27 research outputs found
Eff ectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study
Background The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing
serotypes that are important in low-income and middle-income countries. Vaccine eff ectiveness estimates are scarce
in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the
eff ectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection
and in those not infected with HIV.
Methods Cases of invasive pneumococcal disease in children aged 5 years or younger were identifi ed through national
laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital
controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not
infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic
regression, we calculated vaccine eff ectiveness as a percentage, with the equation 1 â [adjusted odds ratio for
vaccination] Ă 100. We included data from an earlier investigation of PCV7 to assess vaccine eff ectiveness in children
exposed to but not infected with HIV and in malnourished children not infected with HIV.
Findings Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study:
240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV,
and 283 were controls with HIV infection. The eff ectiveness of two or more doses of PCV13 against PCV13-serotype
invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with
HIV and 91% (â35 to 100) among three case-control sets of children with HIV infection. PCV13 eff ectiveness among
26 case-control sets of children not infected with HIV was 52% (95% CI â12 to 79) against all-serotype invasive
pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine eff ectiveness against PCV7-serotype
invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90%
(53 to 98) in malnourished children not infected with HIV.
Interpretation Our results indicate that PCV13 in a 2 + 1 schedule is eff ective for preventing vaccine-type
pneumococcal infections in young children not infected with HIV, including those who are malnourished or who
have been exposed to HIV. Although the point estimate for PCV13 vaccine eff ectiveness in children infected with
HIV was high, it did not reach signifi cance, possibly because of the small sample size. These fi ndings support
recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income
countries
Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol
Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities
Balancing selection at a premature stop mutation in the myostatin gene underlies a recessive leg weakness syndrome in pigs
Balancing selection provides a plausible explanation for the maintenance of deleterious alleles at moderate frequency in livestock, including lethal recessives exhibiting heterozygous advantage in carriers. In the current study, a leg weakness syndrome causing mortality of piglets in a commercial line showed monogenic recessive inheritance, and a region on chromosome 15 associated with the syndrome was identified by homozygosity mapping. Whole genome resequencing of cases and controls identified a mutation causing a premature stop codon within exon 3 of the porcine Myostatin (MSTN) gene, similar to those causing a double-muscling phenotype observed in several mammalian species. The MSTN mutation was in Hardy-Weinberg equilibrium in the population at birth, but significantly distorted amongst animals still in the herd at 110 kg, due to an absence of homozygous mutant genotypes. In heterozygous form, the MSTN mutation was associated with a major increase in muscle depth and decrease in fat depth, suggesting that the deleterious allele was maintained at moderate frequency due to heterozygous advantage (allele frequency, q = 0.22). Knockout of the porcine MSTN by gene editing has previously been linked to problems of low piglet survival and lameness. This MSTN mutation is an example of putative balancing selection in livestock, providing a plausible explanation for the lack of disrupting MSTN mutations in pigs despite many generations of selection for lean growth
Updated recommendations for the management of upper respiratory tract infections in South Africa
Background. Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), most of which are viral, significantly adds to the burden of antibiotic resistance. Since the introduction of pneumococcal conjugate vaccines in South Africa in 2009, the relative frequency of the major bacterial pathogens causing acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS) has changed. Recommendations. Since URTIs are mostly viral in aetiology and bacterial AOM and ABRS frequently resolve spontaneously, these recommendations include diagnostic criteria to assist in separating viral from bacterial causes and hence select those patients who do not require antibiotics. Penicillin remains the drug of choice for tonsillopharyngitis and amoxicillin the drug of choice for both AOM and ABRS. A dose of 90 mg/kg/d is recommended for children, which should be effective for pneumococci with high-level penicillin resistance and will also cover most infections with Haemophilus influenzae. Amoxicillin-clavulanate (in high-dose amoxicillin formulations available for both children and adults) should be considered the initial treatment of choice in patients with recent antibiotic therapy with amoxicillin (previous 30 days) and with resistant H. influenzae infections pending the results of studies of local epidemiology (ÎČ-lactamase production â„15%). The macrolide/azalide class of antibiotics is not recommended routinely for URTIs and is reserved for ÎČ-lactam-allergic patients.Conclusion. These recommendations should facilitate rational antibiotic prescribing for URTIs as a component of antibiotic stewardship. They will require updating when new information becomes available, particularly from randomised controlled trials and surveillance studies of local aetiology and antibiotic susceptibility patterns.
An improved pig reference genome sequence to enable pig genetics and genomics research.
BACKGROUND: The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model given its similarity in size, anatomy, physiology, metabolism, pathology, and pharmacology to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete, and unresolved redundancies, short-range order and orientation errors, and associated misassembled genes limited its utility. RESULTS: We present 2 annotated highly contiguous chromosome-level genome assemblies created with more recent long-read technologies and a whole-genome shotgun strategy, 1 for the same Duroc female (Sscrofa11.1) and 1 for an outbred, composite-breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. CONCLUSIONS: These highly contiguous assemblies plus annotation of a further 11 short-read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs
Pediatriciansâ assessments of caries risk and need for a dental evaluation in preschool aged children
Abstract Background Risk-based prioritization of dental referrals during well-child visits might improve dental access for infants and toddlers. This study identifies pediatrician-assessed risk factors for early childhood caries (ECC) and their association with the need for a dentistâs evaluation. Methods A priority oral health risk assessment and referral tool (PORRT) for children < 36 months was developed collaboratively by physicians and dentists and used by 10 pediatricians during well-child visits. PORRT documented behavioral, clinical, and child health risks for ECC. Pediatricians also assessed overall ECC risk on an 11-point scale and determined the need for a dental evaluation. Logistic regression models calculated the odds for evaluation need for each risk factor and according to a 3-level risk classification. Results In total 1,288 PORRT forms were completed; 6.8% of children were identified as needing a dentist evaluation. Behavioral risk factors were prevalent but not strong predictors of the need for an evaluation. The childâs overall caries risk was the strongest predictor of the need for an evaluation. Cavitated (OR = 17.5; 95% CI = 8.08, 37.97) and non-cavitated (OR = 6.9; 95% CI = 4.47, 10.82) lesions were the strongest predictors when the caries risk scale was excluded from the analysis. Few patients (6.3%) were classified as high risk, but their probability of needing an evaluation was only 0.36. Conclusions Low referral rates for children with disease and prior to disease onset but at elevated risk, indicate interventions are needed to help improve the dental referral rates of physicians
A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations
Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013âMarch 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as â„2 sequences, â„80% local branch support, and maximum genetic distance of all sequence pairs in the cluster â€2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56â7.50]); risk group (OR, 5.65 [95% CI, 3.27â9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64â4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07â3.47]); and younger age groups compared with age â„36 years (OR, 1.83 [95% CI, 1.10â3.05] for age â€25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31â.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions Our findings suggest high levels of transmission and bridging between risk groups
Lawsonia intracellularis exploits ÎČ-catenin/Wnt and Notch signalling pathways during infection of intestinal crypt to alter cell homeostasis and promote cell proliferation
Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. ÎČ-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine ÎČ-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated ÎČ-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of ÎČ-catenin/Wnt signalling and suggesting a potential alteration to ÎČ-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion of ISC population. Overall, simultaneous induction of Notch-1 signalling and the attenuation of ÎČ-catenin/Wnt pathway appear to be associated with the inhibition of goblet cell maturation and enhanced crypt cell proliferation at the peak of L. intracellularis infection. Moreover, the apparent differential regulation of apoptosis between crypt and lumen cells together with the strong induction of Notch-1 signalling and the enhanced SOX9 expression along crypts 14 dpc suggest an expansion of actively dividing transit amplifying and/or absorptive progenitor cells and provide a potential basis for understanding the development and maintenance of PE
To which world regions does the valenceâdominance model of social perception apply?
Over the past 10 years, Oosterhof and Todorovâs valenceâdominance model has emerged as the most prominent account of
how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social
judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether
these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorovâs methodology across
11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorovâs original analysis strategy,
the valenceâdominance model generalized across regions. When we used an alternative methodology to allow for correlated
dimensions, we observed much less generalization. Collectively, these results suggest that, while the valenceâdominance
model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed
when we use different extraction methods and correlate and rotate the dimension reduction solution.C.L. was supported by the Vienna Science and Technology Fund (WWTF VRG13-007);
L.M.D. was supported by ERC 647910 (KINSHIP); D.I.B. and N.I. received funding from
CONICET, Argentina; L.K., F.K. and Ă. Putz were supported by the European Social
Fund (EFOP-3.6.1.-16-2016-00004; âComprehensive Development for Implementing
Smart Specialization Strategies at the University of PĂ©csâ). K.U. and E. Vergauwe were
supported by a grant from the Swiss National Science Foundation (PZ00P1_154911 to E.
Vergauwe). T.G. is supported by the Social Sciences and Humanities Research Council
of Canada (SSHRC). M.A.V. was supported by grants 2016-T1/SOC-1395 (Comunidad
de Madrid) and PSI2017-85159-P (AEI/FEDER UE). K.B. was supported by a grant
from the National Science Centre, Poland (number 2015/19/D/HS6/00641). J. Bonick
and J.W.L. were supported by the Joep Lange Institute. G.B. was supported by the Slovak
Research and Development Agency (APVV-17-0418). H.I.J. and E.S. were supported
by a French National Research Agency âInvestissements dâAvenirâ programme grant
(ANR-15-IDEX-02). T.D.G. was supported by an Australian Government Research
Training Program Scholarship. The Raipur Group is thankful to: (1) the University
Grants Commission, New Delhi, India for the research grants received through its
SAP-DRS (Phase-III) scheme sanctioned to the School of Studies in Life Science;
and (2) the Center for Translational Chronobiology at the School of Studies in Life
Science, PRSU, Raipur, India for providing logistical support. K. Ask was supported by
a small grant from the Department of Psychology, University of Gothenburg. Y.Q. was
supported by grants from the Beijing Natural Science Foundation (5184035) and CAS
Key Laboratory of Behavioral Science, Institute of Psychology. N.A.C. was supported
by the National Science Foundation Graduate Research Fellowship (R010138018). We
acknowledge the following research assistants: J. Muriithi and J. Ngugi (United States
International University Africa); E. Adamo, D. Cafaro, V. Ciambrone, F. Dolce and E.
Tolomeo (Magna GrĂŠcia University of Catanzaro); E. De Stefano (University of Padova);
S. A. Escobar Abadia (University of Lincoln); L. E. Grimstad (Norwegian School of
Economics (NHH)); L. C. Zamora (Franklin and Marshall College); R. E. Liang and R.
C. Lo (Universiti Tunku Abdul Rahman); A. Short and L. Allen (Massey University, New
Zealand), A. AteĆ, E. GĂŒneĆ and S. Can Ăzdemir (BoÄaziçi University); I. Pedersen and T.
Roos (Ă
bo Akademi University); N. Paetz (Escuela de ComunicaciĂłn MĂłnica Herrera);
J. Green (University of Gothenburg); M. Krainz (University of Vienna, Austria); and B.
Todorova (University of Vienna, Austria). The funders had no role in study design, data
collection and analysis, decision to publish or preparation of the manuscript.https://www.nature.com/nathumbehav/am2023BiochemistryGeneticsMicrobiology and Plant Patholog