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Purpose: Standard automated perimetry (SAP) is the gold standard for detecting and monitoring visual field (VF) defects in glaucoma, but frequent re-testing due to unreliable results increase the burden on this frequently used service. This study aims to assess the reliability of the Humphrey visual field (HVF) test in glaucoma-suspect patients with no previous SAP experience and to determine the effect of a VF test educational video on reliability.Study design: The study was conducted as a full cycle audit.Methods: The audit cycle was carried out in four phases: pre-intervention audit, intervention, monitoring, and post-intervention audit. The pre-intervention audit was carried out from January 2020 to May 2020 and the post-intervention audit was carried out from September 2020 to December 2020. The intervention was in the form of a VF test educational video. A post-video assessment pertaining to the contents of the video was given to patients in the intervention group to complete after they watched the video. The results were then tabulated and analysed.Results: The pre-intervention audit showed that only 66.7% of glaucoma-suspect patients with no previous SAP experience had reliable HVF tests. Post-intervention, HVF reliability improved to 87.5% of patients. Based on the reliability parameters, the main reason for the HVF test being classified as unreliable in both the pre- and post-intervention was fixation loss greater than 20% in 36 (90%) and 11 (73.3%) patients, respectively. There were 76.9% of patients with unreliable fields who had < 4 correct answers on the post-video assessment; all patients who had > 4 correct answers had reliable HVF results.Conclusion: HVF reliability performance in glaucoma-suspect patients improved with the introduction of a pre-test educational video. It is a simple and inexpensive method which may reduce the need for repeat HVF tests for those with unreliable tests.

There are few biomarkers to reflect the physiological conditions for substance misuse. In this study, autonomic nervous and cardiovascular parameters were measured for participants in deferred prosecution programs. The goal of this study is to develop significant biomarkers of the above subjects and enhance their motivation to join further substance misuse disorder treatment program. This study recruited 34 participants with a mean age of 35.1 years. The participants spent approximately five minutes filling in the basic information form and another five minutes filling in the Pittsburgh Sleep Quality Index (PSQI). Blood pressure, heart rate, and heart rate variability data were also measured. Their sleep quality was measured by the Pittsburgh Sleep Quality Inventory (PSQI) with an average score of 8.6 and average systolic and diastolic pressure measured of 116.1 ( standard deviation SD = 13.7 ) and 77.9 mmHg ( SD = 8.1 ) during resting, respectively. Average heartbeat rates are 90.4 beats per minute ( SD = 17.0 ); and average low-frequency power ratio is 56.4% ( SD = 19.8 %). Of the participants, 35% exhibited a low-frequency power rate below 30% and above 70%. The average biological HRV age of the participants was 46.0 years ( SD = 22.9 ), which was significantly older than their average actual age ( p = 0.002 ∗ ∗ ). The biological HRV age of the participants is 10 years older than their own actual age, and it effectively reflects the physiological conditions of participants in deferred prosecution programs. These physiological parameters, especially the biological HRV age, can be used in future treatment for substance use disorder counseling programs to increase the illness insight of program participants and increase their motivation to join further substance misuse disorder treatment program.

Adenosine-to-inosine (A-to-I) RNA editing is the most common posttranscriptional editing to create somatic mutations and increase proteomic diversity. However, the functions of the edited mutations are largely underexplored. To identify novel targets in lung adenocarcinoma (LUAD), we conducted a genome-wide somatic A-to-I RNA editing analysis of 23 paired adjacent normal and LUAD transcriptomes and identified 26,280 events, including known nonsynonymous AZIN1-S367G and novel RHOAiso2 (RHOA isoform 2)-R176G, tubulin gamma complex associated protein 2 (TUBGCP2)-N211S, and RBMXL1-I40 M mutations. We validated the edited mutations in silico in multiple databases and in newly collected LUAD tissue pairs with the SEQUENOM MassARRAY® and TaqMan PCR Systems. We selected RHOAiso2-R176G due to its significant level, isoform-specificity, and being the most common somatic edited nonsynonymous mutation of RHOAiso2 to investigate its roles in LUAD tumorigenesis. RHOAiso2 is a ubiquitous but low-expression alternative spliced isoform received a unique Alu-rich exon at the 3' RHOA mRNA to become an editing RNA target, leading to somatic hypermutation and protein diversity. Interestingly, LUAD patients harboring the RHOAiso2-R176G mutation were associated with aberrant RHOA functions, cancer cell proliferation and migration, and poor clinical outcomes in transcriptome analysis. Mechanistically, RHOAiso2-R176G mutation-expressing LUAD cells potentiate RHOA-guanosine triphosphate (GTP) activity to phosphorylate ROCK1/2 effectors and enhance cell proliferation and migration in vitro and increase tumor growth in xenograft and systemic metastasis models in vivo. Taken together, the RHOAiso2-R176G mutation is a common somatic A-to-I edited mutation of the hypermutated RHOA isoform 2. It is an oncogenic and isoform-specific theranostic target that activates RHOA-GTP/p-ROCK1/2 signaling to promote tumor progression.

IntroductionCryptococcal meningitis (CM) is the most common systemic fungal infection in patients with HIV infection. Rapid diagnosis and timely initiation of antifungal therapy are key to reducing mortality rate associated with CM. This study aims to evaluate the ability of four different diagnostic tests (Gram stain, India ink, and two types of commercial lateral flow assay [LFA]) to identify CM-positive patients and to compare the sensitivity and specificity of these tests.MethodsThis was a prospective cross-sectional study on diagnostic tests accuracy conducted in Northern Malawi. The target population was HIV-infected adult patients presenting with features of meningitis. Four types of diagnostic tests were conducted: India ink, Gram stain, and two types of commercial lateral flow assay (LFA) (Immy, Inc., OK, USA and Dynamiker Biotechnology (Tianjin) Co., Ltd), Singapore). Culture was conducted as the reference standard.ResultsA total of 265 samples were collected. The rate of positive CM detection ranged from 6.4% (using India ink) to 14.3% (using LFA). India ink exhibited the lowest sensitivity of 54.8% (95% confidence interval [CI]: 36.0%–72.7%), followed by Gram stain (61.3%; 95% CI: 42.2%–78.2%). The Dynamiker LFA exhibited the highest sensitivity of 100.0% (95% CI: 90.0%–100.0%) but a lower specificity (97.0%; 93.9%–98.8%) compared to the Immy LFA (98.3%; 95% CI: 95.7%–99.5%). ConclusionLFA diagnostic methods have the potential to double the detection rate of CM-positive patients in resource-limited countries such as Malawi. As such, LFAs should be considered to become the main diagnostic tests used for CM diagnostics in these countries. Our data indicate that LFAs may be the best method for diagnosing CM and exhibits the highest diagnostic accuracy as it has shown that it outperforms cell culture, the current gold standard.

In this study, a combinatorial AlN–TiN nanocolumn composite composition spread (library) was fabricated using reactive sputtering, and the formation of TixAl1–xN at the interface between AlN and TiN thickness gradients was investigated. Moreover, the intimate coupling between TixAl1–xN, AlN, and TiN, which enhanced the piezo-related properties of AlN, was analyzed. Location 1 [(1 − x)AlN − xTiN, 0

The effects of the grain size and thickness of Sn films on the kinetics of spontaneous Sn whisker growth have been quantitatively analyzed separately. The results reveal that the length and diameter of the whiskers are related to the parameters of the Sn film. A thicker film has a stronger influence on the whisker morphology than does the grain size. When the biaxial stress in the film reached a steady state, the growth rate was dependent on the grain size and thickness of the film. An equation is proposed to calculate the spontaneous growth rate of Sn whiskers in correlation with the dimension and microstructure of the Sn film. Spontaneous Sn whisker growth can be suppressed by increasing the thickness and grain size of the film.

Background Integrated community case management (CCM) has led to reductions in child mortality in Malawi resulting from illnesses such as malaria, pneumonia, and diarrhea. However, adherence to CCM guidelines is often poor, potentially leading to inappropriate clinical decisions and poor outcomes. We determined the impact of an e-CCM app on the referral, reconsultation, and hospitalization rates of children presenting to village clinics in Malawi. Objective We determined the impact of an electronic version of a smartphone-based CCM (e-CCM) app on the referral, reconsultation, and hospitalization rates of children presenting to village clinics in Malawi. Methods We used a stepped-wedge, cluster-randomized trial to compare paper-based CCM (control) with and without the use of an e-CCM app on smartphones from November 2016 to February 2017. A total of 102 village clinics from 2 districts in northern Malawi were assigned to 1 of 6 clusters, which were randomized on the sequencing of the crossover from the control phase to the intervention phase as well as the duration of exposure in each phase. Children aged ≥2 months to Results A total of 6965 children were recruited—49.11% (3421/6965) in the control phase and 50.88% (3544/6965) in the intervention phase. After adjusting for calendar time, children in the intervention phase were more likely to be urgently referred to a higher-level health facility than children in the control phase (odds ratio [OR] 2.02, 95% CI 1.27-3.23; P=.003). Overall, children in the intervention arm had lower odds of attending a repeat health surveillance assistant consultation (OR 0.45, 95% CI 0.34-0.59; P Conclusions The addition of e-CCM decision support by using smartphones led to a greater proportion of children being referred to higher-level facilities, with no apparent increase in hospital admissions or repeat consultations in village clinics. Our findings provide support for the implementation of e-CCM tools in Malawi and other low- and middle-income countries with a need for ongoing assessments of effectiveness and integration with national digital health strategies. Trial Registration ClinicalTrials.gov NCT02763345; https://clinicaltrials.gov/ct2/show/NCT02763345

BACKGROUND Integrated community case management (CCM) has led to reductions in child mortality in Malawi resulting from illnesses such as malaria, pneumonia, and diarrhea. However, adherence to CCM guidelines is often poor, potentially leading to inappropriate clinical decisions and poor outcomes. We determined the impact of an e-CCM app on the referral, reconsultation, and hospitalization rates of children presenting to village clinics in Malawi. OBJECTIVE We determined the impact of an electronic version of a smartphone-based CCM (e-CCM) app on the referral, reconsultation, and hospitalization rates of children presenting to village clinics in Malawi. METHODS We used a stepped-wedge, cluster-randomized trial to compare paper-based CCM (control) with and without the use of an e-CCM app on smartphones from November 2016 to February 2017. A total of 102 village clinics from 2 districts in northern Malawi were assigned to 1 of 6 clusters, which were randomized on the sequencing of the crossover from the control phase to the intervention phase as well as the duration of exposure in each phase. Children aged ≥2 months to RESULTS A total of 6965 children were recruited—49.11% (3421/6965) in the control phase and 50.88% (3544/6965) in the intervention phase. After adjusting for calendar time, children in the intervention phase were more likely to be urgently referred to a higher-level health facility than children in the control phase (odds ratio [OR] 2.02, 95% CI 1.27-3.23; P=.003). Overall, children in the intervention arm had lower odds of attending a repeat health surveillance assistant consultation (OR 0.45, 95% CI 0.34-0.59; PP=.002), but after adjusting for time, these differences were not significant (P=.07 for consultation; P=.30 for hospital admission). CONCLUSIONS The addition of e-CCM decision support by using smartphones led to a greater proportion of children being referred to higher-level facilities, with no apparent increase in hospital admissions or repeat consultations in village clinics. Our findings provide support for the implementation of e-CCM tools in Malawi and other low- and middle-income countries with a need for ongoing assessments of effectiveness and integration with national digital health strategies. CLINICALTRIAL ClinicalTrials.gov NCT02763345; https://clinicaltrials.gov/ct2/show/NCT02763345

In this paper, we study the rarefaction wave case of the regularized Riemann problem proposed by Chu, Hong and Lee in SIMA MMS, 2020, for compressible Euler equations with a small parameter $$\nu $$ . The solutions $$\rho _\nu $$ and $$v_\nu $$ of such problems stand for the density and velocity of gas flow near vacuum, respectively. We show that as $$\nu $$ approaches 0, the solutions $$\rho _\nu $$ and $$v_\nu $$ converge to the solutions $$\rho $$ and v, respectively, of pressureless compressible Euler equations in $$L^1$$ sense. In addition, the $$L^1$$ convergence rates of these physical quantities in terms of $$\nu $$ are also investigated. The $$L^1$$ convergences and convergence rates are proved by two facts. One is to invent an a priori estimate coupled with the iteration method to the high-order derivatives of Riemann invariants so that we obtain the uniform boundedness of $$\partial _{x}^{i} \rho _{\nu }$$ ( $$i=0,1,2$$ ) and $$\partial _{x}^{j} v_{\nu }$$ ( $$j=0,1,2,3$$ ) on the requisite regions. The other is about convexity of characteristic curves, which is used to estimate the distances among characteristic curves in terms of $$\nu $$ . These theoretic results are also supported by numerical simulations.

(Bi0.25Te0.75)2Te3 (p-Bi2Te3) is thermoelectric material that can harvest waste heat into useful electric power. A severe reaction between p-Bi2Te3 and Sn-based solder decreases the reliability of thermoelectric modules. Sn/p-Bi2Te3 and Sn3.0Ag0.5Cu (SAC305)/p-Bi2Te3 with and without electroless Co-P at the interfaces were investigated in this study. Without a Co-P layer, brittle SnTe, Sn3Sb2, and Bi precipitates formed at the interface. A thin layer of SnTe after reflow results in growth of a layer-type Sn3Sb2 instead of a strip-like Sn3Sb2. The addition of a Co-P layer to both systems successfully inhibited the formation of brittle intermetallic compounds. Shear test results confirmed that the Co-P diffusion barrier also effectively increased the joint strength.

Co-sputtered Cu(Ti) films on SiO2 substrates exhibit the phase separation of Cu and Ti after annealing at 400 °C. In this study, the diffusion behavior and phase separation were investigated using X-ray photoelectron spectroscopy (XPS), grazing angle incident X-ray diffraction (GIXRD), and transmission electron microscopy (TEM). The GIXRD pattern revealed that the Cu peak replaced the Cu2O peak after annealing. The formation Gibbs free energy of TiO2 (−812 kJ) was lower than that of Cu2O (−109 kJ). The calculated diffusivity of Ti in Cu was one order of magnitude smaller than that of Cu in Cu. Thus, Ti was the dominant diffusing species that accumulated near SiO2, whereas Cu atoms were segregated near the surface. A few Cu islands were initially formed, and these Cu islands grew and formed continuous Cu layers after long-term annealing at 400 °C. The Cu(Ti) films were bonded face-to-face through thermo-compression. The nearly oxide-free Cu yields strong Cu bonding and a void-free interface.

Targeting tumor angiogenesis is a common strategy against human hepatocellular carcinoma (HCC). However, identification of molecular targets as biomarker for elevating therapeutic efficacy is critical to prolong HCC patient survival. Here, we showed that EIF3C (eukaryotic translation initiation factor 3 subunit C) is upregulated during HCC tumor progression and associated with poor patient survival. Expression of EIF3C did not alter proliferation and expression of other tumor progressive genes such as HIF1A, TGFβ1 and VEGF, but reduced cell migration in HCC cells. Nevertheless, expression of EIF3C in HCC cells significantly increase secretion of extracellular exosomes confirmed by increased exosomes labelling by PKH26 fluorescent dye, vesicles in exosome size detected by electronic microscopy and nanoparticle tracking analysis, and expression of divergent exosome markers. The EIF3C-increased exosomes were oncogenic to potentiate tumor angiogenesis via tube formation of HUVEC cells and growth of vessels by plugs assays on nude mice. Subcutaneous inoculation of EIF3C-exosomes mixed with Huh7 HCC cells not only promoted growth of vessels but also increased expression of EIF3C in tumors. Conversely, treatment of exosome inhibitor GW4869 reversed aforementioned oncogenic assays. We identified EIF3C activated expression of S100A11 involved in EIF3C-exosome increased tube formation in angiogenesis. Simultaneous high expression of EIF3C and S100A11 in human HCC tumors for RNA level in TCGA and protein level by IHC are associated with poor survival of HCC patients. Collectively, our results demonstrated that EIF3C overexpression is a potential target of angiogenesis for treatment with exosome inhibitor or S100A11 reduction to suppress HCC angiogenesis and tumorigenesis.

The effects of growth temperature on the microstructure, transport and optoelectronic properties of a series of Al-doped ZnO (AZO) films with thickness of ∼30 nm deposited on polished silicon-(100) and glass substrates by the atomic layer deposition (ALD) were investigated. By adopting an in-situ doping growth scheme the critical length effect associated with adjacent Al2O3 layers commonly encountered in previous ALD growth schemes was avoided and effective Al-doping was achieved with the growth temperature ranging from 100 °C to 300 °C. Experimental results showed that, in general, increasing the growth temperature would result in much improved film crystallinity and carrier mobility, with the average transmittance in the visible wavelength range being exceeding 95% in all cases. In particular, for AZO films grown at 300 °C, an unprecedented mobility of 136 cm2V−1s−1 was obtained, comparing to the typical values of 50–60 cm2V−1s−1 reported previously. The resistivity of these 300 °C films (ρ ≈ 6 × 10−4 Ω-cm), nevertheless, is slightly higher than that of some highly-doped ZnO (ρ ≈ 2–4 × 10−4 Ω-cm) prepared by sputtering methods. The secondary ion mass spectroscopy (SIMS) analyses revealed that hydrogen incorporation is the key in reducing the charge trap density and, hence, resulting in much enhanced carrier mobility. The present results promise a keen competitiveness of AZO with the indium tin oxide (ITO) film for thin-film-transistor (TFT) as well as in photovoltaic device applications.

Flow-rate interruption (FRI) atomic layer deposition (ALD) technique was adopted to fabricate AZO/Al 2 O 3 /AZO thin film on a ZnO nanorod array template at low temperature. The high quality amorphous dielectric Al 2 O 3 layer was deposited at 50 °C. The template with an average of 0.73 μm in length was made by a simple hydrothermal method on a c −plane sapphire with an AZO seed layer. Using Polystyrene (PS) microspheres were served as a mask to form vertical and well-aligned ZnO nanostructures. Field-emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) images show ALD to have achieved good step coverage and thickness control in the thin films structure coating. The capacitance density of the arrayed template nanocapacitor increased more than 100% than those of the thin film capacitor at an applied frequency of 10 kHz. These results suggest that the ZnO-arrayed template could enhance energy storage capability by providing significant surface area. This structure provides a concept for high surface-area nanocapacitor applications.

It is described a simple method for the ipso-nitration of aryl substituted 2-halothiophenes, which produce 2-nitrothiophenes with regioselectivity is described. The method involves AgNO3 as the nitration reagent without further additives to conduct the transformation.

Through a simple hydrothermal method, well-aligned and periodic honeycomb-like ZnO nanorod arrays were fabricated on a c-plane sapphire with an aluminum-doped ZnO (AZO) seed layer. Vertical and highly ordered ZnO nanostructures with the orientation were synthesized by employing a self-assembled monolayer of polystyrene (PS) microspheres as a mask. The optimal growth conditions allowed the growth of only one rod in the confined space between the microspheres. A ϕ-scan exhibited six-fold symmetry, which indicates a favorable epitaxial relationship between the ZnO nanorods, seed layer, and c-plane sapphire substrate. The epitaxial relation is as follows: [0001]ZnO∥[0001]AZO∥[0001]c-planesapphire. These results indicate that the AZO seed layer acts as a buffer layer that can relax the strain between ZnO and c-plane sapphire generated by the large lattice mismatch of 18%. The size of the resulting ZnO nanorods of diameter 20–90 nm could be tuned by varying the concentration of the solution, pH, and duration of reaction. The large aspect ratio of the ZnO nanorod arrays can serve as a template for high-surface-area applications.

BackgroundIntegrated community case management (CCM) has led to reductions in child mortality in Malawi from illnesses such as malaria, pneumonia and diarrhoea. However, adherence to CCM guidelines is often poor, potentially leading to inappropriate clinical decisions and outcomes. We determined the impact of an electronic version of CCM (eCCM) application on referral, re-consultation and hospitalization rates of children presenting to village clinics in Malawi.MethodsA stepped-wedge cluster-randomized trial compared paper-based CCM (control) with and without use of an eCCM app on smartphones from November 2016 to April 2017.A total of 102 village clinics from two districts in Northern Malawi were assigned to one of six clusters which were randomized to the sequencing of crossover from the control to the intervention phases, as well as the duration of exposure in each phase. Children ≥2 months to ResultsA total of 6965 children were recruited, 3421 in the control and 3544 in the intervention phase. After adjusting for calendar time, children in the intervention phase were more likely to be urgently referred to a higher-level health facility compared with children in the control phase (OR 2.02, 95% CI 1.27-3.23; p0.05).ConclusionsAddition of eCCM decision support led to a greater proportion of children being referred to higher-level facilities, with no apparent increase in hospital admissions or repeat consultations in village clinics. Our findings provide support for the implementation of eCCM tools in Malawi and other Low and Middle Income Countries (LMIC), with a need for ongoing assessment of effectiveness and integration with national digital health strategies.Trial registrationhttp://ClinicalTrials.gov; NCT02763345. Registered 3 May 2016

Treatment of 1-bromo-2,2-dichloro-3-trimethylsilylcyclopropane with 5 equiv of CsF resulted in the formation of a chlorocyclopropenyl cation, which, under different conditions, further reacted with fluoride ion selectively to generate 3,3-difluorocyclopropene or 1-chloro-3-fluorocyclopropene. The Diels-Alder reactions of fluorinated cyclopropene derivatives with DPIBF yielded only exo or exo-anti adducts. On treatment of fused tricyclic cis-1-chloro-3-fluorocyclopropane derivative with n-BuLi, 3-fluorocyclopropene derivative was formed, which underwent Diels-Alder reaction with DPIBF to give an endo-endo adduct. Additionally, fused tricyclic 3,3-difluorocyclopropane and cis-1-chloro-3-fluorocyclopropane derivatives were underwent ring-opening reaction of cyclopropane by BF3●Et2O, respectively, and 1,4-diphenylnaphthalene derivatives were obtained.

Mitochondrial–nuclear incompatibility has a major role in reproductive isolation between species. However, the underlying mechanism and driving force of mitochondrial–nuclear incompatibility remain elusive. Here, we report a pentatricopeptide repeat‐containing (PPR) protein, Ccm1, and its interacting partner, 15S rRNA, to be involved in hybrid incompatibility between two yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus . S. bayanus ‐Ccm1 has reduced binding affinity for S. cerevisiae ‐15S rRNA, leading to respiratory defects in hybrid cells. This incompatibility can be rescued by single mutations on several individual PPR motifs, demonstrating the highly evolvable nature of PPR proteins. When we examined other PPR proteins in the closely related Saccharomyces sensu stricto yeasts, about two‐thirds of them showed detectable incompatibility. Our results suggest that fast co‐evolution between flexible PPR proteins and their mitochondrial RNA substrates may be a common driving force in the development of mitochondrial–nuclear hybrid incompatibility. ![][1] Mitochondrial–nuclear incompatibility can cause reproductive isolation between species. This study shows that fast co‐evolution between flexible PPR proteins and their mitochondrial RNA targets represents a common driving force in the development of hybrid incompatibility. [1]: /embed/graphic-1.gif