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Background Gemistocytes (GCs) are unique phenotype of reactive astrocytes. In diffuse low-grade gliomas, they are associated with grim prognosis. Less is known regarding their pathogenesis and prognostic significance in glioblastoma (GBM). Previous data on-neoplastic central nervous system (CNS) lesions has linked the presence of GCs with states of uncontrolled hyperglycaemia in diabetes mellitus type 2 patients. study purpose is to find a correlation between systemic metabolic features and the presence of GCs in patients with GBM.Also, to try and correlate between the presence of GCs, molecular changes, and use of anti-diabetic drugs on overall survival of GBM patients. Methods Electronic medical records from newly diagnosed GBM patients were retrospectively reviewed and extracted for demographic, clinical, metabolic, radiological and pathological variables with emphasis on different metabolic - related features. A statistic-based comparison was made between GBM patients with and without GCs for the same variables. We compared DM2 GC-GBM patients to DM2 non-GC GBM patients in a cohort of poorly controlled DM2 (i.e., HBA1C ≥ 8.0). A possible influence of metformin administration on OS of DM2 GBM patients, with and without GCs, and with and without TP53 mutations was investigated. Results A total of 220 patients with newly diagnosed GBM were included in the study. 14.5% were defined as GC-GBM (group 1, n=32) and 85.5% were defined as non-GC GBM (group 2, n=188). The incidence of DM2 was 25% in both groups. The rate of poorly-controlled DM2 was nearly as twice in group 1 than in group 2 (18.75% vs. 9.5%; p=0.130). In the DM2 GBM group, significant differences were found between DM2 GC-GBM (group 1a, n=9) and DM2 non-GC GBM (group 2a, n=49) patients with male gender predominance (89% vs. 50%, p=0.073) and obesity. Patients in group 1a were more likely to have weight ≥85kg (OR 6.16; 95% CI 1.3336 to 28.5147, p=0.0019) and had higher BMI values (mean BMI of 34.1±11.42 vs. 28.7±5.44 for group 1a and 2a respectively; OR= 1.095, 95%CI 1.053-1.207;p=0.034). Similar significant findings were in the poorly-controlled DM2 subgroup. None of the poorly-controlled DM2 GC-GBM patients were using insulin prior to diagnosis (0% vs. 61.10%, p=0.016). Survival analyses have shown trends for differences in overall survival between subgroups in correlation with presence of GCs, p53 mutations and use of metformin. Conclusion GBM patients with systemic metabolic factors that are associated with marked insulin resistance and are not using insulin at time of diagnosis are significantly more likely to have GCs in their initial pathology. This is a novel finding that may add to data on glucose metabolism in astrocytes and in astrocytes-associated tumors. The presence of GCs, molecular changes in the tumor, and under the influence of anti-diabetic drugs such as metformin, may affect the prognosis of different GBM subgroups.

Background Brain metastases are a common complication of non small cell lung cancer (NSCLC). Approximately 10 percent of newly diagnosed patients with advanced NSCLC have brain metastases. The purpose of this study was to determine whether using magnetic resonance imaging (MRI) for early screening of brain metastases can improve survival. Material and Methods A retrospective analysis of newly diagnosed stage IV NSCLC treated at Davidoff Cancer Center, Israel, between the years 2019-2020. Only patients who were neurologically asymptomatic were included in the study. The study population was divided into two groups. Group A included patients who underwent screening MRI within 12 weeks form diagnosis and group B included those who did not undergo screening MRI. Clinical and radiographic data were collected form the medical records. Results 379 patients were included in the study, of whom 170 underwent screening MRI. Of the patients who underwent screening MRI 54 were diagnosed with brain metastases. On univariate analysis screening MRI was correlated with better survival [group A median survival 24 month, group B median survival 18 month, p=0.003 HR 1.4 CI 1.12-1.75]. On multivariate analysis that included functional status (ECOG 0-2 compared to 3 and above) and age- screening MRI correlated with survival (p=0.04 HR 1.28 CI 1.02-1.6). Subgroup analysis according to molecular subgroup will be presented in the conference. Conclusion In this study screening MRI among stage IV NSCLC correlated with better survival even when adjusted to functional status and age.

Our understanding of the climatic teleconnections that drove ice-age cycles has been limited by a paucity of well-dated tropical records of glaciation that span several glacial–interglacial intervals. Glacial deposits offer discrete snapshots of glacier extent but cannot provide the continuous records required for detailed interhemispheric comparisons. By contrast, lakes located within glaciated catchments can provide continuous archives of upstream glacial activity, but few such records extend beyond the last glacial cycle. Here a piston core from Lake Junín in the uppermost Amazon basin provides the first, to our knowledge, continuous, independently dated archive of tropical glaciation spanning 700,000 years. We find that tropical glaciers tracked changes in global ice volume and followed a clear approximately 100,000-year periodicity. An enhancement in the extent of tropical Andean glaciers relative to global ice volume occurred between 200,000 and 400,000 years ago, during sustained intervals of regionally elevated hydrologic balance that modified the regular approximately 23,000-year pacing of monsoon-driven precipitation. Millennial-scale variations in the extent of tropical Andean glaciers during the last glacial cycle were driven by variations in regional monsoon strength that were linked to temperature perturbations in Greenland ice cores1; these interhemispheric connections may have existed during previous glacial cycles.

International audience

An experimentally validated computational model is used to determine quantitative information on convective heat transfer coefficients on all of the external surfaces of a generic residence. The mo...

Background Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. Methods This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. Discussion The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. Trial registration ClinicalTrials.gov NCT 04153864. Registered on November 6, 2019.

Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth‐system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ47) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories. Then we analyzed the four carbonate standards along with three additional standards, spanning a broad range of δ47 and Δ47 values, for a total of 5,329 analyses on 25 individual mass spectrometers from 22 different laboratories. Treating three of the materials as known standards and the other four as unknowns, we find that the use of carbonate reference materials is a robust method for standardization that yields interlaboratory discrepancies entirely consistent with intralaboratory analytical uncertainties. Carbonate reference materials, along with measurement and data processing practices described herein, provide the carbonate clumped isotope community with a robust approach to achieve interlaboratory agreement as we continue to use and improve this powerful geochemical tool. We propose that carbonate clumped isotope data normalized to the carbonate reference materials described in this publication should be reported as Δ47 (I‐CDES) values for Intercarb‐Carbon Dioxide Equilibrium Scale., Key Points The exclusive use of carbonate reference materials is a robust method for the standardization of clumped isotope measurementsMeasurements using different acid temperatures, designs of preparation lines, and mass spectrometers are statistically indistinguishableWe propose new consensus values for a set of seven carbonate reference materials and updated guidelines to report clumped isotope measurements

Additional file 1: Figure S1. The Spirit flow diagram: the schedule of enrollment, intervention and assessments.

Additional file 2. SPIRIT checklist.

Predictions of airborne allergenic pollen concentrations at fine spatial scales require information on source plant location and pollen production. Such data are lacking at the urban scale, largely because manually mapping allergenic pollen producing plants across large areas is infeasible. However, modest-sized field surveys paired with allometric equations, remote sensing, and habitat distribution models can predict where these plants occur and how much pollen they produce. In this study, common ragweed (Ambrosia artemisiifolia) was mapped in a field survey in Detroit, MI, USA. The relationship between ragweed presence and habitat-related variables derived from aerial imagery, LiDAR, and municipal data were used to create a habitat distribution model, which was then used to predict ragweed presence across the study area (392 km2). The relationship between inflorescence length and pollen production was used to predict pollen production in the city. Ragweed occurs in 1.7% of Detroit and total pollen production is 312 × 1012 pollen grains annually, but ragweed presence was highly heterogeneous across the city. Ragweed was predominantly found in in vacant lots (75%) and near demolished structures (48%), and had varying associations with land cover types (e.g., sparse vegetation, trees, pavement) detected by remote sensing. These findings also suggest several management strategies that could help reduce levels of allergenic pollen, including appropriate post-demolition management practices. Spatially-resolved predictions for pollen production will allow mechanistic modeling of airborne allergenic pollen and improved exposure estimates for use in epidemiological and other applications.

The standard model of particle physics describes the vast majority of experiments and observations involving elementary particles. Any deviation from its predictions would be a sign of new, fundamental physics. One long-standing discrepancy concerns the anomalous magnetic moment of the muon, a measure of the magnetic field surrounding that particle. Standard-model predictions

In this issue, contributors were asked to consider the concept of castration anxiety in light of contemporary psychoanalytic thought and practice. Freud’s original formulations of castration anxiet...

Introduction: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic disorder that bears grave ocular prognosis. No consensus exists regarding treatment regimen and very little has been achieved in the way of successful treatment. We present here a case of BDUMP associated with metastatic non–small cell lung carcinoma treated successfully with plasmapheresis. Methods: This is a nonmasked, retrospective interventional case study conducted at a tertiary care center, characterizing bilateral disease in 1 patient, and describing response to plasmapheresis. Outcome measures were resolution of optical coherence tomography (OCT) findings, as well as visual response. Results: Resolution of bilateral exudative retinal detachments was documented with both ophthalmoscopic photography and OCT and accompanied by concurrent improvement in visual function. Conclusion: Bilateral diffuse uveal melanocytic proliferation has been treated with plasmapheresis in only 3 previously reported cases. This case demonstrates and reinforces the great promise in the treatment of this rare and devastating condition.

The Bi-Personal Field: Experiences in Child Psychoanalysis. By Antonino Ferro. New York: Routledge, 1992 (1999). 232 pp. The Intimate Room: Theory and Technique of the Analytic Field. By Giuseppe Civitarese. New York: Routledge, 2008 (2010). 240 pp. The Necessary Dream: New Theories and Techniques of Interpretation in Psychoanalysis. By Giuseppe Civitarese; translated by Ian Harvey. London: Karnac, 2013 (2014). 246 pp. The Analytic Field and Its Transformations. By Antonino Ferro and Giuseppe Civitarese. London: Karnac, 2015. 224 pp.

In Relational Freedom: Emergent properties of the interpersonal field Donnel Stern takes the reader on an intimate journey through an interpersonal landscape. This interpersonal expedition occurs s...

Alzheimer's disease (AD) is the most common cause of dementia, particularly in the elderly. The disease is characterized by cognitive decline that typically starts with insidious memory loss and progresses relentlessly to produce global impairment of all higher cortical functions. Due to better living conditions and health facilities in developed countries, which result in higher overall life spans, these countries report upward trends of AD among their populations. There are, however, no specific diagnostic tests for AD and clinical diagnosis is especially difficult in the earliest stages of the disease. Early diagnosis of AD is frequently subjective and is determined by physicians (generally neurologists, geriatricians, and psychiatrists) depending on their experience. Diagnosing AD requires both medical history and mental status testing. Having trouble with memory does not mean you have AD. AD has no current cure, but treatments for symptoms are available and research continues. In this study, we investigated the potential of infrared microscopy to differentiate between AD patients and controls, using Fourier transform infrared (FTIR) spectroscopy of isolated blood components. FTIR is known as a quick, safe, and minimally invasive method to investigate biological samples. For this goal, we measured infrared spectra from white blood cells (WBCs) and plasma taken from AD patients and controls, with the consent of the patients or their guardians. Applying multivariate analysis, principal component analysis (PCA) followed by linear discriminant analysis (LDA), it was possible to differentiate among the different types of mild, moderate, and severe AD, and the controls, with 85% accuracy when using the WBC spectra and about 77% when using the plasma spectra. When only the moderate and severe stages were included, an 83% accuracy was obtained using the WBC spectra and about 89% when using the plasma spectra.

Rabies is a zoonotic viral disease that remains a serious threat to public health worldwide. The rabies lyssavirus (RABV) genome encodes five structural proteins, multifunctional and significant for pathogenicity. The large protein (L) presents well-conserved genomic regions, which may be a good alternative to generate informative datasets for development of new methods for rabies diagnosis. This paper describes the development of a technique for the identification of L protein in several RABV strains from different hosts, demonstrating that MS-based proteomics is a potential method for antigen identification and a good alternative for rabies diagnosis.

We review recent results on the QCD phase transition line and second-order fluctuations and correlators of conserved charges calculated in lattice QCD. In the case of fluctuations, we compare them to the Hadron Resonance Gas model and construct proxies that allow a direct comparison between first principle simulations and measurements.

Background/purpose We describe a case of full-thickness macular hole formation in a patient with exudative age-related macular degeneration after an intravitreal ranibizumab injection and its surgical management. Methods This case is a retrospective, interventional case report. Results A 77-year-old woman with bilateral exudative age-related macular degeneration and pre-existing retinal pigment epithelium tear developed a full-thickness macular hole after intravitreal ranibizumab. The macular hole was repaired successfully with pars plana vitrectomy, internal limiting membrane peel, and 16% C3F8 gas fill. Conclusion To the best of our knowledge, this is the first reported case of full-thickness macular hole after a retinal pigment epithelium tear repaired successfully with vitrectomy, resulting in improved visual acuity.

Starting in the 1960s, a great deal of effort and capital was invested in an endeavor to significantly improve the quality of surface water around the United States, particularly in metropolises like New York City, New York. The Hudson River has been at the forefront of these efforts and has benefited immensely from this campaign. In parts of the developing world, such as China, similar efforts are beginning to gather the same type of momentum. Within the past decade, the Huangpu River, which flows through Shanghai into the Yangtze Estuary of China, has been a target for ecological restoration and management. It is possible to draw parallels between the cleanup efforts involved in improving the environmental conditions of the Huangpu and Hudson Rivers. Using the methodologies of series comparison (SCM), water quality index (WQI) modeling, consideration of ecological engineering, and policy strategy design, we comparatively studied the topography, functions, environmental conditions, ecological engineering countermeasures, and management policies of the two rivers to assist future forecasting of ecological restoration efforts in China.