Long-term morbidity from severe pneumonia in early childhood in The Gambia, West Africa: a follow-up study

OBJECTIVE: To assess long-term outcomes in severe early childhood pneumonia in The Gambia. DESIGN: Observational cohort study of children hospitalised with severe pneumonia between 1992 and 1 04 compared to age, sex, and neigh bourhood-marched controls on measures of current general and pulmonary health. RESULTS: Of 83 children successfully traced, 68 of the 69 alive at follow-up agreed to participate. Thirteen per Cent of cases and 4% of controls had lung disease clinically or on spirometry. Another 16 (13%) participants had abnormal spirometry but did not meet the American Thoracic Society technical criteria (formally 'inconclusive'). Odds ratios of lung disease among childhood pneumonia cases were 2.93 (95 %CI 0.69-12.48, P = 0.1468) with incon-clusives omitted; 2.53 (95 %CI 0.61-10.59, P = 0.2033) with inconclusives included as normal; and 2.83 (95%CI 1.09-7.36, P = 0.0334) with inconclusives included as lung disease. Among deceased cases, most deaths were reported within weeks of discharge, suggesting a possible connection between admission and subsequent death. CONCLUSION: These African data, while not conclusive, add to previous data suggesting a link between severe early, childhood pneumonia and later chronic lung disease. While larger-scale research is needed, increased awareness of possible long-term morbidity in children with severe pneumonia is warranted to limit its impact and optimise long-term health

Mineral chemistry of igneous melanite garnets from analcite-bearing volcanic rocks, Alberta, Canada

The mineral chemistry of melanite garnets from the Crowsnest volcanic rocks of SW Alberta, Canada, has been investigated by using electron microprobe scans, quantitative analyses and multivariate statistical analysis. The garnets occur with aegirine-augite, sanidine, analcite and rare plagioclase as phenocrysts in trachyte and phonolite flows, agglomerates and tuffs. Wavelength dispersive microprobe scans reveal complex zonation patterns, both normal and oscillatory. The results of fifty quantitative analyses were subjected to R-mode factor analysis to delineate the chemical exchanges producing the zonation. The chemical zonation of the garnets may be attributed to four independent binary exchanges; Al-Fe3+, Si-Ti, Ca-Mn and Mg-Fe2+. The stoichiometry of these garnets, based on microprobe and wet chemical Fe analyses, combined with the strongly antithetic behavior of Si and Ti lead us to infer that the Ti in these garnets is dominantly tetravalent. It is clear from this study that quantitative modelling of the processes of crystal growth and zonation of melanite garnets in alkaline, undersaturated igneous rocks should be aimed at simulating the four chemical exchanges listed above

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Comparative 3D analyses and palaeoecology of giant early amphibians (Temnospondyli: Stereospondyli)

Macroevolutionary, palaeoecological and biomechanical analyses in deep time offer the possibility to decipher the structural constraints, ecomorphological patterns and evolutionary history of extinct groups. Here, 3D comparative biomechanical analyses of the extinct giant early amphibian group of stereospondyls together with living lissamphibians and crocodiles, shows that: i) stereospondyls had peculiar palaeoecological niches with proper bites and stress patterns very different than those of giant salamanders and crocodiles; ii) their extinction may be correlated with the appearance of neosuchians, which display morphofunctional innovations. Stereospondyls weathered the end-Permian mass extinction, re-radiated, acquired gigantic sizes and dominated (semi) aquatic ecosystems during the Triassic. Because these ecosystems are today occupied by crocodilians, and stereospondyls are extinct amphibians, their palaeobiology is a matter of an intensive debate: stereospondyls were a priori compared with putative living analogous such as giant salamanders and/or crocodilians and our new results try to close this debate.Peer ReviewedPostprint (published version

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Ultrafast Light and Electrons: Imaging the Invisible

In this chapter, the evolutionary and revolutionary developments of microscopic imaging are overviewed with focus on ultrashort light and electrons pulses; for simplicity, we shall use the term “ultrafast” for both. From Alhazen’s camera obscura, to Hooke and van Leeuwenhoek’s optical micrography, and on to three- and four-dimensional (4D) electron microscopy, the developments over a millennium have transformed humans’ scope of visualization. The changes in the length and time scales involved are unimaginable, beginning with the visible shadows of candles at the centimeter and second scales, and ending with invisible atoms with space and time dimensions of sub-nanometer and femtosecond, respectively. With these advances it has become possible to determine the structures of matter and to observe their elementary dynamics as they fold and unfold in real time, providing the means for visualizing materials behavior and biological function, with the aim of understanding emergent phenomena in complex systems. Both light and light-generated electrons are now at the forefront of femtosecond and attosecond science and technology, and the scope of applications has reached beyond the nuclear motion as electron dynamics become accessible

Bacteraemia in patients admitted to an urban hospital in West Africa

BACKGROUND: Few studies on bacteraemia in Africa have been published. We aimed to prospectively identify the causative organisms of bacteraemia in The Gambia and their relation to clinical diagnoses, outcome and antimicrobial susceptibility. METHODS: Between November 2003 and February 2005 we studied those admitted to the Medical Research Council hospital who were suspected of having bacteraemia. We documented clinical features, outcome, pathogens identified and their susceptibility patterns, and searched for factors associated with bacteraemia. RESULTS: 871 patients were admitted and had a blood culture taken. The median age was 2 years (range 2 months to 80 years) and 36 of 119 tested were HIV positive; 54.5% were male. 297 (34%) had a positive result and 93 (10.7% overall) were considered a genuine pathogen. Those with bacteraemia were more likely to die in hospital (OR 2.79; 1.17–6.65, p = 0.017) and to have a high white cell count (WCC; OR 1.81;95% CI 1.09–3.02; p = 0.022). Three organisms accounted for 73% of bacteraemias: Streptococcus pneumoniae (45.2%), Staphylococcus aureus (18.3%) and Escherichia coli (9.7%) while non-typhoidal salmonellae (NTS) accounted for 8.6%. Antimicrobial susceptibility of S. pneumoniae was very high to penicillin (97.5%); high resistance was found to co-trimoxazole. S. aureus was generally highly susceptible to cloxacillin, gentamicin and chloramphenicol. E. coli and NTS were all susceptible to ciprofloxacin and mostly susceptible to gentamicin. Thirteen (33%) S. pneumoniae isolates were of serotypes contained in a 7-valent pneumococcal conjugate vaccine and 20 (51.3%) were of the same serogroup. CONCLUSION: In The Gambia, those with bacteraemia are more likely than those without to die in hospital and to have a raised peripheral blood WCC. S. pneumoniae is the most common organism isolated. Introduction of a pneumococcal conjugate vaccine can be expected to lead to a reduction in disease incidence

Early acquisition and high nasopharyngeal co-colonisation by Streptococcus pneumoniae and three respiratory pathogens amongst Gambian new-borns and infants

BACKGROUND: Although Haemophilus influenzae type b (Hib), Staphylococcus aureus and Moraxella catarrhalis are important causes of invasive and mucosal bacterial disease among children, co-carriage with Streptococcus pneumoniae during infancy has not been determined in West Africa. METHODS: Species specific PCR was applied to detect each microbe using purified genomic DNA from 498 nasopharyngeal (NP) swabs collected from 30 Gambian neonates every two weeks from 0 to 6 months and bi-monthly up to 12 months. RESULTS: All infants carried S. pneumoniae, H. influenzae and M. catarrhalis at several time points during infancy. S.pneumoniae co-colonized the infant nasopharynx with at least one other pathogen nine out of ten times. There was early colonization of the newborns and neonates, the average times to first detection were 5, 7, 3 and 14 weeks for S. pneumoniae, H. influenzae, M. catarrhalis and S. aureus respectively. The prevalence of S. pneumoniae, H. influenzae and M. catarrhalis increased among the neonates and exceeded 80% by 13, 15 and 23 weeks respectively. In contrast, the prevalence of S. aureus decreased from 50% among the newborns to 20% amongst nine-week old neonates. S. pneumoniae appeared to have a strong positive association with H. influenzae (OR 5.03; 95% CI 3.02, 8.39; p<0.01) and M. catarrhalis (OR 2.20; 95% CI 1.29; p<0.01) but it was negatively associated with S. aureus (OR 0.53; 95% CI 0.30, 0.94; p=0.03). CONCLUSION: This study shows early acquisition and high co-carriage of three important respiratory pathogens with S. pneumoniae in the nasopharyngeal mucosa among Gambian neonates and infants. This has important potential implications for the aetiology of respiratory polymicrobial infections, biofilm formation and vaccine strategies

A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records

Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0x10-11), 52Kb 3’ of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8x10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9x10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2x10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI

Do list size and remuneration affect GPs' decisions about how they provide consultations?

Background: Doctors' professional behaviour is influenced by the way they are paid. When GPs are paid per item, i.e., on a fee-for-service basis (FFS), there is a clear relationship between workload and income: more work means more money. In the case of capitation based payment, workload is not directly linked to income since the fees per patient are fixed. In this study list size was considered as an indicator for workload and we investigated how list size and remuneration affect GP decisions about how they provide consultations. The main objectives of this study were to investigate a) how list size is related to consultation length, waiting time to get an appointment, and the likelihood that GPs conduct home visits and b) to what extent the relationships between list size and these three variables are affected by remuneration. Methods: List size was used because this is an important determinant of objective workload. List size was corrected for number of older patients and patients who lived in deprived areas. We focussed on three dependent variables that we expected to be related to remuneration and list size: consultation length; waiting time to get an appointment; and home visits. Data were derived from the second Dutch National Survey of General Practice (DNSGP-2), carried out between 2000 and 2002. The data were collected using electronic medical records, videotaped consultations and postal surveys. Multilevel regression analyses were performed to assess the hypothesized relationships. Results: Our results indicate that list size is negatively related to consultation length, especially among GPs with relatively large lists. A correlation between list size and waiting time to get an appointment, and a correlation between list size and the likelihood of a home visit were only found for GPs with small practices. These correlations are modified by the proportion of patients for whom GPs receive capitation fees. Waiting times to get an appointment tend to become shorter with increasing patient lists when there is a larger capitation percentage. The likelihood that GPs will conduct home visit rises with increasing patient lists when the capitation percentage is small. Conclusion: Remuneration appears to affect GPs' decisions about how they provide consultations, especially among GPs with relatively small patient lists. This role is, however, small compared to other factors such as patient characteristics.