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Monterey pine (Pinus radiata) is a species of limited distribution, with three native populations in California. In 1986, a disease known as pitch canker, caused by the fungus Fusarium circinatum, was identified as the cause of extensive mortality in planted Monterey pines in Santa Cruz County. Monitoring studies on the Monterey Peninsula documented rapid progression of the disease in the native forest during the 1990s, with most trees sustaining some level of infection. However, between 1999 and 2013, the severity of pitch canker stabilized, with many previously diseased trees then free of symptoms, and plots monitored between 2011 and 2015 documented a steady decline in the occurrence of new infections. Consequently, whereas pitch canker was once a conspicuous visual blight in the forest, by the end of the observation period, symptomatic trees had become a rarity. The arrested development of pitch canker is suggestive of a reduction in the frequency and duration of fog near the coast, which provides conditions necessary for the pathogen to establish infections.

The ability to detect and respond to vineyard spatial variation can lead to improved management—a practice known as precision viticulture. The goal of this study was to determine if remote sensors can enhance precision viticulture applications by detecting vineyard spatial variation. The hypothesis was that differences in vine spectral reflectance, as detected by remote sensors, would be associated with variations in viticultural variables due to known relationships with vine size, structure, and pigmentation. Riesling grapevines were geolocated within six commercial vineyards across Niagara, Ontario. Water status, vine size, winter hardiness, virus titer, yield components, and berry composition were measured on these vines. Remote sensing technologies subsequently collected multispectral data by unmanned aerial vehicles and by proximal sensing technology (GreenSeeker™), which were transformed into the Normalized Difference Vegetation Index (NDVI). Direct relationships between NDVI and vine size, water status, yield, berry weight, and titratable acidity were observed, as well as inverse relationships between NDVI and Brix and potentially volatile terpenes. Remote sensing demonstrated the ability to detect vineyard areas differing in measures of vine health, yield, and berry composition in certain sites and years; however, more research is needed to determine when these technologies should be used for precision viticulture applications.

Abstract Understanding the thermal decomposition behavior of TATB (1,3,5-triamino-2,4,6-trinitrobenzene) is a major focus in energetic materials research because of safety issues. Previous research and modelling efforts have suggested benzo-monofurazan condensation producing H2O is the initiating decomposition step. However, early evolving CO2 (m/z 44) along with H2O (m/z 18) evolution have been observed by mass spectrometric monitoring of head-space gases in both constant heating rate and isothermal decomposition studies. The source of the CO2 has not been explained, until now. With the recent successful synthesis of 13C6-TATB (13C incorporated into the benzene ring), the same experiments have been used to show the source of the CO2 is the early breakdown of the TATB ring, not adventitious C from impurities and/or adsorbed CO2. A shift in mass m/z 44 (CO2) to m/z 45 is observed throughout the decomposition process indicating the isotopically labeled 13C ring breakdown occurs at the onset of thermal decomposition along with furazan formation. Partially labeled (N18O2)3-TATB confirms at least some of the oxygen comes from the nitro-groups. This finding has a significant bearing on decomposition computational models for prediction of energy release and deflagration to detonation transitions, with respect to conditions which currently do not recognize this oxidation step.

We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Soeurs Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.

Abstract Background During interviews, medical students may feel uncomfortable asking questions that might be important to them, such as parental leave. Parental leave policies may be difficult for applicants to access without asking the program director or other interviewers. The goal of this study is to evaluate whether parental leave information is presented to prospective residents and whether medical students want this information. Methods Fifty-two program directors (PD’s) at 3 sites of a single institution received a survey in 2019 to identify whether parental leave information is presented at residency interviews. Medical students received a separate survey in 2020 to identify their preferences. Fisher exact tests, Pearson χ2 tests and Cochran-Armitage tests were used where appropriate to assess for differences in responses. Results Of the 52 PD’s, 27 responded (52%) and 19 (70%) indicated that information on parental leave was not provided to candidates. The most common reason cited was the belief that the information was not relevant (n = 7; 37%). Of the 373 medical students, 179 responded (48%). Most respondents (92%) wanted parental leave information formally presented, and many anticipated they would feel extremely or somewhat uncomfortable (68%) asking about parental leave. The majority (61%) felt that these policies would impact ranking of programs “somewhat” or “very much.” Conclusions Parental leave policies may not be readily available to interviewees despite strong interest and their impact on ranking of programs by prospective residents.

Chronic graft-versus-host disease (cGVHD) remains a frequent cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. In our single center trials of low-dose interleukin-2 (LD IL-2), the immunomodulatory properties of regulatory T cells (Tregs) have been harnessed to treat steroid-refractory cGVHD (SR-cGVHD) safely and effectively in adults and children. In these trials, 50-60% of patients showed clinical improvement of their cGVHD manifestations with partial responses at the primary response endpoint of 8-12 weeks. Many patients continued extended duration LD IL-2 therapy and achieved deeper clinical responses, including some complete responses. However, the durability of the clinical and immunologic improvement following IL-2 discontinuation has not been reported previously. We examined 20 adult and 2 pediatric patients who received extended duration LD IL-2 for a median of 103 weeks (range, 21-258) and had stable improvement or resolution of their cGVHD symptoms before discontinuing LD IL-2 therapy. The median follow-up after stopping IL-2 was 203 weeks (range 92-599). During this time, 16 patients (73%) were able to wean off all systemic immunosuppression without disease flare or progression. Among 13 patients with available immune cell data, the median fold change in absolute Treg count was 0.58 between 1 to 10 weeks after stopping IL-2 whereas CD4+ conventional T-cell (Tcon) and CD8+ T-cell numbers remained stable. Despite a decline in Treg numbers after IL-2 discontinuation, Treg numbers remained above the pre-treatment baseline. In addition, many patients had sustained clinical improvement after stopping IL-2, suggesting that extended IL-2 therapy can lead to immune tolerance.

The application of direct-current plasma arc furnace technology to the problem of coal gasification is investigated using computational multiphysics models of the plasma arc inside such units. An integrated modelling workflow for the study of DC plasma arc discharges in synthesis gas atmospheres is presented. The thermodynamic and transport properties of the plasma are estimated using statistical mechanics calculations and are shown to have highly non-linear dependencies on the gas composition and temperature. A computational magnetohydrodynamic solver for electromagnetically coupled flows is developed and implemented in the OpenFOAM® framework, and the behaviour of three-dimensional transient simulations of arc formation and dynamics is studied in response to different plasma gas compositions and furnace operating conditions. To demonstrate the utility of the methods presented, practical engineering results are obtained from an ensemble of simulation results for a pilot-scale furnace design. These include the stability of the arc under different operating conditions and the dependence of voltage–current relationships on the arc length, which are relevant in understanding the industrial operability of plasma arc furnaces used for waste coal gasification.

BACKGROUND Gut decontamination (GD) can decrease the incidence and severity of acute graft-versus-host disease (aGVHD) in murine models of allogeneic hematopoietic cell transplantation (HCT). In this pilot study, we examined the impact of GD on gut microbiome composition and the incidence of aGVHD in HCT patients.METHODS We randomized 20 patients undergoing allogeneic HCT to receive (GD) or not receive (no-GD) oral vancomycin-polymyxin B from day –5 through neutrophil engraftment. We evaluated shotgun metagenomic sequencing of serial stool samples to compare the composition and diversity of the gut microbiome between study arms. We assessed clinical outcomes in the 2 arms and performed strain-specific analyses of pathogens that caused bloodstream infections (BSI).RESULTS The 2 arms did not differ in the predefined primary outcome of Shannon diversity of the gut microbiome at 2 weeks post-HCT (genus, P = 0.8; species, P = 0.44) or aGVHD incidence (P = 0.58). Immune reconstitution of T cell and B cell subsets was similar between groups. Five patients in the no-GD arm had 8 BSI episodes versus 1 episode in the GD arm (P = 0.09). The BSI-causing pathogens were traceable to the gut in 7 of 8 BSI episodes in the no-GD arm, including Staphylococcus species.CONCLUSION While GD did not differentially affect Shannon diversity or clinical outcomes, our findings suggest that GD may protect against gut-derived BSI in HCT patients by decreasing the prevalence or abundance of gut pathogens.TRIAL REGISTRATION ClinicalTrials.gov NCT02641236.FUNDING NIH, Damon Runyon Cancer Research Foundation, V Foundation, Sloan Foundation, Emerson Collective, and Stanford Maternal & Child Health Research Institute.

Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak.

Background: Despite decreasing transfusion rates, routine type and screens are frequently used before primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). The aims of this study were to characterize transfusion rates and identify any factors that affect the likelihood of transfusion to determine if it is safe to discontinue routine preoperative type and screens at an academic hospital. Methods: A retrospective chart review was performed for all patients who underwent primary THA or TKA in 2019 at an academic institution by a fellowship-trained arthroplasty surgeon. Data on preoperative type and screens, transfusion rates, bleeding disorders, and anticoagulation status were obtained. Patients were considered to have a preoperative type and screen if it was performed within 30 days before surgery. Results: Overall, 379 patients were included in the study. Of these, 210 underwent primary THA and 169 underwent primary TKA. Four patients received transfusions during their hospitalization for a cumulative transfusion rate of 1.06%. No patients received an intraoperative transfusion. One (0.59%) patient received a postoperative transfusion after TKA, and 3 (1.43%) patients received a postoperative transfusion after THA. The mean preoperative hemoglobin of the 4 transfused patients was 10.8 g/dL. Conclusions: In summary, performing a preoperative routine type and screen is likely unnecessary at academic medical centers. Consideration for obtaining a type and screen may include complex primary surgeries or when patients have preoperative hemoglobin of less than 11 g/dL. Ultimately, preoperative type and screen should be considered on a case-by-case basis using clinical judgment.

Luspatercept is a recombinant fusion protein that enhances late‐stage erythroid maturation. This report describes the population pharmacokinetics and exposure–response relationship of luspatercept in 260 patients with anemia due to myelodysplastic syndromes. Luspatercept displayed linear and time‐invariant pharmacokinetics over a dose range of 0.125–1.75 mg/kg administered subcutaneously once every 3 weeks. Body weight was the only clinically relevant covariate of luspatercept exposure, supporting the weight‐based dosing. The probability of achieving transfusion independence ≥ 8 weeks increased with time‐averaged luspatercept serum exposure, reaching the plateau at doses 1.0–1.75 mg/kg. The probability of achieving multiple efficacy end points increased with slower luspatercept clearance, independent of effects of luspatercept exposure or disease characteristics. The probability of experiencing severe treatment‐emergent adverse events decreased with increasing luspatercept exposure, especially during long‐term treatment. These results provide a positive benefit–risk profile for the titration‐to‐response dose regimen (1.0–1.75 mg/kg) recommended for this population.

Abstract Background Coronavirus‐19 (COVID‐19) is a disease caused by the SARS‐CoV‐2 virus, the seventh coronavirus identified as causing disease in humans. The SARS‐CoV‐2 virus has multiple potential pathophysiologic interconnections with endocrine systems, potentially causing disturbances in glucose metabolism, hypothalamic and pituitary function, adrenal function and mineral metabolism. A growing body of data is revealing both the effects of underlying endocrine disorders on COVID‐19 disease outcome and the effects of the SARS‐CoV‐2 virus on endocrine systems. However, comprehensive assessment of the relationship to endocrine disorders in children has been lacking. Content In this review, we present the effects of SARS‐CoV‐2 infection on endocrine systems and review the current literature on complications of COVID‐19 disease in underlying paediatric endocrine disorders. We provide recommendations on management of endocrinopathies related to SARS‐CoV‐2 infection in this population. Summary and outlook With the surge in COVID‐19 cases worldwide, it is important for paediatric endocrinologists to be aware of the interaction of SARS‐CoV‐2 with the endocrine system and management considerations for patients with underlying disorders who develop COVID‐19 disease. While children and adults share some risk factors that influence risk of complications in SARS‐CoV‐2 infection, it is becoming clear that responses in the paediatric population are distinct and outcomes from adult studies cannot be extrapolated. Evidence emerging from paediatric studies provides some guidance but highlights the need for more research in this area.