Implementation of a patient safety training program in radiation oncology residency: A pilot study.

PURPOSE: An educational program using Radiation Oncology-Incident Learning System (RO-ILS) was developed to improve safety culture and training for radiation oncology (RO) residents. METHODS: The program included a pre-training assessment, interactive training, integration of residents into quality assurance meetings, and a post-training assessment over a 3 month rotation. RESULTS: Twelve residents completed the safety training program. Pre-training assessment mean scores (five-point scale) of experience with Incident Learning Systems (ILS), root-cause analysis (RCA), failure-mode and effect analysis (FMEA), safety training, and culture were 2.3, 2.8, 2.0, 4.0, and 4.4, respectively. Post-training assessment showed a significant increase in ILS 4.0 (p < 0.001), RCA 3.8 (p = 0.008), and FMEA 3.3 (p = 0.006) and safety culture (4.8, p = 0.043). Additionally, residents were anonymously surveyed ≥ 10 months after graduation to determine the long-term value of the program. The overall assessment from the graduated residents indicates that this education is valued by RO in many institutions. The majority of the residents are either currently utilizing or plan to utilize the information gained in this program in their new institutions. CONCLUSIONS: We report a successful implementation of a safety training program in a RO residency with significant improvements in self-reported confidence with the concepts of ILS, RCA, and FMEA and an improved perception of safety culture. This program can be implemented across all residency programs.

Subunit nanovaccine elicited T cell functional activation controls Trypanosoma cruzi mediated maternal and placental tissue damage and improves pregnancy outcomes in mice.

This study investigated a candidate vaccine effect against maternal Trypanosoma cruzi (Tc) infection and improved pregnancy outcomes. For this, TcG2 and TcG4 were cloned in a nanoplasmid optimized for delivery, antigen expression, and regulatory compliance (nano2/4 vaccine). Female C57BL/6 mice were immunized with nano2/4, infected (Tc SylvioX10), and mated 7-days post-infection to enable fetal development during the maternal acute parasitemia phase. Females were euthanized at E12-E17 (gestation) days. Splenic and placental T-cell responses were monitored by flow cytometry. Maternal and placental/fetal tissues were examined for parasites by qPCR and inflammatory infiltrate by histology. Controls included age/immunization-matched non-pregnant females. Nano2/4 exhibited no toxicity and elicited protective IgG2a/IgG1 response in mice. Nano2/4 signaled a splenic expansion of functionally active CD4+ effector/effector memory (Tem) and central memory (Tcm) cells in pregnant mice. Upon challenge infection, nano2/4 increased the splenic CD4+ and CD8+T cells in all mice and increased the proliferation of CD4+Tem, CD4+Tcm, and CD8+Tcm subsets producing IFNγ and cytolytic molecules (PRF1, GZB) in pregnant mice. A balanced serum cytokines/chemokines response and placental immune characteristics indicated that pregnancy prevented the overwhelming damaging immune response in mice. Importantly, pregnancy itself resulted in a significant reduction of parasites in maternal and fetal tissues. Nano2/4 was effective in arresting the Tc-induced tissue inflammatory infiltrate, necrosis, and fibrosis in maternal and placental tissues and improving maternal fertility, placental efficiency, and fetal survival. In conclusion, we show that maternal nano2/4 vaccination is beneficial in controlling the adverse effects of Tc infection on maternal health, fetal survival, and pregnancy outcomes.

Acute muscle mass loss was alleviated with HMGB1 neutralizing antibody treatment in severe burned rats.

Burn injury is associated with muscle wasting, though the involved signaling mechanisms are not well understood. In this study, we aimed to examine the role of high mobility group box 1 (HMGB1) in signaling hyper-inflammation and consequent skeletal muscle impairment after burn. Sprague Dawley rats were randomly assigned into three groups: (1) sham burn, (2) burn, (3) burn/treatment. Animals in group 2 and group 3 received scald burn on 30% of total body surface area (TBSA) and immediately treated with chicken IgY and anti-HMGB1 antibody, respectively. Muscle tissues and other samples were collected at 3-days after burn. Body mass and wet/dry weights of the hind limb muscles (total and individually) were substantially decreased in burn rats. Acute burn provoked the mitochondrial stress and cell death and enhanced the protein ubiquitination and LC3A/B levels that are involved in protein degradation in muscle tissues. Further, an increase in muscle inflammatory infiltrate associated with increased differentiation, maturation and proinflammatory activation of bone marrow myeloid cells and αß CD4+ T and γδ T lymphocytes was noted in in circulation and spleen of burn rats. Treatment with one dose of HMGB1 neutralizing antibody reduced the burn wound size and preserved the wet/dry weights of the hind limb muscles associated with a control in the markers of cell death and autophagy pathways in burn rats. Further, anti-HMGB1 antibody inhibited the myeloid and T cells inflammatory activation and subsequent dysregulated inflammatory infiltrate in the muscle tissues of burn rats. We conclude that neutralization of HMGB1-dependent proteolytic and inflammatory responses has potential beneficial effects in preventing the muscle loss after severe burn injury.

Clinical capability of modern brain tumor segmentation models.

PURPOSE: State-of-the-art automated segmentation methods achieve exceptionally high performance on the Brain Tumor Segmentation (BraTS) challenge, a dataset of uniformly processed and standardized magnetic resonance generated images (MRIs) of gliomas. However, a reasonable concern is that these models may not fare well on clinical MRIs that do not belong to the specially curated BraTS dataset. Research using the previous generation of deep learning models indicates significant performance loss on cross-institutional predictions. Here, we evaluate the cross-institutional applicability and generalzsability of state-of-the-art deep learning models on new clinical data. METHODS: We train a state-of-the-art 3D U-Net model on the conventional BraTS dataset comprising low- and high-grade gliomas. We then evaluate the performance of this model for automatic tumor segmentation of brain tumors on in-house clinical data. This dataset contains MRIs of different tumor types, resolutions, and standardization than those found in the BraTS dataset. Ground truth segmentations to validate the automated segmentation for in-house clinical data were obtained from expert radiation oncologists. RESULTS: We report average Dice scores of 0.764, 0.648, and 0.61 for the whole tumor, tumor core, and enhancing tumor, respectively, in the clinical MRIs. These means are higher than numbers reported previously on same institution and cross-institution datasets of different origin using different methods. There is no statistically significant difference when comparing the dice scores to the inter-annotation variability between two expert clinical radiation oncologists. Although performance on the clinical data is lower than on the BraTS data, these numbers indicate that models trained on the BraTS dataset have impressive segmentation performance on previously unseen images obtained at a separate clinical institution. These images differ in the imaging resolutions, standardization pipelines, and tumor types from the BraTS data. CONCLUSIONS: State-of-the-art deep learning models demonstrate promising performance on cross-institutional predictions. They considerably improve on previous models and can transfer knowledge to new types of brain tumors without additional modeling.

Prevalence and correlates of knowledge and practices regarding infection prevention and control, and triage in primary healthcare settings: A cross-sectional study in Bangladesh.

Background: Despite the high prevalence of healthcare-acquired infection in resource-limited settings, healthcare workers' (HCWs') knowledge and practices of infection prevention and control (IPC) and triage are not well-researched. We examined thisin Bangladesh's primary healthcare facilities (HCFs) during the COVID-19 pandemic. Methods: We surveyed 312 HCWs in 94 community clinics (CCs) and 90 family welfare centres (FWCs) in six districts from February to April 2021. We assessed HCWs' self-reported knowledge and observed practices in four domains: personal hygiene, medical instrument processing, waste management, and triage. We constructed a weighted composite knowledge score and estimated the association between knowledge and background characteristics using a generalised linear mixed effects model. Practices were described through univariate analysis. Findings: On a scale of 100, the mean composite knowledge score was 38.3 (SD: 13.3) overall and 44.0 (SD: 13.1) and 33.8 (SD: 11.6) for FWCs and CCs, respectively. The HCWs of FWCs were more aged, experienced, and educated than those of CCs. Knowledge score was the highest in personal hygiene and the lowest in medical waste segregation. Knowledge was significantly associated with HCWs' designation and education. Concerning practices, not more than one-third of the HCWs or HCFs, on average, followed the recommended protocols, except for wearing face masks while on duty (87.1%) and referring potential COVID-19 patients to higher-level facilities (68.3%). Conclusions: HCWs' capacity in instrument processing, waste management, and triage needs to be improved through formal education and training initiatives. Our study can contribute to the under-researched IPC and triage domains in resource-limited settings.

Implementation barriers and facilitators to a COVID-19 intervention in Bangladesh: The benefits of engaging the community for the delivery of the programme.

BACKGROUND: BRAC (Bangladesh Rural Advancement Committee), the largest NGO globally, implemented a community-based comprehensive social behavior communication intervention to increase community resilience through prevention, protection, and care for COVID-19. We conducted implementation research to assess fidelity and explore the barriers and facilitators of this intervention implementation. METHODS: We adopted a concurrent mixed-method triangulation design. We interviewed 666 members of 60 Community Corona Protection Committees (CCPCs) and 80 members of 60 Community Support Teams (CSTs) through multi-stage cluster sampling using a structured questionnaire. The qualitative components relied on 54 key informant interviews with BRAC implementers and government providers. RESULTS: The knowledge about wearing mask, keeping social distance, washing hands and COVID-19 symptoms were high (on average more than 70%) among CCPC and CST members. While 422 (63.4%) CCPC members reported they 'always' wear a mask while going out, 69 (86.3%) CST members reported the same practice. Only 247 (37.1%) CCPC members distributed masks, and 229 (34.4%) donated soap to the underprivileged population during the last two weeks preceding the survey. The key facilitators included influential community members in the CCPC, greater acceptability of the front-line health workers, free-of-cost materials, and telemedicine services. The important barriers identified were insufficient training, irregular participation of the CCPC members, favouritism of CCPC members in distributing essential COVID-19 preventive materials, disruption in supply and shortage of the COVID-19 preventative materials, improper use of handwashing station, the non-compliant attitude of the community people, challenges to ensure home quarantine, challenges regarding telemedicine with network interruptions, lack of coordination among stakeholders, the short duration of the project. CONCLUSIONS: Engaging the community in combination with health services through a Government-NGO partnership is a sustainable strategy for implementing the COVID-19 prevention program. Engaging the community should be promoted as an integral component of any public health intervention for sustainability. Engagement structures should incorporate a systems perspective to facilitate the relationships, ensure the quality of the delivery program, and be mindful of the heterogeneity of different community members concerning capacity building. Finally, reaching out to the underprivileged through community engagement is also an effective mechanism to progress through universal health coverage.

A comprehensive intervention package improves the linear growth of children under 2-years-old in rural Bangladesh: a community-based cluster randomized controlled trial.

Approximately one-third of children under the age of five are stunted in developing countries and many of them are micronutrient-deficient. We designed a comprehensive intervention package including egg/milk-based snacks to improve linear growth and dietary diversity among 6 to 12-month-old children in rural Bangladesh. In this 1-year community-based cluster randomized controlled longitudinal experiment, 412 mother-infant pairs were randomly assigned to receive either monthly food vouchers (for eggs, milk, semolina, sugar, and oil) to prepare egg and milk-based snacks for their children, along with multiple micronutrient powder (MNP), counseling on child feeding and handwashing, or regular government health communication alone (control; n = 206, treatment; n = 206). The trial was conducted in 12 clusters (small administrative units of sub-district). The primary inclusion criteria were ultra-poor households with limited resources and having children under 2-years-old. The primary and secondary outcomes were differences in children's length gain and dietary diversity. The effect of intervention on child growth was examined using a mixed effect linear regression model. Mean weight and length of the children did not significantly differ between groups at baseline. Around 90% of the children in both groups were breastfed. After receiving intervention for 12 months, LAZ score increased by 0.37 (CI 0.24, 0.51, p < 0.001) and risk of stunting reduced by 73% (OR: 0.27, CI 0.13, 0.58, p = 0.001). This comprehensive intervention package improved the growth and dietary diversity of children in extremely poor Bangladeshi households. A scaling-up of this intervention in contexts with limited resources should be taken into consideration.Trial registration: This trial registered retrospectively at ClinicalTrials.gov as NCT03641001, 21/8/2018.

Unsealed Source: Scope of Practice for Radiopharmaceuticals Among United States Radiation Oncologists.

Purpose: Our purpose was to determine the utilization of and barriers to implementation of radiopharmaceutical therapy (RPT) among U.S. radiation oncologists. Methods and Materials: An anonymous, voluntary 21-item survey directed toward attending radiation oncologists was distributed via social media platforms (Twitter, LinkedIn, Facebook, Student Doctor Network). Questions assessed practice characteristics, specific RPT prescribing patterns, RPT prescribing interest, and perceived barriers to RPT implementation. Nonparametric χ2 test was used for correlation statistics. Results: Of the 142 respondents, 131 (92.3%) practiced in the United States and were included for this analysis. Respondents were well balanced in terms of practicing region, population size served, practice setting, and years in practice. Forty-eight percent (n = 63) reported prescribing at least 1 RPT. An additional 7% (n = 8) participate in RPT administration without billing themselves. Among those that actively prescribed RPT, the mean cumulative cases per month was 4.2 (range, 1-5). The most commonly prescribed radionuclides were radium-223 (40%; mean 2.8 cases/mo), iodine-131 (18%; mean 2.3 cases/mo), yttrium-90 (13%; mean 3.4 cases/mo), "other" (8%), samarium-153 (6%; mean 1.0 cases/mo), and strontrium-89 and phosphorous-32 (2% each; mean 1.8 and 0.4 cases/mo, respectively). Of those who answered "other," lutetium-177 dotatate was most commonly prescribed (8%). No significant (P < .05) association was noted between practice type, practice location, years of practice, or practice volume with utilization of any RPTs. Most radiation oncologists (56%, n = 74) responded they would like to actively prescribe more RPT, although 27% (n = 35) were indifferent, and 17% (n = 22) said they would not like to prescribe more RPT. Perceived barriers to implementation were varied but broadly categorized into treatment infrastructure (44%, n = 57), interspecialty relations (41%, n = 53), lack of training (23%, n = 30), and financial considerations (16%, n = 21). Conclusions: Among surveyed U.S. radiation oncologists, a significant number reported prescribing at least 1 RPT. The majority expressed interest in prescribing additional RPT. Wide-ranging barriers to implementation exist, most commonly interspecialty relations, treatment infrastructure, lack of training, and financial considerations.

Removal of lead ions (Pb2+) from water and wastewater: a review on the low-cost adsorbents.

The presence of lead compounds in the environment is an issue. In particular, supply water consumption has been reported to be a significant source of human exposure to lead compounds, which can pose an elevated risk to humans. Due to its toxicity, the International Agency for Research on Cancer and the US Environmental Protection Agency (USEPA) have classified lead (Pb) and its compounds as probable human carcinogens. The European Community Directive and World Health Organization have set the maximum acceptable lead limits in tap water as 10 µg/L. The USEPA has a guideline value of 15 µg/L in drinking water. Removal of lead ions from water and wastewater is of great importance from regulatory and health perspectives. To date, several hundred publications have been reported on the removal of lead ions from an aqueous solution. This study reviewed the research findings on the low-cost removal of lead ions using different types of adsorbents. The research achievements to date and the limitations were investigated. Different types of adsorbents were compared with respect to adsorption capacity, removal performances, sorbent dose, optimum pH, temperature, initial concentration, and contact time. The best adsorbents and the scopes of improvements were identified. The adsorption capacity of natural materials, industrial byproducts, agricultural waste, forest waste, and biotechnology-based adsorbents were in the ranges of 0.8-333.3 mg/g, 2.5-524.0 mg/g, 0.7-2079 mg/g, 0.4-769.2 mg/g, and 7.6-526.0 mg/g, respectively. The removal efficiency for these adsorbents was in the range of 13.6-100%. Future research to improve these adsorbents might assist in developing low-cost adsorbents for mass-scale applications.

Knowledge and practices related to COVID-19 among mothers of under-2 children and adult males: a cross-sectional study in Bangladesh.

OBJECTIVES: To assess the knowledge and practices related to COVID-19 among Bangladeshi mothers with children aged 2 years or less and adult males. DESIGN: We conducted a cross-sectional study to assess the knowledge and practices using a multistage cluster sampling technique. SETTINGS: Six districts with high COVID-19 infection rates in Bangladesh. PARTICIPANTS: 2185 mothers of under-2 children and 657 adult males were surveyed in December 2020. MAIN OUTCOME MEASURES: We constructed weighted composite knowledge and practice scores and examined associations between composite scores and background characteristics using linear regression models. RESULTS: Knowledge on possible routes of transmission of the novel coronavirus and the critical handwashing and mask-wearing etiquettes was poor. On a scale of 100, the mean composite knowledge scores of mothers and adult males were respectively 33.5 (SD=15; 95% CI 32.9 to 34.1) and 38.2 (SD=14.8; 95% CI 37.1 to 39.4). In contrast to knowledge, adult males obtained lower practice scores than mothers, primarily due to poor physical distancing practices. The mean practice scores of mothers and adult males were 63.0 (SD=18.1; 95% CI 62.3 to 63.8) and 53.4 (SD=17.5; 95% CI 52.0 to 54.7). Moreover, education, household income and access to television and the internet are significantly associated with knowledge. People residing proximal to a city revealed higher knowledge than the relatively distant ones. This was also the case for practice scores; however, the other factors associated with knowledge did not have a significant association with practices. CONCLUSIONS: In general, both mothers and adult males presented with poor knowledge and practices related to COVID-19. While local, national and international institutions should design and implement educational interventions to help improve knowledge, our research shows that mere knowledge may not be enough to ensure practice. Hence, authorities could reinforce positive social norms by setting benchmarks and introducing rewards or sanctions to improve practices.

Removal of Pb2+ from water using the carbon nanotube-g-poly[(sodium methacrylate)-co- 2-(methacryloyloxy)ethyl acetoacetate]: experimental investigation and modeling.

A solid polymer, poly[(sodium methacrylate)-co-2-(methacryloyloxy)ethyl acetoacetate], p(MAA-co-MEAA) was synthesized and then grafted onto carbon nanotubes to prepare poly(MAA-co-MEAA)-grafted carbon nanotubes [CNT-g-p(MAA-co-MEAA)]. NMR, TGA, and FT-IR characterized the synthesized polymers and adsorbents. SEM-EDX was used to investigate the surface characteristics of the adsorbents. Pb2+ was removed from the aqueous solution using the CNT-g-p(MAA-co-MEAA). A batch adsorption experiment was performed at different Pb2+ concentrations (1, 10, 25, 50 mg/L), pH (4 and 6.75), temperature (25 and 35 °C), and contact periods (1, 5, 20, 60, and 1440 min) to study the adsorption kinetics and isotherm. The adsorbent dose of 2.5 g/L could effectively lower the initial Pb2+ concentration of 1000 to 2 ppb. The maximum adsorption capacity of the adsorbent was found to be 1178 mg/g. In addition, the adsorbents have been shown to effectively reduce the coexisting metal ion concentrations from industrial wastewater, which indicated the potential of the proposed adsorbent in removing metal ions from coexisting metals containing wastewater. To predict the adsorption efficiency of Pb2+, various linear, non-linear, and neural network models were established. An additional data set, not incorporated in model training, was used to validate the models. A number of models showed excellent performance with R2 in the range of 0.89-0.98. In model validation studies, the correlation coefficients (r) ranged from 0.94 to 0.99. The novel adsorbent and models will most likely aid in the development of a robust treatment technique for removing Pb2+ ions from water and wastewater.

Disparities in Radiation Therapy: Practice Patterns Analysis of Deep Inspiratory Breath Hold Use in Non-English Speakers.

PURPOSE: Our purpose was to examine current practice patterns in non-English-speaking patients with breast cancer undergoing deep inspiratory breath hold (DIBH). METHODS AND MATERIALS: An anonymous, voluntary REDCap survey was distributed to 60 residency program coordinators of US radiation oncology departments to survey their faculty and recent graduates. Eligibility was limited to board-certified radiation oncologists who had treated breast cancer within the prior 6 months. RESULTS: There were 69 respondents, 53 of whom were eligible. Forty-two percent (n = 22) of eligible respondents were from the main site at an academic center, with 28% (n = 15) representing a satellite site and 30% (n = 16) from private practice. Fifty-three percent reported at least 10% of their patients were non-English speaking. Ninety percent offered DIBH at their institution; of those, 74% used DIBH for at least one-fourth of their patients with breast cancer. Ninety-eight percent of those who use DIBH performed coaching at simulation, with 32% answering they would be "less likely" to use DIBH for non-English speakers. When used, 94% take into consideration potential language barriers for proper execution of DIBH. However, 51% had an interpreter present 76% to 100% of the time at computed tomography simulation, which decreased to 31% at first fraction and 11% at subsequent treatments. For non-English-speaking patients undergoing DIBH coaching without a certified interpreter, 55% of respondents indicated that they provided verbal coaching in English, 32% indicated "not applicable" because they always use a certified interpreter, 11% used visual aids, and 32% indicated "other." Of those who answered "other," the most commonly cited response was using therapists or staff who spoke the patient's native language. CONCLUSIONS: Disparities in the application of DIBH exist despite its established utility in reducing cardiac dose. This study provides evidence that language barriers may affect physician treatment practices from initial consideration of DIBH to subsequent delivery. These data suggest that breast cancer treatment considerations and subsequent execution are negatively affected in non-English-speaking patients.

Mandatory employer-sponsored health financing scheme for semiformal workers in Bangladesh: An experimental assessment.

In this study, we present findings from an experimental evaluation of a mandatory employer-sponsored health insurance scheme in Bangladesh. We randomly introduced the scheme to female artisans to understand the impacts on healthcare utilisation, expenditure and subjective well-being using both survey and administrative data. Our findings suggest that the scheme broke even; however, it covered only six percent of the overall health expenditure and 16 percent of the hospitalisation costs. We find higher inpatient care utilisation, particularly among women, and in favour of empanelled hospitals causally associated with the intervention, consistent with the design of the scheme. We do not find significant healthcare savings or improvement in subjective well-being, consistent with low coverage. The findings suggest the scheme to be financially sustainable and it changes the healthcare seeking behaviours as the scheme incentivises. However, meaningful savings and protection against catastrophic health expenditures will require a higher level of coverage.

Designing and Evaluating Multimodal Interactions for Facilitating Visual Analysis With Dashboards.

Exploring and analyzing data using visualizations is at the heart of many decision-making tasks. Typically, people perform visual data analysis using mouse and touch interactions. While such interactions are often easy to use, they can be inadequate for users to express complex information and may require many steps to complete a task. Recently natural language interaction has emerged as a promising technique for supporting exploration with visualization, as the user can express a complex analytical question more easily. In this paper, we investigate how to synergistically combine language and mouse-based direct manipulations so that the weakness of one modality can be complemented by the other. To this end, we have developed a novel system, named Multimodal Interactions System for Visual Analysis (MIVA), that allows user to provide input using both natural language (e.g., through speech) and direct manipulation (e.g., through mouse or touch) and presents the answer accordingly. To answer the current question in the context of past interactions, the system incorporates previous utterances and direct manipulations made by the user within a finite-state model. The uniqueness of our approach is that unlike most previous approaches which typically support multimodal interactions with a single visualization, MIVA enables multimodal interactions with multiple coordinated visualizations of a dashboard that visually summarizes a dataset. We tested MIVA's applicability on several dashboards including a COVID-19 dashboard that visualizes coronavirus cases around the globe. We further empirically evaluated our system through a user study with twenty participants. The results of our study revealed that MIVA system enhances the flow of visual analysis by enabling fluid, iterative exploration and refinement of data in a dashboard with multiple-coordinated views.

Use of a small molecule integrin activator as a systemically administered vaccine adjuvant in controlling Chagas disease.

The development of suitable safe adjuvants to enhance appropriate antigen-driven immune responses remains a challenge. Here we describe the adjuvant properties of a small molecule activator of the integrins αLß2 and α4ß1, named 7HP349, which can be safely delivered systemically independent of antigen. 7HP349 directly activates integrin cell adhesion receptors crucial for the generation of an immune response. When delivered systemically in a model of Chagas disease following immunization with a DNA subunit vaccine encoding candidate T. cruzi antigens, TcG2 and TcG4, 7HP349 enhanced the vaccine efficacy in both prophylactic and therapeutic settings. In a prophylactic setting, mice immunized with 7HP349 adjuvanted vaccine exhibited significantly improved control of acute parasite burden in cardiac and skeletal muscle as compared to vaccination alone. When administered with vaccine therapeutically, parasite burden was again decreased, with the greatest adjuvant effect of 7HP349 being noted in skeletal muscle. In both settings, adjuvantation with 7HP349 was effective in decreasing pathological inflammatory infiltrate, improving the integrity of tissue, and controlling tissue fibrosis in the heart and skeletal muscle of acutely and chronically infected Chagas mice. The positive effects correlated with increased splenic frequencies of CD8+T effector cells and an increase in the production of IFN-γ and cytolytic molecules (perforin and granzyme) by the CD4+ and CD8+ effector and central memory subsets in response to challenge infection. This demonstrates that 7HP349 can serve as a systemically administered adjuvant to enhance T cell-mediated immune responses to vaccines. This approach could be applied to numerous vaccines with no reformulation of existing stockpiles.

Acute monocyte pro inflammatory response predicts higher positive to negative acute phase reactants ratio and severe hemostatic derangement in dengue fever.

PURPOSE: The present study was intended to investigate whether monocyte immune activation shapes plasma positive to negative acute phase reactants (APRs) ratio and predicts disease severity in dengue infection. METHODS: Serum level of ferritin, ceruloplasmin and transferrin was measured by means of electrochemiluminescence and immunoturbidimetry, respectively. Gene expression and plasma level for TNF-α, IL-6 and IL1-ß was measured by means of RT-qPCR and ELISA. RESULTS: A significant increased serum ferritin to transferrin [6.6 (3-11.7) vs 3.4 (1.9-6.1)] and ceruloplasmin to transferrin ratio [0.48 (0.21-0.87) vs 0.22 (0.13-0.43)] has been detected among the subjects with secondary dengue infection (SDENI) compared to primarily infected (PDENI) subjects (P < 0.001). Significant increased expression for CD14+ monocyte TNF-α, IL-6 and IL-1ß has been detected in SDENI patients (vs PDENI and control, P < 0.001). Plasma ferritin to transferrin ratio was found in a significant association with high level of plasma TNF-α [ρ = 0.6522, 95% CI (0.4714-0.7805)], IL-6 [ρ = 0.6181, 95% CI (0.4257-0.7571)] and IL- 1ß [ρ = 0.4119, 95% CI (0.1689-0.6077)] level among SDENI patients at 5th day time point after progression of the disease, with significantly low platelet [P < 0.001] and prolonging prothrombin time [P < 0.001] compared to control and PDENI subjects, respectively. CONCLUSION: Acute proinflammatory cytokine response is significantly associated with increased positive to negative APRs ratio in SDENI patients, which predicts intense immune activation, and renders SDENI patients extremely susceptible to hemostatic derangement.

Bridging the rural-urban divide in social innovation transfer: the role of values.

This study examines the process of knowledge transfer between a pair of social enterprises, organizations that are embedded in competing social and economic logics. Drawing on a longitudinal case study of the interaction between social enterprises operating in emerging economy settings, it uncovers factors which influence the transfer of a social innovation from a dense, population-rich setting to one where beneficiaries are geographically dispersed and the costs of service delivery are correspondingly elevated. Evidence from the case study suggests that institutional bricolage-the crafting of improvised solutions in resource-constrained settings-can serve as potent driving force in driving innovation transfer, and that this process of re-combining available resources may be facilitated by the extent to which the values between partner social enterprises are aligned. With such alignment, social enterprise partners may be able to increase trust, develop a smoother knowledge-transfer process, and find practical solutions which facilitate the transfer of life-enhancing social innovations to neglected rural settings.

Predicting risk and loss of disability-adjusted life years (DALY) from selected disinfection byproducts in multiple water supply sources in Saudi Arabia.

Disinfection byproducts (DBPs) in drinking water is an issue in many countries. Many DBPs are possible or probable human carcinogens while few DBPs pose cyto- and genotoxic effects to the mammalian cells. The populations are likely to consume DBPs with drinking water throughout their lifetimes. A number of DBPs are regulated in many countries to protect humans. In this study, human exposure, risk and disability-adjusted life years (DALY) were predicted from DBPs in multiple water supply systems, including groundwater (GW), desalinated water (DW) and blend water (BW). The averages of lifetime excess cancer risks from GW, DW and BW were 4.15 × 10-6, 1.75 × 10-5 and 2.59 × 10-5 respectively. The populations in age groups of 0 - <2, 2-16 and >16 years contributed 25.4-25.7%, 28.6-29.6% and 45.0-45.7% to the total risks respectively. The DALY from GW, DW and BW were estimated to be 5.8, 27.0 and 39.9 years, respectively while the corresponding financial burdens were US$ 0.63, 2.93 and 4.34 million respectively. The findings are likely to assist in selecting the supply water sources to better control human exposure and risk from DBPs.

Antigen-Based Nano-Immunotherapy Controls Parasite Persistence, Inflammatory and Oxidative Stress, and Cardiac Fibrosis, the Hallmarks of Chronic Chagas Cardiomyopathy, in A Mouse Model of Trypanosoma cruzi Infection.

Chagas cardiomyopathy is caused by Trypanosoma cruzi (Tc). We identified two candidate antigens (TcG2 and TcG4) that elicit antibodies and T cell responses in naturally infected diverse hosts. In this study, we cloned TcG2 and TcG4 in a nanovector and evaluated whether nano-immunotherapy (referred as nano2/4) offers resistance to chronic Chagas disease. For this, C57BL/6 mice were infected with Tc and given nano2/4 at 21 and 42 days post-infection (pi). Non-infected, infected, and infected mice treated with pcDNA3.1 expression plasmid encoding TcG2/TcG4 (referred as p2/4) were used as controls. All mice responded to Tc infection with expansion and functional activation of splenic lymphocytes. Flow cytometry showed that frequency of splenic, poly-functional CD4+ and CD8+ T cells expressing interferon-γ, perforin, and granzyme B were increased by immunotherapy (Tc.nano2/4 > Tc.p2/4) and associated with 88%-99.7% decline in cardiac and skeletal (SK) tissue levels of parasite burden (Tc.nano2/4 > Tc.p2/4) in Chagas mice. Subsequently, Tc.nano2/4 mice exhibited a significant decline in peripheral and tissues levels of oxidative stress (e.g., 4-hydroxynonenal, protein carbonyls) and inflammatory infiltrate that otherwise were pronounced in Chagas mice. Further, nano2/4 therapy was effective in controlling the tissue infiltration of pro-fibrotic macrophages and established a balanced environment controlling the expression of collagens, metalloproteinases, and other markers of cardiomyopathy and improving the expression of Myh7 (encodes ß myosin heavy chain) and Gsk3b (encodes glycogen synthase kinase 3) required for maintaining cardiac contractility in Chagas heart. We conclude that nano2/4 enhances the systemic T cell immunity that improves the host's ability to control chronic parasite persistence and Chagas cardiomyopathy.