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The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called “quasiparticle poisoning”. Both superconducting qubits and low threshold dark matter calorimeters have observed excess bursts of quasiparticles or phonons that decrease in rate with time. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events. Identifying sources of quasiparticle poisoning is an active problem in superconducting quantum circuits. Here the authors show that the rate of quasiparticle bursts in a cryogenic calorimeter decreases by two orders of magnitude in a low-stress suspended state, suggesting stress as a key mechanism.

A previous study indicated that mutations in the transmembrane protease serine 3 (TMPRSS3) gene, which encodes a transmembrane serine protease, cause nonsyndromic hearing loss (NSHL). This was the first description of a serine protease involved in hearing loss (HL). In Taiwan, however, data on the TMPRSS3 gene’s association with NSHL is still insufficient. In this study, we described 10 mutations of TMPRSS3 genes found in 14 patients after screening 230 children with NSHL. The prevalence of the TMPRSS3 mutation appeared to be 6.09% (14/230). Of the 10 mutations, three were missense mutations: c.239G>A (p.R80H), c.551T>C (p.L184S), and 1253C>T (p.A418V); three were silent mutations, and four were mutations in introns. To determine the functional importance of TMPRSS3 mutations, we constructed plasmids carrying TMPRSS3 mutations of p.R80H, p.L184S, and p.A418V. TMPRSS3 function can be examined by secretory genetic assay for site-specific proteolysis (sGASP) and Xenopus oocyte expression system. Our results showed that p.R80H, p.L184S, and p.A418V TMPRSS3 mutations gave ratios of 19.4%, 13.2%, and 27.6%, respectively, via the sGASP system. Moreover, these three TMPRSS3 mutations failed to activate the epithelial sodium channel (ENaC) in the Xenopus oocyte expression system. These results indicate that the p.R80H, p.L184S, and p.A418V missense mutations of TMPRSS3 resulted in greatly diminishing the proteolytic activity of TMPRSS3. Our study provides information for understanding the importance of TMPRSS3 in the NSHL of Taiwanese children and provides a novel molecular explanation for the role of TMPRSS3 in HL.

Phonon-mediated Kinetic Inductance Detectors (KIDs) on silicon substrates have demonstrated both O (10) eV energy resolution and mm position resolution when used as particle detectors, making them strong candidates for instrumenting next-generation rare event experiments such as in looking for dark matter. Previous work has demonstrated the performance of an 80-KID array on a Si wafer; however, current energy resolution measurements show a ∼ 25 × difference between otherwise identical KIDs—between 5 and 125 eV on energy absorbed by the KID. Here, we use a first principles approach and attempt to identify the drivers behind the variation. In particular, we analyze a subset of 8 KIDs using the unique approach of pulsing neighboring KIDs to generate signals in the target. We tentatively identify differences in quality factor as the likely culprit for the observed differences.

Purpose. To investigate the efficacy and safety of switching to 0.0015% tafluprost ophthalmic solution with reduced benzalkonium chloride (BAK) on primary open-angle glaucoma (POAG) patients with corneal disorders under 0.005% latanoprost treatment. Material and Methods. This was a single-arm, open-label, switching study on adult POAG patients treated with latanoprost 0.005% for more than 3 months, with corneal disorders but no dry eye therapy. All patients were switched to tafluprost 0.0015% and followed up for 3 months. The primary outcome was the change in fluorescein staining score (National Eye Institute/Industry [NEI] score) at the end of the study. Secondary outcomes included changes in intraocular pressure (IOP), tear break-up time (TBUT), hyperemia score, and other ocular and nonocular adverse events. Results. Of the 20 patients initially enrolled, 17 patients, all with POAG, completed the study. At the end of the study, the mean NEI score significantly decreased by 1.8 ± 2.2 (p<0.01). No significant changes in IOP were observed (12.8 ± 4.6 mmHg at baseline vs. 12.3 ± 4.0 mmHg on visit 2; p=0.470). TBUT increased by 1.2 ± 1.7 seconds (p<0.05). The proportions of patients with no sign of hyperemia on the bulbar and palpebral conjunctiva increased from 58.5% to 64.7% at baseline (before switching to tafluprost treatment) to 94.1% and 94.1%, respectively, after switching to tafluprost treatment. Dry eye sensation scores were significantly reduced (p<0.05), while other ocular symptom scores did not change significantly. Conclusion. Switching to tafluprost 0.0015% significantly improved fluorescein staining score, TBUT, and conjunctival hyperemia while maintaining IOP control among POAG patients with corneal disorders.

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985-2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985-1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool.

Coxsackievirus (CV)-B5 is a common human enterovirus reported worldwide; swine vesicular disease virus (SVDV) is a porcine variant of CV-B5. To clarify the transmission dynamics and molecular basis of host switching between CV-B5 and SVDV, we analysed and compared the VP1 and partial 3D pol gene regions of these two viruses. Spatiotemporal dynamics of viral transmission were estimated using a Bayesian statistical inference framework. The detected selection events were used to analyse the key molecules associated with host switching. Analyses of VP1 sequences revealed six CV-B5 genotypes (A1–A4 and B1–B2) and three SVDV genotypes (I–III). Analyses of partial 3D pol revealed five clusters (A–E). The genotypes evolved sequentially over different periods, albeit with some overlap. The major hub of CV-B5 transmission was in China whereas the major hubs of SVDV transmission were in Italy. Network analysis based on deduced amino acid sequences showed a diverse extension of the VP1 structural protein, whereas most sequences were clustered into two haplotypes in the partial 3D pol region. Residue 178 of VP1 showed four epistatic interactions with residues known to play essential roles in viral host tropism, cell entry, and viral decoating.

Background: Preserved prostaglandin analogs (PGAs) have been linked to ocular surface disease (OSD). While the benefits of preservative-low (PL) or -free (PF) Tafluprost (Santen Inc., Japan) were reported in real-world studies in Western countries, this is the first study in Asia to assess the effectiveness and safety of switching from preserved PGA to PL or PF-Tafluprost. Methods: We conducted a meta-analysis on studies that included adults (>18 years of age) with a Corneal Fluorescein Staining Score (CFS) >1. These individuals had switched to PL or PF-tafluprost after using a preserved PGA therapy for at least 3 months for glaucoma and were identified from Santen's tafluprost study database. A total of six studies from South Korea, Philippines, Malaysia, Singapore, Thailand, Taiwan were pooled for analysis. Results: An intraocular pressure (IOP) reduction of 5.9% (0.91 mmHg) was seen in 265 patients. However, this result was not statistically significant (95% CI: -3.64, 1.81; Figure 1). Among 132 patients, a 47.9% reduction in the CFS (95% CI: -3.65, -1.91) was seen. Tear film break-up (n=183) significantly increased by 1.06 seconds (95% CI: 0.65, 1.47). In 88 patients, the bulbar conjunctiva score decreased by -0.46 (95% CI: -0.81, -0.10) and palpebral conjunctiva score decreased by -0.42 (95% CI: -0.670.17). One or more new adverse reactions were reported in 3% of the individuals after switching. Conclusion: Tafluprost IOP reduction is comparable to other PGAs, with significant improvements in the ocular surface and minimal adverse reactions which were already previously reported. Keywords: ocular surface disease, glaucoma, preserved prostaglandins, tafluprost, PGA, preservative-free, preservative-low, Asian population, meta analysis

Background/aims To investigate the risk of developing retinal vein occlusion (RVO) in patients with systemic lupus erythematosus (SLE). Methods In this retrospective population-based cohort study, 6756 patients with SLE and 40 536 controls without SLE (1:6) were selected from the Taiwan National Health Insurance Research Database claims from 2001 to 2006. Results The incidence of RVO was 3.46-times higher in the SLE group than in controls (5.61 vs 1.62 per 10 000 person-years) (adjusted HR=3.883, 95% CI 2.299 to 6.558) calculated using Cox proportional hazard regression. Age was an independent risk factor for RVO, with adjusted HRs of 4.842 for individuals aged ≥50 years compared with those 0–49 years. For each age subgroup, the risk of RVO was significantly higher only in the 0–49-year-old SLE group than in controls. In the 0–49-year-old SLE group the incidence of developing RVO was 7.92 times higher (95% CI 3.60 to 17.45) in the SLE group than in the 0–49-year-old controls. In women with SLE, the incidence of developing RVO was 3.33-times higher (95% CI 1.88 to 5.90) than in female controls. Conclusions SLE was significantly associated with an increased risk of developing RVO.

Significance Psoriasis, a common immune-mediated disease, affects approximately 2 % of the population worldwide. Sudden sensorineural hearing loss (SSNHL) might be a manifestation of systemic vascular involvement in autoimmune disease. However, to the best of our knowledge, there is no systematic English-language examination of the risk of SSNHL in patients with psoriasis. Objectives We tested the hypothesis that psoriasis is a risk factor for developing SSNHL. Methods Using Taiwan’s National Health Insurance Research Database, we conducted a retrospective cohort study to compare patients diagnosed with psoriasis from January 1, 2001 through December 31, 2006 ( n  = 28,817) with gender-, age-, and comorbidities-matched controls ( n  = 28,817). We followed each patient until the end of 2011 and evaluated the incidence of SSNHL for at least 6 years after the initial psoriasis diagnosis. Results The incidence of SSNHL was 1.51 times higher in the psoriasis cohort than in the control cohort (7.12 vs 4.73 per 10,000 person-years). Using Cox proportional hazard regressions, the adjusted hazard ratio (AHR) was 1.51 (95 % confidence interval [CI] 1.18–1.93). Comorbid hypertension was an independent risk factor for SSNHL (AHR 1.49; 95 % CI 1.05–2.13). However, the incidence rate ratios (IRRs) for each comorbidity subgroup in the psoriasis and control cohorts were not significantly different. Conclusions and Relevance Psoriasis was significantly associated with a higher risk of developing SSNHL. We suggest that physicians advise patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL.

Connexins (CXs), as a component of gap junction channel, are homologous four transmembrane-domain proteins, with numerous studies confirming their auditory functions. Among a cohort of patients having incurred non-syndromic hearing loss, we identified two novel missense mutations, p.R15G and p.L23H, in the GJC3 gene encoding CX30.2/CX31.3, as causally related to hearing loss in previous study. However, the functional alteration of CX30.2/CX31.3 caused by the mutant GJC3 gene remains unknown. In this study, we compared the intracellular distribution of mutant CX30.2/CX31.3 (p.R15G and p.L23H) with the wild-type (WT) protein in HeLa cells and the effect of the mutant protein had on those cells. Analytical results indicated that p.R15G and p.L23H mutant exhibited continuous staining along apposed cell membranes in the fluorescent localization assay, which is the same with the WT. Moreover, ATP release (hemichannel function) is less in HeLa cells carrying mutant GJC3 genes than those of WT expressing cells. We believe that although p.R15G and p.L23H mutants do not decrease the trafficking of CX proteins, mutations in GJC3 genes result in a loss of hemichannel function of CX30.2/CX31.3 protein, possibly causing hearing loss. Results of this study provide a novel molecular explanation for the role of GJC3 in hearing loss.