Machine learning can identify newly diagnosed patients with CLL at high risk of infection

Infections have become the major cause of morbidity and mortality among patients with chronic lymphocytic leukemia (CLL) due to immune dysfunction and cytotoxic CLL treatment. Yet, predictive models for infection are missing. In this work, we develop the CLL Treatment-Infection Model (CLL-TIM) that identifies patients at risk of infection or CLL treatment within 2 years of diagnosis as validated on both internal and external cohorts. CLL-TIM is an ensemble algorithm composed of 28 machine learning algorithms based on data from 4,149 patients with CLL. The model is capable of dealing with heterogeneous data, including the high rates of missing data to be expected in the real-world setting, with a precision of 72% and a recall of 75%. To address concerns regarding the use of complex machine learning algorithms in the clinic, for each patient with CLL, CLL-TIM provides explainable predictions through uncertainty estimates and personalized risk factors

The mental health burden of racial and ethnic minorities during the COVID-19 pandemic

Racial/ethnic minorities have been disproportionately impacted by COVID-19. The effects of COVID-19 on the long-term mental health of minorities remains unclear. To evaluate differences in odds of screening positive for depression and anxiety among various racial and ethnic groups during the latter phase of the COVID-19 pandemic, we performed a crosssectional analysis of 691,473 participants nested within the prospective smartphone-based COVID Symptom Study in the United States (U.S.) and United Kingdom (U.K). from February 23, 2021 to June 9, 2021. In the U.S. (n=57,187), compared to White participants, the multivariable odds ratios (ORs) for screening positive for depression were 1 16 (95% CI: 1 02 to 1 31) for Black, 1 23 (1 11 to 1 36) for Hispanic, and 1 15 (1 02 to 1 30) for Asian participants, and 1 34 (1 13 to 1 59) for participants reporting more than one race/other even after accounting for personal factors such as prior history of a mental health disorder, COVID-19 infection status, and surrounding lockdown stringency. Rates of screening positive for anxiety were comparable. In the U.K. (n=643,286), racial/ethnic minorities had similarly elevated rates of positive screening for depression and anxiety. These disparities were not fully explained by changes in leisure time activities. Racial/ethnic minorities bore a disproportionate mental health burden during the COVID-19 pandemic. These differences will need to be considered as health care systems transition from prioritizing infection control to mitigating long-term consequences

Knee-clicks and visual traits indicate fighting ability in eland antelopes: multiple messages and back-up signals

Abstract Background Given the costs of signalling, why do males often advertise their fighting ability to rivals using several signals rather than just one? Multiple signalling theories have developed largely in studies of sexual signals, and less is known about their applicability to intra-sexual communication. We here investigate the evolutionary basis for the intricate agonistic signalling system in eland antelopes, paying particular attention to the evolutionary phenomenon of loud knee-clicking. Results A principal components analysis separated seven male traits into three groups. The dominant frequency of the knee-clicking sound honestly indicated body size, a main determinant of fighting ability. In contrast, the dewlap size increased with estimated age rather than body size, suggesting that, by magnifying the silhouette of older bulls disproportionately, the dewlap acts as an indicator of age-related traits such as fighting experience. Facemask darkness, frontal hairbrush size and body greyness aligned with a third underlying variable, presumed to be androgen-related aggression. A longitudinal study provided independent support of these findings. Conclusion The results show that the multiple agonistic signals in eland reflect three separate components of fighting ability: (1) body size, (2) age and (3) presumably androgen-related aggression, which is reflected in three backup signals. The study highlights how complex agonistic signalling systems can evolve through the simultaneous action of several selective forces, each of which favours multiple signals. Specifically, loud knee-clicking is discovered to be an honest signal of body size, providing an exceptional example of the potential for non-vocal acoustic communication in mammals.</p

The commonness of rarity: Global and future distribution of rarity across land plants

A key feature of life’s diversity is that some species are common but many more are rare. Nonetheless, at global scales, we do not know what fraction of biodiversity consists of rare species. Here, we present the largest compilation of global plant diversity to quantify the fraction of Earth’s plant biodiversity that are rare. A large fraction, ~36.5% of Earth’s ~435,000 plant species, are exceedingly rare. Sampling biases and prominent models, such as neutral theory and the k-niche model, cannot account for the observed prevalence of rarity. Our results indicate that (i) climatically more stable regions have harbored rare species and hence a large fraction of Earth’s plant species via reduced extinction risk but that (ii) climate change and human land use are now disproportionately impacting rare species. Estimates of global species abundance distributions have important implications for risk assessments and conservation planning in this era of rapid global change

Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia

Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events

The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge

BACKGROUND AND AIM:The first genome-wide association study on birth weight was recently published and the most significant associated birth weight lowering variant was the rs900400 C-allele located near LEKR1 and CCNL1. We aimed to replicate the association with birth weight in the Danish Inter99 study and furthermore to evaluate associations between rs900400 and indices of insulin secretion and insulin sensitivity obtained by oral glucose tolerance tests in adults from the Danish Inter99 study and the Finnish, Metabolic Syndrome in Men (METSIM) sample. METHODS:For 4,744 of 6,784 Inter99 participants, midwife journals were traced through the Danish State Archives and association of rs900400 with birth weight was examined. Associations between rs900400 and fasting serum insulin, fasting plasma glucose, insulinogenic index, homeostasis model assessment of insulin resistance (HOMA-IR) and disposition index were studied in 5,484 Danish and 6,915 Finnish non-diabetic individuals and combined in meta-analyses. RESULTS:The C-allele of rs900400 was associated with a 22.1 g lower birth weight ([-41.3;-3.0], P = 0.024) per allele. Moreover, in combined analyses of the Danish Inter99 study and the Finnish METSIM study we found that the birth weight lowering allele was associated with increased insulin release measured by the insulinogenic index (β = 2.25% [0.59; 3.91], P = 0.008) and with an increased disposition index (β = 1.76% [0.04; 3.49], P = 0.05). CONCLUSION:The birth weight lowering effect of the C-allele of rs900400 located near LEKR1 and CCNL1 was replicated in the Danish population. Furthermore the C-allele was associated with increased insulin response following oral glucose stimulation in a meta-analysis based on Danish and Finnish non-diabetic individuals

Mixing of rhyolite, trachyte and basalt magma erupted from a vertically and laterally zoned reservoir, composite flow P1, Gran Canaria

The 14.1 Ma composite welded ignimbrite P1 (45 km3 DRE) on Gran Canaria is compositionally zoned from a felsic lower part to a basaltic top. It is composed of four component magmas mixed in vertically varying proportions: (1) Na-rhyolite (10 km3) zoned from crystal-poor to highly phyric; (2) a continuously zoned, evolved trachyte to sodic trachyandesite magma group (6 km3); (3) a minor fraction of Na-poor trachyandesite (<1 km3); and (4) nearly aphyric basalt (26 km3) zoned from 4.3 to 5.2 wt% MgO. We distinguish three sites and phases of mixing: (a) Mutual mineral inclusions show that mixing between trachytic and rhyolitic magmas occurred during early stages of their intratelluric crystallization, providing evidence for long-term residence in a common reservoir prior to eruption. This first phase of mixing was retarded by increasing viscosity of the rhyolite magma upon massive anorthoclase precipitation and accumulation. (b) All component magmas probably erupted through a ring-fissure from a common upper-crustal reservoir into which the basalt intruded during eruption. The second phase of mixing occurred during simultaneous withdrawal of magmas from the chamber and ascent through the conduit. The overall withdrawal and mixing pattern evolved in response to pre-eruptive chamber zonation and density and viscosity relationships among the magmas. Minor sectorial variations around the caldera reflect both varying configurations at the conduit entrance and unsteady discharge. (c) During each eruptive pulse, fragmentation and particulate transport in the vent and as pyroclastic flows caused additional mixing by reducing the length scale of heterogeneities. Based on considerations of magma density changes during crystallization, magma temperature constraints, and the pattern of withdrawal during eruption, we propose that eruption tapped the P1 magma chamber during a transient state of concentric zonation, which had resulted from destruction of a formerly layered zonation in order to maintain gravitational equilibrium. Our model of magma chamber zonation at the time of eruption envisages a basal high-density Na-poor trachyandesite layer that was overlain by a central mass of highly phyric rhyolite magma mantled by a sheath of vertically zoned trachyte-trachyandesite magma along the chamber walls. A conventional model of vertically stacked horizontal layers cannot account for the deduced density relationships nor for the withdrawal pattern