RESUMEN
BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.
Asunto(s)
Neoplasias de la Mama , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Quimioterapia Adyuvante/métodos , Anciano , Adulto , Ganglios Linfáticos/patología , Anciano de 80 o más AñosRESUMEN
The present study examined and compared the impact of exercise training on redox and molecular properties of human microvascular endothelial cells derived from skeletal muscle biopsies from sedentary recent (RPF, ≤ 5 years as postmenopausal) and late (LPF, ≥ 10 years as postmenopausal) postmenopausal females. Resting skeletal muscle biopsies were obtained before and after 8 weeks of intense aerobic exercise training for isolation of microvascular endothelial cells and determination of skeletal muscle angiogenic proteins and capillarisation. The microvascular endothelial cells were analysed for mitochondrial respiration and production of reactive oxygen species (ROS), glycolysis and proteins related to vascular function, redox balance and oestrogen receptors. Exercise training led to a reduced endothelial cell ROS formation (â¼50%; P = 0.009 and P = 0.020 for intact and permeabilized cells (state 3), respectively) in RPF only, with no effect on endothelial mitochondrial capacity in either group. Basal endothelial cell lactate formation was higher (7%; P = 0.028), indicating increased glycolysis, after compared to before the exercise training period in RPF only. Baseline endothelial G protein-coupled oestrogen receptor (P = 0.028) and muscle capillarisation (P = 0.028) was lower in LPF than in RPF. Muscle vascular endothelial growth factor protein was higher (32%; P = 0.002) following exercise training in LPF only. Exercise training did not influence endothelial cell proliferation or skeletal muscle capillarisation in either group, but the CD31 level in the muscle tissue, indicating endothelial cell content, was higher (>50%; P < 0.05) in both groups. In conclusion, 8 weeks of intense aerobic exercise training reduces ROS formation and enhances glycolysis in microvascular endothelial cells from RPF but does not induce skeletal muscle angiogenesis. KEY POINTS: Late postmenopausal females have been reported to achieve limited vascular adaptations to exercise training. There is a paucity of data on the effect of exercise training on isolated skeletal muscle microvascular endothelial cells (MMECs). In this study the formation of reactive oxygen species in MMECs was reduced and glycolysis increased after 8 weeks of aerobic exercise training in recent but not late postmenopausal females. Late postmenopausal females had lower levels of G protein-coupled oestrogen receptor in MMECs and lower skeletal muscle capillary density at baseline. Eight weeks of intense exercise training altered MMEC properties but did not induce skeletal muscle angiogenesis in postmenopausal females.
Asunto(s)
Células Endoteliales , Ejercicio Físico , Músculo Esquelético , Posmenopausia , Especies Reactivas de Oxígeno , Humanos , Femenino , Posmenopausia/fisiología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/fisiología , Músculo Esquelético/metabolismo , Células Endoteliales/fisiología , Células Endoteliales/metabolismo , Ejercicio Físico/fisiología , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Microvasos/fisiología , Microvasos/citología , Glucólisis/fisiología , Anciano , Receptores de Estrógenos/metabolismoRESUMEN
AIM: We aimed to study sex differences in long-term survival following out-of-hospital cardiac arrest (OHCA) compared to the general population, and determined associations for comorbidities, social characteristics, and resuscitation characteristics with survival in women and men separately. METHODS: We followed 2,452 Danish (530 women and 1,922 men) and 1,255 Dutch (259 women and 996 men) individuals aged ≥25 years, who survived 30 days post-OHCA in 2009-2015, until 2019. Using Poisson regression analyses we assessed sex differences in long-term survival and sex-specific associations of characteristics mutually adjusted, and compared survival with an age- and sex-matched general population. The potential predictive value was assessed with the Concordance-index. RESULTS: Post-OHCA survival was longer in women than men (adjusted incidence rate ratio (IRR) for mortality 0.74, 95%CI 0.61-0.89 in Denmark; 0.86, 95%CI 0.65-1.15 in the Netherlands). Both sexes had a shorter survival than the general population (e.g., IRR for mortality 3.07, 95%CI 2.55-3.70 and IRR 2.15, 95%CI 1.95-2.37 in Danish women and men). Higher age, glucose lowering medication, no dyslipidaemia medication, unemployment, and a non-shockable initial rhythm were associated with shorter survival in both sexes. Cardiovascular medication, depression/anxiety medication, living alone, low household income, and residential OHCA location were associated with shorter survival in men. Not living with children and bystander cardiopulmonary resuscitation provision were associated with shorter survival in women. The Concordance-indexes ranged from 0.51 to 0.63. CONCLUSIONS: Women survived longer than men post-OHCA. Several characteristics were associated with long-term post-OHCA survival, with some sex-specific characteristics. In both sexes, these characteristics had low predictive potential.
Asunto(s)
Reanimación Cardiopulmonar , Comorbilidad , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/mortalidad , Masculino , Femenino , Dinamarca/epidemiología , Persona de Mediana Edad , Países Bajos/epidemiología , Anciano , Reanimación Cardiopulmonar/estadística & datos numéricos , Reanimación Cardiopulmonar/métodos , Factores Sexuales , Adulto , Sistema de Registros , Tasa de Supervivencia/tendenciasRESUMEN
BACKGROUND: Bleeding in the pelvis can lead to a circulatory problem. The widely used whole-body computed tomography (WBCT) scan in the context of treatment in the trauma resuscitation unit (TRU) can give an idea of the source of bleeding (arterial vs. venous/osseous); however, the volume determination of an intrapelvic hematoma by volumetric planimetry cannot be used for a quick estimation of the blood loss. Simplified measurement techniques using geometric models should be used to estimate the extent of bleeding complications. OBJECTIVE: To determine whether simplified geometric models can be used to quickly and reliably determine intrapelvic hematoma volume in fractures type Tile B/C during emergency room diagnostics or whether the time-consuming planimetric method must always be used. MATERIAL AND METHODS: Retrospectively, 42 intrapelvic hemorrhages after pelvic fractures Tile Bâ¯+ C (nâ¯= 8:B, 34:C) at two trauma centers in Germany were selected (66% men, 33% women; mean age 42⯱ 20â¯years) and the CT scans obtained during the initial trauma scan were analyzed in more detail. The CT datasets of the included patients with 1-5â¯mm slice thickness were available for analysis. By area labelling (ROIs) of the hemorrhage areas in the individual slice images, the volume was calculated by CT volumetrically. Comparatively, volumes were calculated using simplified geometric figures (cuboid, ellipsoid, Kothari). A correction factor was determined by calculating the deviation of the volumes of the geometric models from the planimetrically determined hematoma size. RESULTS AND DISCUSSION: The median planimetric bleeding volume in the total collective was 1710â¯ml (10-7152â¯ml). Relevant pelvic bleeding with a total volume >â¯100â¯ml existed in 25 patients. In 42.86% the volume was overestimated in the cuboid model and in 13 cases (30.95%) there was a significant underestimation to the planimetrically measured volume. Thus, we excluded this volume model. In the models ellipsoid and measuring method according to Kothari, an approximation to the planimetrically determined volume could be achieved with a correction factor calculated via a multiple linear regression analysis. The time-saving and approximate quantification of the hematoma volume using a modified ellipsoidal calculation according to Kothari makes it possible to assess the extent of bleeding in the pelvis after trauma if there are signs of a C-problem. This measurement method, as a simple reproducible metric, could be embedded in trauma resuscitation units (TRU) in the future.
Asunto(s)
Fracturas Óseas , Hematoma , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Hematoma/diagnóstico , Hemorragia/diagnóstico , Fracturas Óseas/complicaciones , Tomografía Computarizada por Rayos X/efectos adversos , Centros TraumatológicosRESUMEN
The coherent dynamics of a quantum mechanical two-level system passing through an anti-crossing of two energy levels can give rise to Landau-Zener-Stückelberg-Majorana (LZSM) interference. LZSM interference spectroscopy has proven to be a fruitful tool to investigate charge noise and charge decoherence in semiconductor quantum dots (QDs). Recently, bilayer graphene has developed as a promising platform to host highly tunable QDs potentially useful for hosting spin and valley qubits. So far, in this system no coherent oscillations have been observed and little is known about charge noise in this material. Here, we report coherent charge oscillations and [Formula: see text] charge decoherence times in a bilayer graphene double QD. The charge decoherence times are measured independently using LZSM interference and photon assisted tunneling. Both techniques yield [Formula: see text] average values in the range of 400-500 ps. The observation of charge coherence allows to study the origin and spectral distribution of charge noise in future experiments.
RESUMEN
Particle-hole symmetry plays an important role in the characterization of topological phases in solid-state systems1. It is found, for example, in free-fermion systems at half filling and it is closely related to the notion of antiparticles in relativistic field theories2. In the low-energy limit, graphene is a prime example of a gapless particle-hole symmetric system described by an effective Dirac equation3,4 in which topological phases can be understood by studying ways to open a gap by preserving (or breaking) symmetries5,6. An important example is the intrinsic Kane-Mele spin-orbit gap of graphene, which leads to a lifting of the spin-valley degeneracy and renders graphene a topological insulator in a quantum spin Hall phase7 while preserving particle-hole symmetry. Here we show that bilayer graphene allows the realization of electron-hole double quantum dots that exhibit near-perfect particle-hole symmetry, in which transport occurs via the creation and annihilation of single electron-hole pairs with opposite quantum numbers. Moreover, we show that particle-hole symmetric spin and valley textures lead to a protected single-particle spin-valley blockade. The latter will allow robust spin-to-charge and valley-to-charge conversion, which are essential for the operation of spin and valley qubits.
RESUMEN
AIMS: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression. METHODS: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained). RESULTS: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28). CONCLUSIONS: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Estudios de Cohortes , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Humanos , Tamizaje Masivo , Modelos de Riesgos ProporcionalesRESUMEN
INTRODUCTION: Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. OBJECTIVES: To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years. METHODS: In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010-2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 924) and/or at age 18 months (n = 511) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. RESULTS: Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of prenatal or 18-month exposure to PFDA, BMD Z-scores were lowered by -0.07 (95 % CI -0.10; -0.03) and -0.14 (-0.25; -0.03), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. DISCUSSION: Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.
Asunto(s)
Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Ácidos Alcanesulfónicos/toxicidad , Densidad Ósea , Niño , Preescolar , Cromatografía Liquida , Contaminantes Ambientales/efectos adversos , Femenino , Fluorocarburos/toxicidad , Humanos , Lactante , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios Prospectivos , Espectrometría de Masas en Tándem , VitaminasRESUMEN
OBJECTIVES: Previous research has shown that patients who are older, less educated, or have lower income are less likely to lodge complaints about health care. This variation may reflect less wish to complain or inequitable access to complaint channels or remedies. We aimed to investigate associations between sociodemographic characteristics and health users' wish to complain. STUDY DESIGN: This was a randomized case vignette survey among 6756 Danish men aged 45-70 years (30% response rate). METHODS: Assuming they received the care in vignettes about prostate cancer (prostate-specific antigen) testing, participants rated their wish to complain on a 5-point Likert scale. Information on sociodemographic characteristics was obtained through self-reports and municipality-level information from national registries. RESULTS: Lower education was associated with an increased wish to complain (mean Likert difference 0.44 [95% CI 0.36-0.51]; P < .001). The wish to complain was higher among unemployed men (difference 0.16 [95% CI 0.04-0.28]; P < .011) and those with a chronic illness (difference 0.06 [95% CI 0.02-0.10]; P < .004). Given the same healthcare scenarios, there was no difference in wish to complain among health users who were retired, living rurally, or from lower income groups. CONCLUSIONS: Health users who are less educated, lower income, elderly, or from rural or minority communities appear to be as likely, or more likely, to wish to complain about health care as others. Yet, younger, well-educated, and higher income citizens are overrepresented in actual complaint statistics. The finding suggests persisting inequalities in the suitability or accessibility of complaint processes for some groups of patients.
Asunto(s)
Atención a la Salud , Instituciones de Salud , Anciano , Escolaridad , Humanos , Renta , Masculino , Encuestas y CuestionariosRESUMEN
Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.
Asunto(s)
Biomarcadores , Conservadores de la Densidad Ósea , Densidad Ósea , Remodelación Ósea , Osteoporosis , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Estudios de Cohortes , Colágeno Tipo I/sangre , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Femenino , Humanos , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Fragmentos de Péptidos/sangre , Premenopausia , Procolágeno/sangre , Sistema de RegistrosRESUMEN
AIM: To compare the accuracy and interobserver variation of routine computed tomography (CT) on postoperative day 6-8 to detect anastomotic leakage (AL) verified by re-operation and/or endoscopy. A secondary objective was to identify the predictive values of different CT findings as an indicator for AL. MATERIAL AND METHODS: The material for this study originates from two previous prospective multicentre studies including 277 patients who were scheduled for routine abdominal CT postoperative day 6-8. Inclusion criteria for the present study were routine CT without contrast medium followed by CT with rectal contrast medium. Two independent senior radiologists blinded to the clinical outcome reviewed the CT examinations for specific findings according to a predefined scheme. RESULTS: A total of 52 patients fulfilled the inclusion criteria. AL occurred in 14 patients of which nine were clinical and five subclinical. The two radiologists diagnosed AL at unenhanced CT with sensitivities of 71.4% and 50%, respectively, and of 57.1% and 35.7% with rectal contrast medium. The corresponding specificities were 55.3% and 81.6%, and 94.7% and 92.1%. Peri-anastomotic free air and contrast medium leakage had the highest odds ratios for AL. CONCLUSION: The diagnostic sensitivity and specificity of routine postoperative CT to detect AL after low anterior resection for rectal cancer is low and with considerable interobserver variation.
Asunto(s)
Fuga Anastomótica , Neoplasias del Recto , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/diagnóstico por imagen , Medios de Contraste , Humanos , Variaciones Dependientes del Observador , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The relaxation time of a single-electron spin is an important parameter for solid-state spin qubits, as it directly limits the lifetime of the encoded information. Thanks to the low spin-orbit interaction and low hyperfine coupling, graphene and bilayer graphene (BLG) have long been considered promising platforms for spin qubits. Only recently, it has become possible to control single-electrons in BLG quantum dots (QDs) and to understand their spin-valley texture, while the relaxation dynamics have remained mostly unexplored. Here, we report spin relaxation times (T1) of single-electron states in BLG QDs. Using pulsed-gate spectroscopy, we extract relaxation times exceeding 200 µs at a magnetic field of 1.9 T. The T1 values show a strong dependence on the spin splitting, promising even longer T1 at lower magnetic fields, where our measurements are limited by the signal-to-noise ratio. The relaxation times are more than two orders of magnitude larger than those previously reported for carbon-based QDs, suggesting that graphene is a potentially promising host material for scalable spin qubits.
RESUMEN
The Charlson Comorbidity Index (CCI) may be applicable for predicting fracture risk since several diagnoses from the index are predictors of fracture. Main results were that the CCI was updated to predict risk of hip fracture with fair precision and that the index could be useful in detecting high-risk individuals. PURPOSE: Several of the Charlson Comorbidity Index (CCI) diagnoses are validated predictors of fracture. The purpose of this study was to evaluate the performance of the CCI 1987 by Charlson et al. and of the CCI 2011 by Quan et al. in predicting major osteoporotic fracture (MOF) and hip fracture (HF). Furthermore, it was examined whether the index could be modified to improve fracture risk prediction. METHODS: The study population included the entire Danish population aged 45 + years as per January 1, 2018. The cohort was split randomly 50/50 into a development and a validation cohort. CCI diagnoses and fracture outcomes were identified from hospital diagnoses. The weighting of diagnoses was updated in a new Charlson Fracture Index (CFI) using multivariable logistic regression. Predictive capabilities of the CCI 1987, the updated CCI 2011 and the new Charlson Fracture index were evaluated in the validation cohort by receiver operating characteristics (ROC) curves and area under the curve (AUC). RESULTS: In the validation cohort, the 1987 and 2011 CCIs resulted in AUCs below or around 0.7 in prediction of MOF and HF in both sexes. The CFI resulted in AUCs < 0.7 in prediction of MOF in both sexes. In prediction of HF, the CFI resulted in AUC of 0.755 (95% CI 0.749; 0.761) in women and 0.782 (95% CI 0.772; 0.793) in men. CONCLUSION: The 1987 and 2011 CCIs showed overall poor accuracy in fracture risk prediction. The CFI showed fair accuracy in prediction of HF in women and in men.
Asunto(s)
Fracturas de Cadera , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Cohortes , Comorbilidad , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: Primarily to understand whether clinically relevant factors affect the International Outcome Inventory (IOI-HA) scores and to examine if IOI-HA scores improve when renewing the hearing aids (HA) for experienced users. Secondly, to estimate the overall HA effectiveness using the IOI-HA. DESIGN: A prospective observational study. STUDY SAMPLE: In total, 1961 patients with hearing loss were included. All patients underwent a hearing examination, were fitted with HAs, and answered the IOI-HA. Factor analysis of IOI-HA separated the items into a Factor 1 (use of HA, perceived benefits, satisfaction, and quality of life) and Factor 2 (residual activity limitation, residual participation restriction and impact on others) score. RESULTS: Degree of hearing loss, word recognition score, motivation, HA usage time, tinnitus, asymmetry, and sex were significantly associated with total IOI-HA, Factor 1, or Factor 2 scores. The seven IOI-HA items increased on average by 0.4 (p < 0.001) when renewing HAs. The total median IOI-HA score at follow-up was 29 (7) for experienced (n = 460) and first-time users (n = 1189), respectively. CONCLUSIONS: Degree of hearing loss, word recognition score, motivation, tinnitus, asymmetry, and sex may be used to identify patients who require special attention to become successful HA users.
Asunto(s)
Audífonos , Pérdida Auditiva , Acúfeno , Pérdida Auditiva/rehabilitación , Pérdida Auditiva/terapia , Humanos , Satisfacción del Paciente , Calidad de Vida , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Understanding how the electron spin is coupled to orbital degrees of freedom, such as a valley degree of freedom in solid-state systems, is central to applications in spin-based electronics and quantum computation. Recent developments in the preparation of electrostatically-confined quantum dots in gapped bilayer graphene (BLG) enable to study the low-energy single-electron spectra in BLG quantum dots, which is crucial for potential spin and spin-valley qubit operations. Here, we present the observation of the spin-valley coupling in bilayer graphene quantum dots in the single-electron regime. By making use of highly-tunable double quantum dot devices we achieve an energy resolution allowing us to resolve the lifting of the fourfold spin and valley degeneracy by a Kane-Mele type spin-orbit coupling of ≈ 60 µeV. Furthermore, we find an upper limit of a potentially disorder-induced mixing of the [Formula: see text] and [Formula: see text] states below 20 µeV.
RESUMEN
BACKGROUND: OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial initiated in November 2020. Skull remodeling surgery consists of five burrholes, each 15 mm in diameter, directly over the tumor resection cavity. Preclinical research indicates that this procedure enhances the effect of Tumor Treating Fields considerably. We recently concluded a phase 1 safety/feasibility trial that indicated improved overall survival and no additional toxicity. This phase 2 trial aims to validate the efficacy of the proposed intervention. METHODS: The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients, an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields therapy combined with best physicians choice oncological treatment (control arm) or b) skull remodeling surgery, TTFields therapy and best practice oncology (interventional arm). Major eligibility criteria include age ≥ 18 years, 1st recurrence of supratentorial glioblastoma, Karnofsky performance score ≥ 70, focal tumor, and lack of significant co-morbidity. Study design aims to detect a 20% increase in overall survival after 12 months (OS12), assuming OS12 = 40% in the control group and OS12 = 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective tumor response rate, quality of life, KPS, steroid dose, and toxicity. Toxicity, objective tumor response rate, and QoL will be assessed every 3rd month. Endpoint data will be collected at the end of the trial, including the occurrence of suspected unexpected serious adverse reactions (SUSARs), unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up. DISCUSSION: New treatment modalities are highly needed for first recurrence glioblastoma. Our proposed treatment modality of skull remodeling surgery, Tumor Treating Fields, and best practice medical oncological therapy may increase overall survival significantly. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0422399 , registered 13. January 2020.
Asunto(s)
Neoplasias Encefálicas/cirugía , Glioblastoma/cirugía , Recurrencia Local de Neoplasia/cirugía , Osteotomía/métodos , Cráneo/cirugía , Adulto , Estudios de Seguimiento , Glioblastoma/mortalidad , Humanos , Estado de Ejecución de Karnofsky , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , Estudios Prospectivos , Calidad de Vida , Factores de Tiempo , TransductoresRESUMEN
STUDY QUESTION: Is fecundity, measured as self-reported time to first pregnancy (TTP), a marker for subsequent health and survival? SUMMARY ANSWER: Long TTP was a marker for increased mortality among women and higher hospitalization rates for both women and men. WHAT IS KNOWN ALREADY: Poor semen quality has been linked to increased mortality and morbidity from a wide range of diseases. Associations among fecundity, health and survival among women are still uncertain and studies on actual measures of fecundity and health outcomes are rare. STUDY DESIGN, SIZE, DURATION: We performed a prospective cohort study of 7825 women and 6279 men, aged 18 and above with measures on first TTP, who participated in one of the Danish nation-wide twin surveys in 1994 (twins born 1953-1976) and 1998 (twins born 1931-1952). They were followed-up for mortality and hospital admissions from the interview until 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twins were identified in the Danish Twin Registry and linked to Danish registers. TTP was restricted to the first pregnancy as a categorical outcome with cut-off points at 2, 10 and 18 months. We analysed the association between TTP and survival using a Cox proportional hazards model estimating hazards ratios (HRs) with 95% confidence intervals (CIs). Fine-Gray survival models were used to estimate sub-hazard ratios for specific causes of death allowing for competing risks. Using negative binomial regression, we estimated incidence rate ratios (IRRs) with 95% CIs for all-cause and cause-specific hospitalizations. All analyses were stratified by sex and adjusted for age at interview, birth cohorts, age at first attempt to become pregnant, smoking, years in school and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: In the total study population, 49.9% of women and 52.7% of men reported a TTP of less than 2 months, 30.8% of women and 29.6% of men reported a TTP of 2-9 months, 6.6% of women and 5.7% of men reported a TTP of 10-17 months, and 13.3% of women and 12.0% of men reported a TTP of 18 months or more. Among 1305 deaths, we found a higher mortality for women (HR = 1.46; 95% CI 1.15, 1.87) with a TTP of ≥18 months relative to those with a TTP of <2 months, while the highest mortality was indicated for men with a TTP of 10-17 months (HR = 1.31; 95% CI 0.98, 1.74). Among 53 799 hospitalizations, we found an increased hospitalization rate among women (HR = 1.21; 95% CI 1.0-1.41) and men (HR = 1.16; 95% CI 1.00-1.35) with a TTP of ≥18 months, and for men with a TTP of 2-9 months (HR = 1.14; 95% CI 1.01-1.30). A dose-response relationship was found for women regarding both mortality (P = 0.022) and hospitalizations (P = 0.018). Impaired fecundity was associated with a wide range of diseases and some causes of death, indicating a multi-factorial causal influence on fecundity, especially among women. LIMITATIONS, REASONS FOR CAUTION: A major limitation was that fecundity depends on both partners, which was not considered in this study. Moreover, we could not obtain information on a number of potential confounders. WIDER IMPLICATIONS OF THE FINDINGS: Fecundity seems positively correlated with overall health and may be a universal marker of future health and survival. These results add knowledge to the limited findings showing that reduced fecundity in women and poor semen quality in men may reflect worse health and a shorter life, particularly among women. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by NIH grant HD096468 (M.L.E., T.K.J. and R.L.J.). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.
Asunto(s)
Análisis de Semen , Tiempo para Quedar Embarazada , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Masculino , Embarazo , Estudios ProspectivosRESUMEN
The Toroidal Magnetized System device has been significantly upgraded to enable development of various wall conditioning techniques, including methods based on ion and electron cyclotron (IC/EC) range of frequency plasmas, and to complement plasma-wall interaction research in tokamaks and stellarators. The toroidal magnetic field generated by 16 coils can reach its maximum of 125 mT on the toroidal axis. The EC system is operated at 2.45 GHz with up to 6 kW forward power. The IC system can couple up to 6 kW in the frequency range of 10 MHz-50 MHz. The direct current glow discharge system is based on a graphite anode with a maximum voltage of 1.5 kV and a current of 6 A. A load-lock system with a vertical manipulator allows exposure of material samples. A number of diagnostics have been installed: single- and triple-pin Langmuir probes for radial plasma profiles, a time-of-flight neutral particle analyzer capable of detecting neutrals in the energy range of 10 eV-1000 eV, and a quadrupole mass spectrometer and video systems for plasma imaging. The majority of systems and diagnostics are controlled by the Siemens SIMATIC S7 system, which also provides safety interlocks.