Reinforcing Security and Usability of Crypto-Wallet with Post-Quantum Cryptography and Zero-Knowledge Proof

Crypto-wallets or digital asset wallets are a crucial aspect of managing cryptocurrencies and other digital assets such as NFTs. However, these wallets are not immune to security threats, particularly from the growing risk of quantum computing. The use of traditional public-key cryptography systems in digital asset wallets makes them vulnerable to attacks from quantum computers, which may increase in the future. Moreover, current digital wallets require users to keep track of seed-phrases, which can be challenging and lead to additional security risks. To overcome these challenges, a new algorithm is proposed that uses post-quantum cryptography (PQC) and zero-knowledge proof (ZKP) to enhance the security of digital asset wallets. The research focuses on the use of the Lattice-based Threshold Secret Sharing Scheme (LTSSS), Kyber Algorithm for key generation and ZKP for wallet unlocking, providing a more secure and user-friendly alternative to seed-phrase, brain and multi-sig protocol wallets. This algorithm also includes several innovative security features such as recovery of wallets in case of downtime of the server, and the ability to rekey the private key associated with a specific username-password combination, offering improved security and usability. The incorporation of PQC and ZKP provides a robust and comprehensive framework for securing digital assets in the present and future. This research aims to address the security challenges faced by digital asset wallets and proposes practical solutions to ensure their safety in the era of quantum computing

Numerical and mechanical modeling of the inner ear vestibular apparatus

As you read this text, tilt your head left and right. Note then that the text stands still. Now draw a clear line onto the ground, close your eyes and walk over it. You most likely succeeded. The aforementioned facts or abilities are remarkable skills given by a small inner ear organ set, the vestibular system. Usually operating in the background, this structure infrequently comes to the attention of our conscious mind. In this work, three finite element models (in CATIA V5R18 and COMSOL Multiphysics 3.5a environments) are developed to provide a mechanical understanding of this formidable nature’s gift. In these numerical models, a fluid structure interaction modeling is presented to show the system behavior during a horizontal head spin. Finally, a physical augmented scale model is proposed, including the choice of materials and a similitude study

Noncontact Diffuse Optical Assessment of Blood Flow Changes in Head and Neck Free Tissue Transfer Flaps

Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning “1”) for the calculation of relative BF change (rBF). The rBF changes over the seven successful flaps were 1.89±0.15, 2.26±0.13, and 2.43±0.13 (mean±standard error), respectively, on postoperative days 2, 4, and 7. These postoperative values were significantly higher than the intraoperative baseline values (

Retinal arteriolar vascular reactivity in untreated and progressive primary open-angle glaucoma

PURPOSE. To determine (1) the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated primary open-angle glaucoma (uPOAG) or progressive (p)POAG and in control subjects and (2) the effect of treatment with 2% dorzolamide on retinal vascular reactivity in uPOAG. METHODS. The sample comprised 11 patients with uPOAG (after undergoing treatment, they became treated (t)POAG), 17 patients with pPOAG (i.e., manifesting optic disc hemorrhage), and 17 age-similar control subjects. The partial pressure of end-tidal CO 2 (PETCO 2 ) was stabilized at 38 mm Hg at baseline. After baseline (10 minutes), normoxic hypercapnia was then induced (15 minutes) with an automated gas flow controller. Retinal arteriolar and optic nerve head (ONH) blood hemodynamics were assessed. The procedures were repeated after treatment with 2% dorzolamide for 2 weeks in tPOAG. RESULTS. Baseline arteriolar hemodynamics were not different across the groups. In control subjects, diameter, velocity, and flow increased (P Ͻ 0.001) in response to normoxic hypercapnia. There was no change in all three hemodynamic parameters to normoxic hypercapnia in uPOAG, whereas only blood flow increased (P ϭ 0.030) in pPOAG. Vascular reactivity was decreased in uPOAG and pPOAG patients compared with that in control subjects. After treatment with topical 2% dorzolamide for 2 weeks, the tPOAG group showed an increase in diameter, velocity, and flow (P Յ 0.04) in response to normoxic hypercapnia. Similar trends were noted for ONH vascular reactivity. CONCLUSIONS. A reduced magnitude of arteriolar vascular reactivity in response to normoxic hypercapnia was shown in uPOAG and in pPOAG. Vascular reactivity improved after dorzolamide treatment in POAG. (Invest Ophthalmol Vis Sci

Inconsistent country-wide reporting of adverse drug reactions to antimicrobials in Sierra Leone (2017–2021): A wake-up call to improve reporting

From MDPI via Jisc Publications RouterHistory: accepted 2022-03-08, pub-electronic 2022-03-10Publication status: PublishedBackground: Monitoring of adverse drug reactions (ADRs) to antimicrobials is important, as they can cause life-threatening illness, permanent disabilities, and death. We assessed country-wide ADR reporting on antimicrobials and their outcomes. Methods: A cross-sectional study was conducted using individual case safety reports (ICSRs) entered into the national pharmacovigilance database (VigiFlow) during 2017−2021. Results: Of 566 ICSRs, inconsistent reporting was seen, with the highest reporting in 2017 and 2019 (mass drug campaigns for deworming), zero reporting in 2018 (reasons unknown), and only a handful in 2020 and 2021 (since COVID-19). Of 566 ICSRs, 90% were for antiparasitics (actively reported during mass campaigns), while the rest (passive reporting from health facilities) included 8% antibiotics, 7% antivirals, and 0.2% antifungals. In total, 90% of the reports took >30 days to be entered (median = 165; range 2−420 days), while 44% had 75% of all variables filled in (desired target = 100%). There were 10 serious ADRs, 18 drug withdrawals, and 60% of ADRs affected the gastrointestinal system. The patient outcomes (N-566) were: recovered (59.5%), recovering (35.5%), not recovered (1.4%), death (0.2%), and unknown (3.4%). There was no final ascertainment of ‘recovering’ outcomes. Conclusions: ADR reporting is inconsistent, with delays and incomplete data. This is a wake-up call for introducing active reporting and setting performance targets.19pubpub

Achieving minimum standards for infection prevention and control in Sierra Leone: Urgent need for a quantum leap in progress in the COVID-19 era!

From MDPI via Jisc Publications RouterHistory: accepted 2022-04-20, pub-electronic 2022-05-06Publication status: PublishedIntroduction: Good Infection prevention and control (IPC) is vital for tackling antimicrobial resistance and limiting health care-associated infections. We compared IPC performance before (2019) and during the COVID-19 (2021) era at the national IPC unit and all regional (4) and district hospitals (8) in Sierra Leone. Methods: Cross-sectional assessments using standardized World Health Organizations IPC checklists. IPC performance scores were graded as inadequate = 0−25%, basic = 25.1−50%, intermediate = 50.1−75%, and advanced = 75.1−100%. Results: Overall performance improved from ‘basic’ to ‘intermediate’ at the national IPC unit (41% in 2019 to 58% in 2021) and at regional hospitals (37% in 2019 to 54% in 2021) but remained ‘basic’ at district hospitals (37% in 2019 to 50% in 2021). Priority gaps at the national IPC unit included lack of: a dedicated IPC budget, monitoring the effectiveness of IPC trainings and health care-associated infection surveillance. Gaps at hospitals included no assessment of hospital staffing needs, inadequate infrastructure for IPC and lack of a well-defined monitoring plan with clear goals, targets and activities. Conclusion: Although there is encouraging progress in IPC performance, it is slower than desired in light of the COVID-19 pandemic. There is urgent need to mobilize political will, leadership and resources and make a quantum leap forward.19pubpub

Antibiotic prescribing for upper respiratory infections among children in rural China: a cross-sectional study of outpatient prescriptions

Background: Overuse of antibiotics contributes to the development of antimicrobial resistance. Objective: This study aims to assess the condition of antibiotic use at health facilities at county, township and village levels in rural Guangxi, China. Methods: We conducted a cross-sectional study of outpatient antibiotic prescriptions in 2014 for children aged 2–14 years with upper respiratory infections (URI). Twenty health facilities were randomly selected, including four county hospitals, eight township hospitals and eight village clinics. Prescriptions were extracted from the electronic records in the county hospitals and paper copies in the township hospitals and village clinics. Results: The antibiotic prescription rate was higher in township hospitals (593/877, 68%) compared to county hospitals (2736/8166, 34%) and village clinics (96/297, 32%) (p < 0.001). Among prescriptions containing antibiotics, county hospitals were found to have the highest use rate of broad-spectrum antibiotics (82 vs 57% [township], vs 54% [village], p < 0.001), injectable antibiotics (65 vs 43% [township], vs 33% [village], p < 0.001) and multiple antibiotics (47 vs 15% [township], vs 0% [village], p < 0.001). Logistic regression showed that the likelihood of prescribing an antibiotic was significantly associated with patients being 6–14 years old compared with being 2–5 years old (adjusted odds ratio [aOR] = 1.3, 95% CI 1.2–1.5), and receiving care at township hospitals compared with county hospitals (aOR = 5.0, 95% CI 4.1–6.0). Prescriptions with insurance copayment appeared to lower the risk of prescribing antibiotics compared with those without (aOR = 0.8, 95% CI 0.7–0.9). Conclusions: Inappropriate use of antibiotics was high for outpatient childhood URI in the four counties of Guangxi, China, with the highest rate found in township hospitals. A significant high proportion of prescriptions containing antibiotics were broad-spectrum, by intravenous infusion or with multiple antibiotics, especially at county hospitals. Urgent attention is needed to address this challenge

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio