IgG antibody production and persistence to 6 months following SARS-CoV-2 vaccination: a Northern Ireland observational study

BACKGROUND: This study evaluates spike protein IgG antibody response following Oxford-AstraZeneca COVID-19 vaccination using the AbC-19™ lateral flow device. METHODS: Plasma samples were collected from n=111 individuals from Northern Ireland. The majority were >50 years old and/or clinically vulnerable. Samples were taken at five timepoints from pre-vaccination until 6-months post-first dose. RESULTS: 20.3% of participants had detectable IgG responses pre-vaccination, indicating prior COVID-19. Antibodies were detected in 86.9% of participants three weeks after the first vaccine dose, falling to 74.7% immediately prior to the second dose, and rising to 99% three weeks post-second vaccine. At 6-months post-first dose, this decreased to 90.5%. At all timepoints, previously infected participants had significantly higher antibody levels than those not previously infected. CONCLUSION: This study demonstrates that strong anti-spike protein antibody responses are evoked in almost all individuals that receive two doses of Oxford-AstraZeneca vaccine, and largely persist beyond six months after first vaccination

Does BCR/ABL1 positive Acute Myeloid Leukaemia Exist?

The BCR/ABL1 fusion gene, usually carried by the Philadelphia chromosome (Ph) resulting from t(9;22)(q34;q11) or variants, is pathognomonic for chronic myeloid leukaemia (CML). It is also occasionally found in acute lymphoblastic leukaemia (ALL) mostly in adults and rarely in de novo acute myeloid leukaemia (AML). Array Comparative Genomic Hybridization (aCGH) was used to study six Ph(+)AML, three bi-lineage and four Ph(+)ALL searching for specific genomic profiles. Surprisingly, loss of the IKZF1 and/or CDKN2A genes, the hallmark of Ph(+)ALL, were recurrent findings in Ph(+)AML and accompanied cryptic deletions within the immunoglobulin and T cell receptor genes. The latter two losses have been shown to be part of 'hot spot' genome imbalances associated with BCR/ABL1 positive pre-B lymphoid phenotype in CML and Ph(+)ALL. We applied Significance Analysis of Microarrays (SAM) to data from the 'hot spot' regions to the Ph(+)AML and a further 40 BCR/ABL1(+) samples looking for differentiating features. After exclusion of the most dominant markers, SAM identified aberrations unique to de novo Ph(+)AML that involved relevant genes. While the biological and clinical significance of this specific genome signature remains to be uncovered, the unique loss within the immunoglobulin genes provides a simple test to enable the differentiation of clinically similar de novo Ph(+) AML and myeloid blast crisis of CML. © 2013 John Wiley & Sons Ltd and Crown

Assessing the Health of Richibucto Estuary with the Latent Health Factor Index

The ability to quantitatively assess the health of an ecosystem is often of great interest to those tasked with monitoring and conserving ecosystems. For decades, research in this area has relied upon multimetric indices of various forms. Although indices may be numbers, many are constructed based on procedures that are highly qualitative in nature, thus limiting the quantitative rigour of the practical interpretations made from these indices. The statistical modelling approach to construct the latent health factor index (LHFI) was recently developed to express ecological data, collected to construct conventional multimetric health indices, in a rigorous quantitative model that integrates qualitative features of ecosystem health and preconceived ecological relationships among such features. This hierarchical modelling approach allows (a) statistical inference of health for observed sites and (b) prediction of health for unobserved sites, all accompanied by formal uncertainty statements. Thus far, the LHFI approach has been demonstrated and validated on freshwater ecosystems. The goal of this paper is to adapt this approach to modelling estuarine ecosystem health, particularly that of the previously unassessed system in Richibucto in New Brunswick, Canada. Field data correspond to biotic health metrics that constitute the AZTI marine biotic index (AMBI) and abiotic predictors preconceived to influence biota. We also briefly discuss related LHFI research involving additional metrics that form the infaunal trophic index (ITI). Our paper is the first to construct a scientifically sensible model to rigorously identify the collective explanatory capacity of salinity, distance downstream, channel depth, and silt-clay content --- all regarded a priori as qualitatively important abiotic drivers --- towards site health in the Richibucto ecosystem.Comment: On 2013-05-01, a revised version of this article was accepted for publication in PLoS One. See Journal reference and DOI belo

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

Is chronic pelvic pain a comfortable diagnosis for primary care practitioners: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Chronic pelvic pain (CPP) has a prevalence similar to asthma and chronic back pain, but little is known about how general practitioners (GPs) and practice nurses manage women with this problem. A clearer understanding of current management is necessary to develop appropriate strategies, in keeping with current health care policy, for the supported self-management of patients with long term conditions. The aim of this study was to explore GPs' and practice nurses' understanding and perspectives on the management of chronic pelvic pain.</p> <p>Methods</p> <p>Data were collected using semi-structured interviews with a purposive sample of 21 GPs and 20 practice nurses, in three primary care trusts in the North West of England. Data were analysed using the principles of Framework analysis.</p> <p>Results</p> <p>Analysis suggests that women who present with CPP pose a challenge to GPs and practice nurses. CPP is not necessarily recognized as a diagnostic label and making the diagnosis was achieved only by exclusion. This contrasts with the relative acceptability of labels such as irritable bowel syndrome (IBS). GPs expressed elements of therapeutic nihilism about the condition. Despite practice nurses taking on increasing responsibilities for the management of patients with long term conditions, respondents did not feel that CPP was an area that they were comfortable in managing.</p> <p>Conclusions</p> <p>The study demonstrates an educational/training need for both GPs and practice nurses. GPs described a number of skills and clinical competencies which could be harnessed to develop a more targeted management strategy. There is potential to develop facilitated self- management for use in this patient group, given that this approach has been successful in patients with similar conditions such as IBS.</p

Congenital Plasmodium falciparum infection in neonates in Muheza District, Tanzania

BACKGROUND\ud \ud Although recent reports on congenital malaria suggest that the incidence is increasing, it is difficult to determine whether the clinical disease is due to parasites acquired before delivery or as a result of contamination by maternal blood at birth. Understanding of the method of parasite acquisition is important for estimating the time incidence of congenital malaria and design of preventive measures. The aim of this study was to determine whether the first Plasmodium falciparum malaria disease in infants is due to same parasites present on the placenta at birth.\ud \ud METHODS\ud \ud Babies born to mothers with P. falciparum parasites on the placenta detected by PCR were followed up to two years and observed for malaria episodes. Paired placental and infant peripheral blood samples at first malaria episode within first three months of life were genotyped (msp2) to determine genetic relatedness. Selected amplifications from nested PCR were sequenced and compared between pairs.\ud \ud RESULTS\ud \ud Eighteen (19.1%) out of 95 infants who were followed up developed clinical malaria within the first three months of age. Eight pairs (60%) out of 14 pairs of sequenced placental and cord samples were genetically related while six (40%) were genetically unrelated. One pair (14.3%) out of seven pairs of sequenced placental and infants samples were genetically related. In addition, infants born from primigravidae mothers were more likely to be infected with P. falciparum (P < 0.001) as compared to infants from secundigravidae and multigravidae mothers during the two years of follow up. Infants from multigravidae mothers got the first P. falciparum infection earlier than those from secundigravidae and primigravidae mothers (RR = 1.43).\ud \ud CONCLUSION\ud \ud Plasmodium falciparum malaria parasites present on the placenta as detected by PCR are more likely to result in clinical disease (congenital malaria) in the infant during the first three months of life. However, sequencing data seem to question the validity of this likelihood. Therefore, the relationship between placental parasites and first clinical disease need to be confirmed in larger studies

Altitudinal variation in soil organic carbon stock in coniferous subtropical and broadleaf temperate forests in Garhwal Himalaya

<p>Abstract</p> <p>Background</p> <p>The Himalayan zones, with dense forest vegetation, cover a fifth part of India and store a third part of the country reserves of soil organic carbon (SOC). However, the details of altitudinal distribution of these carbon stocks, which are vulnerable to forest management and climate change impacts, are not well known.</p> <p>Results</p> <p>This article reports the results of measuring the stocks of SOC along altitudinal gradients. The study was carried out in the coniferous subtropical and broadleaf temperate forests of Garhwal Himalaya. The stocks of SOC were found to be decreasing with altitude: from 185.6 to 160.8 t C ha^-1and from 141.6 to 124.8 t C ha^-1in temperature (<it>Quercus leucotrichophora</it>) and subtropical (<it>Pinus roxburghii</it>) forests, respectively.</p> <p>Conclusion</p> <p>The results of this study lead to conclusion that the ability of soil to stabilize soil organic matter depends negatively on altitude and call for comprehensive theoretical explanation</p

A Research Agenda for Helminth Diseases of Humans: Health Research and Capacity Building in Disease-Endemic Countries for Helminthiases Control

Capacity building in health research generally, and helminthiasis research particularly, is pivotal to the implementation of the research and development agenda for the control and elimination of human helminthiases that has been proposed thematically in the preceding reviews of this collection. Since helminth infections affect human populations particularly in marginalised and low-income regions of the world, they belong to the group of poverty-related infectious diseases, and their alleviation through research, policy, and practice is a sine qua non condition for the achievement of the United Nations Millennium Development Goals. Current efforts supporting research capacity building specifically for the control of helminthiases have been devised and funded, almost in their entirety, by international donor agencies, major funding bodies, and academic institutions from the developed world, contributing to the creation of (not always equitable) North–South “partnerships”. There is an urgent need to shift this paradigm in disease-endemic countries (DECs) by refocusing political will, and harnessing unshakeable commitment by the countries' governments, towards health research and capacity building policies to ensure long-term investment in combating and sustaining the control and eventual elimination of infectious diseases of poverty. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. This paper discusses the challenges confronting capacity building for parasitic disease research in DECs, describes current capacity building strategies with particular reference to neglected tropical diseases and human helminthiases, and outlines recommendations to redress the balance of alliances and partnerships for health research between the developed countries of the “North” and the developing countries of the “South”. We argue that investing in South–South collaborative research policies and capacity is as important as their North–South counterparts and is essential for scaled-up and improved control of helminthic diseases and ultimately for regional elimination

Long-term carbon loss in fragmented Neotropical forests

Tropical forests play an important role in the global carbon cycle, as they store a large amount of carbon (C). Tropical forest deforestation has been identified as a major source of CO2 emissions, though biomass loss due to fragmentation—the creation of additional forest edges—has been largely overlooked as an additional CO2 source. Here, through the combination of remote sensing and knowledge on ecological processes, we present long-term carbon loss estimates due to fragmentation of Neotropical forests: within 10 years the Brazilian Atlantic Forest has lost 69 (±14) Tg C, and the Amazon 599 (±120) Tg C due to fragmentation alone. For all tropical forests, we estimate emissions up to 0.2 Pg C y−1 or 9 to 24% of the annual global C loss due to deforestation. In conclusion, tropical forest fragmentation increases carbon loss and should be accounted for when attempting to understand the role of vegetation in the global carbon balance.This study was part of the project ‘Biodiversity conservation in a fragmented landscape at the Atlantic Plateau of São Paulo’ (BIOTA/Caucaia and BioCAPSP) funded by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, project no. 99/05123-4, 01/13309-2, 02/02125-0, 02/02126-7), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, project no. 690144/01-6), Fundação O Boticário de Proteção à Natureza, and by BMBF (German Federal Ministry of Education and Research, project n. 01LB0202). J.P.M. and M.C.R. thank the Brazilian Science Council (Conselho Nacional de Desenvolvimento Científico) for his research fellowship (process no. 307934/2011-0 and 312045/2013-1, respectively). A.H. and S.P. were supported by the ERC advanced grant 233066. M.M. has been supported by BMBF (project n. 01LB0202), and the Department of Ecological Modelling of the Helmholtz Centre for Environmental Research (UFZ). We thank Birgit Felinks for the support during the Mata Atlântica project. Florian Hartig provided valuable comments on an earlier version of this manuscript. S.P. has been funded by the Helmholtz Association of German Research Centres within the project ‘Biomass and Bioenergy systems’. A.H. was also supported by the Helmholtz-Alliance Remote Sensing and Earth System Dynamics. A.H. thanks C. Wissel and H. Bossel for supporting the FORMIND project over the years