Demonstration of Controlled Skyrmion Injection Across a Thickness Step.

Spintronic devices incorporating magnetic skyrmions have attracted significant interest recently. Such devices traditionally focus on controlling magnetic textures in 2D thin films. However, enhanced performance of spintronic properties through the exploitation of higher dimensionalities motivates the investigation of variable-thickness skyrmion devices. We report the demonstration of a skyrmion injection mechanism that utilizes charge currents to drive skyrmions across a thickness step and, consequently, a metastability barrier. Our measurements show that under certain temperature and field conditions skyrmions can be reversibly injected from a thin region of an FeGe lamella, where they exist as an equilibrium state, into a thicker region, where they can only persist as a metastable state. This injection is achieved with a current density of 3 × 108 A m-2, nearly 3 orders of magnitude lower than required to move magnetic domain walls. This highlights the possibility to use such an element as a skyrmion source/drain within future spintronic devices.

Use of real-time immersive digital training and educational technologies to improve patient safety during the processing of reusable medical devices: Quo Vadis?

Hospital acquired infections stemming from contaminated reusable medical devices are of increasing concern. This issue is exaggerated with the introduction of complex medical devices like endoscopes and robotic instrumentation. Although medical device manufacturers validate their cleaning instructions for use, evidence in the literature demonstrates that effective device processing is not being performed consistently within sterile processing departments in clinical settings. The result is increased risks to patient safety. As a solution to this problem, focused one-on-one training increases compliance to the medical device manufacturer's processing instruction. However, often this is not a practical solution for the volume of healthcare staff responsible for device processing activities. This constitutes the first paper to address the blended use of educational and digital technologies to address these challenges and as a result inform safety and sustainability for the medical device sector. Cognitive learning theory is an evidence-based framework for learning. It supports the use of immersive educational experiences using emerging extended reality technologies (e.g., virtual or augmented reality) to increase learning comprehension. The delivery of educational content via these technologies provides an innovative option for repeatable leaning and training outcomes. The motivation is to decrease patient risk of contaminated reusable medical devices. The proposed approach while primary motivated by safety can also enhance sustainability and efficiency enabled by artificial intelligence and robotic instrumentation.

Racial Disparity in HCV Demographics and Treatment Between Interferon Era (2002-2003) and Direct Acting Anti-viral Era (2019).

Introduction  Direct-acting antiviral (DAA) treatment increased the sustained viral response (SVR) rate of patients with the hepatitis C virus (HCV) and eliminated response disparities between African American (AA) and non-AA patients seen with interferon (IFN). The aim of this study was to compare 2019 HCV patients (DAA era) to patients from January 1, 2002 and December 31, 2003 (IFN era) in our predominantly AA clinic population. Methods We extracted data on 585 HCV patients seen in 2019 (DAA era) and compared them to 402 patients seen in the IFN era. Results Most HCV patients were born between 1945 and 1965, but in the DAA era more younger patients were identified. Non-AA patients in both eras were less likely to be infected with genotype 1 compared to AA (95% vs 54%, P<0.001). Fibrosis was not increased in the DAA Era as compared to the IFN era as assessed either by serum-based assays (APRI, FIB-4) or transient elastography (FibroScan) (DAA era) vs biopsy (IFN era). More patients were treated in 2019 compared to 2002-2003 (159/585=27% vs 5/402=1%). For untreated patients, subsequent treatment within one year of the initial visit was low and similar in both eras (35%). Conclusion There continues to be a need to screen patients born between 1945 and 1965 for HCV as well as to identify increasing numbers of patients below this age cohort. Even though current therapies are oral, highly effective, and can be 8-12 weeks in duration, significant numbers of patients were not treated within a year of first visit.

Kappa Opioid Receptors in Mesolimbic Terminals Mediate Escalation of Cocaine Consumption.

Increases in drug consumption over time, also known as escalation, is a key behavioral component of substance use disorder (SUD) that is related to potential harm to users, such as overdose. Studying escalation also allows researchers to investigate the transition from casual drug use to more SUD-like drug use. Understanding the neurobiological systems that drive this transition will inform therapeutic treatments in the aim to prevent increases in drug use and the development of SUD. The kappa opioid receptor (KOR) system is typically known for its role in negative affect, which is commonly found in SUD as well. Furthermore, the KOR system has also been implicated in drug use and importantly, modulating the negative effects of drug use. However, the specific neuronal subpopulation expressing KOR involved has not been identified. Here, we first demonstrated that pharmacologically inhibiting KOR in the nucleus accumbens core (NAcC), as a whole, blocks cocaine escalation under long-access self-administration conditions. We then demonstrated that KOR expressed on ventral tegmental area (VTA) neurons but not NAcC neurons is sufficient for blocking cocaine escalation by utilizing a novel virally-mediated CRISPR-SaCas9 knock-out of the oprk1 gene. Together, this suggests that activation of KOR on VTA terminals in the NAcC drives the transition to the SUD-like phenotype of escalation of cocaine consumption.

Wilkie's Syndrome following Chemotherapy: A Case Report and a Review of Literature.

Superior mesenteric artery (SMA) syndrome is a rare etiology of upper gastrointestinal obstruction. The measured angle between the SMA and the aorta is typically between 38 and 65° and maintained by mesenteric fat. Excessive fat loss can lead to intestinal obstruction due to an exaggerated acute angularity of the SMA, compressing the third part of the duodenum. We present a 22-year-old female with a history of aplastic anemia, status post bone-marrow transplant, who presented with intractable nausea and had confirmed SMA syndrome on CT angiography. Subsequently, the patient underwent nasogastric decompression and successful laparoscopic duodenojejunostomy.

The CAPRA-S Score and Immune Dysfunction as a Guide to Outcome in Men Treated with Prostatectomy Radical as Mono-Therapy for Prostate Cancer

Objective: Incorporate the immune function as determined by the absolute lymphocyte count (ALC) into the CAPRA-S risk stratification score to determine if predictive values could be improved. Materials and Methods: The clinical pathological findings in the surgical specimen and total PSA were used to define the three CAPRA-S risk groups. One month after surgery and at each follow up total PSA and the ALC were determined, until biochemical failure (BF) or the end of the study period. A cut off value of <1,000 lymphocytes/mm3 was used to define lymphocytopenia (LCP). Each CAPRA-S group was sub-divided based on the presence or absence of LCP. Kaplan-Meier biochemical failure free survival (BFFS) curves and restricted mean biochemical failure free survival times were calculated for each group. Results: 404 patients participated of whom 103 (25.5%) underwent BF. 270 men were CAPRA-S low risk (LR), 89 intermediate risk (IR) and 45 high risk (HR), of whom LCP was found in 22 (8%) of low risk, 24 (27%) of intermediate risk and 17 (38%) of high risk men. LCP was significantly associated with a higher PSA, higher Gleason and CAPRA-S scores and BF. HRs were 1.76 for IR, 2.49 for HR and 1.29 for LCP. Five-year BFFS for men without LCP, LR 93.5%, IR 61% and HR 36%, for those with LCP, LR 55%, IR 25% and HR 6%. All patients with LCP and IR or HR scores relapsed within 6 years. 10 year BFFS for men without LCP were 71% LR, 43% IR and 23% HR, LR with LCP 16%. Men with BF had increasing LCP approximately 18 months before BF. Conclusions: The incorporation of the ALC taken one month after surgery with the CAPRA-S improves risk stratification; decreases in the ALC suggest that BF is occuring. These results need to be confirmed with larger studies (AU)

Objetivo: Establecer el riesgo de recidiva bioquímica(RBQ) basado en la puntuación CAPRA-S (riesgo bajo(RB) , riesgo intermedio (RI) y riesgo alto (RA) y recuentoabsoluto de linfocitos (RAL) ≤1000 por mm3(definidiacomo linfocitipenia LCP).Material y Métodos: Entre 2005 y 2020, se realizaun estudio observacional prospectivo de sujetos con cáncerpróstatico tratado con cirugia. Se registran los hallazgos delespécimen quirúrgico y el PSA para definir la CAPRA-S.Un mes pos-cirugía y durante el seguimiento el PSA y RALfueron determinados hasta la RBQ o final del estudio. Seconstruye un modelo de supervivencia flexible paramétrico(FP) para predecir la RBQ a 5 años utilizando la puntuaciónCAPRA-S y la LCP. Se evalúan mediante regresión localponderada mediciones repetidas de los RAL y el tiempo aRBQ o fin del estudio.Resultados: De los 404 participantes observaron 103(25,5%) RBQ. Puntajes de la CAPRA-S: 270 RB, 89 RI y45 RA. La LCP estaba asociada con niveles elevados delPSA, puntuación Gleason, márgenes comprometidos, extensión extracapsular, invasión de vesículas seminales ynodos linfáticos. El modelo FP incorporo en forma independiente y significativa ( coeficiente con valor P<0,01) laLCP ( 1,29), RA (2,49), RI (1,76) y RB (1); mostrando unaC de Harrell de 0,81 con adecuada validez. la media restringida en años (MR) para ocurrencia de RBQ, como lasupervivencia predicha (SP) a 5 años fueron: sin LCP RA(MR: 3,63; SP 42,1%) RI (MR 4,3; SP 63,1%) RB (MR4,83; SP 91,7%) con LCP RA (MR 2,1; SP 4,34%) RI (MR3,14; SP 18,9%) y RB (MR 4,42; SP 73,1%). Los sujetoscon RBQ tuvieron LCP 18 meses previo a la RBQ. LCP más CAPRA-S predicen la RB en sujetos tratado con cirugia (AU)

Celiac Disease Patients With Coronary Artery Disease: A Nationwide Population-Based Study.

Background Coronary artery disease (CAD) is associated with celiac disease (CD) with limited evidence. However, the common risk factors linking CD and CAD are still lacking in the literature. Known CAD risk factors include hypertension, hyperlipidemia, type 2 diabetes, obesity, and tobacco use. Common risk factors linking CD and CAD are poorly documented. Objective There are three objectives: Firstly, to evaluate potential demographic differences between CD patients with CAD and without CAD. Secondly, to analyze the risk factors of CAD in CD patients. Lastly, to compare CD-CAD and matched non-CD CAD to determine whether there are additional CAD risks in individuals with CD. Methods The study is a nationwide retrospective case-control study. The National Inpatient Sample (NIS) database was used to identify patients admitted between 2016 and 2018 with a principal or secondary diagnosis of CD. We analyzed sociodemographic and clinical risk factors of CAD in CD patients and compared the CD-CAD population with the matched non-CD CAD cohort. Results Out of 23,441 hospitalizations with CD in 2016-2018, 4244 (18%) were found to have CAD. Established CAD risk factors identified in CD patients included hypertension, hyperlipidemia, type 2 diabetes, and a family history of CAD. In contrast, tobacco use is not a CAD risk factor in CD patients. Female patients with CD had 55% lesser odds of CAD than male patients. The odds of CAD in CD patients with hyperlipidemia were five times higher, 1.2 times higher with essential hypertension, and two times higher with type 2 diabetes. Patients with CAD had a higher prevalence of iron deficiency anemia (9.33% CD-CAD and 8.28% non-CAD CD Vs. 7.32% non-CD CAD). Conclusions Our study confirms that, as with non-CD individuals, males and the White race are at increased CAD risk in the CD population. CD-CAD patients have a higher hyperlipidemia prevalence than non-CD CAD patients. CD patients with type 1 diabetes have an early diagnosis of CAD compared to CD patients with type 2 diabetes. Iron deficiency anemia is a statistically significant risk factor for CAD in CD patients.

Periarticular calcifications.

Periarticular calcification and ossification is a frequent finding on imaging and may sometimes pose a diagnostic challenge. The differential diagnoses for this radiological finding are wide and can be classified into broad groups such as idiopathic, developmental, trauma, burns, infection, tumor, connective tissue disease, crystalline, metabolic, vascular, and foreign bodies. With careful consideration of the clinical and imaging findings as well as awareness of mimickers of periarticular mineralization, the list of differential diagnoses can be narrowed down. This article aims to review the clinical-radiologic findings of periarticular calcified or ossified lesions with relevant imaging illustrations.

An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials.

The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The structure of PfATP4 has not been determined. Here, we describe a public competition created to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the synthesis of inactive compounds. Competition participants could see all entries as they were submitted. In the final round, featuring private sector entrants specializing in machine learning methods, the best-performing models were used to predict novel inhibitors, of which several were synthesized and evaluated against the parasite. Half possessed biological activity, with one featuring a motif that the human chemists familiar with this series would have dismissed as "ill-advised". Since all data and participant interactions remain in the public domain, this research project "lives" and may be improved by others.

Ipilimumab and Nivolumab-Induced Colitis in a Patient With Recurrent Metastatic Melanoma.

Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. The patient had been treated with ipilimumab and nivolumab in the past two months. The infectious workup was inconclusive. Colonoscopy demonstrated severe colitis, and biopsies were consistent with colitis. Combination chemotherapy was stopped. The patient was treated with intravenous and oral steroids, and her symptoms improved. A combination of ipilimumab and nivolumab increases the chance of immune-mediated colitis, and steroids should be started promptly to avoid complications such as bowel perforation and toxic megacolon.

In the Global Epicenter: Social Work Leadership in a New York City Hospital.

The Mount Sinai Hospital in New York City was in the epicenter of the COVID-19 pandemic and had to transform from a tertiary to crisis care hospital and increase its bed capacity by 50 percent to care for COVID-19 patients. The size, scope, complexity and uncertainty of this crisis was unparalleled. This article describes the comprehensive response of the Department of Social Work Services, one of the largest hospital social work departments in the country. The response was informed by four Departmental principles, as well as crisis intervention strategies. This article describes organizational structures, practice models, policies, and protocols developed to respond quickly and effectively, given infection prevention mandates, to patient, population and workforce needs. Finally, it includes how social workers addressed COVID-19 related physical and psychosocial needs and applied and modified interprofessional communication and collaboration. Lessons learned and clinical and administrative changes that will assist in navigating "new normal" operations are discussed.

Tilted X-Ray Holography of Magnetic Bubbles in MnNiGa Lamellae.

Nanoscopic lamellae of centrosymmetric ferromagnetic alloys have recently been reported to host the biskyrmion spin texture; however, this has been disputed as the misidentication of topologically trivial type-II magnetic bubbles. Here we demonstrate resonant soft X-ray holographic imaging of topological magnetic states in lamellae of the centrosymmetric alloy (Mn1-xNix)0.65Ga0.35 (x = 0.5), showing the presence of magnetic stripes evolving into single core magnetic bubbles. We observe rotation of the stripe phase via the nucleation and destruction of disclination defects. This indicates the system behaves as a conventional uniaxial ferromagnet. By utilizing the holography with extended reference by autocorrelation linear differential operator (HERALDO) method, we show tilted holographic images at 30° incidence confirming the presence of type-II magnetic bubbles in this system. This study demonstrates the utility of X-ray imaging techniques in identifying the topology of localized structures in nanoscale magnetism.

Anthropogenic modification of forests means only 40% of remaining forests have high ecosystem integrity.

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remain poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate a globally consistent, continuous index of forest condition as determined by the degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) has high landscape-level integrity (mostly found in Canada, Russia, the Amazon, Central Africa, and New Guinea) and only 27% of this area is found in nationally designated protected areas. Of the forest inside protected areas, only 56% has high landscape-level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally.

Pembrolizumab-Induced Immune-Mediated Hepatitis and Concurrent Hepatitis B Reactivation in a Patient With Non-Small Cell Lung Cancer.

New immuno-therapeutic agents like pembrolizumab used in cancer treatment are known to cause immune-mediated hepatitis. Most of these cases are straightforward when the onset of transaminitis correlates with the introduction of the medication. This agent causing hepatitis B reactivation has been reported only once. To have both these adverse effects occurring at the same time in a patient is uncommon and presents a clinical challenge. Our patient was a 49-year-old gentleman diagnosed with metastatic adenocarcinoma of the lung seven months ago. He was started on pembrolizumab, as the malignant tissue obtained during biopsy had high program death-ligand 1 (PDL1) expression. On reviewing the labs ordered during the time of cancer diagnosis, this man has evidence of chronic hepatitis B with positive hepatitis B surface antigen and positive hepatitis B core immunoglobulin G (IgG) antibody. He presented with acute hepatitis, and workup showed features of hepatitis B reactivation, but the extent of reactivation was not adequate to explain the presentation, hence investigations were pursued. This led the way to the diagnosis of a combined hepatitis B reactivation and drug-induced immune hepatitis in this case. He responded promptly to the withdrawal of the agent and steroids. On follow-up, his liver function panel had significantly improved.  This case is very unique in two aspects. First, to our knowledge, there is only one case reported of pembrolizumab-induced hepatitis B reactivation. In addition, our patient also had immune-mediated hepatitis induced by pembrolizumab. It is very rare to have a combination of these two presentations to be seen in a patient at the same time. Pembrolizumab-induced immune hepatitis can coexist with hepatitis B reactivation following therapy with this agent.

Prediction of Hemorrhage after Successful Recanalization in Patients with Acute Ischemic Stroke: Improved Risk Stratification Using Dual-Energy CT Parenchymal Iodine Concentration Ratio Relative to the Superior Sagittal Sinus.

BACKGROUND AND PURPOSE: Brain parenchymal hyperdensity on postthrombectomy CT in patients with acute stroke can be due to hemorrhage and/or contrast staining. We aimed to determine whether iodine concentration within contrast-stained parenchyma compared with an internal reference in the superior sagittal sinus on dual-energy CT could predict subsequent intracerebral hemorrhage. MATERIALS AND METHODS: Seventy-one patients with small infarct cores (ASPECTS ≥ 7) and good endovascular recanalization (modified TICI 2b or 3) for anterior circulation large-vessel occlusion were included. Brain parenchymal iodine concentration as per dual-energy CT and the percentage of contrast staining relative to the superior sagittal sinus were recorded and correlated with the development of intracerebral hemorrhage using Mann-Whitney U and Fisher exact tests. RESULTS: Forty-three of 71 patients had parenchymal hyperdensity on initial dual-energy CT. The median relative iodine concentration compared with the superior sagittal sinus was significantly higher in those with subsequent intracerebral hemorrhage (137.9% versus 109.2%, P = .007). By means of receiver operating characteristic analysis, a cutoff value of 100% (iodine concentration relative to the superior sagittal sinus) enabled identification of patients going on to develop intracerebral hemorrhage with 94.75% sensitivity, 43.4% specificity, and a likelihood ratio of 1.71. CONCLUSIONS: Within our cohort of patients, the relative percentage of iodine concentration at dual-energy CT compared with the superior sagittal sinus was a reliable predictor of intracerebral hemorrhage development and may be a useful imaging biomarker for risk stratification after endovascular treatment.

Concussion history associated with increased postural control deficits after subsequent injury.

OBJECTIVE: Postural control deficits have been extensively reported following sport-related concussions. Concussed athletes demonstrate these deficits as early as 24 h post-concussion and may persist for up to six months. Many of these prior studies have included mixed samples with prior injury history that may affect the postural control data. The purpose of this investigation was to evaluate the effect of concussion history on postural control 24-48 h following sport-related concussion in Division I athletes. APPROACH: Twenty-eight Division I athletes (seven athlete controls (CON), seven no history (SRC0), seven with a previous concussion (SRC1), and seven with 2-3 concussions (SRC3) participated in this study. All participants were assessed within 24-48 h post-subsequent SRC and performed three trials of quiet stance in the eyes closed (EC) conditions for 30 s each on a force platform (1000 Hz). The data were analyzed with root mean square (RMS) and mean excursion velocity (MEV) in the anteroposterior (AP) and mediolateral (ML) directions. Two 3 × 2 MANOVAs were run by direction for group comparisons. MAIN RESULTS: SRC2 had significantly greater RMS than CON, SRC0, and SRC1 in the AP direction and ML direction. SRC2 exhibited significantly greater AP and ML MEV than CON, SRC0, and SRC1. SIGNIFICANCE: These results demonstrate that having 2-3 prior concussions negatively affects the postural system after a subsequent head injury. Sports medicine staff should approach the recovery process with caution with those that have a prior history of concussion, due to the negative effects that history of concussion has on postural control strategies.