Search

To investigate if positive changes in the clinical performance of radiologists are associated with reading mammographic test sets.This study investigated the clinical audit history for a cohort of 39 participants in the BreastScreen Reader Assessment Strategy who have read for BreastScreen New South Wales in the period between 2010 and 2018, inclusively. Based on the year in which each radiologist completed his or her first test set, data of multiple clinical audit metrics from two calendar years before test-set reading were compared against similar data from three different periods after test-set completion. The same process was repeated after dividing radiologists into two subgroups based on their median screen-reading volume (3,688), to test if experience is a determinant of post-test set performance.On average, radiologists showed significant improvements (p0.05) in the recall rate for subsequent screening rounds, in positive predictive value 1 (PPV1), and in specificity. When dividing radiologists based on their average annual reading volume, radiologists with higher reading numbers demonstrated similar significant improvements in the recall rate and in PPV1. In addition, they showed significant improvements in the detection rates of invasive breast cancer and ductal carcinoma in situ (DCIS). In contrast, the radiologists with lower reading volume indicated significant changes in the recall rate and in PPV1, both accruing in one of the three compared periods.Mammographic test-set participants improve over time in identifying normal breast screens and detecting breast cancer in association with reading higher volumes of breast screening cases.

Chickpea (Cicer arietinum) is a globally important food legume but its yield is negatively impacted by the fungal pathogen Ascochyta blight (Ascochyta rabiei) causing necrotic lesions leading to plant death. Past studies have found that Ascochyta resistance is polygenic. It is important to find new resistance genes from the wider genepool of chickpeas. This study reports the inheritance of Ascochyta blight resistance of two wide crosses between the cultivar Gokce and wild chickpea accessions of C. reticulatum and C. echinospermum under field conditions in Southern Turkey. Following inoculation, infection damage was scored weekly for six weeks. The families were genotyped for 60 SNPs mapped to the reference genome for quantitative locus (QTL) mapping of resistance. Family lines showed broad resistance score distributions. A late responding QTL on chromosome 7 was identified in the C. reticulatum family and three early responding QTLs on chromosomes 2, 3, and 6 in the C. echinospermum family. Wild alleles mostly showed reduced disease severity, while heterozygous genotypes were most diseased. Interrogation of 200k bp genomic regions of the reference CDC Frontier genome surrounding QTLs identified nine gene candidates involved in disease resistance and cell wall remodeling. This study identifies new candidate chickpea Ascochyta blight resistance QTLs of breeding potential.

Objective of investigation Chickpea is a major global food legume for which seed weight and plant growth habit are important yield and harvestability components for plant breeding. This study tested seed weight and plant growth habit inheritance and identified quantitative trait loci (QTL). Experimental material A 10 nested association mapping (NAM) populations of chickpea were created from crosses between ‘Gokce’, a cultivar and wild crop relative accessions of Cicer reticulatum and Cicer echinospermum. Families were then developed to the F2:4 generation. Method of investigation A 10 families were grown at the Field Experiment Station, Harran University near Şanlıurfa, Turkey during 2019. Data collection A 100-seed weight and prostrate or erect growth habit was scored in the field. Two families were genotyped for 60 single-nucleotide polymorphisms (SNP). Result and conclusions A 100-seed weight showed polygenic control, and three QTLs were found. Growth habit was controlled by one or two QTLs. The two traits were significantly correlated for five populations. The crop wild relatives of chickpea contain variations at novel loci affecting seed weight compared to the literature.

Background Despite the pervasiveness of migraine, the underlying pathophysiological mechanisms initiating migraine attacks are far from well understood and are matter of scientific debate. Objective In this narrative review, we discuss key evidence for that suggest a peripheral origin or central origin and provide directions for future studies that may provide further clarification. Discussion Migraine pathogenesis is considered to involve the trigeminovascular system, a term that encompasses the trigeminal nerve and its axonal projections to the intracranial blood vessels. Beyond any doubt both peripheral and central mechanisms are involved in migraine pathogenesis, but an unresolved question is the how the initial activation occurs in a migraine attack. Evidence favoring a peripheral origin of migraine attacks, i.e., initial events occur outside of the blood–brain barrier, include the importance of sensitization of perivascular sensory afferents early on in a migraine attack. Evidence favoring a central origin include the occurrence of prodromal symptoms, migraine aura, and activation of structures within the central nervous system early in and during a migraine attack. Conclusions Both peripheral and central mechanisms are likely involved in a migraine attack, e.g., peripheral nociceptive input is necessary for pain transmission and cortical activity is necessary for pain perception. Yet, the debate of whether migraine attacks are initiated a peripheral or central site remains unresolved. The increased focus on prodromal symptoms and on the development of a human model of migraine aura will possibly provide key arguments needed to answer this question in the near future. Until then, we cannot draw firm conclusions and the debate goes on. Video link Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at: https://www.youtube.com/watch?v=NC0nlcKohz0. Graphical Abstract

International audience; Halide perovskites doped with magnetic impurities (such as the transition metals Mn2+, Co2+, Ni2+) are being explored for a wide range of applications beyond photovoltaics, such as spintronic devices, stable light-emitting diodes, single-photon emitters, and magneto-optical devices. However, despite several recent studies, there is no consensus on whether the doped magnetic ions will predominantly replace the octahedral B-site metal via substitution or reside at interstitial defect sites. Here, by performing correlated nanoscale X-ray microscopy, spatially and temporally resolved photoluminescence measurements, and magnetic force microscopy on the inorganic 2D perovskite Cs2PbI2Cl2, we show that doping Mn2+ into the structure results in a lattice expansion. The observed lattice expansion contrasts with the predicted contraction expected to arise from the B-site metal substitution, thus implying that Mn2+ does not replace the Pb2+ sites. Photoluminescence and electron paramagnetic resonance measurements confirm the presence of Mn2+ in the lattice, while correlated nano-XRD and X-ray fluorescence track the local strain and chemical composition. Density functional theory calculations predict that Mn2+ atoms reside at the interstitial sites between two octahedra in the triangle formed by one Cl– and two I– atoms, which results in a locally expanded structure. These measurements show the fate of the transition metal dopants, the local structure, and optical emission when they are doped at dilute concentrations into a wide band gap semiconductor.

Spreading depolarizations (SDs) of gray matter occur in the brain in different pathologic conditions, and cause varying degrees of tissue damage depending on the extent of metabolic burden on the tissue. As might be expected for such large depolarizations, neurons exhibit bursts of action potentials (APs) as the wave propagates. However, the specific role of APs in SD propagation is unclear. This is potentially consequential, since sodium channel modulation has not been considered as a therapeutic target for SD-associated disorders, because of ambiguous experimental evidence. Using whole-cell electrophysiology and single-photon imaging in acute cortical slices from male C57Bl6 mice, we tested the effects of AP blockade on SDs generated by two widely used induction paradigms. We found that AP blockade using tetrodotoxin (TTX) restricted propagation of focally induced SDs, and significantly reduced the amplitude of neuronal depolarization, as well as its Ca2+load. TTX also abolished the suppression of spontaneous synaptic activity that is a hallmark of focally induced SD. In contrast, TTX did not affect the propagation of SD induced by global superfusion of high [K+]econtaining artificial CSF (ACSF). Thus, we show that voltage-gated sodium channel (Nav)-mediated neuronal AP bursts are critical for the propagation and downstream effects of focally induced SD but are less important when the ionic balance of the extracellular space is already compromised. In doing so we corroborate the notion that two different SD induction paradigms, each relevant to different clinical situations, vary significantly in their characteristics and potentially their response to treatment.SIGNIFICANCE STATEMENTOur findings suggest that voltage-gated sodium channel (Nav) channels have a critical role in the propagation and downstream neural effects of focally induced spreading depolarization (SD). As SDs are likely induced focally in many disease conditions, these studies support sodium channel modulation, a previously underappreciated therapeutic option in SD-associated disorders, as a viable approach.

The tumor microenvironment (TME) consists of extracellular matrix (ECM), nutrient and oxygen gradients, vascular networks, interstitial flows, and stromal cell types that are not typically found in normal, healthy tissues. To study tumor progression and the metastatic cascade, researchers have used culture models to mimic these aspects of tumor anatomy. Cell patterning techniques have been adapted to control matrix composition and tumor shape, as well as vascular and lymphatic networks near and within tumors, interstitial flows, and interactions between different cell types found in the tumor microenvironment. This chapter describes advances in self-assembled monolayers, self-assembled spheroids, microlithography, and microfluidics for patterning cancer cells. These techniques allow for the replication of many aspects of tumor anatomy, but require improvements to pattern multiple cell types in a way that reflects the proximity of cells in vivo. Additionally, tumor models must allow for ECM remodeling to mimic changes in matrix composition and structure observed during tumor progression. Engineered tumor models permit investigation of the effects of isolated aspects of the TME on tumor progression, which is challenging to explore in vivo.

INTRODUCTION In many western countries, there is good evidence documenting the performance of radiologists reading digital breast tomosynthesis (DBT) images. However, the diagnostic efficiency of Chinese radiologists using DBT, particularly type of errors being made and type of cancers being missed, is understudied. This study aims to investigate the pattern of diagnostic errors across different lesion types produced by Chinese radiologists diagnosing from DBT images. Australian radiologists will be used as a benchmark. METHODS Twelve Chinese radiologists read a DBT test set and located each perceived cancer lesion. True positives, false positives (FP), true negatives and false negatives (FN) were generated. The same test set was also read by 14 Australian radiologists. Z-scores and Pearson correlations were used to compare interpretation of lesions and identification of normal appearances between two groups of radiologists. RESULTS Architectural distortions (p

International audience; Cet article propose d'examiner ce qu'un nom fait à un espace et à la langue dont le nom en est dérivé. Ainsi, le triptyque langue/territoire/groupe est si bien installé dans les idéologies modernes du territoire et de la langue qu'on pouvait légitimement se demander quelles seraient les conséquences de la (re)naissance d'une région appelée Occitanie en 2016 dans le sud de la France actuelle sur une éventuelle politique linguistique favorable à la langue occitane. Analysant le digraphe oc-comme un praxème, nous entreprenons donc une étude idéologique et historique de ce nom d'Occitanie, pour montrer que ce lien langue/territoire ne saurait être prit pour garanti, et ne saurait effacer les conflits locaux sur la création de sens. Même lorsqu'un nom est porteur d'une histoire apparemment inséparable d'une langue, comme ça a été le cas d'Occitanie, ce lien est donc toujours un enjeu idéologique. Cet article s'attache ainsi à montrer comment un mouvement complexe de dépolitisation de la notion d'Occitanie a pu séparer le territoire de sa langue éponyme, et le rendre disponible pour un travail idéologique renouvelé. Quand l'espace, qui n'est qu'un pré-texte écrit par les hommes, dévient prétexte de leurs luttes et de leurs pensées, se crée du territoire.

Diagnostic efficacy in medical imaging is ultimately a reflection of radiologist performance. This can be influenced by numerous factors, some of which are patient related, such as the physical size and density of the breast, and machine related, where some lesions are difficult to visualise on traditional imaging techniques. Other factors are human reader errors that occur during the diagnostic process, which relate to reader experience and their perceptual and cognitive oversights. Given the large-scale nature of breast cancer screening, even small increases in diagnostic performance equate to large numbers of women saved. It is important to identify the causes of diagnostic errors and how detection efficacy can be improved. This narrative review will therefore explore the various factors that influence mammographic performance and the potential solutions used in an attempt to ameliorate the errors made.

Spreading depolarization (SD) has been identified as a key mediator of secondary lesion progression after acute brain injuries, and clinical studies are beginning to pharmacologically target SDs. Although initial work has focused on the N-Methyl-D-aspartate receptor antagonist ketamine, there is also interest in alternatives that may be better tolerated. We recently showed that ketamine can inhibit mechanisms linked to deleterious consequences of SD in brain slices. The present study tested the hypothesis that memantine improves recovery of brain slices after SD and explored the effects of memantine in a clinical case targeting SD. For mechanistic studies, electrophysiological and optical recordings were made from hippocampal area CA1 in acutely prepared brain slices from mice. SDs were initiated by localized microinjection of K+ in conditions of either normal or reduced metabolic substrate availability. Memantine effects were assessed from intrinsic optical signals and extracellular potential recordings. For the clinical report, a subdural strip electrode was used for continuous electrocorticographic recording after the surgical evacuation of a chronic subdural hematoma. In brain slice studies, memantine (10–300 µM) did not prevent the initiation of SD, but impaired SD propagation rate and recovery from SD. Memantine reduced direct current (DC) shift duration and improved recovery of synaptic potentials after SD. In brain slices with reduced metabolic substrate availability, memantine reduced the evidence of structural disruption after the passage of SD. In our clinical case, memantine did not noticeably immediately suppress SD; however, it was associated with a significant reduction of SD duration and a reduction in the electrocorticographic (ECoG) suppression that occurs after SD. SD was completely suppressed, with improvement in neurological examination with the addition of a brief course of ketamine. These data extend recent work showing that N-Methyl-D-aspartate receptor antagonists can improve recovery from SD. These results suggest that memantine could be considered for future clinical trials targeting SD, and in some cases as an adjunct or alternative to ketamine.

The three most common pediatric solid tumors of the abdomen are neuroblastoma, Wilms tumor, and hepatoblastoma. These embryonal tumors most commonly present in the first decade of life. Each tumor ...

Osteoporotic or fragility fractures affect one in two women and one in five men who are older than 50. These events are associated with substantial morbidity, increased mortality, and an impaired quality of life. Recommended general measures for fragility fracture prevention include a balanced diet with an optimal protein and calcium intake and vitamin D sufficiency, together with regular weight-bearing physical exercise. In this narrative Review, we discuss the role of nutrients, foods, and dietary patterns in maintaining bone health. Much of this information comes from observational studies. Bone mineral density, microstructure-estimated bone strength, and trabecular and cortical microstructure are positively associated with total protein intake. Several studies indicate that fracture risk might be lower with a higher dietary protein intake, provided that the calcium supply is sufficient. Dairy products are a valuable source of these two nutrients. Hip fracture risk appears to be lower in consumers of dairy products, particularly fermented dairy products. Consuming less than five servings per day of fruit and vegetables is associated with a higher hip fracture risk. Adherence to a Mediterranean diet or to a prudent diet is associated with a lower fracture risk. These various nutrients and dietary patterns influence gut microbiota composition or function, or both. The conclusions of this Review emphasise the importance of a balanced diet including minerals, protein, and fruit and vegetables for bone health and in the prevention of fragility fractures.

Postkidney transplant diabetes mellitus (PTDM) affects cardiovascular, allograft, and recipient health. We tested whether early intervention with sitagliptin for hyperglycemia (blood glucose200 mg/dL) within the first week of transplant and discontinued at 3 mo could prevent development of PTDM in patients without preexisting diabetes.The primary efficacy objective was to improve 2-h oral glucose tolerance test (OGTT) by20 mg/dL at 3 mo posttransplant. The secondary efficacy objective was to prevent new onset PTDM, defined as a normal OGTT at 3 mo.Sixty-one patients consented, and 50 patients were analyzed. The 3-mo 2-h OGTT (end of treatment) was 141.00 ± 62.44 mg/dL in the sitagliptin arm and 165.22 ± 72.03 mg/dL (P = 0.218) in the placebo arm. The 6-mo 2-h OGTT (end of follow-up) was 174.38 ± 77.93 mg/dL in the sitagliptin arm and 171.86 ± 83.69 ng/dL (P = 0.918) in the placebo arm. Mean intrapatient difference between 3- and 6-mo 2-h OGTT in the 3-mo period off study drug was 27.56 + 52.74 mg/dL in the sitagliptin arm and -0.14 + 45.80 mg/dL in the placebo arm (P = 0.0692). At 3 mo, 61.54% of sitagliptin and 43.48% of placebo patients had a normal 2-h OGTT (P = 0.2062), with the absolute risk reduction 18.06%. There were no differences in HbA1c at 3 or 6 mo between sitagliptin and placebo groups. Participants tolerated sitagliptin well.Although this study did not show a significant difference between groups, it can inform future studies in the use of sitagliptin in the very early posttransplant period.

Current research indicates that therapeutic transcranial magnetic stimulation (TMS) is a safe and likely efficacious treatment for posttraumatic stress disorder (PTSD). While the precise or ideal parameters remain under investigation, the majority of studies to date indicate clinically meaningful effect sizes for PTSD symptom reduction, which often occur alongside other symptomatic improvements, in particular major depressive disorder. This article summarizes the current evidence for different TMS treatment parameters and novel treatment options, and offers directions for future research. Given the clinical improvements observed with TMS appear similar to other first line treatments for PTSD, this article compares TMS to current treatment options, and summarizes early evidence for combining TMS treatment with psychotherapy. Finally, this article examines our current understanding of the neurobiological basis of PTSD and explores how a neurobiological framework can guide advances to better understand TMS treatment response and design novel treatment paradigms.

Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization.A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed4 wk before survey administration.Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138-221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%).SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.