Virtual assessment of coronal balance prior to bone resection with the MAKO robotic-assisted system accurately predicts final balance in TKA.

Total knee arthroplasty (TKA) has traditionally relied on the surgeon's judgement and manual instruments to determine balance. The MAKO robotic system (Stryker Ltd, Kalamazoo, MI, USA) allows assessment of virtual compartmental gaps from CT-derived bone models intra-operatively as a predictor of soft tissue balance that will be achieved, prior to any bony resection. This study aims to assess the accuracy of this pre-resection balancing technique in determining the resultant final soft tissue balance of the TKA. A consecutive prospective cohort of 2027 Robotic-Assisted TKAs (RATKA) were performed between January'17 and March'22. Osteophytes were removed; initial virtual gaps on the virtual bone model were measured at 10° and 90° of flexion prior to bone resections. Optimization of the virtual component positions was then made and final pre-resection gaps were measured. The gaps were then re-assessed post-implantation and compared to the final pre-resection values. Virtual balancing in extension within 1 mm was achieved in 95% of cases. Of those, 98% maintained coronal balance within 1 mm after implantation, with 1.5% requiring a coronal plane soft tissue release. Inability to virtually balance a TKA within 2 mm prior to bone resection resulted in a soft tissue release in 44.4% of cases. The absolute values of the final gaps achieved were a mean of 1.3 mm greater than virtual gaps. The ability to balance a knee on the virtual bone model prior to bone resection, in conjunction with robotic-assisted execution of TKA, consistently achieves a balanced knee after component implantation.

Evolved explainable classifications for lymph node metastases.

A novel evolutionary approach for Explainable Artificial Intelligence is presented: the "Evolved Explanations" model (EvEx). This methodology combines Local Interpretable Model Agnostic Explanations (LIME) with Multi-Objective Genetic Algorithms to allow for automated segmentation parameter tuning in image classification tasks. In this case, the dataset studied is Patch-Camelyon, comprised of patches from pathology whole slide images. A publicly available Convolutional Neural Network (CNN) was trained on this dataset to provide a binary classification for presence/absence of lymph node metastatic tissue. In turn, the classifications are explained by means of evolving segmentations, seeking to optimize three evaluation goals simultaneously. The final explanation is computed as the mean of all explanations generated by Pareto front individuals, evolved by the developed genetic algorithm. To enhance reproducibility and traceability of the explanations, each of them was generated from several different seeds, randomly chosen. The observed results show remarkable agreement between different seeds. Despite the stochastic nature of LIME explanations, regions of high explanation weights proved to have good agreement in the heat maps, as computed by pixel-wise relative standard deviations. The found heat maps coincide with expert medical segmentations, which demonstrates that this methodology can find high quality explanations (according to the evaluation metrics), with the novel advantage of automated parameter fine tuning. These results give additional insight into the inner workings of neural network black box decision making for medical data.

Explainable Artificial Intelligence for Bias Detection in COVID CT-Scan Classifiers.

PROBLEM: An application of Explainable Artificial Intelligence Methods for COVID CT-Scan classifiers is presented. MOTIVATION: It is possible that classifiers are using spurious artifacts in dataset images to achieve high performances, and such explainable techniques can help identify this issue. AIM: For this purpose, several approaches were used in tandem, in order to create a complete overview of the classificatios. METHODOLOGY: The techniques used included GradCAM, LIME, RISE, Squaregrid, and direct Gradient approaches (Vanilla, Smooth, Integrated). MAIN RESULTS: Among the deep neural networks architectures evaluated for this image classification task, VGG16 was shown to be most affected by biases towards spurious artifacts, while DenseNet was notably more robust against them. Further impacts: Results further show that small differences in validation accuracies can cause drastic changes in explanation heatmaps for DenseNet architectures, indicating that small changes in validation accuracy may have large impacts on the biases learned by the networks. Notably, it is important to notice that the strong performance metrics achieved by all these networks (Accuracy, F1 score, AUC all in the 80 to 90% range) could give users the erroneous impression that there is no bias. However, the analysis of the explanation heatmaps highlights the bias.

[Current status of HIV self-testing application].

HIV self-testing is a key measure and strategy to expand the coverage of HIV testing in key populations, which has great value in application and high acceptance in key populations. The World Health Organization (WHO) issued the Guidelines on HIV self-testing and partner notification in 2016 to support the application of HIV self-testing and provide specific guidance for countries and organizations to develop corresponding public health policies for the purpose of improving the accessibility and utilization of HIV diagnostics. HIV self-testing has been promoted in many countries and has achieved great results. This article provides an overview of the current domestic and international HIV self-testing policies, intervention models, the use of self-testing kits, the accuracy of self-testing kits, and the application of pre- and post-testing counseling services to provide reference for the further improvement of HIV self-testing in China.

Zones, spots, and planetary-scale waves beating in brown dwarf atmospheres.

Brown dwarfs are massive analogs of extrasolar giant planets and may host types of atmospheric circulation not seen in the solar system. We analyzed a long-term Spitzer Space Telescope infrared monitoring campaign of brown dwarfs to constrain cloud cover variations over a total of 192 rotations. The infrared brightness evolution is dominated by beat patterns caused by planetary-scale wave pairs and by a small number of bright spots. The beating waves have similar amplitudes but slightly different apparent periods because of differing velocities or directions. The power spectrum of intermediate-temperature brown dwarfs resembles that of Neptune, indicating the presence of zonal temperature and wind speed variations. Our findings explain three previously puzzling behaviors seen in brown dwarf brightness variations.

Evolving Spiking Neural Networks for Recognition of Aged Voices.

The aging of the voice, known as presbyphonia, is a natural process that can cause great change in vocal quality of the individual. This is a relevant problem to those people who use their voices professionally, and its early identification can help determine a suitable treatment to avoid its progress or even to eliminate the problem. This work focuses on the development of a new model for the identification of aging voices (independently of their chronological age), using as input attributes parameters extracted from the voice and glottal signals. The proposed model, named Quantum binary-real evolving Spiking Neural Network (QbrSNN), is based on spiking neural networks (SNNs), with an unsupervised training algorithm, and a Quantum-Inspired Evolutionary Algorithm that automatically determines the most relevant attributes and the optimal parameters that configure the SNN. The QbrSNN model was evaluated in a database composed of 120 records, containing samples from three groups of speakers. The results obtained indicate that the proposed model provides better accuracy than other approaches, with fewer input attributes.

Analysis and Classification of Voice Pathologies Using Glottal Signal Parameters.

The classification of voice diseases has many applications in health, in diseases treatment, and in the design of new medical equipment for helping doctors in diagnosing pathologies related to the voice. This work uses the parameters of the glottal signal to help the identification of two types of voice disorders related to the pathologies of the vocal folds: nodule and unilateral paralysis. The parameters of the glottal signal are obtained through a known inverse filtering method, and they are used as inputs to an Artificial Neural Network, a Support Vector Machine, and also to a Hidden Markov Model, to obtain the classification, and to compare the results, of the voice signals into three different groups: speakers with nodule in the vocal folds; speakers with unilateral paralysis of the vocal folds; and speakers with normal voices, that is, without nodule or unilateral paralysis present in the vocal folds. The database is composed of 248 voice recordings (signals of vowels production) containing samples corresponding to the three groups mentioned. In this study, a larger database was used for the classification when compared with similar studies, and its classification rate is superior to other studies, reaching 97.2%.

ON THE COMPOSITION OF YOUNG, DIRECTLY IMAGED GIANT PLANETS.

The past decade has seen significant progress on the direct detection and characterization of young, self-luminous giant planets at wide orbital separations from their host stars. Some of these planets show evidence for disequilibrium processes like transport-induced quenching in their atmospheres; photochemistry may also be important, despite the large orbital distances. These disequilibrium chemical processes can alter the expected composition, spectral behavior, thermal structure, and cooling history of the planets, and can potentially confuse determinations of bulk elemental ratios, which provide important insights into planet-formation mechanisms. Using a thermo/photochemical kinetics and transport model, we investigate the extent to which disequilibrium chemistry affects the composition and spectra of directly imaged giant exoplanets. Results for specific "young Jupiters" such as HR 8799 b and 51 Eri b are presented, as are general trends as a function of planetary effective temperature, surface gravity, incident ultraviolet flux, and strength of deep atmospheric convection. We find that quenching is very important on young Jupiters, leading to CO/CH4 and N2/NH3 ratios much greater than, and H2O mixing ratios a factor of a few less than, chemical-equilibrium predictions. Photochemistry can also be important on such planets, with CO2 and HCN being key photochemical products. Carbon dioxide becomes a major constituent when stratospheric temperatures are low and recycling of water via the H2 + OH reaction becomes kinetically stifled. Young Jupiters with effective temperatures ≲700 K are in a particularly interesting photochemical regime that differs from both transiting hot Jupiters and our own solar-system giant planets.

Discovery and spectroscopy of the young jovian planet 51 Eri b with the Gemini Planet Imager.

Directly detecting thermal emission from young extrasolar planets allows measurement of their atmospheric compositions and luminosities, which are influenced by their formation mechanisms. Using the Gemini Planet Imager, we discovered a planet orbiting the ~20-million-year-old star 51 Eridani at a projected separation of 13 astronomical units. Near-infrared observations show a spectrum with strong methane and water-vapor absorption. Modeling of the spectra and photometry yields a luminosity (normalized by the luminosity of the Sun) of 1.6 to 4.0 × 10(-6) and an effective temperature of 600 to 750 kelvin. For this age and luminosity, "hot-start" formation models indicate a mass twice that of Jupiter. This planet also has a sufficiently low luminosity to be consistent with the "cold-start" core-accretion process that may have formed Jupiter.

Classification of vocal aging using parameters extracted from the glottal signal.

This article proposes and evaluates a method to classify vocal aging using artificial neural network (ANN) and support vector machine (SVM), using the parameters extracted from the speech signal as inputs. For each recorded speech, from a corpus of male and female speakers of different ages, the corresponding glottal signal is obtained using an inverse filtering algorithm. The Mel Frequency Cepstrum Coefficients (MFCC) also extracted from the voice signal and the features extracted from the glottal signal are supplied to an ANN and an SVM with a previous selection. The selection is performed by a wrapper approach of the most relevant parameters. Three groups are considered for the aging-voice classification: young (aged 15-30 years), adult (aged 31-60 years), and senior (aged 61-90 years). The results are compared using different possibilities: with only the parameters extracted from the glottal signal, with only the MFCC, and with a combination of both. The results demonstrate that the best classification rate is obtained using the glottal signal features, which is a novel result and the main contribution of this article.

Laboratory diagnosis and transmissibility of bovine viral diarrhea virus from a bull with a persistent testicular infection.

Recently, in the United States, a dairy bull was diagnosed as the second confirmed case of persistent testicular infection (PTI) with bovine viral diarrhea virus (BVDV). The first objective of this study was to evaluate the testing methodologies currently used by the artificial insemination industry in order to improve the detection of bulls with PTI. This study evaluated the impact of multiple factors ([1] sample tested, [2] sample handling, [3] assay used, and [4] assay methodology) on the sensitivity of detection of BVDV. The second objective of this study was to evaluate the transmissibility of BVDV from the bull through casual or sexual contact. Results from this study indicate that straws of semen should be transported to the diagnostic laboratory in liquid nitrogen dry shippers. PCR proved to be a more sensitive assay than virus isolation; however, certain PCR protocols exhibited greater diagnostic sensitivity than others. Insemination with cryopreserved semen from this infected bull caused viral transmission to a seronegative heifer resulting in viremia and seroconversion. After 42 months of age, the bull appeared to clear the infection. In conclusion, this bull validates that natural exposure to a 1a strain of BVDV can result in a unique PTI causing contamination of semen with detectable infectious virus. Appropriate handling and testing of samples is necessary in order to detect bulls exhibiting PTI. Additionally, PTI with BVDV may potentially be cleared after an extended duration.

Cluster of Legionnaires disease cases caused by Legionella longbeachae serogroup 1, Scotland, August to September 2013.

We report six confirmed cases of Legionnaires' disease in Scotland caused by Legionella longbeachae serogroup 1, identified over a four-week period in August­September 2013. All cases required admission to hospital intensive care facilities. All cases were amateur gardeners with frequent exposure to horticultural growing media throughout their incubation period. L. longbeachae was identified in five samples of growing media linked to five cases. Product tracing did not identify a common product or manufacturer.

Effect of treatment with a cationic antiviral compound on acute infection with bovine viral diarrhea virus.

Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen capable of causing disease affecting multiple body systems. Previous studies have shown 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) effectively prevents BVDV infection in cell culture. The aim of this project was to assess the efficacy of DB772 for the prevention of acute BVDV infection. Four calves seronegative to BVDV were treated with DB772 and another 4 calves were treated with diluent only on the same dosing schedule. Each calf was subsequently challenged intranasally with BVDV. Virus was isolated consistently from untreated calves on days 4 to 8, while treated calves remained negative by virus isolation during this period. Azotemia was exhibited by all treated calves on day 4 resulting in the euthanasia of 1 calf on day 10 and the death of another on day 13. Virus was isolated from the 2 remaining treated calves on day 14 or 21. On day 21, both remaining treated calves and all 4 untreated calves had anti-BVDV antibody titers > 1:2048. This pilot study indicates that DB772 temporarily prevented acute disease due to BVDV, but carries a significant concern of renal toxicity.

Le virus de la diarrhée virale bovine (BVDV) est un agent pathogène bovin largement répandu capable de causer une pathologie affectant de nombreux systèmes organiques. Des études antérieures ont démontré que le 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phényl] dihydrochlorure furan (DB772) empêche efficacement l'infection par le BVDV en culture cellulaire. L'objectif de ce projet était d'évaluer l'efficacité du DB772 à prévenir une infection aiguë par le BVDV. Quatre veaux séronégatifs pour le BVDV ont été traités avec du DB772 et quatre autres veaux ont été traités avec uniquement du diluant en suivant la même cédule de traitement. Chaque veau a par la suite été infecté par voie intranasale avec du BVDV. Du virus a été isolé de manière constante à partir des veaux non-traités des jours 4 à 8, alors que les veaux traités sont demeurés négatifs pour l'isolement viral durant cette période. Une azotémie a été notée chez tous les veaux traités au jour 4 ce qui entraina l'euthanasie d'un veau au jour 10 et le décès d'un autre au jour 13. Du virus fut isolé à partir des deux veaux traités restant au jour 14 ou 21. Au jour 21, les deux veaux traités restant et les quatre veaux non-traités avaient des titres d'anticorps anti-BVDV > 1:2048. Cette étude pilote montre que le DB772 a empêché temporairement une maladie aiguë due au BVDV, mais laisse entrevoir de sérieuses inquiétudes quant à sa toxicité rénale.(Traduit par Docteur Serge Messier).

Mutations induced in the NS5B gene of bovine viral diarrhea virus by antiviral treatment convey resistance to the compound.

Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen for which there is no specific therapeutic agent. A previous study using 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) to treat calves persistently infected with BVDV resulted in a decrease in the viral load of infected calves but treatment resulted in the rapid selection of drug-resistant mutant isolates. In this article we describe three mutations found in the mutant isolates associated with in vivo and in vitro resistance to DB772. All three mutations are found in the NS5B which functions as the RNA-dependent-RNA-polymerase during viral replication. Growth curves for the mutant isolates were not largely different from those of wild-type isolates when cultured in the absence of DB772. Thus, DB772 appears to act by binding to the specified domain but binding is disrupted or inhibited by the described mutation.

Immunology of chronic BVDV infections.

Bovine viral diarrhea virus can maintain prolonged infections within immunoprivileged sites after an otherwise transient infection of a cow, calf, or bull. Various sites provide unique niches for viral replication which are not susceptible to the complete surveillance commonly provided by the bovine immune system. Evidence indicates that pestiviral infections may be significantly prolonged within ovarian tissue, testicular tissue, central nervous system tissue, and circulating white blood cells. Within avascular portions of the ovarian follicle, granulosa cells and oocytes may maintain BVDV infections which cannot be attacked by cell-mediated immunity. When infections occur within seminiferous tubules in testicular tissue, similar protection from the immune system is provided for BVDV by the blood-testes barrier. Likewise, the blood-brain barrier has been hypothesized to provide protection for BVDV in a case involving neuropathology associated with immunohistochemical detection of BVDV. Furthermore, infections of circulating white blood cells may perturb their stimulation of an adaptive immune response and facilitate chronic infection of these cells. Thus, BVDV has demonstrated an ability to maintain prolonged viral infections in immunoprivileged sites within its natural host. The role of chronic infections in maintaining and disseminating BVDV within the cattle population and heterologous host species remains to be fully understood.

Efficacy of an antiviral compound to inhibit replication of multiple pestivirus species.

Pestiviruses are economically important pathogens of livestock. An aromatic cationic compound (DB772) has previously been shown to inhibit bovine viral diarrhea virus (BVDV) type 1 in vitro at concentrations lacking cytotoxic side effects. The aim of this study was to determine the scope of antiviral activity of DB772 among diverse pestiviruses. Isolates of BVDV 2, border disease virus (BDV), HoBi virus, pronghorn virus and Bungowannah virus were tested for in vitro susceptibility to DB772 by incubating infected cells in medium containing 0, 0.006, 0.01, 0.02, 0.05, 0.1, 0.2, 0.39, 0.78, 1.56, 3.125, 6.25, 12.5 or 25µM DB772. The samples were assayed for the presence of virus by virus isolation and titration (BDV and BVDV 2) or PCR (HoBi, pronghorn and Bungowannah viruses). Cytotoxicity of the compound was assayed for each cell type. Complete inhibition of BVDV 2, BDV, and Pronghorn virus was detected when DB772 was included in the culture media at concentrations of 0.20µM and higher. In two of three tests, a concentration of 0.05µM DB772 was sufficient to completely inhibit HoBi virus replication. Bungowannah virus was completely inhibited at a concentration of 0.01µM DB772. Thus, DB772 effectively inhibits all pestiviruses studied at concentrations >0.20µM. As cytotoxicity is not evident at these concentrations, this antiviral compound potentially represents an effective preventative or therapeutic for diverse pestiviruses.

Reproductive and economic impact following controlled introduction of cattle persistently infected with bovine viral diarrhea virus into a naive group of heifers.

The reproductive impact following controlled introduction of animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) was evaluated in BVDV-naive heifers. Heifers were randomly allocated into two groups: an unexposed control herd (n = 34) and a herd exposed to five persistently infected (PI) animals for 7 mo, beginning 50 days before the breeding season (n = 34). Initiation of the BVDV-challenge was timed to mimic either direct contact with PI calves born in the previous calving season or accidental introduction of PI herd additions prior to the breeding season. The PI animals represented BVDV Types 1a (n = 3), 1b (n = 1) and 2 (n = 1). Two BVDV-free, seropositive bulls were used in each group for 78 days breeding seasons. In both groups, 33 of 34 heifers became pregnant, with similar distribution of fetal ages. Two heifers in each group aborted (etiology undetermined). In addition, one calf was born dead and one calf died 3 days post-partum in the BVDV-exposed group. One calf in the unexposed group died 4 mo post-partum. No calves, including the stillborn calf and the two calves that died prior to weaning, were persistently infected with BVDV. In summary, introduction of PI cattle to a group of BVDV-naive heifers 50 days prior to the breeding season did not negatively impact reproductive performance. To the contrary, the active immunity that developed following field exposure to BVDV provided effective reproductive and fetal protection during the breeding season and subsequent gestations, despite continuous exposure to PI animals until approximately midgestation. Although BVDV can have potentially devastating reproductive effects, timing of infection is a critical determinant in the outcome of a BVDV infection. A controlled breeding season with introduction of herd additions at less critical reproductive time points can mitigate the negative reproductive health consequences of BVDV.

Protective effects against abortion and fetal infection following exposure to bovine viral diarrhea virus and bovine herpesvirus 1 during pregnancy in beef heifers that received two doses of a multivalent modified-live virus vaccine prior to breeding.

OBJECTIVE: To determine whether administration of 2 doses of a multivalent, modified-live virus vaccine prior to breeding of heifers would provide protection against abortion and fetal infection following exposure of pregnant heifers to cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) and cattle with acute bovine herpesvirus 1 (BHV1) infection. DESIGN: Randomized controlled clinical trial. ANIMALS: 33 crossbred beef heifers, 3 steers, 6 bulls, and 25 calves. PROCEDURES: 20 of 22 vaccinated and 10 of 11 unvaccinated heifers became pregnant and were commingled with 3 steers PI with BVDV type 1a, 1b, or 2 for 56 days beginning 102 days after the second vaccination (administered 30 days after the first vaccination). Eighty days following removal of BVDV-PI steers, heifers were commingled with 3 bulls with acute BHV1 infection for 14 days. RESULTS: After BVDV exposure, 1 fetus (not evaluated) was aborted by a vaccinated heifer; BVDV was detected in 0 of 19 calves from vaccinated heifers and in all 4 fetuses (aborted after BHV1 exposure) and 6 calves from unvaccinated heifers. Bovine herpesvirus 1 was not detected in any fetus or calf and associated fetal membranes in either treatment group. Vaccinated heifers had longer gestation periods and calves with greater birth weights, weaning weights, average daily gains, and market value at weaning, compared with those for calves born to unvaccinated heifers. CONCLUSIONS AND CLINICAL RELEVANCE: Prebreeding administration of a modified-live virus vaccine to heifers resulted in fewer abortions and BVDV-PI offspring and improved growth and increased market value of weaned calves.

Inactivation at various temperatures of bovine viral diarrhea virus in beef derived from persistently infected cattle.

Bovine viral diarrhea virus (BVDV) is a pestivirus that is enzootic in most cattle populations throughout the world. This virus is present throughout the body of persistently infected (PI) cattle. Previous research has not assessed the cooking temperature at which BVDV in meat from PI cattle can be inactivated. Therefore, muscle tissue from 6 PI cattle was harvested, refrigerated, frozen, and heated to various internal temperatures. The concentration of virus present was determined by virus isolation. Average cell culture infective doses (50% endpoint; CCID(50)) of BVDV per gram of frozen, uncooked meat from PI cattle were 10(5.85) CCID(50)/g of whole cuts and 10(6.02) CCID(50)/g of ground meat. The virus in whole and ground meat was consistently inactivated when cooked to temperatures greater than or equal to 75°C. A second objective of this research was to thoroughly reassess if Vero cells were permissive to BVDV infection in our laboratory to provide further indication of whether primates, including humans, might be susceptible to BVDV. Vero cells were not permissive to infection with any of 43 different strains of BVDV that readily replicated in Madin Darby bovine kidney cells. In conclusion, this bovine pathogen, which is not considered to be a human pathogen, can be inactivated by cooking ground or whole cuts of meat to 75°C or higher. Care should be taken to ensure that susceptible hosts such as pigs are not fed improperly cooked meat, meat by-products, or waste food originating from PI cattle.

Antiviral treatment of calves persistently infected with bovine viral diarrhoea virus.

BACKGROUND: Animals persistently infected (PI) with bovine viral diarrhoea virus (BVDV) are a key source of viral propagation within and among herds. Currently, no specific therapy exists to treat PI animals. The purpose of this research was to initiate evaluation of the pharmacokinetic and safety data of a novel antiviral agent in BVDV-free calves and to assess the antiviral efficacy of the same agent in PI calves. METHODS: One BVDV-free calf was treated with 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) once at a dose of 1.6 mg/kg intravenously and one BVDV-free calf was treated three times a day for 6 days at 9.5 mg/kg intravenously. Subsequently, four PI calves were treated intravenously with 12 mg/kg DB772 three times a day for 6 days and two PI control calves were treated with an equivalent volume of diluent only. RESULTS: Prior to antiviral treatment, the virus isolated from each calf was susceptible to DB772 in vitro. The antiviral treatment effectively inhibited virus for 14 days in one calf and at least 3 days in three calves. Subsequent virus isolated from the three calves was resistant to DB772 in vitro. No adverse effects of DB772 administration were detected. CONCLUSIONS: Results demonstrate that DB772 administration is safe and exhibits antiviral properties in PI calves while facilitating the rapid development of viral resistance to this novel therapeutic agent.