THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites.

As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available. Estimates limited to monogenomic infections may not be representative, however, and when the average COI is high, they can be difficult or impossible to obtain. Therefore, we developed THE REAL McCOIL, Turning HEterozygous SNP data into Robust Estimates of ALelle frequency, via Markov chain Monte Carlo, and Complexity Of Infection using Likelihood, to incorporate polygenomic samples and simultaneously estimate allele frequency and COI. This approach was tested via simulations then applied to SNP data from cross-sectional surveys performed in three Ugandan sites with varying malaria transmission. We show that THE REAL McCOIL consistently outperforms COIL on simulated data, particularly when most infections are polygenomic. Using field data we show that, unlike with COIL, we can distinguish epidemiologically relevant differences in COI between and within these sites. Surprisingly, for example, we estimated high average COI in a peri-urban subregion with lower transmission intensity, suggesting that many of these cases were imported from surrounding regions with higher transmission intensity. THE REAL McCOIL therefore provides a robust tool for understanding the molecular epidemiology of malaria across transmission settings

Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study.

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10(-6) > P > 5 × 10(-8)). The most strongly associated SNP (rs111513399, P = 5.38 × 10(-7)) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling

Mental health in Europe during the COVID-19 pandemic: a systematic review

The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions

Mental health in Europe during the COVID-19 pandemic: a systematic review

The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions

Malaria Host Candidate Genes Validated by Association With Current, Recent, and Historical Measures of Transmission Intensity

Background: Human malaria susceptibility is determined by multiple genetic factors. It is unclear, however, which genetic variants remain important over time. Methods: Genetic associations of 175 high-quality polymorphisms within several malaria candidate genes were examined in a sample of 8096 individuals from northeast Tanzania using altitude, seroconversion rates, and parasite rates as proxies of historical, recent, and current malaria transmission intensity. A principal component analysis was used to derive 2 alternative measures of overall malaria propensity of a location across different time scales. Results: Common red blood cell polymorphisms (ie, hemoglobin S, glucose-6-phosphate dehydrogenase, and α-thalassemia) were the only ones to be associated with all 3 measures of transmission intensity and the first principal component. Moderate associations were found between some immune response genes (ie, IL3 and IL13) and parasite rates, but these could not be reproduced using the alternative measures of malaria propensity. Conclusions: We have demonstrated the potential of using altitude and seroconversion rate as measures of malaria transmission capturing medium- to long-term time scales to detect genetic associations that are likely to persist over time. These measures also have the advantage of minimizing the deleterious effects of random factors affecting parasite rates on the respective association signals

Geographic-genetic analysis of Plasmodium falciparum parasite populations from surveys of primary school children in Western Kenya.

BACKGROUND: Malaria control, and finally malaria elimination, requires the identification and targeting of residual foci or hotspots of transmission. However, the level of parasite mixing within and between geographical locations is likely to impact the effectiveness and durability of control interventions and thus should be taken into consideration when developing control programs. METHODS: In order to determine the geographic-genetic patterns of Plasmodium falciparum parasite populations at a sub-national level in Kenya, we used the Sequenom platform to genotype 111 genome-wide distributed single nucleotide polymorphic (SNP) positions in 2486 isolates collected from children in 95 primary schools in western Kenya. We analysed these parasite genotypes for genetic structure using principal component analysis and assessed local and global clustering using statistical measures of spatial autocorrelation. We further examined the region for spatial barriers to parasite movement as well as directionality in the patterns of parasite movement. RESULTS: We found no evidence of population structure and little evidence of spatial autocorrelation of parasite genotypes (correlation coefficients <0.03 among parasite pairs in distance classes of 1km, 2km and 5km; p value<0.01). An analysis of the geographical distribution of allele frequencies showed weak evidence of variation in distribution of alleles, with clusters representing a higher than expected number of samples with the major allele being identified for 5 SNPs. Furthermore, we found no evidence of the existence of spatial barriers to parasite movement within the region, but observed directional movement of parasites among schools in two separate sections of the region studied. CONCLUSIONS: Our findings illustrate a pattern of high parasite mixing within the study region. If this mixing is due to rapid gene flow, then "one-off" targeted interventions may not be currently effective at the sub-national scale in Western Kenya, due to the high parasite movement that is likely to lead to re-introduction of infection from surrounding regions. However repeated targeted interventions may reduce transmission in the surrounding regions

Clinical Associations of an Updated Medication Effect Score for Measuring Diabetes Treatment Intensity

OBJECTIVES: The medication effect score reflects overall intensity of a diabetes regimen by consolidating dosage and potency of agents used. Little is understood regarding how medication intensity relates to clinical factors. We updated the medication effect score to account for newer agents and explored associations between medication effect score and patient-level clinical factors. METHODS: Cross-sectional analysis of baseline data from a randomized controlled trial involving 263 Veterans with type 2 diabetes and hemoglobin AIc levels ≥8.0% (≥7.5% if under age 50). Medication effect score was calculated for all patients at baseline, alongside additional measures including demographics, comorbid illnesses, hemoglobin AIc, and self-reported psychosocial factors. We used multivariable regression to explore associations between baseline medication effect score and patient-level clinical factors. RESULTS: Our sample had a mean age of 60.7 (SD = 8.2) years, was 89.4% male, and 57.4% non-White. Older age and younger onset of diabetes were associated with a higher medication effect score, as was higher body mass index. Higher medication effect score was significantly associated with medication nonadherence, although not with hemoglobin AIc, self-reported hypoglycemia, diabetes-related distress, or depression. DISCUSSION: We observed several expected associations between an updated medication effect score and patient-level clinical factors. These associations support the medication effect score as an appropriate measure of diabetes regimen intensity in clinical and research contexts

Mind Perception: Real but Not Artificial Faces Sustain Neural Activity beyond the N170/VPP

Faces are visual objects that hold special significance as the icons of other minds. Previous researchers using event-related potentials (ERPs) have found that faces are uniquely associated with an increased N170/vertex positive potential (VPP) and a more sustained frontal positivity. Here, we examined the processing of faces as objects vs. faces as cues to minds by contrasting images of faces possessing minds (human faces), faces lacking minds (doll faces), and non-face objects (i.e., clocks). Although both doll and human faces were associated with an increased N170/VPP from 175–200 ms following stimulus onset, only human faces were associated with a sustained positivity beyond 400 ms. Our data suggest that the N170/VPP reflects the object-based processing of faces, whether of dolls or humans; on the other hand, the later positivity appears to uniquely index the processing of human faces—which are more salient and convey information about identity and the presence of other minds