Privacy-Oriented Technique for COVID-19 Contact Tracing (PROTECT) Using Homomorphic Encryption: Design and Development Study.

BACKGROUND: Various techniques are used to support contact tracing, which has been shown to be highly effective against the COVID-19 pandemic. To apply the technology, either quarantine authorities should provide the location history of patients with COVID-19, or all users should provide their own location history. This inevitably exposes either the patient's location history or the personal location history of other users. Thus, a privacy issue arises where the public good (via information release) comes in conflict with privacy exposure risks. OBJECTIVE: The objective of this study is to develop an effective contact tracing system that does not expose the location information of the patient with COVID-19 to other users of the system, or the location information of the users to the quarantine authorities. METHODS: We propose a new protocol called PRivacy Oriented Technique for Epidemic Contact Tracing (PROTECT) that securely shares location information of patients with users by using the Brakerski/Fan-Vercauteren homomorphic encryption scheme, along with a new, secure proximity computation method. RESULTS: We developed a mobile app for the end-user and a web service for the quarantine authorities by applying the proposed method, and we verified their effectiveness. The proposed app and web service compute the existence of intersections between the encrypted location history of patients with COVID-19 released by the quarantine authorities and that of the user saved on the user's local device. We also found that this contact tracing smartphone app can identify whether the user has been in contact with such patients within a reasonable time. CONCLUSIONS: This newly developed method for contact tracing shares location information by using homomorphic encryption, without exposing the location information of patients with COVID-19 and other users. Homomorphic encryption is challenging to apply to practical issues despite its high security value. In this study, however, we have designed a system using the Brakerski/Fan-Vercauteren scheme that is applicable to a reasonable size and developed it to an operable format. The developed app and web service can help contact tracing for not only the COVID-19 pandemic but also other epidemics.

Improved Electrical Characteristics of Gallium Oxide/P-Epi Silicon Carbide Static Induction Transistors with UV/Ozone Treatment Fabricated by RF Sputter.

In this study, static induction transistors (SITs) with beta gallium oxide (ß-Ga2O3) channels are grown on a p-epi silicon carbide (SiC) layer via radio frequency sputtering. The Ga2O3 films are subjected to UV/ozone treatment, which results in reduced oxygen vacancies in the X-ray photoelectron spectroscopy data, lower surface roughness (3.51 nm) and resistivity (319 Ω·cm), and higher mobility (4.01 cm2V-1s-1). The gate leakage current is as low as 1.0 × 10-11 A at VGS = 10 V by the depletion layer formed between n-Ga2O3 and p-epi SiC at the gate region with a PN heterojunction. The UV/O3-treated SITs exhibit higher (approximately 1.64 × 102 times) drain current (VDS = 12 V) and on/off ratio (4.32 × 105) than non-treated control devices.

Influence of Gas Annealing on Sensitivity of AlN/4H-Sic-Based Temperature Sensors.

In this study, the physical and electrical characteristics of an AlN/4H-SiC Schottky barrier diode-based temperature sensor annealed in various gas atmospheres were investigated. An aluminum nitride (AlN) thin film was deposited on a 4H-SiC substrate via radio-frequency sputtering followed by annealing in N2 or O2 gas. The chemical composition of the film was determined by X-ray photoelectron spectroscopy (XPS) before and after annealing, and its electrical properties were evaluated by plotting a current-voltage (I-V) curve. The voltage-temperature (V-T) characteristics of the sensor were extracted from the current-voltage-temperature (I-V-T) plots constructed in the temperature range between 475 and 300 K in steps of 25 K. Sensitivities of 9.77, 9.37, and 2.16 mV/K were obtained for the as-grown, N2-annealed, and O2-annealed samples, respectively.

Mitigation of Single-Event Effects in SiGe-HBT Current-Mode Logic Circuits.

It has been known that negative feedback loops (internal and external) in a SiGe heterojunction bipolar transistors (HBT) DC current mirrors improve single-event transient (SET) response; both the peak transient current and the settling time significantly decrease. In the present work, we demonstrate how radiation hardening by design (RHBD) techniques utilized in DC bias blocks only (current mirrors) can also improve the SET response in AC signal paths of switching circuits (e.g., current-mode logic, CML) without any additional hardening in those AC signal paths. Four CML circuits both with and without RHBD current mirrors were fabricated in 130 nm SiGe HBT technology. Two existing RHBD techniques were employed separately in the current mirrors of the CML circuits: (1) applying internal negative feedback and (2) adding a large capacitor in a sensitive node. In addition, these methods are also combined to analyze the overall SET performance. The single-event transients of the fabricated circuits were captured under the two-photon-absorption laser-induced single-event environment. The measurement data clearly show significant improvements in SET response in the AC signal paths of the CML circuits by using the two radiation hardening techniques applied only in DC current mirrors. The peak output transient current is notably reduced, and the settling time upon a laser strike is shortened significantly.

Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Epidemiologic knowledge regarding noncardiovascular and all-cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence-based healthcare guidelines. OBJECTIVES: To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all-cause mortality in AH and pHCM cats. ANIMALS: A total of 1730 client-owned cats (722 AH, 1008 pHCM) from 21 countries. METHODS: Retrospective, multicenter, longitudinal, cohort study. Long-term health data were extracted by medical record review and owner/referring veterinarian interviews. RESULTS: Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight-loss-vomiting-diarrhea-anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All-cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all-cause survival was significantly shorter in pHCM (P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: All-cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.

Characterization of Australian Labradoodle dystrophinopathy.

In humans, dystrophin mutations cause the X-linked recessive disorder known as Duchenne muscular dystrophy (DMD). These mutations result in skeletal and cardiac muscle damage with mortality increasingly associated with cardiomyopathy. We have identified a novel dystrophin mutation in exon 21 in a line of Australian Labradoodles; affected dogs develop progressive clinical signs including poor weight gain and weight loss, gait abnormalities, exercise intolerance, skeletal muscle atrophy, macroglossa, ptyalism, dysphagia, kyphosis, and a plantigrade stance. Echocardiographic abnormalities include hyperechoic foci in the left ventricular papillary muscles, septal hypokinesis, and decreased left ventricular systolic and diastolic volume and internal diameter. Holter recordings found a Mobitz type II second-degree atrioventricular (AV) block in one affected dog. Analysis of phosphocreatine-to-ATP ratios (PCr/ATP) (obtained via cardiac magnetic resonance imaging and spectroscopy evaluation), found no statistically significant difference in the mean PCr/ATP between groups. Histopathologic skeletal muscle changes included fibrofatty infiltration, myocyte degeneration, necrosis, and regeneration, lymphohistiocytic inflammation, and mineralization; cardiac changes were limited to a focal area of mineralization adjacent to the sinoatrial node in the dog with a second-degree AV block. Due to rapidly progressive clinical signs, a severe phenotype, and potential for cardiac involvement, Australian Labradoodle dystrophinopathy may be a useful model to further study DMD pathogenesis.

A prospective, randomized, double-blind, placebo-controlled pilot study of sacubitril/valsartan (Entresto) in dogs with cardiomegaly secondary to myxomatous mitral valve disease.

BACKGROUND: The effects of sacubitril/valsartan (S/V) on the renin-angiotensin-aldosterone system (RAAS) in dogs with cardiomegaly secondary to myxomatous mitral valve disease (MMVD) are currently unknown. OBJECTIVES: To determine the pharmacodynamic effects of S/V on the RAAS, natriuretic peptide concentrations, systolic arterial pressure (SAP), tests of renal function, and serum electrolyte concentrations in dogs with cardiomegaly secondary to MMVD. ANIMALS: Thirteen client-owned dogs weighing 4-15 kg with American College of Veterinary Internal Medicine (ACVIM) Stage B2 MMVD. METHODS: Prospective, randomized, double-blind, placebo-controlled pilot study of S/V in dogs with ACVIM Stage B2 MMVD. RESULTS: Thirteen dogs were recruited: S/V (n = 7) and placebo (n = 6). The median percentage increase in urinary aldosterone to creatinine ratio (UAldo : C) between day 0 and day 30 was significantly lower in the S/V group (12%; P = .032) as compared with the placebo group (195%). The median percentage decrease of NT-proBNP concentration from day 0 to day 30 was not statistically different between groups (P = .68). No statistical differences were seen in echocardiographic, thoracic radiographic, SAP, or serum biochemical test results measured at any time point between groups. No adverse events were observed for dogs in either group. CONCLUSION AND CLINICAL IMPORTANCE: Sacubitril/valsartan may provide a new pharmaceutical method to effectively inhibit the RAAS in dogs with ACVIM Stage B2 MMVD.

Genome-wide sequencing and quantification of circulating microRNAs for dogs with congestive heart failure secondary to myxomatous mitral valve degeneration.

OBJECTIVE To characterize expression profiles of circulating microRNAs via genome-wide sequencing for dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve degeneration (MMVD). ANIMALS 9 healthy client-owned dogs and 8 age-matched client-owned dogs with CHF secondary to MMVD. PROCEDURES Blood samples were collected before administering cardiac medications for the management of CHF. Isolated microRNAs from plasma were classified into microRNA libraries and subjected to next-generation sequencing (NGS) for genome-wide sequencing analysis and quantification of circulating microRNAs. Quantitative reverse transcription PCR (qRT-PCR) assays were used to validate expression profiles of differentially expressed circulating microRNAs identified from NGS analysis of dogs with CHF. RESULTS 326 microRNAs were identified with NGS analysis. Hierarchical analysis revealed distinct expression patterns of circulating microRNAs between healthy dogs and dogs with CHF. Results of qRT-PCR assays confirmed upregulation of 4 microRNAs (miR-133, miR-1, miR-let-7e, and miR-125) and downregulation of 4 selected microRNAs (miR-30c, miR-128, miR-142, and miR-423). Results of qRT-PCR assays were highly correlated with NGS data and supported the specificity of circulating microRNA expression profiles in dogs with CHF secondary to MMVD. CONCLUSIONS AND CLINICAL RELEVANCE These results suggested that circulating microRNA expression patterns were unique and could serve as molecular biomarkers of CHF in dogs with MMVD.

Balloon dilation of congenital supravalvular pulmonic stenosis in a dog.

Percutaneous balloon valvuloplasty is considered the standard of care for treatment of valvular pulmonic stenosis, a common congenital defect in dogs. Supravalvular pulmonic stenosis is a rare form of pulmonic stenosis in dogs and standard treatment has not been established. Although, there have been reports of successful treatment of supravalvular pulmonic stenosis with surgical and stenting techniques, there have been no reports of balloon dilation to treat dogs with this condition. Here, a case of supravalvular pulmonic stenosis diagnosed echocardiographically and angiographically in which a significant reduction in pressure gradient was achieved with balloon dilation alone is presented.

Hyperkalemia secondary to renal hypoperfusion in a dog with third-degree atrioventricular block.

OBJECTIVE: To demonstrate a critical role of artificial cardiac pacing to normalize severe bradyarrhythmia-induced hyperkalemia in a dog with third-degree atrioventricular (AV) block. CASE SUMMARY: A dog was presented for evaluation of severe hyperkalemia and bradyarrhythmia. ECG revealed third-degree AV block with heart rate of 10-20 min, which was lower than usual ventricular escape rate. The etiology of severe hyperkalemia was considered secondary to significantly decreased renal perfusion and potassium excretion as a result of poor cardiac output caused by the AV block. Since potassium disorders may lead to life-threatening conditions such as cardiopulmonary arrest, artificial cardiac pacing was immediately pursued. Within 1 hour, serum potassium concentration was normalized, which confirmed that severe hyperkalemia occurred primarily due to third-degree AV block. The dog was then treated with permanent pacemaker implantation. A recheck evaluation 3-month post pacemaker implantation showed normal serum potassium concentration and the dog was clinically healthy. NEW OR UNIQUE INFORMATION PROVIDED: This report describes hyperkalemia secondary to significantly decreased cardiac output and renal hypoperfusion caused by third-degree AV block. The authors propose that artificial cardiac pacing must be considered as an emergency treatment for bradyarrhythmia-induced hyperkalemia, which ultimately restores cardiac output and renal perfusion and normalizes serum potassium concentration.

Aortopulmonary window characterized with two- and three-dimensional echocardiogram in a dog.

Aortopulmonary window is a rare congenital anomaly, resulting from incomplete septation of the truncus arteriosus into the aorta and the pulmonary artery during embryogenesis. The utility of three-dimensional (3D) echocardiogram has not been previously reported in dogs with aortopulmonary windows. The authors demonstrate the diagnostic potentials of 3D echocardiogram and its ability to more completely define the anatomical features of aortopulmonary window in a dog when compared to two-dimensional imaging. Ultimately 3D echocardiogram was considered to provide information critical to determining the feasibility of beating heart surgical correction in this case.

Enhanced thermoelectric power in nanopatterned carbon nanotube film.

Despite the small or near-zero Seebeck coefficient of metallic nanotubes, a nanotube film can be readily scaled up in length. Thus so can its thermoelectric power. In this work, we inserted a nanomesh pattern into a carbon nanotube film by using an anodized aluminum oxide membrane as an etching mask. We found that by patterning densely packed nanoscale holes into the nanotube film, its total thermoelectric power can be further increased, by as much as 30% (from 29 to 39 µV K(-1)). We present this finding, attributed to electron localization due to nanopatterning, as indicative of the potential of a new degree of freedom.

Evaluation of a fibrillin 2 gene haplotype associated with hip dysplasia and incipient osteoarthritis in dogs.

OBJECTIVE: To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs. ANIMALS: 1,551 dogs. Procedures-Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever-Greyhound crossbreeds. RESULTS: The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage. CONCLUSIONS AND CLINICAL RELEVANCE: The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.

Developmental cardiac hypertrophy in a mouse model of prolidase deficiency.

BACKGROUND: Hypertrophic cardiomyopathy, characterized by thickened ventricular walls and reduced ventricular chamber volume, is a common cause of sudden cardiac death in young people. Most inherited forms result from mutations in genes encoding sarcomeric proteins. METHODS: Histologic analysis identified embryonic cardiac hypertrophy in dark-like mutant mice. BrdU analysis was performed to measure proliferation and cardiomyocytes were isolated to measure cell size. The dark-like mutation was identified by positional cloning. RESULTS: The dark-like mutation causes cardiomyocyte hypertrophy due to loss-of-function of peptidase d (Pepd), which encodes prolidase, a cytosolic enzyme that recycles proline for collagen re-synthesis. Prolidase deficiency is a rare autosomal recessive disease in humans with a broad phenotypic spectrum not reported to include heart defects, but a conserved role for prolidase in heart development was confirmed by morpholino knockdown in zebrafish. We tested the hypothesis that loss of prolidase function disrupts collagen-mediated integrin signaling and determined that the levels of several key integrin transducers were reduced in the hearts of dark-like mutant embryos. CONCLUSIONS: This work identifies dark-like mice as a model of prolidase deficiency that will be valuable for studying the role of proline metabolism in normal physiology and disease processes, and suggests that integrin signaling may regulate the onset of hypertrophic cardiac growth.

The long (and winding) road to gene discovery for canine hip dysplasia.

Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.