Parent engagement and involvement is essential for the successful implementation of augmentative and alternative communication (AAC) systems in the home. The purpose of the current study is to gain a ...deeper understanding of caregivers' experiences with AAC systems and their collaboration with school professionals during the implementation of AAC, which may have led to subsequent abandonment.
This review intentionally included qualitative studies that employed semistructured interviews, focus groups, and ethnographic investigations that documented the experiences and perceptions of families implementing AAC at home. Electronic database search, ancestral search, and forward search procedures resulted in a total of 27 peer-reviewed studies portraying the voices of 319 caregivers.
An inductive analysis was conducted to record recurring themes into codes. The codes were thematically synthesized into three main themes: (a) the family unit, (b) the service providers, and (c) the AAC system.
The results emphasized the need for participatory practices of family involvement in co-constructing a collaborative AAC service provision. Future research directions should implement this practice and explore the outcomes of this process to validate its efficacy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
A subset of children with autism spectrum disorder appear to show an improvement in their behavioural symptoms during the course of a fever, a sign of systemic inflammation
. Here we elucidate the ...molecular and neural mechanisms that underlie the beneficial effects of inflammation on social behaviour deficits in mice. We compared an environmental model of neurodevelopmental disorders in which mice were exposed to maternal immune activation (MIA) during embryogenesis
with mouse models that are genetically deficient for contactin-associated protein-like 2 (Cntnap2)
, fragile X mental retardation-1 (Fmr1)
or Sh3 and multiple ankyrin repeat domains 3 (Shank3)
. We establish that the social behaviour deficits in offspring exposed to MIA can be temporarily rescued by the inflammatory response elicited by the administration of lipopolysaccharide (LPS). This behavioural rescue was accompanied by a reduction in neuronal activity in the primary somatosensory cortex dysgranular zone (S1DZ), the hyperactivity of which was previously implicated in the manifestation of behavioural phenotypes associated with offspring exposed to MIA
. By contrast, we did not observe an LPS-induced rescue of social deficits in the monogenic models. We demonstrate that the differences in responsiveness to the LPS treatment between the MIA and the monogenic models emerge from differences in the levels of cytokine production. LPS treatment in monogenic mutant mice did not induce amounts of interleukin-17a (IL-17a) comparable to those induced in MIA offspring; bypassing this difference by directly delivering IL-17a into S1DZ was sufficient to promote sociability in monogenic mutant mice as well as in MIA offspring. Conversely, abrogating the expression of IL-17 receptor subunit a (IL-17Ra) in the neurons of the S1DZ eliminated the ability of LPS to reverse the sociability phenotypes in MIA offspring. Our data support a neuroimmune mechanism that underlies neurodevelopmental disorders in which the production of IL-17a during inflammation can ameliorate the expression of social behaviour deficits by directly affecting neuronal activity in the central nervous system.
Nanotechnology refers to the interactions of cellular and molecular components and engineered materials—typically, clusters
of atoms, molecules, and molecular fragments into incredibly small ...particles—between 1 and 100 nm. Nanometer-sized particles
have novel optical, electronic, and structural properties that are not available either in individual molecules or bulk solids.
The concept of nanoscale devices has led to the development of biodegradable self-assembled nanoparticles, which are being
engineered for the targeted delivery of anticancer drugs and imaging contrast agents. Nanoconstructs such as these should
serve as customizable, targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutic agents or therapeutic
genes into malignant cells while sparing healthy cells. Such “smart” multifunctional nanodevices hold out the possibility
of radically changing the practice of oncology, allowing easy detection and then followed by effective targeted therapeutics
at the earliest stages of the disease. In this article, we briefly discuss the use of bioconjugated nanoparticles for the
delivery and targeting of anticancer drugs. Mol Cancer Ther 2006;5(8):1909–17
Merkel cell carcinoma (MCC) is a lethal skin cancer that metastasizes rapidly. Few effective treatments are available for patients with metastatic MCC. Poor intratumoral T cell infiltration and ...activation are major barriers that prevent MCC eradication by the immune system. However, the mechanisms that drive the immunologically restrictive tumor microenvironment remain poorly understood. In this study, we discovered that the innate immune regulator stimulator of IFN genes (STING) is completely silenced in MCCs. To reactivate STING in MCC, we developed an application of a human STING mutant, STINGS162A/G230I/Q266I, which we found to be readily stimulated by a mouse STING agonist, DMXAA. This STING molecule was efficiently delivered toMCC cells via an AAV vector. Introducing STINGS162A/G230I/Q266I expression and stimulating its activity by DMXAA in MCC cells reactivates their antitumor inflammatory cytokine/chemokine production. In response to MCC cells with restored STING, cocultured T cells expressing MCPyV-specific T cell receptors (TCRs) showincreased cytokine production,migration toward tumor cells, and tumor cell killing. Our study therefore suggests that STING deficiency contributes to the immune suppressive nature of MCCs. More importantly, DMXAA stimulation of STINGS162A/G230I/Q266I causes robust cell death in MCCs as well as several other STING-silenced cancers. Because tumor antigens and DNA released by dying cancer cells have the potential to amplify innate immune response and activate antitumor adaptive responses, our finding indicates that targeted delivery and activation of STINGS162A/G230I/Q266I in tumor cells holds great therapeutic promise for the treatment of MCC and many other STING-deficient cancers.
Action recognition has become a hot topic within computer vision. However, the action recognition community has focused mainly on relatively simple actions like clapping, walking, jogging, etc. The ...detection of specific events with direct practical use such as fights or in general aggressive behavior has been comparatively less studied. Such capability may be extremely useful in some video surveillance scenarios like prisons, psychiatric centers or even embedded in camera phones. As a consequence, there is growing interest in developing violence detection algorithms. Recent work considered the well-known Bag-of-Words framework for the specific problem of fight detection. Under this framework, spatio-temporal features are extracted from the video sequences and used for classification. Despite encouraging results in which high accuracy rates were achieved, the computational cost of extracting such features is prohibitive for practical applications. This work proposes a novel method to detect violence sequences. Features extracted from motion blobs are used to discriminate fight and non-fight sequences. Although the method is outperformed in accuracy by state of the art, it has a significantly faster computation time thus making it amenable for real-time applications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study exploits time, the relatively unexplored fourth dimension of gene regulatory networks (GRNs), to learn the temporal transcriptional logic underlying dynamic nitrogen (N) signaling in ...plants. Our “just-in-time” analysis of time-series transcriptome data uncovered a temporal cascade of cis elements underlying dynamic N signaling. To infer transcription factor (TF)-target edges in a GRN, we applied a time-based machine learning method to 2,174 dynamic N-responsive genes. We experimentally determined a network precision cutoff, using TF-regulated genome-wide targets of three TF hubs (CRF4, SNZ, and CDF1), used to “prune” the network to 155 TFs and 608 targets. This network precision was reconfirmed using genome-wide TF-target regulation data for four additional TFs (TGA1, HHO5/6, and PHL1) not used in network pruning. These higher-confidence edges in the GRN were further filtered by independent TF-target binding data, used to calculate a TF “N-specificity” index. This refined GRN identifies the temporal relationship of known/validated regulators of N signaling (NLP7/8, TGA1/4, NAC4, HRS1, and LBD37/38/39) and 146 additional regulators. Six TFs—CRF4, SNZ, CDF1, HHO5/6, and PHL1—validated herein regulate a significant number of genes in the dynamic N response, targeting 54% of N-uptake/assimilation pathway genes. Phenotypically, inducible overexpression of CRF4 in planta regulates genes resulting in altered biomass, root development, and 15NO₃⁻ uptake, specifically under low-N conditions. This dynamic N-signaling GRN now provides the temporal “transcriptional logic” for 155 candidate TFs to improve nitrogen use efficiency with potential agricultural applications. Broadly, these time-based approaches can uncover the temporal transcriptional logic for any biological response system in biology, agriculture, or medicine.
Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for ...biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation.
Abstract For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives ...(iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge to developing such an adhesive was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl) -1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crosslinking) iCMBAs still preserved considerable antibacterial and antifungal capabilities that are beneficial for the bioadhesives used as hemostatic adhesives or sealants for wound management.
Smartphone usage is widespread in college classrooms, but there is a lack of measurement studies. We conducted a 14-week measurement study in the wild with 84 first-year college students in Korea. We ...developed a data collection and processing tool for usage logging, mobility tracking, class evaluation, and class attendance detection. Using this dataset, we quantify students' smartphone usage patterns in the classrooms, ranging from simple use duration and frequency to temporal rhythms and interaction patterns. Furthermore, we identify the key predictors of students’ in-class smartphone use and their semester grades. Our results reveal that students use their phones for more than 25% of effective class duration, and phone distractions occur every 3–4 min for over a minute in duration. The key predictors of in-class smartphone use are daily usage habits and class characteristics, and in-class phone usage is negatively correlated with student grades.
•Students used their phones for more than 20 min per class, which is over 25% of the effective class duration.•Phone usage was prevalent throughout the class, and phone distractions happened in every 3–4 min for over a minute.•Considerable underestimation of in-class phone usage was found: self-report: 8.25 vs. measurement: 12.28•Predictors of in-class usage were daily usage behaviors, class size, and lecture organization.•Phone usage patterns such as daily and in-class use habits had a negative relationship with student grades.
Obesity and the metabolic syndrome (MetS) have both been linked to increased risk of postmenopausal breast cancer; however, their relative contributions are poorly understood.
We examined the ...association of metabolic phenotypes of obesity defined by presence of the MetS (yes and no) and body mass index (BMI; normal, overweight, obese) with risk of postmenopausal breast cancer in a prospective analysis of a cohort of postmenopausal women (
∼ 21,000) with baseline measurements of blood glucose, triglycerides, HDL-cholesterol, blood pressure, waist circumference, and BMI. Women were classified into 6 metabolic obesity phenotypes according to their BMI (18.5-<25.0, 25.0-<30.0, ≥30.0 kg/m
) and presence of the MetS (≥3 of the following: waist circumference ≥88 cm, triglycerides ≥150 mg/dL, HDL-C <50 mg/dL, glucose ≥100 mg/dL, and systolic/diastolic blood pressure ≥130/85 mmHg or treatment for hypertension). HRs for incident breast cancer and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models.
Over 15 years of follow-up, 1,176 cases of invasive breast cancer were diagnosed. Obesity, regardless of metabolic health, was associated with increased risk of breast cancer. Being obese and metabolically unhealthy was associated with the highest risk: HR, 1.62; 95% CI, 1.33-1.96. These associations were stronger in women who had never used hormone therapy.
Our findings suggest that both obesity and metabolic dysregulation are associated with breast cancer risk.
Beyond BMI, metabolic health should be considered a clinically relevant and modifiable risk factor for breast cancer.
.