Search

Approximately 2600 km of bison and elk trails have been mapped in West Virginia using historical records, including county histories and travelers' accounts with published dates between 1876 and 1977. Most points of interest associated with these trails document European bison or elk hunting events. We explore some potential uses of the digital trails data and discuss the limitations of the data and need for further refinements. This map of major bison trails (available for download at https://doi.org/10.2737/RDS-2021-0055) is an important resource for telling a more complete story of the history of forests and woodlands of West Virginia.

Therapeutic approaches are needed to promote T cell-mediated destruction of poorly immunogenic, "cold" tumors typically associated with minimal response to immune checkpoint blockade (ICB) therapy. Bispecific T cell engager (BiTE) molecules induce redirected lysis of cancer cells by polyclonal T cells and have demonstrated promising clinical activity against solid tumors in some patients. However, little is understood about the key factors that govern clinical responses to these therapies. Using an immunocompetent mouse model expressing a humanized CD3e chain (huCD3e mice) and BiTE molecules directed against mouse CD19, mouse CLDN18.2, or human EPCAM antigens, we investigated the pharmacokinetic and pharmacodynamic parameters and immune correlates associated with BiTE efficacy across multiple syngeneic solid-tumor models. These studies demonstrated that pretreatment tumor-associated T cell density is a critical determinant of response to BiTE therapy, identified CD8+ T cells as important targets and mediators of BiTE activity, and revealed an antagonistic role for CD4+ T cells in BiTE efficacy. We also identified therapeutic combinations, including ICB and 4-1BB agonism, that synergized with BiTE treatment in poorly T cell-infiltrated, immunotherapy-refractory tumors. In these models, BiTE efficacy was dependent on local expansion of tumor-associated CD8+ T cells, rather than their recruitment from circulation. Our findings highlight the relative contributions of baseline T cell infiltration, local T cell proliferation, and peripheral T cell trafficking for BiTE molecule-mediated efficacy, identify combination strategies capable of overcoming resistance to BiTE therapy, and have clinical relevance for the development of BiTE and other T cell engager therapies.

Supplemental Digital Content is available in the text., Objectives: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. Design: Retrospective study. Setting: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. Patients: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. Interventions: None. Measurements and Main Results: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25–14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16–25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2–7.7 d) and 4 days (1.9–7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. Conclusions: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

BACKGROUND: Neoadjuvant treatment followed by esophagectomy is standard practice in locally advanced esophageal cancer. However, not all patients who started neoadjuvant treatment will undergo esophageal resection. The purpose of our study was to investigate the group of patients, scheduled for neoadjuvant treatment followed by esophagectomy, who never made it to esophageal resection. METHODS: We retrospectively analyzed patients treated between 2002 and 2015 for locally advanced esophageal cancer, who did not undergo esophagectomy after neoadjuvant treatment. Subanalysis was performed according to time period (2002-2010 versus 2011-2015) and histology (adenocarcinoma versus squamous cell carcinoma). RESULTS: In 114 of 679 patients (16.8%), surgery was not performed after neoadjuvant treatment. Reasons for cancelation were disease progression (50 patients, 43.9%), poor general condition (26 patients, 22.8%), irresectability (14 patients, 12.3%), patients' own decision (15 patients, 13.2%), and death during neoadjuvant treatment (9 patients, 7.9%). In the second time period, there were less irresectable tumors (17.7% versus 5.8%; p = 0.044). Median overall survival was not different over time (9.2 versus 12.5 months; p = 0.937). Irresectability (p = 0.032), patients' refusal (p = 0.012), and poor general condition (p = 0.002) were more frequent as reasons for cancelation in squamous cell carcinoma patients. Median overall survival was, respectively, 12.5 and 9.9 months for adenocarcinoma and squamous cell carcinoma patients (p = 0.441). The majority of patients refusing surgery had a clinical complete response (73.3%). They had a median overall survival of 33.2 months. CONCLUSIONS: One in six patients starting neoadjuvant treatment for locally advanced esophageal cancer never made it to esophagectomy, more than half of them for oncological reasons, but also 1.3% because of death during treatment. Over time, irresectability as reason decreased. As a result, the relative weight of medical inoperability increased, indicating the importance of upfront testing of medical operability. Cancelation of surgery was significantly more common in patients with a squamous cell carcinoma, and this histology seems to represent a more complex oncological and functional entity. Refusal of esophagectomy based on clinical complete response showed a significant survival benefit compared to those who did not undergo esophagectomy because of other reasons. ispartof: World J Surg Oncol vol:17 issue:89 pages:1-9 ispartof: location:England status: Published online

Prominent inclusion bodies can develop in the endoplasmic reticulum (ER) when overexpressed antibodies possess intrinsically high condensation propensities. These observations suggest that antibodies deemed to show notable solubility problems may reveal such characteristics preemptively in the form of ER-associated inclusion bodies during antibody overexpression. To define the relationships between solubility problems and inclusion body phenotypes, we investigated the biosynthesis of a model human IgG2λ that shows severe opalescence in an acidic formulation buffer yet retains high solubility at physiological pH. Consistent with the pH-dependent solubility characteristics, the model antibody did not induce notable inclusion body in the physiological pH environment of the ER lumen. However, when individual subunit chains of the antibody were expressed separately, the light chain (LC) spontaneously induced notable crystal-like inclusion bodies in the ER. The LC crystallization event was readily reproducible in vitro by simply concentrating the purified LC protein at physiological pH. Two independent structural determinants for the LC crystallization were identified through rational mutagenesis approach by monitoring the effect of amino acid substitutions on intracellular LC crystallogenesis. The effect of mutations on crystallization was also recapitulated in vitro using purified LC proteins. Importantly, when introduced directly into the model antibody, a mutation that prevents the LC crystallization remediated the antibody's solubility problem without compromising the secretory output or antigen binding. These results illustrate that the ER can serve as a “physiological test tube” that not only reports secretory cargo's high condensation propensity at physiological pH, but also provides an orthogonal method that guides antibody engineering strategy.

Homologous recombination (HR) is an evolutionarily conserved process that is essential for genome plasticity and is thus involved in numerous fundamental biological processes. This chapter summarizes the HR molecular mechanisms in mammals, its roles in DNA double-strand break (DSB) repair and reactivation of arrested replication forks, and the consequences of dysregulation of these processes in human pathologies. HR competes with other pathways of DSB repair; we propose a two-step model for the DSB repair pathway selection. HR is a double-edged sword that favors genome stability maintenance but can generate genome instability. We discuss situations of HR-induced genetic instability and strategies developed to protect against excessive HR, including regulation of the cell cycle, detoxification of HR intermediates, and repression of HR initiation. Then, we discuss HR dysregulation in tumors and anticancer strategies targeting HR. Finally, we discuss the roles of HR in the molecular evolution of the genome.

The death-inducing signaling complex (DISC) is a fundamental multiprotein complex, which triggers the extrinsic apoptosis pathway through stimulation by death ligands. DISC consists of different death domain (DD) and death effector domain (DED) containing proteins such as the death receptor Fas (CD95) in complex with FADD, procaspase-8, and cFLIP. Despite many experimental and theoretical studies in this area, there is no global agreement neither on the DISC architecture nor on the mechanism of action of the involved species. In the current work, we have tried to reconstruct the DISC structure by identifying key protein interactions using a new protein–protein docking meta-approach. We combined the benefits of five of the most employed protein–protein docking engines, HADDOCK, ClusPro, HDOCK, GRAMM-X, and ZDOCK, in order to improve the accuracy of the predicted docking complexes. Free energy of binding and hot spot interacting residues were calculated and determined for each protein–protein interaction using molecular mechanics generalized Born surface area and alanine scanning techniques, respectively. In addition, a series of in-cellulo protein-fragment complementation assays were conducted to validate the protein–protein docking procedure. The results show that the DISC formation initiates by dimerization of adjacent FasDD trimers followed by recruitment of FADD through homotypic DD interactions with the oligomerized death receptor. Furthermore, the in-silico outcomes indicate that cFLIP cannot bind directly to FADD; instead, cFLIP recruitment to the DISC is a hierarchical and cooperative process where FADD initially recruits procaspase-8, which in turn recruits and heterodimerizes with cFLIP. Finally, a possible structure of the entire DISC is proposed based on the docking results.

PURPOSE: To investigate the effect of data quality and quantity on the performance of deep learning (DL) models, for dose prediction of intensity-modulated radiotherapy (IMRT) of esophageal cancer. MATERIAL AND METHODS: Two databases were used: a variable database (VarDB) with 56 clinical cases extracted retrospectively, including user-dependent variability in delineation and planning, different machines and beam configurations; and a homogenized database (HomDB), created to reduce this variability by re-contouring and re-planning all patients with a fixed class-solution protocol. Experiment 1 analysed the user-dependent variability, using 26 patients planned with the same machine and beam setup (E26-VarDB versus E26-HomDB). Experiment 2 increased the training set by groups of 10 patients (E16, E26, E36, E46, and E56) for both databases. Model evaluation metrics were the mean absolute error (MAE) for selected dose-volume metrics and the global MAE for all body voxels. RESULTS: For Experiment 1, E26-HomDB reduced the MAE for the considered dose-volume metrics compared to E26-VarDB (e.g. reduction of 0.2 Gy for D95-PTV, 1.2 Gy for Dmean-heart or 3.3% for V5-lungs). For Experiment 2, increasing the database size slightly improved performance for HomDB models (e.g. decrease in global MAE of 0.13 Gy for E56-HomDB versus E26-HomDB), but increased the error for the VarDB models (e.g. increase in global MAE of 0.20 Gy for E56-VarDB versus E26-VarDB). CONCLUSION: A small database may suffice to obtain good DL prediction performance, provided that homogenous training data is used. Data variability reduces the performance of DL models, which is further pronounced when increasing the training set. ispartof: PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS vol:83 pages:52-63 ispartof: location:Italy status: published

Deferment cutting is a two-aged regeneration method in which the majority of the stand is harvested and a dispersed component of overstory trees—approximately 15–20% of the basal area – is retained for at least one-half rotation and up one full rotation for reasons other than regeneration. Careful consideration of residual trees, in both characteristics and harvesting, is necessary to improve the chances that individual trees will survive until the next planned harvest. A long-term experimental deferment cutting study was established on the Fernow Experimental Forest and Monongahela National Forest in West Virginia, USA in the early 1980s. Repeated tree measurements spanning the approximately 35-year study period permitted a survival analysis of the overstory cohort. The effects on survival were tested for three endogenous factors (dbh, species, crown class) and one exogenous factor (logging damage) using a Cox Proportional Hazards model, with stand effects (multiple trees measured within a stand) accounted for by using as frailty model. Survival rates were high, with 92% of trees surviving (910 of 985 trees). The mortality rate was low at six percent, (60 of 985 trees), and the number of trees cut or destroyed during logging was two percent (15 of 985 trees). Trees injured in the deferment harvest did not show increased risk of mortality, p = 0.91. Crown class also did not contribute to increased mortality, p = 0.35, as the majority of overstory trees retained were in the dominant and codominant classes. Six species, Liriodendron tulipifera L., Prunus serotina Ehrh., Quercus alba L., Quercus montana Willd., Quercus rubra L., Quercus velutina Lam., had sufficient sample sizes to test for species differences. However, species was not significant for survival, p = 0.10. The only significant factor in survival was dbh, p

Childbirth has been positioned as a life changing event that has profound long-term psychological effects upon women. This paper adopts a community psychology approach to explore the role that the ...

A long-term forest management case study on the Fernow Experimental Forest in West Virginia referred to as the Cutting Practice Level study is evaluated after 60 years. Treatments include a commercial clearcut (one time application), a 39 cm diameter-limit (applied 4 times), uneven-aged management using two variations of single-tree selection (applied 7 and 8 times, respectively), and an unmanaged reference area. We examine productivity, species composition and diversity, structure, tree quality, and revenues generated related to each treatment since establishment. The diameter-limit treatment resulted in greatest average periodic annual increment (PAI) of sawtimber volume of 3.1 m3 ha−1 yr−1 while the unmanaged reference area resulted in the least of 2.2 m3 ha−1 yr−1 (based on the difference in standing volume from 1956 to 2008). All types of partial harvesting resulted in greater sawtimber productivity than either the commercial clearcut or the reference area. Post-harvest tree quality, as measured by proportion of grade 1 butt logs, has improved from 1988 to 2008 for all but the diameter-limit treatment, which is similar to conditions in 1968. In 2008, the proportion of grade 1 trees in the residual stand ranged from a high of 0.22 for single-tree selection to 0.15 for diameter-limit harvesting. Species composition is becoming less diverse and more dominated by shade-tolerant species in all treatment groups but the change has been the greatest in the two single-tree selection treatments. Initially, size-class distributions were somewhat unimodal and reflective of even-aged stands with shade tolerant species persisting in the understory. In 2008, the single-tree selection treatments were both characterized by a reverse-J size class distribution and it appears this structure can be maintained due to recruitment of shade-tolerant species in the smaller size classes with concomitant reductions in species diversity. The net present value for each treatment in 2008, the time of the last management intervention, ranged from $20,000 ha−1 for reference area to almost $34,000 ha−1 for the single-tree selection treatment that included management of pole-sized trees based on all revenue and the value of standing timber using an internal rate of return of 4%.

Objective To develop a multicenter, multistakeholder, prospective clinical registry of children and adolescents with migraine to support the collection of real-world data of sufficient quality to support regulatory submissions and provide site-based infrastructure support for future clinical trials. Background As new migraine treatments come to market, pediatric efficacy and safety trials of these agents are needed. A clinical registry is an ideal regulatory strategy to provide both real-world data and site infrastructure to execute these trials. Design Multicenter, multistakeholder, prospective real-world data clinical registry of children and adolescents, 4-17 years of age, diagnosed with migraine with or without aura. Participants will be followed for up to 12 months at 3-month intervals, with interval recording of clinical data at study sites and self-reported data via mobile health application, as well as biobanking. We developed electronic case report forms that incorporated routinely collected clinical data with National Institute of Neurological Disorders and Stroke Headache Common Data Elements (Version 2.0). All data are captured in a 21 CFR Part 11 - compliant electronic data capture system - augmented by a real-time, web-based, and customizable data visualization platform. We engaged vendors to provide ancillary biobanking, patient data entry, and data visualization services. Results We used an iterative and highly collaborative multistakeholder approach to design and implement a streamlined registry protocol with input from all participating US sites. At each design and implementation step, we received input from therapeutic area experts, the US Food and Drug Administration (FDA), the National Institutes of Health, patient and parent advocates, health technology partners, drug developers, and site-based clinical investigators. The registry is governed by a multistakeholder steering committee with representation from sites, industry partners, patient advocates, and a member from the FDA (non-voting with respect to steering committee matters). The multistakeholder and site-driven approach to registry design and execution was highly efficient and resulted in the first patient enrolled within 6 months of concept development. Conclusions By ensuring regulatory compliant implementation of the registry, we created both a source of real-world data and a multisite platform for the conduct of future clinical trials that can be submitted to regulatory authorities to support inclusion of pediatric data in approved drug labeling. A highly collaborative approach with broad stakeholder engagement at all stages of the registry development was a key to our operational success.

Purpose: To explore whether a higher neoadjuvant radiation dose increases the probability of a pathological complete response (pCR) or pathological major response (pMR) response in oesophageal cancer patients. Material and methods: Between 2000 and 2017, 1048 patients from four institutions were stratified according to prescribed neoadjuvant radiation doses of 36.0 Gy (13.3%), 40.0 Gy (7.4%), 41.4 Gy (20.1%), 45.0 Gy (25.5%) or 50.4 Gy (33.7%) in 1.8-2.0 Gy fractions. Endpoints were pCR (tumour regression grade (TRG) 1) and pMR (TRG 1 + 2). Multivariable binary (TRG 1 + 2 vs. TRG > 2) and ordinal (TRG 1 vs. TRG 2 vs. TRG > 2) logistic regression analyses were performed, with subgroup analyses according to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)). Variables entered in the regression model along with neoadjuvant radiation dose were clinical tumour stage (cT), histology, chemotherapy regimen, induction chemotherapy and time from neoadjuvant chemoradiation to surgery. Results: A pCR was observed in 312 patients (29.8%); in 22.7% patients with AC and in 49.6% patients with SCC. No radiation dose-response relation was observed for pCR (OR = 1.01, 95% CI: 0.98-1.05 for AC and OR = 1.03, 95% CI: 0.96-1.10 for SCC). A pMR was observed in 597 patients (57.0%); in 53.4% patients with AC and in 67.2% patients with SCC. A higher radiation dose increased the probability of achieving pMR (OR = 1.04, 95% CI: 1.02-1.05). Factors reducing this probability were advanced cT stage (reference = cT1-2; cT3: OR = 0.54, 95% CI: 0.37-0.80; cT4: OR = 0.45, 95% CI: 0.24-0.84), AC histology (reference = SCC; OR = 0.62, 95% CI: 0.44-0.88), the use of non-platinum based chemotherapy in SCC patients (OR = 0.30, 95% CI: 0.10-0.91) and platinum based chemotherapy without induction chemotherapy in patients with AC (OR = 0.56, 95% CI: 0.42-0.76). The radiation dose-response relation was confirmed in a subgroup analysis of histologic subtypes (OR = 1.02, 95% CI: 1.01-1.04 for AC and OR = 1.05, 95% CI: 1.02-1.08 for SCC). Conclusions: Neoadjuvant radiation dose impacts pathological response in terms of pMR in oesophageal cancer patients. No radiation dose-response effect was observed for pCR. Further prospective trials are needed to investigate the dose-response relation in terms of pCR. ispartof: ACTA ONCOLOGICA vol:58 issue:10 pages:1358-1365 ispartof: location:England status: published

International audience; CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca2+ response via docking of PLC gamma 1 to the calcium-inducing domain (CID) within CD95. This signaling pathway induces accumulation of inflammatory Th17 cells in damaged organs of lupus patients, thereby aggravating disease pathology. A large-scale screen revealed that the HIV protease inhibitor ritonavir is a potent disruptor of the CD95-PLC gamma 1 interaction. A structure-activity relationship approach highlighted that ritonavir is a peptidomimetic that shares structural characteristics with CID with respect to docking to PLC gamma 1. Thus, we synthesized CID peptidomimetics abrogating both the CD95-driven Ca2+ response and transmigration of Th17 cells. Injection of ritonavir and the CID peptidomimetic into lupus mice alleviated clinical symptoms, opening a new avenue for the generation of drugs for lupus patients.

OBJECTIVE: To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT). STUDY DESIGN: This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing therapy, excluding those with pre-existing hypertension or prior dialysis or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90(th) percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for KIM-1, IL-18, EGF, albumin, and creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the bedside CKiD equation. Recent kidney ultrasounds and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy (LVH), respectively. Clinical follow-up data was collected for approximately 2 years following study enrollment. RESULTS: Thirty-two participants (median age 13.6 [IQR: 10.5-16.3] years; 75% ≥Stage 3 WT) were evaluated at a median of 8.7 years (IQR: 6.5-10.8) post-therapy. Twenty-nine participants underwent unilateral radical nephrectomy, 2 bilateral partial nephrectomy, and 1 radical and contralateral partial nephrectomy. 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 ml/min/1.73m(2) (IQR: 84.6-114.0; 11 (34%) had an eGFR

We compared the relative frequencies of witness trees in historical deeds to the relative frequencies of tree species found in the present forests. Changes in relative frequencies of the five dominant tree species were noted in all ecological subsections, although all species found in the past forests are represented in the present. The greatest changes across the study area were a decrease in the representation of white oak and an increase in red maple. The changes in representation by functional groups show a trend toward loss of fire-adapted species of intermediate shade intolerance with associated gains in species of high shade tolerance. Current FIA data on the species composition of trees in the sapling and seedlings size-classes indicate that the trend of reduced of oak species frequency is likely to continue into the near future. This gradual conversion from oak-dominated overstories to maple-dominated understories is a regional trend. Our findings echo a paradox found in the northeastern United States where after 400 years of land use change, forest cover has largely recovered but relative species composition has been transformed. This paradox may add to the difficulty in designing strategies and treatments for ecosystem restoration. However, as we have shown, the changes can be quantified and placed in an ecological context as support for restoration actions.

Objective: This article gives an in-depth insight into the ways in which communication between midwives and the birthing woman shape the birth experience. Background: Birth is a significant life ev...

INTRODUCTION: Radiotherapy is a cornerstone in the multimodality treatment of several gastrointestinal (GI) tumors. Positron-emission tomography (PET) has an established role in the diagnosis, response assessment and (re-)staging of these tumors. Nevertheless, the value of PET in adaptive radiotherapy remains unclear. This review focuses on the role of PET in adaptive radiotherapy, i.e. during the treatment course and in the delineation process. EVIDENCE ACQUISITION: The MEDLINE database was searched for the terms ("Radiotherapy"[Mesh] AND "Positron-Emission Tomography"[Mesh] AND one of the site-specific keywords, yielding a total of 1710 articles. After abstract selection, 27 papers were identified for esophageal neoplasms, 1 for gastric neoplasms, 9 for pancreatic neoplasms, 6 for liver neoplasms, 1 for biliary tract neoplasms, none for colonic neoplasms, 15 for rectal neoplasms and 12 for anus neoplasms. EVIDENCE SYNTHESIS: The use of PET for truly adaptive radiotherapy during treatment for GI tumors has barely been investigated, in contrast to the potential of the PET-defined metabolic tumor volume for optimization of the target volume. The optimized target definition seems useful for treatment individualization such as focal boosting strategies in esophageal, pancreatic and anorectal cancer. Nevertheless, for all GI tumors, further investigation is needed. CONCLUSIONS: In general, too little data are available to conclude on the role of PET imaging during radiotherapy for ART strategies in GI cancer. On the other hand, based on the available evidence, the use of biological imaging for target volume adaptation seems promising and could pave the road towards individualized treatment strategies. ispartof: QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol:62 issue:4 pages:385-403 ispartof: location:Italy status: published

Prior to its decline and functional extinction due to an invasive blight fungus (Cryphonectria parasitica) in the early 20th century, the American chestnut was a key dominant tree species in most eastern deciduous forests. The infection mechanism, and associated factors affecting rates of infection, must be understood if a hybrid chestnut species is to be reintroduced within native range tree stands. The focus of our work was on on the blight fungus itself. Our objectives were to: 1) determine the possibility of hypo-virulent (or less infectious) strains of the fungus being present at our research site, 2) identify factors correlated with infection rates at the site, and 3) examine possible connections between infection and chestnut mortality rates and factors like chestnut type, family, and site location. We sampled each of four types of chestnut (Pure American/Chinese and two hybrids [B3F2 and B3F3]) at the St. George research site where we characterized cankers and tree environment in addition to culturing canker samples under lab conditions. We did not find evidence of hypo-virulent strains of the chestnut blight at the research site, which could be attributed to hypo-virulent fungus having relatively low success rates due to inhibited sporulation. There was no significant relationship between chestnut species/lineage and infection/mortality rates. This research could inform the development and success of hybrids used in the reintroduction of American chestnut in the future.

The composition of soil is determined by plants and their organic waste that has been broken down and recycled throughout the ecosystem. This process is controlled by bugs within the soil, called litter fauna. The analysis of litter fauna under the American Chestnut tree species gives details on the effects of that plant on the environment. The American chestnut has been functionally extinct since the introduction of the Chinese Chestnut blight to America in 1910’s. The American Chestnut used to dominate ecosystems and drive industry related to timber and nut harvest. Hybridization of the different American and Chinese Chestnut tree species has changed their morphology over the years in attempts to create a blight resistant hybrid. Scientists are unaware of the effects of the absence of American chestnuts and the emergence of pollinated hybrids on soil type and presence of litter fauna. Litter fauna diversity and population can help distinguish the health of an ecosystem therefore I hypothesized that abundance of individuals of non-Acarina taxa differs among hybrid tree types. Litter was collected under American Chestnut trees, Chinese Chestnut and two of their hybrids. The fauna was extracted using a Berlese funnel and analyzed. I concluded that there is no functional difference in non-Acarina fauna samples among the hybrids and their pure-bred counterparts. This indicates that the reintroduction of American Chestnuts and their hybrids into the ecosystem will not negatively affect the soil and its litter fauna.

With the increase in natural gas production in the United States, land managers need solutions and best practices to mitigate potential negative impacts of forest and soil disturbance and meet landowner objectives and desired conditions. Mitigation often includes the use of native seed mixes for maintaining plant diversity, controlling nonnative invasive species, and erosion control. The area disturbed by installing a buried pipeline to transport natural gas from a gas well near Parsons, WV was used to test the performance of a native seed mix. The seed mix was applied at the recommended seeding rate (56 kg ha-1; 50 lb ac-1) and triple the recommended rate (168 kg ha-1; 150 lb ac-1) to evaluate whether a higher seeding rate would produce greater native establishment and affect tree, weed, and invasive plant colonization. Sowed native grasses and blackberry (Rubus spp.), the latter of which was not part of the seed mix, dominated the pipeline right-of-way (ROW) 3 years after seeding. Mean coverage of these species was more than 68 percent on all the pipeline study plots. Deer-tongue (Dichanthelium clandestinum [L.] Gould) was by far the most successful species in the seed mix (overall mean cover of 33 percent), and it showed much better establishment on the drier southeast-facing hillside (mean cover of 49 percent). Autumn bentgrass (Agrostis perennans [Walter] Tuck.) fared better on the wetter northwest aspect (mean cover of 24 percent). Specific site characteristics or regeneration needs may explain the absence or limited onsite presence of some native species from the seed mix 3 years after sowing. Our results add support to the argument that a ROW project may require a variety of seed mixtures, especially when growing conditions and soil series vary across the project area.

Purpose The purpose of this study was to compare the effectiveness of controlled breathing (CB), with and without aromatherapy (isopropyl alcohol [IPA]), in the treatment of postoperative nausea (PON) in adult females undergoing elective outpatient laparoscopic procedures. Design A prospective randomized two-group quasi-experimental design was used. Methods A convenience sample was used. Patients were consented and assigned to either a control (CB) or treatment (IPA) group. Symptomatic patients rated nausea severity before and at 2 and 5 minutes after receiving either CB or CB with IPA. Findings Complete data for one episode of nausea were obtained on 82 patients (41 in each group). Results showed that although nausea severity decreased significantly over time, there was no significant difference in PON treatment effectiveness between the two groups, nor was there a difference in requests for rescue medications. Conclusions Patients who experience PON should be encouraged to take slow deep breaths as an initial response to symptoms. This approach has no side effects or costs and could also aid the patient to self-manage symptoms after discharge.

Cabwaylingo State Forest in southern West Virginia has experienced numerous anthropogenic wildfires over the past 36 years. In this case study, we assessed the relationship between fire frequency and recency and stand composition and structure, with emphasis on oak and its competitors. Frequent and recent fire was significantly correlated with reduced red maple overstory stem density and basal area. Overstory oak density did not significantly vary with either fire frequency or recency. Total overstory basal area was greatest in areas of either no fire or nonrecent fire. Oak sapling density was significantly greater with high frequency and recent fire. Red maple sapling densities were greatest when fires were infrequent and recent, and red maple seedlings were greatest in no fire and low-frequency nonrecent fire areas. Our results suggest that recurring fire can enhance the development of large oak advanced reproduction. However, frequent fires without a sufficient fire-free interval could prevent the recruitment of oaks into the overstory.

Designing drugs to treat diseases associated with articular joints, particularly those targeting chondrocytes, is challenging due to unique local environmental constraints including the avascular nature of cartilage, the absence of a closed joint compartment, and a highly cross-linked extracellular matrix. In an effort to address these challenges, we developed a novel strategy to prolong residence time of intra-articularly administered protein therapeutics. Avimer domains are naturally found in membrane polypeptides and mediate diverse protein-protein interactions. Screening of a phage Avimer domain library led to identification of several low affinity type II collagen-binding Avimers. Following several rounds of mutagenesis and reselection, these initial hits were transformed to high affinity, selective type II collagen-binding Avimers. One such Avimer (M26) persisted in rat knees for at least 1 month following intra-articular administration. Fusion of this Avimer to a candidate therapeutic payload, IL-1Ra, yielded a protein construct which simultaneously bound to type II collagen and to IL-1 receptor. In vitro, IL-1Ra_M26 bound selectively to cartilage explants and remained associated even after extensive washing. Binding appeared to occur preferentially to pericellular regions surrounding chondrocytes. An acute intra-articular IL-1-induced IL-6 challenge rat model was employed to assess in vivo pharmacodynamics. Whereas both IL-1Ra_M26 and native IL-1Ra inhibited IL-6 output when co-administered with the IL-1 challenge, only IL-1Ra_M26 inhibited when administered 1 week prior to IL-1 challenge. Collagen-binding Avimers thus represent a promising strategy for enhancing cartilage residence time of protein therapeutics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1238-1247, 2018.

Designing drugs to treat diseases associated with articular joints, particularly those targeting chondrocytes, is challenging due to unique local environmental constraints including the avascular nature of cartilage, the absence of a closed joint compartment, and a highly cross-linked extracellular matrix. In an effort to address these challenges, we developed a novel strategy to prolong residence time of intra-articularly administered protein therapeutics. Avimer domains are naturally found in membrane polypeptides and mediate diverse protein-protein interactions. Screening of a phage Avimer domain library led to identification of several low affinity type II collagen-binding Avimers. Following several rounds of mutagenesis and reselection, these initial hits were transformed to high affinity, selective type II collagen-binding Avimers. One such Avimer (M26) persisted in rat knees for at least 1 month following intra-articular administration. Fusion of this Avimer to a candidate therapeutic payload, IL-1Ra, yielded a protein construct which simultaneously bound to type II collagen and to IL-1 receptor. In vitro, IL-1Ra_M26 bound selectively to cartilage explants and remained associated even after extensive washing. Binding appeared to occur preferentially to pericellular regions surrounding chondrocytes. An acute intra-articular IL-1-induced IL-6 challenge rat model was employed to assess in vivo pharmacodynamics. Whereas both IL-1Ra_M26 and native IL-1Ra inhibited IL-6 output when co-administered with the IL-1 challenge, only IL-1Ra_M26 inhibited when administered 1 week prior to IL-1 challenge. Collagen-binding Avimers thus represent a promising strategy for enhancing cartilage residence time of protein therapeutics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1238-1247, 2018.

Distribution of the death receptor CD95 into lipid rafts (aggregation) and/or its internalization may contribute to the implementation of the apoptotic signal at the detriment of the non-apoptotic signaling pathway [1-6]. Also CD95 can form different protein complexes via dynamic protein-protein interactions (PPIs) according to its interaction with soluble or transmembrane CD95L. Therefore, spatiotemporal identification of these PPIs is pivotal to anticipate the signaling pathway implemented in cells stimulated with different forms of CD95L. Also, many disorders result from dysfunctions in terms of PPI subcellular distribution and/or their intensity, rendering evaluation of these features crucial to better understand pathogenesis.In situ proximity ligation assay (PLA) is a methodology that offers the possibility to identify PPIs and to determine where these PPIs occur in subcellular location (Fig. 1). Moreover, based on imaging, this method allows a quantification of PPIs at the cellular level and with a higher specificity than classical immunofluorescence assays. We here describe PLA used to confirm CD95/FADD interaction, a protocol that may serve to highlight other CD95 partners.

A long-term study on the Fernow Experimental Forest (FEF) in West Virginia provided an opportunity to test for differences in the timber quality of trees harvested from three silvicultural practices (HarvestType): diameter-limit, patch cutting, and single-tree selection. The effects of HarvestType and site index (SI) over time on the harvested proportion of trees with grade 1 butt logs within a compartment were tested using a repeated-measures linear mixed model. HarvestType*Time was a significant interaction (P = 0.0018) and SI had a slight positive effect (P = 0.0036). When examining the harvested proportion of grade 1 butt logs on a volume basis, the two terms were again significant (P = 0.0003 and P = 0.0208, respectively). The diameter-limit proportion of grade 1 butt logs consistently decreased while patch cutting and single-tree selection proportions consistently increase over time. Recent preharvest cruise data show a significantly greater residual proportion of grade 1 butt logs for single-tree selection compartments versus diameter-limit compartments on a per-tree and per-volume basis (P = 0.0013 and P < 0.0001, respectively). Results indicate that the production of grade 1 trees in diameter-limit harvests is not sustainable productivity wise whereas the single-tree selection harvests are. The sustainability of the production of grade 1 logs from patch cutting remains inconclusive.

Active restoration of threatened or endangered species habitat may seem in conflict with the provisions of the Endangered Species Act because of the prohibition of “take,” which can include habitat modification as well as death or harm to individuals. Risk-averse managers may choose to forego active management in known or presumed endangered species habitat to avoid killing an individual or harming critical habitat. We used the landscape-scale model LANDIS-II to simulate red spruce (Picea rubens Sarg.)-dominated forest response to restoration actions for 100 years. Restoration strategies differed in management of the potential habitat for the recently delisted Virginia northern flying squirrel (Glaucomys sabrinus fuscus). Model simulations show that active management with protections for existing red spruce stands resulted in a greater area dominated by red spruce than did larger, areawide protections. However, protecting larger areas of potential habitat resulted in an increase in red spruce in areas of low to moderate probability of occurrence for the flying squirrel, potentially increasing the area’s suitability for this species.

American chestnut restoration depends on a multitude of biological, administrative, and technological factors. Germplasm traditionally bred for resistance to the chestnut blight disease caused by the exotic pathogen Cryphonectria parasitica has been deployed on national forests in the Eastern and Southern Regions of the National Forest System (NFS) since 2009. Trees were challenged by biological factors, primarily deer browse and ink disease (caused by Phytophthora cinnamomi). Because of these problems, inferences regarding resistance or tolerance to blight are premature. Mitigation to improve success includes improved technology in seedling production for planting and selection of appropriate test sites with limited management restrictions. We suggest that chestnut restoration within the USDA Forest Service be conducted through deployment of a series of long-term multidisciplinary tests. Limitations in resources required for this effort necessitate partnership building both within and outside the agency. Vegetation establishment targets that include chestnut test plantings within the NFS should be developed.

Purpose The purpose of this study is to determine patient management strategies and outcomes for self-care of postdischarge nausea and vomiting (PDNV). Design Prospective, comparative, descriptive, and longitudinal study. Methods The sample consisted of 248 patients aged 18 years or older undergoing a procedure requiring general anesthesia. Patients recorded incidence and severity of nausea and vomiting, the impact of symptoms, and actions taken to alleviate symptoms for 7 days postdischarge. Findings The prevalence of PDNV was 56.9%. The methods used to relieve symptoms included antiemetic use by a minority and nonpharmacologic techniques of self-management by some. The effect of nausea on QOL, patient functioning, and patient satisfaction was significantly worse for those who experienced postdischarge nausea on all days. Conclusion Patients with PDNV use minor self-care strategies to manage symptoms. The presence of PDNV affects overall quality of life, patient functioning, and patient satisfaction.

Automated imaging screens are performed mostly on fixed and stained samples to simplify the workflow and increase throughput. Some processes, such as the movement of cells and organelles or measuring membrane integrity and potential, can be measured only in living cells. Developing such assays to screen large compound or RNAi collections is challenging in many respects. Here, we develop a live-cell high-content assay for tracking endocytic organelles in medium throughput. We evaluate the added value of measuring kinetic parameters compared with measuring static parameters solely. We screened 2000 compounds in U-2 OS cells expressing Lamp1-GFP to label late endosomes. All hits have phenotypes in both static and kinetic parameters. However, we show that the kinetic parameters enable better discrimination of the mechanisms of action. Most of the compounds cause a decrease of motility of endosomes, but we identify several compounds that increase endosomal motility. In summary, we show that kinetic data help to better discriminate phenotypes and thereby obtain more subtle phenotypic clustering.

Six types of starch nanocrystals were prepared from corn, barley, potato, tapioca, chickpea, and mungbean starches with an acid hydrolysis method. The yields and morphological, structural, and thermal properties of starch nanocrystals were characterized. Starch nanocrystals had yields ranging from 8.8 to 35.7%, depending on botanical origin. During acid hydrolysis, amylose was effectively degraded, and no amylose was detected in any starch nanocrystal. Shape and size of native starch granules varied between starches, whereas there was no obvious difference in shape among different types of starch nanocrystals. The average particle size of starch nanocrystals was mainly related to crystalline type of native starches. Compared with their native starch counterparts, changes in crystalline diffraction patterns of starch nanocrystals depended on the original botanical source and crystalline structure. Degree of crystallinity, melting temperature, and enthalpy of starch nanocrystals increased, whereas ...

Current forests developed under conditions different from original forests, with higher deer densities, reduced fire frequency, denser canopies, and smaller canopy gaps. These alterations have led to understories dominated by species simultaneously browse tolerant, shade tolerant, and fire sensitive leading to difficulties in the regeneration of oak species (Quercus spp.) in some areas. We evaluated how three key processes — understory fire, canopy gaps, and browsing — influenced tree species in east central West Virginia. We were particularly interested in the response of oak species because they are the dominant overstory species and of maple species (Acer spp.), black birch (Betula lenta L.), and yellow-poplar (Liriodendron tulipifera L.) as these are likely to replace the current forest. Single-process effects were significant and significant interactions among processes were numerous. In general, fire caused significant reductions of seedlings and saplings of red maple (Acer rubrum L.) and striped maple (Acer pensylvanicum L.) and increased the seedlings of black birch and yellow-poplar. Canopy gaps increased the abundance of black birch and yellow-poplar seedlings and saplings. Gaps and fire together caused an increase in the relative abundance of yellow-poplar. Excluding browsers and creating canopy gaps together nearly doubled oak sapling importance values versus either treatment alone; however, oak importance values remained low. Given the significant interactions of browse control with the other two processes, browse control should be considered when planning oak regeneration treatments such as canopy gaps or prescribed fire.

Understanding and mapping presettlement fire regimes is vitally important for ecosystem restoration, helping ensure the proper placement of fire back into ecosystems that formerly burned. Witness trees can support this endeavor by serving as pyro-indicators of the past. We mapped fire-adapted traits across a landscape by categorizing trees into two classes, pyrophiles and pyrophobes, and applying this classification to a geospatial layer of witness-tree points centered on the Monongahela National Forest, West Virginia. A pyrophilic percentage was calculated for each point and spatially extrapolated via ordinary kriging to form a continuous geospatial cover. Regression analyses showed pyrophilic percentage was significantly related to a number of key environmental factors and changed along an elevation gradient from low, dry valleys (high pyrophilic percentage) to high, wet mountaintops (low pyrophilic percentage). This approach represents a significant advancement through the direct use of witness trees to depict past fire regimes applicable to both Public Land Survey and metes-and-bounds records.

BACKGROUND: Organ dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration, allowing to describe the clinical outcome of critically ill children throughout their stay. This score is increasingly used in clinical trials in specific subpopulation. Our objective was to assess the performance of the PELOD-2 score in a subpopulation of critically ill children requiring plasma transfusions.METHODS: This was an ancillary study of a prospective observational study on plasma transfusions over a 6-week period, in 101 PICUs in 21 countries. All critically ill children who received at least one plasma transfusion during the observation period were included. PELOD-2 scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion. Performance of the score was assessed by the determination of the discrimination (area under the ROC curve: AUC) and the calibration (Hosmer-Lemeshow test).RESULTS: Four hundred and forty-three patients were enrolled in the study (median age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was 26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71-0.81) and the Hosmer-Lemeshow test was p = 0.76. The serial evaluation of the changes in the daily PELOD-2 scores from day 1 demonstrated a significant association with death, adjusted for the PELOD-2 score on day 1.CONCLUSIONS: In a subpopulation of critically ill children requiring plasma transfusion, the PELOD-2 score has a lower but acceptable discrimination than in an entire population. This score should therefore be used cautiously in this specific subpopulation.

The flight planning process is the most critical time for the turbulence forecaster. It is the time that routes and altitudes are selected, and fuel is added for any necessary deviations. Aviation meteorologists can have a significant impact at this stage of flight planning. Internationally, flights are given preference for route and altitude selection based on the time the flight plan is filed. It is difficult for flights to change altitude once the flight plan has been accepted, since flights over the oceans cannot be seen on radar and have to be sequenced in space and time. If turbulence is not considered at the planning stage, altitude deviations for turbulence may not be allowed if there are other aircraft above and below the flight. Therefore, advanced knowledge of turbulence gives the advantage to the airlines that forecast turbulence accurately.

Manual pilot reporting of weather conditions, including turbulence, has been standard procedure during most of the Twentieth century. By the late 1940s, the International Civil Aviation Organization (ICAO) had developed standards which included aircraft-based weather observations by pilots and subsequent government distribution. In the USA, commercial airlines developed their own collection and distribution methods. This was in response to Federal Aviation Administration (FAA) requirements that pilots should report hazardous weather, and airlines should have ability to monitor the progress of every flight. By the 1980s, flight location as well as wind and temperature were being automatically reported in some areas of the world. But automated turbulence report capability was mainly a research effort with some operational capability introduced during the 1990s and 2000s.

Worldwide, oesophageal cancer, including cancer of the gastro-oesophageal junction (GEJ), is the sixth leading cause of death from cancer. Despite recent advances, treatment of oesophageal cancer remains challenging and is best approached by an experienced multidisciplinary team. Surgery alone is the treatment of choice in early stage carcinoma although in superficial cancers (T1a) endoscopic resection is to be preferred. In locally advanced tumours induction therapy followed by surgery is the preferred treatment. In selected cases definitive chemoradiotherapy could be considered as a valuable alternative. The role of adjuvant chemotherapy is unclear, but could be considered for selected GEJ adenocarcinoma patients. Adjuvant chemoradiotherapy should be considered in all patients with advanced disease or positive margins who did not receive neo-adjuvant radiotherapy. For metastatic disease, the goal is to prolong and maximize quality of life. Regarding the palliative treatment of dysphagia, brachytherapy was shown to be more effective than stenting.

Knowledge, both of the historical range of spruce-dominated forests and associated site conditions, is needed by land managers to help define restoration goals and potential sites for restoration. We used an existing digital database of witness trees listed in deeds from 1752 to 1899 to compare characteristics of red spruce (Picea rubens Sarg.) sites to non-red spruce sites to gain an understanding of historical spruce-dominated forests in West Virginia. The analysis revealed that red spruce witness trees were found at significantly higher elevations than non-spruce witness trees across the study area. However, spruce witness trees in the Western Allegheny Mountains subsection were found at significantly lower elevations than non-spruce witness trees. Indicator species analysis determined red spruce to be associated with toe slopes, benches, and valleys, although most locations were on side slopes. Across the entire study area, red spruce witness trees were more likely to be found on northeastern aspects and on acidic and frigid soils of the Mandy series. Historically, red spruce was associated with American beech (Fagus grandifolia Ehrh.), birch (Betula L.), and hemlock (Tsuga canadensis (L.) Carriere). This information should be used to guide red spruce restoration efforts and shows that a range of ecological settings should be considered when setting goals and implementing active management.

Evidence shows that disparities in pain care exist, and this problem spans across all health care settings. Health care disparities are complex, and stem from the health system climate, limitations imposed by laws and regulations, and discriminatory practices that are deep seated in biases, stereotypes, and uncertainties surrounding communication and decision-making processes. A search of the Internet identified thousands of Web sites, documents, reports, and educational materials pertaining to health and pain disparities. Web sites for federal agencies, private foundations, and professional and consumer-oriented organizations provide useful information on disparities related to age, race, ethnicity, geography, socioeconomic status, and specific populations. The contents of 10 Web sites are examined for resources to assist health professionals and consumers in better understanding health and pain disparities and ways to overcome them in practice.

This brief complements the brief on “Recommendations for Successfully Recruiting and Retaining District Participation in a Teen Pregnancy Prevention Impact Evaluation.â€

People love big trees, people love to find big trees, and people love to find big trees in the place they call home. Having been suspicious for years, my coauthor and historian Rob Whetsell, approached me with a species identification challenge. There are several photographs of giant trees used by many people to illustrate the past forests of West Virginia, specifically, these photographs are claimed to be of a giant white oak (Quercus alba) in Tucker County, West Virginia. Rob was sure these were of a species not found in West Virginia…and he was right.