Influence of infection on malaria-specific antibody dynamics in a cohort exposed to intense malaria transmission in northern Uganda.

The role of submicroscopic infections in modulating malaria antibody responses is poorly understood and requires longitudinal studies. A cohort of 249 children ≤5 years of age, 126 children between 6 and 10 years and 134 adults ≥20 years was recruited in an area of intense malaria transmission in Apac, Uganda and treated with artemether/lumefantrine at enrolment. Parasite carriage was determined at enrolment and after 6 and 16 weeks using microscopy and PCR. Antibody prevalence and titres to circumsporozoite protein, apical membrane antigen-1 (AMA-1), merozoite surface protein-1 (MSP-119 ), merozoite surface protein-2 (MSP-2) and Anopheles gambiae salivary gland protein 6 (gSG6) were determined by ELISA. Plasmodium falciparum infections were detected in 38·1% (194/509) of the individuals by microscopy and in 57·1% (284/493) of the individuals by PCR at enrolment. Antibody prevalence and titre against AMA-1, MSP-119 , MSP-2 and gSG6 were related to concurrent (sub-)microscopic parasitaemia. Responses were stable in children who were continuously infected with malaria parasites but declined in children who were never parasitaemic during the study or were not re-infected after treatment. These findings indicate that continued malaria infections are required to maintain antibody titres in an area of intense malaria transmission

Patient journey following lumbar spinal fusion surgery (LSFS): protocol for a multicentre qualitative analysis of the patient rehabilitation experience (FuJourn)

INTRODUCTION: There has been a 65% increase in lumbar spinal fusion surgery (LSFS) worldwide over the last 13 years, with costs of £26 million to the UK National Health Service annually. Patient dissatisfaction with outcome and persistent pain and disability incurs further costs. Three trials provide low-quality evidence for the role of physiotherapy. Our UK surveys investigating physiotherapy/surgeon practice concluded rehabilitation should be tailored to the individual patient owing to considerable clinical heterogeneity. This study will explore the perceptions of patients who undergo LSFS to inform precision rehabilitation. METHODS AND ANALYSIS: A qualitative study, using interpretive phenomenological analysis, will recruit a purposive sample (n=40) to ensure patterns of similarity and difference in their journeys can be explored. In-depth semistructured interviews will be undertaken following discharge from hospital and at 12 months postsurgery. Patients' preoperative and postoperative experiences, underlying attitudes and beliefs towards the surgical intervention, facilitators and barriers to recovery, adherence to advice and physiotherapy, experiences of rehabilitation and return to normal function/activity/work will be explored. A 12-month patient diary will provide real time access to patient data, capturing a weekly record of life as lived, including symptoms, medication, experiences of stages of recovery, rehabilitation adherence, healthcare professional appointments, attitudes, their feelings and experiences throughout their journey. Data will be analysed in a number of stages in accordance with interpretive phenomenological analysis, supported using NVivo software. Analysis of the first interviews and patient diaries will afford a rich density of data to build an overall understanding of the patients' lived experiences, informing the 12-month interview. Strategies (eg, reflexivity) will ensure trustworthiness. ETHICS AND DISSEMINATION: The study has ethical approval (IRAS 223283). Findings will ensure that patient-driven data inform precision rehabilitation by understanding the patient journey. Findings will be disseminated through peer-reviewed journals and conferences

Hosing of a long relativistic particle bunch in plasma

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing

Intersectional inequalities in mental health by education, income, gender, and age before and during the COVID-19 pandemic in the Netherlands:a longitudinal study

Background: It remains unclear how COVID-19 has disproportionately affected the mental health of different vulnerable groups. This study explores how mental health inequalities changed between 2014 (pre-COVID-19) and 2021 (during COVID-19) in the Netherlands across intersectional social strata defined by interplays of educational attainment, income level, gender, and age. Methods: Using 2014 and 2021 self-reported cohort data on health and living conditions of the adult population of Eindhoven and surroundings (N = 1,157), a Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) was applied to explore intersectional inequalities in mental health in 2014, 2021, and in mental health changes (2014–2021). We examined this using the Mental Health Inventory-5 across 53 intersectional social strata based on interplays of education, income, gender, and age in 2014. Results: There were substantial differences in mental health trajectories across social strata. Between-stratum mental health inequalities were patterned additively, indicating that inequality patterns along one axis (such as income) tended to be consistent across other axes of comparison. Additive trends revealed that women with a low income were at highest risk of poor mental health in 2014 and 2021, and people over 65 were at highest risk of mental health setbacks over time. Nonsignificant educational inequalities were found in 2014 and 2021. Income inequalities persisted, but slightly decreased in 2021 due to stronger mental health setbacks among those with high incomes. Women experienced persisting disadvantages that slightly flattened over time, and the mental health advantages of older age diminished over time. Conclusions:Inequalities in mental health add up for those who experience multiple axes of disadvantage, such as women and those with low incomes, but no disproportionate intersectional interaction effects were found. Effort is needed to ensure that mental health support is accessible for all, especially those with low incomes. Given the especially strong mental health declines among those over 65, responses to future crises need to include measures to protect the mental health of the elderly. Future research should investigate intersectional inequalities along other axes of disadvantage, such as ethnicity, employment and family status.</p

Efek Konseling Apoteker Terhadap Kepatuhan Minum Obat dan Kualitas Hidup Penderita Skizofrenia di Rumah Sakit Jiwa Menur Surabaya

Skizofrenia merupakan gangguan psikiatri yang kompleks ditandai dengan gangguan kognitif, emosi, persepsi, berpikir dan berperilaku. Penelitian ini dilakukan untuk mengetahui perbedaan tingkat kepatuhan minum obat pasien skizofrenia sebelum dan setelah diberikan konseling oleh apoteker serta untuk mengetahui kualitas hidupnya. Metode penelitian ini adalah one-grup pretest-posttest yang bersifat prospektif. Pengambilan sampel terhadap responden sesuai kriteria inklusi dilakukan di Instalasi Farmasi Rumah Sakit Jiwa Menur pada bulan Mei sampai Juli tahun 2018. Sebelum pengambilan data dilakukan, responden yang sesuai dengan kriteria inklusi diberikan penjelasan tentang tujuan dan gambaran penelitian. Apabila setuju menjadi subjek, pasien atau keluarganya diwajibkan mengisi informed consent. Wawancara sesuai kuesioner Medication Adherence Rating Score (MARS) dan The World Health Organization Quality of Life (WHOQOL)-BREF pada responden dilakukan dua kali, yakni pada kedatangan pertama sebelum dilakukan konseling dan satu bulan kemudian saat subjek kontrol kembali. Total responden sebanyak 100 orang. Data dianalisis menggunakan uji beda (uji T). Hasil penelitian menunjukkan terdapat perbedaan bermakna pada kepatuhan minum obat responden antara prepost konseling oleh apoteker (p=0,033). Hasil penelitian ini menunjukkan bahwa kualitas hidup subjek memiliki perbedaan bermakna hanya terkait domain lingkungan (p=0,00), sedangkan pada domain fisik, mental dan sosial tidak memiliki perbedaan bermakna (p>0,05)

Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We # hypothesised that these ‘‘resistant smokers’’ may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the ‘‘resistant smokers’’ and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.3461024) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke

Genome wide linkage study, using a 250K SNP map, of Plasmodium falciparum infection and mild malaria attack in a Senegalese population

Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genomewide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5 x 10(-5) and 96 x 10(-5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5 x 10(-4)). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31-q33 region (p-value = 3.7 x 10(-5)). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31-q33 region

Experimental Observation of Proton Bunch Modulation in a Plasma at Varying Plasma Densities

We give direct experimental evidence for the observation of the full transverse self-modulation of a long, relativistic proton bunch propagating through a dense plasma. The bunch exits the plasma with a periodic density modulation resulting from radial wakefield effects. We show that the modulation is seeded by a relativistic ionization front created using an intense laser pulse copropagating with the proton bunch. The modulation extends over the length of the proton bunch following the seed point. By varying the plasma density over one order of magnitude, we show that the modulation frequency scales with the expected dependence on the plasma density, i.e., it is equal to the plasma frequency, as expected from theory

Trapped in vicious cycles: unraveling the health experiences and needs of adults living with socioeconomic insecurity

Background: This study explores the role of health in daily life and needs of Dutch adults (aged 25–49) experiencing one or more forms of socioeconomic insecurity stemming from their financial, housing, or employment situations. Methods: 28 in-depth, semi-structured interviews were conducted in the Netherlands between October 2022 and February 2023. The interview guide included questions on participants’ socioeconomic situation, the role of health in their daily lives, their health-related and broader needs. Data was interpreted using inductive reflexive thematic analysis. An advisory board consisting of adults with lived experiences of socioeconomic insecurity were consulted at multiple stages of the study (recruitment, interview guide, interpretation of results). Results: Housing insecurity was widely experienced by participants. When asked about their financial situation, most participants expressed having no issues getting by, but later on, described vigorous efforts to minimize expenses. Participants’ narratives revealed four key themes in relation to the role of health in daily life and associated needs. Firstly, socioeconomic insecurity led to diminished control over life, which led to the disruption of routines. Secondly, experiencing socioeconomic insecurity compelled participants to prioritize stress reduction and mental health improvement through calming yet potentially damaging coping mechanisms. Thirdly, those who experienced little opportunity for improvement in their already long-lasting socioeconomic insecurity shared a sense of stagnation in life, which co-occurred with stagnation in unhealthy routines and diminished well-being. Fourthly, participants expressed the need for someone to speak with. This support may help participants regain control over their lives, identify opportunities for more socioeconomic security, and focus on increased health and well-being. Conclusions: This study sheds light on the challenges individuals face in dealing with socioeconomic insecurity, how it may affect their health, and their needs. Gaining perspective for improved socioeconomic security and having accessible professional support tailored to self-identified needs could have health-promoting effects for individuals living with socioeconomic insecurity. It is recommended to integrate professional support and assistance regarding social security into health policies and interventions. In future research, measures of financial strain should be adjusted to include the effort needed to get by

The current state of complex systems research on socioeconomic inequalities in health and health behavior: a systematic scoping review

Background: Interest in applying a complex systems approach to understanding socioeconomic inequalities in health is growing, but an overview of existing research on this topic is lacking. In this systematic scoping review, we summarize the current state of the literature, identify shared drivers of multiple health and health behavior outcomes, and highlight areas ripe for future research. Methods: SCOPUS, Web of Science, and PubMed databases were searched in April 2023 for peer-reviewed, English-language studies in high-income OECD countries containing a conceptual systems model or simulation model of socioeconomic inequalities in health or health behavior in the adult general population. Two independent reviewers screened abstracts and full texts. Data on study aim, type of model, all model elements, and all relationships were extracted. Model elements were categorized based on the Commission on Social Determinants of Health framework, and relationships between grouped elements were visualized in a summary conceptual systems map. Results: A total of 42 publications were included; 18 only contained a simulation model, 20 only contained a conceptual model, and 4 contained both types of models. General health outcomes (e.g., health status, well-being) were modeled more often than specific outcomes like obesity. Dietary behavior and physical activity were by far the most commonly modeled health behaviors. Intermediary determinants of health (e.g., material circumstances, social cohesion) were included in nearly all models, whereas structural determinants (e.g., policies, societal values) were included in about a third of models. Using the summary conceptual systems map, we identified 15 shared drivers of socioeconomic inequalities in multiple health and health behavior outcomes. Conclusions: The interconnectedness of socioeconomic position, multiple health and health behavior outcomes, and determinants of socioeconomic inequalities in health is clear from this review. Factors central to the complex system as it is currently understood in the literature (e.g., financial strain) may be both efficient and effective policy levers, and factors less well represented in the literature (e.g., sleep, structural determinants) may warrant more research. Our systematic, comprehensive synthesis of the literature may serve as a basis for, among other things, a complex systems framework for socioeconomic inequalities in health