Explore the vast range of titles available.

IntroductionHuman papillomavirus type 16 (HPV16) E6 antibodies may be an early biomarker of anal cancer. We cross-sectionally evaluated when in the course of anal disease, HPV16 antibodies are induced.MethodsA nested case-control study of 846 men who have sex with men (MSM) was conducted within a prospective study of men with and without HIV. Cases of anal HPV16 (N=262), biopsy-confirmed high-grade squamous intraepithelial lesion (HSIL;N=140), and anal cancer (N=21) were individually matched to controls (N=423) on HIV status, study-participation duration, and age. Serum samples closest to diagnosis underwent HPV serologic testing; prediagnostic serial samples were tested for anal cancers only. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs).ResultsHPV16 E6 seroprevalence was non-significantly elevated in anal disease: OR:1.6 (95%CI:0.7-3.6) for HPV16 infection; OR:1.4 (95%CI:0.5-3.8) for HSIL; and OR:1.5 (95%CI:0.3-9.0) for anal cancer. HPV16 E6 seroprevalence was dramatically lower among men with versus without HIV with the same disease stage: 1.5% vs. 11.2% ( <0.001) for anal HPV16 infection; 4.2% vs. 13.6% ( =0.043) for HSIL; and 5.6% vs. 66.7% ( =0.005) for anal cancer. HPV16 E6 seroprevalence was only associated with anal HPV16 among men without HIV (OR:2.9 [95%CI:1.0-8.0]); no significant associations between HPV16 E6 seroprevalence and anal disease were observed among men with HIV. Among the 21 anal cancers, 66.7% (2/3) without HIV and 5.6% (1/18) with HIV were HPV16 E6 seropositive before diagnosis.ConclusionsHPV16 E6 antibodies show poor sensitivity for anal cancer and its precursors, particularly among men with HIV.

Objectives/Goals: Identify genetic variants associated with the development of diabetic retinopathy (DR) and its advanced complication, diabetic macular edema (DME). Despite DME being a leading cause of vision loss among people with diabetes, genetic findings have been limited by small sample size, underrepresentation of diverse populations, and poor study design. Methods/Study Population: Genome-wide association studies (GWAS) were conducted to identify genetic variants linked to DME. GWAS were conducted separately by ancestry (African, European, and Admixed American) in the Million Veteran Program and All of Us cohorts, adjusted for age, sex, BMI, diabetes duration, mean HbA1c, and 10 principal components. We then combined population groups to perform a multi-ancestry meta-analysis (Multi) using a software called METAL. Analyses included autosomes and chromosome X for DME versus DR controls (14,211 cases and 47,005 controls). Gene expression analyses were performed using S-PrediXcan across 49 tissues to identify genes whose predicted expression is associated with DME risk. APOL1 variant and haplotype analyses were conducted to assess ancestry-specific associations with DME and type 2 diabetes. Results/Anticipated Results: Genome-wide significant loci included G6PD (Multi and African), previously reported to influence diabetes diagnosis, and APOL1 (Multi and European), previously linked to kidney disease in African ancestry. Gene expression analyses revealed 32 significant gene–tissue pairs (Multi 18 and African 18), corresponding to 9 unique genes. In APOL1, E150K was strongly associated with DME in Europeans (OR=1.22, P=2.9×10 −8 ) and modestly in Africans (OR=1.18, P=5.3×10 −4 ). N264K also showed significant effects in Europeans (OR=1.42, P=9.8×10 −4 ) and weaker but consistent effects in Africans (OR=1.04, P=0.025). The high-risk G1/G2 haplotype demonstrated a modest association in African ancestry (OR=1.15, P=0.048). Discussion/Significance of Impact: This is the largest genetic study of DME, uncovering genetic risk factors that could potentially be driving risk, such as APOL1, a gene historically tied to kidney disease among individuals of African ancestry. Our results indicate its involvement may extend to diabetic complications more generally.

The advancement of renewable energy technologies and the deregulation of the electricity market have seen the emergence of Demand response (DR) programs. Demand response is a cost-effective load management strategy which enables the electricity suppliers to maintain the integrity of the power grid during high peak periods, when the customers' electrical load is high. DR programs are designed to influence electricity users to alter their normal consumption patterns by offering them financial incentives. A well designed incentive-based DR scheme that offer competitive electricity pricing structure can result in numerous benefits to all the players in the electricity market. Lower power consumption during peak periods will significantly enhance the robustness of constrained networks by reducing the level of power of generation and transmission infrastructure needed to provide electric service. Therefore, this will ease the pressure of building new power networks as we avoiding costly energy procurements thereby translating into huge financial savings for the power suppliers. Peak load reduction will also reduce the inconveniences suffered by end users as a result of brownouts or blackouts. Demand response will also drastically lower the price peaks associated with wholesale markets. This will in turn reduce the electricity costs and risks for all the players in the energy market. Additionally, DR is environmentally friendly since it enhances the flexibility of the power grid through accommodation of renewable energy resources. Despite its many benefits, DR has not been embraced by most electricity networks. This can be attributed to the fact that the existing programs do not provide enough incentives to the end users and, therefore, most electricity users are not willing to participate in them. To overcome these challenges, most utilities are coming up with innovative strategies that will be more attractive to their customers. Thus, this dissertation presents various demand response schemes that can be deployed by electricity providers to manage customer loads. This study also addresses the problem of manual demand response by proposing smart systems that will autonomously execute the DR programs without the direct involvement of the customers.

This study reviews the topic of big data management in the 21st-century. There are various developments that have facilitated the extensive use of that form of data in different organizations. The most prominent beneficiaries are internet businesses and big companies that used vast volumes of data even before the computational era. The research looks at the definitions of big data and the factors that influence its access and use for different persons around the globe. Most people consider the internet as the most significant source of this data and more specifically on cloud computing and social networking platforms. It requires sufficient and adequate management procedures to achieve the efficient use of the big data. The study revisits some of the conventional methods that companies use to attain this. There are different challenges such as cost and security that limit the use of big data. Despite these problems, there are various benefits that everyone can exploit by implementing it, and they are the focus for most enterprises.

This study concerns the security challenges that the people face in the usage and implementation of cloud computing. Despite its growth in the past few decades, this platform has experienced different challenges. They all arise from the concern of data safety that the nature of sharing in the cloud presents. This paper looks to identify the benefits of using a cloud computing platform and the issue of information security. The paper also reviews the concept of information hiding and its relevance to the cloud. This technique has two ways about it that impact how people use cloud computing in their organizations and even for personal implementations. First it presents the potential to circulate harmful information and files that can adversely affect the data those users upload on those platforms. It is also the basis of the strategies such as steganalysis and cryptographic storage architecture that are essential for data security.

A globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www.gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale.

Introduction The conventional clinical criteria for diagnosing a periprosthetic joint infection (PJI) rely on acute inflammatory readouts such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and synovial white blood cell counts. These metrics only detect actively septic joint replacements and may miss detecting biofilm-embedded bacteria that suppress neutrophil signaling and persist as a “hidden” subset of implants with a dormant infection. We hypothesize that previously infected joint replacements have a high prevalence of dormant infection that can be distinguished from aseptic revision joint replacements (replaced for instability, loosening, wear, and fracture) by the persistent inflammatory response within synovial fluid and/or circulating plasma, and that detecting a dormant infection indicates an increased risk of infection relapse. Methods This is an observational cohort study using synovial fluid and plasma proteomics of 96 immuno-oncology mediators (Olink Proteomics, Sweden) with three-year clinical follow-up from a single academic medical center (Stanford University, USA). Thirty patients undergoing revision joint replacement: culture-positive actively septic joint replacements ( n  = 7), aseptic revision joint replacements ( n  = 12), and re-implantations of joint replacements previously classified as infection-free by 2018 Musculoskeletal Infection Society (MSIS) criteria ( n  = 11). Differential expression, unsupervised clustering, Euclidean distance mapping, principal-component analysis, and gene-set variation analysis were used to define the inflammatory signature of dormant infection present in joint replacements with a prior infection. The identified biomarkers of dormant infection were correlated with the three-year incidence of infection relapse. Results Eight of eleven MSIS-cleared joint replacements (73%) clustered with culture-positive active infections despite normal ESR, CRP, and scant synovial neutrophils revealing the synovial inflammatory signature of dormant infection. A nine-analyte synovial panel consisting of PDGF-B, CXCL5, CXCL11, MCP-2 (CCL8), ANGPT1, TIE2, EGF, NOS3, and Gal-1 distinguished dormant infection from truly aseptic cases with 100% specificity and positive predictive value (sensitivity 22%, negative predictive value 74%). Synovial CXCL5 over-expression was a universal hallmark of both active and dormant infection, whereas matched plasma profiles showed no discriminatory power for all immuno-oncology mediators tested. Dormant infections exhibited downregulation of granulocyte activation and T-cell proliferation pathways (FDR < 0.001), mirroring immune evasion programs seen in cancer microenvironments. After a mean of 3 years follow-up, infection relapse occurred in 22% of the biomarker-positive dormant infections, but relapse did not occur in any of the biomarker-negative aseptic cases. Discussion Profiling of the persistent inflammatory response within the synovial fluid of two-stage re-implantations classified as “infection-free” by the MSIS criteria unmasked a clinically silent reservoir of biofilm-embedded bacteria that suppress clinical diagnostic criteria of active infection and define the novel clinical state of dormant infection. We used that profile to identify a novel culture-free panel of rule-out biomarkers for determining which re-implantations were safe from infection relapse. These findings challenge the use of conventional clinical diagnostic criteria, which are over-reliant on acute phase reactants and neutrophil recruitment, and creates a new prognostic clinical paradigm that now includes a future with precision, immune-guided management of dormant infections likely present in many implant-associated infections.

Background The WHO Safe Childbirth Checklist (SCC) contains 29 evidence-based practices (EBPs) across four pause points spanning admission to discharge. It has been shown to increase EBP uptake and has been tailored to specific contexts. However, little research has been conducted in East Africa on use of the SCC to improve intrapartum care, particularly for preterm birth despite its burden. We describe checklist adaptation, user acceptability, implementation and lessons learned. Methods The East Africa Preterm Birth Initiative (PTBi EA) modified the SCC for use in 23 facilities in Western Kenya and Eastern Uganda as part of a cluster randomized controlled trial evaluating a package of facility-based interventions to improve preterm birth outcomes. The modified SCC (mSCC) for prematurity included: addition of a triage pause point before admission; focus on gestational age assessment, identification and management of preterm labour; and alignment with national guidelines. Following introduction, implementation lasted 24 and 34 months in Uganda and Kenya respectively and was supported through complementary mentoring and data strengthening at all sites. PRONTO® simulation training and quality improvement (QI) activities further supported mSCC use at intervention facilities only. A mixed methods approach, including checklist monitoring, provider surveys and in-depth interviews, was used in this analysis. Results A total of 19,443 and 2229 checklists were assessed in Kenya and Uganda, respectively. In both countries, triage and admission pause points had the highest rates of completion. Kenya’s completion was greater than 70% for all pause points; Uganda ranged from 39 to 75%. Intervention facilities exposed to PRONTO and QI had higher completion rates than control sites. Provider perceptions cited clinical utility of the checklist, particularly when integrated into patient charts. However, some felt it repeated information in other documentation tools. Completion was hindered by workload and staffing issues. Conclusion This study highlights the feasibility and importance of adaptation, iterative modification and complementary activities to reinforce SCC use. There are important opportunities to improve its clinical utility by the addition of prompts specific to the needs of different contexts. The trial assessing the PTBi EA intervention package was registered at ClinicalTrials.gov NCT03112018 Registered December 2016, retrospectively registered.

Monkeypox virus (MPXV) is endemic in western and Central Africa, and in May 2022, a clade IIb lineage (B.1) caused a global outbreak outside Africa, resulting in its detection in 116 countries and territories. To understand the global phylogenetics of MPXV, we analyzed all available MPXV sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024. Our analysis reveals high mobility of clade I viruses within Central Africa, sustained human-to-human transmission of clade IIb lineage A viruses within the Eastern Mediterranean region and distinct mutational signatures that can distinguish sustained human-to-human from animal-to-animal transmission. Moreover, distinct clade I sequences from Sudan suggest local MPXV circulation in areas of eastern Africa over the past four decades. Our study underscores the importance of genomic surveillance in tracking spatiotemporal dynamics of MXPV clades and the need to strengthen such surveillance, including in some parts of eastern Africa. An analysis of all available mpox virus sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024, unveils the circulation pattern and spatiotemporal dynamics underlying the spread of the different viral clades.

Poultry production technologies adoption, such as improved Indigenous Chicken (IC) breeds and fabricated brooders, remain a viable option for enhancing IC productivity. However, the uptake of improved IC technologies remains low, especially in developing countries. This study investigated the adoption and intensity of the use of IC technologies in Machakos County, Kenya. The study adopted a cross-sectional survey to collect data from 374 households selected through a multi-stage sampling technique. A structured questionnaire and focus group discussion were employed, and data were analyzed using descriptive statistics and the Double-Hurdle model. The double hurdle results revealed that farmer experience, land size, non-farm activities, group membership, access to credit, awareness of IC technologies, and use of intensive/semi-intensive production systems were positively associated with IC technology adoption. However, household size was negatively associated with IC technology adoption. The intensity of use of IC technology was positively associated with gender, active labor, credit access, distance to the weather roads, and intensive production system. The study recommends that there is a need for agricultural stakeholders to promote membership in farmer associations and credit access, create awareness of IC technology, and improve opportunities for non-farm activities to help improve the adoption and intensity of the use of IC technologies. The integration of improved Indigenous Chicken (IC) technologies plays an essential role in bridging the existing demand for white meat in developing nations. The present popularity of the indigenous chicken is due to the ease of feed conversion, the organic nature of production, scavenging ability, and delicious products. Despite the increased demand, the rate of uptake of the improved IC technologies remained low. The findings underscore the crucial role of human-specific, economic, and institutional factors in determining the decision and intensity of IC technologies in the arid and semi-arid lands of Kenya. The focus should be on targeted interventions such as programs suited to the requirements of the region's farmers, increasing access to credit and extension services, and campaigning for supporting government policies and programs that stimulate the use of improved IC technologies.