Does angiotensin-1 converting enzyme genotype influence motor or cognitive development after pre-term birth?

BACKGROUND: Raised activity of the renin-angiotensin system (RAS) may both amplify inflammatory and free radical responses and decrease tissue metabolic efficiency and thus enhance cerebral injury in the preterm infant. The angiotensin-converting enzyme (ACE) DD genotype is associated with raised ACE and RAS activity as well as potentially adverse stimuli such as inflammation. The DD genotype has been associated with neurological impairments in the elderly, and thus may be also associated with poorer motor or cognitive development amongst children born preterm prematurely. METHODS: The association of DD genotype with developmental progress amongst 176 Caucasian children born at less than 33 weeks gestation (median birthweight 1475 g, range 645–2480 g; gestation 30 weeks, range 22–32; 108 male) was examined at 2 and 5 1/2 years of age. Measured neuro-cognitive outcomes were cranial ultrasound abnormalities, cerebral palsy, disability, Griffiths Developmental Quotient [DQ] at 2 yrs, and General Cognitive Ability [British Ability Scales-11] and motor performance [ABC Movement], both performed at 5 1/2 yrs. All outcomes were correlated with ACE genotype. RESULTS: The DD genotype was not associated with lower developmental quotients even after accounting for important social variables. CONCLUSION: These data do not support either a role for ACE in the development of cognitive or motor function in surviving infants born preterm or inhibition of ACE as a neuroprotective therapy

Rorty’s Social Theory and the Narrative of U.S. History Curriculum

This paper explores the implications for creating a U.S. history narrative from a Rortyan perspective. First, we review Rorty’s social theory. Second, we discuss implications of his ideas regarding the creation of a U.S. history narrative based upon his ideas. Finally, we examine two concerns that would likely emerge if a Rortyan U.S. history curriculum was taught in our public schools

Measuring health inequality among children in developing countries: does the choice of the indicator of economic status matter?

Background Currently, poor-rich inequalities in health in developing countries receive a lot of attention from both researchers and policy makers. Since measuring economic status in developing countries is often problematic, different indicators of wealth are used in different studies. Until now, there is a lack of evidence on the extent to which the use of different measures of economic status affects the observed magnitude of health inequalities. Methods This paper provides this empirical evidence for 10 developing countries, using the Demographic and Health Surveys data-set. We compared the World Bank asset index to three alternative wealth indices, all based on household assets. Under-5 mortality and measles immunisation coverage were the health outcomes studied. Poor-rich inequalities in under-5 mortality and measles immunisation coverage were measured using the Relative Index of Inequality. Results Comparing the World Bank index to the alternative indices, we found that (1) the relative position of households in the national wealth hierarchy varied to an important extent with the asset index used, (2) observed poor-rich inequalities in under-5 mortality and immunisation coverage often changed, in some cases to an important extent, and that (3) the size and direction of this change varied per country, index, and health indicator. Conclusion Researchers and policy makers should be aware that the choice of the measure of economic status influences the observed magnitude of health inequalities, and that differences in health inequalities between countries or time periods, may be an artefact of different wealth measures used

Evidence for the classical integrability of the complete AdS(4) x CP(3) superstring

We construct a zero-curvature Lax connection in a sub-sector of the superstring theory on AdS(4) x CP(3) which is not described by the OSp(6|4)/U(3) x SO(1,3) supercoset sigma-model. In this sub-sector worldsheet fermions associated to eight broken supersymmetries of the type IIA background are physical fields. As such, the prescription for the construction of the Lax connection based on the Z_4-automorphism of the isometry superalgebra OSp(6|4) does not do the job. So, to construct the Lax connection we have used an alternative method which nevertheless relies on the isometry of the target superspace and kappa-symmetry of the Green-Schwarz superstring.Comment: 1+26 pages; v2: minor typos corrected, acknowledgements adde

The attitude of patients with progressive ataxias towards clinical trials

Background The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. Results Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. Conclusions Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials

Issues in the construction of wealth indices for the measurement of socio-economic position in low-income countries

BACKGROUND: Epidemiological studies often require measures of socio-economic position (SEP). The application of principal components analysis (PCA) to data on asset-ownership is one popular approach to household SEP measurement. Proponents suggest that the approach provides a rational method for weighting asset data in a single indicator, captures the most important aspect of SEP for health studies, and is based on data that are readily available and/or simple to collect. However, the use of PCA on asset data may not be the best approach to SEP measurement. There remains concern that this approach can obscure the meaning of the final index and is statistically inappropriate for use with discrete data. In addition, the choice of assets to include and the level of agreement between wealth indices and more conventional measures of SEP such as consumption expenditure remain unclear. We discuss these issues, illustrating our examples with data from the Malawi Integrated Household Survey 2004-5. METHODS: Wealth indices were constructed using the assets on which data are collected within Demographic and Health Surveys. Indices were constructed using five weighting methods: PCA, PCA using dichotomised versions of categorical variables, equal weights, weights equal to the inverse of the proportion of households owning the item, and Multiple Correspondence Analysis. Agreement between indices was assessed. Indices were compared with per capita consumption expenditure, and the difference in agreement assessed when different methods were used to adjust consumption expenditure for household size and composition. RESULTS: All indices demonstrated similarly modest agreement with consumption expenditure. The indices constructed using dichotomised data showed strong agreement with each other, as did the indices constructed using categorical data. Agreement was lower between indices using data coded in different ways. The level of agreement between wealth indices and consumption expenditure did not differ when different consumption equivalence scales were applied. CONCLUSION: This study questions the appropriateness of wealth indices as proxies for consumption expenditure. The choice of data included had a greater influence on the wealth index than the method used to weight the data. Despite the limitations of PCA, alternative methods also all had disadvantages

Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci

Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other

Low-Weight Primes for Lightweight Elliptic Curve Cryptography on 8-bit AVR Processors

Small 8-bit RISC processors and micro-controllers based on the AVR instruction set architecture are widely used in the embedded domain with applications ranging from smartcards over control systems to wireless sensor nodes. Many of these applications require asymmetric encryption or authentication, which has spurred a body of research into implementation aspects of Elliptic Curve Cryptography (ECC) on the AVR platform. In this paper, we study the suitability of a special class of finite fields, the so-called Optimal Prime Fields (OPFs), for a "lightweight" implementation of ECC with a view towards high performance and security. An OPF is a finite field Fp defined by a prime of the form p = u*2^k + v, whereby both u and v are "small" (in relation to 2^k) so that they fit into one or two registers of an AVR processor. OPFs have a low Hamming weight, which allows for a very efficient implementation of the modular reduction since only the non-zero words of p need to be processed. We describe a special variant of Montgomery multiplication for OPFs that does not execute any input-dependent conditional statements (e.g. branch instructions) and is, hence, resistant against certain side-channel attacks. When executed on an Atmel ATmega processor, a multiplication in a 160-bit OPF takes just 3237 cycles, which compares favorably with other implementations of 160-bit modular multiplication on an 8-bit processor. We also describe a performance-optimized and a security-optimized implementation of elliptic curve scalar multiplication over OPFs. The former uses a GLV curve and executes in 4.19M cycles (over a 160-bit OPF), while the latter is based on a Montgomery curve and has an execution time of approximately 5.93M cycles. Both results improve the state-of-the-art in lightweight ECC on 8-bit processors

Outpatient treatment with AZD7442 (tixagevimab/cilgavimab) prevented Covid-19 hospitalizations over 6 months and reduced symptom progression in the TACKLE randomized trial

Introduction We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study. Methods Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset. Results Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1–2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively. Conclusions AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19. Clinical Trial Registration Clinicaltrials.gov, NCT04723394. (https://beta.clinicaltrials.gov/study/NCT04723394)