Recent years have seen an increase in the use of Life Cycle Assessment (LCA) to inform urban water systems research. The attraction of LCA is its capacity to identify trade-offs across a broad range ...of environmental issues and a broad range of technologies. However, without some additional perspective on the scale of the results, prioritisation of these concerns will remain difficult. LCA studies at the whole-of-system level are required to identify the diversity of life cycle environmental burdens associated with urban water systems, and the main contributors to these impacts.
In this study, environmental impact profiles were generated for two city-scale urban water systems: one typical of many urban centres, with a high reliance on freshwater extraction and the majority of treated wastewater being discharged to the sea; and one that adopts a more diverse range of water supply and wastewater recycling technologies. The profiles were based on measured data for most system components, otherwise best available empirical data from the literature. Impact models were chosen considering the substantial methodological developments that have occurred in recent years.
System operations, directly within the sphere of influence of water system managers, play the dominant role in all but one of the 14 life cycle impact categories considered. While energy use is the main cause of changes in the impact profiles when the alternative water supply technologies are included, it is not the only important driver of impacts associated with city-scale urban water systems. Also extremely important are process emissions related to wastewater treatment and dams (notably fugitive gases, wastewater discharges, and biosolids disposal).
The results clearly indicate a diverse range of environmental impacts of relevance, extending beyond the traditional concerns of water use and nutrient discharge. Neither energy use, nor greenhouse gas footprints, are likely to be an adequate proxy for representing these additional concerns. However, methodological improvements will be required for certain LCA impact models to support future case study analysis, as will a comprehensive critique of the implications from selecting different impact models.
•Diversified water supply systems incur considerable life-cycle environmental burdens.•Sewage treatment is a major source of life-cycle impacts for urban water systems.•Direct GHG emissions could be 20% or more of the urban water system GHG footprint.•Changes in Ozone Layer protection policy could impact on the urban water industry.•LCA of water systems must consider carefully the choice of impact assessment models.
Although Staphylococcus aureus is best known for infecting humans, bovine-specific strains are a major cause of mastitis in dairy cattle. The bicomponent leukocidin LukMF', exclusively harbored by S. ...aureus of ruminant origin, is a virulence factor associated with bovine infections. In this study, the molecular basis of the host specificity of LukMF' is elucidated by identification of chemokine receptor CCR1 as its target. Bovine neutrophils, the major effector cells in the defense against staphylococci, express significant cell surface levels of CCR1, whereas human neutrophils do not. This causes the particular susceptibility of bovine neutrophils to pore formation induced by LukMF'. Bovine S. aureus strains produce high levels of LukMF' in vitro. In culture supernatant of the mastitis field isolate S1444, LukMF' was the most important cytotoxic agent for bovine neutrophils. In a fibrin gel matrix, the effects of the in situ secreted toxins on neutrophils migrating toward S. aureus were visualized. Under these physiological ex vivo conditions, bovine S. aureus S1444 efficiently killed approaching neutrophils at a distance through secretion of LukMF'. Altogether, our findings illustrate the coevolution of pathogen and host, provide new targets for therapeutic and vaccine approaches to treat staphylococcal diseases in the cow, and emphasize the importance of staphylococcal toxins in general.
This study explains the mechanism of action of LukMF', a bicomponent toxin found in bovine lineages of S. aureus that is associated with mastitis in cattle. At a molecular level, we describe how LukMF' can specifically kill bovine neutrophils. Here, we demonstrate the contribution of toxins in the determination of host specificity and contribute to the understanding of mechanisms of coevolution of pathogen and host. Our study provides new targets that can be used in therapeutic and vaccine approaches to treat staphylococcal diseases in the cow. We also demonstrate the importance of toxins in specific elimination of immune cells, which has broader implications, especially in human infections.
In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume ...decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD.
The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE).
In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-005949-16 .
To sustainably contribute to food security of a growing and richer world population, livestock production systems are challenged to increase production levels while reducing environmental impact, ...being economically viable, and socially responsible. Knowledge about the sustainability performance of current livestock production systems may help to formulate strategies for future systems. Our study provides a systematic overview of differences between conventional and organic livestock production systems on a broad range of sustainability aspects and animal species available in peer-reviewed literature. Systems were compared on economy, productivity, environmental impact, animal welfare and public health. The review was limited to dairy cattle, beef cattle, pigs, broilers and laying hens, and to Europe, North America and New Zealand. Results per indicators are presented as in the articles without performing additional calculations. Out of 4171 initial search hits, 179 articles were analysed. Studies varied widely in indicators, research design, sample size and location and context. Quite some studies used small samples. No study analysed all aspects of sustainability simultaneously. Conventional systems had lower labour requirements per unit product, lower income risk per animal, higher production per animal per time unit, higher reproduction numbers, lower feed conversion ratio, lower land use, generally lower acidification and eutrophication potential per unit product, equal or better udder health for cows and equal or lower microbiological contamination. Organic systems had higher income per animal or full time employee, lower impact on biodiversity, lower eutrophication and acidification potential per unit land, equal or lower likelihood of antibiotic resistance in bacteria and higher beneficial fatty acid levels in cow milk. For most sustainability aspects, sometimes conventional and sometimes organic systems performed better, except for productivity, which was consistently higher in conventional systems. For many aspects and animal species, more data are needed to conclude on a difference between organic and conventional livestock production systems.
The glucagonoma syndrome is a rare disease in which a typical skin disorder, necrolytic migratory erythema, is often one of the first presenting symptoms. Weight loss and diabetes mellitus are two ...other prevalent characteristics of this syndrome. Necrolytic migratory erythema belongs to the recently recognized family of deficiency dermatoses of which zinc deficiency, necrolytic acral erythema and pellagra are also members. It is typically characterized on skin biopsies by necrolysis of the upper epidermis with vacuolated keratinocytes. In persistent hyperglucagonemia, excessive stimulation of basic metabolic pathways results in diabetes mellitus at the expense of tissue glycogen stores, and muscle and fat mass. Multiple (essential) nutrient and vitamin B deficiencies develop, which contribute to the dermatosis. In addition, glucagonomas may produce various other products, like pancreatic polypeptide, that add to the catabolic effects of glucagon.
Background
Surgery has been the treatment of choice for patients with rectal cancer. For locally advanced cancer results were poor, with high rates of locoregional recurrences and poor overall ...survival data. Adding (chemo)radiotherapy upfront improved results mainly in locoregional control. Adding hyperthermia to radiotherapy preoperatively might have an equivalent beneficial effect.
Objectives
To quantify the potential beneficial effect of thermo radiation compared to chemo‐radiation with respect to pathological complete responses, overall survival and toxicity in rectal cancer therapy.
Search methods
We identified the relevant phase II and III randomised controlled trials in any language trough electronic searches May 2007 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various trial databases were searched for the identification of recent completed and ongoing trials (metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies identified until May 2007 were considered for inclusion in the present study.
Selection criteria
Only phase II and III randomised controlled clinical trials were included in the analysis.
Data collection and analysis
All identified studies were assessed by two independent reviewers. A weighted estimate of the treatment effect was computed for 2, 3, 4 and 5‐year survival, for local tumour recurrence, severe acute and late toxicity and complete tumour response (CR). CR was defined either clinically by disappearance of all pretreatment signs of local tumour or pathologically by microscopically free margins. The risk ratio (RR) and hazard ratio (HR) were used. Analyses were performed with the Reference Manager (RevMan).
Main results
Six RCTs published between 1990 and 2007 were identified. A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT) and 262 in the radiotherapy‐hyperthermia arm (RHT).
Four studies (424 patients) reported overall survival (OS) rates. After 2 years, OS was significantly better in the RHT group (HR 2.06; 95% CI 1.33‐3.17; p=.001), but this difference disappeared after a longer period (3, 4 and 5 year OS).
All but one studies reported CR rates. A significant higher CR rate was observed in the RHT group (RR 2.81; 95% CI 1.22‐6.45; p=.01).
Only 2 studies reported on acute toxicity. In these 2 studies no significant differences were observed between the RT and the RHT group. Late toxicity data were not reported.
Authors' conclusions
Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.
Background: Colorectal cancer (CRC) in the indigenous African population of South Africa is uncommon (age standardised incidence rates of 11.29 for males and 7.27/100 000 for females) and tends to ...occur at a young age. Lynch syndrome (LS), an inherited mismatch repair (MMR) gene abnormality, accounts for 3-4% of newly diagnosed CRCs in high incidence areas. There is some evidence that the contribution of an MMR abnormality to the overall CRC burden may be increased in low incidence areas. We aimed to determine the prevalence of MMR deficiency in an indigenous African population. Methods: A cohort of 66 self-declared indigenous African patients, less than 50 years of age at diagnosis with CRC was identified from clinical and pathological records. The original histopathology was reviewed to confirm the diagnosis and features suggestive of MMR abnormality determined (pushing edge, mucinous, lymphocytic infiltration, Crohn's like reaction). Where sufficient tissue was available, samples were sectioned and stained for the four MMR proteins. Results: Histopathological examination confirmed adenocarcinoma in 31 individuals. At least one feature suggestive of MMR was identified in 22 of these specimens. Twenty-seven cases were stained for all four MMR proteins using standard immunohistochemistry (IHC). MMR deficiency was found in 37% (n = 10/27) of cases. Median age of diagnosis was 35 years in the MMR-proficient group and 44 years in the MMR-deficient group, p < 0.008. No other significant differences between the groups were noted. Conclusion: MMR deficiency was common in colorectal carcinomas in the older patients in this cohort, but very young indigenous Africans CRCs do not appear to result from mismatch repair gene mutations. Keywords: inherited colorectal cancer, mismatch repair status
Engineered gene-drive techniques for population modification and/or suppression have the potential for tackling complex challenges, including reducing the spread of diseases and invasive species. ...Gene-drive systems with low threshold frequencies for invasion, such as homing-based gene drive, require initially few transgenic individuals to spread and are therefore easy to introduce. The self-propelled behavior of such drives presents a double-edged sword, however, as the low threshold can allow transgenic elements to expand beyond a target population. By contrast, systems where a high threshold frequency must be reached before alleles can spread-above a fitness valley-are less susceptible to spillover but require introduction at a high frequency. We model a proposed drive system, called "daisy quorum drive," that transitions over time from a low-threshold daisy-chain system (involving homing-based gene drive such as CRISPR-Cas9) to a high-threshold fitness-valley system (requiring a high frequency-a "quorum"-to spread). The daisy-chain construct temporarily lowers the high thresholds required for spread of the fitness-valley construct, facilitating use in a wide variety of species that are challenging to breed and release in large numbers. Because elements in the daisy chain only drive subsequent elements in the chain and not themselves and also carry deleterious alleles ("drive load"), the daisy chain is expected to exhaust itself, removing all CRISPR elements and leaving only the high-threshold fitness-valley construct, whose spread is more spatially restricted. Developing and analyzing both discrete patch and continuous space models, we explore how various attributes of daisy quorum drive affect the chance of modifying local population characteristics and the risk that transgenic elements expand beyond a target area. We also briefly explore daisy quorum drive when population suppression is the goal. We find that daisy quorum drive can provide a promising bridge between gene-drive and fitness-valley constructs, allowing spread from a low frequency in the short term and better containment in the long term, without requiring repeated introductions or persistence of CRISPR elements.
This article presents the background to and prospects for a new initiative in archaeological field survey and database integration. The Roman Hinterland Project combines data from the Tiber Valley ...Project, Roman Suburbium Project, and the Pontine Region Project into a single database, which the authors believe to be one of the most complete repositories of data for the hinterland of a major ancient metropolis, covering nearly 2000 years of history. The logic of combining these databases in the context of studying the Roman landscape is explained and illustrated with analyses that show their capacity to contribute to major debates in Roman economy, demography, and the longue durée of the human condition in a globalizing world.
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