β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study.

BACKGROUND: Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy

β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study

Abstract Background Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. Methods To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. Results There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. Conclusions ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy

Nursing considerations to complement the Surviving Sepsis Campaign guidelines

Objectives: To provide a series of recommendations based on the best available evidence to guide clinicians providing nursing care to patients with severe sepsis. Design: Modified Delphi method involving international experts and key individuals in subgroup work and electronic-based discussion among the entire group to achieve consensus. Methods: We used the Surviving Sepsis Campaign guidelines as a framework to inform the structure and content of these guidelines. We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system to rate the quality of evidence from high (A) to very low (D) and to determine the strength of recommendations, with grade 1 indicating clear benefit in the septic population and grade 2 indicating less confidence in the benefits in the septic population. In areas without complete agreement between all authors, a process of electronic discussion of all evidence was undertaken until consensus was reached. This process was conducted independently of any funding. Results: Sixty-three recommendations relating to the nursing care of severe sepsis patients are made. Prevention recommendations relate to education, accountability, surveillance of nosocomial infections, hand hygiene, and prevention of respiratory, central line-related, surgical site, and urinary tract infections, whereas infection management recommendations related to both control of the infection source and transmission-based precautions. Recommendations related to initial resuscitation include improved recognition of the deteriorating patient, diagnosis of severe sepsis, seeking further assistance, and initiating early resuscitation measures. Important elements of hemodynamic support relate to improving both tissue oxygenation and macrocirculation. Recommendations related to supportive nursing care incorporate aspects of nutrition, mouth and eye care, and pressure ulcer prevention and management. Pediatric recommendations relate to the use of antibiotics, steroids, vasopressors and inotropes, fluid resuscitation, sedation and analgesia, and the role of therapeutic end points. Conclusion: Consensus was reached regarding many aspects of nursing care of the severe sepsis patient. Despite this, there is an urgent need for further evidence to better inform this area of critical care

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

The homeless mentally ill: an audit from an inner city hospital.

Objectives: To determine the proportion of those that are homeless attending the Mater Misericordiae Hospital's (MUH) psychiatric service, including those presenting to accident and emergency who were homeless, and to compare the homeless group with the non-homeless so as to obtain a profile of this group. Methods: All adults over 16, referred for psychiatric assessment, attending A&E were included, as were those attending outpatient clinics, liaison consultations and inpatients in the psychiatric unit, in the six-month period from January to June 2003. Excluded were those who were under 16, who refused to participate, who did not speak English, those with a diagnosis of personality disorder and organic brain damage. Questionnaires were completed by psychiatric registrars and a community psychiatric nurse,with an ICD-10 diagnosis recorded on each individual, in consultation with the treating consultant psychiatrist. Results: A total of 628 patients were seen in MUH during the study period, and 13.8% were homeless. Of the homeless, 56.3% were seen as emergency referrals in the A&E, 23% were inpatients (including the psychiatric unit and consultations in medical/surgical wards) and 20.7% were seen in the outpatient department. Of all the A&E referrals to psychiatry, 34.8% were homeless. The homeless presented most commonly in suicidal crisis (26.6%) compared with 12.5% in the non-homeless group. Substance-abuse disorders were the primary diagnosis in 42.3% of the homeless group, accounting for 14.2% in the housed sample. Outcome for both groups was similar, with slightly more homeless being referred for psychiatric admission (17.8%), as compared to 12.0% in the nonhomeless group. Conclusions: Mental illness and the need for psychiatric services remain a serious issue for a significant segment of the homeless population. The homeless are overrepresented in our accident and emergency department, with their psychological and medical needs not being met in primary care. An integrated multi-disciplinary treatment approach, including outreach work, that addresses their many needs, appears to hold the greatest promise of success in this population

Learning modern foreign languages in the Republic of Ireland : a study of the learning experiences of upper-secondary level students

THESIS 9735This study investigates the learning experiences of upper-secondary level students in the Republic of Ireland whilst learning modern foreign languages at school. Essentially this study has sought to capture the students? voice. It is a snapshot in time of the learning experiences of upper-secondary level students. An initial analysis of European educational policy in modern foreign languages education has shown how the period from the European White Paper on Education in 1995 marked a time of greater consultation and investment in modern foreign languages in European education. Thus, in the evaluation phase of this project, questionnaire data from 732 non-sixth year senior cycle students were obtained to provide an understanding of government commitment to the realisation of the Council of Europe policy of \u27mother tongue plus two foreign languages\u27 before the end of compulsory schooling in Ireland - determined in this study by (i) the provision, uptake and retention of modern foreign language subjects in secondary education; (ii) the current situation regarding grade achievement in state examinations in modern foreign language subjects at school; (iii) the development of levels of fluency and proficiency in modern foreign languages at school; (iv) provision for ?prior knowledge? and ?language and linguistic awareness? in modern foreign language study at school; and (v) student motivation and learning strategies in the pursuit of learning modern foreign languages at school

Student Council Minutes - March 27, 1950

Student Counci

Psychometric Analysis of the Comfort with Communication in Palliative and End-of-Life (C-COPE) Instrument.

Background: Nurses must be comfortable facilitating palliative and end-of-life communication with patients and their families.Aim: A validated instrument measuring the comfort of nurses with conducting end-of-life communication is essential for meeting the goals and wishes of patient care. This study aimed to develop and conduct a psychometric evaluation of the Comfort with Communication in Palliative and End-of-Life Care (C-COPE) instrument.Methods: Face, content, and construct validity, including test-retest reliability, were conducted.Results: our experts subjectively confirmed face content validity and the quantitative item content validity index (I-CVI) ranged from 0.67 to 1 and scale content validity index (S-CVI/Ave) was 0.98. Principal axis factoring with Promax rotation yielded a five-factor solution accounting for 66.2% of the variance. The items loading on the five factors ranged from 0.46–0.96 (factor 1), 0.67–0.93 (factor 2), 0.49–0.86 (factor 3), 0.68–0.79 (factor 4), and 0.24–0.96 (factor 5). Internal consistency reliability (coefficient a) was 0.90 for the total C-COPE, and above 0.75 for each factor. The five factors are ‘cultural/spiritual considerations,’ ‘team considerations,’ ‘addressing decision-making,’ ‘addressing symptomatology,’ and ‘deliberate awareness.’ Test-retest reliability yielded an intraclass correlation coefficient (ICC) of 0.87 (CI 95%, 0.82–0.91).Conclusions: The C-COPE is a reliable and valid instrument measuring nurse comfort with palliative and end of-life care communication, yet requires testing in more diverse samples