Nationwide epidemiological study of severe gallstone disease in Taiwan

<p>Abstract</p> <p>Background</p> <p>Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20.</p> <p>Methods</p> <p>A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution.</p> <p>Results</p> <p>The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy.</p> <p>Conclusion</p> <p>This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.</p

SEPTIN12 Genetic Variants Confer Susceptibility to Teratozoospermia

It is estimated that 10–15% of couples are infertile and male factors account for about half of these cases. With the advent of intracytoplasmic sperm injection (ICSI), many infertile men have been able to father offspring. However, teratozoospermia still remains a big challenge to tackle. Septins belong to a family of cytoskeletal proteins with GTPase activity and are involved in various biological processes e.g. morphogenesis, compartmentalization, apoptosis and cytokinesis. SEPTIN12, identified by c-DNA microarray analysis of infertile men, is exclusively expressed in the post meiotic male germ cells. Septin12+/+/Septin12+/− chimeric mice have multiple reproductive defects including the presence of immature sperm in the semen, and sperm with bent neck (defect of the annulus) and nuclear DNA damage. These facts make SEPTIN12 a potential sterile gene in humans. In this study, we sequenced the entire coding region of SEPTIN12 in infertile men (n = 160) and fertile controls (n = 200) and identified ten variants. Among them is the c.474 G>A variant within exon 5 that encodes part of the GTP binding domain. The variant creates a novel splice donor site that causes skipping of a portion of exon 5, resulting in a truncated protein lacking the C-terminal half of SEPTIN12. Most individuals homozygous for the c.474 A allele had teratozoospermia (abnormal sperm <14%) and their sperm showed bent tail and de-condensed nucleus with significant DNA damage. Ex vivo experiment showed truncated SEPT12 inhibits filament formation in a dose-dependent manner. This study provides the first causal link between SEPTIN12 genetic variant and male infertility with distinctive sperm pathology. Our finding also suggests vital roles of SEPT12 in sperm nuclear integrity and tail development

Transforming Growth Factor-β1 Suppresses Hepatitis B Virus Replication by the Reduction of Hepatocyte Nuclear Factor-4α Expression

Several studies have demonstrated that cytokine-mediated noncytopathic suppression of hepatitis B virus (HBV) replication may provide an alternative therapeutic strategy for the treatment of chronic hepatitis B infection. In our previous study, we showed that transforming growth factor-beta1 (TGF-β1) could effectively suppress HBV replication at physiological concentrations. Here, we provide more evidence that TGF-β1 specifically diminishes HBV core promoter activity, which subsequently results in a reduction in the level of viral pregenomic RNA (pgRNA), core protein (HBc), nucleocapsid, and consequently suppresses HBV replication. The hepatocyte nuclear factor 4alpha (HNF-4α) binding element(s) within the HBV core promoter region was characterized to be responsive for the inhibitory effect of TGF-β1 on HBV regulation. Furthermore, we found that TGF-β1 treatment significantly repressed HNF-4α expression at both mRNA and protein levels. We demonstrated that RNAi-mediated depletion of HNF-4α was sufficient to reduce HBc synthesis as TGF-β1 did. Prevention of HNF-4α degradation by treating with proteasome inhibitor MG132 also prevented the inhibitory effect of TGF-β1. Finally, we confirmed that HBV replication could be rescued by ectopic expression of HNF-4α in TGF-β1-treated cells. Our data clarify the mechanism by which TGF-β1 suppresses HBV replication, primarily through modulating the expression of HNF-4α gene

Low-threshold ultrahigh-energy neutrino search with the Askaryan Radio Array

In the pursuit of the measurement of the still-elusive ultrahigh-energy (UHE) neutrino flux at energies of order EeV, detectors using the in-ice Askaryan radio technique have increasingly targeted lower trigger thresholds. This has led to improved trigger-level sensitivity to UHE neutrinos. Working with data collected by the Askaryan Radio Array (ARA), we search for neutrino candidates at the lowest threshold achieved to date, leading to improved analysis-level sensitivities. A neutrino search on a data set with 208.7 days of livetime from the reduced-threshold fifth ARA station is performed, achieving a 68% analysis efficiency over all energies on a simulated mixed-composition neutrino flux with an expected background of 0.10-0.04+0.06 events passing the analysis. We observe one event passing our analysis and proceed to set a neutrino flux limit using a Feldman-Cousins construction. We show that the improved trigger-level sensitivity can be carried through an analysis, motivating the phased array triggering technique for use in future radio-detection experiments. We also include a projection using all available data from this detector. Finally, we find that future analyses will benefit from studies of events near the surface to fully understand the background expected for a large-scale detector

A Template-based UHE Neutrino Search Strategy for the Askaryan Radio Array (ARA)

The Askaryan Radio Array (ARA) is a gigaton-size neutrino radio telescope located near the geographic South Pole. ARA has five independent stations designed to detect Askaryan emission coming from the interactions between ultra-high energy neutrinos (> 10 PeV) and Antarctic ice. Each station includes of 16 antenna deployed in a matrix shape at up to 200 m deep in the ice. A simulated neutrino template, including the detector response model, was implemented in a new search technique for reducing background noise and improving the vertex reconstruction resolution. The template is used to scan through the data using the matched filter method, inspired by LIGO, looking for a low SNR neutrino signature and ultimately aiming to lower the detector’s energy threshold at the analysis level. I will present the estimated sensitivity improvements to ARA analyses through the application of the template technique with results from simulation

The Calibration of the Geometry and Antenna delay in Askaryan Radio Array Station 4 and 5

The Askaryan Radio Array (ARA) experiment at the South Pole is designed to detect the radio signals produced by ultra high energy cosmic neutrino interactions in the ice. There are 5 independent ARA stations, one of which (A5) includes a low-threshold phased array trigger string. Each ARA station is designed to work as an autonomous detector. The Data Acquisition System in all ARA stations is equipped with the Ice Ray Sampler second-generation (IRS2) chip, a custom-made, application-specific integrated circuit (ASIC) for high-speed sampling and digitization. In this contribution, we describe the methodology used to calibrate the IRS2 digitizer chip and the station geometry, namely the relative timing between each pair of ARA antennas, deployed at 200 m below the Antarctic ice surface, and their geometrical positions in the ice, for ARA stations 4 and 5. Our calibration allows for proper timing correlations between incoming signals, which is crucial for radio vertex reconstruction and thus detection of ultra high energy neutrinos through the Askaryan effect. We achieve a signal timing precision on a sub-nanosecond level and an antenna position precision within 10 cm

A neural network based UHE neutrino reconstruction method for the Askaryan Radio Array (ARA)

The Askaryan Radio Array (ARA) is an ultra-high energy (UHE) neutrino (Eν > 1017 eV) detector at South Pole. ARA aims to utilize radio signals detected from UHE neutrino interactions in the glacial ice to infer properties about the interaction vertex as well as the incident neutrino. To retrieve these properties from experiment data, the first step is to extract timing, amplitude and frequency information from waveforms of different antennas buried in the deep ice. These features can then be utilized in a neural network to reconstruct the neutrino interaction vertex position, incoming neutrino direction and shower energy. So far, vertex can be reconstructed through interferometry while neutrino reconstruction is still under investigation. Here I will present a solution based on multi-task deep neural networks which can perform reconstruction of both vertex and incoming neutrinos with a reasonable precision. After training, this solution is capable of rapid reconstructions (e.g. 0.1 ms/event compared to 10000 ms/event in a conventional routine) useful for trigger and filter decisions, and can be easily generalized to different station configurations for both design and analysis purposes

Implementing a Low-Threshold Analysis with the Askaryan Radio Array (ARA)

The Askaryan Radio Array (ARA) is a ground-based radio detector at the South Pole designed to capture Askaryan emission from ultra-high energy neutrinos interacting within the Antarctic ice. The newest ARA station has been equipped with a phased array trigger, in which radio signals in multiple antennas are summed in predetermined directions prior to the trigger. In this way, impulsive signals add coherently, while noise likely does not, allowing the trigger threshold to be lower than a traditional ARA station. Early results on just a fraction of available data from this new system prove the feasibility of a low-threshold analysis