Tool-use learning by common marmosets (Callithrix jacchus)

One of the most critical and common features of tool use is that the tool essentially functions as a part of the body. This feature is likely rooted in biological features that are shared by tool users. To establish an ideal primate model to explore the neurobiological mechanisms supporting tool-use behaviours, we trained common marmosets, a small New World monkey species that is not usually associated with tool use, to use a rake-shaped tool to retrieve food. Five naive common marmosets were systematically trained to manipulate the tool using a 4-stage, step-by-step protocol. The relative positions of the tool and the food were manipulated, so that the marmosets were required to (1) pull the tool vertically, (2) move the tool horizontally, (3) make an arc to retrieve a food item located behind the tool and (4) retrieve the food item. We found considerable individual differences in tool-use technique; for example, one animal consistently used a unilateral hand movement for all of the steps, whereas the others (n = 4) used both hands to move the tool depending on the location of the food item. After extensive training, all of the marmosets could manipulate the rake-shaped tool, which is reported in this species for the first time. The common marmoset is thus a model primate for such studies. This study sets the stage for future research to examine the biological mechanisms underlying the cognitive ability of tool use at the molecular and genetic levels

Hypoxia Alters Cell Cycle Regulatory Protein Expression and Induces Premature Maturation of Oligodendrocyte Precursor Cells

Periventricular white matter injury (PWMI) is a common form of brain injury sustained by preterm infants. A major factor that predisposes to PWMI is hypoxia. Because oligodendrocytes (OLs) are responsible for myelination of axons, abnormal OL development or function may affect brain myelination. At present our understanding of the influences of hypoxia on OL development is limited. To examine isolated effects of hypoxia on OLs, we examined the influences of hypoxia on OL development in vitro.Cultures of oligodendrocyte precursor cells (OPCs) were prepared from mixed glial cultures and were 99% pure. OPCs were maintained at 21% O(2) or hypoxia (1% or 4% O(2)) for up to 7 days. We observed that 1% O(2) lead to an increase in the proportion of myelin basic protein (MBP)-positive OLs after 1 week in culture, and a decrease in the proportion of platelet-derived growth factor receptor alpha (PDGFRalpha)-positive cells suggesting premature OL maturation. Increased expression of the cell cycle regulatory proteins p27(Kip1) and phospho-cdc2, which play a role in OL differentiation, was seen as well.These results show that hypoxia interferes with the normal process of OL differentiation by inducing premature OPC maturation

Trypanosoma brucei PUF9 Regulates mRNAs for Proteins Involved in Replicative Processes over the Cell Cycle

Many genes that are required at specific points in the cell cycle exhibit cell cycle–dependent expression. In the early-diverging model eukaryote and important human pathogen Trypanosoma brucei, regulation of gene expression in the cell cycle and other processes is almost entirely post-transcriptional. Here, we show that the T. brucei RNA-binding protein PUF9 stabilizes certain transcripts during S-phase. Target transcripts of PUF9—LIGKA, PNT1 and PNT2—were identified by affinity purification with TAP-tagged PUF9. RNAi against PUF9 caused an accumulation of cells in G2/M phase and unexpectedly destabilized the PUF9 target mRNAs, despite the fact that most known Puf-domain proteins promote degradation of their target mRNAs. The levels of the PUF9-regulated transcripts were cell cycle dependent, peaking in mid- to late- S-phase, and this effect was abolished when PUF9 was targeted by RNAi. The sequence UUGUACC was over-represented in the 3′ UTRs of PUF9 targets; a point mutation in this motif abolished PUF9-dependent stabilization of a reporter transcript carrying the PNT1 3′ UTR. LIGKA is involved in replication of the kinetoplast, and here we show that PNT1 is also kinetoplast-associated and its over-expression causes kinetoplast-related defects, while PNT2 is localized to the nucleus in G1 phase and redistributes to the mitotic spindle during mitosis. PUF9 targets may constitute a post-transcriptional regulon, encoding proteins involved in temporally coordinated replicative processes in early G2 phase

Use of a health information exchange system in the emergency care of children

<p>Abstract</p> <p>Background</p> <p>Children may benefit greatly in terms of safety and care coordination from the information sharing promised by health information exchange (HIE). While information exchange capability is a required feature of the certified electronic health record, we known little regarding how this technology is used in general and for pediatric patients specifically.</p> <p>Methods</p> <p>Using data from an operational HIE effort in central Texas, we examined the factors associated with actual system usage. The clinical and demographic characteristics of pediatric ED encounters (n = 179,445) were linked to the HIE system user logs. Based on the patterns of HIE system screens accessed by users, we classified each encounter as: no system usage, basic system usage, or novel system usage. Using crossed random effects logistic regression, we modeled the factors associated with basic and novel system usage.</p> <p>Results</p> <p>Users accessed the system for 8.7% of encounters. Increasing patient comorbidity was associated with a 5% higher odds of basic usage and 15% higher odds for novel usage. The odds of basic system usage were lower in the face of time constraints and for patients who had not been to that location in the previous 12 months.</p> <p>Conclusions</p> <p>HIE systems may be a source to fulfill users' information needs about complex patients. However, time constraints may be a barrier to usage. In addition, results suggest HIE is more likely to be useful to pediatric patients visiting ED repeatedly. This study helps fill an existing gap in the study of technological applications in the care of children and improves knowledge about how HIE systems are utilized.</p

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

Treatment patterns, health state, and health care resource utilization of patients with radioactive iodine refractory differentiated thyroid cancer

Andrew G Gianoukakis,1 Natalia M Flores,2 Corey L Pelletier,3 Anna Forsythe,3 Gregory R Wolfe,2 Matthew H Taylor41Division of Endocrinology and Metabolism, Harbor-UCLA Medical Center, The University of California, Los Angeles, 2Health Outcomes Research, Kantar Health, Foster City, CA, 3Global Value and Access, Eisai, Inc., Woodcliff Lakes, NJ, 4Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USABackground: Patients with differentiated thyroid cancer (DTC) often respond well to treatment but some become refractory to radioactive iodine (RAI) treatment, and treatment options are limited. Despite the humanistic and economic burden RAI refractory disease imposes on patients, published research concerning treatment patterns and health care resource utilization is sparse.Methods: Data were collected from an online retrospective chart review study in the US and five European Union (EU) countries (France, Germany, Italy, Spain, and UK) with physicians recruited from an online panel. Physicians (N=211) provided demographics, disease history, treatment information, and health care resource utilization for one to four of their patients with radioactive iodine refractory differentiated thyroid cancer (RR-DTC).Results: The majority of the patients with RR-DTC (N=623) were female (56%), and their mean age was 58.2 years. In this sample, 63.2% had papillary thyroid cancer and 57.0% were in Stage IV when deemed RAI refractory. Patients with RR-DTC experienced regional recurrence in the thyroid bed/central neck area (25.3%) and had distant metastatic disease (53.6%). At the time data were collected, 50.7% were receiving systemic treatment. Of those, 78.5% were on first-line treatment and 62.7% were receiving multikinase inhibitors. Regional differences for prescribed treatments were observed; the US was more likely to have patients receiving multikinase inhibitors (79.2%) compared with UK (41.2%) and Italy (17.1%). Additional details regarding treatment patterns and resource utilization are discussed.Conclusion: The current study aimed to obtain a greater understanding of RR-DTC treatment globally. These results can assist in the development and implementation of treatment guidelines and ultimately enhance the care of patients with RR-DTC.Keywords: thyroid cancer, disease burden, therapy options, cost of illnes

An extended Galerkin weak form and a point interpolation method with continuous strain field and superconvergence using triangular mesh

A point interpolation method (PIM) with continuous strain field (PIM-CS) is developed for mechanics problems using triangular background mesh, in which PIM shape functions are used to construct both displacement and strain fields. The strain field constructed is continuous in the entire problem domain, which is achieved by simple linear interpolations using locally smoothed strains around the nodes and points required for the interpolation. A general parameterized functional with a real adjustable parameter α are then proposed for establishing PIM-CS models of special property. We prove theoretically that the PIM-CS has an excellent bound property: strain energy obtained using PIM-CS lies in between those of the compatible FEM and NS-PIM models of the same mesh. Techniques and procedures are then presented to compute the upper and lower bound solutions using the PIM-CS. It is discovered that an extended Galerkin (x-Galerkin) model, as special case resulted from the extended parameterized functional with α = 1, is outstanding in terms of both performance and efficiency. Intensive numerical studies show that upper and lower bound solutions can always be obtained, there exist α values at which the solutions of PIM-CS are of superconvergence, and the x-Galerkin model is capable of producing superconvergent solutions of ultra accuracy that is about 10 times that of the FEM using the same mes