A Close-up Examination of Racial Disparities in Infant and Maternal Outcomes in Montgomery County, Ohio

Background: Infant and maternal outcomes in Montgomery County, Ohio, are among the worst in the state and rival that of many low-income nations. This study compares maternal and infant outcomes across 3 zip codes in Montgomery County to discern factors that are influencing health outcomes for their residents. The zip codes represent 3 distinct communities with unique racial and socioeconomic makeups. Methods: A cohort of mother-infant dyads (n=5098) who delivered at Miami Valley Hospital and Good Samaritan Hospital from January 1, 2009, to January 1, 2019, was analyzed via retrospective chart review. Maternal health outcome composite score (MCS) and infant health outcome composite score (ICS) from Trotwood, Ohio, (zip code 45426) were compared to those of 2 nearby zip codes (45415 and 45424), which were chosen for their lower infant mortality rates and proximity to Trotwood. Continuous variables were compared by ANOVA followed by post hoc Tukey tests. Categorical variables were compared via chi-square analysis. Results: The MCS and ICS were stratified by zip code and maternal age, race, and BMI. There was a statistically significant difference in MCS for race and BMI across all zip codes, but no statistically significant difference for maternal age. There was no statistically significant difference in ICS across maternal age, race, and BMI. Conclusion: Maternal outcomes for Black women were consistently worse across communities while outcomes for other races varied. Our study shows that maternal outcomes did not correlate with infant outcomes, indicating that interventions focusing on improving maternal outcomes may be inadequate at addressing infant outcomes. Investigations surrounding race-specific interventions in all populations are needed

Seasonal Changes in Brown Fat and Pelage in Southern Short-Tailed Shrews

We examined cellular changes in interscapular brown adipose tissue and pelage characteristics in Blarina carolinensis collected throughout the year in eastern Virginia. Cellular volume occupied by mitochondria and maximum mitochondrial size were significantly greater in the brown adipose tissue of winter shrews than in summer shrews. Lipid droplets occupied greater volume and were larger in shrews in summer than winter shrews. There were no seasonal differences in hair density; Type I and Type II guard hairs were significantly longer in winter than summer by a factor of 1.3. Woolly hairs were 1.2 times longer in winter than summer, a non-significant difference

Headloop suppression PCR and its application to selective amplification of methylated DNA sequences

Selective amplification in PCR is principally determined by the sequence of the primers and the temperature of the annealing step. We have developed a new PCR technique for distinguishing related sequences in which additional selectivity is dependent on sequences within the amplicon. A 5′ extension is included in one (or both) primer(s) that corresponds to sequences within one of the related amplicons. After copying and incorporation into the PCR product this sequence is then able to loop back, anneal to the internal sequences and prime to form a hairpin structure—this structure is then refractory to further amplification. Thus, amplification of sequences containing a perfect match to the 5′ extension is suppressed while amplification of sequences containing mismatches or lacking the sequence is unaffected. We have applied Headloop PCR to DNA that had been bisulphite-treated for the selective amplification of methylated sequences of the human GSTP1 gene in the presence of up to a 10(5)-fold excess of unmethylated sequences. Headloop PCR has a potential for clinical application in the detection of differently methylated DNAs following bisulphite treatment as well as for selective amplification of sequence variants or mutants in the presence of an excess of closely related DNA sequences

Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia

Deletion of exon 9 from Cullin‐3 (CUL3, residues 403–459: CUL3Δ403–459) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form of familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 and various substrate adaptors to form Cullin‐RING‐ubiquitin‐ligase complexes. Bound to KLHL3, CUL3‐RBX1 ubiquitylates WNK kinases, promoting their ubiquitin‐mediated proteasomal degradation. Since WNK kinases activate Na/Cl co‐transporters to promote salt retention, CUL3 regulates blood pressure. Mutations in both KLHL3 and WNK kinases cause PHA2 by disrupting Cullin‐RING‐ligase formation. We report here that the PHA2E mutant, CUL3Δ403–459, is severely compromised in its ability to ubiquitylate WNKs, possibly due to altered structural flexibility. Instead, CUL3Δ403–459 auto‐ubiquitylates and loses interaction with two important Cullin regulators: the COP9‐signalosome and CAND1. A novel knock‐in mouse model of CUL3WT/Δ403–459 closely recapitulates the human PHA2E phenotype. These mice also show changes in the arterial pulse waveform, suggesting a vascular contribution to their hypertension not reported in previous FHHt models. These findings may explain the severity of the FHHt phenotype caused by CUL3 mutations compared to those reported in KLHL3 or WNK kinases

Investigating the New Landscapes of Welfare: Housing Policy, Politics and the Emerging Research Agenda

As debates about housing form an increasingly important arena of political controversy, much has been written about the new fissures that have appeared as governments not only struggle to reduce public expenditure deficits but also attempt to address problems such as affordability and homelessness. It is widely anticipated that new conflicts will be played out in the private rental market as access to homeownership becomes unrealistic and the supply of social housing diminishes. However, what other tensions might surface; that hitherto have not been subject to the critical gaze of housing research? In this paper, we provide some thoughts on the nascent policy issues as well as the ideological schisms that are likely to develop in coming years, offering suggestions as to how the focus of housing policy research might be reoriented towards a “politics” framework to capture and better understand the conflicts that are likely to arise

Active Amplification of the Terrestrial Albedo to Mitigate Climate Change: An Exploratory Study

This study explores the potential to enhance the reflectance of solar insolation by the human settlement and grassland components of the Earth's terrestrial surface as a climate change mitigation measure. Preliminary estimates derived using a static radiative transfer model indicate that such efforts could amplify the planetary albedo enough to offset the current global annual average level of radiative forcing caused by anthropogenic greenhouse gases by as much as 30 percent or 0.76 W/m2. Terrestrial albedo amplification may thus extend, by about 25 years, the time available to advance the development and use of low-emission energy conversion technologies which ultimately remain essential to mitigate long-term climate change. However, additional study is needed to confirm the estimates reported here and to assess the economic and environmental impacts of active land-surface albedo amplification as a climate change mitigation measure.Comment: 21 pages, 3 figures. In press with Mitigation and Adaptation Strategies for Global Change, Springer, N

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

The Rise of the Resilient Local Authority?

The term resilience is increasingly being utilised within the study of public policy to depict how individuals, communities and organisations can adapt, cope, and ‘bounce back’ when faced with external shocks such as climate change, economic recession and cuts in public expenditure. In focussing on the local dimensions of the resilience debate, this article argues that the term can provide useful insights into how the challenges facing local authorities in the UK can be reformulated and reinterpreted. The article also distinguishes between resilience as ‘recovery’ and resilience as ‘transformation’, with the latter's focus on ‘bouncing forward’ from external shocks seen as offering a more radical framework within which the opportunities for local innovation and creativity can be assessed and explained. While also acknowledging some of the weaknesses of the resilience debate, the dangers of conceptual ‘stretching’, and the extent of local vulnerabilities, the article highlights a range of examples where local authorities – and crucially, local communities – have enhanced their adaptive capacity, within existing powers and responsibilities. From this viewpoint, some of the barriers to the development of resilient local government are not insurmountable, and can be overcome by ‘digging deep’ to draw upon existing resources and capabilities, promoting a strategic approach to risk, exhibiting greater ambition and imagination, and creating space for local communities to develop their own resilience

Longer First Introns Are a General Property of Eukaryotic Gene Structure

While many properties of eukaryotic gene structure are well characterized, differences in the form and function of introns that occur at different positions within a transcript are less well understood. In particular, the dynamics of intron length variation with respect to intron position has received relatively little attention. This study analyzes all available data on intron lengths in GenBank and finds a significant trend of increased length in first introns throughout a wide range of species. This trend was found to be even stronger when using high-confidence gene annotation data for three model organisms (Arabidopsis thaliana, Caenorhabditis elegans, and Drosophila melanogaster) which show that the first intron in the 5′ UTR is - on average - significantly longer than all downstream introns within a gene. A partial explanation for increased first intron length in A. thaliana is suggested by the increased frequency of certain motifs that are present in first introns. The phenomenon of longer first introns can potentially be used to improve gene prediction software and also to detect errors in existing gene annotations