Search

BACKGROUND: About one-third of older adults aged 65 years and older often have mild cognitive impairment or dementia. Acoustic and psycho-linguistic features derived from conversation may be of great diagnostic value because speech involves verbal memory and cognitive and neuromuscular processes. The relative decline in these processes, however, may not be linear and remains understudied. OBJECTIVE: This study aims to establish associations between cognitive abilities and various attributes of speech and natural language production. To date, the majority of research has been cross-sectional, relying mostly on data from structured interactions and restricted to textual versus acoustic analyses. METHODS: In a sample of 71 older (mean age 83.3, SD 7.0 years) community-dwelling adults who completed qualitative interviews and cognitive testing, we investigated the performance of both acoustic and psycholinguistic features associated with cognitive deficits contemporaneously and at a 1-2 years follow up (mean follow-up time 512.3, SD 84.5 days). RESULTS: Combined acoustic and psycholinguistic features achieved high performance (F1-scores 0.73-0.86) and sensitivity (up to 0.90) in estimating cognitive deficits across multiple domains. Performance remained high when acoustic and psycholinguistic features were used to predict follow-up cognitive performance. The psycholinguistic features that were most successful at classifying high cognitive impairment reflected vocabulary richness, the quantity of speech produced, and the fragmentation of speech, whereas the analogous top-ranked acoustic features reflected breathing and nonverbal vocalizations such as giggles or laughter. CONCLUSIONS: These results suggest that both acoustic and psycholinguistic features extracted from qualitative interviews may be reliable markers of cognitive deficits in late life.

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. [ABSTRACT FROM AUTHOR]

Objective: This systematic review investigates the long-term effect of cochlear implantation (CI) on clinical outcomes in tinnitus patients with sensorineural hearing loss (SNHL). Database Sources: PubMed, Embase, and the Cochrane Library were searched from inception to 30 April 2024. Manual searches of reference lists supplemented these searches when necessary. Review Methods: Original studies included in the meta-analysis had to contain comparative pre- and postoperative data for SNHL patients who underwent CI. Outcomes measured were the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), and Tinnitus Questionnaire (TQ). Results: A total of 28 studies comprising 853 patients showed significant tinnitus improvement after CI: THI mean difference (MD) −14.02 [95%CI −15.29 to −12.76, p < 0.001], TQ MD −15.85 [95%CI −18.97 to −12.74, p < 0.05], and VAS MD −3.12 [95%CI −3.49 to −2.76, p < 0.05]. Subgroup analysis indicated a significant difference between follow-up periods in THI (p < 0.0001) and VAS loudness (p = 0.02). Conclusions: Cochlear implantation substantially improves tinnitus in patients with hearing loss, though the effect may diminish over time. Further research is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

CI chondrites are the most significant extra-terrestrial samples for estimating the composition of primordial materials in the Solar System. However, CIs lose many primary features because of heavy parent body aqueous alteration. However, CI and CI-related Ryugu particles contain small amounts of relict anhydrous minerals, indicating primary occurrences of chondrules and refractory inclusions. In this study, we estimated the primordial abundance of chondrules in CIs from calculations of the bulk major element compositions. The constraints for the calculation were as follows: 1) CI chondrites primarily comprised chondrules, refractory inclusions, opaque minerals, and a matrix similar to other carbonaceous (C) chondrites. 2) The chemical compositions of these components were similar to those of the unaltered C chondrites. 3) The primary matrix composition of the CI was close to the mean bulk composition. 4) The alteration occurred isochemically. We used the mean major elemental compositions of chondrules and refractory inclusions in an almost unaltered chondrite, Y-81020, CO3.05. Our results were within the range of previously reported CI bulk chemical compositions in the case where chondrule abundances are ≲10 wt%. We also calculated the bulk chemical composition of Tagish Lake, ungrouped C2, which primarily contained ≲20 wt% chondrules. The CI chondrites and Tagish Lake were formed in the outer Solar System. The low primary abundance of chondrules in CIs is closely related to the formation conditions of chondrules in such regions. We suggest that dust with abundant ice and minor chondrules accreted onto the parent bodies of the CI and Tagish Lake in the outer Solar System. Primordial chondrule abundance is the key to clarifying the physical and chemical conditions and evolution of the early Solar System. [ABSTRACT FROM AUTHOR]

Copyright of e & i Elektrotechnik und Informationstechnik is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PurposeTo report an image analysis pipeline, DDLSNet, consisting of a rim segmentation (RimNet) branch and a disc size classification (DiscNet) branch to automate estimation of the disc damage likelihood scale (DDLS).DesignRetrospective observational.ParticipantsRimNet and DiscNet were developed with 1208 and 11 536 optic disc photographs (ODPs), respectively. DDLSNet performance was evaluated on 120 ODPs from the RimNet test set, for which the DDLS scores were graded by clinicians. Reproducibility was evaluated on a group of 781 eyes, each with 2 ODPs taken within 4 years apart.MethodsDisc damage likelihood scale calculation requires estimation of optic disc size, provided by DiscNet (VGG19 network), and the minimum rim-to-disc ratio (mRDR) or absent rim width (ARW), provided by RimNet (InceptionV3/LinkNet segmentation model). To build RimNet's dataset, glaucoma specialists marked optic disc rim and cup boundaries on ODPs. The "ground truth" mRDR or ARW was calculated. For DiscNet's dataset, corresponding OCT images provided "ground truth" disc size. Optic disc photographs were split into 80/10/10 for training, validation, and testing, respectively, for RimNet and DiscNet. DDLSNet estimation was tested against manual grading of DDLS by clinicians with the average score used as "ground truth." Reproducibility of DDLSNet grading was evaluated by repeating DDLS estimation on a dataset of nonprogressing paired ODPs taken at separate times.Main outcome measuresThe main outcome measure was a weighted kappa score between clinicians and the DDLSNet pipeline with agreement defined as ± 1 DDLS score difference.ResultsRimNet achieved an mRDR mean absolute error (MAE) of 0.04 (± 0.03) and an ARW MAE of 48.9 (± 35.9) degrees when compared to clinician segmentations. DiscNet achieved 73% (95% confidence interval [CI]: 70%, 75%) classification accuracy. DDLSNet achieved an average weighted kappa agreement of 0.54 (95% CI: 0.40, 0.68) compared to clinicians. Average interclinician agreement was 0.52 (95% CI: 0.49, 0.56). Reproducibility testing demonstrated that 96% of ODP pairs had a difference of ≤ 1 DDLS score.ConclusionsDDLSNet achieved moderate agreement with clinicians for DDLS grading. This novel approach illustrates the feasibility of automated ODP grading for assessing glaucoma severity. Further improvements may be achieved by increasing the number of incomplete rims sample size, expanding the hyperparameter search, and increasing the agreement of clinicians grading ODPs.

PurposeTo compare the diagnostic accuracy and explainability of a Vision Transformer deep learning technique, Data-efficient image Transformer (DeiT), and ResNet-50, trained on fundus photographs from the Ocular Hypertension Treatment Study (OHTS) to detect primary open-angle glaucoma (POAG) and identify the salient areas of the photographs most important for each model's decision-making process.DesignEvaluation of a diagnostic technology.Subjects participants and controlsOverall 66 715 photographs from 1636 OHTS participants and an additional 5 external datasets of 16 137 photographs of healthy and glaucoma eyes.MethodsData-efficient image Transformer models were trained to detect 5 ground-truth OHTS POAG classifications: OHTS end point committee POAG determinations because of disc changes (model 1), visual field (VF) changes (model 2), or either disc or VF changes (model 3) and Reading Center determinations based on disc (model 4) and VFs (model 5). The best-performing DeiT models were compared with ResNet-50 models on OHTS and 5 external datasets.Main outcome measuresDiagnostic performance was compared using areas under the receiver operating characteristic curve (AUROC) and sensitivities at fixed specificities. The explainability of the DeiT and ResNet-50 models was compared by evaluating the attention maps derived directly from DeiT to 3 gradient-weighted class activation map strategies.ResultsCompared with our best-performing ResNet-50 models, the DeiT models demonstrated similar performance on the OHTS test sets for all 5 ground-truth POAG labels; AUROC ranged from 0.82 (model 5) to 0.91 (model 1). Data-efficient image Transformer AUROC was consistently higher than ResNet-50 on the 5 external datasets. For example, AUROC for the main OHTS end point (model 3) was between 0.08 and 0.20 higher in the DeiT than ResNet-50 models. The saliency maps from the DeiT highlight localized areas of the neuroretinal rim, suggesting important rim features for classification. The same maps in the ResNet-50 models show a more diffuse, generalized distribution around the optic disc.ConclusionsVision Transformers have the potential to improve generalizability and explainability in deep learning models, detecting eye disease and possibly other medical conditions that rely on imaging for clinical diagnosis and management.

Plague is an endemic infectious disease caused by Yersinia pestis. In this study, we isolated fourteen phages with similar sequence arrangements to phage 186; these phages exhibited different lytic abilities in Enterobacteriaceae strains. To illustrate the phylogenetic relationships and evolutionary relationships between previously designated 186-type phages, we analysed the complete sequences and important genes of the phages, including whole-genome average nucleotide identity (ANI) and collinearity comparison, evolutionary analysis of four conserved structural genes (V, T, R, and Q genes), and analysis of the regulatory genes (cI, apl, and cII) and integrase gene (int). Phylogenetic analysis revealed that thirteen of the newly isolated phages belong to the genus Eganvirus and one belongs to the genus Felsduovirus in the family Peduoviridae, and these Eganvirus phages can be roughly clustered into three subgroups. The topological relationships exhibited by the whole-genome and structural genes seemed similar and stable, while the regulatory genes presented different topological relationships with the structural genes, and these results indicated that there was some homologous recombination in the regulatory genes. These newly isolated 186-type phages were mostly isolated from dogs, suggesting that the resistance of Canidae to Y. pestis infection may be related to the wide distribution of phages with lytic capability. [ABSTRACT FROM AUTHOR]

To investigate the magnetic resonance imaging (MRI) features of women with prior second-trimester pregnancy loss, and to establish a nomogram prediction model for subsequent miscarriage. Methods: A retrospective cohort study of women with prior second-trimester pregnancy loss from January 2018 to December 2021 in Second Affiliated Hospital of Soochow University was performed. A total of 245 patients were included. Data from January 2018 to December 2019 were used to construct the model, and data from January 2020 to December 2021 were used to evaluate the model. Data on maternal demographic characteristics, MRI cervical measurements were extracted. The prediction model was constructed with independent variables determined by multivariate logistic regression analyses. Through receiver-operating characteristic (ROC) curve analysis, the predictive ability of the model for subsequent second trimester pregnancy loss in women was evaluated, and internal validation was performed through validation data. Results: Thin cervix was observed in 77 (31.42%) women with prior second-trimester pregnancy loss, the mean longitudinal diameter of cervical canal on MRI was 11.76± 2.75mm. The model reached a sensitivity of 80%, specificity of 75.90%, positive predictive value (PPV) of 55.80% and negative predictive value of 90.90%; ROC characteristics proved that the model was superior to any single parameter with an AUC of 0.826. Conclusion: Our observations showed that thin cervix and longitudinal diameter of cervical canal reliably predicted second trimester pregnancy loss. We developed and validated a nomogram model to predict the individual probability of second trimester pregnancy loss in the next pregnancy and hopefully improve the prediction and indication of interventions. [ABSTRACT FROM AUTHOR]

The construction environment of deep rock tunnels is complex, and effectively enhancing tunnel boring machine (TBM) tunneling efficiency is paramount. Increasing rock-breaking efficiency and minimizing cutter consumption are essential strategies for improving TBM tunneling efficiency. Selecting suitable tunneling parameters is crucial for enhancing rock-breaking efficiency and reducing cutter consumption. Existing research on the optimization of the ratio of maximum cutter spacing to penetration (Smax/P) based on field-measured data is limited, and few studies compare and analyze the relationship between SE, CI, and the Smax/P ratio separately. Consequently, this study determined optimal tunneling parameters for various types of surrounding rock and construction environments, aiming to more accurately optimize TBM tunneling performance during construction processes based on on-site construction data. This study conducted a comparative analysis of specific energy (SE) and the coarseness index (CI). Under both working conditions, the quadratic fitting coefficients of the CI are 4.2% and 10.6% higher than those of the SE, respectively, with the CI selected to represent the particle size distribution of rock chips. Finally, taking into account both the correlations between the CI and the ratio of maximum cutter spacing to penetration (Smax/P), as well as cutter consumption and the Smax/P ratio, an optimization method for the TBM tunneling parameter was established under both dry and saturated conditions. The research findings indicate that cutter consumption exhibits an exponential increase with a higher rock Cerchar Abrasivity Index (CAI); it initially decreases as the Smax/P ratio increases and subsequently increases in both dry and saturated conditions. Instead, the CI demonstrates an initial increase and subsequent decrease as the Smax/P ratio increases. Maximizing rock-breaking efficiency and minimizing cutter consumption are crucial for improving tunneling performance. In saturated conditions, the corresponding optimal Smax/P ratio ranges are 7.055–8.319 for soft rock, 8.606–8.931 for medium–hard rock, and 13.50–14.00 for hard rock, and these optimal ranges under dry conditions are 8.495–9.457, 10.972–12.169, and 16.5–17.5 for the same rock types. This study provides optimal Smax/P ratio ranges for TBM tunneling, thereby significantly enhancing tunneling efficiency. [ABSTRACT FROM AUTHOR]

In this study, we investigated the metabolic signatures of different mitochondrial defects (two different complex I and complex V, and the one MDH2 defect) in human skin fibroblasts (HSF). We hypothesized that using a selective culture medium would cause defect specific adaptation of the metabolome and further our understanding of the biochemical implications for the studied defects. All cells were cultivated under galactose stress condition and compared to glucose‐based cell culture condition. We investigated the bioenergetic profile using Seahorse XFe96 cell analyzer and assessed the extracellular metabolic footprints and the intracellular metabolic fingerprints using NMR. The galactose‐based culture condition forced a bioenergetic switch from a glycolytic to an oxidative state in all cell lines which improved overall separation of controls from the different defect groups. The extracellular metabolome was discriminative for separating controls from defects but not the specific defects, whereas the intracellular metabolome suggests CI and CV changes and revealed clear MDH2 defect‐specific changes in metabolites associated with the TCA cycle, malate aspartate shuttle, and the choline metabolism, which are pronounced under galactose condition. [ABSTRACT FROM AUTHOR]

A cerebral infarction (CI), often known as a stroke, is a cognitive impairment in which a group of brain cells perishes from a lack of blood supply. The early prediction and evaluation of this problem are essential to avoid atrial fibrillation, heart valve disease, and other cardiac disorders. Different clinical strategies like Computerized tomography (CT) scans, Magnetic resonance imaging (MRI), and Carotid (ka-ROT-id) ultrasound are available to diagnose this problem. However, these methods are time-consuming and expensive. Wearable devices based on photoplethysmography (PPG) are gaining prevalence in diagnosing various cardiovascular diseases. This work uses the PPG signal to classify the CI subjects from the normal. We propose an automated framework and fiducial point-independent approach to predict CI with sufficient accuracy. The experiment is performed with a publicly available database having PPG and other physiological data of 219 individuals. The best validation and test accuracy of 91.8 % and 91.3 % are obtained after diagnosis with Coarse Gaussian SVM. The proposed work aims to extract cerebral infarction pathology by extracting relevant entropy features from higher order PPG derivatives for the prediction of CI and offers a simple, automated and inexpensive approach for early detection of CI and promotes awareness for the subjects to undergo further treatment to avoid major disorders. [ABSTRACT FROM AUTHOR]

Objective: This systematic review investigates the long-term effect of cochlear implantation (CI) on clinical outcomes in tinnitus patients with sensorineural hearing loss (SNHL). Database Sources: PubMed, Embase, and the Cochrane Library were searched from inception to 30 April 2024. Manual searches of reference lists supplemented these searches when necessary. Review Methods: Original studies included in the meta-analysis had to contain comparative pre- and postoperative data for SNHL patients who underwent CI. Outcomes measured were the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), and Tinnitus Questionnaire (TQ). Results: A total of 28 studies comprising 853 patients showed significant tinnitus improvement after CI: THI mean difference (MD) −14.02 [95%CI −15.29 to −12.76, p < 0.001], TQ MD −15.85 [95%CI −18.97 to −12.74, p < 0.05], and VAS MD −3.12 [95%CI −3.49 to −2.76, p < 0.05]. Subgroup analysis indicated a significant difference between follow-up periods in THI (p < 0.0001) and VAS loudness (p = 0.02). Conclusions: Cochlear implantation substantially improves tinnitus in patients with hearing loss, though the effect may diminish over time. Further research is needed to confirm these findings.

BackgroundWe evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort.MethodsThis prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed.Findings1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs

BackgroundEarly detection of melanoma is critical for positive outcomes. However, access for the diagnosis of melanoma remains problematic for segments of the general population.ObjectiveTo compare the rates of dermatology and family medicine practitioner acceptances for a public insurance (Medicaid) versus private insurance (Anthem Blue Cross) and clinic wait times for an appointment for a changing pigmented skin lesion concerning melanoma in rural and urban regions in California.MethodsCross-sectional audit study between June 2017 and March 2019; scripted phone calls were made to dermatology and family medicine practices (FMPs).ResultsFamily medicine and dermatology practices in both regions had significantly decreased acceptance of Medicaid. Dermatology practices had 11.3% to 13.0% Medicaid acceptance rates that were less than FMP rates of 28% to 36%. In both regions, FMP wait times were 2.4- to 3.2-fold longer for public versus private insurance; there were little differences in wait times for the 2 insurance types in dermatology practices, in both regions.LimitationsAssessment of only 2 regions in the state of California.ConclusionDelays at FMPs and insurance types limit access to melanoma screening in California for underserved segments of the general population, which has implications for melanoma outcomes and health policy.

ObjectiveTo explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs.MethodsWe derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from the ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE therapy. The National Inpatient Sample estimated event costs (facility and professional) and daily IPE treatment cost was approximated at $4.59.ResultsWe estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion).ConclusionsTreating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.

PurposeDevelop computer vision models for image-based differentiation of bacterial and fungal corneal ulcers and compare their performance against human experts.DesignCross-sectional comparison of diagnostic performance.ParticipantsPatients with acute, culture-proven bacterial or fungal keratitis from 4 centers in South India.MethodsFive convolutional neural networks (CNNs) were trained using images from handheld cameras collected from patients with culture-proven corneal ulcers in South India recruited as part of clinical trials conducted between 2006 and 2015. Their performance was evaluated on 2 hold-out test sets (1 single center and 1 multicenter) from South India. Twelve local expert cornea specialists performed remote interpretation of the images in the multicenter test set to enable direct comparison against CNN performance.Main outcome measuresArea under the receiver operating characteristic curve (AUC) individually and for each group collectively (i.e., CNN ensemble and human ensemble).ResultsThe best-performing CNN architecture was MobileNet, which attained an AUC of 0.86 on the single-center test set (other CNNs range, 0.68-0.84) and 0.83 on the multicenter test set (other CNNs range, 0.75-0.83). Expert human AUCs on the multicenter test set ranged from 0.42 to 0.79. The CNN ensemble achieved a statistically significantly higher AUC (0.84) than the human ensemble (0.76; P < 0.01). CNNs showed relatively higher accuracy for fungal (81%) versus bacterial (75%) ulcers, whereas humans showed relatively higher accuracy for bacterial (88%) versus fungal (56%) ulcers. An ensemble of the best-performing CNN and best-performing human achieved the highest AUC of 0.87, although this was not statistically significantly higher than the best CNN (0.83; P = 0.17) or best human (0.79; P = 0.09).ConclusionsComputer vision models achieved superhuman performance in identifying the underlying infectious cause of corneal ulcers compared with cornea specialists. The best-performing model, MobileNet, attained an AUC of 0.83 to 0.86 without any additional clinical or historical information. These findings suggest the potential for future implementation of these models to enable earlier directed antimicrobial therapy in the management of infectious keratitis, which may improve visual outcomes. Additional studies are ongoing to incorporate clinical history and expert opinion into predictive models.

Purpose: The focus on treating patients with Menière's Disease (MD) lies on the reduction of vertigo attacks and the preservation of sensory function. Endolympathic hydrops is considered as an epiphenomenon in MD, which can potentially be altered by endolymphatic sac surgery (ESS). Purpose of the study was to investigate the influences on vertigo control through manipulation of the perilymphatic system with or without ESS. Methods: Retrospective data analysis of 86 consecutive patients with MD according to current diagnostic criteria after endolymphatic sac surgery alone (ESSalone; n = 45), cochlear implantation (CI) alone (CIalone; n = 12), and ESS with CI (ESS + CI; n = 29), treated at a tertiary referral center. Main Outcome Measures: vertigo control, speech perception pre- and postoperatively. Results: Gender, side, and preoperative treatment were similar in all groups. Age was younger in the ESSalone-group with 56.2 ± 13.0 years (CIalone = 64.2 ± 11.4 years; ESS + CI = 63.1 ± 9.7 years). Definitive MD was present in all the CIalone, in 79.3% of the ESS + CI and in 59.6% of the ESSalone-patients. Likewise, vertigo control rate was 100% in the CIalone, 89.7% in the ESS + CI and 66.0% in the ESSalone-group. Conclusions: Vertigo control was improved in all three groups, however, superior in groups treated with CI, potentially contributed by the manipulation of both the endo- and perilymphatic systems. A more systematic characterization of the patients with larger case numbers and documentation of follow up data would be needed to evaluate a clinical effect more properly. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated neuroplastic changes induced by postlingual single-sided deafness (SSD) and the effects of a cochlear implantation for the deaf ear. Neural processing of acoustic signals from the normal hearing ear to the brain was studied before and after implantation using a positron emission tomography (PET)/CT scanner. Methods: Eight patients with postlingual SSD received a cochlear implant (CI) in a prospective clinical trial. Dynamic imaging was performed in a PET/CT scanner using radioactively labeled water ([15O]H2O) to localize changes in the regional cerebral blood flow (rCBF) with and without an auditory task of logatomes containing speech-like elements without meaningful context. The normal hearing ear was stimulated before implantation and after the use of the cochlear implant for at least 8 months (mean 13.5, range 8.1–26.6). Eight age- and gender-matched subjects with normal hearing on both sides served as healthy control subjects (HCS). Results: When the normal hearing ear of SSD patients was stimulated before CI implantation, the [15O]H2O-PET showed a more symmetrical rCBF in the auditory regions of both hemispheres in comparison to the HCS. The use of CI increased the asymmetry index (AI) in six of eight patients indicating an increase of activity of the contralateral hemisphere. Non-parametric statistics revealed a significant difference in the AI between patients before CI implantation and HCS (p <.01), which disappeared after CI implantation (p =.195). Conclusion: The functional neuroimaging data showed a tendency towards normalization of neuronal activity after CI implantation, which supports the effectiveness of CI in SSD patients. Trial Registration: ClinicalTrials.gov Identifier: NCT01749592, December 13, 2012. [ABSTRACT FROM AUTHOR]

Objective: Compare cochlear implant (CI) outcomes in English speakers, Spanish speakers, and bilingual Hispanics. Study Design: Retrospective review. Setting: Academic tertiary care center. Methods: Eighty‐five postlingually deafened adults unilaterally implanted between January 2014 and December 2018 were stratified by primary language. Primary outcomes were: (1) English consonant‐nucleus‐consonant and Spanish bisyllables word tests in quiet, and (2) English AzBio and Latin American Hearing In Noise Test (LA‐HINT) sentence tests in quiet and in noise at multiple time‐intervals postactivation. Results: In the respective languages, primary Spanish speakers (n = 24), and English speakers (n = 61) experienced the greatest increases in average scores for word and sentence tests in quiet during the first 6 months postactivation, with gradual increases in average scores over time. English speakers performed significantly worse on AzBio tests in noise, compared to quiet, while the addition of noise did not significantly affect average LA‐HINT scores in Spanish speakers across multiple time intervals. An early ceiling effect was also demonstrated for LA‐HINT. Although not significant, bilingual Hispanics (n = 12) had lower average AzBio in quiet scores than English speakers and higher average LA‐HINT in quiet scores than the Spanish speakers across multiple time intervals. Conclusion: English and Spanish CI users experienced the greatest increases in speech understanding in quiet the first few months after implant activation. An early ceiling effect is demonstrated with LA‐HINT, indicating LA‐HINT is not appropriate for evaluating longitudinal CI outcomes in Spanish speakers. Bilingual Hispanics represent a unique group, and further investigations are necessary to understand speech perception patterns in both languages and develop the best CI test strategies for these individuals. [ABSTRACT FROM AUTHOR]

PurposeTo assess whether the predictive accuracy of machine learning algorithms using Kalman filtering for forecasting future values of global indices on perimetry can be enhanced by adding global retinal nerve fiber layer (RNFL) data and whether model performance is influenced by the racial composition of the training and testing sets.DesignRetrospective, longitudinal cohort study.ParticipantsPatients with open-angle glaucoma (OAG) or glaucoma suspects enrolled in the African Descent and Glaucoma Evaluation Study or Diagnostic Innovation in Glaucoma Study.MethodsWe developed a Kalman filter (KF) with tonometry and perimetry data (KF-TP) and another KF with tonometry, perimetry, and global RNFL data (KF-TPO), comparing these models with one another and with 2 linear regression (LR) models for predicting mean deviation (MD) and pattern standard deviation values 36 months into the future for patients with OAG and glaucoma suspects. We also compared KF model performance when trained on individuals of European and African descent and tested on patients of the same versus the other race.Main outcome measuresPredictive accuracy (percentage of MD values forecasted within the 95% repeatability interval) differences among the models.ResultsAmong 362 eligible patients, the mean ± standard deviation age at baseline was 71.3 ± 10.4 years; 196 patients (54.1%) were women; 202 patients (55.8%) were of European descent, and 139 (38.4%) were of African descent. Among patients with OAG (n = 296), the predictive accuracy for 36 months in the future was higher for the KF models (73.5% for KF-TP, 71.2% for KF-TPO) than for the LR models (57.5%, 58.0%). Predictive accuracy did not differ significantly between KF-TP and KF-TPO (P = 0.20). If the races of the training and testing set patients were aligned (versus nonaligned), the mean absolute prediction error of future MD improved 0.39 dB for KF-TP and 0.48 dB for KF-TPO.ConclusionsAdding global RNFL data to existing KFs minimally improved their predictive accuracy. Although KFs attained better predictive accuracy when the races of the training and testing sets were aligned, these improvements were modest. These findings will help to guide implementation of KFs in clinical practice.

Despite substantial technical advances and wider clinical use, cochlear implant (CI) users continue to report high and elevated listening effort especially under challenging noisy conditions. Among all the objective measures to quantify listening effort, pupillometry is one of the most widely used and robust physiological measures. Previous studies with normally hearing (NH) and hearing-impaired (HI) listeners have shown that the relation between speech performance in noise and listening effort (as measured by peak pupil dilation) is not linear and exhibits an inverted-U shape. However, it is unclear whether the same psychometric relation exists in CI users, and whether individual differences in auditory sensitivity and central cognitive capacity affect this relation. Therefore, we recruited 17 post-lingually deaf CI adults to perform speech-in-noise tasks from 0 to 20 dB SNR with a 4 dB step size. Simultaneously, their pupillary responses and self-reported subjective effort were recorded. To characterize top-down and bottom-up individual variabilities, a spectro-temporal modulation task and a set of cognitive abilities were measured. Clinical word recognition in quiet and Quality of Life (QoL) were also collected. Results showed that at a group level, an inverted-U shape psychometric curve between task difficulty (SNR) and peak pupil dilation (PPD) was not observed. Individual shape of the psychometric curve was significantly associated with some individual factors: CI users with higher clinical word and speech-in-noise recognition showed a quadratic decrease of PPD over increasing SNRs; CI users with better non-verbal intelligence and lower QoL showed smaller average PPD. To summarize, individual differences in CI users had a significant impact on the psychometric relation between pupillary response and task difficulty, hence affecting the interpretation of pupillary response as listening effort (or engagement) at different task difficulty levels. Future research and clinical applications should further characterize the possible effects of individual factors (such as motivation or engagement) in modulating CI users’ occurrence of ‘tipping point’ on their psychometric functions, and develop an individualized method for reliably quantifying listening effort using pupillometry.

A percentage (i.e., 5.6%) of Cochlear Implant (CI) users reportedly experience unwanted facial nerve stimulation (FNS). For some, the effort to control this problem results in changing stimulation parameters, thereby reducing their hearing performance. For others, the only viable solution is to deactivate the CI completely. A growing body of evidence in the form of case reports suggests that undesired FNS can be effectively addressed through re-implantation with an Oticon Medical (OM) Neuro-Zti implant. However, the root of this benefit is still unknown: is it due to surgical adjustments, such as varied array geometries and/or positioning, or does it stem from differences in stimulation parameters and/or grounding? The OM device exhibits two distinct features: (1) unique stimulation parameters, including anodic leading pulses and loudness controlled by pulse duration—not current—resulting in lower overall current amplitudes; and (2) unconventional grounding, including both passive (capacitive) discharge, which creates a pseudo-monophasic pulse shape, and a 'distributed-all-polar' (DAP) grounding scheme, which is thought to reduce current spread. Unfortunately, case reports alone cannot distinguish between surgical factors and these implant-related ones. In this paper, we present a novel follow-up study of two CI subjects who previously experienced FNS before re-implantation with Neuro-Zti implants. We used the Oticon Medical Research Platform (OMRP) to stimulate a single electrode in each subject in two ways: (1) with traditional monopolar biphasic cathodic-first pulses, and (2) with distinct OM clinical stimulation. We progressively increased the stimulation intensity until FNS occurred or the sound became excessively loud. Non-auditory/FNS sensations were observed with the traditional stimulation but not with the OM clinical one. This provides the first direct evidence demonstrating that stimulation parameters and/or grounding—not surgical factors—play a key role in mitigating FNS. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Educational Psychology is the property of International Journal of Educational Psychology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Excess maternal weight gain during pregnancy has been associated with childhood overweight and obesity both in mothers with and without obesity. Latinx children are at higher risk for earlier obesity compared with other population groups. A cohort of 82 self-identified pregnant Latina women were recruited at the prenatal clinics of Zuckerberg San Francisco General Hospital (ZSFG) prior to delivery during the second and third trimesters of pregnancy in 2011 and 2012. Maternal pre-pregnancy weight and weight prior to delivery were collected by self-report to calculate maternal pre-pregnancy body mass index (BMI) and weight gain in pregnancy. At delivery, anthropometric measurements of infants were obtained and cord blood and maternal finger stick blood samples were collected for hormonal assays. Fifty-three point seven percent of women had excessive weight gain in pregnancy. A high percentage of the cohort was overweight and obese prior to pregnancy (67.1%) with mean pre-pregnancy BMI 27.4 ± 4.5 kg/m2 and greater pre-pregnancy weight was independently associated with weight gain during pregnancy (OR 1.05, 95%CI 1.002-1.09). Mean infant birthweight was 3377.2 ± 481.5 g and excessive weight gain in pregnancy was independently associated with birthweight percentile (OR 13.46, 95%CI 2.43-34.50). Excessive gestational gain was positively associated with cord blood insulin-like growth factor-1 (IGF-1) and negatively with Peptide YY (PYY) levels. Latina women with pre-pregnancy overweight and obesity have a high rate of excessive gestational gain in pregnancy and could benefit from early counseling about appropriate gain in pregnancy. Excessive gestational weight impacts the intrauterine environment in high-risk infants impacting fetal growth and development.

BACKGROUND: There are limited data to guide oncology and cardiology decision-making in patients with a left ventricular assist device (LVAD) and concurrent active malignancy. OBJECTIVES: The goal of this study was to describe cancer treatment approaches, complications, and survival among patients with active cancer on LVAD support in 2 tertiary heart failure and oncology programs. METHODS: In this retrospective cohort study, LVAD databases were reviewed to identify patients with a cancer diagnosis at the time of or after LVAD implantation. We created a 3:1 matched cohort based on age, sex, etiology of cardiomyopathy, LVAD implant strategy, and INTERMACS profile stratified by site. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival between patients with cancer and non-cancer comparators. RESULTS: Among 1,123 patients who underwent LVAD implantation between 2005 and 2019, 22 patients with LVADs with active cancer and 66 matched non-cancer comparators were identified. Median age was 62 years (range 41 to 73 years); 50% of patients with cancer were African-American, and 27% were women. Prostate cancer, followed by renal cell cancer and hematologic malignancies were the most common diagnoses. There was no significant difference in unadjusted Kaplan-Meier median survival estimates from the time of LVAD placement between patients with cancer (3.53 years; 95% confidence interval [CI]: 1.41 to 5.33) and non-cancer comparators (3.03 years; 95% CI: 1.83 to 5.26; log-rank P = 0.99). In Cox proportional hazard models, cancer diagnosis as a time-varying variable was associated with a statistically significant increase in death (hazard ratio: 2.05; 95% CI: 1.03 to 4.12; P = 0.04). Patients with cancer had less gastrointestinal bleeding compared with matched non-cancer comparators (P = 0.016). Other complications were not significantly different. CONCLUSIONS: Our study provides initial feasibility and safety data and set a framework for multidisciplinary team management of patients with cancer and LVADs.

Targeting angiotensinogen (AGT) may provide a novel approach to more optimally inhibit the renin-angiotensin-aldosterone system pathway. Double-blind, placebo-controlled clinical trials were performed in subjects with hypertension as monotherapy or as an add-on to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with IONIS-AGT-LRx versus placebo up to 2 months. IONIS-AGT-LRx was well tolerated with no significant changes in platelet count, potassium levels, or liver and renal function. IONIS-AGT-LRx significantly reduced AGT levels compared with placebo in all 3 studies. Although not powered for this endpoint, trends were noted in blood pressure reduction. In conclusion, IONIS-AGT-LRx significantly reduces AGT with a favorable safety, tolerability, and on-target profile. (A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx; NCT04083222; A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously to Hypertensive Subjects With Controlled Blood Pressure; NCT03714776; Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ionis AGT-LRx in Healthy Volunteers; NCT03101878).

Pistachio nuts are a nutrient-dense source of good quality plant protein, commonly consumed as a minimally processed snack food or ingredient. The present paper is based on a symposium held during the 13th FENS (Federation of European Nutrition Societies) 2019 conference in Dublin that explored recent research and practical applications of pistachios as a plant-based snack, in particular, for appetite control and healthy weight management; and for glycaemic control during pregnancy. Individual nut types, whilst similar in nutritional composition, have unique characteristics which may have a significant impact on potential health effects. Recognising this, the further purpose here is to explore future research needs for pistachios, based on work completed to date and the discussion that ensued among researchers at this event, in order to advance the full scope of health benefits from pistachios, in particular, taking into account of both sustainability and nutritional health.

BackgroundThe burden of amyloidosis among hospitalized patients is increasing over time. However, amyloidosis remains an underdiagnosed cause of heart failure (HF) hospitalization among older adults.ObjectivesWe investigated the prevalence and prognostic implications of amyloidosis among patients hospitalized with HF.MethodsAll hospitalizations for primary diagnosis of HF between January 1, 2010, and August 31, 2015, identified in the Nationwide Readmissions Database were categorized into those with and without a secondary diagnosis of amyloidosis. HF hospitalizations with amyloidosis were then matched in a 3:1 fashion to HF hospitalizations without amyloidosis using the year of admission, discharge quarter, age, sex, and Charlson comorbidity index. Primary outcomes were inpatient mortality and 30-day readmission. Multivariable logistic regression was used to estimate the association between HF with amyloidosis and clinical outcomes.ResultsOf 1,593,360 HF hospitalizations that met inclusion criteria, 2,846 (0.18%) had HF with a secondary diagnosis of amyloidosis and were matched to 8,515 hospitalizations for HF without amyloidosis. Hospitalizations for HF with amyloidosis were associated with higher prevalence of kidney disease (56% vs. 45%), malignancy (20% vs. 4%), and higher inpatient mortality (6% vs. 3%) as compared with HF without amyloidosis. In adjusted analyses, HF with amyloidosis was associated with higher odds of in-hospital mortality (odds ratio: 1.46; 95% confidence interval [CI]: 1.17 to 1.82), 30-day readmission (odds ratio: 1.17; 95% CI: 1.05 to 1.31), and longer mean length of stay (least-squares mean difference: 1.46; 95% CI: 1.12 to 1.80).ConclusionsIn patients hospitalized with decompensated HF, presence of amyloidosis was associated with higher risk of inpatient mortality and 30-day readmission.

Plague is an endemic infectious disease caused by Yersinia pestis. In this study, we isolated fourteen phages with similar sequence arrangements to phage 186; these phages exhibited different lytic abilities in Enterobacteriaceae strains. To illustrate the phylogenetic relationships and evolutionary relationships between previously designated 186-type phages, we analysed the complete sequences and important genes of the phages, including whole-genome average nucleotide identity (ANI) and collinearity comparison, evolutionary analysis of four conserved structural genes (V, T, R, and Q genes), and analysis of the regulatory genes (cI, apl, and cII) and integrase gene (int). Phylogenetic analysis revealed that thirteen of the newly isolated phages belong to the genus Eganvirus and one belongs to the genus Felsduovirus in the family Peduoviridae, and these Eganvirus phages can be roughly clustered into three subgroups. The topological relationships exhibited by the whole-genome and structural genes seemed similar and stable, while the regulatory genes presented different topological relationships with the structural genes, and these results indicated that there was some homologous recombination in the regulatory genes. These newly isolated 186-type phages were mostly isolated from dogs, suggesting that the resistance of Canidae to Y. pestis infection may be related to the wide distribution of phages with lytic capability.

The construction environment of deep rock tunnels is complex, and effectively enhancing tunnel boring machine (TBM) tunneling efficiency is paramount. Increasing rock-breaking efficiency and minimizing cutter consumption are essential strategies for improving TBM tunneling efficiency. Selecting suitable tunneling parameters is crucial for enhancing rock-breaking efficiency and reducing cutter consumption. Existing research on the optimization of the ratio of maximum cutter spacing to penetration (Smax/P) based on field-measured data is limited, and few studies compare and analyze the relationship between SE, CI, and the Smax/P ratio separately. Consequently, this study determined optimal tunneling parameters for various types of surrounding rock and construction environments, aiming to more accurately optimize TBM tunneling performance during construction processes based on on-site construction data. This study conducted a comparative analysis of specific energy (SE) and the coarseness index (CI). Under both working conditions, the quadratic fitting coefficients of the CI are 4.2% and 10.6% higher than those of the SE, respectively, with the CI selected to represent the particle size distribution of rock chips. Finally, taking into account both the correlations between the CI and the ratio of maximum cutter spacing to penetration (Smax/P), as well as cutter consumption and the Smax/P ratio, an optimization method for the TBM tunneling parameter was established under both dry and saturated conditions. The research findings indicate that cutter consumption exhibits an exponential increase with a higher rock Cerchar Abrasivity Index (CAI); it initially decreases as the Smax/P ratio increases and subsequently increases in both dry and saturated conditions. Instead, the CI demonstrates an initial increase and subsequent decrease as the Smax/P ratio increases. Maximizing rock-breaking efficiency and minimizing cutter consumption are crucial for improving tunneling performance. In saturated conditions, the corresponding optimal Smax/P ratio ranges are 7.055–8.319 for soft rock, 8.606–8.931 for medium–hard rock, and 13.50–14.00 for hard rock, and these optimal ranges under dry conditions are 8.495–9.457, 10.972–12.169, and 16.5–17.5 for the same rock types. This study provides optimal Smax/P ratio ranges for TBM tunneling, thereby significantly enhancing tunneling efficiency.

Background: Competitive intelligence (CI) involves recognising that intelligence is the basis of firms engaging in strategic activities in a competitive marketplace. Numerous studies have demonstrated the benefits of CI in strategic planning processes, but the impact of CI on strategy execution has received less academic attention. Objectives: This study aims to critically examine the current state of the CI and the strategy implementation literature. It also identifies gaps and limitations in the existing literature. Method: This study employed systematic literature with the selection criterion to identify 33 publications published between 2008 and 2022. Thematic content analysis provided a range of analytic options. Academic Search Complete, EBSCOhost, and Google Scholar databases were used to locate peer-reviewed journal articles. The publications were grouped by journal names, year of publication, and article count. Results: The study found that CI played a vital role in developing company strategies and practices. Our study also showed that a plethora of peer-reviewed academic articles on CI were published in developed countries such as North America and Europe. Only a few CI-related studies have been published in developing countries. Conclusion: Most authors have not examined how CI leads to strategy implementation, even though CI research has gained traction internationally over the years. Competitive intelligence was not found to have a relationship with implementing, evaluating, and monitoring strategies pointing out gaps in the literature and suggesting future research. Contribution: This study examines the current state of the literature on CI and strategy implementation, and identifies gaps in the existing literature. Furthermore, the study contributes to academic knowledge by emphasising the significance of a well-defined and structured CI process in achieving strategy implementation outcomes.

The use of environmentally friendly corrosion inhibitors (CIs) is an effective way to overcome the environmental problems caused by existing CIs that contain nitrogen or phosphorus components. Plant extracts, as a type of environmentally friendly CI, have attracted considerable attention. In this work, the corrosion inhibition properties of spinach extract (AESPE) on Q235 steel were studied in a hydrochloric acid medium. First, AESPE was extracted from spinach by an ethanol-acetone reflux method and its main structural and stability parameters in hydrochloric acid medium were determined by infrared spectroscopy (FTIR) and ultraviolet spectroscopy (UV–vis). Second, the corrosion inhibition properties of AESPE on Q235 steel in a 0.5 M hydrochloric acid solution were studied by weight loss (WTL), dynamic potential polarisation (PDP), linear polarisation (LPR), electrochemical impedance spectroscopy (EIS) and quantum chemical calculation methods. The results showed that AESPE could significantly slow the corrosion rate (Vcorr) of Q235 steel in 0.5 M hydrochloric acid medium, which was via a mixed corrosion inhibition mechanism at the cathode and anode. As the AESPE concentration increased, the cathode and anode currents decreased and the active corrosion sites were blocked; thus, the Vcorr decreased and the corrosion inhibition efficiency (E (%)) increased. Under the conditions of 303 K and 300 mg⋅L–1 AESPE, the E (%) of AESPE for Q235 steel was>90%. As the system temperature increased, the E% of AESPE for Q235 steel decreased but the extent of this decrease was small. This work shows that AESPE is an environmentally friendly CI with a good corrosion inhibition effect.

Here, we show that 3,5-bis[(1E)-2-(2,6-dichlorophenyl)ethenyl]-1H-pyrazole 2l depolymerizes microtubules and reduces the number of growing tips of microtubules. The fluorescence recovery after photobleaching experiment in live MCF-7 cells showed that pyrazole 2l suppresses spindle microtubule dynamics. Further, the compound inhibits chromosome movements, activates the spindle assembly checkpoint and blocks mitosis in MCF-7 cells. Pyrazole 2l treatment induced cell death in a variety of pathways. Pyrazole 2l induces cell death independent of BubR1 and p53 levels of MCF-7 cells upon microtubule depolymerization. Further, pyrazole 2l increases the interaction between NF-κB and microtubules and enhances the nuclear localization of NF-κB at its half-maximal proliferation inhibitory concentration while a high concentration of the compound reduced the nuclear localization of NF-κB. Interestingly, the compound exerted significantly stronger antiproliferative effects in cancerous cells than in non-cancerous cells. The results indicated that pyrazole 2l inhibits mitosis by targeting microtubules, induces several types of cell death stimuli and suggests its potential as a lead in developing anticancer agent. [ABSTRACT FROM AUTHOR]

Day by day new technologies are emerging to focus on reducing power, area and increasing the speed of operation. Reversible logic is an emerging technology in the field of low power computation. Shift registers are among the most important elements in fabricating reversible memory circuits and Arithmetic Logic units. In this paper, we represent efficient design of 4-bit and 8-bit reversible shift registers SIPO (Serial IN and Parallel Out), SISO (Serial IN and Serial Out), PIPO (Parallel IN and Parallel Out), PISO (Parallel IN and Out) and Universal Shift Registers (USR). Garbage reduction is achieved by the existing designs. All Shift Registers are built with ‘0’ garbage output (GO) and reduced constant inputs (CI). 4Bit SIPO is built with 3 CI and it is 62.5% improvement over the existing design. The same circuit does SISO functionality too. In this improvement of 25% in CI and 100% in GO is achieved. 4 Bit PIPO circuit is built with 3 CI and it is 25% improvement over existing design. The same circuit does PISO functionality too. The proposed design of SIPO, SISO and PIPO shift registers. 4 Bit PISO is built with 3 CI and 4 GO with an improvement of 60% and 70% respectively. 4-Bit universal shift register is built with 11 CI and 15 GI. CI of 4 bit USR is improved by 65.6% over one design and 50% over another design. GO of 4-bit USR is improved by 6.25% over one design and 53.1% over another design. The 8-bit shift registers of all configurations are built. [ABSTRACT FROM AUTHOR]

BackgroundMany parents develop stress-related symptoms and depression when their preterm infant is hospitalised in the neonatal intensive care unit (NICU) after birth. We reviewed the evidence of parent well-being with preterm infants hospitalised in single family rooms (SFRs) or in open bay neonatal units (OBUs).MethodsFor this systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) databases from inception through 22 November 2019 using controlled terms and text words related to prematurity and NICU-design. We included randomised and non-randomised studies comparing outcomes in parents with preterm infants admitted to SFRs or OBUs. Methodological quality was assessed using Cochrane Collaboration's Risk of Bias Tool for randomised controlled trials and the Risk of Bias Tool for Non-Randomised Studies of Interventions (ROBINS-I). Outcomes included: parental stress, satisfaction, participation (presence/involvement/skin-to-skin care), self-efficacy, parent-infant-bonding, depression, anxiety, post-traumatic stress, empowerment, and degree of family-centred care. Summary estimates were calculated using random effects models with standardised mean differences (SMDs). PROSPERO registration: CRD42016050643.FindingsWe identified 614 unique publications. Eleven study populations (1, 850 preterm infants, 1, 549 mothers and 379 fathers) were included. All but one study were at serious to critical risk of bias. SFRs were associated with higher levels of parental presence, involvement, and skin-to-skin care. Upon discharge, SFRs were associated with lower stress levels (n = 828 parents, SMD-0·30,95%CI -0·50;-0·09, p

OBJECTIVES: This study will compare the incidence of major adverse cardiovascular events (MACEs) with androgen deprivation therapy (ADT) among men with advanced prostate cancer who are being treated with a gonadotropin-releasing hormone (GnRH) antagonist versus a GnRH agonist. BACKGROUND: Treatment of advanced prostate cancer with ADT might increase the risk of subsequent cardiovascular events among men with known atherosclerotic cardiovascular disease (ASCVD), but a recent meta-analysis suggested that this risk might be lower with ADT using a GnRH antagonist versus a GnRH agonist. METHODS: PRONOUNCE is a multicenter, prospective, randomized, open, blinded endpoint trial that will enroll approximately 900 patients with advanced prostate cancer and pre-existing ASCVD who will be treated with ADT. Participants will be randomized to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide as ADT for 12 months. The primary endpoint is time from randomization to first confirmed, adjudicated occurrence of a MACE, which is defined as a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke through 12 months of ADT treatment. Baseline cardiovascular biomarkers (high-sensitivity C-reactive protein, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide), as well as serial inflammatory and immune biomarkers, will be evaluated in exploratory analyses. RESULTS: As of October 1, 2019, a total of 364 patients have been enrolled. The mean age is 74 years, 90% are white, 80% have hypertension or dyslipidemia, 30% diabetes mellitus, 40% have had a previous myocardial infarction, and 65% have had previous revascularization. Regarding prostate cancer features at randomization, 48% of the patients had localized disease, 23% had locally advanced disease, and 18% had metastatic disease. CONCLUSIONS: PRONOUNCE is the first prospective cardiovascular outcomes trial in advanced prostate cancer that will delineate whether the risk of subsequent cardiovascular events associated with ADT is lower with a GnRH antagonist versus a GnRH agonist for men with pre-existing ASCVD. (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease [PRONOUNCE]; NCT02663908).

MicroRNAs (miRNAs or miRs) are small noncoding RNAs derived from genome to control target gene expression. Recently we have developed a novel platform permitting high-yield production of bioengineered miRNA agents (BERA). This study is to produce and utilize novel fully-humanized BERA/miR-328-3p molecule (hBERA/miR-328) to delineate the role of miR-328-3p in controlling nutrient uptake essential for cell metabolism. We first demonstrated successful high-level expression of hBERA/miR-328 in bacteria and purification to high degree of homogeneity (>98%). Biologic miR-328-3p prodrug was selectively processed to miR-328-3p to suppress the growth of highly-proliferative human osteosarcoma (OS) cells. Besides glucose transporter protein type 1, gene symbol solute carrier family 2 member 1 (GLUT1/SLC2A1), we identified and verified large neutral amino acid transporter 1, gene symbol solute carrier family 7 member 5 (LAT1/SLC7A5) as a direct target for miR-328-3p. While reduction of LAT1 protein levels by miR-328-3p did not alter homeostasis of amino acids within OS cells, suppression of GLUT1 led to a significantly lower glucose uptake and decline in intracellular levels of glucose and glycolytic metabolite lactate. Moreover, combination treatment with hBERA/miR-328 and cisplatin or doxorubicin exerted a strong synergism in the inhibition of OS cell proliferation. These findings support the utility of novel bioengineered RNA molecules and establish an important role of miR-328-3p in the control of nutrient transport and homeostasis behind cancer metabolism.

The present study aims to investigate the usage and benefits of cochlear implants (CIs) in elderly patients aged ≥85 years, including their device-handling issues, follow-ups, and the influence on their well-being. The patients answered one questionnaire regarding quality of life, EQ5D-3L, and one questionnaire, obtained from the Swedish CI quality register, regarding usage, handling, satisfaction, remaining difficulties, etc. The medical records were searched for the implantation date, implant model, speech processor model, monosyllabic (MS) word scores, infections over the implant, and compliance regarding scheduled visits to the clinic. The results show that most elderly patients are satisfied full-time users of their implants. Even though most patients had no problems handling their CI, handling issues must be considered. Recurring guidance and training on device operation are needed. We suggest that follow-up visits are essentially needed for this group of patients on a regular basis. CI surgery is considered a safe treatment, even for the elderly. Upgrads to new external equipment (e.g., sound processors) should not be excluded because of their age. The results suggested that the CI positively affected their well-being. This study was approved by the Swedish Ethical Review Authority (5/10-2021, Dnr: 2021-04970).

Background: Lung cancer is a common disease for patients over the age of 50 years, especially males due to smoking habits. This study aimed to compare the modulation complexity score (MCS) for the advanced treatment planning techniques which the intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Materials and Methods: Thirty patients who had non-small lung cancerous tumors on their left side participated in this study. The range ages were 68 to 98 years, the heights were between 151 and 182cm and they having weights from 46 to 79 kg. For Each patient will create two plans dial using two different techniques, which will be Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) in the Monaco 5.1 version, and then those plans will be forwarded to the Infinity Linear Accelerator (LINAC). For the purposes of evaluation, the dose volume histogram is utilized to perform the calculation necessary to determine the dose for tumors and Organs at Risk (OAR). After that, the modulation complexity score, also known as the MCS, was determined using the multiyear collimators of the plans. Results: Showed that the mean age of males was (82.6 ± 4.93) years, while the mean age of females was (72.12 ± 3.13) years. The proportion of males was significantly higher than that of females. The female patient had a higher body mass index than the male patient. The mean height of men in this study was (172.85 ± 2.02) cm, while the mean height of women was (156.32± 1.21) cm. The coverage planning target volume (PTV) for the left lung tumor shows that the VMAT was significantly higher than the IMRT at 95%, 98%, 5%, and 2%. When comparing IMRT and VMAT for the PTV 105%, there was no discernible difference between the two. According to the statistics, the conformity and homogeneity of the dose delivered by the VMAT was noticeably higher than those delivered by the IMRT. According to the findings of the study, the MCS score for the VMAT is noticeably higher than that of the IMRT. In the case of the IMRT technique, the relationship between the MCS and the total number of monitor units was found to be positive and direct, whereas in the case of the VMAT technique, the relationship was found to be negative and inverse. Conclusions: The volumetric modulated arc therapy (VMAT) shows a better coverage and less complexity technique and could protect the heart, spinal cord, and right lung than the IMRT. [ABSTRACT FROM AUTHOR]

The primary objective of the current study was to create a mathematical model utilizing fractional-order calculus for the purpose of analyzing the symmetrical characteristics of Wolbachia dissemination among Aedesaegypti mosquitoes. We investigated various strains of Wolbachia to determine the most sustainable one through predicting their dynamics. Wolbachia is an effective tool for controlling mosquito-borne diseases, and several strains have been tested in laboratories and released into outbreak locations. This study aimed to determine the symmetrical features of the most efficient strain from a mathematical perspective. This was accomplished by integrating a density-dependent death rate and the rate of cytoplasmic incompatibility (CI) into the model to examine the spread of Wolbachia and non- Wolbachia mosquitoes. The fractional-order mathematical model developed here is physically meaningful and was assessed for equilibrium points in the presence and absence of disease. Eight equilibrium points were determined, and their local and global stability were determined using the Routh–Hurwitz criterion and linear matrix inequality theory. The basic reproduction number was calculated using the next-generation matrix method. The research also involved conducting numerical simulations to evaluate the behavior of the basic reproduction number for different equilibrium points and identify the optimal CI value for reducing disease spread. [ABSTRACT FROM AUTHOR]