Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Redesigning the photosynthetic light reactions to enhance photosynthesis - the PhotoRedesign consortium.

In this Perspective article, we describe the visions of the PhotoRedesign consortium funded by the European Research Council of how to enhance photosynthesis. The light reactions of photosynthesis in individual phototrophic species use only a fraction of the solar spectrum, and high light intensities can impair and even damage the process. In consequence, expanding the solar spectrum and enhancing the overall energy capacity of the process, while developing resilience to stresses imposed by high light intensities, could have a strong positive impact on food and energy production. So far, the complexity of the photosynthetic machinery has largely prevented improvements by conventional approaches. Therefore, there is an urgent need to develop concepts to redesign the light-harvesting and photochemical capacity of photosynthesis, as well as to establish new model systems and toolkits for the next generation of photosynthesis researchers. The overall objective of PhotoRedesign is to reconfigure the photosynthetic light reactions so they can harvest and safely convert energy from an expanded solar spectrum. To this end, a variety of synthetic biology approaches, including de novo design, will combine the attributes of photosystems from different photoautotrophic model organisms, namely the purple bacterium Rhodobacter sphaeroides, the cyanobacterium Synechocystis sp. PCC 6803 and the plant Arabidopsis thaliana. In parallel, adaptive laboratory evolution will be applied to improve the capacity of reimagined organisms to cope with enhanced input of solar energy, particularly in high and fluctuating light.

Microplastic concentrations in river water and bed sediments in a tropical river: implications for water quality monitoring.

Recent increase in awareness of the extent of microplastic contamination in marine and freshwater systems has heightened concerns over the ecological and human health risks of this ubiquitous material. Assessing risks posed by microplastic in freshwater systems requires sampling to establish contamination levels, but standard sampling protocols have yet to be established. An important question is whether sampling and assessment should focus on microplastic concentrations in the water or the amount deposited on the bed. On three dates, five replicated water and bed sediment samples were collected from each of the eight sites along the upper reach of the Semenyih River, Malaysia. Microplastics were found in all 160 samples, with mean concentrations of 3.12 ± 2.49 particles/L in river water and 6027.39 ± 16,585.87 particles/m2 deposited on the surface of riverbed sediments. Fibres were the dominant type of microplastic in all samples, but fragments made up a greater proportion of the material on the bed than in the water. Within-site variability in microplastic abundance was high for both water and bed sediments, and very often greater than between-site variability. Patterns suggest that microplastic accumulation on the bed is spatially variable, and single samples are therefore inadequate for assessing bed contamination levels at a site. Sites with the highest mean concentrations in samples of water were not those with the highest concentrations on the bed, indicating that monitoring based only on water samples may not provide a good picture of either relative or absolute bed contamination levels, nor the risks posed to benthic organisms.

Relative contributions of different local sources to riverborne microplastic in a mixed landuse area within a tropical catchment.

Information on the relative contributions of microplastics coming from different sources is important to help prioritise measures to reduce river contamination levels and limit human and ecological health risks. This paper reports on work which aimed to quantitatively assess the relative concentrations and types of microplastic delivered from differed sources to a second order river. The study was undertaken in a mixed landuse area within a rapidly urbanising catchment in Malaysia. Over a six-week period, water samples were collected from road culverts and drains in residential and industrial areas across the area to assess microplastic concentrations, while inputs from atmospheric deposition and wastewater treatment plants (WWTPs) were also quantified. Microplastic fibres and fragments were the dominant material in all sources, with the majority consisting of styrene-butadiene rubber and nylon. Culverts draining main roads were the main contributor to riverborne microplastic, delivering 42.20 ± 35.29 particles/L directly to the river channel. Road inputs were up to seven times greater than those from residential (8.53 ± 9.91 particles/L) and industrial (5.67 ± 4.88 particles/L) areas. The five WWTPs had removal efficiencies of between 30.95 ± 5.51% and 69.94 ± 22.17%, with their outflows delivering microplastics to the river in concentrations similar to those in uncontrolled residential and industrial drains. Atmospheric deposition across the study area was estimated to be 76.07 ± 32.85 particles/m2/day (=8.35 ± 5.11 particles/L). Mitigation strategies in the study area should focus on improving management of water draining roads, and re-routing discharges from domestic and industrial areas to WWTPs rather than allowing them to flow directly to the river. The low efficiencies of some of the WWTPs are not unusual, and indicate the need for additional water treatment to deal with microplastic present in wastewater.

Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.

The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. Unlike the matched, traditionally grown tumor cell lines, TSCs derived directly from primary glioblastomas harbor extensive similarities to normal neural stem cells and recapitulate the genotype, gene expression patterns, and in vivo biology of human glioblastomas. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors.

Microplastic pollution in freshwater systems in Southeast Asia: contamination levels, sources, and ecological impacts.

Plastics are synthetic polymers known for their outstanding durability and versatility, and have replaced traditional materials in many applications. Unfortunately, their unique traits ensure that they pose a major threat to the environment. While literature on freshwater microplastic contamination has grown over the recent years, research undertaken in rapidly developing countries, where plastic production and use are increasing dramatically, has lagged behind that in other parts of the world. In the South East Asia (SEA) region, basic information on levels of contamination is very limited and, as a consequence, the risk to human and ecological health remains hard to assess. This review synthesises what is currently known about microplastic contamination of freshwater ecosystems in SEA, with a particular focus on Malaysia. The review 1) summarises published studies that have assessed levels of contamination in freshwater systems in SEA, 2) discusses key sources and transport pathways of microplastic in freshwaters, 3) outlines what is known of the impacts of microplastic on freshwater organisms, and 4) identifies key knowledge gaps related to our understanding of the transport, fate and effects of microplastic.

Spatio-temporal variation of microplastic along a rural to urban transition in a tropical river.

Microplastic pollution is widely recognised as a global issue, posing risks to natural ecosystems and human health. The combination of rapid industrial and urban development and relatively limited environmental regulation in many tropical countries may increase the amount of microplastic entering rivers, but basic data on contamination levels are lacking. This is especially the case in tropical South East Asian countries. In this paper, the abundance, composition and spatio-temporal variation of microplastic in the Langat River, Malaysia, were assessed, and the relationship between microplastic concentration and river discharge was investigated. Water samples were collected over a 12-month period from 8 sampling sites on the Langat, extending from forested to heavily urbanised and industrial areas. All 508 water samples collected over this period contained microplastic; mean concentration across all sites and times was 4.39 particles/L but extended up to 90.00 particles/L in some urban tributaries. Most microplastics were secondary in origin, and dominated by fibres. Microplastic counts correlated directly with river discharge, and counts increased and decreased in response to changes in flow. A time-integrated assessment of the microplastic load conveyed by the Langat suggested that the river is typically (50 % of the time) delivering around 5 billion particles per day to the ocean. The positive correlation between the concentration of microplastics and suspended sediments in the Langat suggested that continuously logging turbidity sensors could be used to provide better estimates of microplastic loads and improve assessment of human and ecological health risks.

Source of drugs for prescription opioid analgesic abusers: a role for the Internet?

OBJECTIVE: There has been a sharp increase in the abuse of prescription opioid analgesics in the United States in the past decade. It has been asserted, particularly by several governmental and regulatory agencies, that the Internet has become a significant source of these drugs which may account to a great extent for the surge in abuse. We have studied whether this is correct. DESIGN: We asked 1,116 prescription drug abusers admitted for treatment, through standardized questionnaires, where they obtained their drugs. We also attempted to purchase scheduled II and III drugs from a random sample of Internet sites offering such sales. RESULTS: Dealers, friends or relatives, and doctors' prescriptions were listed as a source of drugs with equal frequency ( approximately 50-65%), with theft and forgery far behind at 20%. The Internet was mentioned by fewer than 6% of the total responders. Because these data suggest either lack of availability or that our sample has not yet realized that the Internet is a potential source, we attempted to purchase scheduled II and III opioids and the unscheduled opioid, tramadol, from a random sample of 10% of the sites listing such sales. We were unsuccessful in purchasing a single scheduled opioid analgesic, but found that tramadol, as an unscheduled drug, was freely available. CONCLUSIONS: The assertion that the Internet has become a dangerous new avenue for the diversion of scheduled prescription opioid analgesics appears to be based on no empirical evidence and is largely incorrect.

Improvements in Radiation Monitoring Trending.

One of the main goals for Radiation Safety Professionals is to help maintain radiation worker doses below administrative control levels. In the radiation safety field there is an increasing recognition of the value of dosimetry-related data that can be used to enhance safety programs and regulatory compliance. Mining radiation dosimetry data and rendering results in the form of dashboards provides insights for the Radiation Safety Professionals that could help improve the radiological protection programs effectiveness, enhances quality, and reduces cost. Quite often the professionals spend more time assembling data than analyzing for trends and acting to improve the radiation safety program. Data analysis tools were developed allowing the radiation safety professionals to perform surveillance on key parameters in the dosimetry program that can help identifying risks and insure early intervention. More than 2,200 institutions chosen from different industries were surveyed for more than 2 years after the implementation of this tool. Four indicators: dose per participant, collective dose, dosimeter return compliance, and number of workers exceeding ALARA levels were chosen as meaningful parameters in characterizing the health of the program. These parameters were tracked, analyzed, and compared to benchmarks developed based on more than 1 million monitored workers.

High-resolution global genomic survey of 178 gliomas reveals novel regions of copy number alteration and allelic imbalances.

Primary brain tumors are the fourth leading cause of cancer mortality in adults under the age of 54 years and the leading cause of cancer mortality in children in the United States. Therapy for the most common type of primary brain tumors, gliomas, remains suboptimal. The development of new and more effective treatments will likely require a better understanding of the biology of these tumors. Here, we show that use of the high-density 100K single-nucleotide polymorphism arrays in a large number of primary tumor samples allows for a much higher resolution survey of the glioma genome than has been previously reported in any tumor type. We not only confirmed alterations in genomic areas previously reported to be affected in gliomas, but we also refined the location of those sites and uncovered multiple, previously unknown regions that are affected by copy number alterations (amplifications, homozygous and heterozygous deletions) as well as allelic imbalances (loss of heterozygosity/gene conversions). The wealth of genomic data produced may allow for the development of a more rational molecular classification of gliomas and serve as an important starting point in the search for new molecular therapeutic targets.