But is this really the ‘parent’ or ‘guardian’? Practical strategies for consent to child research in South Africa

Research ethics committees (RECs) in South Africa may require consent from a parent or legal guardian for child research. In instances where an REC determines that parental or guardianship consent is required, how far should researchers go to establish if the accompanying adult is in fact the parent or guardian? Should researchers accept disclosures at face value, probe assertions that are made, or even call for supporting documentation? In this article we set out the facts research staff should possess, propose key questions they could ask, and recommend practical steps for uncertain cases. We recognise that a parental/guardianship consent strategy may not be appropriate in all instances, but do not debate that issue in this article. This article is confined to practical advice for researchers wishing to implement a parental or guardianship consent approach

Using the concept of ‘parental responsibilities and rights’ to identify adults able to provide proxy consent to child research in South Africa

There are circumstances where independent consent to research by children is appropriate (for example, where the participants are older adolescents and the research approximates minimal risk). However, in many instances an important safeguard will be a dual consenting process involving an appropriate adult alongside the potential child participant (according to their evolving capacities). But what adults are appropriate in what instances? We attempt to use principles set out in the Children’s Act (2010) to address this question. This article differentiates between those adults who according to the Children’s Act (2010) have full parental responsibilities and rights (i.e. parents/guardians) and those who have no parental responsibilities and rights (i.e. caregivers). We argue that some responsibilities accorded to caregivers are substantially similar to the authority to provide proxy consent to research in which the research risks approximate those risks present in the child’s everyday life. In these instances, we argue that where parents and guardians are not available, caregivers should be considered by research ethics committees as a possible source of proxy consent for younger children. This approach might not be logically extended to caregiver consent for clinical trial enrolment, for which alternative arguments may need to be debated

Does the PI3K pathway promote or antagonize regulatory T cell development and function?

Regulatory T cells (Tregs) prevent autoimmunity and inflammation by suppressing the activation of other T cells and antigen presenting cells. The role of phosphoinositide 3-kinase (PI3K) signaling in Treg is controversial. Some studies suggest that inhibition of the PI3K pathway is essential for the development of Tregs whereas other studies have shown reduced Treg numbers and function when PI3K activity is suppressed. Here we attempt to reconcile the different studies that have explored PI3K and the downstream effectors Akt, Foxo, and mTOR in regulatory T cell development and function and discuss the implications for health and therapeutic intervention

The role of lumbar puncture in children with suspected central nervous system infection

BACKGROUND: The use of the lumbar puncture in the diagnosis of central nervous system infection in acutely ill children is controversial. Recommendations have been published but it is unclear whether they are being followed. METHODS: The medical case notes of 415 acute medical admissions in a children's hospital were examined to identify children with suspected central nervous system infection and suspected meningococcal septicaemia. We determined whether lumbar punctures were indicated or contraindicated, whether they had been performed, and whether the results contributed to the patients' management. RESULTS: Fifty-two children with suspected central nervous system infections, and 43 with suspected meningococcal septicaemia were identified. No lumbar punctures were performed in patients with contraindications, but only 25 (53%) of 47 children with suspected central nervous system infection and no contraindications received a lumbar puncture. Lumbar puncture findings contributed to the management in 18 (72%) of these patients, by identifying a causative organism or excluding bacterial meningitis. CONCLUSION: The recommendations for undertaking lumbar punctures in children with suspected central nervous system infection are not being followed because many children that should receive lumbar punctures are not getting them. When they are performed, lumbar puncture findings make a useful contribution to the patients' management

Lack of association of two common polymorphisms on 9p21 with risk of coronary heart disease and myocardial infarction; results from a prospective cohort study

Background: Recent genome wide association (GWA) studies identified two Single Nucleotide Polymorphisms (SNP) (rs10757278 and rs10757274) in the region of the CDK2NA and CDK2NB genes to be consistently associated with the risks of coronary heart disease (CHD) and myocardial infarction (MI). We examined the SNPs in relation to the risk of CHD and MI in a large population based study of elderly population. Methods: The Rotterdam Study is a population-based, prospective cohort study among 7983 participants aged 55 years and older. Associations of the polymorphisms with CHD and MI were assessed by use of Cox proportional hazards analyses. Results: In an additive model, the age and sex adjusted hazard ratios (HRs) (95% confidence interval) for CHD and MI were 1.03 (0.90, 1.18) and 0.94 (0.82, 1.08) per copy of the G allele of rs10757274. The corresponding HRs were 1.03 (0.90, 1.18) and 0.93 (0.81, 1.06) for the G allele of rs10757278. The association of the SNPs with CHD and MI was not significant in any of the subgroups of CHD risk factors. Conclusion: We were not able to show an association of the studied SNPs with risks of CHD and MI. This may be due to differences in genes involved in the occurrence of CHD in young and older people

Xnrs and Activin Regulate Distinct Genes during Xenopus Development: Activin Regulates Cell Division

BACKGROUND: The mesoderm of the amphibian embryo is formed through an inductive interaction in which vegetal cells of the blastula-staged embryo act on overlying equatorial cells. Candidate mesoderm-inducing factors include members of the transforming growth factor type β family such as Vg1, activin B, the nodal-related proteins and derrière. METHODOLOGY AND PRINCIPLE FINDINGS: Microarray analysis reveals different functions for activin B and the nodal-related proteins during early Xenopus development. Inhibition of nodal-related protein function causes the down-regulation of regionally expressed genes such as chordin, dickkopf and XSox17α/β, while genes that are mis-regulated in the absence of activin B tend to be more widely expressed and, interestingly, include several that are involved in cell cycle regulation. Consistent with the latter observation, cells of the involuting dorsal axial mesoderm, which normally undergo cell cycle arrest, continue to proliferate when the function of activin B is inhibited. CONCLUSIONS/SIGNIFICANCE: These observations reveal distinct functions for these two classes of the TGF-β family during early Xenopus development, and in doing so identify a new role for activin B during gastrulation

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Statistical Modeling of Single Target Cell Encapsulation

High throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems.Wallace H. Coulter Foundation (Young Investigator in Bioengineering Award)National Institutes of Health (U.S.) (Grant R01AI081534)National Institutes of Health (U.S.) (Grant R21AI087107

Competition of Escherichia coli DNA Polymerases I, II and III with DNA Pol IV in Stressed Cells

Escherichia coli has five DNA polymerases, one of which, the low-fidelity Pol IV or DinB, is required for stress-induced mutagenesis in the well-studied Lac frameshift-reversion assay. Although normally present at ∼200 molecules per cell, Pol IV is recruited to acts of DNA double-strand-break repair, and causes mutagenesis, only when at least two cellular stress responses are activated: the SOS DNA-damage response, which upregulates DinB ∼10-fold, and the RpoS-controlled general-stress response, which upregulates Pol IV about 2-fold. DNA Pol III was also implicated but its role in mutagenesis was unclear. We sought in vivo evidence on the presence and interactions of multiple DNA polymerases during stress-induced mutagenesis. Using multiply mutant strains, we provide evidence of competition of DNA Pols I, II and III with Pol IV, implying that they are all present at sites of stress-induced mutagenesis. Previous data indicate that Pol V is also present. We show that the interactions of Pols I, II and III with Pol IV result neither from, first, induction of the SOS response when particular DNA polymerases are removed, nor second, from proofreading of DNA Pol IV errors by the editing functions of Pol I or Pol III. Third, we provide evidence that Pol III itself does not assist with but rather inhibits Pol IV-dependent mutagenesis. The data support the remaining hypothesis that during the acts of DNA double-strand-break (DSB) repair, shown previously to underlie stress-induced mutagenesis in the Lac system, there is competition of DNA polymerases I, II and III with DNA Pol IV for action at the primer terminus. Up-regulation of Pol IV, and possibly other stress-response-controlled factor(s), tilt the competition in favor of error-prone Pol IV at the expense of more accurate polymerases, thus producing stress-induced mutations. This mutagenesis assay reveals the DNA polymerases operating in DSB repair during stress and also provides a sensitive indicator for DNA polymerase competition and choice in vivo