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A retrospective cohort study to compare post-injury admissions for infectious diseases in burn patients, non-burn trauma patients and uninjured people

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Burns & Trauma 2018年第2期6卷 129-139页

作者： Janine m.Duke sean m.randall James H.Boyd mark W.Fear Suzanne Rea Fiona m.Wood Burn Injury Research Unit Faculty Health and Medical SciencesThe University of Western AustraliaPerthWAAustralia Centre for Data Linkage Curtin UniversityPerthWAAustralia Burns Service of Western Australia Fiona Stanley Hospital and Princess Margaret HospitalPerthWAAustralia.

Background: Injury triggers a range of systemic effects including inflammation and immune responses. This study aimed to compare infectious disease admissions after burn and other types of injury using linked hospital admissions data. methods: A retrospective longitudinal study using linked health data of all patients admitted with burns in Western Australia (n = 30,997), 1980–2012, and age and gender frequency matched cohorts of people with non-burn trauma (n = 28,647) and no injury admissions (n = 123,399). Analyses included direct standardisation, negative binomial regression and Cox proportional hazards regression. Results: Annual age-standardised infectious disease admission rates were highest for the burn cohort, followed by the non-burn trauma and uninjured cohorts. Age-standardised admission rates by decade showed different patterns across major categories of infectious diseases, with the lower respiratory and skin and soft tissue infections the most common for those with burns and other open trauma. Compared with the uninjured, those with burns had twice the admission rate for infectious disease after discharge (incident rate ratio (IRR), 95% confidence interval (CI): 2.04, 1.98–2.11) while non-burn trauma experienced 1.74 times higher rates (95%CI: 1.68–1.81). The burn cohort experienced 10% higher rates of first-time admissions after discharge when compared with the non-burn trauma (hazard ratio (HR), 95%CI: 1.10, 1.05–1.15). Compared with the uninjured cohort, incident admissions were highest during the first 30 days after discharge for burns (HR, 95%CI: 5.18, 4.15–6.48) and non-burn trauma (HR, 95%CI: 5.06, 4.03–6.34). While incident rates remained high over the study period, the magnitude decreased with increasing time from discharge: burn vs uninjured: HR, 95%CI: 30 days to 1 year: 1.69, 1.53–1.87;1 to 10 years: 1.40, 1.33–1.47;10 years to end of study period: 1.16, 1.08–1.24;non-burn trauma vs uninjured: HR, 95%CI: 30 days to 1 year: 1.71, 1.55–1.90;

关键词： Burn Non-burn trauma No injury Infectious diseases Cohort Population-based

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Long-term mental health outcomes after unintentional burns sustained during childhood:a retrospective cohort study

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Burns & Trauma 2018年第4期6卷 269-278页

作者： Janine m.Duke sean m.randall Thirthar P.Vetrichevvel Sarah mcGarry James H.Boyd Suzanne Rea Fiona m.Wood Burn Injury Research Unit Faculty Health and Medical SciencesThe University of Western AustraliaM31835 Stirling HighwayCrawleyPerthWestern Australia 6009Australia Centre for Data Linkage Curtin UniversityPerthWestern AustraliaAustralia Curtin medical School Curtin UniversityPerthWestern AustraliaAustralia School of Occupational Therapy Social work and Speech Pathology Curtin UniversityPerthWestern AustraliaAustralia Burns Service of Western Australia Royal Perth Hospital and Princess Margaret HospitalPerthWestern AustraliaAustralia

Background:Burns are a devastating injury that can cause physical and psychological issues. Limited data exist on long-term mental health (mH) after unintentional burns sustained during childhood. This study assessed long-term mH admissions after paediatric burns. methods:This retrospective cohort study included all children (matched uninjured comparison cohort (n=46,548). Linked hospital, mH and death data were examined. multivariable negative binomial regression modelling was used to generate incidence rate ratios (IRR) and 95%confidence intervals (CI). Results:The burn cohort had a significantly higher adjusted rate of post-burn mH admissions compared to the uninjured cohort (IRR, 95%CI:2.55, 2.07–3.15). Post-burn mH admission rates were twice as high for those younger than 5 years at index burn (IRR, 95%CI 2.06, 1.54–2.74), three times higher for those 5–9 years and 15–18 years (IRR, 95%CI:3.21, 1.92–5.37 and 3.37, 2.13–5.33, respectively) and almost five times higher for those aged 10–14 (IRR, 95%CI:4.90, 3.10–7.76), when compared with respective ages of uninjured children. The burn cohort had higher admission rates for mood and anxiety disorders (IRR, 95%CI:2.79, 2.20–3.53), psychotic disorders (IRR, 95%CI:2.82, 1.97–4.03) and mental and behavioural conditions relating to drug and alcohol abuse (IRR, 95%CI:4.25, 3.39–5.32). Conclusions:Ongoing mH support is indicated for paediatric burn patients for a prolonged period after discharge to potentially prevent psychiatric morbidity and associated academic, social and psychological issues.

关键词： Paediatric burns Depression Anxiety Substance abuse Longitudinal study mental health

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A population-based comparison study of the mental health of patients with intentional and unintentional burns

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Burns & Trauma 2018年第4期6卷 287-296页

作者： Thirthar P Vetrichevvel sean m.randall Fiona m Wood Suzanne Rea James H Boyd Janine m Duke Burn Injury Research Unit Faculty of Health and Medical SciencesThe University of Western AustraliaM318 35 Stirling HighwayCrawleyPerthWestern Australia 6009Australia Curtin medical School Curtin UniversityPerthAustralia Centre for Data Linkage Curtin UniversityPerthWestern AustraliaAustralia Burns Service of Western Australia Fiona Stanley Hospital and Princess Margaret HospitalPerthWestern AustraliaAustralia

Background:A number of studies report high prevalence of mental health conditions among burn patients. However there is a need to understand differences in the temporal relationship between mental health conditions and intentional and unintentional burns to hasten psychological prevention and intervention. This study aims to compare the socio-demographic profile, burn characteristics and pre-and post-burn psychiatric morbidity of burn patients by intent-of-injury. methods:De-identified linked hospital, death and mental health (mH) case registry data of burn patients hospitalised in Western Australia between 1 January 1980 and 30 June 2012 were analysed. Crude (observed) post-burn rates of mental health admissions were generated by burn intent-of-injury. Descriptive statistics were performed to compare the characteristics of the burn patients. Results:A total of 30,997 individuals were hospitalised for a first burn;360 (1.2%) had self-harm burns and 206 (0.7%) assault burns. Over the study period, admission rates for assault burns increased by 4.8%per year (95%confidence interval (CI) 3.1–6.5%) and self-harm burns increased 6.9%per year (95%CI 4.8–9.1%). Self-harm and assault burns occurred mainly among those aged 15 to 44 years (median age, interquartile range (IQR):self-harm 30 years, 22–40;assault 31 years, 23–38). Those with self-harm burns had a longer index hospital stay (median (IQR):self-harm 15 days (5–35) vs 4 days (1–11) assault vs 4 days (1–10) unintentional) and higher in-hospital mortality (7.2%self-harm vs 1.9%assault burns vs 0.8%unintentional). more than half (55.0%) of self-harm burns had a prior hospitalisation (5-year lookback) for a mH condition vs 10.7%of assault burns and 2.8%of unintentional burns. Crude post-burn rates of mH admissions per 100 person-years (PY) by intent-of-burn subgroups:self-harm 209 per 100 PY, assault burns 11 per 100 PY and unintentional burns 3 per 100 PY. Conclusions:Intentional burn patients experienced significantly

关键词： Intentional burns mental health Self-harm burns Assault burns Epidemiology

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management of stage Ⅳ rectal cancer: Palliative options

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World Journal of Gastroenterology 2011年第7期17卷 835-847页

作者： sean m Ronnekleiv-Kelly Gregory D Kennedy Department of Surgery Section of Colon and Rectal Surgery University of Wisconsin School of Medicine and Public Health 600 HighlandAvenue G4/701A CSC Madison WI 53792 United States

Approximately 30% of patients with rectal cancer present with metastatic disease. many of these patients have symptoms of bleeding or obstruction. Several treatment options are available to deal with the various complications that may afflict these patients. Endorectal stenting, laser ablation, and operative resection are a few of the options available to the patient with a malignant large bowel obstruction. A thorough understanding of treatment options will ensure the patient is offered the most effective therapy with the least amount of associated morbidity. In this review, we describe various options for palliation of symptoms in patients with metastatic rectal cancer. Additionally, we briefly discuss treatment for asymptomatic patients with metastatic disease.

关键词： Palliative therapy Rectal cancer malignant bleeding malignant obstruction Endorectal stenting Laser ablation

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Designing chimeric enzymes inspired by fungal cellulosomes

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Synthetic and Systems Biotechnology 2020年第1期5卷 23-32页

作者： sean P.Gilmore Stephen P.Lillington Charles H.Haitjema randall de Groot michelle A.O'malley Department of Chemical Engineering University of CaliforniaSanta BarbaraSanta BarbaraCA93106United States mC 5080 University of CaliforniaSanta BarbaraCA93106-5080United States

Cellulosomes are synthesized by anaerobic bacteria and fungi to degrade lignocellulose via synergistic action of multiple enzymes fused to a protein *** templating key protein domains(cohesin and dockerin),designer cellulosomes have been engineered from bacterial motifs to alter the activity,stability,and degradation efficiency of enzyme *** a parts list for fungal cellulosomes from the anaerobic fungi(Neocallimastigomycota)was determined,which revealed sequence divergent fungal cohesin,dockerin,and scaffoldin domains that could be used to expand the available toolbox to synthesize designer *** this work,multi-domain carbohydrate active enzymes(CAZymes)from 3 cellulosome-producing fungi were analyzed to inform the design of chimeric proteins for synthetic cellulosomes inspired by anaerobic *** particular,Piromyces finnis was used as a structural template for chimeric carbohydrate active *** enzymes with retained properties were engineered by combining thermophilic glycosyl hydrolase domains from Thermotoga maritima with dockerin domains from Piromyces *** preserving the protein domain order from ***,chimeric enzymes retained catalytic activity at temperatures over 80°C and were able to associate with cellulosomes purified from anaerobic *** cellulosomes harbor a wide diversity of glycoside hydrolases,each representing templates for the design of chimeric *** conserving dockerin domain position within the primary structure of each protein,the activity of both the catalytic domain and dockerin domain was retained in enzyme *** further,the domain positioning inferred from native fungal cellulosome proteins can be used to engineer multi-domain proteins with non-native favorable properties,such as thermostability.

关键词： Cellulosome Dockerin Scaffoldin Anaerobic fungi Thermophile Enzyme

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Network analyses:Inhibition of androgen receptor signaling reduces inflammation in the lung through AR-mAF-IL6 signaling axes

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Genes & Diseases 2024年第3期11卷 140-143页

作者： Albert R.Wang Andrew m.Baschnagel Zijian Ni sean R.Brennan Hypatia K.Newton Darya Buehler Christina Kendziorski randall J.Kimple Gopal lyer Department of Human Oncology University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA Department of Biomedical Engineering University of Wisconsin-MadisonMadisonWI 53705USA University of Wisconsin Carbone Cancer Center MadisonWI 53705USA Department of Biostatistics and medical Informatics University of Wisconsin-MadisonMadisonWI 53706USA Department of Biology Tufts UniversityMedfordMA 02155USA Department of Pathology and Laboratory medicine University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA

Androgen receptor(AR)is a major transcription factor that plays a role in inflammatory response including interleukin-6(IL6)signaling.1 While AR regulation through paracrine loop signaling in prostate tissue is well-studied,its impact through an IL6 autocrine loop in the lung has not been wellstudied despite the organ's response to respiratory viral *** inhibition and RNA knockdown of AR identified a bZIP transcription factor mAF to be a common target of inflammation using these perturbations in lung cells.

关键词： inflammation lung respiratory

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The consequences of genomic architecture on ecological speciation in postglacial fishes

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Current Zoology 2013年第1期59卷 53-71页

作者： sean m. ROGERS Jonathan A. mEE Ella BOWLES Department of Biological Sciences University of Calgary 2500 University Drive NW Calgary Alberta T2N 1N4 Canada

The quest for the origin of species has entered the genomics era. Despite decades of evidence confirming the role of the environment in ecological speciation, an understanding of the genomics of ecological speciation is still in its infancy. In this review, we explore the role of genomic architecture in ecological speciation in postglacial fishes. Growing evidence for the num- ber, location, effect size, and interactions among the genes underlying population persistence, adaptive trait divergence, and re- productive isolation in these fishes reinforces the importance of considering genomic architecture in studies of ecological speci- ation. Additionally, these populations likely adapt to new freshwater environments by selection on standing genetic variation, as de novo mutations are unlikely under such recent divergence times. We hypothesize that modular genomic architectures in post- glacial fish taxa may be associated with the probability of population persistence. Empirical studies have confirmed the genic na- ture of ecological speciation, implicating surprisingly extensive linkage disequilibrium across the genome. An understanding of these genomic mosaics and how they contribute to reproductive barriers remains unclear, but migration rates and the strength of selection at these loci is predicted to influence the likelihood of population divergence. Altogether, understanding the role of ge- nomic architecture is an important component of speciation research and postglacial fishes continue to provide excellent organ- isms to test these questions, both from the perspective of variation in architectures among taxa, and with respect to the distinct environments they have colonized. However, more empirical tests of ecological speciation predictions are needed [Current Zoo- logy 59 （1）： 53-71, 2013].

关键词： Adaptation Ecological speciation Genomic architecture modularity Postglacial fishes QTL

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Overcoming maladaptive plasticity through plastic compensation

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Current Zoology 2013年第4期59卷 526-536页

作者： matthew R.J. mORRIS sean m. ROGERS Department of Biological Sciences University of Calgary Calgary AB Canada T2N 1N4

most species evolve within fluctuating environments, and have developed adaptations to meet the challenges posed by environmental heterogeneity. One such adaptation is phenotypic plasticity, or the ability of a single genotype to produce multiple environmentally-induced phenotypes. Yet, not all plasticity is adaptive. Despite the renewed interest in adaptive phenotypic plas- ticity and its consequences for evolution, much less is known about maladaptive plasticity. However, maladaptive plasticity is likely an important driver of phenotypic similarity among populations living in different environments. This paper traces four strategies for overcoming maladaptive plasticity that result in phenotypic similarity, two of which involve genetic changes （standing genetic variation, genetic compensation） and two of which do not （standing epigenetic variation, plastic compensation）. Plastic compensation is defined as adaptive plasticity overcoming maladaptive plasticity. In particular, plastic compensation may increase the likelihood of genetic compensation by facilitating population persistence. We provide key terms to disentangle these aspects of phenotypic plasticity and introduce examples to reinforce the potential importance of plastic compensation for under- standing evolutionary change

关键词： Homeostasis Canalization Ecological speciation Standing genetic variation Genetic compensation Countergradi-ent variation

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Can we protect the brain via preconditioning?Role of microRNAs in neuroprotection

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Neural Regeneration Research 2016年第3期11卷 388-389页

作者： sean Quinlan Eva m.Jimenez-mateos Department of Physiology and medical Physics Royal College of Surgeons in Ireland

Preconditioning stimulus：Preconditioning is an adaptive response,whereby a small dose of a harmful substance protects the brain from a subsequent damaging insult（Dirnagl et al.,2009）.The concept of preconditioning was first described in an ischemic heart model,it was observed that brief ischemic episodes protect against a subsequent ischemic insult（murry et al., 1986）.

关键词： subsequent protect harmful brief targeting synaptic stimulus epileptic targeted RNA

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Can glucagon-like peptide-1(GLP-1) analogues make neuroprotection a reality?

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Neural Regeneration Research 2020年第10期15卷 1852-1853页

作者： maryna V.Basalay sean m.Davidson Derek m.Yellon The Hatter Cardiovascular Institute University College London

Currently,ischemic stroke remains one of the most costly and devastating clinical syndromes,accounting for 9%of all deaths and being the second leading cause of death in the world(Davidson et al.,2018).Approximately 20%of strokes are caused by intracerebral hemorrhage,while the other^80%are classified as *** the discovery of thrombolysis,reperfusion therapy became an option for the treatment of ischemic *** recently,endovascular recanalization with mechanical thrombectomy has brought about a paradigm shift in the optimal management of patients with large vessel ***,early reperfusion is the only therapy that is proven to limit infarct size in patients with acute ischemic ***,despite a successful recanalization being achieved in more than 70% of patients treated with mechanical thrombectomy+/–intravenous tissue recombinant plasminogen activator,functional independence(modified Rankin score 0–2 at 3 months after ischemic stroke)is obtained only in^45% of *** reveals the further need to develop new adjunctive neuroprotective treatment strategies alongside reperfusion therapy.

关键词： protective treatment independence

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