Dear editor, we read with great interest the well written article by Dr Kerget et al with the main objective of investigating the role of TREM-1/TREM-2 ratio on patients with COVID-19 pneumonia. The article pointed that TREM-1 and TREM-2 have important role in inflammation and TREM-1/TREM-2 ratio was higher in severe COVID-19 patients compared with moderate COVID-19 patients. We have certain comments to understand the conclusions of this article. Firstly, triggering receptor expressed on myeloid cells-1 (TREM-1) is mainly express on neutrophils and monocytes in a cell membrane-bound form. A soluble form of TREM-1(sTREM-1), which lacks the cytoplasmic tail and transmembrane part, were detected in the blood in recent studies. Since you have mentioned “serum TREM-1”, we were confused whether you detected TREM-1 or sTREM-1. Secondly, we wanted to know more about the treatment and the kidney functions of the patients. Thirdly, We are curious to see if high TREM-1/TREM-2 ratio could predict the distribution of ILD. We would be glad to hear the opinion of the author on the points, to get a more convincing conclusion.

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There is paucity of evidence to support clinical decision making and counseling related to medication use in pregnancy. Despite multiple efforts from legislative bodies and advocacy groups, the inclusion of pregnant women in clinical drug trials assessing efficacy and safety remains scarce. Pregnancy can be complicated by multiple co-morbidities that require pharmacological intervention; these interventions primarily target the pregnant women but also sometimes have secondary effects for the fetus. The U.S. Food and Drug Administration has issued multiple guidance documents on incorporating pregnant women in clinical trials to aid pharmaceutical companies in designing a protocol to ensure safety and adherence to ethical standards. Advances in pediatric pharmacology studies provide lessons for researchers on the best practice of designing clinical trials with inclusion of patients from special populations. In this review, we present the status of pregnant women in clinical trials, highlighting the ethical stigma and possible future directives.

Typical applications of process- or physically-based models aim to gain a better process understanding or provide the basis for a decision-making process. To adequately represent the physical system, models should include all essential processes. However, model errors can still occur. Other than large systematic observation errors, simplified, misrepresented, inadequately parametrized or missing processes are potential sources of errors. This study presents a set of methods and a proposed workflow for analyzing errors of process-based models as a basis for relating them to process representations. The evaluated approach consists of three steps: (i) training a machine learning (ml) error-model using the input data of the process-based model and other available variables, (ii) estimation of local explanations (i.e., contributions of each variable to a individual prediction) for each predicted model error using SHapley Additive exPlanations (SHAP) in combination with principal component analysis, (iii) clustering of SHAP values of all predicted errors to derive groups with similar error generation characteristics. By analyzing these groups of different error-variable association, hypotheses on error generation and corresponding processes can be formulated. That can ultimately lead to improvements in process understanding and prediction. The approach is applied to a process-based stream water temperature model HFLUX in a case study for modelling an alpine stream in the Canadian Rocky Mountains. By using available meteorological and hydrological variables as inputs, the applied ml model is able to predict model residuals. Clustering of SHAP values results in three distinct error groups that are mainly related to shading and vegetation emitted longwave radiation. Model errors are rarely random and often contain valuable information. Assessing model error associations is ultimately a way of enhancing trust in implemented processes and of providing information on potential areas of improvement to the model.

INTRODUCTION Home-based treatment of low-risk febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing a low-risk FN program, incorporating home-based intravenous antibiotics, in a tertiary pediatric hospital. METHODS A decision analytic model was constructed to compare costs and outcomes of the low-risk FN program, with usual in-hospital treatment with intravenous antibiotics. The program included a clinical decision rule to identify patients at low-risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality-of-life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data. Patient-level costs were extracted from hospital records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). FINDINGS The mean healthcare cost of home-based FN treatment in low-risk patients was A$7,765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 (95% CI,12,496-12,767)). Overall, the low-risk FN program was the dominant strategy, being more effective (0.0011 QALY (95% CI,0.0011-0.0012)) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care program. CONCLUSION Compared to in-hospital FN care, the low-risk FN program is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the program.

Microinvasive, catheter-based mitral valve repair of severe mitral regurgitation utilizes less invasive approaches with less procedural morbidity and mortality. The procedural steps and clinical benefits of the transcatheter transapical mitral valve annuloplasty (AMEND mitral repair implant) and transcatheter transapical chordal repair systems (Neochord DS 1000 device and Harpoon Mitral Valve Repair System) are reviewed in this manuscript.

Background: Allergic rhinitis (AR) is the most common allergic disease in children and is closely associated with asthma in the context of atopic march. The development process of AR in early childhood, however, is not well understood due to the absence of definitive diagnostic criteria. We prospectively investigated the process in regard to not only the nasal symptoms and sensitization, but also the nasal cytology, in relation to asthma in a high-risk cohort. Methods: Infants under 2 years of age with atopic dermatitis (AD) and/or food allergy (FA) without a diagnosis of asthma were recruited and followed prospectively for 2 years. The phenotype of perennial AR was classified based on the presence/absence of 1) persistent nasal symptoms, 2) nasal eosinophils and 3) HDM sensitization, the most common allergen for perennial AR in Japan. AR-like phenotypes were defined as positive for at least 2 of those 3 categories. Results: A total of 304 children were enrolled, and 242 subjects (80%) completed the 2-year observation. The prevalence of eosinophilia in nasal secretions increased from 18.5% to 69.9%, while HDM-specific IgE >0.35 kUA/L increased from 30.6% to 74.8%. AR-like phenotypes increased from 18.4% to 65.0%. The cumulative incidence of physician-diagnosed asthma during the 2-year follow-up was significantly higher in the subjects with an AR-like phenotype at 1 year than in those with a non-AR phenotypes. Conclusions: The prevalence of an HDM-related AR-like phenotype was markedly increased during infancy in high-risk infants with AD/FA and was associated with asthma.

Evaluating the factors that promote invasive ant abundance is critical to assess their ecological impact and inform their management. Many invasive ant species show reduced nestmate recognition and an absence of boundaries between unrelated nests, which allow populations to achieve greater densities due to reduced intraspecific competition. We examined nestmate discrimination and colony boundaries in introduced populations of the red imported fire ant (Solenopsis invicta; hereafter, fire ant). Fire ants occur in two social forms: monogyne (colonies with a single egg-laying queen) and polygyne (colonies with multiple egg-laying queens). In contrast with monogyne nests, polygyne nests are thought to be interconnected due to the reduced antagonism between non-nestmate polygyne workers, perhaps because polygyne workers habituate the colony to an odor unique to Gp-9b-carrying adults. However, colony boundaries and nestmate discrimination are poorly documented, particularly for worker-brood interactions. To delimit boundaries between field colonies, we correlated the exchange of a 15N-glycine tracer dissolved in a sucrose solution with social form. We also evaluated nestmate discrimination between polygyne workers and larvae in the laboratory. Counter to our expectations, polygyne colonies behaved identically to monogyne colonies, suggesting both social forms maintain strict colony boundaries. Polygyne workers also preferentially fed larval nestmates and may have selectively cannibalized non-nestmates. The levels of relatedness among workers in polygyne colonies was higher than those previously reported in North America (mean ±SE: 0.269 ± 0.037). Our study highlights the importance of combining genetic analyses with direct quantification of resource exchange to better understand the factors influencing ant invasions.

We presenting a patient suffering from a multi-focal liver abscess. Due to the corona pandemic the patient was treated conservatively using recurring out-patient visits. Follow-up was carried through dialogue with the GP, as well as daily telemedicine visits. The virtual visits were supplemented by episodical ultrasound scans.

Background. In the United States, infection with SARS-CoV-2 caused 380,000 reported deaths from March to December 2020. Methods. We adapted the Moving Epidemic Method to all-cause mortality data from the United States to assess the severity of the COVID-19 pandemic across age groups and all 50 states. By comparing all-cause mortality during the pandemic with intensity thresholds derived from recent, historical all-cause mortality, we categorized each week from March to December 2020 as either low severity, moderate severity, high severity, or very high severity. Results. Nationally for all ages combined, all-cause mortality was in the very high severity category for 9 weeks. Among people 18 to 49 years of age, there were 29 weeks of consecutive very high severity mortality. Forty-seven states, the District of Columbia, and New York City each experienced at least one week of very high severity mortality for all ages combined. Conclusions. These periods of very high severity of mortality during March through December 2020 are likely directly or indirectly attributable to the COVID-19 pandemic. This method for standardized comparison of severity over time across different geographies and demographic groups provides valuable information to understand the impact of the COVID-19 pandemic and to identify specific locations or subgroups for deeper investigations into differences in severity.

Mammals have experienced a massive decline in their populations and geographic ranges worldwide. The sloth bear, Melursus ursinus (Shaw, 1791), is one of many species facing conservation threats. Despite being endangered in Nepal, decades of inattention to the situation have hindered their conservation and management. We assessed the distribution and patterns of habitat use by sloth bears in Chitwan National Park (CNP), Nepal. We conducted sign surveys from March to June, 2020, in 4 × 4 km grids (n = 45). We collected detection/non-detection data along a 4-km trail that was divided into 20 continuous segments of 200 m each. We obtained environmental, ecological, and anthropogenic covariates to understand determinants of sloth bear habitat occupancy. The data were analyzed using the single-species single-season occupancy method, with a spatially correlated detection. Using repeated observations, these models accounted for the imperfect detectability of the species to provide robust estimates of habitat occupancy. The model-averaged occupancy estimate for the sloth bear was 69% and the detection probability was 0.25. The probability of habitat occupancy by sloth bears increased with the presence of termites and fruits and in rugged, dry, open, undisturbed habitats. Our results indicate that the sloth bear is elusive, functionally unique, and widespread in CNP. Future conservation interventions and action plans aimed at sloth bear management must adequately consider their habitat requirements.

Abstract A mediastinal carcinoid is a low-grade malignant tumor, which has low risk of metastasis, and cardiac metastasis is even rarer. When a patient has cardiac metastasis, the primary carcinoid is usually widely metastasized. In this case report, we presented occurrence of isolated left-sided cardiac metastases ten years after surgical removal of left anterior superior mediastinal carcinoid.

Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for paediatric urticaria are implemented. Methods: The EAACI Taskforce for paediatric CU disseminated an online clinical survey among EAACI paediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centres. Results: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly paediatric allergists (80%) and paediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (e.g., autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2nd generation antihistamine as first- line treatment of whom 64.8% up dosed as a second- line. Omalizumab, was used as a second line treatment by 1.7% and third-line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). Conclusions: Even though most members of the Paediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re-evaluate, update and standardize guidelines on the diagnosis and management of CU in children.

Letter to the Editor RE: Modification of oxytocin use through a coaching-based intervention based on the WHO Safe Childbirth Checklist in Uttar Pradesh, India: a secondary analysis of a cluster randomized controlled trialAvir Sarkar, MD1; Shalini Venkatappa, MD1; Isha Wadhawan, MD, Diplomate to ABOG21 – Department of Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India2 – Department of Obstetrics and Gynecology, Fortis Escorts Hospital, Faridabad, Haryana, IndiaCorresponding author: Avir SarkarAddress: House number 12, Block F, NIT-3, Faridabad, Haryana-121001, IndiaE mail: [email protected] of article: Letter to the EditorWord count: 464Number of references: 2Conflict of interest between authors: None declared

Conspicuous female signals have recently received substantial scientific attention, but it remains unclear if their evolution is the result of selection acting on females independently of males or if mutual selection facilitates female change. Species that express female, but not male, phenotypic variation among populations represent a useful opportunity to address this knowledge gap. White-shouldered fairywrens (Malurus alboscapulatus) are tropical songbirds with a well-resolved phylogeny where female, but not male, coloration varies allopatrically across subspecies. We explored how four distinct signaling modalities, each putatively associated with increased social selection, are expressed in two populations that vary in competitive pressure on females. Females in a derived subspecies (M. a. moretoni) have evolved more ornamented plumage and have shorter tails (a signal of social dominance) relative to an ancestral subspecies (M. a. lorentzi) with drab females. In response to simulated territorial intrusions broadcasting female song, both sexes of M. a. moretoni are more aggressive and more coordinated with their mates in both movement and vocalizations. Finally, M. a. moretoni songs are more complex than M. a. lorentzi, but song complexity does not vary between sexes in either population. These results suggest that correlated phenotypic shifts in coloration and tail morphology in females as well as song complexity and aggression in both sexes may have occurred in response to changes in the intensity of social selection pressures. This highlights increased competitive pressures in both sexes can facilitate the evolution of complex multimodal signals.

Vegetation plays important roles in the development and protection of permafrost; it is one of the main local and ecosystemic factors that affect the thermal stability of the underlying soil strata. Multi-period land use and cover change (LUCC) data and long-time series of air temperature were chosed. Based on these data, spatiotemporal changes in mean annual air temperature (MAAT) were simulated by the Ordinary Least Squares (OLS) method and Ordinary Kriging (OK) model in the 1980s-2010s in Northeast China. The influences of LUCC on MAAT in Northeast China and distribution of the Xing’an permafrost were analyzed and the results showed that: (1) Decadal average of MAAT increased from 4.60oC (1980s) to 5.38oC (2010s) in Northeast China, with an upward trend of 0.25oC/10a. (2) During the 1980s to 2010s, the total permafrost area showed a decreasing trend (3.668×104 km2/10a). (3) In permafrost regions, LUCC had undergone significant structural changes: forested land showed a consistent decreasing trend and other lands showed an overall increasing trend. (4) The effects of different LUCC on MAAT in the permafrost region varied substantially. The mean MAAT of forested land was the lowest (2.33oC), and; that of unused land, the highest (0.37oC). The change rate in MAAT of cultivated land was the highest (0.37oC/10a), and; that of unused land, the lowest (0.28oC/10a). (5) The degradation rates of permafrost in forested land (1.822×104 km2/10a) and grassland (1.397×104 km2/10a) were the largest from 1980s to 2010s.

In this report, we present a rare case of severe mitral regurgitation due to isolated mitral valve chordal rupture without valve leaflet prolapse in a patient with Fabry cardiomyopathy. This finding could be due to subvalvular apparatus storage of glycosphingolipids rather than fibro-elastic deficiency, underlying how close cardiological follow-up of Fabry patients must be comprehensive and not only focused on left ventricular hypertrophy and arrhythmias. We feel that our finding could be of interest for the readership of your Journal.

Background. We have observed reopening of the occluded “no-touch” saphenous vein (NT SV) composite grafts on follow-up angiograms in patients who underwent coronary artery bypass graftings (CABG). Methods. Between 2008 and 2018, 1283 patients received NT SV conduits without or with surrounding pedicle tissue as composite grafts based on the in situ left internal thoracic artery (ITA) for CABG and underwent early postoperative angiographies. Among the 1283 patients, 53 patients showed 55 occluded SV conduit anastomoses, and 46 patients who had 48 occluded SV anastomoses were re-evaluated by 1-year postoperative angiographies. Results. Early postoperative angiographies in 1283 patients demonstrated overall occlusion rates of 1.2% (56/4518); occlusion rates of the ITA and SV were 0.08% (1/1259) and 1.7% (55/3260), respectively. One-year angiograms demonstrated that 14 occluded SV anastomoses (29.2% [14/48 occluded SV]) of 14 patients became patent. Reopening of occluded SV conduits occurred more frequently in NT SV with pedicle tissue than in NT SV without pedicle tissue (45.0% [9/20] versus 17.9% [5/28]; P=0.057). When we examined the preoperative and 1-year postoperative angiograms, reopening of the occluded SV conduits was not related with progression (P=0.258) or preoperative reversibility score (P=0.115) of native target coronary artery disease. Conclusions. More than a quarter of the occluded SV composite grafts on early postoperative angiograms were patent in the 1-year angiograms. The reopening rates were higher in patients who had received NT SV conduits with pedicle tissue than those who had received NT SV conduits without pedicle tissue.