Cellular density and variability in laryngeal and pharyngeal squamous cell carcinoma using confocal laser endomicroscopy.

OBJECTIVE: Confocal laser endomicroscopy (CLE) allows the visualization of epithelium in a thousand-fold magnification. This study analyzes the architectural differences at the cellular level of the mucosa and squamous cell carcinoma (SCC). PATIENTS AND METHODS: A total of 60 CLE sequences recorded in 5 patients with SCC undergoing laryngectomy between October 2020 and February 2021 were analyzed. The corresponding histologic sample derived from H&E staining was assigned to each sequence, capturing CLE images of the tumor and healthy mucosa. In addition, the cellular structure analysis was performed to diagnose SCC by measuring the total number of cells and cell size in 60 sequences in a fixed field of view (FOV) with 240 µm in diameter (45,239 µm2). RESULTS: Out of 3,600 images, 1,620 (45%) showed benign mucosa and 1,980 (55%) SCC. The automated analysis yielded a difference in cell size, with healthy epithelial cells being 171.9±82.0 µm2 smaller than SCC cells, which were 246.3±171.9 µm2 and showed greater variability in size (p=0.037). In addition, due to the probe's fixed FOV, there was a difference in cell count with a total of 188.7±38.3 and 124.8±38.6 cells in images of normal epithelium and SCC (p<0.001), respectively. Regarding cell density as a criterion for the differentiation of benign/malign, using a cut-off value of 145.5 cells/FOV, we obtained sensitivity and specificity of 88.0% and 71.9%, respectively. CONCLUSIONS: SCC reveals marked differences at a cellular level compared to the healthy epithelium. Our results further support the importance of this feature for identifying SCC during CLE imaging.

F18-FDG PET/CT imaging early predicts pathologic complete response to induction chemoimmunotherapy of locally advanced head and neck cancer: preliminary single-center analysis of the checkrad-cd8 trial.

AIM: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. METHODS: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3-14 days before (pre-ICIT) and 21-28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). RESULTS: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. CONCLUSION: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT03426657.

The COVID-19 pandemic and its consequences for the diagnosis and therapy of head and neck malignancies.

OBJECTIVE: The COVID-19 pandemic and the measures accompanying it have been accused of having a negative influence on the frequency and methods of treatment of various diseases including head and neck cancer (HNSCC). To go further into this assumption, the diagnoses made, and treatments performed at one of Germany's largest head and neck cancer centres were evaluated. PATIENTS AND METHODS: This study consisted of one single centre and involved a retrospective review of all patients with newly diagnosed or recurrent HNSCC. The diagnosis and treatment methods used in the pre-COVID-19 time period between March 1st, 2019, and March 1st, 2020, were analysed and compared with the COVID-19 time period from April 1st, 2020, until April 1st, 2021. The primary objective was defined as the number of malignant diagnoses and the secondary objectives as the disease stage and the time to therapy. RESULTS: A total of 612 patients (160♀; mean 63 yrs.) were included. 319 patients (52%) were treated in the pre-COVID-19 time. The two groups did not differ in terms of age (p=0.304), gender (p=0.941), presence of recurrent disease (p=0.866), tumour subsite (p=0.194) or the duration from presentation to the multidisciplinary tumour board until start of therapy (p=0.202). There were no significant differences in the T stage (p=0.777), N stage (p=0.067) or UICC stage (p=0.922). During the pre-COVID-19 period more patients presented with distant metastases (n= 23 vs. n=8; p=0.011). CONCLUSIONS: This study shows that there was no significant change in either the number and severity of HNSCC diagnoses or the time until start of therapy at this large head and neck cancer centre as a result of the COVID-19 pandemic.

Neoadjuvant concurrent chemoradiotherapy with and without hyperthermia in retroperitoneal sarcomas: feasibility, efficacy, toxicity, and long-term outcome.

PURPOSE: Retroperitoneal (RPS) sarcomas are associated with poor local and abdominal tumor control. However, the benefit of preoperative radio- or chemotherapy alone for these entities is currently unclear. Moreover, as intermediate- and high-grade sarcomas have a tendency toward early metastasis, exploration of neoadjuvant strategies is of high importance. This analysis reports the results of our 20-year single-institution experience with preoperative neoadjuvant concurrent chemoradiation. METHODS: From 2000-2019, 27 patients with intermediate- or high-grade RPS (12 dedifferentiated liposarcoma, 10 leiomyosarcoma, 5 others) were treated with radiotherapy (median dose: 50.4 Gy; range 45-75 Gy) and two cycles of chemotherapy (doxorubicin 50 mg/m2 BSA/d3 q28 and ifosfamide 1.5 g/m2 BSA/d1­5 q28) in neoadjuvant intent. Chemotherapy consisted of doxorubicin alone in two cases and ifosfamide alone in one case. Fifteen patients (56%) additionally received deep regional hyperthermia. RESULTS: The median follow-up time was 53 months (±56.7 months). 92% of patients received two cycles of chemotherapy as planned and 92% underwent surgery. At 5 and 10 years, abdominal-recurrence-free survival was 74.6% (±10.1%) and 66.3% (±11.9%), distant metastasis-free survival was 67.2% (±9.7%) and 59.7% (±11.1%), and overall survival was 60.3% (±10.5%) and 60.3% (±10.5%), respectively. CTC grade III and IV toxicities were leukocytopenia (85%), thrombocytopenia (33%), and anemia (11%). There were no treatment-related deaths. CONCLUSION: Neoadjuvant chemoradiotherapy with and without hyperthermia for retroperitoneal sarcomas is feasible and provided high local control of intermediate- and high-grade sarcoma.

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer.

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.

Deep learning for diagnosis and survival prediction in soft tissue sarcoma.

BACKGROUND: Clinical management of soft tissue sarcoma (STS) is particularly challenging. Here, we used digital pathology and deep learning (DL) for diagnosis and prognosis prediction of STS. PATIENTS AND METHODS: Our retrospective, multicenter study included a total of 506 histopathological slides from 291 patients with STS. The Cancer Genome Atlas cohort (240 patients) served as training and validation set. A second, multicenter cohort (51 patients) served as an additional test set. The use of the DL model (DLM) as a clinical decision support system was evaluated by nine pathologists with different levels of expertise. For prognosis prediction, 139 slides from 85 patients with leiomyosarcoma (LMS) were used. Area under the receiver operating characteristic (AUROC) and accuracy served as main outcome measures. RESULTS: The DLM achieved a mean AUROC of 0.97 (±0.01) and an accuracy of 79.9% (±6.1%) in diagnosing the five most common STS subtypes. The DLM significantly improved the accuracy of the pathologists from 46.3% (±15.5%) to 87.1% (±11.1%). Furthermore, they were significantly faster and more certain in their diagnosis. In LMS, the mean AUROC in predicting the disease-specific survival status was 0.91 (±0.1) and the accuracy was 88.9% (±9.9%). Cox regression showed the DLM's prediction to be a significant independent prognostic factor (P = 0.008, hazard ratio 5.5, 95% confidence interval 1.56-19.7) in these patients, outperforming other risk factors. CONCLUSIONS: DL can be used to accurately diagnose frequent subtypes of STS from conventional histopathological slides. It might be used for prognosis prediction in LMS, the most prevalent STS subtype in our cohort. It can also help pathologists to make faster and more accurate diagnoses. This could substantially improve the clinical management of STS patients.

Feasibility of sentinel lymph node detection by near-infrared endoscopy in squamous cell carcinoma of the oral cavity: a pilot study.

OBJECTIVE: Near-Infrared (NIR) fluorescence imaging is a novel technique for intraoperative sentinel lymph node (SLN) identification. It has demonstrated promising results in several surgical specialties. The study aims to evaluate the feasibility of identifying the SLN by indocyanine green (ICG) enhanced NIR endoscopy in squamous cell carcinoma of the oral cavity (OCSCC). PATIENTS AND METHODS: Seven patients with (cT1-3 N0) OCSCC were included. We injected 1-1.25 ml of ICG (5 mg/ml) at four to five points around the primary. After the elevation of a platysma flap and posterior retraction of the sternocleidomastoid muscle, fluorescence images were taken via IMAGE1 STM NIR/ICG system to define the SLN(s). We sampled fluorescence marked SLN(s) stratified to lymph node levels, followed by level-specified elective neck dissection. RESULTS: The detection of at least one unilateral or bilateral SLN (range 1-5) was possible in every case. The fluorescence signal occurred, on average, 5.0 ± 2.2 minutes after injection. A total of 22 SLN could be identified. Among 331 histologically examined lymph nodes we could detect one micrometastasis, which was correctly defined as SLN (1/22). There were no false-negative findings. No adverse reactions to ICG occurred. CONCLUSIONS: Our first results are indicating the concept of SLN concerning OCSCC after the application of real-time NIR fluorescence endoscopy. However, this has to be verified by more extended studies.

People with type 1 diabetes and impaired awareness of hypoglycaemia have a delayed reaction to performing a glucose scan during hypoglycaemia: a prospective observational study.

AIMS: Considering that people with type 1 diabetes and impaired awareness of hypoglycaemia (IAH) have a delayed perception of hypoglycaemia, the question arises whether they perform scans later in case of hypoglycaemia than people without IAH. We assessed whether time to performing a scan after reaching hypoglycaemia while using a flash glucose monitoring (flash GM) system is different in people with IAH compared with people without IAH. METHODS: Ninety-two people with type 1 diabetes [mean (± sd) age 42 ± 14 years, HbA1c 57 ± 9 mmol/mol] using a flash GM system for 3 months were included. Flash GM data were assessed for time until scan after reaching hypoglycaemia level 1 (< 3.9 mmol/l) and level 2 (< 3.0 mmol/l) and compared for type 1 diabetes with vs. without IAH via unpaired t-test/Mann-Whitney U test (P < 0.05). RESULTS: Significant differences were found only for the delay between reaching hypoglycaemia and scan between people with and without IAH for Gold score [hypoglycaemia level 1: IAH 78 (51-105) min vs. without IAH 63 (42-89) min, P = 0.03; night-time hypoglycaemia level 2: IAH 140 (107-227) min vs. without IAH 96 (41-155) min, P = 0.004] and Pedersen-Bjergaard score [hypoglycaemia level 1: IAH 76 (52-97) min vs. without IAH 54 (38-71) min, P = 0.011; night-time hypoglycaemia level 1: IAH 132 (79-209) min vs. without IAH 89 (59-143) min, P = 0.011; night-time hypoglycaemia level 2: IAH 134 (66-212) min vs. without IAH 80 (37-131) min, P = 0.002). Data are shown as median (i.q.r.). CONCLUSIONS: Time until scan after reaching hypoglycaemia might be an objective assessment tool for IAH, but needs to be investigated comprehensively in future studies.

Erratum: Ultrafast Doublon Dynamics in Photoexcited 1T-TaS_{2} [Phys. Rev. Lett. 120, 166401 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.120.166401.

Impact of physical exercise on sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system in people with Type 1 diabetes: a randomized crossover trial.

AIMS: To evaluate the sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system using reference blood glucose levels during moderate-intensity exercise while on either full or reduced basal insulin dose in people with Type 1 diabetes. METHODS: Ten participants with Type 1 diabetes [four women, mean ± sd age 31.4 ± 9.0 years, BMI 25.5±3.8 kg/m2 , HbA1c 55±7 mmol/mol (7.2±0.6%)] exercised on a cycle ergometer for 55 min at a moderate intensity for 5 consecutive days at the clinical research facility, while receiving either their usual or a 75% basal insulin dose. After a 4-week washout period, participants performed the second exercise period having switched to the alternative basal insulin dose. During exercise, reference capillary blood glucose values were analysed using the fully enzymatic-amperometric method and compared with the interstitial glucose values obtained. Intermittently viewed continuous glucose monitoring accuracy was analysed according to median (interquartile range) absolute relative difference, and Clarke error grid and Bland-Altman analysis for overall glucose levels during exercise, stratified by glycaemic range and basal insulin dosing scheme (P<0.05). RESULTS: A total of 845 glucose values were available during exercise to evaluate intermittently viewed continuous glucose monitoring sensor performance. The median (interquartile range) absolute relative difference between the reference values and those obtained by the sensor across the glycaemic range overall was 22 (13.9-29.7)%, and was 36.3 (24.2-45.2)% during hypoglycaemia, 22.8 (14.6-30.6)% during euglycaemia and 15.4 (9-21)% during hyperglycaemia. Usual basal insulin dose was associated with a worse sensor performance during exercise compared with the reduced (75%) basal insulin dose [median (interquartile range) absolute relative difference: 23.7 (17.2-30.7)% vs 20.5 (12-28.1)%; P<0.001). CONCLUSIONS: The intermittently viewed continuous glucose monitoring sensor showed diminished accuracy during exercise. Absolute glucose readings derived from the sensor should be used cautiously and need confirmation by additional finger-prick blood glucose measurements.

Physical exercise and non-insulin glucose-lowering therapies in the management of Type 2 diabetes mellitus: a clinical review.

In the UK the National Institute of Health and Care Excellence (NICE) advocates intensive lifestyle programmes that attain the levels of daily physical activity set out by the Chief Medical Officer as a first-line strategy for improving the health of people at risk of developing diabetes or reducing the risk of development of Type 2 diabetes. For people with Type 2 diabetes, lifestyle measures complement pharmacological treatments that include both oral and injectable therapies. In line with this, NICE guidelines also support intensification of efforts to improve patient lifestyle along with these glucose-lowering therapies. There is a paucity of evidence, however, in the available published literature examining the association between glucose-lowering therapies and exercise metabolism. In the present review we explore the current knowledge with regard to the potential interactions of oral and non-insulin injectable therapies with physical activity in people at risk of, or who have, Type 2 diabetes, and present evidence that may inform healthcare professionals of the need to monitor patients more closely in their adaptation to both pharmacological therapy and physical activity.

CRAC channels in dental enamel cells.

Enamel mineralization relies on Ca2+ availability provided by Ca2+ release activated Ca2+ (CRAC) channels. CRAC channels are modulated by the endoplasmic reticulum Ca2+ sensor STIM1 which gates the pore subunit of the channel known as ORAI1, found the in plasma membrane, to enable sustained Ca2+ influx. Mutations in the STIM1 and ORAI1 genes result in CRAC channelopathy, an ensemble of diseases including immunodeficiency, muscular hypotonia, ectodermal dysplasia with defects in sweat gland function and abnormal enamel mineralization similar to amelogenesis imperfecta (AI). In some reports, the chief medical complain has been the patient's dental health, highlighting the direct and important link between CRAC channels and enamel. The reported enamel defects are apparent in both the deciduous and in permanent teeth and often require extensive dental treatment to provide the patient with a functional dentition. Among the dental phenotypes observed in the patients, discoloration, increased wear, hypoplasias (thinning of enamel) and chipping has been reported. These findings are not universal in all patients. Here we review the mutations in STIM1 and ORAI1 causing AI-like phenotype, and evaluate the enamel defects in CRAC channel deficient mice. We also provide a brief overview of the role of CRAC channels in other mineralizing systems such as dentine and bone.

Ultrafast Doublon Dynamics in Photoexcited 1T-TaS_{2}.

Strongly correlated materials exhibit intriguing properties caused by intertwined microscopic interactions that are hard to disentangle in equilibrium. Employing nonequilibrium time-resolved photoemission spectroscopy on the quasi-two-dimensional transition-metal dichalcogenide 1T-TaS_{2}, we identify a spectroscopic signature of doubly occupied sites (doublons) that reflects fundamental Mott physics. Doublon-hole recombination is estimated to occur on timescales of electronic hopping ℏ/J≈14 fs. Despite strong electron-phonon coupling, the dynamics can be explained by purely electronic effects captured by the single-band Hubbard model under the assumption of weak hole doping, in agreement with our static sample characterization. This sensitive interplay of static doping and vicinity to the metal-insulator transition suggests a way to modify doublon relaxation on the few-femtosecond timescale.

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer.

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n=57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P=0.0009) and ESR1 (P=0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR=2.11, CI 1.11-4.21, P=0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P=0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR=4.41, CI 1.53-18.71, P=0.004) and Luminal B (HR=1.96, CI 0.99-4.08, P=0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

Ultrafast optical modification of exchange interactions in iron oxides.

Ultrafast non-thermal manipulation of magnetization by light relies on either indirect coupling of the electric field component of the light with spins via spin-orbit interaction or direct coupling between the magnetic field component and spins. Here we propose a scenario for coupling between the electric field of light and spins via optical modification of the exchange interaction, one of the strongest quantum effects with strength of 10(3) Tesla. We demonstrate that this isotropic opto-magnetic effect, which can be called inverse magneto-refraction, is allowed in a material of any symmetry. Its existence is corroborated by the experimental observation of terahertz emission by spin resonances optically excited in a broad class of iron oxides with a canted spin configuration. From its strength we estimate that a sub-picosecond modification of the exchange interaction by laser pulses with fluence of about 1 mJ cm(-2) acts as a pulsed effective magnetic field of 0.01 Tesla.

Store-operated Ca2+ Entry Modulates the Expression of Enamel Genes.

Dental enamel formation is an intricate process tightly regulated by ameloblast cells. The correct spatiotemporal patterning of enamel matrix protein (EMP) expression is fundamental to orchestrate the formation of enamel crystals, which depend on a robust supply of Ca2+. In the extracellular milieu, Ca2+ -EMP interactions occur at different levels. Despite its recognized role in enamel development, the molecular machinery involved in Ca2+ homeostasis in ameloblasts remains poorly understood. A common mechanism for Ca2+ influx is store-operated Ca2+ entry (SOCE). We evaluated the possibility that Ca2+ influx in enamel cells might be mediated by SOCE and the Ca2+ release-activated Ca2+ (CRAC) channel, the prototypical SOCE channel. Using ameloblast-like LS8 cells, we demonstrate that these cells express Ca2+ -handling molecules and mediate Ca2+ influx through SOCE. As a rise in the cytosolic Ca2+ concentration is a versatile signal that can modulate gene expression, we assessed whether SOCE in enamel cells had any effect on the expression of EMPs. Our results demonstrate that stimulating LS8 cells or murine primary enamel organ cells with thapsigargin to activate SOCE leads to increased expression of Amelx, Ambn, Enam, Mmp20. This effect is reversed when cells are treated with a CRAC channel inhibitor. These data indicate that Ca2+ influx in LS8 cells and enamel organ cells is mediated by CRAC channels and that Ca2+ signals enhance the expression of EMPs. Ca2+ plays an important role not only in mineralizing dental enamel but also in regulating the expression of EMPs.

Ultrafast and reversible control of the exchange interaction in Mott insulators.

The strongest interaction between microscopic spins in magnetic materials is the exchange interaction Jex. Therefore, ultrafast control of Jex holds the promise to control spins on ultimately fast timescales. We demonstrate that time-periodic modulation of the electronic structure by electric fields can be used to reversibly control Jex on ultrafast timescales in extended antiferromagnetic Mott insulators. In the regime of weak driving strength, we find that Jex can be enhanced and reduced for frequencies below and above the Mott gap, respectively. Moreover, for strong driving strength, even the sign of Jex can be reversed and we show that this causes time reversal of the associated quantum spin dynamics. These results suggest wide applications, not only to control magnetism in condensed matter systems, for example, via the excitation of spin resonances, but also to assess fundamental questions concerning the reversibility of the quantum many-body dynamics in cold atom systems.

The effects of an overnight holding of whole blood at room temperature on haemoglobin modification and in vitro markers of red blood cell aging.

BACKGROUND: Some effects of the red blood cell (RBC) storage lesion are well documented whereas others are not. Whether a period of room temperature hold (RTH) during RBC production enhances the RBC storage lesion has remained controversial. In this study, we compared whole blood (WB)-derived RBCs produced after 24-h RTH with rapidly cooled (RC) RBCs and tested them for classical metabolic markers and signs of oxidative damage. STUDY DESIGN AND METHODS: SAGM-RBCs were prepared from mixed and split pairs (n = 12) of WB units. RBCs prepared after a 24-h period of RTH on day+1 after collection (RTH-RBCs) were compared with RC-RBCs. All RBCs were stored at 4°C for 42 days with assay of in vitro variables on days+1, +15, +22, +29 and +42. The study examined standard quality parameters, glutathione, catalase and superoxide dismutase (SOD) activities, and indicative markers of oxidative cell damage including post-translational haemoglobin modification, malondialdehyde (MDA), and phosphatidylserine expression. RESULTS: RTH-RBCs exhibited decreased levels of potassium (1·98 ± 0·26 vs. 5·23 ± 0·65 mmol/l) and of 2,3-diphosphoglycerate (2,3-DPG) on day+1 compared with RC-RBCs. Haemolysis rate on day+42 was higher in RTH-RBCs than in RC-RBCs (0·52 ± 0·13 vs. 0·37 ± 0·12%). The phosphatidylserine expression amounted to 0·25 ± 0·20% in RTH-RBCs and 0·07 ± 0·12% in RC-RBCs. Haemoglobin modification was not different between both RBC groups. RTH-RBCs showed slightly higher MDA concentration on days +29 and +42. CONCLUSIONS: RC-RBCs and RTH-RBCs show only small differences of classical in vitro parameters and no relevant differences in antioxidative metabolism and oxidative haemoglobin modification. These findings do not explain the loss observed in in vivo survival studies with RBCs.

Ultrafast quenching of the exchange interaction in a Mott insulator.

We investigate how fast and how effective photocarrier excitation can modify the exchange interaction J_{ex} in the prototype Mott-Hubbard insulator. We demonstrate an ultrafast quenching of J_{ex} both by evaluating exchange integrals from a time-dependent response formalism and by explicitly simulating laser-induced spin precession in an antiferromagnet that is canted by an external magnetic field. In both cases, the electron dynamics is obtained from nonequilibrium dynamical mean-field theory. We find that the modified J_{ex} emerges already within a few electron hopping times after the pulse, with a reduction that is comparable to the effect of chemical doping.