960 resultados para Non-targeted Metabolomics


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In this article we contribute to the expansion of lesbian, gay, bisexual, transgender and queer (LGBTQ) health psychology beyond the confines of sexual health by examining the experiences of lesbian, gay and bisexual people living with non-HIV related chronic illness. Using a (predominantly) qualitative online survey, the perspectives of 190 LGB people with 52 different chronic illnesses from eight countries were collected. The five most commonly reported physical conditions were arthritis, hypertension, diabetes, asthma and chronic fatigue syndrome. Our analysis focuses on four themes within participants’ written comments: (1) ableism within LGBT communities; (2) isolation from LGBT communities and other LGB people living with chronic illness; (3)heteronormativity within sources of information and support and; (4) homophobia from healthcare professionals. We conclude by suggesting that LGBTQ psychology could usefully draw on critical health psychology principles and frameworks to explore non-heterosexual’s lived experiences of chronic illness, and also that there remains a need for specifically targeted support groups and services for LGB people with chronic illnesses.

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Development of mass spectrometry techniques to detect protein oxidation, which contributes to signalling and inflammation, is important. Label-free approaches have the advantage of reduced sample manipulation, but are challenging in complex samples owing to undirected analysis of large data sets using statistical search engines. To identify oxidised proteins in biological samples, we previously developed a targeted approach involving precursor ion scanning for diagnostic MS3 ions from oxidised residues. Here, we tested this approach for other oxidations, and compared it with an alternative approach involving the use of extracted ion chromatograms (XICs) generated from high-resolution MSMS data using very narrow mass windows. This accurate mass XIC data methodology was effective at identifying nitrotyrosine, chlorotyrosine, and oxidative deamination of lysine, and for tyrosine oxidations highlighted more modified peptide species than precursor ion scanning or statistical database searches. Although some false positive peaks still occurred in the XICs, these could be identified by comparative assessment of the peak intensities. The method has the advantage that a number of different modifications can be analysed simultaneously in a single LC-MSMS run. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. Biological significance: The use of accurate mass extracted product ion chromatograms to detect oxidised peptides could improve the identification of oxidatively damaged proteins in inflammatory conditions. © 2013 Elsevier B.V.

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Cell death and removal of cell corpses in a timely manner is a key event in both physiological and pathological situations including tissue homeostasis and the resolution of inflammation. Phagocytic clearance of cells dying by apoptosis is a complex sequential process comprising attraction, recognition, tethering, signalling and ultimately phagocytosis and degradation of cell corpses. A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within this process. The role of myeloid cell CD14 in mediating apoptotic cell interactions with macrophages has long been known though key molecules and residues involved have not been defined. Here we sought to further dissect the function of CD14 in apoptotic cell clearance. A novel panel of THP-1 cell-derived phagocytes was employed to demonstrate that CD14 mediates effective apoptotic cell interactions with macrophages in the absence of detectable TLR4 whilst binding and responsiveness to LPS requires TLR4. Using a targeted series of CD14 point mutants expressed in non-myeloid cells we reveal CD14 residue 11 as key in the binding of apoptotic cells whilst other residues are reported as key for LPS binding. Importantly we note that expression of CD14 in non-myeloid cells confers the ability to bind rapidly to apoptotic cells. Analysis of a panel of epithelial cells reveals that a number naturally express CD14 and that this is competent to mediate apoptotic cell clearance. Taken together these data suggest that CD14 relies on residue 11 for apoptotic cell tethering and it may be an important tethering molecule on so called 'non-professional' phagocytes thus contributing to apoptotic cell clearance in a non-myeloid setting. Furthermore these data establish CD14 as a rapid-acting tethering molecule, expressed in monocytes, which may thus confer responsiveness of circulating monocytes to apoptotic cell derived material. © 2013 Thomas et al.

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This thesis explores the interaction between Micros (<10 employees) from non-creative sectors and website designers ("Creatives") that occurred when creating a website of a higher order than a basic template site. The research used Straussian Grounded Theory Method with a longitudinal design, in order to identify what knowledge transferred to the Micros during the collaboration, how it transferred, what factors affected the transfer and outcomes of the transfer including behavioural additionality. To identify whether the research could be extended beyond this, five other design areas were also examined, as well as five Small to Medium Enterprises (SMEs) engaged in website and branding projects. The findings were that, at the start of the design process, many Micros could not articulate their customer knowledge, and had poor marketing and visual language skills, knowledge core to web design, enabling targeted communication to customers through images. Despite these gaps, most Micros still tried to lead the process. To overcome this disjoint, the majority of the designers used a knowledge transfer strategy termed in this thesis as ‘Bi-Modal Knowledge Transfer’, where the Creative was aware of the transfer but the Micro was unaware, both for drawing out customer knowledge from the Micro and for transferring visual language skills to the Micro. Two models were developed to represent this process. Two models were also created to map changes in the knowledge landscapes of customer knowledge and visual language – the Knowledge Placement Model and the Visual Language Scale. The Knowledge Placement model was used to map the placement of customer knowledge within the consciousness, extending the known Automatic-Unconscious -Conscious model, adding two more locations – Peripheral Consciousness and Occasional Consciousness. Peripheral Consciousness is where potential knowledge is held, but not used. Occasional Consciousness is where potential knowledge is held but used only for specific tasks. The Visual Language Scale was created to measure visual language ability from visually responsive, where the participant only responds personally to visual symbols, to visually multi-lingual, where the participant can use visual symbols to communicate with multiple thought-worlds. With successful Bi-Modal Knowledge Transfer, the outcome included not only an effective website but also changes in the knowledge landscape for the Micros and ongoing behavioural changes, especially in marketing. These effects were not seen in the other design projects, and only in two of the SME projects. The key factors for this difference between SMEs and Micros appeared to be an expectation of knowledge by the Creatives and failure by the SMEs to transfer knowledge within the company.

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Establishing an association between the scent a perpetrator left at a crime scene to the odor of the suspect of that crime is the basis for the use of human scent identification evidence in a court of law. Law enforcement agencies gather evidence through the collection of scent from the objects that a perpetrator may have handled during the execution of the criminal act. The collected scent evidence is consequently presented to the canines for identification line-up procedures with the apprehended suspects. Presently, canine scent identification is admitted as expert witness testimony, however, the accurate behavior of the dogs and the scent collection methods used are often challenged by the court system. The primary focus of this research project entailed an evaluation of contact and non-contact scent collection techniques with an emphasis on the optimization of collection materials of different fiber chemistries to evaluate the chemical odor profiles obtained using varying environment conditions to provide a better scientific understanding of human scent as a discriminative tool in the identification of suspects. The collection of hand odor from female and male subjects through both contact and non-contact sampling approaches yielded new insights into the types of VOCs collected when different materials are utilized, which had never been instrumentally performed. Furthermore, the collected scent mass was shown to be obtained in the highest amounts for both gender hand odor samples on cotton sorbent materials. Compared to non-contact sampling, the contact sampling methods yielded a higher number of volatiles, an enhancement of up to 3 times, as well as a higher scent mass than non-contact methods by more than an order of magnitude. The evaluation of the STU-100 as a non-contact methodology highlighted strong instrumental drawbacks that need to be targeted for enhanced scientific validation of current field practices. These results demonstrated that an individual's human scent components vary considerably depending on the method used to collect scent from the same body region. This study demonstrated the importance of collection medium selection as well as the collection method employed in providing a reproducible human scent sample that can be used to differentiate individuals.

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Non-native predators may have negative impacts on native communities, and these effects may be dependent on interactions among multiple non-native predators. Sequential invasions by predators can enhance risk for native prey. Prey have a limited ability to respond to multiple threats since appropriate responses may conflict, and interactions with recent invaders may be novel. We examined predator–prey interactions among two non-native predators, a recent invader, the African jewelfish, and the longer-established Mayan cichlid, and a native Florida Everglades prey assemblage. Using field enclosures and laboratory aquaria, we compared predatory effects and antipredator responses across five prey taxa. Total predation rates were higher for Mayan cichlids, which also targeted more prey types. The cichlid invaders had similar microhabitat use, but varied in foraging styles, with African jewelfish being more active. The three prey species that experienced predation were those that overlapped in habitat use with predators. Flagfish were consumed by both predators, while riverine grass shrimp and bluefin killifish were eaten only by Mayan cichlids. In mixed predator treatments, we saw no evidence of emergent effects, since interactions between the two cichlid predators were low. Prey responded to predator threats by altering activity but not vertical distribution. Results suggest that prey vulnerability is affected by activity and habitat domain overlap with predators and may be lower to newly invading predators, perhaps due to novelty in the interaction.

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As most hospitality industry managers in the U.S. are already aware, there is a growing and persistent shortage of labor available for service-sector, non-career jobs, the very jobs so vital to the industry. In most cases, recruitment efforts for these jobs are targeted toward younger workers, those under age 25. The authors explore issues regarding the attractiveness of non-career jobs in the eyes of young persons and suggest that, in addition to factors related to the job itself (pay, hours, type of work), the type of procedures used by employers to make selection decisions are equally influential. Recommendations are made concerning how hospitality employers with non-career positions to fill can maximize the chances of successfully staffing their organizations.

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Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood–brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.

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Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.

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The individual effects that echoic, mand, and sign language training procedures have on the acquisition of verbal behavior have been widely demonstrated, but more efficient strategies are still needed. This study combined all three treatment strategies into one treatment intervention in order to investigate the joint effects they may have on verbal behavior. Six participants took part in the study. Intervention totaled 1 hour/day for 5 days/week until mastery criterion for motor echoic behavior was achieved. Although motor echoic behavior were solely targeted for acquisition, significant increases in spontaneous motor mands were noted in all treatment participants. Additionally, 4 treatment participants also demonstrated significant gains in vocal echoics and spontaneous vocal mands. No significant increases were noted for the control participant. Results suggest that the aforementioned procedure may provide more efficient results as a first-step to teaching a functional repertoire of verbal behavior to developmentally delayed children.

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Background: To determine the portion sizes of traditional and non-traditional foods being consumed by Inuit adults in three remote communities in Nunavut, Canada. Methods. A cross-sectional study was carried out between June and October, 2008. Trained field workers collected dietary data using a culturally appropriate, validated quantitative food frequency questionnaire (QFFQ) developed specifically for the study population. Results: Caribou, muktuk (whale blubber and skin) and Arctic char (salmon family), were the most commonly consumed traditional foods; mean portion sizes for traditional foods ranged from 10 g for fermented seal fat to 424 g for fried caribou. Fried bannock and white bread were consumed by >85% of participants; mean portion sizes for these foods were 189 g and 70 g, respectively. Sugar-sweetened beverages and energy-dense, nutrient-poor foods were also widely consumed. Mean portion sizes for regular pop and sweetened juices with added sugar were 663 g and 572 g, respectively. Mean portion sizes for potato chips, pilot biscuits, cakes, chocolate and cookies were 59 g, 59 g, 106 g, 59 g, and 46 g, respectively. Conclusions: The present study provides further evidence of the nutrition transition that is occurring among Inuit in the Canadian Arctic. It also highlights a number of foods and beverages that could be targeted in future nutritional intervention programs aimed at obesity and diet-related chronic disease prevention in these and other Inuit communities.

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A large proportion of the variation in traits between individuals can be attributed to variation in the nucleotide sequence of the genome. The most commonly studied traits in human genetics are related to disease and disease susceptibility. Although scientists have identified genetic causes for over 4,000 monogenic diseases, the underlying mechanisms of many highly prevalent multifactorial inheritance disorders such as diabetes, obesity, and cardiovascular disease remain largely unknown. Identifying genetic mechanisms for complex traits has been challenging because most of the variants are located outside of protein-coding regions, and determining the effects of such non-coding variants remains difficult. In this dissertation, I evaluate the hypothesis that such non-coding variants contribute to human traits and diseases by altering the regulation of genes rather than the sequence of those genes. I will specifically focus on studies to determine the functional impacts of genetic variation associated with two related complex traits: gestational hyperglycemia and fetal adiposity. At the genomic locus associated with maternal hyperglycemia, we found that genetic variation in regulatory elements altered the expression of the HKDC1 gene. Furthermore, we demonstrated that HKDC1 phosphorylates glucose in vitro and in vivo, thus demonstrating that HKDC1 is a fifth human hexokinase gene. At the fetal-adiposity associated locus, we identified variants that likely alter VEPH1 expression in preadipocytes during differentiation. To make such studies of regulatory variation high-throughput and routine, we developed POP-STARR, a novel high throughput reporter assay that can empirically measure the effects of regulatory variants directly from patient DNA. By combining targeted genome capture technologies with STARR-seq, we assayed thousands of haplotypes from 760 individuals in a single experiment. We subsequently used POP-STARR to identify three key features of regulatory variants: that regulatory variants typically have weak effects on gene expression; that the effects of regulatory variants are often coordinated with respect to disease-risk, suggesting a general mechanism by which the weak effects can together have phenotypic impact; and that nucleotide transversions have larger impacts on enhancer activity than transitions. Together, the findings presented here demonstrate successful strategies for determining the regulatory mechanisms underlying genetic associations with human traits and diseases, and value of doing so for driving novel biological discovery.

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Background

It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
Objectives

To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
Search methods

We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
Selection criteria

Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
Data collection and analysis

Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
Main results

Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
Authors' conclusions

Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

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This dissertation examines the price sensitivity of demand for higher education among non-traditional students in the United States. Chapter 1 discusses the issues related to the demand for higher education. It presents the recent trends and reviews the literature addressing these issues. A major conclusion that emerges from this chapter is that the price sensitivity of demand for higher education appears to depend on the source of the variation in price and the characteristics of the students who face the price change. The baseline estimate for the price sensitivity of demand is that a $1,000 (in year 2000 dollars) decrease in tuition costs should result in a 4 percentage-point increase in enrollment for the traditional 18- to 24-year-old student. Chapter 2 examines the price sensitivity of demand for higher education for military spouses resulting from variation in tuition due to military-mandated moves across states. The data suggest that a $1,000 (in year 2000 dollars) decrease in the cost of 2-year schools is associated with a 1--1.5 percentage-point increase in the probability of attending college. This estimate is less than half the previous estimates due to in-state tuition price differences faced by the civilian 18- to 24-year-old population on a percentage-point basis. However, this represents a 7--10 percent increase for this population, and the magnitude of this metric is in line with previous estimates. This suggests tuition assistance can be an effective means of increasing enrollment for military spouses, but other barriers to education for this population may also need to be addressed. Chapter 3 examines the impact of a change in the tax treatment of savings set aside for higher education by those who decide to suspend their education and enter the workforce. The taxation of these funds appears to have increased the rate at which these funds are included in an employee's initial contract and the quantity of funds allocated. These results are counterintuitive if the tax preference was the primary reason for the savings plan. However, these results suggest the rationale for the savings plan was to offer targeted additional compensation to recruits with greater negotiating power. Taxation of funds previously set aside did not appear to have a statistically significant impact on their utilization. Point estimates of the price sensitivity of demand from changes in the out-of-pocket costs for higher education induced by the taxation of these funds were small and often not statistically significant. The results from this dissertation show responses to changes in the net cost of college that differ by the source of price variation and the population experiencing them. This is consistent with the previous literature. This dissertation contributes to the literature by providing estimates for the price sensitivity of demand for higher education to previously understudied non-traditional students.

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In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders.