Search

Introduction: Hundreds of children suffer burn injuries each day, yet care guidelines regarding the need for acute inpatient treatment vs outpatient follow-up vs no required follow-up remain nebulous. This gap in the literature is particularly salient for the emergency clinician, who must be able to rapidly determine appropriate disposition. Methods: This was a retrospective review of patients presenting to a Level II pediatric trauma center, January 1, 2017-December 31, 2019, and discharged with an International Classification of Diseases, Rev 10, burn diagnosis. We obtained and analyzed demographics, burn characteristics, and follow-up data using univariate and bivariate analysis as well as logistic regression modeling. Patients were stratified into three outcome groups: group 1-patients who underwent emergent evaluation at a burn center or were admitted at their first follow-up appointment; group 2-patients who followed up at a burn center (as an outpatient) or at the emergency department (and were discharged home); and group 3-patients with no known follow-up. Results: A total of 572 patients were included in this study; 58.9% of patients were 1-5 years of age. Sixty-five patients met group 1 criteria, 189 patients met group 2 criteria, and 318 patients met group 3 criteria. Sixty-five percent of patients met at least one American Burn Association criteria, and 79% of all burns were second-degree burns. Flame and scald burns were associated with increased odds (odds ratio [OR] 1.21, OR 1.12) of group 1 vs group 2 + group 3 (P = 0.02, P < 0.001). Second/third-degree burns and concern for non-accidental trauma were also associated with increased odds of group 1 vs 2 or 3 (OR = 1.11, 1.35, P ≤ 0.001, 0.001, respectively). Scald burns were associated with increased odds of group 2 compared to group 3 (OR 1.11, P = 0.04). Second/third degree burns were also associated with increased odds of group 2 vs 3 (OR 1.19, P ≤ 0.001). Conclusion: There were few statistically significant variables strongly associated with group 1 (emergent treatment/admission) vs group 2 (follow-up/outpatient treatment) vs group 3 (no follow- up). However, one notable finding in this study was the association of scald burns with treatment (admission or follow-up) suggesting that the presence of a scald burn in a child may signify to clinicians that a burn center consult is warranted. [ABSTRACT FROM AUTHOR]

The demand for high-resolution imaging, and high sample throughputs in LA-ICP-MS experiments has led to developing rapid-response ablation cells with low dispersion. These cells can achieve short transient signals called single pulse responses (SPRs), whose width is in the single-digit millisecond range at 1% of the maximum. However, coupled with ICP-Q-MS, recording those short signals poses a problem due to the sequential measurement of selected m/z ratios. If more than one m/z ratio is targeted, the time resolution of quadrupole detection systems is insufficient for accurately determining short SPRs. This work focuses on utilizing rapid response ablation cells for the analysis of multiple elements with quadrupole-based detection systems in the SPR mode. To achieve this, an ArF-excimer laser equipped with a rapid-response ablation chamber is coupled to an ICP-MS with a short settling time of 0.2 ms and below. The two naturally occurring Ag-isotopes were analyzed in the NIST SRM 612 to optimize the dwell times for ideal data acquisition. The data shows that the ratio of the dwell time and the settling time, plays a crucial role. With the optimized parameters, the natural ratio of 107Ag and 109Ag within a 10 ms FW0.01M transient signal could be determined. This concept of LA-ICP-MS was then applied for depth profiling analysis of Al-doped SiC, a wide bandgap semiconductor. This procedure acquired depth profiles on 30 different sample locations in approximately 2 minutes with an exceptional depth resolution of 55 nm. [ABSTRACT FROM AUTHOR]

The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent. [ABSTRACT FROM AUTHOR]

Purpose: The usefulness of closed suction drains (CSD) after open reduction and internal fixation (ORIF) of tibial plateau fractures is a contested topic. The purpose of this study was to examine the impact of CSD in postoperative outcomes after tibial plateau fracture. Methods: Data were retrospectively collected from patients who underwent primary repair of closed tibial plateau fractures via an anterolateral approach between June 2021 to May 2022 at a single academic center. Fifty-six patients were included and 28 received CSDs at time of surgery. P values less than 0.05 were considered significant. Results: Fifty-six patients were included. There was no significant difference in demographics, pre- and post-op hemoglobin, estimated blood loss during surgery, length of stay, postoperative MMEs and pain at 3 month follow-up, deep vein thrombosis (DVT), compartment syndrome, flexion contracture, use of incisional vac, infection rate, wound drainage, hematoma, neurologic pain, dehiscence, additional surgery, or range of motion at 3 months follow-up. We noted a significant difference in Defense and Veterans Pain Rating Scale (DVPRS) on POD1, demonstrating greater pain in those in the CSD group. Conclusion: Our findings suggest that the use of CSD in ORIF of tibial plateau fractures may not be of significant prophylactic benefit. CSDs in ORIF patients were associated with increased early postoperative pain and had no identifiable benefits. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Background: The application of different approaches calculating the anthropogenic carbon net flux from land, leads to estimates that vary considerably. One reason for these variations is the extent to which approaches consider forest land to be "managed" by humans, and thus contributing to the net anthropogenic flux. Global Earth Observation (EO) datasets characterising spatio-temporal changes in land cover and carbon stocks provide an independent and consistent approach to estimate forest carbon fluxes. These can be compared against results reported in National Greenhouse Gas Inventories (NGHGIs) to support accurate and timely measuring, reporting and verification (MRV). Using Brazil as a primary case study, with additional analysis in Indonesia and Malaysia, we compare a Global EO-based dataset of forest carbon fluxes to results reported in NGHGIs. Results: Between 2001 and 2020, the EO-derived estimates of all forest-related emissions and removals indicate that Brazil was a net sink of carbon (− 0.2 GtCO2yr−1), while Brazil's NGHGI reported a net carbon source (+ 0.8 GtCO2yr−1). After adjusting the EO estimate to use the Brazilian NGHGI definition of managed forest and other assumptions used in the inventory's methodology, the EO net flux became a source of + 0.6 GtCO2yr−1, comparable to the NGHGI. Remaining discrepancies are due largely to differing carbon removal factors and forest types applied in the two datasets. In Indonesia, the EO and NGHGI net flux estimates were similar (+ 0.6 GtCO2 yr−1), but in Malaysia, they differed in both magnitude and sign (NGHGI: -0.2 GtCO2 yr−1; Global EO: + 0.2 GtCO2 yr−1). Spatially explicit datasets on forest types were not publicly available for analysis from either NGHGI, limiting the possibility of detailed adjustments. Conclusions: By adjusting the EO dataset to improve comparability with carbon fluxes estimated for managed forests in the Brazilian NGHGI, initially diverging estimates were largely reconciled and remaining differences can be explained. Despite limited spatial data available for Indonesia and Malaysia, our comparison indicated specific aspects where differing approaches may explain divergence, including uncertainties and inaccuracies. Our study highlights the importance of enhanced transparency, as set out by the Paris Agreement, to enable alignment between different approaches for independent measuring and verification. [ABSTRACT FROM AUTHOR]

Background: Recent advances have begun to identify the nonphysical factors facilitating successful return to sport (RTS) after shoulder instability surgery, yet little is currently known regarding psychological factors and RTS. Purpose/Hypothesis: The purposes of this study were to (1) identify psychological factors associated with RTS, (2) evaluate the prognostic utility of various psychological factors, and (3) evaluate the available metrics used to assess psychological RTS readiness. It was hypothesized that psychological factors would be identified as critical elements influencing a patient's RTS. Study Design: Systematic review; Level of evidence, 4. Methods: Clinical studies reporting on the psychological determinants of RTS for patients who had surgery for shoulder instability between 1996 and 2022 were identified from MEDLINE, Embase, and Cochrane databases. Demographic, clinical, and psychometric properties were extracted for pooled weighted analysis. Results: Of the 969 studies screened, 24 (2.5%) met inclusion criteria. Overall, 2135 patients were included (mean age, 26.0 years; range, 17.4-35.5 years; 84.7% male). The mean time to RTS was 6.8 months (range, 3.7-11.9 months). There was a 76.3% rate of any RTS; of the 1212 patients who reported level of play at return, 305 (25.2%) were unable to perform at their prior level. Psychological reasons were cited by 85% (n = 360) of patients who did not RTS. Fear of reinjury was the most common reason (n = 154; 42.8%); other psychological factors included lack of confidence (n = 46; 12.8%), anxiety (n = 45; 12.5%), depression (n = 44; 12.2%), psychosocial factors (n = 48; 13.3%), and lack of motivation (n = 23; 6.4%). The Shoulder Instability Return to Sport after Injury, Western Ontario Shoulder Instability Index, Quick Inventory of Depressive Symptoms Self Report, Degree of Shoulder Involvement in Sports, Tampa Scale of Kinesiophobia-11, and Veterans Rand 12-Item Health Survey were reported measures for assessing psychology and RTS. Conclusion: Fear of reinjury was found to be the most commonly reported impediment to RTS. The psychological characteristics identified through this review may be incorporated into future RTS protocols seeking to address resilience and nonphysical factors associated with RTS. [ABSTRACT FROM AUTHOR]

Background It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D–binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear. Methods We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression. Results In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P  =  .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (P interaction   =  .003). Conclusions Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma—specifically from thicker, higher-risk melanoma—than individuals without this Gc1f haplotype. [ABSTRACT FROM AUTHOR]

The efficacy of PD-1 monoclonals such as pembrolizumab can be modulated by the signals delivered via their Fc region. Tumour/inflammation associated proteases can generate F(ab')2 fragments of therapeutic monoclonals, and subsequent recognition of F(ab')2 epitopes by circulating anti-hinge antibodies (AHA) can then, potentially, link F(ab')2 binding to the target antigen with novel Fc signalling. Although elevated in inflammatory diseases, AHA levels in cancer patients have not been investigated and functional studies utilising the full repertoire of AHA present in sera have been limited. AHA levels in pembrolizumab treated melanoma patients (n = 23) were therefore compared to those of normal donors and adalimumab treated patients. A subset of melanoma patients and the majority of adalimumab patients had elevated levels of AHA reactive with F(ab')2 fragments of IgG4 anti-PD-1 monoclonals (nivolumab, pembrolizumab) and IgG1 therapeutic monoclonals (rituximab, adalimumab). Survival analysis was restricted by the small patient numbers but those melanoma patients with the highest levels (>75% percentile, n = 5) of pembrolizumab-F(ab')2 reactive AHA had significantly better overall survival post pembrolizumab treatment (p = 0.039). In vitro functional studies demonstrated that the presence of AHA+ sera restored the neutrophil activating capacity of pembrolizumab to its F(ab')2 fragment. Neither pembrolizumab nor its F(ab')2 fragments can induce NK cell or complement dependent cytotoxicity (CDC). However, AHA+ sera in combination with pembrolizumab-F(ab')2 provided Fc regions that could activate NK cells. The ability of AHA+ sera to restore CDC activity was more restricted and observed using only one pembrolizumab and one adalimumab patient serum in combination with rituximab- F(ab')2. This study reports the presence of elevated AHA levels in pembrolizumab treated melanoma patients and highlight the potential for AHA to provide additional Fc signaling. The issue of whether tumour associated proteolysis of PD-1 mAbs and subsequent AHA recognition impacts on treatment efficacy requires further study. [ABSTRACT FROM AUTHOR]

Background: There are several approaches such as the Bankart repair, Latarjet, and Remplissage to treat recurrent glenohumeral instability. Indications: We chose to augment an arthroscopic Bankart repair with a Remplissage in this 26-year-old patient given the presence of a Hill-Sachs lesion, history of recurrent shoulder dislocations, and young age of the patient. Technique Description: We established four portals using previously well-documented techniques. The Hill-Sachs lesion was evaluated using the anterosuperior portal. Two anchors were placed, one on both the superior and inferior aspects of the Hill-Sachs lesion. The sutures were shuttled through the knotless anchor mechanism and tensioned after confirming the cannula was through the deltoid. Then, we completed the Remplissage by repairing the infraspinatus tendon and capsule into the posterior humeral head. Results: The Remplissage procedure is very successful at reducing recurrent instability in young, active patients. Previous studies have reported very low rates, even 0% recurrent instability, after surgery with 80% to 90% of patients returning to sports. Studies have also documented excellent patient-reported outcomes at short- to mid-term follow-up. Complication rates are historically lower when the Remplissage is done with an arthroscopic Bankart repair than the Bankart repair alone. Discussion/Conclusion: The Remplissage procedure is a safe, effective option at reducing future instances of shoulder dislocations in conjunction with Bankart repairs. Patients can expect to return to their active lifestyles, with many patients achieving the same level of activity as before the initial shoulder dislocation. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

Summary Gene set scoring (or enrichment) is a common dimension reduction task in bioinformatics that can be focused on the differences between groups or at the single sample level. Gene sets can represent biological functions, molecular pathways, cell identities, and more. Gene set scores are context dependent values that are useful for interpreting biological changes following experiments or perturbations. Single sample scoring produces a set of scores, one for each member of a group, which can be analyzed with statistical models that can include additional clinically important factors such as gender or age. However, the sparsity and technical noise of single-cell expression measures create difficulties for these methods, which were originally designed for bulk expression profiling (microarrays, RNAseq). This can be greatly remedied by first applying a smoothing transformation that shares gene measure information within transcriptomic neighborhoods. In this work, we use the nearest neighbor graph of cells for matrix smoothing to produce high quality gene set scores on a per-cell, per-group, level which is useful for visualization and statistical analysis. Availability and implementation The gssnng software is available using the python package index (PyPI) and works with Scanpy AnnData objects. It can be installed using "pip install gssnng." More information and demo notebooks: see https://github.com/IlyaLab/gssnng. [ABSTRACT FROM AUTHOR]

2 Cover Bull riding fracture Case series We conducted a retrospective review at Children's Hospital of Orange County (CHOC) in California, of pediatric patients treated for injuries associated with mechanical bull riding. We reviewed a series of pediatric patients who suffered head injuries/skull fractures caused by mechanical bull riding, many of which required surgical intervention. Pediatric patients suffering a skull fracture may also be at risk of growing skull fractures and traumatic encephaloceles [[4]]. [Extracted from the article]

Background: Proximal junctional thoracic kyphosis (PJK) is common following adult spinal deformity (ASD) surgery and may require revision operations. In this case series, we present delayed complications associated with the use of sublaminar banding (SLBs) for PJK prophylaxis. Case Description: Three patients underwent long-segment thoracolumbar decompression and fusions for ASD. All had undergone SLB placement for PJK prophylaxis. All three subsequently developed neurologic complications secondary to cephalad spinal cord compression/stenosis requiring urgent revision surgery. Conclusion: The placement of SLBs placed to prevent PJK may lead to sublaminar inflammation contributing to severe cephalad spinal canal stenosis and myelopathy following ASD surgery. Surgeons should be aware of this potential complication and may consider alternatives to SLB placement to avoid this complication. [ABSTRACT FROM AUTHOR]

Interprofessional education (IPE) has grown in popularity over the years because it is effective in training future health professionals and serves as the engine of productivity in healthcare-related research. The research team, consisting of higher education faculty in various health profession disciplines, conducted a systematic review of existent IPE literature targeting both graduate and under-graduate students. The main purpose of the systematic review was to categorize research and analyze IPE studies to determine sub-constructs that entail both barriers and facilitators often related to occurrences in primary provider, learner, and researcher IPE initiatives. If identified, IPE training and related curriculum plans were also analyzed in this review. The research team wanted to identify any/all potential instances of the use of research activities in coordination with IPE training to identify underlying constructs to support future college and program-specific andragogy initiatives. Review results demonstrate three categorical constructs related to IPE initiatives in higher education health professions programs (provider, learner, and researcher stakeholder perspectives). Results further demonstrate provider IPE challenges surrounding limited resources and a willingness to participate, while both patient experience and teamwork foci were identified as common IPE session themes. Further, the learners' perspectives included a challenge related to a willingness to participate, as well as the patient experience focus. Review constructs were further validated using supplementary topic modeling. To the best of our knowledge, this is the first study that combined systematic review with a supplementary topic modeling. Findings support ongoing pedagogy and research efforts related to IPE activities for health professions programs in higher education. [ABSTRACT FROM AUTHOR]

There has been a growing interest by both academics and policymakers at the local and regional scales in the development of a green economy both to promote economic development and to achieve environmental policy aims. Despite this, there is little evidence about whether either the economic or the environmental aims are being met, nor how local and regional authorities are promoting and developing green economies in their localities. In order to address these issues, this paper explores the development of the offshore wind industry in North West Germany, drawing upon sustainability transitions research and the path creation literature. [ABSTRACT FROM AUTHOR]

Development of a growth factor delivery vehicle providing appropriate temporal-spatial release together with an appropriate preclinical large animal model to evaluate bone formation is critical in the development of delivery strategies for bone tissue regeneration. Smectite nanoclays such as LAPONITE™ possess unique thixotropic and protein retention properties offering promise for use in growth factor delivery in bone repair and regeneration. This study has examined bone formation mediated by a clinically approved growth factor delivery system (InductOs®) in combination with Laponite gel in an aged female ovine femoral condyle defect preclinical model (10 weeks). Two different designs, one containing a low volume of Laponite gel (LLG) in combination with the InductOs® absorbable collagen sponge (ACS), the other in which Laponite gel formed the implant (HLG), were compared against InductOs® alone and an autograft positive control. Thus, five groups: (i) empty defect, (ii) autograft, (iii) BMP2 + ACS, (iv) BMP2 + ACS + LLG and (v) BMP2 + HLG + ACS were examined in 9 mm × 12 mm defects performed bilaterally in the medial femoral condyles of 24 aged (>5 years) sheep. Bone formation within the defect was assessed using micro-computed tomography (micro-CT), digital volume correlation (DVC) for biomechanical characterisation as well as histology. The autograft and InductOs® mediated enhanced bone formation (p < 0001) compared to blank controls, while no significant differences were observed between the Laponite/Collagen/BMP delivery vehicles. However, the current study illustrated the excellent biocompatibility of Laponite and its ability to deliver localised active BMP-2, with the opportunity for improved efficacy with further optimisation. Interestingly, DVC-computed strain distributions indicated that the regenerated bone structure is mechanically adapted to bear external loads from the early remodelling stages of the bone reparation cascade. The current studies of selected nanoclay delivery platforms for BMP, assessed in a clinically relevant large animal model auger well for the development of bone fracture therapeutics for an ageing population. [ABSTRACT FROM AUTHOR]

Development of a growth factor delivery vehicle providing appropriate temporal-spatial release together with an appropriate preclinical large animal model to evaluate bone formation is critical in the development of delivery strategies for bone tissue regeneration. Smectite nanoclays such as LAPONITE™ possess unique thixotropic and protein retention properties offering promise for use in growth factor delivery in bone repair and regeneration. This study has examined bone formation mediated by a clinically approved growth factor delivery system (InductOs®) in combination with Laponite gel in an aged female ovine femoral condyle defect preclinical model (10 weeks). Two different designs, one containing a low volume of Laponite gel (LLG) in combination with the InductOs® absorbable collagen sponge (ACS), the other in which Laponite gel formed the implant (HLG), were compared against InductOs® alone and an autograft positive control. Thus, five groups: (i) empty defect, (ii) autograft, (iii) BMP2 + ACS, (iv) BMP2 + ACS + LLG and (v) BMP2 + HLG + ACS were examined in 9 mm × 12 mm defects performed bilaterally in the medial femoral condyles of 24 aged (>5 years) sheep. Bone formation within the defect was assessed using micro-computed tomography (micro-CT), digital volume correlation (DVC) for biomechanical characterisation as well as histology. The autograft and InductOs® mediated enhanced bone formation (p < 0001) compared to blank controls, while no significant differences were observed between the Laponite/Collagen/BMP delivery vehicles. However, the current study illustrated the excellent biocompatibility of Laponite and its ability to deliver localised active BMP-2, with the opportunity for improved efficacy with further optimisation. Interestingly, DVC-computed strain distributions indicated that the regenerated bone structure is mechanically adapted to bear external loads from the early remodelling stages of the bone reparation cascade. The current studies of selected nanoclay delivery platforms for BMP, assessed in a clinically relevant large animal model auger well for the development of bone fracture therapeutics for an ageing population. [ABSTRACT FROM AUTHOR]

Basic science literature strongly supports a role of oxidative stress in colorectal cancer (CRC) etiology, but in epidemiologic studies, associations of most individual exposures with CRC have been weak or inconsistent. However, recent epidemiologic evidence suggests that the collective effects of these exposures on oxidative balance and CRC risk may be substantial. Using food frequency and lifestyle questionnaire data from the prospective Iowa Women's Health Study (1986-2012), we investigated associations of 11-component dietary and 4-component lifestyle oxidative balance scores (OBS) with incident CRC using multivariable Cox proportional hazards regression. Of the 33,736 cancer-free women aged 55-69 years at baseline, 1,632 developed CRC during follow-up. Among participants in the highest relative to the lowest dietary and lifestyle OBS quintiles (higher anti-oxidant relative to pro-oxidant exposures), the adjusted hazard ratios (HRs) and their 95% confidence intervals (CI) were, respectively, 0.77 (0.63, 0.94) (Ptrend=0.02) and 0.61 (0.52, 0.71) (Ptrend<0.0001). Among those in the highest relative to the lowest joint lifestyle/dietary OBS quintile, the HR was 0.45 (95% CI 0.26, 0.77). Our findings suggest that a predominance of antioxidant over pro-oxidant dietary and lifestyle exposures—separately and especially jointly—may be inversely associated with CRC risk among older women. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) and candidate pathway studies have identified low-penetrant genetic variants associated with cutaneous melanoma. We investigated the association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival. The Genes, Environment, and Melanoma Study enrolled 3285 European origin participants with incident invasive primary melanoma. For each of 47 melanoma-risk single nucleotide polymorphisms (SNPs), we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and odds ratios for presence of ulceration, mitoses, and tumor-infiltrating lymphocytes (TILs). We also used Cox proportional hazards regression modeling to estimate the per allele hazard ratios for melanoma-specific survival. Passing the false discovery threshold (p = 0.0026) were associations of IRF4 rs12203592 and CCND1 rs1485993 with log of Breslow thickness, and association of TERT rs2242652 with presence of mitoses. IRF4 rs12203592 also had nominal associations (p < 0.05) with presence of mitoses and melanomaspecific survival, as well as a borderline association (p = 0.07) with ulceration. CCND1 rs1485993 also had a borderline association with presence of mitoses (p = 0.06). MX2 rs45430 had nominal associations with log of Breslow thickness, presence of mitoses, and melanoma-specific survival. Our study indicates that further research investigating the associations of these genetic variants with underlying biologic pathways related to tumor progression is warranted. [ABSTRACT FROM AUTHOR]

Background: Eutrophication of freshwater ecosystems resulting from nitrogen and phosphorus pollution is a major environmental stressor across the globe. In this systematic review, we compiled and synthesized literature on sestonic and benthic chlorophyll a (chl-a) responses to total nitrogen (TN) and total phosphorus (TP) concentrations in the water column in streams and rivers to provide a state-of-the-science summary of nutrient impacts on these endpoints. This review was motivated by the need for comprehensive information on stressor-response relationships for the most common nutrient and biotic response measures used by state-level environmental managers in the United States to assess eutrophication of lotic ecosystems and support environmental decision making. Methods: Searches for peer-reviewed and non-peer-reviewed articles were conducted using bibliographic databases, specialist websites, and search engines. These returns were supplemented with citation mapping and requests for material from experts. Articles were screened for relevance using pre-determined eligibility criteria, and risk of bias was evaluated for each included article based on study type-specific criteria. Narrative summaries and meta-analysis were used to evaluate four primary stressor-response relationships: TN-benthic chl-a, TP-benthic chl-a, TN-sestonic chl-a, and TP-sestonic chl-a. Potential effects of modifying factors and study validity on review conclusions were assessed via sensitivity and sub-group analysis and meta-regression. Results: Meta-analysis of 105 articles, representing 439 cause-effect pairs, showed that mean effect sizes of both benthic and sestonic chl-a responses to TN and TP were positive. Of the four stressor-response relationships examined, TP-sestonic chl-a had the most positive relationship, followed by TN-benthic chl-a, TN-sestonic chl-a, and TP-benthic chl-a. For individual U.S. states, mean effect sizes for the four stressor-response relationships were mostly positive, with a few exceptions. Chlorophyll measurement method had a moderately significant influence on mean effect size for TP-sestonic chl-a, with chl-a responding more strongly to TP if fluorometry versus spectrophotometry was used. Year of publication had a significant negative effect on mean effect size, as did mean nutrient concentration for both sestonic chl-a nutrient relationships. When the same study measured both TN and TP, chl-a tended to respond similarly to both nutrients. Sensitivity analysis indicated that conclusions are robust to studies with high risk of bias. Conclusions: This systematic review confirms that nutrients consistently impact primary producer biomass in streams and rivers worldwide. It builds on previous literature syntheses evaluating chl-a responses to nutrient concentrations and confirms that benthic and sestonic chl-a respond positively to nutrients across a range of stream and river conditions, but also points to limits on these relationships (e.g., potential saturation at high nutrient concentrations). Lack of consistent reporting of contextual data limited our ability to examine how moderating factors influenced these stressor-response relationships. Overall, we provide nutrient managers responsible for protecting the quality of lotic ecosystems with a comprehensive evidence base for chl-a responses to TN and TP concentrations in the water column. [ABSTRACT FROM AUTHOR]

The maintenance and function of tissues in health and disease depends on cell–cell communication. This work shows how high-level features, representing cell–cell communication, can be defined and used to associate certain signaling "axes" with clinical outcomes. We generated a scaffold of cell–cell interactions and defined a probabilistic method for creating per-patient weighted graphs based on gene expression and cell deconvolution results. With this method, we generated over 9,000 graphs for The Cancer Genome Atlas (TCGA) patient samples, each representing likely channels of intercellular communication in the tumor microenvironment (TME). It was shown that cell–cell edges were strongly associated with disease severity and progression, in terms of survival time and tumor stage. Within individual tumor types, there are predominant cell types, and the collection of associated edges were found to be predictive of clinical phenotypes. Additionally, genes associated with differentially weighted edges were enriched in Gene Ontology terms associated with tissue structure and immune response. Code, data, and notebooks are provided to enable the application of this method to any expression dataset (https://github.com/IlyaLab/Pan-Cancer-Cell-Cell-Comm-Net). [ABSTRACT FROM AUTHOR]

Purpose: Ethical concerns about the use of the Mental Health Act (MHA) have led to calls for developmental disorders to be removed from the list of mental disorders for which individuals can be detained. In parallel, there are long-standing concerns of ethnic disparity in the application of the MHA. Nonetheless, the impact of the intersections of developmental disorder diagnosis, adolescence and ethnicity on the application of the MHA is unknown. This study aims to explore ethnic differences in MHA sections and the factors accounting for this, in an adolescent inpatient developmental disorder service. Design/methodology/approach: File reviews were conducted to explore differences in MHA status, as well as demographic, clinical and risk factors that may account for this, between 39 white British and ethnic minority adolescents detained to a specialist inpatient developmental disorder service. Findings: Consistent with adult literature, adolescents of an ethnic minority were overrepresented in the sample and were significantly more likely to be detained on Part III or "forensic" sections of the MHA than White British counterparts, with five times greater risk. Analyses revealed no significant differences between ethnic minority and white British participants on demographic variables, clinical needs, risk behaviours, risk measures nor application of restrictive practices and safeguarding procedures. Practical implications: National audits exploring patterns of detention under the MHA across adolescent developmental disorder populations need to include analysis of intersections to ensure that the MHA is used as a means of last resort and in an equitable manner. Originality/value: To the best of the authors' knowledge, this paper is the first comprehensive exploration of the impact of ethnicity on detention patterns in ethnic minority and White British populations. [ABSTRACT FROM AUTHOR]

Changing environmental conditions are forcing natural resource managers and communities to adapt their strategies to account for global shifts in precipitation, temperature, sea level and more, all of which are occurring in addition to local human impacts. Adapting to threats from climate change requires a fundamental shift in the practice of natural resource management through the development of forward-looking "climate-smart" goals and strategies. Here we present a proof-of-concept application of a decision-support tool to help design climate-smart management actions for the watershed and coral reef management plan for Guánica Bay watershed in southwest Puerto Rico. We also explore the connection between adaptation planning and coral reef resilience, using a recently developed Puerto Rico-wide reef resilience assessment. In the first phase of the study, we used the publicly available Adaptation Design Tool to draft initial climate-smart versions of twelve proposed management actions. In the second phase, two actions (dirt road management on steep slopes, and coral reef restoration) were further refined through consultations with local experts to make more detailed design adjustments; this included the option to use information from the coral reef resilience assessment to inform design improvements. The first phase resulted in moderately detailed assessments that broadly accounted for anticipated direct and indirect effects of climate change on the planned management actions. The second phase resulted in more site-specific technical assessments and additional important design details. The expert panel charged with discussing climate-smart reef restoration around Guánica used the reef resilience assessment to guide discussion of reef restoration, highlighting the importance of having such information available for adaptation planning. This study demonstrates how climate change impacts can be effectively incorporated into a management plan at the most granular level of planning and how a structured, formalized process can be as valuable as the resulting adaptation information. [ABSTRACT FROM AUTHOR]

There is increasing excitement in the healthcare field about using behavioral data and healthcare analytics for disease risk prediction, clinical decision support, and overall improvement of personalized medicine. However, this excitement has not effectively translated to improved clinical outcomes due to knowledge gaps, a lack of behavioral risk models, and resistance to evidence-based practice. Reportedly, only 10–20% of clinical decisions are known to be evidence-based and this problem is further highlighted by the fact that the US spends more money on healthcare per person than any other nation, while still wrestling with poor health outcomes. Critics say there are inadequate technological resources and analytical education for clinicians to make behavioral data useful in the medical world. Healthcare technology innovators often neglect important aspects of the reality of integrating clinical data into electronic healthcare solutions. In this study, we developed a decision tree model using R statistical software to predict diabetes since it is among the top causes of death in the US, can be poorly managed, and provides an opportunity for improvement using analytics. This study examined behavioral data and healthcare analytics for use in clinical applications, demonstrating that health information professionals can develop behavioral risk factor prediction models to bridge the gap. Results indicated that decision trees are effective in classifying diabetes in an individual at up to 89.36% accuracy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine if routine chest X-rays (CXRs) performed after chest tube (CT) removal in pediatric patients provide additional benefit for clinical management compared to observation of symptoms alone. Methods: A single-center retrospective study was conducted of inpatients, 18 years or younger, who had a CT managed by the pediatric surgery team between July 2017 and May 2019. The study compared two groups: (1) patients who received a post-pull CXR and (2) those who did not. The primary outcome of the study was the need for intervention after CT removal. Results: 102 patients had 116 CTs and met inclusion criteria; 79 post-pull CXRs were performed; the remaining 37 CT pulls did not have a follow-up CXR. No patients required CT replacement or surgery in the absence of symptoms. Three patients exhibited clinical symptoms that would have prompted intervention regardless of post-pull CXR results. One patient had an intervention guided by post-pull CXR results alone. Meanwhile, another patient had delayed onset of symptoms and intervention. No patients required an intervention in the group that did not have a post-pull CXR. Conclusion: Chest X-ray after CT removal had a very low yield for changing clinical management of asymptomatic patients. Clinical symptoms predict the need for an intervention. [ABSTRACT FROM AUTHOR]

Published reports suggest efforts designed to prevent the occurrence of harmful algal blooms and hypoxia by reducing non‐point and point source phosphorus (P) pollution are not delivering water quality improvements in many areas. Part of the uncertainty in evaluating watershed responses to management practices is the lack of standardized estimates of phosphorus inputs and outputs. To assess P trends across the conterminous United States, we compiled an inventory using publicly available datasets of agricultural P fluxes, atmospheric P deposition, human P demand and waste, and point source discharges for 2002, 2007, and 2012 at the scale of the 8‐digit Hydrologic Unit Code subbasin (∼1,800 km2). Estimates of agricultural legacy P surplus accumulated from 1945 to 2001 were also developed. Fertilizer and manure inputs were found to exceed crop removal rates by up to 50% in many agricultural regions. This excess in inputs has led to the continued accumulation of legacy P in agricultural lands. Atmospheric P deposition increased throughout the Rockies, potentially contributing to reported increases in surface water P concentrations in undisturbed watersheds. In some urban areas, P fluxes associated with human waste and non‐farm fertilizer use has declined despite population growth, likely due, in part, to various sales bans on P‐containing detergents and fertilizers. Although regions and individual subbasins have different contemporary and legacy P sources, a standardized method of accounting for large and small fluxes and ready to use inventory numbers provide essential infromation to coordinate targeted interventions to reduce P concentrations in the nation's waters. Plain Language Summary: Excessive phosphorus (P) concentrations in surface water endanger public health and welfare by contributing to harmful algal blooms and hypoxic zones. Many efforts to decrease P pollution to the nation's waters have not achieved desired outcomes. To help decision‐makers develop strategies to decrease P loads, we developed an inventory of inputs and outputs of P across the United States. This inventory reveals the source and magnitude of P in a local area and how it changes through time. We found that agricultural P inputs were the largest source of P nationwide and inefficiencies in use contribute to the continued accumulation of phosphorus across the landscape. This excess phosphorus may make it more difficult to achieve water quality goals. However, many agricultural regions in the eastern and western United States demonstrated more efficient use of phosphorus fertilizer in 2012. On another positive note, urban areas in certain regions have likely decreased their fertilizer application rates, the amount of P being released by detergents, and point source loads. These efforts may have contributed to recent reports of improved water quality in more urbanized watersheds. Decision makers should consider the role of current fluxes and legacy P when designing strategies to reduce P pollution. Key Points: Agricultural surplus declined by 8% for the entire US and declines are seen in many subbasins of the eastern and western United StatesAtmospheric phosphorus (P) deposition increased by 9% from 2002 to 2012, coincident with increases in stream P concentrations in undisturbed watershedsSummed legacy P surplus accumulation is more than 50 times contemporary P surplus and may perpetuate eutrophication in the nation's waters [ABSTRACT FROM AUTHOR]

Background: Exogenous exposures collectively may contribute to chronic, low-grade inflammation and increase risks for major chronic diseases and mortality. We previously developed, validated, and reported a novel, FFQ-based and lifestyle questionnaire-based, inflammation biomarker panel-weighted, predominantly whole foods-based 19-component dietary inflammation score (DIS) and 4-component lifestyle inflammation score (LIS; comprising physical activity, alcohol intake, BMI, and current smoking status). Both scores were more strongly associated with circulating biomarkers of inflammation in 3 populations than were previously reported dietary inflammation indices. Associations of the DIS and LIS with mortality risk have not been reported.Objectives: To investigate separate and joint associations of the DIS and LIS with all-cause, all-cancer, and cardiovascular disease (CVD) mortality risks in the prospective Iowa Women's Health Study (1986-2012; n = 33,155 women, ages 55-69 years, of whom 17,431 died during follow-up, including 4379 from cancer and 6574 from CVD).Methods: We summed each study participant's scores' components, weighted by their published weights, to yield the participant's inflammation score; a higher score was considered more pro-inflammatory. We assessed DIS and LIS mortality associations using multivariable Cox proportional hazards regression.Results: Among participants in the highest relative to the lowest DIS and LIS quintiles, the adjusted HRs for all-cause mortality were 1.11 (95% CI: 1.05-1.16) and 1.60 (95% CI: 1.53-1.68), respectively; for all-cancer mortality were 1.07 (95% CI: 0.97-1.17) and 1.51 (95% CI: 1.38-1.66), respectively; and for CVD mortality were 1.12 (95% CI: 1.03-1.21) and 1.79 (95% CI: 1.66-1.94), respectively (all Ptrend values < 0.01). Among those in the highest relative to the lowest joint LIS/DIS quintiles, the HRs for all-cause, all-cancer, and all-CVD mortality were 1.88 (95% CI: 1.71-2.08), 1.82 (95% CI: 1.50-2.20), and 1.92 (95% CI: 1.64-2.24), respectively.Conclusions: More pro-inflammatory diets and lifestyles, separately but especially jointly, may be associated with higher all-cause, all-cancer, and all-CVD mortality risks among women. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) is a complex, debilitating disease with few available medical therapies in its later stages. Methods: We reviewed current clinical approaches for caring for AS patients with an emphasis on the risks and outcomes associated with surgical intervention. Results: It is critical to understand the natural history and surgical outcomes of patient with AS. Surgery is not without risks, as a vertebral body osteotomy is often required to re-establish spinopelvic equilibrium. However, surgery can lead to clinical improvements in pain, disability, cardiac function, respiration, digestion, and sexual activity. Conclusion: Deformity correction for AS should be carefully considered in symptomatic patients. [ABSTRACT FROM AUTHOR]

Objectives: Patellar instability may cause significant pain and disability and recurrent dislocations are often treated with reconstruction of the medial patellofemoral ligament (MPFL). Obesity is a known risk factor for complications following numerous surgical procedures, yet there exists a lack of data regarding the influence of body mass index (BMI) on outcomes following MPFL reconstruction. The purpose of this study was to evaluate complications and outcomes following isolated MPFL reconstruction in obese and non-obese patients. We hypothesized that patients with a BMI > 30 would exhibit increased complication risk and worse patient-reported outcomes. Methods: A billing query identified all patients at one academic medical center who underwent isolated MPFL reconstruction over an 8 year period. Chart review extracted demographic, physical exam, radiographic, surgical, and complication data. Patients were contacted and outcomes were assessed with the Norwich Patellar Instability (NPI) score, Marx activity rating, and Knee Injury and Osteoarthritis Outcome Score (KOOS). Complications and outcomes were compared based on the presence of a BMI ≥ 30 kg/m². Results: A total of 161 patients who underwent isolated MPFL reconstruction were included. Of this cohort, there were115 with BMI < 30 and 46 with BMI ≥ 30. Early outcomes (time in brace, time to weight bearing) and postop complications (deep vein thrombosis, infection, pain, repeat dislocation/instability) were similar between groups (p>0.50). A total of 97 patients (60%) completed patient-reported outcomes at a mean of 5 years post-operative, with no differences noted in patient- reported outcomes based on BMI (Table). Conclusions: Obesity (defined as BMI ≥ 30) was not associated with increased complications of poorer patient-reported outcomes 5 years following isolated MPFL reconstruction. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) is a complex, debilitating disease with few available medical therapies in its later stages. Methods: We reviewed current clinical approaches for caring for AS patients with an emphasis on the risks and outcomes associated with surgical intervention. Results: It is critical to understand the natural history and surgical outcomes of patient with AS. Surgery is not without risks, as a vertebral body osteotomy is often required to re-establish spinopelvic equilibrium. However, surgery can lead to clinical improvements in pain, disability, cardiac function, respiration, digestion, and sexual activity. Conclusion: Deformity correction for AS should be carefully considered in symptomatic patients. [ABSTRACT FROM AUTHOR]

Lower prediagnostic circulating 25‐hydroxyvitamin D (25[OH]D)—considered the best marker of total vitamin D exposure—is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D‐binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D‐mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study‐II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 ‐ <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable‐adjusted hazard ratios (HRs) for CRC‐specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44‐3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68‐1.22) among cases without Gc2 (Pinteraction =.0002). The corresponding HRs for all‐cause mortality were 1.80 (95% CI 1.24‐2.60) among those with Gc2, and 1.12 (95% CI 0.84‐1.51) among those without Gc2 (Pinteraction =.004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis. What's new? Vitamin D regulates molecular pathways that are relevant to cancer progression. In patients with colorectal cancer (CRC), low serum levels of vitamin D have been associated with increased mortality. A protein called GC binds vitamin D and delivers it to tissues. In this study, the authors found that the increased mortality risk with low vitamin D was only seen in those CRC patients who carry a genetic variant of GC called Gc2. These results may help to identify a vulnerable subgroup of CRC patients, who may particularly benefit from vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Copyright of Urban Studies (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide1,2. Regrowing natural forests is a prominent strategy for capturing additional carbon3, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates2,3. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC)4,5 may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported3 owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy. A one-kilometre-resolution map of aboveground carbon accumulation rates of forest regrowth shows 100-fold variation across the globe, with rates 32% higher on average than IPCC estimates. [ABSTRACT FROM AUTHOR]

Based upon an increasing academic and business interest in greening the industrial supply chains, this paper establishes the need for a state-of-the-art decision support system (DSS) for carbon emissions accounting and management, mainly across the product supply chains by identifying methodological shortcomings in existing tools, and proposing a supply chain (SC) framework which provide businesses with a holistic understanding of their supply chains and ensuring partners within supply chain collaborative networks have a shared understanding of their emissions. It describes the design and development of a DSS now known as supply chain environmental analysis tool (SCEnAT) in detail, putting its unique and innovative features into a comparative perspective vis-à-vis existing tools and software of different types. The methodological framework used to design and develop SCEnAT integrates different individual techniques/methods of supply chain (SC) mapping, SC carbon accounting, SC interventions and SC interventions evaluation on a range of key performance indicators (KPIs). These individual methods have been used and applied innovatively to the challenge of designing SCEnAT within the desired framework. Finally, we demonstrate the application of SCEnAT, especially the advantage of using a robust carbon accounting methodology, to a SC case study. The SCEnAT framework pushes the theoretical boundary by addressing the problems of intra-organisational approach in decision making for lowering carbon along the supply chain; with an open innovation, cutting edge, hybridised framework that considers the supply chain as a whole in co-decision making for lowering carbon along the supply chain with the most robust methodology of hybrid life cycle analysis (LCA) that considers direct and indirect emissions and interventional performance evaluation for low carbon technology investment and business case building in order to adapt and mitigate climate change problems. This research has implications for future sustainability research in SC, decisions science, management theory, practice and policy. [ABSTRACT FROM AUTHOR]

Objective: Emergency department (ED) return visits within 72 h may be a sign of poor quality of care and entail unnecessary use of healthcare resources. In this study, we compare the performance of two leading statistical and machine learning classification algorithms, and we use the best performing approach to identify novel risk factors of ED return visits. Methods: We analyzed 3.2 million ED encounters with at least one diagnosis under "injury, poisoning and certain other consequences of external causes" and "external causes of morbidity." These encounters included patients 18 years or older from across 128 emergency room facilities in the USA. For each encounter, we calculated the 72-h ED return status and retrieved 57 features from demographics, diagnoses, procedures, and medications administered during the process of administration of medical care. We implemented a mixed-effects model to assess the effects of the covariates while accounting for the hierarchical structure of the data. Additionally, we investigated the predictive accuracy of the extreme gradient boosting tree ensemble approach and compared the performance of the two methods. Results: The mixed-effects model indicates that certain blunt force and non-blunt trauma inflates the risk of a return visit. Notably, patients with trauma to the head and patients with burns and corrosions have elevated risks. This is in addition to 11 other classes of both blunt force and non-blunt force traumas. In addition, prior healthcare resource utilization, patients who have had one or more prior return visits within the last 6 months, prior ED visits, and the number of hospitalizations within the 6 months are associated with increased risk of returning to the ED after discharge. On the one hand, the area under the receiver characteristic curve (AUROC) of the mixed-effects model was 0.710 (0.707, 0.712). On the other hand, the gradient boosting tree ensemble had a lower AUROC of 0.698 CI (0.696, 0.700) on the independent test model. Conclusions: The proposed mixed-effects model achieved the highest known AUC and resulted in the identification of novel risk factors. The model outperformed one of the leading machine learning ensemble classifiers, the extreme gradient boosting tree in terms of model performance. The risk factors we identified can assist emergency departments to decrease the number of unplanned return visits within 72 h. [ABSTRACT FROM AUTHOR]

Background Mechanistic models, when combined with pertinent data, can improve our knowledge regarding important molecular and cellular mechanisms found in cancer. These models make the prediction of tissue-level response to drug treatment possible, which can lead to new therapies and improved patient outcomes. Here we present a data-driven multiscale modeling framework to study molecular interactions between cancer, stromal, and immune cells found in the tumor microenvironment. We also develop methods to use molecular data available in The Cancer Genome Atlas to generate sample-specific models of cancer. Results By combining published models of different cells relevant to pancreatic ductal adenocarcinoma (PDAC), we built an agent-based model of the multicellular pancreatic tumor microenvironment, formally describing cell type–specific molecular interactions and cytokine-mediated cell-cell communications. We used an ensemble-based modeling approach to systematically explore how variations in the tumor microenvironment affect the viability of cancer cells. The results suggest that the autocrine loop involving EGF signaling is a key interaction modulator between pancreatic cancer and stellate cells. EGF is also found to be associated with previously described subtypes of PDAC. Moreover, the model allows a systematic exploration of the effect of possible therapeutic perturbations; our simulations suggest that reducing bFGF secretion by stellate cells will have, on average, a positive impact on cancer apoptosis. Conclusions The developed framework allows model-driven hypotheses to be generated regarding therapeutically relevant PDAC states with potential molecular and cellular drivers indicating specific intervention strategies. [ABSTRACT FROM AUTHOR]

Immune cell infiltration of tumors and the tumor microenvironment can be an important component for determining patient outcomes. For example, immune and stromal cell presence inferred by deconvolving patient gene expression data may help identify high risk patients or suggest a course of treatment. One particularly powerful family of deconvolution techniques uses signature matrices of genes that uniquely identify each cell type as determined from single cell type purified gene expression data. Many methods from this family have been recently published, often including new signature matrices appropriate for a single purpose, such as investigating a specific type of tumor. The package ADAPTS helps users make the most of this expanding knowledge base by introducing a framework for cell type deconvolution. ADAPTS implements modular tools for customizing signature matrices for new tissue types by adding custom cell types or building new matrices de novo, including from single cell RNAseq data. It includes a common interface to several popular deconvolution algorithms that use a signature matrix to estimate the proportion of cell types present in heterogenous samples. ADAPTS also implements a novel method for clustering cell types into groups that are difficult to distinguish by deconvolution and then re-splitting those clusters using hierarchical deconvolution. We demonstrate that the techniques implemented in ADAPTS improve the ability to reconstruct the cell types present in a single cell RNAseq data set in a blind predictive analysis. ADAPTS is currently available for use in R on CRAN and GitHub. [ABSTRACT FROM AUTHOR]