Functional genomics in chickens:development of integrated-systems microarrays for transcriptional profiling and discovery of regulatory pathways

The genetic networks that govern the differentiation and growth of major tissues of economic importance in the chicken are largely unknown. Under a functional genomics project, our consortium has generated 30 609 expressed sequence tags (ESTs) and developed several chicken DNA microarrays, which represent the Chicken Metabolic/Somatic (10 K) and Neuroendocrine/Reproductive (8 K) Systems (http://udgenome.ags.udel.edu/cogburn/). One of the major challenges facing functional genomics is the development of mathematical models to reconstruct functional gene networks and regulatory pathways from vast volumes of microarray data. In initial studies with liver-specific microarrays (3.1 K), we have examined gene expression profiles in liver during the peri-hatch transition and during a strong metabolic perturbation—fasting and re-feeding—in divergently selected broiler chickens (fast vs. slow-growth lines). The expression of many genes controlling metabolic pathways is dramatically altered by these perturbations. Our analysis has revealed a large number of clusters of functionally related genes (mainly metabolic enzymes and transcription factors) that control major metabolic pathways. Currently, we are conducting transcriptional profiling studies of multiple tissues during development of two sets of divergently selected broiler chickens (fast vs. slow growing and fat vs. lean lines). Transcriptional profiling across multiple tissues should permit construction of a detailed genetic blueprint that illustrates the developmental events and hierarchy of genes that govern growth and development of chickens. This review will briefly describe the recent acquisition of chicken genomic resources (ESTs and microarrays) and our consortium's efforts to help launch the new era of functional genomics in the chicken

Transcriptional profiling and pathway analysis reveal differences in pituitary gland function, morphology, and vascularization in chickens genetically selected for high or low body weight

Though intensive genetic selection has led to extraordinary advances in growth rate and feed efficiency in production of meat-type chickens, endocrine processes controlling these traits are still poorly understood. The anterior pituitary gland is a central component of the neuroendocrine system and plays a key role in regulating important physiological processes that directly impact broiler production efficiency, though how differences in pituitary gland function contribute to various growth and body composition phenotypes is not fully understood.https://doi.org/10.1186/s12864-019-5670-

On biases in precise point positioning with multi-constellation and multi-frequency GNSS data

© 2016 IOP Publishing Ltd. Various types of biases in Global Navigation Satellite System (GNSS) data preclude integer ambiguity fixing and degrade solution accuracy when not being corrected during precise point positioning (PPP). In this contribution, these biases are first reviewed, including satellite and receiver hardware biases, differential code biases, differential phase biases, initial fractional phase biases, inter-system receiver time biases, and system time scale offset. PPP models that take account of these biases are presented for two cases using ionosphere-free observations. The first case is when using primary signals that are used to generate precise orbits and clock corrections. The second case applies when using additional signals to the primary ones. In both cases, measurements from single and multiple constellations are addressed. It is suggested that the satellite-related code biases be handled as calibrated quantities that are obtained from multi-GNSS experiment products and the fractional phase cycle biases obtained from a network to allow for integer ambiguity fixing. Some receiver-related biases are removed using between-satellite single differencing, whereas other receiver biases such as inter-system biases are lumped with differential code and phase biases and need to be estimated. The testing results show that the treatment of biases significantly improves solution convergence in the float ambiguity PPP mode, and leads to ambiguity-fixed PPP within a few minutes with a small improvement in solution precision

Use of group records of feed intake to select for feed efficiency in rabbit

Models for genetic evaluation of feed efficiency (FE) for animals housed in groups when they are either fed ad libitum (F) or on restricted (R) feeding were implemented. Definitions of FE on F included group records of feed intake (¯FI_F) and individual records of growth rate (GF) and metabolic weight (MF). Growth rate (GR) as FE measurement on R was used. Data corresponded to 5,336 kits from a rabbit sire line, from 1,255 litters in 14 batches and 667 cages. A five-trait mixed model (also with metabolic weight on R, MR) was implemented including, for each trait, the systematic effects of batch, body weight at weaning, parity order and litter size; and the random effects of litter, additive genetic and individual. A Bayesian analysis was performed. Conditional traits such as ¯FI_F |M_F,G_F and G_F |M_F,¯FI_F were obtained from elements of additive genetics ( ( ¯FI_F |M_F,G_F )_g and ( G_F |M_F,¯FI_F )_g ) or phenotypic (( ¯FI_F |M_F,G_F )_p and ( G_F |M_F,¯FI_F )_p ) (co)variance matrices. In the first case, heritabilities were low (0.07 and 0.06 for ( ¯FI_F |M_F,G_F )_g and ( G_F |M_F,¯FI_F )_g, respectively) but null genetic correlation between the conditional and conditioning traits is guaranteed. In the second case, heritabilities were higher (0.22 and 0.16 for ( ¯FI_F |M_F,G_F )_p and ( G_F |M_F,¯FI_F )_p, respectively) but the genetic correlation between ( ¯FI_F |M_F,G_F )_p and G_F was moderate (0.58). Heritability of GR was low (0.08). This trait was negatively correlated with ( G_F |M_F,¯FI_F )_p and ( G_F |M_F,¯FI_F )_gof animals on F, which indicate a different genetic background. The correlation between GR and GF was also low to moderate (0.48) and the additive variance of GF was almost 4 times that of GR, suggesting the presence of a substantial genotype by feeding regimen interaction.info:eu-repo/semantics/acceptedVersio

Sub-Optimal Vitamin B-12 Levels among ART-Naïve HIV-Positive Individuals in an Urban Cohort in Uganda

Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART) naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals’ Joint AIDS Program (MJAP) or the Infectious Diseases Institute (IDI) clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200–900). Sub-optimal vitamin B-12 levels (<300 pg/ml) were found in 75/204 (36.8%). Twenty-one of 204 (10.3%) had vitamin B-12 deficiency (<200 pg/ml) while 54/204 (26.5%) had marginal depletion (200–300 pg/ml). Irritable mood was observed more among individuals with sub-optimal vitamin B-12 levels (OR 2.5, 95% CI; 1.1–5.6, P = 0.03). Increasing MCV was associated with decreasing serum B-12 category; 86.9 fl (±5.1) vs. 83 fl (±8.4) vs. 82 fl (±8.4) for B-12 deficiency, marginal and normal B-12 categories respectively (test for trend, P = 0.017). Compared to normal B-12, individuals with vitamin B-12 deficiency had a longer known duration of HIV infection: 42.2 months (±27.1) vs. 29.4 months (±23.8; P = 0.02). Participants eligible for ART (CD4<350 cells/µl) with sub-optimal B-12 had a higher mean rate of CD4 decline compared to counterparts with normal B-12; 118 (±145) vs. 22 (±115) cells/µl/year, P = 0.01 respectively. The prevalence of a sub-optimal vitamin B-12 was high in this HIV-infected, ART-naïve adult clinic population in urban Uganda. We recommend prospective studies to further clarify the causal relationships of sub-optimal vitamin B-12, and explore the role of vitamin B-12 supplementation in immune recovery

Experience of safety monitoring in the context of a prospective observational study of artemether-lumefantrine in rural Tanzania: lessons learned for pharmacovigilance reporting

<p>Abstract</p> <p>Objectives</p> <p>To identify and implement strategies that help meet safety monitoring requirements in the context of an observational study for artemether-lumefantrine (AL) administered as first-line treatment for uncomplicated malaria in rural Tanzania.</p> <p>Methods</p> <p>Pharmacovigilance procedures were developed through collaboration between the investigating bodies, the relevant regulatory authority and the manufacturer of AL. Training and refresher sessions on the pharmacovigilance system were provided for healthcare workers from local health facilities and field recorders of the Ifakara Health Demographic Surveillance System (IHDSS). Three distinct channels for identification of adverse events (AEs) and serious adverse events (SAEs) were identified and implemented. Passive reporting took place through IHDSS and health care facilities, starting in October 2007. The third channel was through solicited reporting that was included in the context of a survey on AL as part of the ALIVE (<b>A</b>rtemether-<b>L</b>umefantrine <b>I</b>n <b>V</b>ulnerable patients: <b>E</b>xploring health impact) study (conducted only in March-April 2008).</p> <p>Results</p> <p>Training was provided for 40 healthcare providers (with refresher training 18 months later) and for six field recorders. During the period 1^stSeptember 2007 to 31^stMarch 2010, 67 AEs were reported including 52 under AL, five under sulphadoxine-pyrimethamine, one under metakelfin, two after antibiotics; the remaining seven were due to anti-pyretic or anti-parasite medications. Twenty patients experienced SAEs; in 16 cases, a relation to AL was suspected. Six of the 20 cases were reported within 24 hours of occurrence.</p> <p>Discussion</p> <p>Safety monitoring and reporting is possible even in settings with weak health infrastructure. Reporting can be enhanced by regular and appropriate training of healthcare providers. SMS text alerts provide a practical solution to communication challenges.</p> <p>Conclusion</p> <p>Experience gained in this setting could help to improve spontaneous reporting of AEs and SAEs to health authorities or marketing authorization holders.</p

Biophysics of Lower Back Pain

Lower back pain is one of the most predominant problems in the general public. It has been traditionally regarded as a mechanical problem by both orthodox and complementary practitioners. This study was conducted to evaluate the lumbosacral angle which is an inherent cause of lower back pain and also investigate the shearing and compressing forces on the lumbar spine. The study was carried out at in a Hospital within the …. Metropolis. A total of 210 patients’ data consisting of 72 males and 138 females was considered. The lumbosacral angle was measured using Ferguson’s method with the MicroDicom software. Patients were grouped into ages; 0 – 20, 21 – 30, 31 – 40, 41 – 50, 51 – 60, 61 – 70, 71 – 80 and 81 – 100. The number of patients in each age group was; 7, 12, 26, 28, 56, 27, 11 and 7 respectively. The average lumbosacral angle evaluated, according to age group was; 36.3º, 39º, 35.81º, 36.23º, 36.55º, 37.5º, 35.89 º and 34.92º. The overall lumbosacral mean was determined to be 36.50º. The lumbosacral angle evaluated was used to determine the corresponding compressive and shear forces at the lumbar region which are the principal predictors of the lower back pain

A Multifaceted Intervention to Implement Guidelines and Improve Admission Paediatric Care in Kenyan District Hospitals: A Cluster Randomised Trial

Philip Ayieko and colleagues report the outcomes of a cluster-randomized trial carried out in eight Kenyan district hospitals evaluating the effects of a complex intervention involving improved training and supervision for clinicians. They found a higher performance of hospitals assigned to the complex intervention on a variety of process of care measures, as compared to those receiving the control intervention

On the cost-effectiveness of insecticide-treated wall liner and indoor residual spraying as additions to insecticide treated bed nets to prevent malaria: findings from cluster randomized trials in Tanzania.

BACKGROUND: Despite widespread use of long-lasting insecticidal nets (LLINs) and other tools, malaria caused 409,000 deaths worldwide in 2019. While indoor residual spraying (IRS) is an effective supplement, IRS is moderately expensive and logistically challenging. In endemic areas, IRS requires yearly application just before the main rainy season and potential interim reapplications. A new technology, insecticide-treated wall liner (ITWL), might overcome these challenges. METHODS: We conducted a 44-cluster two-arm randomized controlled trial in Muheza, Tanzania from 2015 to 2016 to evaluate the cost and efficacy of a non-pyrethroid ITWL to supplement LLINs, analyzing operational changes over three installation phases. The estimated efficacy (with 95% confidence intervals) of IRS as a supplement to LLINs came mainly from a published randomized trial in Muleba, Tanzania. We obtained financial costs of IRS from published reports and conducted a household survey of a similar IRS program near Muleba to determine household costs. The costs of ITWL were amortized over its 4-year expected lifetime and converted to 2019 US dollars using Tanzania's GDP deflator and market exchange rates. RESULTS: Operational improvements from phases 1 to 3 raised ITWL coverage from 35.1 to 67.1% of initially targeted households while reducing economic cost from $34.18 to$30.56 per person covered. However, 90 days after installing ITWL in 5666 households, the randomized trial was terminated prematurely because cone bioassay tests showed that ITWL no longer killed mosquitoes and therefore could not prevent malaria. The ITWL cost $10.11 per person per year compared to$5.69 for IRS. With an efficacy of 57% (3-81%), IRS averted 1162 (61-1651) disability-adjusted life years (DALYs) per 100,000 population yearly. Its incremental cost-effectiveness ratio (ICER) per DALY averted was $490 (45% of Tanzania's per capita gross national income). CONCLUSIONS: These findings provide design specifications for future ITWL development and implementation. It would need to be efficacious and more effective and/or less costly than IRS, so more persons could be protected with a given budget. The durability of a previous ITWL, progress in non-pyrethroid tools, economies of scale and competition (as occurred with LLINs), strengthened community engagement, and more efficient installation and management procedures all offer promise of achieving these goals. Therefore, ITWLs merit ongoing study. FIRST POSTED: 2015 ( NCT02533336 )