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Bayesian networks are a popular class of multivariate probabilistic models as they allow for the translation of prior beliefs about conditional dependencies between variables to be easily encoded into their model structure. Due to their widespread usage, they are often applied to spatial data for inferring properties of the systems under study and also generating predictions for how these systems may behave in the future. We review published research on methodologies for representing spatial data with Bayesian networks and also summarize the application areas for which Bayesian networks are employed in the modeling of spatial data. We find that a wide variety of perspectives are taken, including a GIS-centric focus on efficiently generating geospatial predictions, a statistical focus on rigorously constructing graphical models controlling for spatial correlation, as well as a range of problem-specific heuristics for mitigating the effects of spatial correlation and dependency arising in spatial data analysis. Special attention is also paid to potential future directions for the integration of Bayesian networks with spatial processes.

The Person-Case Constraint (PCC) is a family of restrictions on the relative person of the two objects of a ditransitive. PCC effects offer a testing ground for theories of Agree and of syntactic features, both those on nominals and those found on agreement probes. This article offers a new theory of PCC effects in an interaction/satisfaction theory of Agree (Deal 2015a) and shows the advantages of this framework in capturing PCC typology. On this model, probes are specified for interaction, determining which features will be copied to them, and for satisfaction, determining which features will cause probing to stop. Applied to the PCC, this theory (a) captures all four types of PCC effect recognized by Nevins (2007) under a unified notion of Agree; (b) captures the restriction of PCC effects to contexts of “Double Weakness” in many prominent examples (e.g., in Italian, Greek, and Basque, where PCC effects hold only when both objects are expressed with clitics); (c) naturally extends to PCC effects in syntactic environments without visible clitics or agreement for one or both objects, as well as to the absence of PCC effects in some languages with clitics or agreement for both objects. Two refinements of the interaction/satisfaction theory are offered: a new notation for probes’ interaction and satisfaction specifications, clarifying the absence of uninterpretable/unvalued features as drivers of Agree; and a proposal for the way that probes’ behavior may change over the course of a derivation, dubbed dynamic interaction.

Various literature has seen the potential of Social media as one of the interventions to distance learning, particularly amidst the global health crisis. It establishes that some applications are not only meant for entertainment, some of which can be of great value to learning. For this reason, this study aims to test the Effectiveness and Utilization of Social Media as an Academic Medium in the UNC College of Education to provide concrete evidence of what particular activities social media be integrated with the teaching-learning process. The study used a mixed-method design. It adopted a survey and interview instrument towards the perspective of students and teachers on social media as a tool for academic medium. The researchers determined the number of participants for the college professors through a Non-probability sampling technique, while the purposive sampling technique was utilized in determining the number of students. The study results show that most students and teachers used social media, particularly Facebook and Messenger, for communication and collaborative learning. Also, the study proves that social media platforms were highly effective and served as students' alternative LMS, which increases students' engagement with the teaching-learning process. The study realized that social media platforms help students develop learning experiences and creativity towards attaining academic achievement and boosting academic performance in making projects or assignments. Moreover, social media platforms offer a variety of activities that can be integrated into the achievement of teaching- learning. Some were used as a communication tool, be an alternative LMS where students could submit assignments, and be an announcement board where teachers could send updates and notifications. Therefore, it was recommended that social media platforms be maximized in the classroom, and teachers ensure that the student-teacher relationship remains despite the restriction to face-to-face learning. However, further research should be conducted to determine the risks and impact of too much use of these platforms on the students' mental, physical, and mental aspects and how this may affect their academic performance if misused.

Plasma sulforaphane concentrations by day, dose, and pre- or post-BSE-SFN administration

We report new records of the fisheries-harvested subtropical greater amberjack Seriola dumerili for the south-east Pacific Ocean. Despite local fishers' asserting that three Seriola morphotypes exist in the region, only one species (the yellowtail amberjack Seriola lalandi) was previously scientifically recorded for Rapa Nui (also known as Easter Island). Whilst we present the first "scientific record", S. dumerili, traditional ecological knowledge suggests that this is likely a pre-existing (albeit transient) species of the Rapa Nui ecoregion. Establishing the existing/historic distributional limits of commercially and ecologically valuable species is key for observing climate-driven distribution shifts, and the inclusion of traditional ecological knowledge is particularly important in areas with relatively lower scientific effort.

Treatment significantly affects the circulating immune compartment.

Representative gating strategy illustrating (A) CD4 and CD8 T cell identification (B) expression of ICOS on CD4 positive T cells (C) expression of PD-1 and Ki-67 within PD-1 positive cells and (D) expression of CD38/HLA-DR, PD-1 and KI-67 within CD8+ PD-1+ T cells is shown.

Representative gating strategy illustrating (A) CD4 and CD8 T cell identification (B) expression of ICOS on CD4 positive T cells (C) expression of PD-1 and Ki-67 within PD-1 positive cells and (D) expression of CD38/HLA-DR, PD-1 and KI-67 within CD8+ PD-1+ T cells is shown.

Treatment significantly affects the circulating immune compartment.

Purpose:Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma.Patients and Methods:Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m2/day i.v., 5 days per week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery.Results:A total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2–43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5–85.8], with a 43% (95% CI: 27.3–60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively).Conclusions:Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.See related commentary by Menzies et al., p. 4133

Intratumoral TLR9 agonists and anti-PD-1 provide durable clinical responses and broad immune activation. To evaluate efficacy and mechanisms of action of this combined treatment, we conducted a single-arm phase 2 neoadjuvant study of TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab (vidu/nivo) in patients with high-risk resectable melanoma. In 30 evaluable patients, 57% (17/30) had major pathologic response (pR), with eight grade 3 treatment-related adverse events. pR was associated with lower residual viable tumor, necrosis, and melanophagocytosis with increased CD8+ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment and increased frequencies of Ki67+ CD8+ and CD4+ T cells, pDCs, and monocytes peripherally. Gene signatures associated with pR included increased pDC density, macrophage activation, and phagocytosis engulfment. Gut microbial signatures in pR were enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and to the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidu/nivo treatment stimulates a broad antitumor immune response and is associated with a distinct baseline gut microbiome composition.

Bowel ischaemia significantly increases morbidity and mortality from adhesional small bowel obstruction. Current biomarkers and clinical parameters have poor predictive value for ischaemia. Our study investigated whether neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) could be used to predict bowel ischaemia in adhesional small bowel obstruction.This single-centre retrospective study collected clinical, biochemical and radiological data from patients with adhesional small bowel obstruction between 2017 and 2020 who underwent operative management. The presence or absence of bowel ischaemia/infarction was used to distinguish two populations. Biochemical markers on admission and immediately prior to operation were collected to give platelet-lymphocyte ratio (PLRTwenty-seven patients had intra-operative bowel ischaemia whilst the remaining 73 had no evidence of bowel ischaemia. Both median PLRRaised NLR is predictive of bowel ischaemia in patients with adhesional small bowel obstruction.

Eutrophication modifies lakes' ecological balances and threatens its viability. To date, eutrophication management strategies have been related to nutrient reduction in the lakes' water column. However, nutrient reduction strategies are complicated by the variations of the lake's water level, nutrient concentration, and eutrophication symptom, which are primarily known to be influenced by the local rainfall patterns. Therefore, this study aimed to compare the variability of water level, total phosphorus, and total chlorophyll-a concentrations in Slim River Lake during wet and dry seasons. In this study, water sampling and depth measurements were carried out from six sampling points for 1 year. Water samples were used to quantify total phosphorus and total chlorophyll-a. Our results showed that mean water levels in the studied lake ranged from 1.36 m to 5.46 m in the wet season and from 1.31 m to 5.41 m in the dry season, which implicated no significant difference (p > .05) between seasons in most sampling points. Total phosphorus present at concentrations exceeding 10 mg/L and showed small variations between wet and dry seasons. Mean total phosphorus concentrations varied from 10.55 mg/L to 26.66 mg/L in the wet season and 10.77 mg/L to 21.76 mg/L in the dry season and showed no significant difference between seasons. In addition, mean chlorophyll-a concentrations ranged from 14.35 mg/m3 to 180.13 mg/m3 and from 14.15 mg/m3 to 39.27 mg/m3 in wet and dry seasons, respectively. Chlorophyll-a concentrations showed significant differences (p

While overall survival has improved significantly for children with cancer over the past 75 years, cancer remains the leading cause of death from disease among children and adolescents. Further, despite the many advances in medical and nursing care, children with cancer still experience significant physical and emotional suffering over the course of their illness, especially at the end of life (EOL). Children endure significant rates of high-intensity medical interventions (e.g., intubation, intensive care unit admission) at the EOL despite many parents, adolescents, and young adult patients identifying home as their preferred location of death. Hospice care has the potential to ease suffering at the EOL and facilitate home deaths, and yet, most children still die in acute care settings without hospice care. Numerous barriers prevent timely enrollment in hospice among children with cancer who are in the EOL period. This report describes the development and testing of a palliative care/EOL communication intervention designed to overcome some of these barriers and subsequently improve EOL outcomes (i.e., earlier hospice enrollment, less use of high-intensity medical interventions, reduced pain and suffering) among children with cancer and their parents (i.e., less emotional distress and uncertainty, improved hope and healthcare satisfaction).

Purpose:Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma.Patients and Methods:Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m2/day i.v., 5 days per week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery.Results:A total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2–43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5–85.8], with a 43% (95% CI: 27.3–60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively).Conclusions:Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.See related commentary by Menzies et al., p. 4133

New fecal microbiota for cancer patients The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti–PD-1 immunotherapy (see the Perspective by Woelk and Snyder). Both studies observed evidence of clinical benefit in a subset of treated patients. This included increased abundance of taxa previously shown to be associated with response to anti–PD-1, increased CD8 + T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells, which are involved in immunosuppression. These studies provide proof-of-concept evidence for the ability of FMT to affect immunotherapy response in cancer patients. Science , this issue p. 602 , p. 595 ; see also p. 573

The purpose of this project was to explore the influence of international service-learning on the personal and professional development of future special educators and speech-language pathologists. The service-learning students engaged in educational site visits, presentation of workshops, cultural activities, and interprofessional exchange in Botswana. Students completed surveys at the end of the trip and then participated in a focus group interview nine months after the study abroad course was completed. Findings from a qualitative content analysis revealed five emerging themes: open-mindedness, boundary spanning, cultural humility, skill development, and confidence. Implications for cross-cultural collaboration are discussed along with consideration for predeparture activities, high-impact educational practices, and student confidence in achieving professional skills standards.

Background: Chronic edema (CO) is a complex condition, arising from different factors, including immobility and obesity. Edema and obesity can have a significant impact on quality of life of patien...

BackgroundA first-in-human, randomized pilot phase II clinical trial combining vaccines targeting overexpressed, non-mutated tumor blood vessel antigens (TBVA) and tyrosine kinase inhibitor dasatinib was conducted in human leukocyte antigen (HLA)-A2+ patients with advanced melanoma.MethodsPatient monocyte-derived type-1-polarized dendritic cells were loaded with HLA-A2-presented peptides derived from TBVA (DLK1, EphA2, HBB, NRP1, RGS5, TEM1) and injected intradermally as a vaccine into the upper extremities every other week. Patients were randomized into one of two treatment arms receiving oral dasatinib (70 mg two times per day) beginning in week 5 (Arm A) or in week 1 (Arm B). Trial endpoints included T cell response to vaccine peptides (interferon-γ enzyme-linked immunosorbent spot), objective clinical response (Response Evaluation Criteria in Solid Tumors V.1.1) and exploratory tumor, blood and serum profiling of immune-associated genes/proteins.ResultsSixteen patients with advanced-stage cutaneous (n=10), mucosal (n=1) or uveal (n=5) melanoma were accrued, 15 of whom had previously progressed on programmed cell death protein 1 (PD-1) blockade. Of 13 evaluable patients, 6 patients developed specific peripheral blood T cell responses against ≥3 vaccine-associated peptides, with further evidence of epitope spreading. All six patients with specific CD8+ T cell response to vaccine-targeted antigens exhibited evidence of T cell receptor (TCR) convergence in association with preferred clinical outcomes (four partial response and two stabilization of disease (SD)). Seven patients failed to respond to vaccination (one SD and six progressive disease). Patients in Arm B (immediate dasatinib) outperformed those in Arm A (delayed dasatinib) for immune response rate (IRR; 66.7% vs 28.6%), objective response rate (ORR) (66.7% vs 0%), overall survival (median 15.45 vs 3.47 months; p=0.0086) and progression-free survival (median 7.87 vs 1.97 months; p=0.063). IRR (80% vs 25%) and ORR (60% vs 12.5%) was greater for females versus male patients. Tumors in patients exhibiting response to treatment displayed (1) evidence of innate and adaptive immune-mediated inflammation and TCR convergence at baseline, (2) on-treatment transcriptional changes associated with reduced hypoxia/acidosis/glycolysis, and (3) increased inflammatory immune cell infiltration and tertiary lymphoid structure neogenesis.ConclusionsCombined vaccination against TBVA plus dasatinib was safe and resulted in coordinating immunologic and/or objective clinical responses in 6/13 (46%) evaluable patients with melanoma, particularly those initiating treatment with both agents.Trial registration numberNCT01876212.

Nutrient input from internal and external sources could regulate the variability and abundance of algal and macrophytes in freshwater lakes. This study explores the response of algal and macrophyte growth in relation to internal and external nutrient loading. This study was conducted over a 12-month period in a eutrophic shallow urban lake known as Slim River Lake, which located in Perak state, Malaysia. The internal nutrient loading was calculated during five identified dry periods. Meanwhile, external nutrient loading was measured from stormwater runoff after storm events. Algal biomass was measured twice a month, while total macrophyte abundance was measured once in a month. In this lake, internal nutrient loading could contribute up to 7538.33 kg total phosphorus and 42.23 kg total nitrogen during dry periods. Meanwhile, external nutrient loading quantified from the stormwater runoff contributed up to 401,500 kg total phosphorus and 4611.67 kg total nitrogen. The highest monthly mean for algal biomass and total macrophyte abundance was recorded as 60,343.75 cells/mL and 821.50, respectively. Based on the Pearson correlation analysis, algal biomass was significantly correlated with the internal total phosphorus loading (r = 0.54, p 0.05). In addition, algal biomass also shows an inverse relationship with the external total phosphorus loading (r = - 0.44, p 0.05). In contrast, total macrophyte abundance was significantly correlated with the external total phosphorus loading (r = 0.50, p 0.05) and external total nitrogen loading (r = 0.44, p 0.05). These results suggest that variation of nutrient sources triggers a different response by algal and macrophytes in the study lake. In implications, these findings show that a combination approach in reducing nutrients from sediment and anthropogenic sources is required for potential lake restoration.

The experiences of pediatric oncology nurses with prognosis-related communication (PRC) remain largely unknown. The purpose of this article is to report results of focus groups wherein 15 pediatric oncology nurses from three Midwestern pediatric cancer programs provided descriptions of PRC and how they experience PRC within their daily practice. Data from focus groups were analyzed via an interpretive descriptive approach, which resulted in three themes: (1) nurses’ operational definition of PRC, (2) nurses’ roles in PRC, and (3) nurses’ preparation for engagement in PRC. From discussions within the focus groups, nurses recognized that PRC occurs across a continuum. Nurses distinguished that the definition of PRC expands beyond simply reporting life expectancy to describing the consequences of cancer- and treatment-related toxicities and effects. When nurses are not actively invited by their physician partners to participate in PRC, nurses will often develop workarounds to ensure that they understand what was said to patients and families. This allows them to function more effectively as supporters, advocates, and informants. Nurses described little preparation to participate in such challenging conversations. Pediatric oncology nurses need to acknowledge and embrace that they are an integral part of PRC. Interprofessional communication training is necessary to enhance the comfort and confidence of nurses engaging in PRC.

CONTEXT: Cancer and symptom experiences of adolescents and young adults (AYAs) with cancer can be highly variable, creating challenges for clinicians and researchers who seek to optimize AYAs’ health outcomes. Understanding the heuristics AYAs use to designate priority symptoms can provide insight into the meaning they assign to their symptoms and self-management behaviors. OBJECTIVES: This study described the frequency and characteristics of priority symptoms. It qualitatively explored reasons for a symptom’s designation as a priority symptom, perceived causes of priority symptoms, and strategies AYAs use to manage priority symptoms. METHODS: Participants in this single group, longitudinal study reported symptoms using a heuristics-based symptom reporting tool, the Computerized Symptom Capture Tool, at two scheduled visits for chemotherapy. AYAs designated priority symptoms and responded to two short answer questions: What makes this a priority symptom? and What do you do to make it better? RESULTS: Eighty-six AYAs, 15-29 years of age (median 19 years), identified 189 priority symptoms. Priority symptoms were of greater severity (t=3.43; p< .01) and distress (t=4.02; p< .01) compared with non-priority symptoms. Lack of energy, nausea, difficulty sleeping, and pain comprised 39% of priority symptoms. Reasons for priority designation included the impact of the symptom and the attributes of the symptom. Categories of self-management strategies included “Physical Care Strategies,” “Things I take (or not),” and “Psychosocial Care Strategies.” CONCLUSION: Supporting AYAs to identify their priority symptoms may facilitate a more personalized approach to care. Seeking the patient’s perspective regarding priority symptoms could enhance patient-clinician collaboration in symptom management.

Urban areas presently consume around 75% of global primary energy supply, which is expected to significantly increase in the future due to urban growth. Having sustainable, universal energy access ...

The COVID-19 pandemic caused by the β-coronavirus SARS-CoV-2 has made the development of safe and effective vaccines a critical global priority. To date, four vaccines have already been approved by European and American authorities for preventing COVID-19 but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle, a technology previously utilized for cancer vaccines. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 Spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax – a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein RBD – induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function and significantly lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started in Italy.

Aircraft Induced Clouds (AIC), also known as Contrails, absorb, scatter and reflect back to the Earth an estimated 33% of the outgoing "thermal" radiation emitted from the Earth that is directed at the cloud. The resulting global warming is estimated to account for 55% of aviation’s total contribution to global warming. The CO2 emissions from aircraft is estimated to account for only 39% of aviation’s total contribution. Recent studies of options to mitigate the global warming effects of AIC identified that the most cost effective and near-term solution is an "operational" change such that flights fly over the Ice Super Saturated Regions (ISSR) in the atmosphere in which AIC are generated. This operational change would affect, on average, only 15% of the flights each day and would add no net direct operating cost to the airlines or Air Traffic Control while reducing global warming immediately.When the industry decides to take advantage of this global warming mitigation opportunity, an AIC Abatement Program (AAP) will need to put in place. This paper provides a System Design for a collaborative Airline and Air Traffic Control system to mitigate AIC by managing Cruise Flight Level assignment relative to the presence of ISSRs. The paper identifies the objectives of the system, protocol, incentives, rules to prevent "gaming the system," and a functional description of an evaluation tool to operate the proposed AAP. The implications and limitations of the proposed system, along with topics for future work are discussed.

In the coming decades, our planet will witness unprecedented urban population growth in both established and emerging communities. The development and maintenance of urban infrastructures are highly energy-intensive. Urban areas are dictated by complex intersections among physical, engineered, and human dimensions that have significant implications for traffic congestion, emissions, and energy usage. In this chapter, we highlight recent research and development efforts at Oak Ridge National Laboratory (ORNL), the largest multipurpose science laboratory within the U.S. Department of Energy’s (DOE) national laboratory system, that characterizes the interactions between the human dynamics and critical infrastructures in conjunction with the integration of four distinct components: data, critical infrastructure models, and scalable computation and visualization, all within the context of physical and social systems. Discussions focus on four key topical themes: population and land use, sustainable mobility, the energy-water nexus, and urban resiliency, that are mutually aligned with DOE’s mission and ORNL’s signature science and technology capabilities. Using scalable computing, data visualization, and unique datasets from a variety of sources, the institute fosters innovative interdisciplinary research that integrates ORNL expertise in critical infrastructures including energy, water, transportation, and cyber, and their interactions with the human population.

EnvironmentAsia, 14, 1, 63-68