Peripheral immune function and Alzheimer's disease: a living systematic review and critical appraisal.

BACKGROUND: A growing body of literature examines the relationship between peripheral immune function and Alzheimer's Disease (AD) in human populations. Our living systematic review summarizes the characteristics and findings of these studies, appraises their quality, and formulates recommendations for future research. METHODS: We searched the electronic databases PubMed, PsycINFO, and Web of Science, and reviewed references of previous reviews and meta-analyses to identify human studies examining the relationship between any peripheral immune biomarkers and AD up to September 7th, 2023. We examined patterns of reported statistical associations (positive, negative, and null) between each biomarker and AD across studies. Evidence for each biomarker was categorized into four groups based on the proportion of studies reporting different associations: corroborating a positive association with AD, a negative association, a null association, and presenting contradictory findings. A modified Newcastle-Ottawa scale (NOS) was employed to assess the quality of the included studies. FINDINGS: In total, 286 studies were included in this review. The majority were cross-sectional (n = 245, 85.7%) and hospital-based (n = 248, 86.7%), examining relationships between 187 different peripheral immune biomarkers and AD. Cytokines were the most frequently studied group of peripheral immune biomarkers. Evidence supported a positive association with AD for six biomarkers, including IL-6, IL-1ß, IFN-γ, ACT, IL-18, and IL-12, and a negative association for two biomarkers, including lymphocytes and IL-6R. Only a small proportion of included studies (n = 22, 7.7%) were deemed to be of high quality based on quality assessment. INTERPRETATION: Existing research on peripheral immune function and AD exhibits substantial methodological variations and limitations, with a notable lack of longitudinal, population-based studies investigating a broad range of biomarkers with prospective AD outcomes. The extent and manner in which peripheral immune function can contribute to AD pathophysiology remain open questions. Given the biomarkers that we identified to be associated with AD, we posit that targeting peripheral immune dysregulation may present a promising intervention point to reduce the burden of AD.

A GIS-based methodology for selecting stormwater disconnection opportunities.

The purpose of this paper is to introduce a geographic information system (GIS)-based decision support tool that assists the user to select not only areas where (retrofit) sustainable drainage systems (SuDS) could be implemented within a large catchment (>100 ha), but also to allow discrimination between suitable SuDS techniques based on their likely feasibility and effectiveness. The tool is applied to a case study catchment within London, UK, with the aim of increasing receiving water quality by reducing combined sewer overflow (CSO) spill frequency and volume. The key benefit of the tool presented is to allow rapid assessment of the retrofit SuDS potential of large catchments. It is not intended to replace detailed site investigations, but may help to direct attention to sites that have the greatest potential for retrofit SuDS implementation. Preliminary InfoWorks CS modelling of 'global disconnections' within the case study catchment, e.g. the removal of 50% of the total impervious area, showed that CSO spill volume could be reduced by 55 to 78% during a typical year. Using the disconnection hierarchy developed by the authors, the feasibility of retrofit SuDS deployment within the case study catchment is assessed, and the implications discussed.

Towards quantification of uncertainty in predicting water quality failures in integrated catchment model studies.

This paper describes the development and application of a method for estimating uncertainty in the prediction of sewer flow quantity and quality and how this may impact on the prediction of water quality failures in integrated catchment modelling (ICM) studies. The method is generic and readily adaptable for use with different flow quality prediction models that are used in ICM studies. Use is made of the elicitation concept, whereby expert knowledge combined with a limited amount of data are translated into probability distributions describing the level of uncertainty of various input and model variables. This type of approach can be used even if little or no site specific data is available. Integrated catchment modelling studies often use complex deterministic models. To apply the results of elicitation in a case study, a computational reduction method has been developed in order to determine levels of uncertainty in model outputs with a reasonably practical level of computational effort. This approach was applied to determine the level of uncertainty in the number of water quality failures predicted by an ICM study, due to uncertainty associated with input and model parameters of the urban drainage model component of the ICM. For a small case study catchment in the UK, it was shown that the predicted number of water quality failures in the receiving water could vary by around 45% of the number predicted without consideration of model uncertainty for dissolved oxygen and around 32% for unionised ammonia. It was concluded that the potential overall levels of uncertainty in the ICM outputs could be significant. Any solutions designed using modelling approaches that do not consider uncertainty associated with model input and model parameters may be significantly over-dimensioned or under-dimensioned. With changing external inputs, such as rainfall and river flows due to climate change, better accounting for uncertainty is required.

In-sewer sedimentation associated with active flow control.

Active flow control using automated gates and weirs aims to utilise available dispersed storage within sewer systems to alleviate the severity and frequency of localised flooding incidents. Whilst a previous study has demonstrated its potential, a key operational concern before implementation was sedimentation. An experimental programme was designed to investigate the sediment deposition created when using a flow control device. Tests were also undertaken to examine the potential for rapid gate opening to flush away any resulting deposits. In catchments dominated by fine material in suspension, the use of an active flow control device can result in a uniformly thick deposit upstream of the gate. Rapid gate opening results in deposited material eroding in large sections starting at the gate and moving in an upstream direction. Granular sediment forms a series of discrete bedforms which are fairly uniform regardless of the flow conditions and a larger deposit further upstream. The potential for flushing granular deposits is limited and modification of the operation of the gate has shown little potential for increasing the effectiveness. Therefore, active flow control using a single downstream gate may only be suitable in systems with fine material moving in suspension during dry weather flow and not where there is significant granular sediment.

Estimation of uncertainty in long term combined sewer sediment behaviour predictions, a UK case study.

There are regulatory driven requirements for UK water companies to reduce the number of properties at risk of sewer flooding. One of the potential causes of sewer flooding is the presence of persistent sediment deposits in sewers. This is a common problem in many combined sewers. Although the regulation is risk based, there is a gap in current knowledge on how risk assessment is affected by the uncertainty in sewer solids behaviour prediction. This paper describes a UK case study exploring the possibility of estimating uncertainty in sewer sediment deposit level predictions, using Monte Carlo simulations combined with a response database.

Sewer system design moving into the 21st century--a UK perspective.

Change in external factors, such as environmental legislation and climate change, will mean the future of sewerage systems is likely to be different from the past. Combined sewerage systems comprise the vast majority of existing sewers in countries such as the UK. A study funded by UK Water Industry Research Ltd has reviewed the current state of sewerage within the UK, the likely drivers for change and the consequent future impacts over a 75 year timescale. Potential responses to address the anticipated changes have also been considered. It is concluded that due to the wide extent and value of existing sewer systems, these will continue to be used for the foreseeable future. However, in order to meet the major challenges as a result of changing external factors, these need to be operated more effectively, new ideas need to be explored and moves to develop better and more integrated water management systems need to be started if sewer systems in the UK are to provide the anticipated required levels of service well into the 21st century.

Implementation impediments to institutionalising the practice of sustainable urban water management.

It is now well accepted that there are significant challenges to realising the widespread and self-sustaining implementation of sustainable urban water management. It is argued that these challenges are entrenched within the broader socio-political framework, yet often unsuccessfully addressed within the more narrow scope of improving technical knowledge and design capacity. This hypothesis is investigated through a comparative analysis of three independent research projects investigating different dimensions of the water cycle, including stormwater management in Australia and sanitary waste management and implementation of innovative technologies in the U.K. The analysis reveals significant and common socio-political impediments to improved practice. It was evident that the administrative regime, including implementing professionals and institutions, appears to be largely driven by an implicit expectation that there is a technical solution to solve water management issues. This is in contrast to addressing the issues through broader strategies such as political leadership, institutional reform and social change. It is recognised that this technocratic culture is inadvertently underpinned by the need to demonstrate implementation success within short-term political cycles that conflict with both urban renewal and ecological cycles. Addressing this dilemma demands dedicated socio-technical research programs to enable the much needed shift towards a more sustainable regime.

Improved formulations for rapid erosion of diverse solids in combined sewers.

For more than a decade, research carried out in Scotland has investigated the movement of sediment in sewers and the associated pollutant release. Pollution by discharges from combined sewer overflows can adversely affect watercourses, particularly those in urban areas. Solids and dissolved contaminants, many derived from in-sewer deposits during a storm event, can be especially significant. This phenomenon can occur during events known as 'foul flushes'. In combined sewers these typically occur in the initial period of storm flows, when the concentration of suspended sediments and other pollutants is significantly higher than at other times. It has become apparent that much of the suspended load originates from solids eroded from the bed. The 'near bed solids' which are re-entrained into the flow, together with solids eroded from the bulk bed, account for large changes in the suspended sediment concentration under time varying flow conditions. This paper describes some of the methods employed to investigate the solids eroding in combined sewers during peak flow events. The work examined the potential for sediment re-suspension under high flow conditions both in the laboratory and in the field.

Flooding in the future--predicting climate change, risks and responses in urban areas.

Engineering infrastructure is provided at high cost and is expected to have a useful operational life of decades. However, it is clear that the future is uncertain. Traditional approaches to designing and operating urban storm drainage assets have relied on past performance of natural systems and the ability to extrapolate this performance, together with that of the assets across the usable lifetime. Whether or not climate change is going to significantly alter future weather patterns in Europe, it is clear that it is now incumbent on designers and operators of storm drainage systems to prepare for greater uncertainty in the effectiveness of storm drainage systems. A recent U.K. Government study considered the potential effects of climate and socio-economic change in the U.K. in terms of four future scenarios and what the implications are for the performance of existing storm drainage facilities. In this paper the modelling that was undertaken to try to quantify the changes in risk, together with the effectiveness of responses in managing that risk, are described. It shows that flood risks may increase by a factor of almost 30 times and that traditional engineering measures alone are unlikely to be able to provide protection.

The influence of biodegradability of sewer solids for the management of CSOs.

The re-suspension of sediments in combined sewers and the associated pollutants into the bulk water during wet weather flows can cause pollutants to be carried further downstream to receiving waters or discharged via Combined Sewer Overflows (CSO). A typical pollutograph shows the trend of released bulk pollutants with time but does not consider information on the biodegradability of these pollutants. A new prediction methodology based on Oxygen Utilisation Rate (respirometric method) and Erosionmeter (laboratory device replicating in-sewer erosion) experiments is proposed which is able to predict the trends in biodegradability during in-sewer sediment erosion in wet weather conditions. The proposed new prediction methodology is also based on COD fractionation techniques.

The acoustic attenuation and hydraulic roughness in a large section sewer pipe with periodical obstacles.

The acoustic attenuation, relative sound pressure levels and the equivalent Nikuradse wall roughness under variable flow conditions in a 600 mm concrete sewer pipe are experimentally investigated. The values of the acoustic attenuation are obtained in the case of airborne sound propagation in the dry pipe. A range of values of the equivalent wall roughness is artificially generated by deploying a periodical array of engineering bricks. A novel method of rapid evaluation of the acoustic attenuation is proposed. The method relies upon sound reflections from the adjacent manholes. The results demonstrate that the acoustic attenuation depends strongly on the value of the equivalent wall roughness. This work can pave the way to the efficient methodology for the in-situ, physical evaluation of the equivalent hydraulic roughness of new and existing sewer networks.

Sewer sediment transport studies using an environmentally controlled annular flume.

This paper provides an overview and some preliminary results of a collaborative project recently completed at WL Delft Hydraulics. It describes tests in an annular flume, in which sediment deposits were formed under carefully controlled and monitored environmental conditions. The deposits were then subjected to a series of time steps in which the rotational speed of the flume's top and bottom plates was increased, progressively increasing the bed shear stress. The sediment deposits were formed using three different types of sediment. An artificial organic sediment, together with a uniformly sized sand were selected as surrogate sewer sediments. The deposits in the remaining experiments were real in-sewer sediments, from catchments in the UK (Dundee) and The Netherlands (Loenen). During the erosion test, total and volatile suspended solids concentration, particle size distribution of the eroded sediment, and COD and DO levels were recorded. The bed surface topography was also measured so that the influence of the deposit formation condition on bedforms could also be examined. Where bed consolidation times were least 24 hours a biologically active surficial layer was observed to develop at the sediment/water interface. The initial deposit conditions (temperature and deposit duration) were both found to have a significant impact on the subsequent erosion of the deposit.

The utilisation of engineered invert traps in the management of near bed solids in sewer networks.

Large existing sewers are considerable assets which wastewater utilities will require to operate for the foreseeable future to maintain health and the quality of life in cities. Despite their existence for more than a century there is surprisingly little guidance available to manage these systems to minimise problems associated with in-sewer solids. A joint study has been undertaken in the UK, to refine and utilise new knowledge gained from field data, laboratory results and Computational Fluid Dynamics (CFD) simulations to devise cost beneficial engineering tools for the application of small invert traps to localise the deposition of sediments in sewers at accessible points for collection. New guidance has been produced for trap siting and this has been linked to a risk-cost-effectiveness assessment procedure to enable system operators to approach in-sewer sediment management pro-actively rather than reactively as currently happens.

Life cycle analysis and sewer solids.

The search for sustainable ways of living has necessitated a new look at the way in which water services are provided. The new paradigm includes whole-system perspectives for each of the primary criteria groups: social, environmental and economic. Whilst Life Cycle Analysis (LCA) techniques have been used successfully for products, they are much less used to assess processes. Nonetheless there is much to learn from the use of LCA for a much wider range of applications. An application is described whereby LCA has been used to determine energy, mass flows and environmental impacts for a number of sewer-related options for handling sewer solids, using the SimaPro software. This work has been part of a wider study to provide enhanced decision support systems for water utilities.

The effect of extended in-sewer storage on wastewater treatment plant performance.

A project funded by UKWIR is under way in the UK to develop a relatively simple methodology whereby the effects of the introduction of extended in-sewer storage at CSOs on downstream sewerage and treatment can be assessed. Recent legislation (UK and European) has compelled many sewer system operators to introduce systems which increase in-sewer retention times, and also retain more flow and load within sewer networks. The project has reviewed existing knowledge about the interaction between in-sewer flow and treatment plants, together with available models. The study is utilising a "benchmark" of 3 configurations of treatment plant and dynamic simulation using the WRc STOAT software, with minor modifications to ensure that effects on odour generation and nutrient removal processes are adequately modelled. As no existing sewer flow quality model can represent the range of conditions possible in sewer networks, a combined application of the Hydroworks model and a new model developed at Aalborg University is being used for this part of the study.

The impact of the controlled emptying of in-sewer storage on wastewater treatment plant performance.

The use of in-sewer storage is generally considered to be an effective means of minimising the effects of intermittent discharges into receiving watercourses during combined flows. Despite this, very little information is available about the consequential effects these flows may have on recipient wastewater treatment plant performance. Typical problems may include biomass washout (hydraulic), and reduced biological reactor performance due to dilute loading (biological). A study is described where detailed analysis was carried out to ascertain the consequential effects of prolonged dilute loading on an activated sludge wastewater treatment plant in Perth, Scotland. Consideration was given to likely storage volumes which may have been utilised in the catchment to resolve local problems. A comprehensive analysis of resulting treatment plant performance was carried out for variations in flow and various wet weather loadings. It is concluded that storage may cause little or no benefit with respect to ammonia total emissions due to reduced treatment of dry weather flows subsequent to the prolonged combined loading period. This was exacerbated by the long regeneration times of nitrifying bacteria. However, an overall benefit with respect to BOD total emissions would always be expected, as appropriately sized storage would retain the first foul flush at the CSOs, thereby compensating the increased emissions from the downstream wastewater treatment plant.

Managing sewer solids for the reduction of foul flush effects--Forfar WTP.

In times of high sewer flow, conditions can exist which enable previously deposited material to be re-entrained back into the body of the flow column. Pulses of this highly polluted flow have been recorded in many instances at the recently constructed wastewater treatment plant (WTP) in Forfar, Scotland. Investigations have been undertaken to characterise the incoming flows and to suggest remedial measures to manage the quality fluctuations. Initial visits to the works and incoming pipes indicated a high degree of sediment deposition in the two inlet pipes. Analyses were carried out and consequently, changes to the hydraulic regime were made. Measurements of sediment level, sediment quality, wall slime and bulk water quality were monitored in the period following the remedial works to observe any improvements. Dramatic alterations in each of the determinands measured were recorded. Analyses were then undertaken to determine long term sediment behaviour and to assess the future usefulness of existing upstream sediment traps. It was concluded that with proper maintenance of the traps, the new hydraulic regime is sufficient to prevent further significant build up of sediment deposits and reduce impacts on the WTP. Further investigations made by North of Scotland Water Authority highlighted trade inputs to the system which may also have contributed to the now managed foul flush problem.