Identifying the determinants of chronic absenteeism: A bioecological systems approach

Background/Context: Chronic school absenteeism is a pervasive problem across the US; in early education, it is most rampant in kindergarten and its consequences are particularly detrimental, often leading to poorer academic, behavioral and developmental outcomes later in life. Though prior empirical research has identified a broad range of determinants of chronic absenteeism, there lacks a single, unified theoretically driven investigation examining how such factors concurrently explain the incidence of chronic absenteeism among our nation 's youngest schoolchildren. Thus, it is difficult to determine the relative importance of one factor over another, hence making it challenging to develop appropriate supports and services to reduce school absences. Purpose/Research Questions: Our study filled this critical void-we investigated multiple determinants of chronic absenteeism that were grounded, theoretically and empirically, in Bronfenbrenner's bioecological model of development. Specifically, using data from the Early Childhood Longitudinal Study, Kindergarten Class of 2010-11 and the method of hierarchical generalized linear modeling, we analyzed how the co-occurrence of key (a) process, (b) person, and (c) context (micro-, meso-, exo- and macrosystem) factors was associated with kindergarteners' probability of being chronically absent. Findings/Results: Children who have poorer health, higher internalizing behaviors, and more frequent engagement in learning activities at home had higher odds of chronic absenteeism. Also, children from larger families and of lower socioeconomic status faced increased odds of chronic absenteeism. Conversely, children holding positive attitudes towards school had lowered odds of chronic absenteeism, a finding that remained robust across socioeconomic status groups. Finally, parent-school connections were associated with lowered odds of absenteeism. Conclusions/Recommendations: Overall, our findings strongly suggested that addressing chronic absenteeism will require comprehensive and multifaceted approaches that recognize these multiple factors. With this theoretically grounded, more descriptive approach, it is more feasible to identify key factors and subsequently design policies and practices to prevent absence behavior

Trajectory Analysis and Semantic Region Modeling Using A Nonparametric Bayesian Model

We propose a novel nonparametric Bayesian model, Dual Hierarchical Dirichlet Processes (Dual-HDP), for trajectory analysis and semantic region modeling in surveillance settings, in an unsupervised way. In our approach, trajectories are treated as documents and observations of an object on a trajectory are treated as words in a document. Trajectories are clustered into different activities. Abnormal trajectories are detected as samples with low likelihoods. The semantic regions, which are intersections of paths commonly taken by objects, related to activities in the scene are also modeled. Dual-HDP advances the existing Hierarchical Dirichlet Processes (HDP) language model. HDP only clusters co-occurring words from documents into topics and automatically decides the number of topics. Dual-HDP co-clusters both words and documents. It learns both the numbers of word topics and document clusters from data. Under our problem settings, HDP only clusters observations of objects, while Dual-HDP clusters both observations and trajectories. Experiments are evaluated on two data sets, radar tracks collected from a maritime port and visual tracks collected from a parking lot

Use of the nominal group technique to identify UK stakeholder views of the measures and domains used in the assessment of therapeutic exercise adherence for patients with musculoskeletal disorders

OBJECTIVES: The objective was to the undertake nominal group technique (NGT) to evaluate current exercise adherence measures and isolated domains to develop stakeholder consensus on the domains to include in the measurement of therapeutic exercise adherence for patients with musculoskeletal disorders. DESIGN: A 1-day NGT workshop was convened. Six exercise adherence measures were presented to the group that were identified in our recent systematic review. Discussions considered these measures and isolated domains of exercise adherence. Following discussions, consensus voting identified stakeholder agreement on the suitability of the six offered adherence measures and the inclusion of isolated domains of exercise adherence in future measurement. SETTING: One stakeholder NGT workshop held in Sheffield, UK. PARTICIPANTS: Key stakeholders from the UK were invited to participate from four identified populations. 14 participants represented patients, clinicians, researchers and service managers. RESULTS: All six exercise adherence measures were deemed not appropriate for use in clinical research or routine practice with no measure reaching 70% group agreement for suitability, relevance, acceptability or appropriateness. Three measures were deemed feasible to use in clinical practice. 25 constructs of exercise adherence did reach consensus threshold and were supported to be included as domains in the future measurement of exercise adherence. CONCLUSION: A mixed UK-based stakeholder group felt these six measures of exercise adherence were unacceptable. Differences in opinion within the stakeholder group highlighted the lack of consensus as to what should be measured, the type of assessment that is required and whose perspective should be sought when assessing exercise adherence. Previously unused domains may be needed alongside current ones, from both a clinician's and patient's perspective, to gain understanding and to inform future measurement development. Further conceptualisation of exercise adherence is required from similar mixed stakeholder groups in various socioeconomic and cultural populations

Unbalanced expression of VEGF and PEDF in ischemia-induced retinal neovascularization

AbstractRetinal levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), an angiogenic inhibitor, were measured and correlated with the ischemia-induced retinal neovascularization in rats. The retinas with neovascularization showed a 5-fold increase in VEGF while 2-fold decrease in PEDF, compared to the age-matched controls, resulting in an increased VEGF/PEDF ratio. The time course of the VEGF/PEDF ratio change correlated with the progression of retinal neovascularization. Changes in the VEGF and PEDF mRNAs preceded their protein level changes. These results suggest that an unbalance between angiogenic stimulators and inhibitors may contribute to retinal neovascularization

Stigmergy co-ordinates multicellular collective behaviours during Myxococcus xanthus surface migration

Surface translocation by the soil bacterium Myxococcus xanthus is a complex multicellular phenomenon that entails two motility systems. However, the mechanisms by which the activities of individual cells are coordinated to manifest this collective behaviour are currently unclear. Here we have developed a novel assay that enables detailed microscopic examination of M. xanthus motility at the interstitial interface between solidified nutrient medium and a glass coverslip. Under these conditions, M. xanthus motility is characterised by extensive micro-morphological patterning that is considerably more elaborate than occurs at an air-surface interface. We have found that during motility on solidified nutrient medium, M. xanthus forges an interconnected furrow network that is lined with an extracellular matrix comprised of exopolysaccharides, extracellular lipids, membrane vesicles and an unidentified slime. Our observations have revealed that M. xanthus motility on solidified nutrient medium is a stigmergic phenomenon in which multi-cellular collective behaviours are co-ordinated through trail-following that is guided by physical furrows and extracellular matrix materials

Dynein structure and power stroke

Dynein ATPases are microtubule motors that are critical to diverse processes such as vesicle transport and the beating of sperm tails; however, their mechanism of force generation is unknown. Each dynein comprises a head, from which a stalk and a stem emerge. Here we use electron microscopy and image processing to reveal new structural details of dynein c, an isoform from Chlamydomonas reinhardtii flagella, at the start and end of its power stroke. Both stem and stalk are flexible, and the stem connects to the head by means of a linker approximately 10 nm long that we propose lies across the head. With both ADP and vanadate bound, the stem and stalk emerge from the head 10 nm apart. However, without nucleotide they emerge much closer together owing to a change in linker orientation, and the coiled-coil stalk becomes stiffer. The net result is a shortening of the molecule coupled to an approximately 15-nm displacement of the tip of the stalk. These changes indicate a mechanism for the dynein power stroke

High-Efficiency Transduction of Liver Cancer Cells by Recombinant Adeno-Associated Virus Serotype 3 Vectors

Recombinant vectors based on a non-pathogenic human parvovirus, the adeno-associated virus 2 (AAV2) have been developed, and are currently in use in a number of gene therapy clinical trials. More recently, a number of additional AAV serotypes have also been isolated, which have been shown to exhibit selective tissue-tropism in various small and large animal models1. Of the 10 most commonly used AAV serotypes, AAV3 is by far the least efficient in transducing cells and tissues in vitro as well as in vivo

Sequential binding and sensing of Zn(II) by Bacillus subtilis Zur

Bacillus subtilis Zur (BsZur) represses high-affinity zinc-uptake systems and alternative ribosomal proteins in response to zinc replete conditions. Sequence alignments and structural studies of related Fur family proteins suggest that BsZur may contain three zinc-binding sites (sites 1–3). Mutational analyses confirm the essential structural role of site 1, while mutants affected in sites 2 and 3 retain partial repressor function. Purified BsZur binds a maximum of two Zn(II) per monomer at site 1 and site 2. Site 3 residues are important for dimerization, but do not directly bind Zn(II). Analyses of metal-binding affinities reveals negative cooperativity between the two site 2 binding events in each dimer. DNA-binding studies indicate that BsZur is sequentially activated from an inactive dimer (Zur2:Zn2) to a partially active asymmetric dimer (Zur2:Zn3), and finally to the fully zinc-loaded active form (Zur2:Zn4). BsZur with a C84S mutation in site 2 forms a Zur2:Zn3 form with normal metal- and DNA-binding affinities but is impaired in formation of the Zur2:Zn4 high affinity DNA-binding state. This mutant retains partial repressor activity in vivo, thereby supporting a model in which stepwise activation by zinc serves to broaden the physiological response to a wider range of metal concentrations

Role of miR-10b in breast cancer metastasis

Ninety percent of cancer-related mortality is caused by metastasis. Current cancer treatments can control many primary tumors but rarely stop the metastatic spread. Accumulating evidence demonstrates that miRNAs are involved in cancer initiation and progression. Furthermore, several miRNAs have been found to regulate metastasis. In particular, recent studies provide the first functional evidence that overexpression of a specific miRNA, miR-10b, can contribute to the development of metastasis, which can be exploited therapeutically in treating breast cancer metastasis in mice. Further in-depth analysis should provide more precise evaluation of the roles, mechanisms, and therapeutic utility of this miRNA in breast cancer

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator

Zuranolone (SAGE-217) is a novel, synthetic, clinical stage neuroactive steroid GABAA receptor positive allosteric modulator designed with the pharmacokinetic properties to support oral daily dosing. In vitro, zuranolone enhanced GABAA receptor current at nine unique human recombinant receptor subtypes, including representative receptors for both synaptic (γ subunit-containing) and extrasynaptic (δ subunit-containing) configurations. At a representative synaptic subunit configuration, α1β2γ2, zuranolone potentiated GABA currents synergistically with the benzodiazepine diazepam, consistent with the non-competitive activity and distinct binding sites of the two classes of compounds at synaptic receptors. In a brain slice preparation, zuranolone produced a sustained increase in GABA currents consistent with metabotropic trafficking of GABAA receptors to the cell surface. In vivo, zuranolone exhibited potent activity, indicating its ability to modulate GABAA receptors in the central nervous system after oral dosing by protecting against chemo-convulsant seizures in a mouse model and enhancing electroencephalogram β-frequency power in rats. Together, these data establish zuranolone as a potent and efficacious neuroactive steroid GABAA receptor positive allosteric modulator with drug-like properties and CNS exposure in preclinical models. Recent clinical data support the therapeutic promise of neuroactive steroid GABAA receptor positive modulators for treating mood disorders; brexanolone is the first therapeutic approved specifically for the treatment of postpartum depression. Zuranolone is currently under clinical investigation for the treatment of major depressive episodes in major depressive disorder, postpartum depression, and bipolar depression