Random Matrix Theories in Quantum Physics: Common Concepts

We review the development of random-matrix theory (RMT) during the last decade. We emphasize both the theoretical aspects, and the application of the theory to a number of fields. These comprise chaotic and disordered systems, the localization problem, many-body quantum systems, the Calogero-Sutherland model, chiral symmetry breaking in QCD, and quantum gravity in two dimensions. The review is preceded by a brief historical survey of the developments of RMT and of localization theory since their inception. We emphasize the concepts common to the above-mentioned fields as well as the great diversity of RMT. In view of the universality of RMT, we suggest that the current development signals the emergence of a new "statistical mechanics": Stochasticity and general symmetry requirements lead to universal laws not based on dynamical principles.Comment: 178 pages, Revtex, 45 figures, submitted to Physics Report

Lung Hyperinflation as Treatable Trait in Chronic Obstructive Pulmonary Disease: A Narrative Review

Maud Koopman,1– 3 Rein Posthuma,1– 3 Lowie EGW Vanfleteren,4 Sami O Simons,2,3 Frits ME Franssen1– 3 1Research and Development, Ciro+, Horn, the Netherlands; 2NUTRIM, Institute of Nutrition and Translational Research in Metabolism, University Maastricht, Maastricht, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands; 4COPD Center, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, SwedenCorrespondence: Frits ME Franssen, CIRO+, Hornerheide 1, Horn, 6085, NM, the Netherlands, Email [email protected]: Lung hyperinflation (LH) is a common clinical feature in patients with chronic obstructive pulmonary disease (COPD). It results from a combination of reduced elastic lung recoil as a consequence of irreversible destruction of lung parenchyma and expiratory airflow limitation. LH is an important determinant of morbidity and mortality in COPD, partially independent of the degree of airflow limitation. Therefore, reducing LH has become a major target in the treatment of COPD over the last decades. Advances were made in the diagnostics of LH and several effective interventions became available. Moreover, there is increasing evidence suggesting that LH is not only an isolated feature in COPD but rather part of a distinct clinical phenotype that may require a more integrated management. This narrative review focuses on the pathophysiology and adverse consequences of LH, the assessment of LH with lung function measurements and imaging techniques and highlights LH as a treatable trait in COPD. Finally, several suggestions regarding future studies in this field are made.Keywords: COPD, hyperinflation, treatable trait, emphysema, phenotyp

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

What People Believe about How Memory Works: A Representative Survey of the U.S. Population

Incorrect beliefs about the properties of memory have broad implications: The media conflate normal forgetting and inadvertent memory distortion with intentional deceit, juries issue verdicts based on flawed intuitions about the accuracy and confidence of testimony, and students misunderstand the role of memory in learning. We conducted a large representative telephone survey of the U.S. population to assess common beliefs about the properties of memory. Substantial numbers of respondents agreed with propositions that conflict with expert consensus: Amnesia results in the inability to remember one's own identity (83% of respondents agreed), unexpected objects generally grab attention (78%), memory works like a video camera (63%), memory can be enhanced through hypnosis (55%), memory is permanent (48%), and the testimony of a single confident eyewitness should be enough to convict a criminal defendant (37%). This discrepancy between popular belief and scientific consensus has implications from the classroom to the courtroom

Significance of Residual Nodal Disease in Clinically Node-Negative Breast Cancer After Neoadjuvant Chemotherapy

Background: Trials evaluating omission of axillary dissection (ALND) in patients with cN0 breast cancer with positive sentinel lymph nodes (SLNs) have excluded neoadjuvant chemotherapy (NACT). It remains unclear whether the data can be extrapolated to cN0 patients undergoing NACT. This study sought to identify factors associated with positive SLNs and additional disease on ALND in cT1-2N0 disease after NACT. Methods: The authors queried their database for cT1-2N0 patients treated with NACT followed by SLN biopsy from 1996 to 2022. Physical examination and ultrasound determined clinical nodal status. Multivariable logistic regression identified factors associated with positive SLNs and disease on ALND. Results: Of 1930 patients, 234 (12.1%) had positive SLNs. Positive SLNs were predicted by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) status (odds ratio [OR] 2.5; p &lt; 0.0001), lobular histology (OR 1.8; p = 0.007), multifocality (OR 2; p = 0.001), grade 1 tumors (OR 2.5; p = 0.002), and cT2 category (OR 1.9; p = 0.004). Of the 234 patients with positive SLNs and known SLN metastasis size, 148 (63.2%) underwent ALND, and 39 (26.4%) had additional positive nodes. Increasing patient age predicted disease on ALND (OR 1.03; p = 0.02). No additional positive nodes on ALND were identified in patients with only isolated tumor cells compared with 12.3% who had micrometastases and 37.6% who had macrometastases (p = 0.01). During a 5-year median follow-up period of the SLN-positive patients, three (1.3%) experienced axillary recurrence and two of the three underwent ALND at the initial surgery with no additional positive nodes. Conclusions: In cT1-2N0 breast cancer, HR+/HER2– status, lobular histology, multifocality and cT2 category predicted positive SLNs after NACT. Older age predicted positive nodes on ALND. Patients with positive SLNs had low axillary recurrence rates. These findings support investigation into omission of ALND in cN0 breast cancer and a low volume of SLN disease after NACT.</p

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust

Temporal Dynamics of Cardiovascular Risk in Patients with Chronic Obstructive Pulmonary Disease During Stable Disease and Exacerbations: Review of the Mechanisms and Implications

Sami O Simons,1,2 Amy B Heptinstall,3 Zoe Marjenberg,3 Jonathan Marshall,4 Hana Mullerova,4 Paola Rogliani,5 Clementine Nordon,4 Nathaniel M Hawkins6 1Department of Respiratory Medicine, NUTRIM Institute for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; 2Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands; 3Maverex Ltd, Newcastle Upon Tyne, UK; 4BioPharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Cambridge, UK; 5Department of Experimental Medicine, Unit of Respiratory Medicine, University of Rome ‘Tor Vergata’, Rome, Italy; 6Cardiology, University of British Columbia, Vancouver, CanadaCorrespondence: Clementine Nordon, AstraZeneca, Academy House, 136 Hills Road, Cambridge, CB2 8PA, UK, Email [email protected]: Exacerbations of chronic obstructive pulmonary disease (COPD) are risk factors for severe cardiovascular (CV) events, with the risk remaining significantly elevated long after the symptomatic phase of the exacerbation. The pathophysiology underpinning the relationship between acute events of both COPD and CV diseases has been understudied. Our objectives were to review the mechanisms by which COPD exacerbations increase the risk of CV events and understand the temporality of this risk.Methods: A pragmatic and targeted literature review was conducted with a focus on identifying recent, high-impact papers up to June 2023, guided by insights from subject matter experts including pulmonologists and cardiologists.Results: A substantial number of inter-related mechanisms underpin the spiral of anatomical and functional deterioration of lung and heart affecting COPD patients during stable state. In turn, an exacerbation of COPD may trigger a CV event, during and beyond the symptomatic phase, due to ventilation/perfusion mismatch, oxygen supply-demand imbalance, oxidative stress, systemic inflammation, hypercoagulable state, dynamic hyperinflation, pulmonary hypertension, and sympathetic activation. However, no study was identified that explored the mechanisms by which an exacerbation confers a sustained risk of CV event.Conclusion: While our review identified multiple dynamic and interacting pathophysiological mechanisms during and after an exacerbation of COPD that contribute to increasing the risk of a wide range of cardiac events, little is known regarding the precise long-term mechanisms after acute exacerbation to explain the persistent increased CV event risk beyond the symptomatic phase. The temporal changes in static and dynamic substrates need further characterization to better understand the different risk factors and risk periods for a CV event following the onset of an exacerbation. Moreover, guideline-directed cardiopulmonary therapies should be implemented at every opportunity; preventing exacerbations and intensively treating traditional CV risk factors should be a focus in COPD management.Keywords: acute events, cardiovascular disease, cardiovascular events, cardiopulmonar

Mycobacterium tuberculosis ribosomal protein S1 (RpsA) and variants with truncated C-terminal end show absence of interaction with pyrazinoic acid.

Pyrazinamide (PZA) is an antibiotic used in first- and second-line tuberculosis treatment regimens. Approximately 50% of multidrug-resistant tuberculosis and over 90% of extensively drug-resistant tuberculosis strains are also PZA resistant. Despite the key role played by PZA, its mechanisms of action are not yet fully understood. It has been postulated that pyrazinoic acid (POA), the hydrolyzed product of PZA, could inhibit trans-translation by binding to Ribosomal protein S1 (RpsA) and competing with tmRNA, the natural cofactor of RpsA. Subsequent data, however, indicate that these early findings resulted from experimental artifact. Hence, in this study we assess the capacity of POA to compete with tmRNA for RpsA. We evaluated RpsA wild type (WT), RpsA ∆A438, and RpsA ∆A438 variants with truncations towards the carboxy terminal end. Interactions were measured using Nuclear Magnetic Resonance spectroscopy (NMR), Isothermal Titration Calorimetry (ITC), Microscale Thermophoresis (MST), and Electrophoretic Mobility Shift Assay (EMSA). We found no measurable binding between POA and RpsA (WT or variants). This suggests that RpsA may not be involved in the mechanism of action of PZA in Mycobacterium tuberculosis, as previously thought. Interactions observed between tmRNA and RpsA WT, RpsA ∆A438, and each of the truncated variants of RpsA ∆A438, are reported