| 1. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 2. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 3. |
- Morawska, Lidia, et al.
(författare)
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COVID-19 and airborne transmission : science rejected, lives lost : can society do better?
- 2023
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 76:10, s. 1854-1859
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Tidskriftsartikel (refereegranskat)abstract
- This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the Covid-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization (WHO) about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story, we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions.
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| 4. |
- Morawska, Lidia, et al.
(författare)
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How can airborne transmission of COVID-19 indoors be minimised?
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- During the rapid rise in COVID-19 illnesses and deaths globally, and notwithstanding recommended precautions, questions are voiced about routes of transmission for this pandemic disease. Inhaling small airborne droplets is probable as a third route of infection, in addition to more widely recognized transmission via larger respiratory droplets and direct contact with infected people or contaminated surfaces. While uncertainties remain regarding the relative contributions of the different transmission pathways, we argue that existing evidence is sufficiently strong to warrant engineering controls targeting airborne transmission as part of an overall strategy to limit infection risk indoors. Appropriate building engineering controls include sufficient and effective ventilation, possibly enhanced by particle filtration and air disinfection, avoiding air recirculation and avoiding overcrowding. Often, such measures can be easily implemented and without much cost, but if only they are recognised as significant in contributing to infection control goals. We believe that the use of engineering controls in public buildings, including hospitals, shops, offices, schools, kindergartens, libraries, restaurants, cruise ships, elevators, conference rooms or public transport, in parallel with effective application of other controls (including isolation and quarantine, social distancing and hand hygiene), would be an additional important measure globally to reduce the likelihood of transmission and thereby protect healthcare workers, patients and the general public.
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| 5. |
- Morawska, Lidia, et al.
(författare)
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Mandating indoor air quality for public buildings : if some countries lead by example, standards may increasingly become normalized
- 2024
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Ingår i: Science. - 0036-8075. ; 383:6690, s. 1418-1420
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Tidskriftsartikel (refereegranskat)abstract
- People living in urban and industrialized societies, which are expanding globally, spend more than 90% of their time in the indoor environment, breathing indoor air (IA). Despite decades of research and advocacy, most countries do not have legislated indoor air quality (IAQ) performance standards for public spaces that address concentration levels of IA pollutants. Few building codes address operation, maintenance, and retrofitting, and most do not focus on airborne disease transmission. But the COVID-19 pandemic has made all levels of society, from community members to decision-makers, realize the importance of IAQ for human health, wellbeing, productivity, and learning. We propose that IAQ standards be mandatory for public spaces. Although enforcement of IAQ performance standards in homes is not possible, homes must be designed and equipped so that they could meet the standards.For the past two decades, scientists have called for national IAQ standards and laws to be established (2), but so far, little action has been taken. The approach to IA contrasts sharply with outdoor air, for which quality is regulated and monitored and compliance with regulations is enforced. The World Health Organization (WHO) Global Air Quality Guidelines (AQG) published in 2021 provide recommendations for concentration levels of six pollutants and their averaging times (PM2.5, PM10, NO2, SO2, CO, and O3) and apply to both outdoor air and IA (3).In cases for which IAQ standard and guideline values were established by national or association working groups, the outcomes were inconsistent; often the criteria for the same parameter differed by orders of magnitude. The reasons cited for limited progress include different criteria in the selection of the critical study, in the starting point, and in the derivation procedure; the complex political, social, and legislative situation regarding IAQ; the lack of an open, systematic, and harmonized approach; and that establishing an IAQ standard is always the result of a compromise between scientific knowledge and political will. Because of the heterogenous landscape of approaches needed, such barriers remain intact despite the considerable IAQ research and evidence base developed over the past decades.
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| 6. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 7. |
- Sadeghian, Parastoo
(författare)
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A new generation of hospital operating room ventilation
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surgical site infection is responsible for 38 percent of reported infections after surgery. This infection increases mortality and treatment costs, and prolongs the hospitalization of patients. Bacteria-carrying particles are the main cause of surgical site infection and one of the main sources of these particles is skin fragments released from the surgical personnel during an ongoing surgery. Ventilation systems reduce the concentration of bacteria-carrying particles by supplying clean air in the operating room. The performance of operating room ventilation systems is affected by internal disruptions such as medical equipment, surgical lamps, number of staff and their behaviour during the surgery.Using computational fluid dynamics, this thesis investigates the airflow behaviour and distribution of the contamination in the operating room under the presence of various internal disruptions. In this regard, three common ventilation systems are considered: laminar airflow, turbulent mixing and temperature-controlled airflow ventilations. This study tries to overcome the weaknesses of the ventilation systems by providing sustainable solutions and continuously being in contact with design companies.It is common to use warming blankets to prevent reduction in the core body temperature of the patient during major surgeries. However, there is a major concern that these blankets disrupt the supplied airflow, which results in rising contaminant concentration. Most of the studies about warming blankets are clinical works and it is still not clear whether or not these blankets should be used. The results of the present study show that using warming blankets had no impact on increase of contamination level at the surgical zone. However, one common type of warming blanket – a forced-air warming blanket – can considerably increase the concentration of bacteria-carrying particles at the wound area if it becomes contaminated.The simulated results of the airflow field and particle tracking showed that the laminar airflow ventilation system was disturbed more easily by the local heat loads than overall heat loads in the operating room.Surgical lamps are considered as an obstacle in the supplied airflow path. These lamps create a stagnant area above the operating table and increase the contamination level. In this regard, a novel design of surgical lamp, a fan-mounted surgical lamp, was introduced to operating rooms.This device was used in the operating rooms equipped with laminar airflow and mixing ventilation system. The simulated results revealed that this lamp significantly reduced the contamination level at the operating table.Visualization techniques were adopted to teach and improve the understanding of surgical personnel about transmission of contaminated particles in operating rooms. Here, a virtual and augmented reality interface was used to visualize the impact of differences in ventilation principle, surgical staff constellation and work practice.
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| 8. |
- Sadeghian, Parastoo
(författare)
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Computational fluid dynamics application in indoor air quality and health
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Indoor air quality directly affects the comfort, performance, and well-being of occupants. Indoor pollution can cause immediate or long-term health effects and has been responsible for 4.1% of global deaths in recent decades. In operating rooms, providing a high indoor air quality is especially critical as surgical site infection can occur in patients due to air contamination in operating rooms.Surgical site infections due to antibiotic resistant bacteria may threaten the safety and lives of millions of people each year. To moderate and reduce indoor contamination, it is necessary to select a proper ventilation strategy.Improving ventilation system performance requires a deep understanding of airflow patterns and contamination distribution.This thesis adopted computational fluid dynamics to evaluate airflow patterns and the spread of airborne contaminations in indoor environments. Moreover, we sought to provide an approach to facilitate transferring the obtained knowledge to medical experts and decisionmakers to reduce the infection risk after the surgery.The use of warming blankets has raised the concern about surgical site infections. Warming blankets are used to prevent hypothermia in patients during surgery. However, our results showed that these warming blankets reduce the bacteria-carrying particles level at the wound due to warm upward airflows.Surgical lamps can block the airflow and generate a low-velocity area under the lamp that increases the accumulation of contaminants. The simulation results revealed that a novel fan-mounted surgical lamp reduced the contamination level to an acceptable range for infection-prone surgeries. This novel surgical lamp successfully reduced contamination in the operating room supplied with both turbulent mixing and laminar airflow ventilations.In another study, we implemented a protective curtain and showed that this strategy could significantly reduce the exposure level of the medical team to a patient with infectious respiratory disease. This novel protective curtain is located between the patient’s upper body and the lower part during surgery. We found a 57% reduction in bacteria-carrying particle concentration at the wound by adopting this curtain. Thus, using this protective curtain can reduce the exposure level of both patient and surgical team in the operating room.Besides investigating the performance of ventilation systems in hospitals, we investigated the application of diffuse ceilings ventilations in clinics, especially waiting rooms. Diffuse ceiling ventilation systems are common air distribution systems in offices and schools. Based on simulation results, a diffuse ceiling with a central opening and evenly distributed heat loads resulted in the highest cooling capacity and thermal comfort in clinic waiting rooms.We have visualised the airflow field and airborne particles in operating rooms with the help of virtual reality techniques. We found the virtual reality environment more engaging to understand the airflow field and particle movements in operating rooms.
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