.1) hours. The maximal preoperative lactate level was 3.1 mmol/L, and most (11/12) postoperative lactate levels returned to <4 mmol/L at 27.5 ± 12.8 hours after surgery (range 15-58, median 24), displaying a trend toward delayed extubation time in 10 recipients (P < .01). Blood glucose levels elevated significantly from preoperative 148.9 ± 45.2 to 375.7 ± 96.9 mg/dL at peak lactate level (P < .01). Four patients died in the ICU (range 5-32 days), 4 died after discharge (range 5-57 months), with 6 in total surviving over 1 year. CONCLUSION: Extreme hyperlactatemia commonly occurred early after heart transplantation and mostly recovered within 30 hours; however, with delayed extubation time after operation.

Octreotide decreased liver metabolic activity in patients with hepatitis B surface antigen-positive cirrhosis.

The influence of octreotide and somatostatin on liver metabolic activity were studied in 16 patients with cirrhosis that was positive for hepatitis B surface antigen (HBsAg). In patients receiving a 50 micrograms bolus and a 50 micrograms/hr infusion of octreotide, the hepatic blood flow, hepatic clearance, and the maximum velocity/metabolic elimination rate constant (Vmax/km) were significantly reduced after octreotide infusion compared with basal values. Similarly, the hepatic blood flow, hepatic clearance, and Vmax/km were significantly decreased in patients receiving a 250 micrograms bolus and a 250 micrograms/hr infusion of somatostatin. The extraction ratio and the systemic hemodynamic values, including cardiac index, heart rate, mean arterial pressure, and systemic vascular resistance, showed no significant changes in patients receiving either octreotide or somatostatin. These findings suggest that, as with somatostatin, octreotide reduced hepatic blood flow and impaired liver metabolic activity in patients with HBsAg-positive cirrhosis. These effects may have important clinical implications in the management of bleeding esophageal varices in patients with cirrhosis.

The influence of verapamil and nifedipine on hepatic indocyanine green clearance in patients with HBsAg-positive cirrhosis and ascites.

The influence of verapamil and nifedipine on hepatic indocyanine green kinetics was studied in 12 patients with HBsAg-positive cirrhosis and ascites. Hepatic clearance and its two biologic determinants, hepatic blood flow and metabolic activity (intrinsic clearance [maximum velocity/metabolite elimination rate constant, or Vmax/km]), were determined from hepatic indocyanine green elimination at steady state in patients with cirrhosis. Acute intravenous administration 10 mg verapamil significantly increased the hepatic indocyanine green blood flow (p less than 0.05), but significantly decreased the hepatic clearance (p less than 0.05), extraction ratio (p less than 0.05) and Vmax/km (p less than 0.05). However, acute sublingual administration of 10 mg nifedipine resulted in no significant change in any parameters of hepatic elimination function. These results show that verapamil, but not nifedipine, might impair the transhepatic extraction activity of hepatocytes in patients with HBsAg-positive cirrhosis and ascites.

Heat probe thermocoagulation as a substitute for surgical intervention to arrest massive peptic ulcer hemorrhage: an experience in 153 cases.

In a period of 2 years 7 months, we performed heat probe (HP) thermocoagulation in 153 cases of massive peptic ulcer hemorrhage. The male/female sex ratio was 125/28. The average age was 57.6 +/- 1.3 years (mean +/- SEM; range, 17 to 88). There were 69 cases (45.1%) of spurting hemorrhage, 50 cases (32.7%) of oozing hemorrhage, and 34 cases (22.2%) of nonbleeding visible vessels. Seventy-seven patients (50.3%) were in shock before therapy. After therapy we obtained initial success in 147 cases (96.1%). Rebleeding episodes occurred in 23 patients (15.6%) within 1 month after therapy. Nineteen patients received a second therapy, and treatment in 15 of these cases (78.9%) was ultimately successful. Finally, treatment in 142 cases (92.8%) was ultimately successful. The duration of hospitalization was 6.3 +/- 0.4 days (mean +/- SEM). After discharge all patients were followed at the outpatient department for at least 1 month. Sixty-seven patients were followed endoscopically for at least 2 to 3 months after therapy. Fifty-six patients (83.6%) had a healed scar at the previous bleeding site 2 months after therapy, and 62 patients (92.5%) had a healed scar 3 months after therapy. We conclude that HP thermocoagulation is an ideal and reliable modality of therapeutic endoscopy in arrest of massive peptic ulcer hemorrhage. HP thermocoagulation may become the first choice of therapy for massive peptic ulcer bleeding in the near future.

Simplified rat intubation using a new oropharyngeal intubation wedge.

Our new oropharyngeal intubation wedge made from a plastic 3-ml syringe has been used successfully for the expansion of the oropharyngeal cavity and visualization of vocal cords for endotracheal intubation in the rat. All the animals we used tolerated the intubation and ventilation procedures in a series of experiments. After the proper setting of the respirator, vital signs were maintained within normal range. The postmortem examination and measurements in the upper airway confirmed that the endotracheal tube was properly sited and also demonstrated the precise size of the device that should be used. The main advantages of this method include low cost, simplicity, and reliability. Furthermore, because no expensive, elaborate, difficult-to-operate, or hard-to-get special equipment is needed, this technique can be used in every laboratory.

Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection.

A total of 20 patients with histologically proven primary hepatocellular carcinoma (PHC) received mitoxantrone IV at a dose of 10-16 mg/m2 every 3 weeks. All patients had previous hepatitis B infection. None underwent remission after treatment; 2 had stable disease and 18 progressive disease. The median overall survival was 13 weeks (range, 1-59 weeks). There was no evidence of significant antitumor activity for mitoxantrone in our patients with PHC. Hematotoxicity occurred in 100% of the patients with grades 2-4 leukopenia, 89% of those with grades 1-4 anemia, and 26% of those with grades 2-3 thrombocytopenia. Cardiotoxicity occurred in 20% of the patients after 14-30 mg/m2 mitoxantrone; these included complete heart block with fatal outcome in one case, decreased ventricular ejection fraction in one, and sinus tachycardia in two. Nausea, vomiting, fever, diarrhea, and alopecia were mild and occurred in 15%-45% of the patients Therefore, patients with PHC following hepatitis B infection may be less tolerant to mitoxantrone, resulting in the apparent increase in toxicities.

Transcatheter arterial chemoembolization for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) was treated with transcatheter arterial chemoembolization (TACE) in a sample of 129 patients. The cumulative survival rate was 49% at 1 year and 22% at 2 years. The median survival time was 11.9 months. The survival rates at 1 year of 84 patients in Child's group A and 27 in Child's group B were 56% and 40%; out of 52 HCC patients with portal vein patent and 77 with portal vein invasion 75% and 40% survived, and the 1-year survival rates for 33 HCC patients with capsule intact, 14 with capsule broken and 82 with no capsule were 85%, 65% and 40% respectively. From the above results there were statistically significant differences in survival time in those with good clinical performance status by Child's classification, those showing patency of the portal vein and those where the capsule was present. Therefore, we would like to recommend, TACE of HCC in well-selected patients presenting with good clinical status, patency of the portal vein and without broken capsule, in order to achieve better clinical results.

Clinical significance of ultrasonography, computed tomography, and biochemical tests in the rapid diagnosis of gallstone-related pancreatitis: a prospective study.

Real-time ultrasonography (US), computed tomography (CT), and biochemical tests were prospectively performed to detect gallstones in 88 consecutive patients immediately after the onset of an attack of acute pancreatitis. The sensitivity of biochemical tests was 84.6% when the patients had three or more positives of five parameters [including serum bilirubin, alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT), and alanine transaminase-aspartate transaminase (ALT-AST) ratio]. The sensitivity, specificity, and accuracy were 71.8, 98.0, and 86.4% for US, and 52.9%, 100%, and 79.5% for CT. The sensitivity, specificity, and accuracy were improved to 82.1, 100, and 93.2% by the combination of US and CT, and 94.9, 100, and 97.7% by the combination of US and biochemical tests. Adding CT to the combination of US and biochemical tests resulted in only a slight improvement in sensitivity and accuracy. In conclusion, a combination of US and biochemical tests can provide the best noninvasive method in rapidly detecting gallstones as an etiological factor in acute pancreatitis. Computed tomography is not cost-effective. A positive result of biochemical tests despite a negative finding in US calls for an intensive search for gallstones by further investigation with endoscopic retrograde cholangiography or repeated US examinations.

Pancreatic enzymes in uremic patients with or without dialysis.

One hundred thirty blood samples from 87 patients with renal failure, but without abdominal pain, were analyzed for blood urea nitrogen (BUN), creatinine, amylase, p-isoamylase, and lipase simultaneously. We found that 74, 78, and 80% of the patients had hyperamylasemia, hyperisoamylasemia, and hyperlipasemia. None had amylase higher than five times the upper limit. A few patients (2.3%) had lipase elevated to more than 10 times the upper limit. No significant change of pancreatic enzyme level was noted as a result of hemodialysis, but a significant amount of amylase was removed from the circulation in patients receiving intermittent peritoneal dialysis. Significantly lower pancreatic enzyme levels were observed in patients with less impairment of renal function. We conclude that elevation of pancreatic enzymes in uremic patients is more frequent and more extensive than most articles indicate, and that the extent of increase is related more to renal function than to the modalities of dialysis the patients received.

Arteriovenous fistula using transposed basilic vein in chronic hypotensive hemodialysis patients.

AIM: Chronic hypotension is not uncommon in uremic patients on regular hemodialysis. This subset of patients often requires multiple operations to maintain their vascular access due to frequent thrombosis and occlusion of the arteriovenous fistula. Our aims was to assess whether surgical intervention with the brachial artery-transposed basilic vein fistula is effective in chronic hypotensive hemodialysis patients. MATERIALS AND METHODS: Fifty-four hemodialysis patients with chronic hypotension were enrolled in this study. Most ofthem were referred from local hospitals. They were 23 men and 31 women. The brachial artery-transposed basilic vein arteriovenous fistula was performed in a period of 46 months at the teaching hospital. Primary patency was defined as the length of time from the fistula creation until the development of thrombosis or a complication that required operative revision ofthe fistula. Secondary patency was defined by whether the fistula could be salvaged by revision such that blood flow was maintained. RESULTS: There was no technical failure and none of these patients died due to the surgical operation. The primary patency rate was 89.80% at 1 year, 73.08% at 2 years, and 64.710% at 3 years. The secondary patency rate was 95.92% at 1 year, 84.62% at 2 years, and 76.47% at 3 years. CONCLUSIONS: Brachial artery-transposed basilic vein arteriovenous fistula may present good primary alternative vascular access in chronic hypotensive hemodialysis patients.