Altermagnetic lifting of Kramers spin degeneracy.

Lifted Kramers spin degeneracy (LKSD) has been among the central topics of condensed-matter physics since the dawn of the band theory of solids1,2. It underpins established practical applications as well as current frontier research, ranging from magnetic-memory technology3-7 to topological quantum matter8-14. Traditionally, LKSD has been considered to originate from two possible internal symmetry-breaking mechanisms. The first refers to time-reversal symmetry breaking by magnetization of ferromagnets and tends to be strong because of the non-relativistic exchange origin15. The second applies to crystals with broken inversion symmetry and tends to be comparatively weaker, as it originates from the relativistic spin-orbit coupling (SOC)16-19. A recent theory work based on spin-symmetry classification has identified an unconventional magnetic phase, dubbed altermagnetic20,21, that allows for LKSD without net magnetization and inversion-symmetry breaking. Here we provide the confirmation using photoemission spectroscopy and ab initio calculations. We identify two distinct unconventional mechanisms of LKSD generated by the altermagnetic phase of centrosymmetric MnTe with vanishing net magnetization20-23. Our observation of the altermagnetic LKSD can have broad consequences in magnetism. It motivates exploration and exploitation of the unconventional nature of this magnetic phase in an extended family of materials, ranging from insulators and semiconductors to metals and superconductors20,21, that have been either identified recently or perceived for many decades as conventional antiferromagnets21,24,25.

High-energy photoemission final states beyond the free-electron approximation.

Three-dimensional (3D) electronic band structure is fundamental for understanding a vast diversity of physical phenomena in solid-state systems, including topological phases, interlayer interactions in van der Waals materials, dimensionality-driven phase transitions, etc. Interpretation of ARPES data in terms of 3D electron dispersions is commonly based on the free-electron approximation for the photoemission final states. Our soft-X-ray ARPES data on Ag metal reveals, however, that even at high excitation energies the final states can be a way more complex, incorporating several Bloch waves with different out-of-plane momenta. Such multiband final states manifest themselves as a complex structure and added broadening of the spectral peaks from 3D electron states. We analyse the origins of this phenomenon, and trace it to other materials such as Si and GaN. Our findings are essential for accurate determination of the 3D band structure over a wide range of materials and excitation energies in the ARPES experiment.

Five-year cause-specific survival after meningioma surgery. A nationwide population-based study.

BACKGROUND: Survival after meningioma surgery is often reported with inadequate allowance for competing causes of death. METHODS: We processed the French administrative medical database (Système National des Données de Santé: SNDS), to retrieve appropriate cases of surgically treated meningioma. Cause-specific survival in meningioma-related death was analyzed with the Fine & Gray (F&G) and cause-specific (CS) Cox models to identify associated factors. RESULTS: Five-year cumulative incidence was 2.85% for meningioma-related death and 6.3% for unrelated death (P<0.001). In the adjusted F&G and cause-specific Cox regression models for meningioma-related death, gender, age at surgery, co-morbidities, neurofibromatosis type 2, tumor insertion, tumor grade, cerebrospinal fluid (CSF) shunt insertion, preoperative embolization and need for redo surgery for recurrence emerged as independent prognostic factors of cause-specific survival (CSS) in meningioma-related death. CONCLUSION: At 5 years, the risk of meningioma-unrelated death was 2.21-fold greater than the risk of dying from the meningioma disease. Five-year CSS after meningioma surgery was greater in younger adults with benign spinal meningioma with low comorbidity. Those with malignant cranial tumor requiring preoperative embolization or CSF shunting for associated hydrocephalus and with severely degraded overall health status showed a significantly increased risk of meningioma-related death. Redo surgery for recurrence failed to improve the risk of meningioma-related death. We recommend the use of net survival methods such as CSS in meningioma studies where unrelated mortality is predominant, as this approach results in more accurate estimates of disease risk and associated predictors.

Value of a national administrative database to guide public decisions: From the système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France.

In 1999, French legislators asked health insurance funds to develop a système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) [national health insurance information system] in order to more precisely determine and evaluate health care utilization and health care expenditure of beneficiaries. These data, based on almost 66 million inhabitants in 2015, have already been the subject of numerous international publications on various topics: prevalence and incidence of diseases, patient care pathways, health status and health care utilization of specific populations, real-life use of drugs, assessment of adverse effects of drugs or other health care procedures, monitoring of national health insurance expenditure, etc. SNIIRAM comprises individual information on the sociodemographic and medical characteristics of beneficiaries and all hospital care and office medicine reimbursements, coded according to various systems. Access to data is controlled by permissions dependent on the type of data requested or used, their temporality and the researcher's status. In general, data can be analyzed by accredited agencies over a period covering the last three years plus the current year, and specific requests can be submitted to extract data over longer periods. A 1/97th random sample of SNIIRAM, the échantillon généraliste des bénéficiaires (EGB), representative of the national population of health insurance beneficiaries, was composed in 2005 to allow 20-year follow-up with facilitated access for medical research. The EGB is an open cohort, which includes new beneficiaries and newborn infants. SNIIRAM has continued to grow and extend to become, in 2016, the cornerstone of the future système national des données de santé (SNDS) [national health data system], which will gradually integrate new information (causes of death, social and medical data and complementary health insurance). In parallel, the modalities of data access and protection systems have also evolved. This article describes the SNIIRAM data warehouse and its transformation into SNDS, the data collected, the tools developed in order to facilitate data analysis, the limitations encountered, and changing access permissions.

The VCDQ--a Questionnaire for symptom monitoring in vocal cord dysfunction.

BACKGROUND: Vocal cord dysfunction (VCD) typically involves abnormal adduction of the vocal cords during inspiration, mimics the symptoms of asthma and leads to the prescription of ineffective medications. OBJECTIVE: We aimed to develop a clinical tool to monitor symptoms and response to treatment in confirmed VCD. METHODS: We collated symptoms of VCD from focus groups comprising patients and healthcare professionals; phrases describing these symptoms were assessed for face validity and internal correlation and rated for importance. The resultant 12-item questionnaire (VCDQ) rated the impact of each on a 5-point Likert scale (total score range 12-60) and was tested for reliability, concurrent validity and performance in 31 patients with endoscopically confirmed VCD (± asthma), 29 asthmatics with no history of VCD and 14 healthy controls. We assessed response to speech and language therapy and the minimal important difference by measuring the VCDQ pre- and post- therapy in a 20 new patients. RESULTS: The VCDQ had excellent test-retest reliability and differentiated VCD vs. healthy (Mann-Whitney U-test: z = -5.390, P < 0.001) and asthma (z = -5.730, P < 0.001). All patients improved post-therapy, assessed both by a global rating of change score (GRCS) and by the VCDQ [median (IQR) score pre-therapy 50.5 (48.0 - 54.8), post-therapy 35.0 (29.3 - 41.8), P < 0.001]. The minimal important difference in the VCDQ associated with a rating of 'minimally better' on the GRCS was 4 points. CONCLUSIONS AND CLINICAL RELEVANCE: The VCDQ is a valid and responsive tool suitable for measuring changes in symptoms in patients with VCD. It also gives insight into which symptoms are important to patients and could guide future therapy refinements. Future assessments of novel therapies for this condition should use an appropriately validated tool such as the VCDQ to measure response.

A 2D MEMS mirror with sidewall electrodes applied for confocal MACROscope imaging.

This paper presents microelectromechanical system micromirrors with sidewall electrodes applied for use as a Confocal MACROscope for biomedical imaging. The MACROscope is a fluorescence and brightfield confocal laser scanning microscope with a very large field of view. In this paper, a microelectromechanical system mirror with sidewall electrodes replaces the galvo-scanner and XYZ-stage to improve the confocal MACROscope design and obtain an image. Two micromirror-based optical configurations are developed and tested to optimize the optical design through scanning angle, field of view and numerical aperture improvement. Meanwhile, the scanning frequency and control waveform of the micromirror are tested. Analysing the scan frequency and waveform becomes a key factor to optimize the micromirror-based confocal MACROscope. When the micromirror is integrated into the MACROscope and works at 40 Hz, the micromirror with open-loop control possesses good repeatability, so that the synchronization among the scanner, XYZ-stage and image acquisition can be realized. A laser scanning microscope system based on the micromirror with 2 µm width torsion bars was built and a 2D image was obtained as well. This work forms the experimental basis for building a practical confocal MACROscope.

Extending immunofluorescence detection limits in whole paraffin-embedded formalin fixed tissues using hyperspectral confocal fluorescence imaging.

A major problem in microscopic imaging of ex vivo tissue sections stained with fluorescent agents (e.g. antibodies, peptides) is the confounding presence of background tissue autofluorescence. Autofluorescence limits (1) the accuracy of differentiating background signals from single and multiple fluorescence labels and (2) reliable quantification of fluorescent signals. Advanced techniques such as hyperspectral imaging and spectral unmixing can be applied to essentially remove this autofluorescent signal contribution, and this work attempts to quantify the effectiveness of autofluorescence spectral unmixing in a tumour xenograft model. Whole-specimen single-channel fluorescence images were acquired using excitation wavelengths of 488 nm (producing high autofluorescence) and 568 nm (producing negligible autofluorescence). These single-channel data sets are quantified against hyperspectral images acquired at 488 nm using a prototype whole-slide hyperspectral fluorescence scanner developed in our facility. The development and further refinement of this instrument will improve the quantification of weak fluorescent signals in fluorescence microscopy studies of ex vivo tissues in both preclinical and clinical applications.

Imaging of whole tumor cut sections using a novel scanning beam confocal fluorescence MACROscope.

Hypoxia caused by inadequate structure and function of the tumor vasculature has been found to negatively determine the prognosis of cancer patients. Hence, understanding the biological basis of tumor hypoxia is of significant clinical interest. To study solid tumor microenvironments in sufficient detail, large areas (several mm in diameter) need to be imaged at microm resolutions. We have used a novel confocal scanning laser MACROscope (CSLM) capable of acquiring images over fields of view up to 2cm x 2cm. To demonstrate its performance, frozen sections from a cervical carcinoma xenograft were triple labeled for tissue hypoxia, blood vessels and hypoxia-inducible transcription factor 1 alpha (HIF-1alpha), imaged using the CSLM and compared to images obtained using a standard epifluorescence microscope imaging system. The results indicate that the CSLM is a useful instrument for imaging tissue-based fluorescence at resolutions comparable to standard low-power microscope objectives.

Molecular structure and activity toward DNA of baicalein, a flavone constituent of the Asian herbal medicine "Sho-saiko-to".

Baicalein (5,6,7-trihydroxyflavone, 1) is of interest because of its broad spectrum of biological activity. It is a constituent of the east Asian herbal remedy, "Sho-saiko-to". The 3D structure of 1 was determined using X-ray diffraction. The compound exists in an almost planar conformation with a C-2-C-1' bond distance of 1.476(5) A. Hydrogen-bonding interactions predominate in the crystal structure. The position of the three hydroxyl groups maximizes intramolecular hydrogen bonding, and each of the hydroxyl hydrogen atoms is a donor in a three-center hydrogen bond. The carbonyl oxygen, O-4, is an acceptor in an intramolecular hydrogen bond (with OH-5). Two molecules of 1 exist as hydrogen-bonded dimers related by inversion center (-x + 1, -y, -z + 1). O-4 is also an acceptor in an intermolecular hydrogen bond with OH-6. The planarity of the flavone framework is dependent on structural and/or electronic forces that stabilize the negative charge on the exocyclic oxygen atom, O-4. Compound 1, therefore, is planar in any situation where forces can stabilize the negative charge on O-4. Consistent with this, UV absorbance studies performed on 1-DNA complexes with varying concentrations of 1 strongly suggest intercalation of 1 within the double helix, followed by possible interstrand cross-links.

Evaluation of a computer-mediated eating disorder intervention program.

OBJECTIVE: This study evaluated an eating disorder intervention multimedia program modeled after self-help eating disorder treatment programs. It was hypothesized that women who completed the program would increase their body satisfaction and decrease their preoccupation with weight and frequency of disordered eating behaviors. METHOD: Participants were 57 undergraduate females randomly assigned to either the intervention or control group. Psychological functioning was assessed at baseline, at 3 months postintervention, and at 3 months follow-up. RESULTS: Intervention group subjects significantly improved their scores on all psychological measures over time. When compared to the control group, however, only the intervention group's improvements on the Body Shape Questionnaire were statistically significant. DISCUSSION: This study has demonstrated that minimally effective eating disorder intervention programs can be delivered. A revised program that eliminates interface problems and increases the structure of the intervention is likely to be even better received and more effective.

Low risk for tuberculosis in a regional pediatric hospital: nine-year study of community rates and the mandatory employee tuberculin skin-test program.

OBJECTIVE: To assess the risk of Mycobacterium tuberculosis infection and disease among patients and workers in a regional pediatric hospital. DESIGN: Descriptive epidemiological study of the mandatory tuberculin skin testing program of hospital employees at hire and during annual reevaluation, pediatric patients with tuberculosis (TB), efficacy of hospital infection control measures, and community rates of TB. SETTING: 361-bed, university, pediatric hospital serving Cincinnati (1.7 million population). RESULTS: During 1986 through 1994, 2,275 to 4,356 employees were compliant with Mantoux skin testing and screening each year. This represented >97% of the population who were eligible for screening. The cumulative rate of M tuberculosis infection from a previous positive tuberculin skin test was 10% to 12% per year during 1986 through 1994. Among new Mantoux skin-test converters in employees at annual reevaluation, the risk of TB infection was 0.3% in 1993 and 1994. There were no active cases of TB identified during new employee screening or annual reevaluation. Of 62 new Mantoux skin-test converters in 9 years, 23% were foreign-born, 13% were Asian, 23% were African American, 11% received the bacillus of Calmette-Guérin vaccine, and 60% had direct patient care or indirect patient contact. A cluster of five converters occurred in a department with no patient care or contact. Mantoux conversion rates were 1.9 per 1,000 employee patient-care or contact-years and 2.2 per 1,000 employee non-patient-contact years. Twenty pediatric patients with active TB were identified during 1991 to 1994, with < or =6 cases per year, placing this hospital in the low-risk category for M tuberculosis disease. Three children with pulmonary TB were admitted without immediate respiratory isolation, possibly exposing 9 patients and 42 employees; none converted their Mantoux skin tests on retesting. Rates of active TB in Cincinnati were stable during the period (eg, 8/100,000 population in 1994). CONCLUSIONS: Despite intense active surveillance among thousands of hospital employees with >97% annual compliance, tuberculin conversion rates were low, and no cases of active TB were identified during 9 years of follow-up. There was no evidence of transmission of M tuberculosis from infected patients to employees during uncontrolled exposures. Rates of TB in the community were low. These data suggest that rigorous application of the Centers for Disease Control and Prevention guidelines and Occupation Safety and Health Administration regulations for preventing nosocomial TB in pediatric hospitals may be excessive and costly. Special provisions should be made for pediatric hospitals with a proven low risk of transmission of M tuberculosis.

The interactive image tool: adding structure to images.

The interactive image format and tool were developed by the Stanford University Medical Media and Information Technologies (SUMMIT) group to allow medical educators to add interactive annotations and outlines to medical cross-sections, gross dissections, and clinical images. The interactive image tool (IIT) format offers a general specification for adding structural information to images. The IIT format has been used to create rich databases of image/structure information which are employed in educational software created at SUMMIT. These databases consist of information which is re-usable in other applications as well as a standalone image database. Future extensions to the IIT format will provide a means to organize information based on the structure of that information rather than on the arbitrary or haphazard links of current hypertext and hypermedia information networks.

Transforming information for computer-aided instruction: using a Socratic Dialogue method to teach gross anatomy.

Traditional teaching of anatomy can be a difficult process of rote memorization. Computers allow information presentation to be much more dynamic, and interactive; the same information can be presented in multiple organizations. Using this idea, we have implemented a new pedagogy for computer-assisted instruction in The Anatomy Lesson, an interactive digital teacher which uses a "Socratic Dialogue" metaphor, as well as a textbook-like approach, to facilitate conceptual learning in anatomy.