Explore the vast range of titles available.

The use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso’s subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso’s role in breast cancer progression.Through automated image analysis, Singhal et al quantify nuclear versus cytoplasmic distribution of the Kaiso transcription factor in breast cancer patient tissue. They find that Kaiso distribution correlates with breast cancer subtype and overall survival, and discover a link between cytoplasmic Kaiso and autophagy marker LC3.

Detection of integrated human papillomavirus type 16 (HPV-16) DNA in SiHa and CaSki cells was used as a model system to demonstrate sensitivity and resolution of a well defined target. Using 293- to 1987-base polymerase chain reaction (PCR)-synthesized probes to the E6 and E7 open reading frames of HPV-16, several fluorescent in situ hybridization (FISH) detection methods, enhanced with tyramide signal amplification (TSA), were compared. The synthetic probes were biotin labeled by a nick translation method and the hybridized probes were detected by various fluorescent TSA methods using cyanine 3 tyramide, biotinyl tyramide and a biotin TSA Plus reagent. High sensitivity detection in SiHa cells was demonstrated using a 619-base probe to detect two single copies of integrated HPV-16 DNA. In CaSki cells, which contain up to 600 copies of HPV-16 DNA, a 293-base probe was used for detection. The results of these comparisons show that with refinement of TSA methods and reagents, increasing levels of high sensitivity detection can be achieved and that these methods allow subnuclear localization as well.

A method was developed to produce a murine antibody in ascitic fluid to human factor VIII/von Willebrand factor. The murine antiserum was comparable to a commercial rabbit antiserum when used to quantitate factor VIII related antigen by immunoelectrophoresis and enzyme immunoassay. The structure of factor VIII/von Willebrand factor was examined by circular dichroism spectroscopy. F VIII/vWF was found to have approximately 50% unordered or random coil structure and less than 15% (alpha) helical structure. It appears to be a structurally stable protein since changes in its CD spectrum were minimal after heating, and in the pH range 5-9. F VIII/vWF most likely contains many disulfide bonds which are responsible for its stability. This is evident in the change in its CD spectrum on the addition of dithiothreitol. The interaction between F VIII/vWF and heparin was investigated. F VIII/vWF bound to heparin at physiological pH and ionic strength. By increasing the ionic strength, F VIII/vWF eluted retaining all of its biological activities. From the pH dependence, and the effect of calcium and citrate on the interaction, it appears that it occurs by two independent mechanisms. One is through a positively charged residue on F VIII/vWF and the other involves intrinsic calcium. The replacement of calcium by terbium was undetectable by fluorescence.

Objective Community-based peer and community health worker-led diabetes self-management programs (COMP-DSMP) can benefit diabetes care, but the supporting evidence has been inadequately assessed. This systematic review explores the nature of COMP-DSMP in low- and middle-income countries’ (LMIC) primary care settings and evaluates implementation strategies and diabetes-related health outcomes. Methods We searched the Cochrane Library, PubMed-MEDLINE, SCOPUS, CINAHL PsycINFO Database, International Clinical Trials Registry Platform, Clinicaltrials.gov , Pan African Clinical Trials Registry (PACTR), and HINARI (Health InterNetwork Access to Research Initiative) for studies that evaluated a COMP-DSMP in adults with either type 1 or type 2 diabetes in World Bank-defined LMIC from January 2000 to December 2019. Randomised and non-randomised controlled trials with at least 3 months follow-up and reporting on a behavioural, a primary psychological, and/or a clinical outcome were included. Implementation strategies were analysed using the standardised implementation framework by Proctor et al. Heterogeneity in study designs, outcomes, the scale of measurements, and measurement times precluded meta-analysis; thus, a narrative description of studies is provided. Results Of the 702 records identified, eleven studies with 6090 participants were included. COMP-DSMPs were inconsistently associated with improvements in clinical, behavioural, and psychological outcomes. Many of the included studies were evaluated as being of low quality, most had a substantial risk of bias, and there was a significant heterogeneity of the intervention characteristics (for example, peer definition, selection, recruitment, training and type, dose, and duration of delivered intervention), such that generalisation was not possible. Conclusions The level of evidence of this systematic review was considered low according to the GRADE criteria. The existing evidence however does show some improvements in outcomes. We recommend ongoing, but well-designed studies using a framework such as the MRC framework for the development and evaluation of complex interventions to inform the evidence base on the contribution of COMP-DSMP in LMIC.

BackgroundMaintaining a suppressed HIV plasma viral load (pVL) is critical to the optimal management of people living with HIV (PLWH), and to prevent HIV transmission. We examined trends and determinants of unsuppressed pVL among PLWH from April 2005 to March 2020 in British Columbia (BC), Canada by HIV exposure groups.MethodsWe analyzed data from all PLWH in BC identified in a provincial database linking testing, treatment, laboratory, pharmacy and administrative health data. For each year, individuals were classified as having an unsuppressed pVL if they were newly diagnosed, had any pVL ≥ 200 copies/mL test result, or had no pVL measurement. We used univariate generalized estimating equations (GEE) to examine trends over time and multivariate GEE modelling to examine factors associated with unsuppressed pVL.ResultsPLWH in BC increased from 5712 in 2005 to 8012 in 2020, and the proportion of those with pVL ≥ 200 copies/mL decreased from 66.4% to 18.1% (p < 0.0001, test of trend). Those who were people who inject drugs (PWID) (adjusted odds ratio [aOR] = 1.92; 95% CI 1.77–2.08) and those with only heterosexual exposures (aOR = 1.16; 95% CI 1.07–1.26) or other exposures (aOR = 1.23; 95% CI 1.06–1.42) had increased odds of unsuppressed pVL, compared with men who have sex with men (MSM). Unsuppressed pVL was also associated with female gender identity (p = 0.0109), first CD4 cell count result (p = 0.0085), year of ART initiation, health authority residence, hepatitis C seropositivity, and younger age at diagnosis (p < 0.001 for all).ConclusionsThe proportion and number of PLWH with unsuppressed pVL in BC fell signficantly over a 15-year period, with different trends by HIV exposure categories. Those who are PWID, females, and youth may require additional supports to be retained in effective HIV care.

In this pathbreaking study, authors Davis B. Bobrow and Mark A. Boyer argue for \"muted optimism\" about the future of international cooperation. Leaders of a growing movement that integrates constructivism into traditional international studies concepts and methods, Bobrow and Boyer analyze four key international issues: development cooperation, debt management, peacekeeping operations, and environmental affairs. Their approach integrates elements of public goods theory, identity theory, new institutionalism, and rational choice. Defensive Internationalism is a well-written, creative and coherent synthesis of ideas that have up to now been considered irreconcilable. It is appropriate for upper-level undergraduate and graduate students in international relations, conflict studies, and political economy, and promises to become a foundational work in its field.

This article examines the ways and degrees to which nation-states participate in and financially support United Nations peacekeeping operations (UN PKOs). The authors contend that UN PKOs are impure public goods whose provision conforms to expectations from public goods theory that deals with the provision of impure public goods and club goods, and much less to the hegemonic stability variant of the public goods approach. Conceptual arguments are followed by an examination of general patterns of UN PKOs, personnel and financial contributions to them, and the U.S. role in them. The authors conclude that the post-cold war period has seen a notable increase in the volume of provision of peacekeeping and in the quantity and diversity of contributors and beneficiaries. They recognize the difficulties posed by recent U.S. nonpayments and suggest the possibility of adjustments that will reestablish the financial basis that continuing substantial provision will require.

Effectively tackling the growing noncommunicable disease (NCD) burden in low- and middle-income countries (LMIC) is a major challenge. To address research needs in this setting for NCDs, in 2009, National Heart, Lung, and Blood Institute (NHLBI) and UnitedHealth Group (UHG) engaged in a public-private partnership that supported a network of 11 LMIC-based research centers and created the NHLBI-UnitedHealth Global Health Centers of Excellence (COE) Program. The Program's overall goal was to contribute to reducing the cardiovascular and lung disease burdens by catalyzing in-country research institutions to develop a global network of biomedical research centers. Key elements of the Program included team science and collaborative approaches, developing research and training platforms for future investigators, and creating a data commons. This Program embraced a strategic approach for tackling NCDs in LMICs and will provide capacity for locally driven research efforts that can identify and address priority health issues in specific countries' settings. •A public-private partnership created the Program.•Forming the Program captured all the elements of team science.•The Program used best practices of collaborative science.•Research training for future investigators was a high priority.

We discuss design considerations in moving practice through the boundary from physical to virtual places. Although the examples are grounded in a school environment, we believe that the design tradeoffs apply to any networked collaborative space. The context for discussion is Pueblo, a MOO-based, cross-generation network learning community centered around a K-6 elementary school. The development of practice in Pueblo draws upon teachers' and students' experience with semi-structured classroom participation frameworks – informal structures of social interaction which foster certain ways of thinking, doing, and learning through guided activities and conversations. We have translated several familiar frameworks into the Pueblo setting, using the classroom versions as models to be adapted and transformed as they are aligned with the affordances of the MOO. We identify four design dimensions that have emerged as particularly interesting and important in this process: audience, asynchrony and synchrony, attention and awareness, and prompts for reflection. We illustrate design choices in each dimension using several of the participation frameworks that have been translated into Pueblo. We discuss the relation between MOO affordances and design choices and provide examples of successful and unsuccessful alignment between them.

Programs are judged not only by whether they faithfully carry out the intended processing but also by whether they are understandable and easily changed. Programming systems for artificial intelligence applications use specialized languages, environments, and knowledge-based tools to reduce the complexity of the programming task. Language styles based on procedures, objects, logic, rules, and constraints reflect different models for organizing programs and facilitate program evolution and understandability. To make programming easier, multiple styles can be integrated as sublanguages in a programming environment. Programming environments provide tools that analyze programs and create informative displays of their structure. Programs can be modified by direct interaction with these displays. These tools and languages are helping computer scientists to regain a sense of control over systems that have become increasingly complex.