Atomic Displacements Enabling the Observation of the Anomalous Hall Effect in a Non-Collinear Antiferromagnet.

Antiferromagnets with non-collinear spin structures display various properties that make them attractive for spintronic devices. Some of the most interesting examples are an anomalous Hall effect despite negligible magnetization and a spin Hall effect with unusual spin polarization directions. However, these effects can only be observed when the sample is set predominantly into a single antiferromagnetic domain state. This can only be achieved when the compensated spin structure is perturbed and displays weak moments due to spin canting that allows for external domain control. In thin films of cubic non-collinear antiferromagnets, this imbalance is previously assumed to require tetragonal distortions induced by substrate strain. Here, it is shown that in Mn3 SnN and Mn3 GaN, spin canting is due to structural symmetry lowering induced by large displacements of the magnetic manganese atoms away from high-symmetry positions. These displacements remain hidden in X-ray diffraction when only probing the lattice metric and require measurement of a large set of scattering vectors to resolve the local atomic positions. In Mn3 SnN, the induced net moments enable the observation of the anomalous Hall effect with an unusual temperature dependence, which is conjectured to result from a bulk-like temperature-dependent coherent spin rotation within the kagome plane.

Assessing What Matters to People Affected by Alzheimer's Disease: A Quantitative Analysis.

INTRODUCTION: In this phase of the ongoing What Matters Most study series, designed to evaluate concepts that are meaningful to people affected by Alzheimer's disease (AD), we quantified the importance of symptoms, impacts, and outcomes of AD to people at risk for or with AD and care partners of people with AD. METHODS: We administered a web-based survey to individuals at risk for or with AD (Group 1: unimpaired cognition with evidence of AD pathology; Group 2: AD risk factors and subjective cognitive complaints/mild cognitive impairment; Group 3: mild AD) and to care partners of individuals with moderate AD (Group 4) or severe AD (Group 5). Respondents rated the importance of 42 symptoms, impacts, and outcomes on a scale ranging from 1 ("not at all important") to 5 ("extremely important"). RESULTS: Among the 274 respondents (70.4% female; 63.1% white), over half of patient respondents rated all 42 items as "very important" or "extremely important," while care partners rated fewer items as "very important" or "extremely important." Among the three patient groups, the minimum (maximum) mean importance rating for any item was 3.4 (4.6), indicating that all items were at least moderately to very important. Among care partners of people with moderate or severe AD, the minimum (maximum) mean importance rating was 2.1 (4.4), indicating that most items were rated as at least moderately important. Overall, taking medications correctly, not feeling down or depressed, and staying safe had the highest importance ratings among both patients and care partners, regardless of AD phase. CONCLUSION: Concepts of importance to individuals affected by AD go beyond the common understanding of "cognition" or "function" alone, reflecting a desire to maintain independence, overall physical and mental health, emotional well-being, and safety. Preservation of these attributes may be key to understanding whether interventions deliver clinically meaningful outcomes.

Technical Review of Clinical Outcomes Assessments Across the Continuum of Alzheimer's Disease.

INTRODUCTION: Insight into the relationship between concepts that matter to the people affected by Alzheimer's disease (AD) and the clinical outcome assessments (COAs) commonly used in AD clinical studies is limited. Phases 1 and 2 of the What Matters Most (WMM) study series identified and quantitatively confirmed 42 treatment-related outcomes that are important to people affected by AD. METHODS: We compared WMM concepts rated as "very important" or higher to items included in COAs used commonly in AD studies. RESULTS: Twenty COAs designed to assess signs, symptoms, and impacts across the spectrum of AD were selected for review. Among these 20 COAs, only 5 reflected 12 or more WMM concepts [Integrated Alzheimer's Disease Rating Scale (iADRS), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment (ADCS-ADL-MCI), Alzheimer's Disease Composite Scores (ADCOMS), and Clinical Dementia Rating; Clinical Dementia Rating-Sum of Boxes (CDR/CDR-SB)]. Multiple symptoms and impacts of AD identified as important and meaningful in the WMM studies map only indirectly at best to 7 of the 20 most widely used COAs. CONCLUSION: While many frequently used COAs in AD capture some concepts identified as important to AD populations and their care partners, overlap between any single measure and the concepts that matter to people affected by AD is limited. The highest singly matched COA reflects fewer than half (45%) of WMM concepts. Use of multiple COAs expands coverage of meaningful concepts. Future research should explore the content validity of AD COAs planned for AD trials based on further confirmation of the ecological validity of the WMM items. This research should inform development and use of core outcome sets that capture WMM items and selection or development of new companion tools to fully demonstrate clinically meaningful outcomes spanning WMM.

Setting of the magnetic structure of chiral kagome antiferromagnets by a seeded spin-orbit torque.

The current-induced spin-orbit torque switching of ferromagnets has had huge impact in spintronics. However, short spin-diffusion lengths limit the thickness of switchable ferromagnetic layers, thereby limiting their thermal stability. Here, we report a previously unobserved seeded spin-orbit torque (SSOT) by which current can set the magnetic states of even thick layers of the chiral kagome antiferromagnet Mn3Sn. The mechanism involves setting the orientation of the antiferromagnetic domains in a thin region at the interface with spin currents arising from an adjacent heavy metal while also heating the layer above its magnetic ordering temperature. This interface region seeds the resulting spin texture of the entire layer as it cools down and, thereby, overcomes the thickness limitation of conventional spin-orbit torques. SSOT switching in Mn3Sn can be extended beyond chiral antiferromagnets to diverse magnetic systems and provides a path toward the development of highly efficient, high-speed, and thermally stable spintronic devices.

Intrinsic 2D-XY ferromagnetism in a van der Waals monolayer.

The physics and universality scaling of phase transitions in low-dimensional systems has historically been a topic of great interest. Recently, two-dimensional (2D) materials exhibiting intriguing long-range magnetic order have been in the spotlight. Although an out-of-plane anisotropy has been shown to stabilize 2D magnetic order, the demonstration of a 2D magnet with in-plane rotational symmetry has remained elusive. We constructed a nearly ideal easy-plane system, a single CrCl3 monolayer on graphene/6H-SiC(0001), and observed robust ferromagnetic ordering with critical scaling characteristic of a 2D-XY system. These observations indicate the realization of a finite-size Berezinskii-Kosterlitz-Thouless phase transition in a large-area, quasi­free-standing van der Waals monolayer magnet with an XY universality class. This offers a material platform to host 2D superfluid spin transport and topological magnetic textures.

High-Dose-Rate Brachytherapy for the Treatment of Basal and Squamous Cell Carcinomas on Sensitive Areas of the Face: A Report of Clinical Outcomes and Acute and Subacute Toxicities.

PURPOSE: Basal cell and cutaneous squamous cell carcinoma are common malignancies (keratinocyte carcinomas [KCs]). Surgical resection is the standard of care. Radiation using high-dose rate brachytherapy (HDR-BT) may serve as a superior alternative where surgical scars may be of cosmetic concern or in elderly patients with significant comorbidity. We aim to describe the clinical and cosmetic outcomes as well as posttreatment radiation toxicities associated with HDR-BT in patients who were treated for KCs of the face. METHODS AND MATERIALS: Patients with KCs treated with HDR-BT from 2015 to 2018 were included in the study. Patient medical records and clinical photos were reviewed at multiple time points: start of treatment, end of treatment, short-term (2 week) follow-up, 3-month follow-up, and if needed at 6 months. Radiation toxicity was graded using the Radiation Therapy Oncology Grading (RTOG) acute toxicity scale. Median (range) toxicity grades at follow-up intervals were calculated. Clinical outcomes including local recurrence were evaluated for all patients. RESULTS: The study included 19 patients and 20 KCs. The median radiation dose was 42 Gy (39-42 Gy) over 6 fractions. The median toxicity at completion of treatment was RTOG grade 2 (85% of patients). At short-term follow-up, 50% of patients (n = 10) improved to RTOG grade 1 (0-2). At 3 months, 70% of patients (n = 14) had RTOG grade 0, and by 6 months, 100% of patients (n = 18) had RTOG grade 0. No RTOG grade 3 or higher skin toxicity was observed. With a median follow-up of 7.2 months (range, 1.3-54.4 months), the local recurrence-free survival was 95%. CONCLUSIONS: We demonstrate that HDR-BT can be used as definitive treatment of KCs of the face with excellent cosmetic outcomes and local control. Acute and subacute skin toxicities were most commonly RTOG grade 2 or less with resolution of patient's skin toxicity by 3 months.

Dosimetric Comparisons of Simulation Techniques for Left-Sided Breast Cancer in the COVID-19 Era: Techniques to Reduce Viral Transmission and Respect the Therapeutic Ratio.

Background The COVID-19 pandemic challenges our ability to safely treat breast cancer patients and requires revisiting current techniques to evaluate optimal strategies. Potential long-term sequelae of breast radiation have been addressed by deep inspiration breath-hold (DIBH), prone positioning, and four-dimensional computed tomography (4DCT) average intensity projection (AveIP)-based planning techniques. Dosimetric comparisons to determine the optimal technique to minimize the normal tissue dose for left-sided breast cancers have not been performed. Methods Ten patients with left-sided, early-stage breast cancer undergoing whole breast radiation were simulated in the prone position, supine with DIBH, and with a free-breathing 4DCT scan. The target and organs at risk (OAR) contours were delineated in all scans. Target volume coverage and OAR doses were assessed. One-way analysis of variance (ANOVA) and Kruskal-Wallis one-way ANOVA were used to detect differences in dosimetric parameters among the different treatment plans. Significance was set as p < 0.05. Results We demonstrate differences in heart and lung dose by the simulation technique. The mean heart doses in the prone, DIBH, and AveIP plans were 129 cGy, 154 cGy, and 262 cGy, respectively (p=0.02). The lung V20 in the prone, DIBH, and AveIP groups was 0.5%, 10.3% and 9.5%, respectively (p <0.001). Regardless of technique, lumpectomy planning target volume (PTV) coverage did not differ between the three plans with 95% of the lumpectomy PTV volume covered by 100.4% in prone plans, 98.5% in AveIP plans, and 99.3% in DIBH plans (p=0.7). Conclusions Prone positioning provides dosimetric advantages as compared to DIBH. When infection risks are considered as in the current coronavirus disease 2019 (COVID-19) pandemic, prone plans have advantages in reducing the risk of disease transmission. In instances where prone positioning is not feasible, obtaining an AveIP simulation may be useful in more accurately assessing heart and lung toxicity and informing a risk/benefit discussion of DIBH vs free breath-hold techniques.

Prophylactic cranial irradiation or MRI surveillance for extensive stage small cell lung cancer.

The treatment paradigm for extensive stage small cell lung cancer (ES-SCLC) is evolving. Prophylactic cranial irradiation (PCI) has long been considered a component of standard treatment in patients with extensive stage disease who respond to chemotherapy. However, in the modern era of magnetic resonance imaging, the role of PCI has become an area of controversy following conflicting level I evidence. Due to conflicting data and toxicity concerns, the routine use of PCI has declined. Recent improvements in systemic disease control with the use of immunotherapy and reductions in the toxicity attributable to PCI with hippocampal avoidance and memantine have reignited the discussion. As such, we present here a narrative review of PCI with a focus on historical milestones, randomized data, risk mitigation and future directions.

The Impact of Prostate Cancer Treatment on Quality of Life: A Narrative Review with a Focus on Randomized Data.

Despite excellent oncologic outcomes, the management of localized prostate cancer remains complex and is dependent on multiple factors, including patient life expectancy, medical comorbidities, tumor characteristics, and genetic risk factors. Decades of iterative clinical trials have improved the optimization and utilization of surgical and radiation-based modalities, as well as their combinatorial use with anti-androgen and systemic therapies. While cure rates are high and converging on equivalent disease control should an upfront surgical or radiotherapeutic approach be optimized, the long-term side effects of surgical and radiation-based treatments can differ significantly in nature. Decisions regarding the selection of therapy are therefore best made in an informed and shared medical decision-making process between clinician and patient with respect to cancer control as well as adverse effects. We outline in this narrative review an understanding regarding implications of surgical and radiation treatment on quality of life after treatment, and how these data may be considered in the context of advising patients regarding the selection of therapy. This narrative review largely focuses on the quality of life data obtained from prospective randomized trials of men treated for prostate cancer. We believe this provides the best assessment of the quality of life and can be used to inform patients when making treatment decisions.

Impact of Sarcopenia on Survival in Patients With Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy.

Background Sarcopenia has been associated with poor survival among cancer patients. Normalized total psoas area (NTPA) has been used as a surrogate for defining sarcopenia. Few data exist characterizing the impact of sarcopenia and other metrics of fitness on clinical outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated non-invasively with stereotactic body radiotherapy (SBRT). Methods To assess the association between sarcopenia and clinical outcomes, we conducted a retrospective analysis of consecutive patients treated with SBRT from 2013 to 2019 . Overall survival (OS), local failure free survival (LFS), distant failure free survival (DFS), NTPA, body mass index (BMI), and Charlson comorbidity index (CCI) were included for analysis. NTPA was calculated by measuring the psoas volume at the L3 vertebra and normalizing for patient height and gender. Survival functions were evaluated using the Kaplan-Meier method. Log-rank test and Cox-proportional hazards were performed for categorical and continuous variables, respectively. Significance was set as p < 0.05. Results A total of 91 patients met the criteria. The median age was seven years and Karnofsky Performance Status score (KPS) was 80 (range: 60-100). Approximately 79% of patients had T1 tumors. Median radiation dose and number of fractions were 60 Gy (range: 45-60) and 5 fractions (range: 3-5). Median NTPA was 531.16 mm2/m2 (range: 90.4-1356.2). After normalization (sarcopenia: <385 mm2/m2, female; <585 mm2/m2, male), 39 patients (42.8%) had sarcopenia. NTPA had no association with OS (p = 0.7), LFS (p = 0.9), or DFS (p = 0.5). Increasing BMI was associated with improved OS (HR 0.90, 95% CI 0.83-0.98). With a median follow-up of 23.4 months, median OS was 60, 60, and 45.9 months (p = 0.37) in all patients, non-sarcopenic patients, and sarcopenic patients, respectively. Conclusion Sarcopenia was not associated with OS, LFS, or DFS. Increasing BMI is associated with improved OS. Future, prospective work is needed to define the impact of sarcopenia and other fitness metrics on clinical outcomes among NSCLC patients treated non-invasively with SBRT.

Topological Hall Signatures of Two Chiral Spin Textures Hosted in a Single Tetragonal Inverse Heusler Thin Film.

Magnetic skyrmions and antiskyrmions are observed in material classes with different crystal symmetries, where the Dzyaloshinskii-Moriya interaction stabilizes either skyrmions or antiskyrmions. Here, we report the observation of two distinct peaks in the topological Hall effect in a thin film of Mn2RhSn. Utilizing a phenomenological approach and electronic transport simulations, these topological Hall effect features are attributed to be direct signatures of two topologically distinct chiral spin objects, namely, skyrmions and antiskyrmions. Topological Hall effect studies allow us to determine the existence of these two topological objects over a wide range of temperature and magnetic fields. In particular, we find skyrmions to be stable at low temperatures, suggesting the increased importance of dipolar interactions.

Target treatment with stereotactic radiation for recurrent gliomas.

High grade gliomas (HGG) have a propensity to recur locally and have poor outcomes. As such, safe and effective treatment is paramount. Target treatment with stereotactic radiation allows safe re-irradiation through minimizing normal brain tissue radiation due to its high precision. In this review, we evaluated the clinical experiences using SRS and FSRT for re-irradiation in HGG. We report the radiobiological advantages and disadvantages of both modalities as well as the safety and efficacy published in current literature.

The Underappreciated Role of the Humoral Immune System and B Cells in Tumorigenesis and Cancer Therapeutics: A Review.

The advent of immunotherapy has ushered in a new era in both cancer research and cancer treatment strategies. Published reviews have described potential mechanisms for therapeutic synergisms from the combination of radiation therapy and immunotherapy, largely overlooking the role of humoral immunity by only focusing on cellular immunity. Given that these 2 branches of the immune system are highly interdependent, in this review we detail both what has already been established regarding the role of humoral immunity in cancer and propose potential avenues that are ripe for further investigation and potential clinical applications.

Comparing Radiotherapy to Prostatectomy for High-Risk Prostate Cancer: A Narrative Review of Mortality and Quality-of-Life Outcomes.

There is currently a lack of level 1 evidence regarding the relative efficacy of radical prostatectomy compared with radiotherapy combined with androgen deprivation therapy for high-risk prostate cancer. There has recently been an improved optimization of treatment, achieving superior biochemical outcomes and cancer-specific mortality through the use of combined modality therapy strategies. Combined modality therapies have also increasingly incorporated brachytherapy boost. Although available observational data must be interpreted with caution because of the effects of potential residual confounding, we present here a narrative review of recent advances in understanding the relative efficacy of the principal combined modality approaches for treating high-risk prostate cancer. As the trend has demonstrated approaching equivalence between well-selected combined modality therapies, an increasing emphasis should be placed on selecting therapy tailored toward a patient's goals regarding quality of life. We present here an outline of efforts to date to understand the implications of treatment on functional outcomes and quality-of-life endpoints.

Identification of CD37, cystatin A, and IL-23A gene expression in association with brain metastasis: analysis of a prospective trial.

PURPOSE/OBJECTIVES: We aimed to assess the predictive value of a lung cancer gene panel for the development of brain metastases. MATERIALS/METHODS: Between 2011 and 2015, 102 patients with lung cancer were prospectively enrolled in a clinical trial in which a diagnostic fine-needle aspirate was obtained. Gene expression was conducted on all samples that rendered a diagnosis of non-small cell lung cancer (NSCLC). Subsequent retrospective analysis of brain metastases-related outcomes was performed by reviewing patient electronic medical records. A competing risk multivariable regression was performed to estimate the adjusted hazard ratio for the development of brain metastases and non-brain metastases from NSCLC. RESULTS: A total of 49 of 102 patients had died by the last follow-up. Median time of follow-up was 13 months (range 0.23-67 months). A total of 17 patients developed brain metastases. Median survival time after diagnosis of brain metastases was 3.58 months (95% confidence interval (CI) 2.17, not available). A total of 30 patients developed metastases without any evidence of brain metastases until the time of death or last follow-up. Competing risk analysis identified three genes that were downregulated differentially in the patients with brain metastases versus non-brain metastatic disease: CD37 (0.017), cystatin A (0.022), and IL-23A (0.027). Other factors associated with brain metastases include: stage T ( P ⩽ 8.3e-6) and stage N ( P= 6.8e-4). CONCLUSIONS: We have identified three genes, CD37, cystatin A, and IL-23A, for which downregulation of gene expression was associated with a greater propensity for developing brain metastases. Validation of these biomarkers could have implications on surveillance patterns in patients with brain metastases from NSCLC.

Gamma Knife Stereotactic Radiosurgery for the Treatment of Brain Metastases from Primary Tumors of the Urinary Bladder.

BACKGROUND/AIMS: Brain metastases from bladder cancer are rare and published outcomes data are sparse. To date, no institutions have reported a series of patients with brain metastases from bladder cancer treated with stereotactic radiosurgery (SRS). Our aim was to identify patients with brain metastases from bladder primaries treated with SRS with or without surgical resection and report the clinical outcomes. METHODS: Patients meeting eligibility criteria at our institution between 2000 and 2017 were included. The clinical variables of interest, including overall survival (OS), local recurrence, V12, distant brain failure (DBF), and initial brain metastases velocity, were calculated. Cox proportional hazards analysis was performed to identify predictors of time-to-event outcomes. RESULTS: A total of 14 patients were included. The median OS from the time of treatment was 2.1 months. Factors predictive of OS include intracranial resection (HR 0.21, p = 0.03). The cumulative incidence of local failure was 21% at 6 months and 30% at 12 months. The cumulative incidence of DBF at 6 and 12 months was 23 and 31%, respectively. CONCLUSIONS: The prognosis in this patient population remains guarded. Factors associated with improved survival include intracranial resection. Future, prospective work is needed to further define optimal management.

Intolerance of uncertainty predicts increased striatal volume.

Oversensitivity to uncertain future threat is usefully conceptualized as intolerance of uncertainty (IU). Neuroimaging studies of IU to date have largely focused on its relationship with brain function, but few studies have documented the association between IU and the quantitative properties of brain structure. Here, we examined potential gray and white-matter brain structural correlates of IU from 61 healthy participants. Voxel-based morphometric analysis highlighted a robust positive correlation between IU and striatal volume, particularly the putamen. Conversely, tract-based spatial statistical analysis showed no evidence for a relationship between IU and the structural integrity of white-matter fiber tracts. Current results converge upon findings from individuals with anxiety disorders such as obsessive-compulsive disorder (OCD) or generalized anxiety disorder (GAD), where abnormally increased IU and striatal volume are consistently reported. They also converge with neurobehavioral data implicating the putamen in predictive coding. Most notably, the relationship between IU and striatal volume is observed at a preclinical level, suggesting that the volumetric properties of the striatum reflect the processing of uncertainty per se as it relates to this dimensional personality characteristic. Such a relationship could then potentially contribute to the onset of OCD or GAD, rather than being unique to their pathophysiology. (PsycINFO Database Record

Oral health and human papillomavirus-associated head and neck squamous cell carcinoma.

BACKGROUND: Indicators of poor oral health, including smoking, have been associated with increased risk of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell carcinoma (OPSCC), yet few studies have examined whether this association is modified by human papillomavirus (HPV) status. METHODS: Data from interviews and tumor HPV status from a large population-based case-control study, the Carolina Head and Neck Cancer Study (CHANCE), were used to estimate the association between oral health indicators and smoking among 102 HPV-positive patients and 145 HPV-negative patients with OPSCC and 1396 controls. HPV status was determined by p16INK4a (p16) immunohistochemistry. Unconditional, multinomial logistic regression was used to estimate odds ratios (ORs) for all oral health indictors adjusting for important covariates. RESULTS: Routine dental examinations were associated with a decreased risk of both HPV-negative OPSCC (OR, 0.52; 95% confidence interval [CI], 0.35-0.76) and HPV-positive OPSCC (OR, 0.55; 95% CI, 0.36-.86). Tooth mobility (a proxy for periodontal disease) increased the risk of HPV-negative disease (OR, 1.70; 95% CI, 1.18-2.43) slightly more than the risk for HPV-positive disease (OR, 1.45; 95% CI, 0.95-2.20). Ten or more pack-years of cigarette smoking were strongly associated with an increased risk of HPV-negative OPSCC (OR, 4.26; 95% CI, 2.85-6.37) and were associated less with an increased risk of HPV-positive OPSCC (OR, 1.62; 95% CI, 1.10-2.38). CONCLUSIONS: Although HPV-positive and HPV-negative HNSCC differ significantly with respect to etiology and tumorigenesis, the current findings suggest a similar pattern of association between poor oral health, frequency of dental examinations, and both HPV-positive and HPV-negative OPSCC. Future research is required to elucidate interactions between poor oral health, tobacco use, and HPV in the development of OPSCC. Cancer 2017;71-80. © 2016 American Cancer Society.

The Inverse Relationship between the Microstructural Variability of Amygdala-Prefrontal Pathways and Trait Anxiety Is Moderated by Sex.

Anxiety impacts the quality of everyday life and may facilitate the development of affective disorders, possibly through concurrent alterations in neural circuitry. Findings from multimodal neuroimaging studies suggest that trait-anxious individuals may have a reduced capacity for efficient communication between the amygdala and the ventral prefrontal cortex (vPFC). A diffusion-weighted imaging protocol with 61 directions was used to identify lateral and medial amygdala-vPFC white matter pathways. The structural integrity of both pathways was inversely correlated with self-reported levels of trait anxiety. When this mask from our first dataset was then applied to an independent validation dataset, both pathways again showed a consistent inverse relationship with trait anxiety. Importantly, a moderating effect of sex was found, demonstrating that the observed brain-anxiety relationship was stronger in females. These data reveal a potential neuroanatomical mediator of previously documented functional alterations in amygdala-prefrontal connectivity that is associated with trait anxiety, which might prove informative for future studies of psychopathology.