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The diagnostic categories in psychiatry often encompass heterogeneous symptom profiles associated with differences in the underlying etiology, pathogenesis and prognosis. Prior work demonstrated that some of this heterogeneity can be quantified though dimensional analysis of the Depression Anxiety Stress Scale (DASS), yielding unique transdiagnostic symptom subtypes. This study investigated whether classifying patients according to these symptom profiles would have prognostic value for the treatment response to therapeutic transcranial magnetic stimulation (TMS) in comorbid major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). A linear discriminant model was constructed using a simulation dataset to classify 35 participants into one of the following six pre-defined symptom profiles: Normative Mood, Tension, Anxious Arousal, Generalized Anxiety, Anhedonia and Melancholia. Clinical outcomes with TMS across MDD and PTSD were assessed. All six symptom profiles were present. After TMS, participants with anxious arousal were less likely to achieve MDD remission compared to other subtypes (FET, odds ratio 0.16, p = 0.034), exhibited poorer PTSD symptom reduction (21% vs. 46%; t (33) = 2.025, p = 0.051) and were less likely to complete TMS (FET, odds ratio 0.066, p = 0.011). These results offer preliminary evidence that classifying individuals according to these transdiagnostic symptom profiles may offer a simple method to inform TMS treatment decisions.

U.S. regulatory and research agencies use ecotoxicity test data to assess the hazards associated with substances that may be released into the environment, including but not limited to industrial chemicals, pharmaceuticals, pesticides, food additives, and color additives. These data are used to conduct hazard assessments and evaluate potential risks to aquatic life (e.g., invertebrates, fish), birds, wildlife species, or the environment. To identify opportunities for regulatory uses of non-animal replacements for ecotoxicity tests, the needs and uses for data from tests utilizing animals must first be clarified. Accordingly, the objective of this review was to identify the ecotoxicity test data relied upon by U.S. federal agencies. The standards, test guidelines, guidance documents, and/or endpoints that are used to address each of the agencies' regulatory and research needs regarding ecotoxicity testing are described in the context of their application to decision-making. Testing and information use, needs, and/or requirements relevant to the regulatory or programmatic mandates of the agencies taking part in the Interagency Coordinating Committee on the Validation of Alternative Methods Ecotoxicology Workgroup are captured. This information will be useful for coordinating efforts to develop and implement alternative test methods to reduce, refine, or replace animal use in chemical safety evaluations.

Muscle weakness has been recognized as a hallmark feature of vitamin D deficiency for many years. Until recently, the direct biomolecular effects of vitamin D on skeletal muscle have been unclear. Although in the past, some reservations have been raised regarding the expression of the vitamin D receptor in muscle tissue, this special issue review article outlines the clear evidence from preclinical studies for not only the expression of the receptor in muscle but also the roles of vitamin D activity in muscle development, mass, and strength. Additionally, muscle may also serve as a dynamic storage site for vitamin D, and play a central role in the maintenance of circulating 25‐hydroxy vitamin D levels during periods of low sun exposure. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Background: Within 2 min of severe ischemia, spreading depolarization (SD) propagates like a wave through compromised gray matter of the higher brain. More SDs arise over hours in adjacent tissue, expanding the neuronal damage. This period represents a therapeutic window to inhibit SD and so reduce impending tissue injury. Yet most neuroscientists assume that the course of early brain injury can be explained by glutamate excitotoxicity, the concept that immediate glutamate release promotes early and downstream brain injury. There are many problems with glutamate release being the unseen culprit, the most practical being that the concept has yielded zero therapeutics over the past 30 years. But the basic science is also flawed, arising from dubious foundational observations beginning in the 1950s Methods: Literature pertaining to excitotoxicity and to SD over the past 60 years is critiqued. Results: Excitotoxicity theory centers on the immediate and excessive release of glutamate with resulting neuronal hyperexcitation. This instigates poststroke cascades with subsequent secondary neuronal injury. By contrast, SD theory argues that although SD evokes some brief glutamate release, acute neuronal damage and the subsequent cascade of injury to neurons are elicited by the metabolic stress of SD, not by excessive glutamate release. The challenge we present here is to find new clinical targets based on more informed basic science. This is motivated by the continuing failure by neuroscientists and by industry to develop drugs that can reduce brain injury following ischemic stroke, traumatic brain injury, or sudden cardiac arrest. One important step is to recognize that SD plays a central role in promoting early neuronal damage. We argue that uncovering the molecular biology of SD initiation and propagation is essential because ischemic neurons are usually not acutely injured unless SD propagates through them. The role of glutamate excitotoxicity theory and how it has shaped SD research is then addressed, followed by a critique of its fading relevance to the study of brain injury. Conclusions: Spreading depolarizations better account for the acute neuronal injury arising from brain ischemia than does the early and excessive release of glutamate., Grants to RDA from the Canadian Heart & Stroke Foundation, National Science Engineering and Research Council and the New Frontiers in Research Fund, to E.F from the National Research, Development and Innovation Office of Hungary, grant no. K134377; and the EU’s Horizon 2020 research and innovation program under grant agreement No. 739593, and to JPD from the DFG (German research Council) (DFG DR323/5-1,DFG DR 323/10-1) BMBF Bundesministerium fuer Bildung und Forschung (Era-Net Neuron EBio2, with funds from BMBF 01EW2004).

Background Growing gender disparities in levels of physical inactivity put women and female youths at a greater risk of associated health problems. Mother-daughter interventions have been proposed as means to promote physical activity in this at-risk cohort. However, there is a lack of clarity as to if and why these types of interventions might be effective. Methods This systematic review examined the intervention characteristics, and behaviour change theory and techniques used in these interventions to promote physical activity for daughters and their mothers. PubMed, EMBASE, PsycINFO, CINAHL and Cochrane Library (Wiley) databases were searched for English language studies from inception to 13th May 2020. Interventions of any design that targeted daughters and mothers' physical activity were included in the review. Data was extracted using the Template for Intervention Description and Replication checklist, and the Behaviour Change Technique Taxonomy v1. Results 4962 articles were screened and 11 unique studies met the inclusion criteria. Risk of bias was generally high. Narrative summary highlighted that many studies used social cognitive theory as a theoretical foundation, were based in the community and less than three months in duration with multiple sessions per week. Thirty-seven behaviour change techniques were identified across studies. Some techniques were deemed potentially effective including credible source, information on the health consequences of the behaviour and the self-regulatory related techniques of goal-setting, self-monitoring and problem-solving. Conclusions Future research should consider using checklists, frameworks and formative work with mothers and daughters to ensure interventions are rigorously designed, implemented, and evaluated, which can inform public policy to combat physical inactivity in this at-risk cohort. Key messages This is the first review to assess the intervention characteristics, and behaviour change theory and techniques of mother-daughter interventions targeting physical activity. This review advances the evidence base for future intervention development and more broadly can inform public policy to tackle physical inactivity in this at-risk cohort.

Rationale and Objectives Breast cancer is a highly complex heterogeneous disease. Current validated prognostic factors (e.g., histological grade, lymph node involvement, receptor status, and proliferation index), as well as multigene tests (e.g., Oncotype DX and PAM50) are helpful to describe breast cancer characteristics and predict the chance of recurrence risk and survival. Nevertheless, they are invasive and cannot capture a complete heterogeneity of the entire breast tumor resulting in up to 30% of patients being either over- or under-treated for breast cancer. Furthermore, multigene testings are time consuming and expensive. Radiomics is emerging as a reliable, accurate, non-invasive, and cost-effective approach of using quantitative image features to classify breast cancer characteristics and predict patient outcomes. Several recent radiomics reviews have been conducted in breast cancer, however, specific mammography-based radiomics studies have not been well discussed. This scoping review aims to assess and summarize the current evidence on the potential usefulness of mammography-based (i.e., digital mammography, digital breast tomosynthesis, and contrast-enhanced mammography) radiomics in predicting factors that describe breast cancer characteristics, recurrence, and survival. Materials and Methods PubMed database and eligible text reference were searched using relevant keywords to identify studies published between 2015 and December 19, 2020. Studies collected were screened and assessed based on the inclusion and exclusion criteria. Results Eighteen eligible studies were included and organized into three main sections: radiomics predicting breast cancer characteristics, radiomics predicting breast cancer recurrence and survival, and radiomics integrating with clinical data. Majority of publications reported retrospective studies while three studies examined prospective cohorts. Encouraging results were reported, suggesting the potential clinical value of mammography-based radiomics. Further efforts are required to standardize radiomics approaches and catalogue reproducible and relevant mammographic radiomic features. The role of integrating radiomics with other information is discussed. Conclusion The potential role of mammography-based radiomics appears promising but more efforts are required to further evaluate its reliability as a routine clinical tool.

In medical imaging a benefit to risk analysis is required when justifying or implementing diagnostic procedures. Screening mammography is no exception and in particular concerns around the use of radiation to help diagnose cancer must be addressed.The Medline database and various established reports on breast screening and radiological protection were utilised to explore this review.The benefit of screening is well argued; the ability to detect and treat breast cancer has led to a 91% 5-year survival rate and 497 deaths prevented from breast cancer amongst 100,000 screened women. Subsequently, screening guidelines by various countries recommend annual, biennial or triennial screening from ages somewhere between 40-74 years. Whilst the literature presents different perspectives on screening younger and older women, the current evidence of benefit for screening women40 and ≥75 years is currently not strong. The radiation dose and associated risk delivered to each woman for a single examination is dependent upon age, breast density and breast thickness, however the average mean glandular dose is around 2.5-3 mGy, and this would result in 65 induced cancers and 8 deaths per 100,000 women over a screening lifetime from 40-74 years. This results in a ratio of lives saved to deaths from induced cancer of 62:1.Therefore, compared to the potential mortality reduction achievable with screening mammography, the risk is small.

One of the imaging modalities offered by the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron is Xray phase-contrast propagation-based computed tomography (PB-CT). The unique combination of high coherence and high brightness of radiation produced by synchrotron X-ray sources enables phase contrast imaging with excellent sensitivity to small density differences in soft tissues and tumors. The PB-CT images using spatially coherent radiation show high signal-to-noise ratio (SNR) without reducing the spatial resolution. This is due to the combined effect of forward free-space propagation and the advanced step of phase retrieval in the reconstruction processes that allows to accommodate noisier recorded images. This gives an advantage of potentially reducing the radiation dose delivered to the sample whilst preserving the reconstructed image quality. It is expected that the PB-CT technique will be well suited for diagnostic breast imaging in the near future with the advantage that it could provide better tumor detection and characterization/grading than mammography and other breast imaging modalities/techniques in general. The PB-CT technique is expected to reduce false negative and false positive cancer diagnoses that result from overlapping regions of tissue in 2D mammography and avoid patient pain and discomfort that results from breast compression. The present paper demonstrates that PB-CT produces superior results for imaging low-density materials such as breast mastectomy samples, when compared to the conventional absorption-based CT collected at the same radiation dose. The performance was quantified in terms of both the measured objective image characteristics and the subjective scores from radiological assessments. This work is part of the ongoing research project aimed at the introduction of 3D X-ray medical imaging at the IMBL as innovative tomographic methods to improve the detection and diagnosis of breast cancer. Major progress of this project includes the characterization of a large number of mastectomy samples, both normal and cancerous.

Context Osteoglycin (OGN) is a proteoglycan released from bone and muscle which has been associated with markers of metabolic health. However, it is not clear whether the levels of circulating OGN change throughout the adult lifespan or if they are associated with clinical metabolic markers or fitness. Objective We aimed to identify the levels of circulating OGN across the lifespan and to further explore the relationship between OGN and aerobic capacity as well as OGN’s association with glucose and HOMA-IR. Methods 107 individuals (46 males and 61 females) aged 21-87 years were included in the study. Serum OGN levels, aerobic capacity (VO2peak), glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed. T-tests were used to compare participant characteristics between sexes. Regression analyses were performed to assess the relationship between OGN and age, and OGN and fitness and metabolic markers. Results OGN displayed a nonlinear, weak “U-shaped” relationship with age across both sexes. Men had higher levels of OGN than women across the lifespan (β = 0.23, P = .03). Age and sex explained 16% of the variance in OGN (adjusted R2 = 0.16; P < .001). Higher OGN was associated with higher VO2peak (β = 0.02, P = .001); however, those aged 50. A higher OGN level was associated with a higher circulating glucose level (β = 0.17, P < .01). No association was observed between OGN and HOMA-IR. Conclusion OGN was characterized by a U-shaped curve across the lifespan which was similar between sexes. Those with a higher aerobic capacity or higher glucose concentration had higher OGN levels. Our data suggest an association between OGN and aerobic fitness and glucose regulation. Future studies should focus on exploring the potential of OGN as a biomarker for chronic disease.

An American Society of Anesthesiology-Physical Status (ASA-PS) score is assigned topatients prior to undergoing anesthesia as a means of quantifying the impact of a patient's comorbidities. While this is the most common use, ASA-PS scores are also usedinclinical research and to determinefinancial reimbursement for anesthesia services.

BACKGROUND Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis. METHODS To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two-center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1-year post-KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL]

What is known and objective There has been a paucity of vaccine and vaccine‐related definitions within the scientific and medical peer‐reviewed literature, particularly with the arrival of COVID‐19. Therefore, it was the aim of this commentary to collate definitions to 44 vaccine‐ and vaccinology‐related key terms, from four international and respected sources of information (where available), including (i) the World Health Organisation (WHO), (ii) the US Centers for Disease Control and Prevention (CDC), (iii) The Department of Health, Government of Australia and (iv) the European Union. In addition, it was a further aim to develop a lay person's definition to each of these 44 key terms, to act as a published and citeable reference point for pharmacists and other healthcare professionals, when communicating with patients and other public‐facing stakeholders. Comment Definitions are important in health care in order to (i) provide concise insight on a specific topic, (ii) provide a common understanding and (iii) set reference points to allow the adoption of a standard uniform approach. What is new and conclusion The collation of definitions of key vaccine terms was compiled from four respected sources of information. A glossary of 44 key terms was produced to help pharmacists and other healthcare professionals explain such terms professionally, as well as to patient stakeholders in lay person's vocabulary. These lay definitions had superior readability metrics than definitions from any of the four professional sources, indicating their suitability for engagement with patient‐facing stakeholders. Understanding the barriers to vaccine uptake is crucial for health professionals and policymakers to achieve improved uptake rates. This commentary has aimed at adding value to healthcare professionals and patients, by providing an up‐to‐date glossary of several professional definitions, from respected sources, as well as an accompanying lay definition to support the healthcare professional‐patient communicative interface. Vaccines have become an important preventative tool, particularly in the context of the COVID‐19 pandemic, to help mitigate disease severity and to help control the pandemic locally, nationally and internationally. Accessible and robust definitions help inform the dialogue to achieve this goal and the avoidance of obscurum per obscurius., A glossary of 44 key terms relating to vaccine and vaccinology was produced to help pharmacists and other healthcare professionals explain such terms professionally, as well as to patient stakeholders in lay person's vocabulary. These lay definitions had superior readability metrics than definitions from any of the four professional sources (WHO, CDC, Australian Government, EU), indicating their suitability for engagement with patient‐facing stakeholders.

BACKGROUND: Despite advances in immune suppression, kidney allograft rejection and other injuries remain a significant clinical concern, particularly with regards to long-term allograft survival. Evaluation of immune activity can provide information about rejection status and help guide interventions to extend allograft life. Here, we describe the validation of a blood gene expression classifier developed to differentiate immune quiescence from both T cell–mediated rejection (TCMR) and antibody-mediated rejection (ABMR). METHODS: A five-gene classifier (DCAF12, MARCH8, FLT3, IL1R2, and PDCD1) was developed on 56 peripheral blood samples and validated on two sample sets independent of the training cohort. The primary validation set comprised 98 quiescence samples and 18 rejection samples: seven TCMR, ten ABMR, and one mixed rejection. The second validation set included eight quiescence and 11 rejection samples: seven TCMR, two ABMR, and two mixed rejection. AlloSure donor-derived cell-free DNA (dd-cfDNA) was also evaluated. RESULTS: AlloMap Kidney classifier scores in the primary validation set differed significantly between quiescence (median, 9.49; IQR, 7.68–11.53) and rejection (median, 13.09; IQR, 11.25–15.28), with P

Several meningococcal vaccines have been recently introduced into the infant and adolescent vaccination schedules in Northern Ireland to promote immunity toVaccination data was retrieved from the Cover of Vaccination Evaluated Rapidly (COVER) database, for meningococcal vaccines (MenACWY, HiB/MenC4CMenB, as well as for MMR vaccine as a non-meningococcal control). Vaccine coverage data assessed included (i). Two doses of MenB by 12 months, (ii). All 3 doses of MenB by 24 months, (iii). HiB/MenC coverage, (iv). MenACWY (Year 12s, for NI) (v). First dose of MMR. Northern Ireland Multiple Deprivation Measures 2017 (NIMDM2017) were examined against 38 indicators in 7 domains. NI HSCT vaccine uptake dataset for each vaccine was correlated with each indicator in the HSCT NIMDM2017 dataset. Regression analysis was performed to determine the relationship between vaccine uptake and deprivation indicators and coefficient of variation (RFor 4CMenB (all 3 doses by 24 Months), HiB/MenC, MenACWY and for MMR, correlation of variation (RWithin the last two decades, incidence of meningococcal disease has been on the decline. The introduction of meningococcal vaccines has contributed to this decrease and uptake of such vaccines should remain a public health priority to maintain the decline in meningococcal disease. Identifying contributing factors to low vaccine uptake, such as, the association between local deprivation and uptake of meningococcal vaccines, should be of public health importance and acknowledged by local governments and policy makers in their efforts to enhance vaccine uptake, both infant and teenage vaccination. There is a clear correlation with educational deprivation measures such as absenteeism and poor educational attainment and reduced vaccine uptake, perhaps through lack of understanding and willingness to vaccinate. This is where the importance of a clear and coherent public health message surrounding meningococcal vaccination should be prioritised, particularly to establish innovative modalities in a multidisciplinary team approach, to reach out to and increase vaccine uptake rates in socially deprived communities in Northern Ireland.

Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a high likelihood of developing retinoblastoma and other malignancies later in life. Genetically engineered mouse models of retinoblastoma share some similarities with human retinoblastoma but there are differences in their cellular differentiation. To develop a laboratory model of human retinoblastoma formation, we make induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. Each of the stem cell lines is validated, characterized and then differentiated into retina using a 3-dimensional organoid culture system. After 45 days in culture, the retinal organoids are dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs have molecular, cellular and genomic features indistinguishable from human retinoblastomas. This model of human cancer based on patient-derived iPSCs with germline cancer predisposing mutations provides valuable insights into the cellular origins of this debilitating childhood disease as well as the mechanism of tumorigenesis following RB1 gene inactivation., Retinoblastoma is a heritable pediatric cancer driven by mutations in RB1. Here, the authors demonstrate the first patient derived model of retinoblastoma using iPSCs from patients with germline mutations in RB1.

Background Indocyanine green (ICG), a water-soluble tricarbocyanine fluorophore, is being increasingly used for tumor localization based on its passive intra-tumoral accumulation due to enhanced permeability and retention in tumor tissue. Therefore, we hypothesized that ICG can provide contrast to facilitate accurate, real-time recognition of renal tumors at the time of nephron-sparing surgery in children. Methods This retrospective study examined the feasibility of ICG in guiding nephron-sparing surgery for pediatric renal tumors. Results We reviewed the medical records of 8 pediatric patients with renal tumors in 12 kidneys. Intraoperative localization of tumor with near infrared guidance was successful in all 12 kidneys. However, we consistently found an inverse pattern of near infrared signal in which the normal kidney demonstrated increased fluorescent signal relative to the kidney tumor. Conclusions Fluorescence-guided renal tumor delineation is unique because it has an inverse pattern of near infrared signal in which the normal kidney demonstrates increased signal relative to the adjacent tumor. Nevertheless fluorescence-guided distinguishing of renal tumor from surrounding normal kidney is feasible.

BACKGROUND Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in transplant recipients; however, the relationship between dd-cfDNA and other clinical parameters associated with adverse allograft outcomes is not well-characterized. METHODS We performed a retrospective analysis of kidney transplant recipients from the DART cohort (ClinicalTrials.gov Identifier: NCT02424227) to evaluate the associations between eGFR decline, de novo donor-specific antibodies (dnDSA), and dd-cfDNA. RESULTS Both elevated dd-cfDNA (≥1%) and dd-cfDNA variability (≥.34%) in the first post-transplant year were associated with decline in eGFR ≥25% in the second year (21.4% vs. 4.1%, P = .005; 25% vs. 3.6%, P = .002, respectively). Compared to samples from DSA negative patients, samples from patients with concurrent de novo HLA DSAs had higher dd-cfDNA levels (P

Purpose: Breast cancer is the most common cancer in women in developing and developed countries and is responsible for 15% of women’s cancer deaths worldwide. Conventional absorption-based breast imaging techniques lack sufficient contrast for comprehensive diagnosis. Propagation-based phase-contrast computed tomography (PB-CT) is a developing technique that exploits a more contrast-sensitive property of x-rays: x-ray refraction. X-ray absorption, refraction, and contrast-to-noise in the corresponding images depend on the x-ray energy used, for the same/fixed radiation dose. The aim of this paper is to explore the relationship between x-ray energy and radiological image quality in PB-CT imaging. Approach: Thirty-nine mastectomy samples were scanned at the imaging and medical beamline at the Australian Synchrotron. Samples were scanned at various x-ray energies of 26, 28, 30, 32, 34, and 60 keV using a Hamamatsu Flat Panel detector at the same object-to-detector distance of 6 m and mean glandular dose of 4 mGy. A total of 132 image sets were produced for analysis. Seven observers rated PB-CT images against absorption-based CT (AB-CT) images of the same samples on a five-point scale. A visual grading characteristics (VGC) study was used to determine the difference in image quality. Results: PB-CT images produced at 28, 30, 32, and 34 keV x-ray energies demonstrated statistically significant higher image quality than reference AB-CT images. The optimum x-ray energy, 30 keV, displayed the largest area under the curve [Formula: see text] of 0.754 ([Formula: see text]). This was followed by 32 keV ([Formula: see text] , [Formula: see text]), 34 keV ([Formula: see text] , [Formula: see text]), and 28 keV ([Formula: see text] , [Formula: see text]). Conclusions: An optimum energy range (around 30 keV) in the PB-CT technique allows for higher image quality at a dose comparable to conventional mammographic techniques. This results in improved radiological image quality compared with conventional techniques, which may ultimately lead to higher diagnostic efficacy and a reduction in breast cancer mortalities.

INTRODUCTION Phase-contrast imaging (PCI) is a novel technology that can visualise variations in X-ray refraction (phase contrast) in addition to differences in X-ray attenuation (absorption contrast). Compared to radiography using conventional methods (i.e. absorption-based imaging), PCI techniques can potentially produce images with higher contrast-to-noise ratio and superior spatial resolution at the same or lower radiation doses. This has led PCI to be explored for implementation in medical imaging. While interest in this research field is increasing, the whole body of PCI research in medical imaging has been under-investigated. This paper provides an overview of PCI literature and then focusses on evaluating its development within the scope of medical imaging. METHODS Bibliographic data between 1995 and 2018 were used to visualise collaboration networks between countries, institutions and authors. Social network analysis techniques were implemented to measure these networks in terms of centrality and cohesion. These techniques also assisted in the exploration of underlying research paradigms of clinical X-ray PCI investigations. RESULTS Forty-one countries, 592 institutions and 2073 authors contributed 796 investigations towards clinical PCI research. The most influential contributors and network collaboration characteristics were identified. Italy was the most influential country, with the European Synchrotron Radiation Facility being the most influential institution. At an author level, F. Pfeiffer was found to be the most influential researcher. Among various PCI techniques, grating interferometry was the most investigated, while computed tomography was the most frequently examined modality. CONCLUSIONS By gaining an understanding of collaborations and trends within clinical X-ray PCI research, the links between existing collaborators were identified, which can aid future collaborations between emerging and established collaborators. Moreover, exploring the paradigm of past investigations can shape future research - well-researched PCI techniques may be studied to bring X-ray PCI closer to clinical implementation, or the potential of seldom-investigated techniques may be explored.

Objectives Proposing a machine learning model to predict readers’ performances, as measured by the area under the receiver operating characteristics curve (AUC) and lesion sensitivity, using the readers’ characteristics. Methods Data were collected from 905 radiologists and breast physicians who completed at least one case-set of 60 mammographic images containing 40 normal and 20 biopsy-proven cancer cases. Nine different case-sets were available. Using a questionnaire, we collected radiologists’ demographic details, such as reading volume and years of experience. These characteristics along with a case set difficulty measure were fed into two ensemble of regression trees to predict the readers’ AUCs and lesion sensitivities. We calculated the Pearson correlation coefficient between the predicted values by the model and the actual AUC and lesion sensitivity. The usefulness of the model to categorize readers as low and high performers based on different criteria was also evaluated. The performances of the models were evaluated using leave-one-out cross-validation. Results The Pearson correlation coefficient between the predicted AUC and actual one was 0.60 (p Conclusion A machine learning model can be used to categorize readers as high- or low-performing. Such model could be useful for screening programs for designing a targeted quality assurance and optimizing the double reading practice.

We recently found that, in human osteoblasts, Homer1 complexes to Calcium-sensing receptor (CaSR) and mediates AKT initiation via mechanistic target of rapamycin complex (mTOR) complex 2 (mTORC2) leading to beneficial effects in osteoblasts including β-catenin stabilization and mTOR complex 1 (mTORC1) activation. Herein we further investigated the relationship between Homer1 and CaSR and demonstrate a link between the protein levels of CaSR and Homer1 in human osteoblasts in primary culture. Thus, when siRNA was used to suppress the CaSR, we observed upregulated Homer1 levels, and when siRNA was used to suppress Homer1 we observed downregulated CaSR protein levels using immunofluorescence staining of cultured osteoblasts as well as Western blot analyses of cell protein extracts. This finding was confirmed in vivo as the bone cells from osteoblast specific CaSR−/− mice showed increased Homer1 expression compared to wild-type (wt). CaSR and Homer1 protein were both expressed in osteocytes embedded in the long bones of wt mice, and immunofluorescent studies of these cells revealed that Homer1 protein sub-cellular localization was markedly altered in the osteocytes of CaSR−/− mice compared to wt. The study identifies additional roles for Homer1 in the control of the protein level and subcellular localization of CaSR in cells of the osteoblast lineage, in addition to its established role of mTORC2 activation downstream of the receptor.

Light-induced halide segregation is an intrinsic instability of mixed-halide perovskites, which complicates their successful use in tandem solar cells. Methods to suppress this phenomenon remain elusive because of its ambiguous origin. Beal et al. demonstrate that photostability is not an exclusive property of perovskite crystal structure and instead highlight the need for a microscopic understanding of the phenomenon.

Background Cannabis is categorized as an illicit drug in most US states, but legalization for medical indications is increasing. Policies and guidance on cannabis use in transplant patients remain controversial. Methods We examined a database linking national kidney transplant records (n = 52 689) with Medicare claims to identify diagnoses of cannabis dependence or abuse (CDOA) and associations [adjusted hazard ratio (aHR) with 95% upper and lower confidence limits (CLs)] with graft, patient, and other clinical outcomes. Results CDOA was diagnosed in only 0.5% (n = 254) and 0.3% (n = 163) of kidney transplant recipients in the years before and after transplant, respectively. Patients with pretransplant CDOA were more likely to be 19 to 30 years of age and of black race, and less likely to be obese, college-educated, and employed. After multivariate and propensity adjustment, CDOA in the year before transplant was not associated with death or graft failure in the year after transplant, but was associated with posttransplant psychosocial problems such as alcohol abuse, other drug abuse, noncompliance, schizophrenia, and depression. Furthermore, CDOA in the first year posttransplant was associated with an approximately 2-fold increased risk of death-censored graft failure (aHR, 2.29; 95% CL, 1.59-3.32), all-cause graft loss (aHR, 2.09; 95% CL, 1.50-2.91), and death (aHR, 1.79; 95% CL, 1.06-3.04) in the subsequent 2 years. Posttransplant CDOA was also associated with cardiovascular, pulmonary, and psychosocial problems, and with events such as accidents and fractures. Conclusions Although associations likely, in part, reflect associated conditions or behaviors, clinical diagnosis of CDOA in the year after transplant appears to have prognostic implications for allograft and patient outcomes. Recipients with posttransplant CDOA warrant focused monitoring and support.

Artificial intelligence (AI) is heralded as the most disruptive technology to health services in the 21st century. Many commentary articles published in the general public and health domains recognise that medical imaging is at the forefront of these changes due to our large digital data footprint. Radiomics is transforming medical images into mineable high‐dimensional data to optimise clinical decision‐making; however, some would argue that AI could infiltrate workplaces with very few ethical checks and balances. In this commentary article, we describe how AI is beginning to change medical imaging services and the innovations that are on the horizon. We explore how AI and its various forms, including machine learning, will challenge the way medical imaging is delivered from workflow, image acquisition, image registration to interpretation. Diagnostic radiographers will need to learn to work alongside our ‘virtual colleagues’, and we argue that there are vital changes to entry and advanced curricula together with national professional capabilities to ensure machine‐learning tools are used in the safest and most effective manner for our patients., This article summarises the opportunities for artificial intelligence (AI) translation into medical imaging in the near future. The changing roles for diagnostic radiographers are explored, and a discussion of the challenges for the ethical implementation of AI is included.

Purpose: We sought to evaluate whether combining a humanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte–macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoin were then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123I-metaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6–88.0]. This was accompanied by primary tumor volume reductions (median, –76%; range, –100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9–93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

The number of live kidney donors has declined since 2005. This decline parallels the evolving knowledge of risk for biologically related, black, and younger donors. To responsibly promote donation, we sought to identify declining low-risk donor subgroups that might serve as targets for future interventions. We analyzed a national registry of 77 427 donors and quantified the change in number of donors per 5-year increment from 2005 to 2017 using Poisson regression stratified by donor-recipient relationship and race/ethnicity. Among related donors aged

The aim of this study was to determine diagnostic reference levels (DRLs) for cardiac computed tomography (CCT) in Jordan. Volume computed tomography dose index (CTDIvol) and dose–length product (DLP) were collected from 228 CCTs performed at seven Jordanian hospitals specialized in cardiac CT. DRLs for cardiac CT were defined at the 75th percentile of CTDIvol and DLP. CTDIvol and DLP were collected from 30 successive cardiac CT in each center except for one center (18 scans). The 75th percentile of the CTDIvol and the DLP of the centers calculated from mixed retrospective and prospective gated modes were 47.74 milligray (mGy) and 1035 mGy/cm, respectively. This study demonstrated wide dose variations among the surveyed hospitals for cardiac CT scans; there was a 5.1‐fold difference between the highest and lowest median DLP with a range of 223.2–1146.7 mGy/cm. Differences were associated with variations in the mAs and kVp. This study confirmed large variability in CTDIvol and DLP for cardiac CT scans; variation was associated with acquisition protocols and highlights the need for dose optimization. DRLs are proposed for CCT; there remains substantial potential for optimization of cardiac CT examinations for adults in Jordan.

Visual search behaviour and the interpretation of mammograms have been studied for errors in breast cancer detection. We aim to ascertain whether machine-learning models can learn about radiologists’ attentional level and the interpretation of mammograms. We seek to determine whether these models are practical and feasible for use in training and teaching programmes. Eight radiologists of varying experience levels in reading mammograms reviewed 120 two-view digital mammography cases (59 cancers). Their search behaviour and decisions were captured using a head-mounted eye-tracking device and software allowing them to record their decisions. This information from radiologists was used to build an ensembled machine-learning model using top-down hierarchical deep convolution neural network. Separately, a model to determine type of missed cancer (search, perception or decision-making) was also built. Analysis and comparison of variants of these models using different convolution networks with and without transfer learning were also performed. Our ensembled deep-learning network architecture can be trained to learn about radiologists’ attentional level and decisions. High accuracy (95%, p value ≅ 0 [better than dumb/random model]) and high agreement between true and predicted values (kappa = 0.83) in such modelling can be achieved. Transfer learning techniques improve by

In the United States, kidney donation from international (noncitizen/nonresident) living kidney donors (LKDs) is permitted; however, given the heterogeneity of healthcare systems, concerns remain regarding the international LKD practice and recipient outcomes. We studied a US cohort of 102 315 LKD transplants from 2000-2016, including 2088 international LKDs, as reported to the Organ Procurement and Transplantation Network. International LKDs were more tightly clustered among a small number of centers than domestic LKDs (Gini coefficient 0.76 vs 0.58, P < .001). Compared with domestic LKDs, international LKDs were more often young, male, Hispanic or Asian, and biologically related to their recipient (P < .001). Policy-compliant donor follow-up was substantially lower for international LKDs at 6, 12, and 24 months postnephrectomy (2015 cohort: 45%, 33%, 36% vs 76%, 71%, 70% for domestic LKDs, P < .001). Among international LKDs, Hispanic (aOR = 0.23 0.360.56 , P < .001) and biologically related (aOR = 0.39 0.590.89 , P < .01) donors were more compliant in donor follow-up than white and unrelated donors. Recipients of international living donor kidney transplant (LDKT) had similar graft failure (aHR = 0.78 0.891.02 , P = .1) but lower mortality (aHR = 0.53 0.620.72 , P < .001) compared with the recipients of domestic LDKT after adjusting for recipient, transplant, and donor factors. International LKDs may provide an alternative opportunity for living donation. However, efforts to improve international LKD follow-up and engagement are warranted.

Short-term administration of glucocorticoids (GCs) impairs muscle insulin sensitivity at least in part via the reduction of undercarboxylated osteocalcin (ucOC). However, whether ucOC treatment reverses the GC-induced muscle insulin resistance remains unclear. To test the hypothesis that ucOC directly ameliorates impaired insulin-stimulated glucose uptake (ISGU) induced by short-term GC administration in mice muscle and to identify the molecular mechanisms, mice were implanted with placebo or corticosterone (CS) slow-release pellets. Two days post-surgery, insulin-tolerance tests (ITTs) were performed. On day 3, serum was collected and extensor digitorum longus (EDL) and soleus muscles were isolated and treated ex vivo with vehicle, ucOC (30 ng/mL), insulin (60 µU/mL), or both. Circulating hormone levels, muscle glucose uptake, and muscle signaling proteins were assessed. CS administration reduced both serum osteocalcin and ucOC levels, whole-body insulin sensitivity, and muscle ISGU in EDL. Ex vivo ucOC treatment restored ISGU in CS-affected muscle, without increasing non-insulin-stimulated glucose uptake. In CS-affected EDL muscle, ucOC enhanced insulin action on phosphorylated (p-)protein kinase B (Akt)Ser473 and the p-extracellular signal-regulated kinase isoform 2 (ERK2)Thr202/Tyr204 /total (t)ERK2 ratio, which correlated with ISGU. In CS-affected soleus muscle, ucOC enhanced insulin action on p-mammalian target of rapamycin (mTOR)Ser2481 , the p-mTORSer2481 /tmTOR ratio, p-Akt substrate of 160kD (AS160)Thr642 , and p-protein kinase C (PKC) (pan)Thr410 , which correlated with ISGU. Furthermore, p-PKC (pan)Thr410 correlated with p-AktSer473 and p-AS160Thr642 . ucOC exerts direct insulin-sensitizing effects on CS-affected mouse muscle, likely through an enhancement in activity of key proteins involved in both insulin and ucOC signaling pathways. Furthermore, these effects are muscle type-dependent. © 2019 American Society for Bone and Mineral Research.

Rationale and Objectives To establish the efficacy of pairing readers randomly and evaluate the merits of developing optimal pairing methodologies. Materials and Methods Sensitivity, specificity, and proportion correct were computed for three different case sets that were independently read by 16 radiologists. Performance of radiologists as single readers was compared to expected double reading performance. We theoretically evaluated all possible pairing methodologies. Bootstrap resampling methods were used for statistical analyses. Results Significant improvements in expected performance for double versus single reading (ie, delta performance) were shown for all performance measures and case-sets (p ≤ .003), with overall delta performance across all theoretically possible pairing schemes (n = 10,395) ranging between .05 and .08. Delta performance for the 20 best pairing schemes was significant (p Conclusion Significant benefits accrue from double reading, and while random reader pairing achieves most double reading benefits, a strategic pairing approach may maximize the benefits of double reading.

Introduction Osteocalcin (OC) is used as a surrogate marker for bone turnover in clinical settings. As bone mineral density (BMD) is largely heritable, we tested the hypothesis that a) bone-associated genetic variants previously identified in Genome-Wide Association Studies (GWAS) and combined into a genetic risk score (GRS) are associated with a) circulating levels of OC and b) the changes in OC following acute exercise. Methods Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 73 healthy Caucasian males at baseline and after a single bout of high-intensity interval exercise. In addition, genotyping was conducted targeting GWAS variants previously reported to be associated with BMD and then combined into a GRS. Potential associations between the GRS and tOC, ucOC and cOC were tested with linear regressions adjusted for age. Results At baseline none of the individual SNPs associated with tOC, ucOC and cOC. However, when combined, a higher GRS was associated with higher tOC (β = 0.193 ng/mL; p = 0.037; 95% CI = 0.012, 0.361) and cOC (β = 0.188 ng/mL; p = 0.04; 95% CI = 0.004, 0.433). Following exercise, GRS was associated with ucOC levels, (β = 3.864 ng/mL; p-value = 0.008; 95% CI = 1.063, 6.664) but not with tOC or cOC. Conclusion Screening for genetic variations may assist in identifying people at risk for abnormal circulating levels of OC at baseline/rest. Genetic variations in BMD predicted the ucOC response to acute exercise indicating that physiological functional response to exercise may be influenced by bone-related gene variants.

Objectives: To compare the mammographic densities and other characteristics of Aboriginal and non-Aboriginal women screened in Australia. Methods: Population screening programme data of Aboriginal (n = 857) and non-Aboriginal women (n = 3236) were used. Mann–Whitney U test compared ages at screening and Chi-square tests compared personal and clinical information. Logistic regression analysis was used for density groupings. OR and 95% CI were calculated for multivariate association for density. Results: Mammographic density was lower amongst Aboriginal women (P

This report describes the results of 2 international randomized trials (total of 508 kidney transplant recipients). The primary objective was to assess the noninferiority of rabbit anti‐thymocyte globulin (rATG, Thymoglobulin®) versus interleukin‐2 receptor antagonists (IL2RAs) for the quadruple endpoint (treatment failure defined as biopsy‐proven acute rejection, graft loss, death, or loss to follow‐up) to serve as the pivotal data for United States (US) regulatory approval of rATG. The pooled analysis provided an incidence of treatment failure of 25.1% in the rATG and 36.0% in the IL2RA treatment groups, an absolute difference of −10.9% (95% confidence interval [CI] −18.8% to −2.9%) supporting noninferiority (noninferiority margin was 10%) and superiority of rATG to IL2RA. In a meta‐analysis of 7 trials comparing rATG with an IL2RA, the difference in the proportion of patients with BPAR at 12 months was −4.8% (95% CI −8.6% to −0.9%) in favor of rATG. In conclusion, a rigorous reanalysis of patient‐level data from 2 prior randomized, controlled trials comparing rATG versus IL‐2R monoclonal antibodies provided support for regulatory approval for rATG for induction therapy in renal transplant, making it the first T cell–depleting therapy approved for the prophylaxis of acute rejection in patients receiving a kidney transplant in the United States., A rigorous reanalysis of patient‐level data from two prior randomized, controlled trials comparing rATG versus IL‐2R monoclonal antibodies provides support for regulatory approval of rATG for induction therapy in renal transplantation, making it the first T cell–depleting therapy approved for the prophylaxis of acute rejection in patients receiving a kidney transplant in the US.