The German cochlear implant registry: one year experience and first results on demographic data.

PURPOSE: Clinical registries have great potential for quality control of medical procedures regarding the indications, therapeutic processes and results, including their possible complications. This is particularly true when providing patients with severe hearing loss or deafness with a cochlear implant (CI). This treatment represents a lifelong care process that requires continuous quality control over time. On the initiative of the Executive Committee of the German Society of Otorhinolaryngology (Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V., DGHNO-KHC), a national German CI registry (Deutsches Cochlear Implant Register, DCIR) was established in January 2022. This article focuses on the first demographic and baseline data of the DCIR. METHODS: The DCIR covers the complete therapeutic process from indication, surgery, fitting and lifelong aftercare in CI therapy. By the end of 2022, 75 hospitals in Germany had agreed to contribute to the DCIR. RESULTS: During the year 2022, 63 hospitals actively contributed data to the DCIR. Pseudonymized data from 2,292 CI implantations (2,176 primary implantations, 99 explantations with immediate re-implantations and 17 re-implantations following an earlier explantation) in 2,108 patients were documented. Cochlear implantation was accomplished in 1,807 adults (≥ 18 years) and 301 children (< 18 years). Fourty patients (1,9%) were children < 1 year of age and 55 (2,6%) were patients > 85 years. From the total of 2,292 implantations, 226 (9.9%) were performed as simultaneous bilateral implantations (CI implantation in both ears of 113 patients on the same day of surgery) and 412 implantations (19.1% of 2,162 implantations with data provided on the contralateral ear's hearing status) were in patients with single sided deafness (normal hearing in the contralateral ear). In addition, the reported complications in 2022 were also evaluated. Seven reports (0.4%) of mild to moderate severe facial nerve dysfunctions were documented. No reports of severe or total facial nerve dysfunction (House-Brackmann grade V/VI), meningitis or death related to CI therapy were documented. CONCLUSION: Although still in the start-up phase, these initial DCIR data already provide an interesting first insight into the demographic structure and baseline data of CI therapy in Germany. The successful implementation of the DCIR represents an important step towards continuous quality control of CI care.

Monitoring Cochlear Health With Intracochlear Electrocochleography During Cochlear Implantation: Findings From an International Clinical Investigation.

OBJECTIVES: Electrocochleography (ECochG) is emerging as a tool for monitoring cochlear function during cochlear implant (CI) surgery. ECochG may be recorded directly from electrodes on the implant array intraoperatively. For low-frequency stimulation, its amplitude tends to rise or may plateau as the electrode is inserted. The aim of this study was to explore whether compromise of the ECochG signal, defined as a fall in its amplitude of 30% or more during insertion, whether transient or permanent, is associated with poorer postoperative acoustic hearing, and to examine how preoperative hearing levels may influence the ability to record ECochG. The specific hypotheses tested were threefold: (a) deterioration in the pure-tone average of low-frequency hearing at the first postoperative follow-up interval (follow-up visit 1 [FUV1], 4 to 6 weeks) will be associated with compromise of the cochlear microphonic (CM) amplitude during electrode insertion (primary hypothesis); (b) an association is observed at the second postoperative follow-up interval (FUV2, 3 months) (secondary hypothesis 1); and (c) the CM response will be recorded earlier during electrode array insertion when the preoperative high-frequency hearing is better (secondary hypothesis 2). DESIGN: International, multi-site prospective, observational, between groups design, targeting 41 adult participants in each of two groups, (compromised CM versus preserved CM). Adult CI candidates who were scheduled to receive a Cochlear Nucleus CI with a Slim Straight or a Slim Modiolar electrode array and had a preoperative audiometric low-frequency average thresholds of ≤80 dB HL at 500, 750, and 1000 Hz in the ear to be implanted, were recruited from eight international implant sites. Pure tone audiometry was measured preoperatively and at postoperative visits (FUV1 and follow-up visit 2 [FUV2]). ECochG was measured during and immediately after the implantation of the array. RESULTS: From a total of 78 enrolled individuals (80 ears), 77 participants (79 ears) underwent surgery. Due to protocol deviations, 18 ears (23%) were excluded. Of the 61 ears with ECochG responses, amplitudes were < 1 µV throughout implantation for 18 ears (23%) and deemed "unclear" for classification. EcochG responses >1 µV in 43 ears (55%) were stable throughout implantation for 8 ears and compromised in 35 ears. For the primary endpoint at FUV1, 7/41 ears (17%) with preserved CM had a median hearing loss of 12.6 dB versus 34/41 ears (83%) with compromised CM and a median hearing loss of 26.9 dB ( p < 0.014). In assessing the practicalities of measuring intraoperative ECochG, the presence of a measurable CM (>1 µV) during implantation was dependent on preoperative, low-frequency thresholds, particularly at the stimulus frequency (0.5 kHz). High-frequency, preoperative thresholds were also associated with a measurable CM > 1 µV during surgery. CONCLUSIONS: Our data shows that CM drops occurring during electrode insertion were correlated with significantly poorer hearing preservation postoperatively compared to CMs that remained stable throughout the electrode insertion. The practicality of measuring ECochG in a large cohort is discussed, regarding the suggested optimal preoperative low-frequency hearing levels ( < 80 dB HL) considered necessary to obtain a CM signal >1 µV.

Genome-wide re-sequencing reveals population structure and genetic diversity of Bohai Black cattle.

Bohai Black (BHB) cattle, one of eight representative indigenous breeds in China, is well known for its high resistance to disease, endurance under unfavorable feeding conditions and excellent meat quality. Over recent, the number of BHB cattle has decreased sharply. To investigate the population structure and genetic diversity of this breed, the whole-genome data of 35 individuals from a conservation farm were obtained using the Illumina 150 bp paired-end platform. The results of the genetic structure and diversity analyses showed that BHB cattle had mixed Bos taurus and Bos indicus ancestry, close phylogenic relationships with Jiaxian Red and Luxi cattle and abundant genetic diversity. The bulls tested here could be divided into six families. This study presents a comprehensive evaluation of the genetic structure and diversity of the BHB cattle, and lays the theoretical basis for conservation and utilization of the valuable germplasm resource.

Two-step aggregation of gold nanoparticles based on charge neutralization for detection of melamine by colorimetric and surface-enhanced Raman spectroscopy platform.

A colorimetric and surface-enhanced Raman scattering (SERS) signal amplification platform based on 2-step aggregation of gold nanoparticles (AuNP) was constructed for the sensitive detection of melamine. In this study, the positively charged SYBR Green I was used for the first step of aggregation of AuNP, via charge neutralization, to obtain small-sized AuNP aggregates. The positively charged SYBR Green I decreased the negative charges of the surface of AuNP, which was beneficial to the aggregation of AuNP. In addition, the melamine could aggregate AuNP by decreasing the negative charges of the surface of AuNP and self-assemble with each other on the surface of AuNP by hydrogen bonds. Therefore, the second efficient aggregation of small-sized AuNP aggregates could be achieved with melamine at low concentration, resulting in significant signal changes of color and SERS. The sensitivity of a colorimetric (0.60 mg/L) and SERS (0.089 mg/L) platform, based on 2-step aggregation of AuNP, was 15 and 2.2 times higher than that based on 1-step aggregation of AuNP for detecting melamine.

[Successful prediction and the process of the weaning of veno-arterial extracorporeal membrane oxygenation].

The weaning of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is one of the clinical challenges, and hospitals have developed experience-based strategies, so there is still a lack of unified standards and procedures for weaning. This paper discusses this issue from the definition of weaning success, evaluation of patients before weaning, predictive indicators, weaning process, etc. Summarizing research progress and problems so that providing guidance for the development of ECMO in the future, such as perfecting weaning process and putting forward scoring system to predict weaning success and clinical outcome.

[Correlation analysis between lactic, procalcitonin and disease severity in patients with imported malaria from Africa].

Objective: To explore the clinical characteristics, the correlation between lactate, procalcitonin and disease severity of imported malaria from Africa. Methods: The clinical data of 186 patients with imported malaria were collected from January 1, 2018 to April 30, 2021 in the Guangzhou Eighth People's Hospital, Guangzhou Medical University. The general conditions, clinical symptoms, laboratory tests, treatment, and prognosis of the patients were analyzed retrospectively. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of relevant indicators in predicting severe malaria. Results: A total of 186 patients were divided into severe cases (n=48) and non-severe cases (n=138) in this study, of which the mean age was (38.3±10.3) years, 169(90.9%) cases were male, 17(9.1%) cases were female. The main infection species was Plasmodium falciparum, in a total of 166 cases (89.2%). The severe cases were all falciparum malarias. Compared with the non-severe group, the lactic, procalcitonin, white blood cell count and neutrophil count of the severe group were all increased, the differences were all statistically significant (all P<0.01); the percentage of monocytes, red blood cell count, hemoglobin, hematocrit and platelet count were all decreased, the difference were all statistically significant (all P<0.01). The areas under the ROC curves (AUC)(95%CI) of lactate, procalcitonin, red blood cell count, hemoglobin, hematocrit and platelet count for predicting severe malaria was 0.753(0.663-0.844), 0.755(0.670-0.841), 0.782(0.700-0.864), 0.738(0.652-0.823), 0.760(0.676-0.844), 0.778(0.699-0.857), respectively (all P<0.01). When the Youden indexes were at their maximum, the best cut-off value of lactic was 2.29 mmol/L, with sensitivity in predicting of severe malaria was 56.3%, and the specificity was 93.5%; the best cut-off value of procalcitonin was 2.12 µg/L, with sensitivity in predicting of severe malaria was 77.1%, and the specificity was 68.1%. The fatality rate of severe malaria was 4.2% (2/48). Conclusions: Anemia and thrombocytopenia are common indicators for predicting the severity of malaria. Lactic and procalcitonin also have higher predictive value for severe malaria, which could help to identify severe malaria as early as possible, improve the cure rate and reduce the risk of death.

Small bowel obstruction secondary to crab shell bezoar: A case report.

Small bowel obstruction is a common surgical condition that needs surgical intervention if conservative measures fail. Bezoar is a rare aetiology of small bowel obstruction with incidence of 4.5%. The bezoars can be grouped, according to the content, into four common types: phytobezoars, trichobezoars, pharmacobezoars, and lactobezoars. However, unusual bezoars like plastic bezoars and metal bezoars have been reported too. Herein, we report a case of an elderly lady who was treated for small bowel obstruction due to crab shell bezoar. This is the first case reported in literature. Ingestion of large intact pieces of crab shell should be avoided due to the potential of causing small bowel obstruction.

Pneumoperitoneum following an Endoscopic Retrograde Cholangiopancreatography (ERCP): A case report.

Post Endoscopic Retrograde Cholangiopancreatography (ERCP) pneumoperitoneum is commonly associated with perforated viscus but is rarely associated with benign causes. We present a case of 29 years old lady who underwent ERCP, who was found to have benign pneumoperitoneum subsequently. She was treated conservatively and recovered without complication. Although rare, post ERCP pneumoperitoneum of benign causes should be investigated as the course of treatment and outcome differ largely.

COVID-19 in patients with lung cancer.

BACKGROUND: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma.

V-domain Ig-containing suppressor of T-cell activation (VISTA) is an immune checkpoint gene that inhibits anti-tumor immune responses. Since most malignant pleural mesotheliomas do not respond to anti-programmed cell death(-ligand)1 (PD-(L)1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy and given the recent finding of The Cancer Genome Atlas Study that pleural mesothelioma displays the highest expression of VISTA among all cancers studied, we examined VISTA expression in a large pleural mesothelioma cohort. VISTA and PD-L1 immunohistochemistry were performed on tissue microarray of immunotherapy-naive pleural mesotheliomas (254 epithelioid, 24 biphasic and 41 sarcomatoid) and ten whole-tissue sections of benign pleura (VISTA only). Percentages of tumor and inflammatory cells with positive staining were assessed. Optimal prognostic cutoff percentages were determined using maximally selected rank statistics. Overall survival was evaluated using Kaplan-Meier methods and Cox proportional hazard analysis. All benign mesothelium expressed VISTA. Eighty-five percent of 319 and 38% of 304 mesotheliomas expressed VISTA and PD-L1 (88% and 33% of epithelioid, 90% and 43% of biphasic, and 42% and 75% of sarcomatoid), respectively. Median VISTA score was significantly higher in epithelioid (50%) (vs. biphasic [20%] and sarcomatoid [0]) (p < 0.001), while median PD-L1 score was significantly higher in sarcomatoid tumors (20%) (vs. biphasic and epithelioid [both 0%]) (p < 0.001). VISTA and PD-L1 were expressed in inflammatory cells in 94% (n = 317) and 24% (n = 303) of mesothelioma, respectively. Optimal prognostic cutoffs for VISTA and PD-L1 were 40% and 30%, respectively. On multivariable analysis, VISTA and PD-L1 expression in mesothelioma were associated with better and worse overall survival (p = 0.001 and p = 0.002), respectively, independent of histology. In a large cohort of mesothelioma, we report frequent expression of VISTA and infrequent expression of PD-L1 with favorable and unfavorable survival correlations, respectively. These findings may explain poor responses to anti-PD-(L)1 immunotherapy and suggest VISTA as a potential novel target in pleural mesothelioma.

Metabolic disposition of H3B-8800, an orally available small-molecule splicing modulator, in rats, monkeys, and humans.

H3B-8800, a novel orally available modulator of the SF3b complex, which potently and preferentially kills spliceosome-mutant tumor cells, is in clinical development for the treatment of advanced myeloid malignancies. We characterized the pharmacokinetics, metabolism and disposition of H3B-8800 in rats, monkeys and humans.In vitro, H3B-8800 is a substrate of CYP3A4/5, flavin-containing monooxygenases (FMOs) and P-glycoprotein (P-gp), and showed a favorable drug-drug interaction profile as a perpetrator.Following oral dosing of 14C-H3B-8800 in bile-duct cannulated SD rats, 54.7% of the dosed radioactivity was excreted in the bile, with less found in feces (36.8%). The low amount in urine (3.7%), suggests that renal elimination is a minor pathway of clearance for H3B-8800.In Long-Evans rats, radioactivity derived from 14C-H3B-8800 was rapidly absorbed, with the highest distribution in the ocular, metabolic/excretory, and gastrointestinal tract tissues. No radioactivity was detected in the central nervous system.Seven metabolites were observed in human plasma following 4 daily doses of 40 mg H3B-8800. H3B-68736 (N-desmethyl), H3B-77176 (N-oxide), and unchanged H3B-8800 were the prominent components in human plasma, at 27.3%, 18.1%, and 33.2%, respectively, of the total drug-related material in a pooled AUC0-24h sample. The same 7 metabolites were observed in monkey plasma.

Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers.

BACKGROUND: Mutations in human epidermal growth factor receptor 2 (HER2; also known as ERBB2) are found in approximately 2% of lung adenocarcinomas. The frequency and clinical course of brain metastases in this oncogenic subset are ill defined. METHODS: Baseline and subsequent development of brain metastases was evaluated in consecutive patients with HER2-mutant (n = 98), epidermal growth factor receptor (EGFR)-mutant (n = 200), and KRAS-mutant lung cancers (n = 200). RESULTS: At metastatic diagnosis, the odds ratio (ORs) for brain metastases was similar for patients whose tumors harbored HER2 mutations (19%) in comparison with patients with KRAS mutations (24%; OR for HER2 vs KRAS, 0.7; P = .33) but lower compared to patients with EGFR mutations (31%; OR for HER2 vs EGFR, 0.5; P = .03). Patients with lung cancer and HER2 mutations developed more brain metastases on treatment than patients with KRAS mutations (28% vs 8%; hazard ratio [HR], 5.2; P < .001) and trended more than patients with EGFR mutations (28% vs 16%; HR, 1.7; P = .06). Patients with HER2 YVMA mutations also developed more brain metastases on treatment than patients with KRAS mutations (HR, 5.9; P < .001). The median overall survival (OS) was shorter for patients with HER2-mutant (1.6 years; P < .001) or KRAS-mutant lung cancers (1.1 years; P < .001) than patients with EGFR-mutant lung cancers (3.0 years). Brain metastases occurred in 47% of patients with HER2-mutant lung cancers, which imparted shorter OS (HR, 2.7; P < .001). CONCLUSIONS: These data provide a framework for brain imaging surveillance in patients with HER2-mutant lung cancers and underpin the need to develop HER2-targeted agents with central nervous system activity.

Neuropilin-1 drives tumor-specific uptake of chlorotoxin.

BACKGROUND: Chlorotoxin (Cltx) isolated from scorpion venom is an established tumor targeting and antiangiogenic peptide. Radiolabeled Cltx therapeutic (131I-TM601) yielded promising results in human glioma clinical studies, and the imaging agent tozuleristide, is under investigation in CNS cancer studies. Several binding targets have previously been proposed for Cltx but none effectively explain its pleiotropic effects; its true target remains ambiguous and is the focus of this study. METHODS: A peptide-drug conjugate (ER-472) composed of Cltx linked to cryptophycin as warhead was developed as a tool to probe the molecular target and mechanism of action of Cltx, using multiple xenograft models. RESULTS: Neuropilin-1 (NRP1), an endocytic receptor on tumor and endothelial cells, was identified as a novel Cltx target, and NRP1 binding by Cltx increased drug uptake into tumor. Metabolism of Cltx to peptide bearing free C-terminal arginine, a prerequisite for NRP1 binding, took place in the tumor microenvironment, while native scorpion Cltx with amidated C-terminal arginine did not bind NRP1, and instead acts as a cryptic peptide. Antitumor activity of ER-472 in xenografts correlated to tumor NRP1 expression. Potency was significantly reduced by treatment with NRP1 blocking antibodies or knockout in tumor cells, confirming a role for NRP1-binding in ER-472 activity. Higher cryptophycin metabolite levels were measured in NRP1-expressing tumors, evidence of NRP1-mediated enhanced drug uptake and presumably responsible for the superior antitumor efficacy. CONCLUSIONS: NRP1 was identified as a novel Cltx target which enhances tumor drug uptake. This finding should facilitate tumor selection for chlorotoxin-based therapeutics and diagnostics.

PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers.

Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. Results: We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%-49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P < 0.001, n = 78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P < 0.001, n = 62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman's rho=0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9 months (95% CI 1.7-2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. Conclusion: A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.

FV3-like ranavirus infection outbreak in black-spotted pond frogs (Rana nigromaculata) in China.

In April 2016, an outbreak emerged in a cultured population of black-spotted pond frog tadpoles in Shuangliu County, China, whereas tadpoles were suffering from substantial mortality (90%). Principal clinical signs of diseased tadpoles were comprised haemorrhage on their body surface, swollen abdomen with yellow ascites, congestion and swelling of the liver. The diseased tadpole's homogenates tissue were inoculated into epithelioma papulosum cyprini (EPC) cells at 25 °C for 4 days which caused typical cytopathic effect, and the viral titer TCID50 reached 107/0.1 mL. In pathogenicity tests, tadpoles were immersed in 2‰ virus fluid for 8 h, the clinical signs were observed similar to those recognized in naturally infected tadpoles and mortality rate were reached up to 80%, which affirms that the virus was the main cause for this disease. In addition, transmission electron microscopy of EPC cells infected with isolated virus reflected that the virus was in a regular hexagon way (shape) with capsule like structure. The diagonal diameter was recorded 135 ±â€¯8 nm, wherever virus particles were arrayed in crystalline manner in the cytoplasm. The electrophoresis of MCP gene PCR-product showed that the samples of diseased tadpoles, aquaculture water source and isolated virus were all positive. The sequence of the isolate revealed more than 99% similarities to ranavirus based on homology and genetic evolution analysis of the whole MCP gene, and the isolate belongs to FV3-like virus group. This study confirmed that ranavirus was the causative agent of this outbreak, and named the virus as Rana nigromaculata ranavirus (RNRV).

Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3A interacting drugs.

AIMS: Avatrombopag, a thrombopoietin receptor agonist, is a substrate of cytochrome P450 (CYP) 2C9 and CYP3A. We assessed three drug-drug interactions of avatrombopag as a victim with dual or selective CYP2C9/3A inhibitors and inducers. METHODS: This was a three-part, open-label study. Forty-eight healthy subjects received single 20 mg doses of avatrombopag alone or with one of 3 CYP2C9/3A inhibitors or inducers: fluconazole 400 mg once daily for 16 days, itraconazole 200 mg twice daily on Day 1 and 200 mg once daily on Days 2-16, or rifampicin 600 mg once daily for 16 days. Pharmacokinetics, pharmacodynamics (platelet count) and safety of avatrombopag were evaluated. RESULTS: Coadministration of a single 20-mg dose of avatrombopag with fluconazole at steady-state resulted in 2.16-fold increase of AUC of avatrombopag, prolonged terminal elimination phase half-life (from 19.7 h to 39.9 h) and led to a clinically significant increase in maximum platelet count (1.66-fold). Itraconazole had a mild increase on both avatrombopag pharmacokinetics and pharmacodynamics compared to fluconazole. Coadministration of rifampicin caused a 0.5-fold decrease in AUC and shortened terminal elimination phase half-life (from 20.3 h to 9.84 h), but has no impact on maximum platelet count. Coadministration with interacting drugs was found to be generally safe and well-tolerated. CONCLUSIONS: The results from coadministration of fluconazole or itraconazole suggest that CYP2C9 plays a more predominant role in metabolic clearance of avatrombopag than CYP3A. To achieve comparable platelet count increases when avatrombopag is coadministered with CYP3A and CYP2C9 inhibitors, an adjustment in the dose or duration of treatment is recommended, while coadministration with strong inducers is not currently recommended.

The Impact of the Shallow-Trench Isolation Effect on Flicker Noise of Source Follower MOSFETs in a CMOS Image Sensor.

The flicker noise of source follower transistors is the dominant noise source in image sensors. This paper reports a systematic study of the shallow trench isolation effect in transistors with different sizes under high temperature conditions that correspond to the quantity of empty defect sites. The effects of shallow trench isolation sidewall defects on flicker noise characteristics are investigated. In addition, the low-frequency noise and subthreshold swing degrade simultaneously in accordance to the device gate width scaling. Both serious subthreshold leakage and considerable noise can be attributed to the high trap density near the STI edge. Consequently, we propose a coincidental relationship between the noise level and the subthreshold characteristic; its trend is identical to the experiments and simulation results.

Effectiveness of a Self Help Cognitive Behavioural Treatment Program for Problem Gamblers: A Randomised Controlled Trial.

The study aimed to strengthen the scarce literature on self-help treatments for Problem Gambling (PG) by comparing the effectiveness of a Self-Help Cognitive Behavioral Treatment (SHCBT) program (n = 23) with a 6-week Waitlist condition (n = 32) in problem gamblers. Participants were community volunteers with gambling problems and were randomly allocated to the Waitlist and treatment conditions. Results showed significant improvements at post-treatment in gambling behaviors including frequency of gambling, average amount gambled per day and PG symptoms as well as a number of gambling correlates including psychological states (e.g., depression, anxiety and stress), gambling cognitions, gambling urges, gambling related self-efficacy, satisfaction with life, and quality of life among those who completed the SHCBT program, when compared with the waitlist condition. The effect size (partial η 2) ranged from .25 to .57 for all assessed outcomes that showed significant improvement from pre- to post-treatment. It was concluded that a self-help CBT program can be beneficial for treating community problem gamblers.

Molecular characterization of Moniezia sichuanensis in captive musk deer (Moschus berezovskii).

The musk deer (Moschus berezovskii) is an economically important species from which musk is extracted and used in perfumes and medicines. Cestodes (parasitic flatworms) of the genus Moniezia are important parasites that infect this endangered species and can cause high mortality in young deer. In 1982, Moniezia (S.) sichuanensis sp. nov. was described from a specimen obtained from wild musk deer. The new species was distinct from the other described species of Moniezia by the sawtooth-shaped interproglottidal glands, the thick vagina and the absence of a cirrus spine. In the present study, 12 cestodes collected from musk deer were examined morphologically and confirmed to be M. sichuanensis. Molecular characterization was performed by amplifying and comparing the internal transcribed spacer 1 (ITS1) and 5.8S rRNA gene (ITS1-5.8S) of ribosomal DNA with available sequences from other Moniezia species. The amplified sequences ranged from 761 to 764 bp and similarity ranged from 98.7-100%, compared to 67.8-92.4% with other Moniezia spp. Construction of a phylogenetic tree using the neighbour-joining method indicated that all 12 ITS1-5.8S sequences formed a single clade, confirming M. sichuanensis as a separate species. This study provides novel molecular insight into M. sichuanensis that could prove useful for future diagnosis and control of monieziasis in musk deer.