To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD).
The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian ...family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis.
A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb.
A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.
We hypothesized that percutaneous coronary intervention (PCI) preceded by early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or with abciximab alone ...(abciximab-facilitated PCI) would improve outcomes in patients with acute ST-segment elevation myocardial infarction, as compared with abciximab administered immediately before the procedure (primary PCI).
In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximab-facilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization.
A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P=0.01 and P=0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P=0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P=0.49).
Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228 ClinicalTrials.gov.)
Removal of seven active pharmaceutical substances (ibuprofen, ketoprofen, naproxen, diclofenac, clofibric acid, mefenamic acid, and gemfibrozil) was assessed by batch experiments, with suspended ...biofilm carriers and activated sludge from several full-scale wastewater treatment plants. A distinct difference between nitrifying activated sludge and suspended biofilm carrier removal of several pharmaceuticals was demonstrated. Biofilm carriers from full-scale nitrifying wastewater treatment plants, demonstrated considerably higher removal rates per unit biomass (i.e. suspended solids for the sludges and attached solids for the carriers) of diclofenac, ketoprofen, gemfibrozil, clofibric acid and mefenamic acid compared to the sludges. Among the target pharmaceuticals, only ibuprofen and naproxen showed similar removal rates per unit biomass for the sludges and biofilm carriers. In contrast to the pharmaceutical removal, the nitrification capacity per unit biomass was lower for the carriers than the sludges, which suggests that neither the nitrite nor the ammonia oxidizing bacteria are primarily responsible for the observed differences in pharmaceutical removal. The low ability of ammonia oxidizing bacteria to degrade or transform the target pharmaceuticals was further demonstrated by the limited pharmaceutical removal in an experiment with continuous nitritation and biofilm carriers from a partial nitritation/anammox sludge liquor treatment process.
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► This study compares biofilm carrier and activated sludge removal of pharmaceuticals. ► Biofilm carriers show higher pharmaceutical removal, compared to activated sludge. ► Diclofenac and Clofibric acid were only removed with biofilm carriers. ► No clear link between pharmaceutical removal and nitrifying capacity was observed.
Engineering of materials with specific physical properties has recently focused on the effect of nano-sized 'guest domains' in a 'host matrix' that enable tuning of electrical, mechanical, ...photo-optical or thermal properties. A low thermal conductivity is a prerequisite for obtaining effective thermoelectric materials, and the challenge is to limit the conduction of heat by phonons, without simultaneously reducing the charge transport. This is named the 'phonon glass-electron crystal' concept and may be realized in host-guest systems. The guest entities are believed to have independent oscillations, so-called rattler modes, which scatter the acoustic phonons and reduce the thermal conductivity. We have investigated the phonon dispersion relation in the phonon glass-electron crystal material Ba(8)Ga(16)Ge(30) using neutron triple-axis spectroscopy. The results disclose unambiguously the theoretically predicted avoided crossing of the rattler modes and the acoustic-phonon branches. The observed phonon lifetimes are longer than expected, and a new explanation for the low kappa(L) is provided.
Summary Objective To investigate the presence of mast cells in the osteoarthritic (OA) synovium and their association with clinical parameters in comparison with rheumatoid arthritis (RA) samples. ...Method Synovial tissues of 56 symptomatic OA and 49 RA patients were obtained. Two to three paraffin slides were used to quantify inflammation using haematoxylin and eosin (H&E) staining (synovitis score 0–9), and numbers of mast cells (per 10 high-power fields) using double immunofluorescence for CD117 and tryptase. Average scores per patient were used for analysis. Knee radiographs of OA patients were scored according to the Kellgren and Lawrence (KL) system and pain was determined in OA patients at baseline by visual analogue scale (VAS). Results Median (range) of mast cells was significantly higher in OA samples 45 (1–168) compared to RA samples 4 (1–47) ( P -value < 0.001), despite a lower median (range) synovitis score in OA (2.5 (0–6.0)) compared to 4.6 (0–8.0) in RA samples. The synovitis score was significantly correlated with the number of mast cells (in OA Spearman's rho ( P -value) 0.3 (0.023) and RA 0.5 ( P -value < 0.001)). Interestingly, we observed a trend towards an association between the number of mast cells and an increased KL-grade ( P -value 0.05) in OA patients, independently of synovitis. No associations were found with self-reported pain. Conclusion Prevalence of mast cells in OA synovial tissue is relatively high and associates with structural damage in OA patients, suggesting a role of mast cells in this disease.
Objective
To assess disparities in pre‐eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries.
Design
Cross‐country comparative study of ...linked population‐based databases.
Setting
Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden.
Population
All immigrant and non‐immigrant women delivering in the six industrialised countries within the most recent 10‐year period available to each participating centre (1995–2010).
Methods
Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within‐country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI).
Main outcome measures
Pre‐eclampsia, eclampsia and pre‐eclampsia with prolonged hospitalisation (cases per 1000 deliveries).
Results
There were 9 028 802 deliveries (3 031 399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub‐Saharan Africa and Latin America & the Caribbean were at higher risk of pre‐eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native‐born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest.
Conclusion
Immigrant women from Sub‐Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre‐eclampsia and eclampsia.
In this contribution, we analyse scenarios of advanced wastewater treatment for the removal of micropollutants. By this we refer to current mainstream, broad spectrum processes including ozonation ...and sorption onto activated carbon. We argue that advanced treatment requires properly implemented tertiary (nutrient removal) treatment in order to be effective. We review the critical aspects of the main advanced treatment options, their advantages and disadvantages. We propose a quantification of the costs of implementing advanced treatment, as well as upgrading plants from secondary to tertiary treatment when needed, and we illustrate what drives the costs of advanced treatment for a set of standard configurations. We propose a cost function to represent the total costs (investment, operation and maintenance) of advanced treatment. We quantify the implications of advanced treatment in terms of greenhouse gas emissions. Based on the indicators of total toxic discharge, toxicity at the discharge points and toxicity across the stream network discussed in Pistocchi et al. (2022), we compare costs and effectiveness of different scenarios of advanced treatment. In principle the total toxic load and toxicity at the points of discharge could be reduced by about 75 % if advanced treatment processes were implemented virtually at all wastewater treatment plants, but this would entail costs of about 4 billion euro/year for the European Union as a whole. We consider a “compromise” scenario where advanced treatment is required at plants of 100 thousand population equivalents (PE) or larger, or at plants between 10 and 100 thousand PE if the dilution ratio at the discharge point is 10 or less. Under this scenario, the length of the stream network exposed to high toxicity would not increase significantly compared to the previous scenario, and the other indicators would not deteriorate significantly, while the costs would remain at about 1.5 billion Euro/year. Arguably, costs could be further reduced, without a worsening of water quality, if we replace a local risk assessment to generic criteria of plant capacity and dilution in order to determine if a WWTP requires advanced treatment.
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•Cost/effectiveness of advanced treatment scenarios for wastewater micropollutants.•Pollution down by 75 % with advanced treatment everywhere, but costs ~4 bn €/y•Acceptably protective, “compromise” scenario costs about 1.5 bn €/y.•Large plants should treat, risk assessment to decide on treatment at a small plant.
Reproductive longevity is essential for fertility and influences healthy ageing in women
, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we ...identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations
. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
Parabens are commonly used as preservatives due to anti-bactericidal and anti-fungicidal properties and they are ubiquitously present in personal care products, pharmaceuticals, food, industrial and ...domestic commodities. They are suspected of causing endocrine disrupting effects to aquatic organisms and adverse effects in humans and, thus, it is highly relevant to identify and quantify their sources and transportation pathways in the urban environment. Here a substance flow analysis (SFA) was performed in order to map and comprehend the substances’ flow on a national basis. Many household commodities were found to contain parabens; cleaning detergents, slimy toys, and water-based paint. The presence and concentration of parabens are regulated in cosmetics and food. Use of parabens in pharmaceuticals as excipients is documented in Denmark. The import of parabens is increasing; although the number of industrial parabens containing commodities is decreasing and manufacturer reports phase-out of parabens. The vast majority of the paraben containing commodities has a durability of 18–30 months, thus the average lifetime of the paraben stock is perceived to be limited. The inflow was ca. 154
tonnes via pure chemicals and 7.2–73
tonnes via commodities in 2004. This corresponds to an average wastewater concentration of 640–900
μg/L, when excluding discharge to solid waste, soil, biodegradation and metabolism. This is in the same order of magnitudes as can be found in industrial wastewater but higher than that seen in domestic wastewater. The data needed for the SFA is sparse, dispersed, and difficult to access and associated with a great deal of uncertainty.
Background
Dementia is an overarching term for memory-affecting and progressive diseases interfering with cognitive abilities, behaviour and daily living of persons affected. Deterioration of ...cognitive function influences the processes of memory, thinking, orientation, comprehension, learning and language capacity as well as judgement. Alzheimer's disease (AD) is the most common form of dementia, prevalent in approximately 50-70% of the dementia cases. In 2015, there were 47 million people affected by dementia worldwide, and the figure was estimated to increase to 75 million by 2030 and to 132 million by 2050. Genetics, environmental factors and lifestyle patterns are risk factors for developing AD.
Methods
In the framework of the “European Human Biomonitoring Initiative” (HBM4EU, https://www.hbm4eu.eu/), a set of 18 substances or substance groups were prioritized for investigation. For each of these, a scoping document was developed, summarizing current knowledge and policy-related knowledge gaps. This work presents a scoping review of chemical substances, which may be associated with AD, based on the HBM4EU scoping documents and relevant recent scientific literature.
Results
Exposure to pesticides is possibly a risk factor for AD. Exposure to mercury is possibly associated with AD development, but results are inconsistent. Though results on cadmium and arsenic and AD are conflicting, they are possibly associated with the risk of disease. The evidence regarding lead is weak. Harmful exposures to these substances in Europe were mostly connected to occupational settings.
Conclusions
Although there is tentative evidence on exposure to environmental substances and risk for AD, more research is needed. Some evidence is inconsistent and there is a lack of extensive human studies. Attention should be paid to certain occupations, such as farmers exposed to pesticides and workers exposed to heavy metals, since these substances may be linked to increased disease rates of AD.
Key messages
Exposure to pesticides, mercury, cadmium and arsenic may adversely affect cognitive abilities and contribute to risk of AD. High-quality epidemiological research is needed to confirm the findings.
Because adverse environmental chemical exposures affect both workers in certain occupations and general public, protecting humans from the chemical hazards is an essential public health issue.
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