119 research outputs found
Never Deaf of Learning with Heart: Understanding the Essence of Handling Pupils with Hearing Impairment
This transcendental phenomenology study aimed at describing and understanding the lived experience of eight (8) Special education teachers handling learners with hearing impairment.Specifically, they were private school teachers in the cities of Biñan, Sta. Rosa and San Pedro Laguna, Philippines who were purposively selected using inclusion criteria. Framed with the approach of Moustakas (1994) as cited by Creswell (2007), the researchers carefully analyzed the participantsâ verbatim accounts which resulted in six (6) themes categorized into textural and structural descriptions. Collectively taken, the essence of the study highlighted the participantsâ experience in handling hearing-impaired learners which covered engaging them in different activities (Theme 1), customized communication with them (Theme 2), and love and drive to reach out to these individuals (Theme 3). They coped with the challenges they face by clinging to the vital role of assessment tools (Theme 4), highlighting values in teaching (Theme 5) and viewing their profession as a calling of commitment and devotion (Theme 6). The lived experiences of special education teachers with learners diagnosed with hearing impairment may serve as a feedback for special education instructional materials suppliers or developers in improving the contents of their works to better cater the needs of special education teachers in terms of the choice of innovated instructional materials that specifically address the learning needs of students in special education
Phenotype and in vitro function of mature MDDC generated from cryopreserved PBMC of cancer patients are equivalent to those from healthy donors
Effects of health and social care spending constraints on mortality in England: a time trend analysis.
OBJECTIVE: Since 2010, England has experienced relative constraints in public expenditure on healthcare (PEH) and social care (PES). We sought to determine whether these constraints have affected mortality rates. METHODS: We collected data on health and social care resources and finances for England from 2001 to 2014. Time trend analyses were conducted to compare the actual mortality rates in 2011-2014 with the counterfactual rates expected based on trends before spending constraints. Fixed-effects regression analyses were conducted using annual data on PES and PEH with mortality as the outcome, with further adjustments for macroeconomic factors and resources. Analyses were stratified by age group, place of death and lower-tier local authority (n=325). Mortality rates to 2020 were projected based on recent trends. RESULTS: Spending constraints between 2010 and 2014 were associated with an estimated 45â368 (95% CI 34â530 to 56 206) higher than expected number of deaths compared with pre-2010 trends. Deaths in those aged â„60âand in care homes accounted for the majority. PES was more strongly linked with care home and home mortality than PEH, with each ÂŁ10 per capita decline in real PES associated with an increase of 5.10 (3.65-6.54) (p<0.001) care home deaths per 100â000. These associations persisted in lag analyses and after adjustment for macroeconomic factors. Furthermore, we found that changes in real PES per capita may be linked to mortality mostly via changes in nurse numbers. Projections to 2020 based on 2009-2014 trend was cumulatively linked to an estimated 152â141 (95% CI 134â597 and 169 685) additional deaths. CONCLUSIONS: Spending constraints, especially PES, are associated with a substantial mortality gap. We suggest that spending should be targeted on improving care delivered in care homes and at home; and maintaining or increasing nurse numbers
Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways
Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-a levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology (PEst C/SAU/LA0003/2013). This work is funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (NORTE 07 0124 FEDER 000024; FCOMP-01-0124-FEDER028188; FCOMP-01-0124-FEDER 041276) and National Funds through the FCT-Foundation for Science and Technology (EXPL/CTM-BIO/0762/2013, PTDC/BBB-EBI/0786/2012) and acknowledges support by the EuropeanUnion (Seventh Framework Programme GastricGlycoExplorer project, grant number 316929). Grants were received from FCT, POPH (Programa Operacional Potencial Humano) and FSE (Fundo Social Europeu) (SFRH/BPD/75871/2011 to AM;SFRH/SINTD/60034/2009 to RMP; SFRH/BPD/84084/2012 to RMF; SFRH/BPD/89764/2012 to PO). AM acknowledges EMBO for a Short-Term Fellowship (EMBO ASTF 330-212). Transcript analysis was funded by NIH (grant P41GM103490) to KWM
Bibliotherapy Storybook Construction: A Creative Interpretation Based on Children\u27s Goals, Wants, and Hindrances
The difficulty to continue education in the Philippines, especially in the case of children, more often than not results from lack of motivation amid poverty. This problem brought the reason for this study â to create a way to spark motivation to continue education through a bibliotherapy storybook. Data were collected among twelve respondents, ages 6-12, through questionnaires describing their goals, wants, and hindrances, using coloring materials. Through thematic analysis, results show that most of the respondents were inclined to choose social service occupations that will help provide housing for their family. However, a considerable number of them expressed fear of not being able to finish school. The results were utilized to undertake a creative interpretation, completing the production process from narrative components to digital artwork. The created bibliotherapy storybook, Ang Paligsahan ng Hari sa Kastilyo, was then validated by eight experts and received an exemplary rating as a qualified material for bibliotherapy. This study successfully provided a method on how to construct a bibliotherapy storybook from one\u27s perspective. Hence, further studies may be conducted to test the created bibliotherapy for its motivational effects from the user\u27s perspective
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1ÎČ, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1ÎČ innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, PÂ =Â 1.65Â ĂÂ 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, PÂ =Â 2.3Â ĂÂ 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, PÂ =Â 3.98Â ĂÂ Â 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, PÂ =Â 4.99Â ĂÂ 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNetÂź convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNetÂź model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
AdesĂŁo Ă terapia antiretroviral para HIV/AIDS
A nĂŁo-adesĂŁo Ă terapĂȘutica antiretroviral altamente eficaz (HAART) Ă© considerada, no plano individual, como um dos mais ameaçadores perigos para a efetividade do tratamento da pessoa com HIV/aids e para a disseminação de vĂrus-resistĂȘncia, no plano coletivo. Assim, o objetivo deste estudo foi analisar, mediante revisĂŁo de literatura, os fatores de risco para nĂŁo-adesĂŁo Ă HAART, alĂ©m de agrupĂĄ-los e relacionĂĄ-los Ă pessoa em tratamento, Ă doença, ao tratamento e ao serviço de saĂșde e suporte social. A literatura aponta para a necessidade da realização de estudos que avaliem aspectos socioculturais, crenças, qualidade do serviço prestado, relaçÔes do cliente com a equipe multiprofissional e outros referentes Ă raça e aos efeitos colaterais dos anti-retrovirais. Estes estudos visam a favorecer o estabelecimento de estratĂ©gias que melhorem a adesĂŁo dos clientes Ă HAART, ao mesmo tempo em e que contribuem para a construção e exercĂcio da cidadania
The Fukushima Daiichi Accident
The Fukushima Daiichi Accident consists of a Report by the IAEA Director General and five technical volumes. It is the result of an extensive international collaborative effort involving five working groups with about 180 experts from 42 Member States with and without nuclear power programmes and several international bodies. It provides a description of the accident and its causes, evolution and consequences, based on the evaluation of data and information from a large number of sources available at the time of writing.
The set contains six printed parts and five supplementary CD-ROMs.
Contents: Report by the Director General; Technical Volume 1/5, Description and Context of the Accident; Technical Volume 2/5, Safety Assessment; Technical Volume 3/5, Emergency Preparedness and Response; Technical Volume 4/5, Radiological Consequences; Technical Volume 5/5, Post-accident Recovery; Annexes.
The JRC contributed to volumes 1,2 and 3, which are attached.JRC.F.5-Nuclear Reactor Safety Assessmen
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