New insight into the causes, consequences, and correction of hematopoietic stem cell aging

Aging of hematopoietic stem cells (HSCs) is characterized by lineage bias, increased clonal expansion, and functional decrease. At the molecular level, aged HSCs typically display metabolic dysregulation, upregulation of inflammatory pathways, and downregulation of DNA repair pathways. Cellular aging of HSCs, driven by cell-intrinsic and cell-extrinsic factors, causes a predisposition to anemia, adaptive immune compromise, myelodys, plasia, and malignancy. Most hematologic diseases are strongly associated with age. But what is the biological foundation for decreased fitness with age? And are there therapeutic windows to resolve age-related hematopoietic decline? These questions were the focus of the International Society for Experimental Hematology (ISEH) New Investigator Committee Fall 2022 Webinar. This review touches on the latest insights from two leading laboratories into inflammatory- and niche-driven stem cell aging and includes speculation on strategies to prevent or correct age-related decline in HSC function

Exercise-based interventions targeting balance and falls in people with COPD: a systematic review and meta-analysis

Copyright \ua9 The authors 2024. INTRODUCTION: This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD. METHODS: A structured search strategy (2000-2023) was applied to eight databases to identify studies evaluating the impact of exercise-based interventions (≥14 days in duration) on balance or falls in people with COPD. Pooled mean treatment effects (95% confidence intervals (CIs), 95% prediction intervals (PIs)) were calculated for outcomes reported in five or more studies. Inter-individual response variance and the promise of behaviour change techniques (BCTs) were explored. RESULTS: 34 studies (n=1712) were included. There were greater improvements in balance post intervention compared to controls for the Berg Balance Scale (BBS) (mean 2.51, 95% CI 0.22-4.80, 95% PI -4.60-9.63), Timed Up and Go (TUG) test (mean -1.12 s, 95% CI -1.69- -0.55 s, 95% PI -2.78-0.54 s), Single-Leg Stance (SLS) test (mean 3.25 s, 95% CI 2.72-3.77 s, 95% PI 2.64-3.86 s) and Activities-specific Balance Confidence (ABC) scale (mean 8.50%, 95% CI 2.41-14.58%, 95% PI -8.92-25.92%). Effect on falls remains unknown. Treatment effects were larger in male versus mixed-sex groups for the ABC scale and SLS test, and in balance training versus other exercise-based interventions for the BBS and TUG test. Falls history was not associated with changes in balance. Meta-analysis of individual response variance was not possible and study-level results were inconclusive. Eleven promising BCTs were identified (promise ratio ≥2). CONCLUSION: Evidence for the effect of exercise-based interventions eliciting clinically important improvements in balance for people with COPD is weak, but targeted balance training produces the greatest benefits. Future exercise interventions may benefit from inclusion of the identified promising BCTs

The Association of Pain with Incident Falls in People with Chronic Obstructive Pulmonary Disease: Evidence from the English Longitudinal Study of Ageing

Abstract: People with chronic obstructive pulmonary disease (COPD) have a higher prevalence of pain and a greater risk of falls than their healthy peers. As pain has been associated with an increased risk of falls in older adults, this study investigated the association between pain and falls in people with COPD compared to healthy controls. Data from the English Longitudinal Study of Ageing were used to establish an association between pain and falls when modelled with a generalised ordinal logistic regression and adjusted for sex, age, wealth, and education (complete case analysis only; n = 806 COPD, n = 3898 healthy controls). The odds were then converted to the predicted probabilities of falling. The predicted probability of falling for people with COPD was greater across all pain categories than for healthy controls; for COPD with (predicted probability % [95%CI]), no pain was 20% [17 to 25], with mild pain was 28% [18 to 38], with moderate pain was 28% [22 to 34] with severe pain was 39% [30 to 47] and for healthy controls with no pain was 17% [16 to 18], mild pain 22% [18 to 27], moderate pain 25% [20 to 29] and severe pain 27% [20 to 35]. The probability of falling increased across pain categories in individuals with COPD, with the most severe pain category at a nearly 40% probability of falling, indicating a potential interaction between COPD and pain

Moving beyond methodising theory in preparing for the profession

For those preparing for outdoor education and related professions, formal theory has an important role to play in terms of informing professional practice and understandings of teaching-learning dynamics. Despite this, surprisingly little is understood about how pre-service outdoor educators (POEs) view and engage with it in their preparation courses. Drawing on findings of a case study in an Australian outdoor education teacher education (OETE) course, this article explores POE theory engagement focussing on a problematic tendency to methodise formal theory, that is, to treat theories as formula for action. The authors argue that this tendency is concerning because it ignores the complexity and problematic nature of both theory-practice relationships and outdoor education pedagogy. The discussion highlights contributing factors and implications for OETE, especially with respect to enabling aspiring outdoor educators in tertiary courses to move beyond methodising theory as they enter the outdoor profession

Complete intersections: Moduli, Torelli, and good reduction

We study the arithmetic of complete intersections in projective space over number fields. Our main results include arithmetic Torelli theorems and versions of the Shafarevich conjecture, as proved for curves and abelian varieties by Faltings. For example, we prove an analogue of the Shafarevich conjecture for cubic and quartic threefolds and intersections of two quadrics.Comment: 37 pages. Typo's fixed. Expanded Section 2.

Melody Generation using an Interactive Evolutionary Algorithm

Music generation with the aid of computers has been recently grabbed the attention of many scientists in the area of artificial intelligence. Deep learning techniques have evolved sequence production methods for this purpose. Yet, a challenging problem is how to evaluate generated music by a machine. In this paper, a methodology has been developed based upon an interactive evolutionary optimization method, with which the scoring of the generated melodies is primarily performed by human expertise, during the training. This music quality scoring is modeled using a Bi-LSTM recurrent neural network. Moreover, the innovative generated melody through a Genetic algorithm will then be evaluated using this Bi-LSTM network. The results of this mechanism clearly show that the proposed method is able to create pleasurable melodies with desired styles and pieces. This method is also quite fast, compared to the state-of-the-art data-oriented evolutionary systems.Comment: 5 pages, 4 images, submitted to MEDPRAI2019 conferenc

The price of rapid exit in venture capital-backed IPOs

This paper proposes an explanation for two empirical puzzles surrounding initial public offerings (IPOs). Firstly, it is well documented that IPO underpricing increases during “hot issue” periods. Secondly, venture capital (VC) backed IPOs are less underpriced than non-venture capital backed IPOs during normal periods of activity, but the reverse is true during hot issue periods: VC backed IPOs are more underpriced than non-VC backed ones. This paper shows that when IPOs are driven by the initial investor’s desire to exit from an existing investment in order to finance a new venture, both the value of the new venture and the value of the existing firm to be sold in the IPO drive the investor’s choice of price and fraction of shares sold in the IPO. When this is the case, the availability of attractive new ventures increases equilibrium underpricing, which is what we observe during hot issue periods. Moreover, I show that underpricing is affected by the severity of the moral hazard problem between an investor and the firm’s manager. In the presence of a moral hazard problem the degree of equilibrium underpricing is more sensitive to changes in the value of the new venture. This can explain why venture capitalists, who often finance firms with more severe moral hazard problems, underprice IPOs less in normal periods, but underprice more strongly during hot issue periods. Further empirical implications relating the fraction of shares sold and the degree of underpricing are presented

Emissões públicas de ações, volatilidade e insider information na Bovespa

O trabalho utiliza um estudo de evento para examinar os retornos de ações relacionados a emissões públicas por empresas brasileiras listadas na BOVESPA, realizadas entre 1992 e 2002, buscando determinar como o mercado reagiu antes, durante e depois da data do anúncio da emissão. Após utilizar a metodologia convencional de mensuração de retornos anormais por OLS, foram utilizados modelos ARCH e GARCH, que levam em consideração a heteroscedasticidade condicional da volatilidade dos retornos anormais, em mais de 70% da amostra, após a constatação da presença desses processos nos resíduos originais. Os resultados mostram que 1) há evidências de insider information antes da data do anúncio, (2) que ocorrem retornos anormais negativos na data do anúncio e (3) que, no período de um ano após as emissões, as ações das empresas que captaram recursos via underwriting tiveram retornos negativos após ajuste ao risco e ao mercado