Social robots: a meta-analysis of learning outcomes

NMDA Receptors Control Cue-Outcome Selectivity and Plasticity of Orbitofrontal Firing Patterns during Associative Stimulus-Reward Learning

Staff shortages and the implementation of social robotics in forensic care. Forensic care is provided under political and societal pressure. At the same time this sector faces an increasing lack of qualified personnel. This study describes whether, and if so in which way, social robots can contribute to the quality of forensic care and relieve the burden on staff. As no studies have yet been conducted on the applicability of this technology in forensic care, first literature was searched for studies on experiences with social robots in general mental health care. Subsequently, by means of desk research, forensic treatment methods were identified for which social robotics could currently be used. For three tasks for which potential for social robots was seen prototypes were developed, namely ADL, Companionship and Early Recognition Method. Two focus groups in which a total of twelve employees from the forensic field discussed the applicability of these prototypes as well as social robotics in general in forensic care. The participants saw various opportunities for social robots to contribute to the quality of treatment. It was concluded that the use of robots should be seen as a supplement to or deepening of current care, and not as a replacement for care as it is currently provided by humans. It is also emphasized that the implementation of social robotics in forensic care requires specialized knowledge and skills from the already heavily burdened forensic care providers.

Synaptic and Extrasynaptic NMDA Receptors Are Gated by Different Endogenous Coagonists

Purpose Social robots are a promising assistive technology to support older adults in home and healthcare environments. Engaging end-users in all stages of social robot research, development, and deployment is critical to adoption. However, the voices of end-users are missing from policies about social robots. This work consults with end-users of social robots to capture their perspectives on social robot policies and co-create expert-driven policy recommendations to guide the future implementation of social robots for aging. Materials and Methods In this two-part study, we performed a content analysis of n = 47 international policies on social robotics followed by seventeen semi-structured interviews with experts on aging and dementia from both professional (n = 6) and lived experience (n = 11) perspectives to capture their opinions about social robot policies. Results Our analysis highlights alignments between social robot policy recommendations and perspectives of the dementia community including upholding respect for human rights and dignity, the need for clear and consistent regulation, and the need for public engagement. Participants further recommended that policies should prioritize cost and accessibility considerations and focus on aging- and dementia-specific considerations. Participants reported that the responsibility for social robot policy development lay primarily with governments and the healthcare sector. Increased consultation with end-users, minority groups and medical professionals was suggested for future policy development. Conclusion Findings contribute to the ethical co-creation of social robots as assistive technologies for older adults and provide actionable steps for the development of policies that reflect the values and perspectives of end-users.

Recently, our research team found a strong and significant association between loss-of-function (LOF) mutations in filaggrin (FLG), a gene that encodes a skin barrier protein, in European and Canadian individuals with peanut allergy (PA).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar These mutations result in a barrier defect and have been associated with atopic dermatitis, asthma, and allergic rhinitis.2Irvine A.D. McLean W.H. Leung D.Y. Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (812) Google Scholar This finding represents the strongest genetic risk factor found to date for PA, a highly heritable disease,3Sicherer S.H. Furlong T.J. Maes H.H. Desnick R.J. Sampson H.A. Gelb B.D. Genetics of peanut allergy: a twin study.J Allergy Clin Immunol. 2000; 106: 53-56Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar with an estimated odds ratio (OR) between 1.9 (Canadian) and 5.3 (English, Dutch, and Irish combined).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar Because there is no uniformly accepted definition of PA short of oral food challenge, it is worthwhile to examine whether the association between the FLG LOF mutations and PA varies with the diagnostic criteria for PA. Furthermore, the frequent coexistence of PA with other atopic conditions may mean that the association between PA and FLG LOF mutations is confounded. Although we controlled for eczema in the European populations in our previous work, data on eczema were not available for the Canadian control group; however, data on asthma were available. Asthma is a potential confounder, as it has known relationships with both PA4Liu A.H. Jaramillo R. Sicherer S.H. Wood R.A. Bock S.A. Burks A.W. et al.National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006.J Allergy Clin Immunol. 2010; 126: 798-806.e13Abstract Full Text Full Text PDF PubMed Scopus (379) Google Scholar and FLG mutations.5Palmer C.N. Ismail T. Lee S.P. Terron-Kwiatkowski A. Zhao Y. Liao H. et al.Filaggrin null mutations are associated with increased asthma severity in children and young adults.J Allergy Clin Immunol. 2007; 120: 64-68Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar By using statistical sensitivity analyses, we examined the effect of PA diagnostic criteria and asthma on the relationship between PA and FLG LOF mutations in a Canadian PA case group. Because the PA case group was composed of both English- and French-speaking individuals, we also investigated whether the difference in OR between the Canadian and European populations could be due to some common French-Canadian mutations not yet identified in FLG.Caucasian subjects from a well-described Canadian pediatric PA case group were recruited (n = 679), and DNA was isolated from salivary samples.1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar One control group consisted of adult Caucasians recruited from the general population of Ontario, Canada; DNA was provided by the Ontario Population Genomics Platform at The Centre for Applied Genomics (Toronto) (n = 894). A second control group of newborn babies from Quebec City was sampled on the basis of French-Canadian surname (stored blood; n = 268).6Girouard J. Giguere Y. Delage R. Rousseau F. Prevalence of HFE gene C282Y and H63D mutations in a French-Canadian population of neonates and in referred patients.Hum Mol Genet. 2002; 11: 185-189Crossref PubMed Scopus (18) Google Scholar All samples were genotyped in Dundee, Scotland, for the 4 most common FLG LOF mutations found in Caucasians (R501X, 2282del4, R2447X, and S3247X). rs and accession numbers for mutations are available in the Online Repository at www.jacionline.org (see Table E1)."Mutation carriers" were defined as those with heterozygous, homozygous, or compound heterozygous mutations. Those individuals with none of the 4 FLG mutations were classified as "nonmutation carriers." The association between mutation status and PA was compared with the Ontario control group, the Quebec control group, and the combined control group. To evaluate whether the association between PA and mutation status changed with case definition, a continuum of PA case definitions was constructed and the resulting OR trends with case definition were examined by using the combined control groups. The methodology and rationale for these definitions are given in the Online Repository available at www.jacionline.org (see Tables E2 and E3). To increase power, case definitions were transformed into an ordered variable and the association between PA and FLG mutations was examined by using regression modeling through increasingly stringent definitions of PA to see whether the OR changed significantly.We also examined the effect of asthma on FLG mutation status and PA. Logistic regression using the Ontario control group was conducted with PA status, age, sex, asthma, and interaction terms for PA and age, PA and sex, and PA and asthma. Because there may be interaction between mutation status, asthma, and smoking,7Berg N.D. Husemoen L.L. Thuesen B.H. Hersoug L.G. Elberling J. Thyssen J.P. et al.Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.J Allergy Clin Immunol. 2012; 129 (e1-2): 374-380Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar and self-identified asthmatic patients may have significant misclassification, analyses controlled for smoking history in the controls and misclassification in the asthma variable in both controls and cases. A constructed atopic asthma variable was used to control for the effect of smoking with 4 assumptions: (1) Those individuals who have atopic asthma in childhood are less likely to smoke as adults. (2) Those adults who have asthma and have never smoked are more likely to have atopic asthma. (3) If a patient reports bronchial emphysema, he or she does not have atopic asthma. (4) Asthma reported in the case group is atopic. To examine the possibility of error due to self-report of asthma, we completed a sensitivity analysis taking into account data from the PA registry that found that 6% had "forgotten" previously noted atopic history, while 12% more reported atopic history on the current questionnaire than at baseline registry recruitment. Random sampling and subsequent logistic regression modeling was completed 100 times to see the overall effect of error in asthma reporting on the relationship of PA and FLG LOF mutations using these parameters.Finally, a similar sensitivity analysis of PA status was conducted, as PA status could be affected by the age disparity between the Ontario control group and the cases, because it is estimated that up to 20% of individuals with PA may have resolution of their allergy.8Skolnick H.S. Conover-Walker M.K. Koerner C.B. Sampson H.A. Burks W. Wood R.A. The natural history of peanut allergy.J Allergy Clin Immunol. 2001; 107: 367-374Abstract Full Text Full Text PDF PubMed Scopus (467) Google Scholar This sensitivity analysis also took into account the 1% prevalence of PA in the general population.9Ben-Shoshan M. Harrington D.W. Soller L. Fragapane J. Joseph L. St Pierre Y. et al.A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada.J Allergy Clin Immunol. 2010; 125: 1327-1335Abstract Full Text Full Text PDF PubMed Scopus (174) Google ScholarOf the 679 cases eligible to participate, 99.3% had good quality DNA. Demographic information is presented in Table I. The 674 cases had approximately twice as many mutations as the controls (20% vs 11%), and the OR for PA and FLG mutation status was similar in the Ontario and Quebec control groups (Table II). The genotype frequencies in cases and controls are shown in the Online Repository available at www.jacionline.org (see Table E4). Among the 13 case definitions, there was no significant difference in the OR for the relationship between PA and FLG mutation status. Seven representative case definitions are shown in Table III. Logistic regression of the ordered case definition criteria variable produced similar results.Table IDemographics: PA cases and controlsCharacteristicPA casesOntario controlsQuebec controlsNo. of subjects674894268Age (y)∗Age on January 1, 2009. Mean ± SD9.3 ± 4.065.5 ± 10.29.7 ± 0.5 Range0-2133-847-10 No. with missing data020Sex No. of males416281157 Proportion of males (CI)0.617 (0.580-0.654)0.315 (0.284-0.346)0.586 (0.526-0.645)∗ Age on January 1, 2009. Open table in a new tab Table IIFLG genotypes and statistical tests of PA cases compared with control groupsPA casesOntario controlsQuebec controlsCombined controlsNo. of analyzed subjects∗Genotyping failures occurred in 11 PA cases, 5 of the Ontario controls, and 1 of the Quebec controls.6638892671156No. of FLG heterozygotes†One FLG mutation detected.1129429123No. of FLG homozygotes/compound heterozygotes‡Two of the same (FLG homozygote) or 2 different (compound heterozygote) FLG mutations detected.18415Total no. with 1 or 2 FLG mutations1309830128Proportion with 1 or 2 FLG mutations0.1960.1100.1120.110ORNA1.971.931.9695% CINA1.47-2.651.24-3.061.49-2.58χ2 test (P value)NA22.33 (2.30 × 10−6)9.37 (2.21 × 10−3)25.22 (5.12 × 10−7)NA, Not applicable.∗ Genotyping failures occurred in 11 PA cases, 5 of the Ontario controls, and 1 of the Quebec controls.† One FLG mutation detected.‡ Two of the same (FLG homozygote) or 2 different (compound heterozygote) FLG mutations detected. Open table in a new tab Table IIIPA case definition analysis (PA cases compared with the combined control group)No. of subjectsOR95% CIMinimum criteria to be considered for inclusion:a.Convincing history of PA∗A convincing history was defined as a minimum of 2 mild symptoms/signs or either 1 moderate or 1 severe symptom/sign occurring within 120 min after peanut contact or ingestion. (1) Mild: pruritus, urticaria, flushing, and/or rhinoconjunctivitis. (2) Moderate: angioedema, throat tightness, change in voice, coughing, difficulty breathing (other than wheeze), nausea and/or vomiting, and/or abdominal pain. (3) Severe: wheezing, stridor, cyanosis, and/or circulatory collapse. and (i) SPT ≥3 mm or (ii) psIgE ≥ 0.35 kU/L orb.No history of peanut ingestion/uncertain history of allergy and (i) SPT ≥3 mm and (ii) psIgE ≥15 kU/L orc.Any history suggestive of an IgE-mediated reaction not compatible with anaphylaxis and (i) SPT ≥8 mm or (ii) SPT ≥4 mm if <2 y old or (iii) psIgE ≥15 kU/L ord.Positive OFC6741.961.49-2.58psIgE ≥15 kU/L or SPT ≥8 mm, or positive OFC†The definition used in our previous work1 required a history of anaphylaxis or a history suggestive of type I hypersensitivity to peanut along with SPT ≥8 mm and psIgE ≥15 kU/L.5261.971.47-2.65psIgE ≥57 kU/L or SPT ≥8 mm, or positive OFC4862.071.53-2.78psIgE ≥57 kU/L or SPT ≥15 mm, or positive OFC2672.071.42-2.96psIgE ≥15 kU/L, or SPT ≥8 mm AND anaphylaxis, or positive OFC2662.091.44-3.00psIgE ≥57 kU/L, or SPT ≥8 mm AND anaphylaxis, or positive OFC2532.211.52-3.18psIgE ≥57 kU/L, or SPT ≥15 mm AND anaphylaxis, or positive OFC1222.281.38-3.69OFC, Oral food challenge; psIgE, peanut-specific immunoglobulin E; SPT, skin prick test.∗ A convincing history was defined as a minimum of 2 mild symptoms/signs or either 1 moderate or 1 severe symptom/sign occurring within 120 min after peanut contact or ingestion. (1) Mild: pruritus, urticaria, flushing, and/or rhinoconjunctivitis. (2) Moderate: angioedema, throat tightness, change in voice, coughing, difficulty breathing (other than wheeze), nausea and/or vomiting, and/or abdominal pain. (3) Severe: wheezing, stridor, cyanosis, and/or circulatory collapse.† The definition used in our previous work1 required a history of anaphylaxis or a history suggestive of type I hypersensitivity to peanut along with SPT ≥8 mm and psIgE ≥15 kU/L. Open table in a new tab The self-reported prevalence of asthma was 11% in the Ontario controls, compared with 65% in the PA cases (see Table E5 in this article's Online Repository at www.jacionline.org). Univariate analysis found PA status to be the strongest predictor of a mutation, followed by asthma. Neither age nor gender had an appreciable relationship with the presence of FLG mutations on univariate or multivariate analysis and were not included in the final model. Multivariate logistic regression found no evidence for an effect of asthma (OR, 1.12; 95% CI, 0.79-1.59) on the relationship between PA (OR, 1.81; 95% CI, 1.29-2.55) and FLG LOF mutations. The proportion of mutations was similar in those PA cases with and without asthma. Peanut-allergic individuals with asthma had at least 1 mutation in 19.8% of the cases (95% CI, 0.159-0.236), while 18.7% (95% CI, 0.136-0.238) of the PA cases without asthma had at least 1 mutation.An additional analysis using a constructed atopic asthma variable to control for the effect of smoking yielded similar results. PA status remained significant (OR, 1.88; 95% CI, 1.27-2.80), while history of atopic asthma was not (OR, 1.44; 95% CI, 0.59-3.53). Results were also unchanged after the sensitivity analysis of the self-reported asthma variable, with only PA status remaining significant in the multivariate analysis. The sensitivity analysis on PA status similarly had little effect on the findings. While 20% resolution in cases alone finds that both PA and asthma status are nonsignificant, modeling 20% resolution of cases with 1% prevalence in the general population finds that only PA status remains significant in the multivariate model.This study substantiates the relationship between PA and FLG LOF mutations, and moreover this relationship appears independent of diagnostic criteria of PA and history of asthma, although residual confounding is always possible. All sets of diagnostic criteria used in this study were intended to define individuals with clinical allergy, although it is possible that some individuals who were merely sensitized could have been included in the less stringent definitions of PA. Despite this possibility, the association between the FLG LOF mutations and PA does not appear to vary with the diagnostic criteria for PA. Although the point estimates for the OR increase as the PA definition becomes more stringent, the sample size decreases and the CIs overlap; thus, the differences are not statistically significant.The similarity of the OR in the 2 control groups provides indirect evidence that it is unlikely that there are common FLG mutations not yet identified in French-Canadians, under the assumption of similar prevalence of PA. If unidentified common French-Canadian FLG variants exist, one would expect the observed OR to be higher when the PA cases were compared with the Quebec controls, due to a lower detection of mutations in the control group. However, further evidence such as the sequencing of FLG in French-Canadians would be of interest.Limitations of this study include the inability to verify ethnicity by using genetic markers of ethnicity, which were not available for either the cases or controls. However, of the 47 identified FLG mutations, those examined here are shared in many European populations2Irvine A.D. McLean W.H. Leung D.Y. Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (812) Google Scholar (see Table E6 in this article's Online Repository at www.jacionline.org), including the expected ancestries of our case and control groups, giving us confidence that population stratification is not the cause of the difference in mutation frequency in the cases and controls. The rate of mutations in the control groups is comparable to the number seen in other Caucasian general populations (Table E6), which also leads us to believe that we have not overestimated the association. This study was also impeded by the inability to confirm asthma status by diagnostic means and that the only control group for which we had asthma and smoking history was a group of adults. While genotype will not change with age, the age difference could have affected ethnicity (eg, through different times of immigration) and PA status because of generational lifestyle, dietary, or environmental differences. Asthma status could also be affected by this age difference, because of smoking history, failure to remember a history of childhood asthma, as well as the possibility that cases have not yet developed asthma, although there is already a large proportion of PA cases who report asthma. In an effort to address these issues, sensitivity analyses of both PA and smoking status were undertaken, which found no appreciable effects on the findings of this study.The results of this study lend credence to the hypothesis that sensitization in allergic in at least some patients may through the J. J. I. R. to peanut oral and allergic PubMed Scopus Google Scholar peanut is a risk factor for the of H. peanut as a risk factor for the of peanut allergy.J Allergy Clin Immunol. Full Text Full Text PDF PubMed Scopus Google Scholar and may be a for the of peanut for a young to peanut may be to to such as that with peanut R. M. The prevalence of peanut sensitization in childhood is due to to 2011; PubMed Scopus Google Scholar filaggrin is not the to these through the skin or could result in to If the to either barrier or may allergic research in barrier and environmental is to further of the of atopic Recently, our research team found a strong and significant association between loss-of-function (LOF) mutations in filaggrin (FLG), a gene that encodes a skin barrier protein, in European and Canadian individuals with peanut allergy (PA).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar These mutations result in a barrier defect and have been associated with atopic dermatitis, asthma, and allergic rhinitis.2Irvine A.D. McLean W.H. Leung D.Y. Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (812) Google Scholar This finding represents the strongest genetic risk factor found to date for PA, a highly heritable disease,3Sicherer S.H. Furlong T.J. Maes H.H. Desnick R.J. Sampson H.A. Gelb B.D. Genetics of peanut allergy: a twin study.J Allergy Clin Immunol. 2000; 106: 53-56Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar with an estimated odds ratio (OR) between 1.9 (Canadian) and 5.3 (English, Dutch, and Irish combined).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar Because there is no uniformly accepted definition of PA short of oral food challenge, it is worthwhile to examine whether the association between the FLG LOF mutations and PA varies with the diagnostic criteria for PA. Furthermore, the frequent coexistence of PA with other atopic conditions may mean that the association between PA and FLG LOF mutations is confounded. Although we controlled for eczema in the European populations in our previous work, data on eczema were not available for the Canadian control group; however, data on asthma were available. Asthma is a potential confounder, as it has known relationships with both PA4Liu A.H. Jaramillo R. Sicherer S.H. Wood R.A. Bock S.A. Burks A.W. et al.National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006.J Allergy Clin Immunol. 2010; 126: 798-806.e13Abstract Full Text Full Text PDF PubMed Scopus (379) Google Scholar and FLG mutations.5Palmer C.N. Ismail T. Lee S.P. Terron-Kwiatkowski A. Zhao Y. Liao H. et al.Filaggrin null mutations are associated with increased asthma severity in children and young adults.J Allergy Clin Immunol. 2007; 120: 64-68Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar By using statistical sensitivity analyses, we examined the effect of PA diagnostic criteria and asthma on the relationship between PA and FLG LOF mutations in a Canadian PA case group. Because the PA case group was composed of both English- and French-speaking individuals, we also investigated whether the difference in OR between the Canadian and European populations could be due to some common French-Canadian mutations not yet identified in Caucasian subjects from a well-described Canadian pediatric PA case group were recruited (n = 679), and DNA was isolated from salivary samples.1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar One control group consisted of adult Caucasians recruited from the general population of Ontario, Canada; DNA was provided by the Ontario Population Genomics Platform at The Centre for Applied Genomics (Toronto) (n = 894). A second control group of newborn babies from Quebec City was sampled on the basis of French-Canadian surname (stored blood; n = 268).6Girouard J. Giguere Y. Delage R. Rousseau F. Prevalence of HFE gene C282Y and H63D mutations in a French-Canadian population of neonates and in referred patients.Hum Mol Genet. 2002; 11: 185-189Crossref PubMed Scopus (18) Google Scholar All samples were genotyped in Dundee, Scotland, for the 4 most common FLG LOF mutations found in Caucasians (R501X, 2282del4, R2447X, and S3247X). rs and accession numbers for mutations are available in the Online Repository at www.jacionline.org (see Table carriers" were defined as those with heterozygous, homozygous, or compound heterozygous mutations. Those individuals with none of the 4 FLG mutations were classified as "nonmutation carriers." The association between mutation status and PA was compared with the Ontario control group, the Quebec control group, and the combined control group. To evaluate whether the association between PA and mutation status changed with case definition, a continuum of PA case definitions was constructed and the resulting OR trends with case definition were examined by using the combined control groups. The methodology and rationale for these definitions are given in the Online Repository available at www.jacionline.org (see Tables E2 and E3). To increase power, case definitions were transformed into an ordered variable and the association between PA and FLG mutations was examined by using regression modeling through increasingly stringent definitions of PA to see whether the OR changed also examined the effect of asthma on FLG mutation status and PA. Logistic regression using the Ontario control group was conducted with PA status, age, sex, asthma, and interaction terms for PA and age, PA and sex, and PA and asthma. Because there may be interaction between mutation status, asthma, and smoking,7Berg N.D. Husemoen L.L. Thuesen B.H. Hersoug L.G. Elberling J. Thyssen J.P. et al.Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.J Allergy Clin Immunol. 2012; 129 (e1-2): 374-380Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar and self-identified asthmatic patients may have significant misclassification, analyses controlled for smoking history in the controls and misclassification in the asthma variable in both controls and cases. A constructed atopic asthma variable was used to control for the effect of smoking with 4 assumptions: (1) Those individuals who have atopic asthma in childhood are less likely to smoke as adults. (2) Those adults who have asthma and have never smoked are more likely to have atopic asthma. (3) If a patient reports bronchial emphysema, he or she does not have atopic asthma. (4) Asthma reported in the case group is atopic. To examine the possibility of error due to self-report of asthma, we completed a sensitivity analysis taking into account data from the PA registry that found that 6% had "forgotten" previously noted atopic history, while 12% more reported atopic history on the current questionnaire than at baseline registry recruitment. Random sampling and subsequent logistic regression modeling was completed 100 times to see the overall effect of error in asthma reporting on the relationship of PA and FLG LOF mutations using these a similar sensitivity analysis of PA status was conducted, as PA status could be affected by the age disparity between the Ontario control group and the cases, because it is estimated that up to 20% of individuals with PA may have resolution of their allergy.8Skolnick H.S. Conover-Walker M.K. Koerner C.B. Sampson H.A. Burks W. Wood R.A. The natural history of peanut allergy.J Allergy Clin Immunol. 2001; 107: 367-374Abstract Full Text Full Text PDF PubMed Scopus (467) Google Scholar This sensitivity analysis also took into account the 1% prevalence of PA in the general population.9Ben-Shoshan M. Harrington D.W. Soller L. Fragapane J. Joseph L. St Pierre Y. et al.A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada.J Allergy Clin Immunol. 2010; 125: 1327-1335Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar the 679 cases eligible to participate, 99.3% had good quality DNA. Demographic information is presented in Table I. The 674 cases had approximately twice as many mutations as the controls (20% vs 11%), and the OR for PA and FLG mutation status was similar in the Ontario and Quebec control groups (Table II). The genotype frequencies in cases and controls are shown in the Online Repository available at www.jacionline.org (see Table E4). Among the 13 case definitions, there was no significant difference in the OR for the relationship between PA and FLG mutation status. Seven representative case definitions are shown in Table III. Logistic regression of the ordered case definition criteria variable produced similar results. Not Oral food challenge; psIgE, peanut-specific immunoglobulin E; SPT, skin prick The self-reported prevalence of asthma was 11% in the Ontario controls, compared with 65% in the PA cases (see Table E5 in this article's Online Repository at www.jacionline.org). Univariate analysis found PA status to be the strongest predictor of a mutation, followed by asthma. Neither age nor gender had an appreciable relationship with the presence of FLG mutations on univariate or multivariate analysis and were not included in the final model. Multivariate logistic regression found no evidence for an effect of asthma (OR, 1.12; 95% CI, 0.79-1.59) on the relationship between PA (OR, 1.81; 95% CI, 1.29-2.55) and FLG LOF mutations. The proportion of mutations was similar in those PA cases with and without asthma. Peanut-allergic individuals with asthma had at least 1 mutation in 19.8% of the cases (95% CI, 0.159-0.236), while 18.7% (95% CI, 0.136-0.238) of the PA cases without asthma had at least 1 additional analysis using a constructed atopic asthma variable to control for the effect of smoking yielded similar results. PA status remained significant (OR, 1.88; 95% CI, 1.27-2.80), while history of atopic asthma was not (OR, 1.44; 95% CI, 0.59-3.53). Results were also unchanged after the sensitivity analysis of the self-reported asthma variable, with only PA status remaining significant in the multivariate analysis. The sensitivity analysis on PA status similarly had little effect on the findings. While 20% resolution in cases alone finds that both PA and asthma status are nonsignificant, modeling 20% resolution of cases with 1% prevalence in the general population finds that only PA status remains significant in the multivariate

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Hypoxia is a pro-fibrotic stimulus, which is associated with enhanced collagen synthesis, as well as with augmented collagen prolyl 4-hydroxylase (C-P4H) activity. C-P4H activity is controlled mainly by regulated expression of the alpha C-P4H subunit. In this study we demonstrate that the increased synthesis of C-P4H-alpha(I) protein in human HT1080 fibroblasts under long term hypoxia (36 h, 1% oxygen) is controlled at the translational level. This is mediated by an interaction of RNA-binding protein nucleolin (approximately 64 kDa form) at the 5'- and 3'-untranslated regions (UTR) of the mRNA. The 5'/3'-UTR-dependent mechanism elevates the C-P4H-alpha(I) expression rate 2.3-fold, and participates in a 5.3-fold increased protein level under long term hypoxia. The interaction of nucleolin at the 5'-UTR occurs directly and depends on the existence of an AU-rich element. Statistical evaluation of the approximately 64-kDa nucleolin/RNA interaction studies revealed a core binding sequence, corresponding to UAAAUC or AAAUCU. At the 3'-UTR, nucleolin assembles indirectly via protein/protein interaction, with the help of another 3'-UTR-binding protein, presumably annexin A2. The increased protein level of the approximately 64-kDa nucleolin under hypoxia can be attributed to an autocatalytic cleavage of a high molecular weight nucleolin form, without alterations in nucleolin mRNA concentration. Thus, the alteration of translational efficiency by nucleolin, which occurs through a hypoxia inducible factor independent pathway, is an important step in C-P4H-alpha(I) regulation under hypoxia.

Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

ESPEN Guidelines on Enteral Nutrition: Intensive care

Collagen prolyl 4-hydroxylase (C-P4H) alpha-subunit is of regulatory importance in the assembling of C-P4H tetramers, which are necessary for the hydroxylation of procollagen chains. Change in collagen expression by hypoxia or iron diminishment is a significant issue in extracellular matrix remodeling. It was proposed that C-P4H-alpha (I) is regulated at the posttrancriptional level under these conditions. Here we report that the induction of C-P4H-alpha (I) in human fibrosarcoma cells HT1080 by the iron chelator 2,2-dipyridyl is predominantly caused by an enhancement of mRNA stability. This effect is mediated by an increased synthesis and binding of heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1, which interacts with a (U)(16) element located in the 3'-untranslated region of C-P4H-alpha (I) mRNA. Luciferase reporter gene assays depending on C-P4H-alpha (I) 3'-untranslated region and co-transfection with hnRNP-A2/B1 provide evidence that the (U)(16) element is necessary and sufficient for posttranscriptional control of C-P4H-alpha (I) synthesis under the analyzed conditions. Further indication for the significance of hnRNP-A2/B1 in C-P4H-alpha (I) induction was obtained by micro array experiments. In a data set representing 686 independent physiological conditions, we found a significant positive correlation between hnRNP-A2/B1 and C-P4H-alpha (I) mRNAs.

In recent years new and innovative technologies have been introduced in many sectors, including the field of Education. Augmented Reality (AR) can be beneficial for students, facilitating learning. At the same time, the use of social robots as tutors seems to have positive outcomes in the educational process. In the present study, we examined the use of those technologies in teaching Geography to primary school students, comparing the learning outcomes with each technology. Two experimental and one control group were formed. The control group was taught Geography using a Powerpoint presentation and a human teacher. In one experimental group, AR technology was implemented, while in the other experimental group, social robot NAO acted as the tutor. Pre-tests, post-tests, delayed post-tests and observation sheets were used to collect the data. The results showed that there is no significant difference between the groups regarding students’ learning achievement. However, the implementations provided useful feedback regarding the utilization of AR and social robotics in the classroom. Future research will examine the simultaneous use of both AR and social robots in the classroom to study its applicability, characteristics and outcomes.

Elimination of Progressive Mammary Cancer by Repeated Administrations of Chimeric Antigen Receptor-Modified T Cells

Along with the development of speech and language technologies and growing market interest, social robots have attracted more academic and commercial attention in recent decades. Their multimodal embodiment offers a broad range of possibilities, which have gained importance in the education sector. It has also led to a new technology-based field of language education: robot-assisted language learning (RALL). RALL has developed rapidly in second language learning, especially driven by the need to compensate for the shortage of first-language tutors. There are many implementation cases and studies of social robots, from early government-led attempts in Japan and South Korea to increasing research interests in Europe and worldwide. Compared with RALL used for English as a foreign language (EFL), however, there are fewer studies on applying RALL for teaching Chinese as a foreign language (CFL). One potential reason is that RALL is not well-known in the CFL field. This scope review paper attempts to fill this gap by addressing the balance between classroom implementation and research frontiers of social robots. The review first introduces the technical tool used in RALL, namely the social robot, at a high level. It then presents a historical overview of the real-life implementation of social robots in language classrooms in East Asia and Europe. It then provides a summary of the evaluation of RALL from the perspectives of L2 learners, teachers and technology developers. The overall goal of this paper is to gain insights into RALL's potential and challenges and identify a rich set of open research questions for applying RALL to CFL. It is hoped that the review may inform interdisciplinary analysis and practice for scientific research and front-line teaching in future.

Quality of Life and Depression in CKD: Improving Hope and Health