Leibniz on the Simplicity of Substance

Paper by Robert C. Sleigh, Jr

Methods used for successful follow-up in a large scale national cohort study in Thailand

Background: Ensuring successful follow-up is essential when conducting a prospective cohort study. Most existing literature reviewing methods to ensure a high response rate is based on experience in developed nations. Findings: We report our 4-year follow-up success for a national cohort study examining the health transition underway in Thailand. We began the cohort study in 2005 with a baseline postal questionnaire sent to all 200,000 Thais enrolled as distance learning students at Sukhothai Thammathirat Open University and residing all over Thailand; 87,134 or 44% of the students responded. Subsequently we used University and national media to inform cohort members of study progress. Also, we prepared a health book with study results and health advice which was distributed to all cohort members. After 4 years we repeated the survey and achieved a 71% response rate. In this paper we report the methods used to achieve this response The initial follow-up mail-out generated a response rate of about 48% reflecting the extensive preparatory work between baseline and follow-up. After 4 rounds of telephone contact (more than 100,000 phone calls) and 4 related mail-out rounds progressively over 16 months an overall response rate was achieved of just over 71% (n = 60,774). The total cost was US$4.06/respondent - 19% for printing, 21% for postage, 14% for tape measures (included in mail-out), 18% for data processing 22% for prizes and 6% for telephone. Conclusions: Many of the methods reported as effective for mail questionnaire and cohort response rates held true for Thailand. These included being associated with a university, incentivating cooperation, follow-up contact, providing a second copy of questionnaire where necessary, and assurance of confidentiality. Telephone contact with the cohort and the small prizes given to responders were particularly important in the Thai context as was Thai leadership of the research team

The architecture and effect of participation: a systematic review of community participation for communicable disease control and elimination. Implications for malaria elimination

Community engagement and participation has played a critical role in successful disease control and elimination campaigns in many countries. Despite this, its benefits for malaria control and elimination are yet to be fully realized. This may be due to a limited understanding of the influences on participation in developing countries as well as inadequate investment in infrastructure and resources to support sustainable community participation. This paper reports the findings of an atypical systematic review of 60 years of literature in order to arrive at a more comprehensive awareness of the constructs of participation for communicable disease control and elimination and provide guidance for the current malaria elimination campaign.Evidence derived from quantitative research was considered both independently and collectively with qualitative research papers and case reports. All papers included in the review were systematically coded using a pre-determined qualitative coding matrix that identified influences on community participation at the individual, household, community and government/civil society levels. Colour coding was also carried out to reflect the key primary health care period in which community participation programmes originated. These processes allowed exhaustive content analysis and synthesis of data in an attempt to realize conceptual development beyond that able to be achieved by individual empirical studies or case reports.Of the 60 papers meeting the selection criteria, only four studies attempted to determine the effect of community participation on disease transmission. Due to inherent differences in their design, interventions and outcome measures, results could not be compared. However, these studies showed statistically significant reductions in disease incidence or prevalence using various forms of community participation. The use of locally selected volunteers provided with adequate training, supervision and resources are common and important elements of the success of the interventions in these studies. In addition, qualitative synthesis of all 60 papers elucidates the complex architecture of community participation for communicable disease control and elimination which is presented herein.The current global malaria elimination campaign calls for a health systems strengthening approach to provide an enabling environment for programmes in developing countries. In order to realize the benefits of this approach it is vital to provide adequate investment in the 'people' component of health systems and understand the multi-level factors that influence their participation. The challenges of strengthening this component of health systems are discussed, as is the importance of ensuring that current global malaria elimination efforts do not derail renewed momentum towards the comprehensive primary health care approach. It is recommended that the application of the results of this systematic review be considered for other diseases of poverty in order to harmonize efforts at building 'competent communities' for communicable disease control and optimising health system effectiveness

Physical hydrodynamic propulsion model study for creeping viscous flow through a ciliated porous tube

The present investigation focuses on a mathematical study of creeping viscous flow induced by metachronal wave propagation in a horizontal ciliated tube containing porous media. Creeping flow limitations are imposed i.e. inertial forces are small compared with viscous forces and therefore very low Reynolds number (Re<<1) is taken into account. The wavelength of metachronal wave is also considered as very large for cilia movement. The physical problem is linearized and exact solutions are developed for the differential equation problem. Mathematica software is used to compute and illustrate numerical results. The influence of slip parameter and Darcy number on velocity profile, pressure gradient and trapping of bolus are discussed with the aid of graphs. It is found that with increasing magnitude of slip parameter the trapped bolus inside the streamlines increases in size. The study is relevant to biological propulsion of medical micro-machines in drug delivery

Pyronaridine-Artesunate versus Chloroquine in Patients with Acute Plasmodium vivax Malaria: A Randomized, Double-Blind, Non-Inferiority Trial

BACKGROUND: New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. METHODS AND FINDINGS: This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-infection were randomized (1:1) to receive pyronaridine-artesunate (target dose 7.2:2.4 mg/kg to 13.8:4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference -0.5% (95%CI -2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than -10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; p<0.0001), as was fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017). Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate. CONCLUSION: Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug. TRIAL REGISTRATION: Clinicaltrials.gov NCT00440999

Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified

Stress granules, RNA-binding proteins and polyglutamine diseases: too much aggregation?

Stress granules (SGs) are membraneless cell compartments formed in response to different stress stimuli, wherein translation factors, mRNAs, RNA-binding proteins (RBPs) and other proteins coalesce together. SGs assembly is crucial for cell survival, since SGs are implicated in the regulation of translation, mRNA storage and stabilization and cell signalling, during stress. One defining feature of SGs is their dynamism, as they are quickly assembled upon stress and then rapidly dispersed after the stress source is no longer present. Recently, SGs dynamics, their components and their functions have begun to be studied in the context of human diseases. Interestingly, the regulated protein self-assembly that mediates SG formation contrasts with the pathological protein aggregation that is a feature of several neurodegenerative diseases. In particular, aberrant protein coalescence is a key feature of polyglutamine (PolyQ) diseases, a group of nine disorders that are caused by an abnormal expansion of PolyQ tract-bearing proteins, which increases the propensity of those proteins to aggregate. Available data concerning the abnormal properties of the mutant PolyQ disease-causing proteins and their involvement in stress response dysregulation strongly suggests an important role for SGs in the pathogenesis of PolyQ disorders. This review aims at discussing the evidence supporting the existence of a link between SGs functionality and PolyQ disorders, by focusing on the biology of SGs and on the way it can be altered in a PolyQ disease context.ALG-01-0145-FEDER-29480, SFRH/BD/133192/2017, SFRH/BD/133192/2017, SFRH/BD/148533/2019info:eu-repo/semantics/publishedVersio

Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species

Modelling the spatial and seasonal distribution of suitable habitats of schistosomiasis intermediate host snails using Maxent in Ndumo area, KwaZulu-Natal Province, South Africa

Abstract Background Schistosomiasis is a snail-borne disease endemic in sub-Saharan Africa transmitted by freshwater snails. The distribution of schistosomiasis coincides with that of the intermediate hosts as determined by climatic and environmental factors. The aim of this paper was to model the spatial and seasonal distribution of suitable habitats for Bulinus globosus and Biomphalaria pfeifferi snail species (intermediate hosts for Schistosoma haematobium and Schistosoma mansoni, respectively) in the Ndumo area of uMkhanyakude district, South Africa. Methods Maximum Entropy (Maxent) modelling technique was used to predict the distribution of suitable habitats for B. globosus and B. pfeifferi using presence-only datasets with ≥ 5 and ≤ 12 sampling points in different seasons. Precipitation, maximum and minimum temperatures, Normalised Difference Vegetation Index (NDVI), Normalised Difference Water Index (NDWI), pH, slope and Enhanced Vegetation Index (EVI) were the background variables in the Maxent models. The models were validated using the area under the curve (AUC) and omission rate. Results The predicted suitable habitats for intermediate snail hosts varied with seasons. The AUC for models in all seasons ranged from 0.71 to 1 and the prediction rates were between 0.8 and 0.9. Although B. globosus was found at more localities in the Ndumo area, there was also evidence of cohabiting with B. pfiefferi at some of the locations. NDWI had significant contribution to the models in all seasons. Conclusion The Maxent model is robust in snail habitat suitability modelling even with small dataset of presence-only sampling sites. Application of the methods and design used in this study may be useful in developing a control and management programme for schistosomiasis in the Ndumo area