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The unexpected discovery of felsic magma by the Iceland Deep Drilling Project-1 (IDDP-1) in the Krafla volcanic system (KVS) presents a unique opportunity to investigate pre-eruptive lithium (Li) dynamics and establish a more direct connection between magma reservoirs and volcanic deposits. Our study provides new insights into Li abundances and isotope compositions in bulk-rock, minerals, and groundmass glass from rhyolitic lavas at KVS, encompassing various stages of groundmass crystallisation. Additionally, we examined felsic cuttings retrieved from the IDDP-1 well, comprising crystal-poor obsidian and crystal-bearing to -rich 'felsite' particles. Groundmass glasses from surface lavas show limited variability in K/Na, indicating limited secondary hydration of the glasses and that their Li contents seem to not be affected by this post-eruptive process. Lithium inventories in groundmass glasses and minerals within lavas exhibit variations consistent with the cooling history of the deposit, resembling patterns seen in Snake River Plain ignimbrites. Lithium contents of glassy rhyolitic lavas, whether bulk-rock (avg. 27.2 ± 3.1 µg/g) or groundmass glass (average 28.4 ± 4.7 µg/g), and their bulk isotopic compositions (avg. δ7Li =+ 4.4 ± 0.2) overlap with those observed in IDDP-1 obsidian cuts (avg. 24.9 µg/g Li in bulk, 28.6 ± 1.5 µg/g in groundmass glass, and δ7Li = 4.5 ± 0.2). Glassy lavas lacking spherulites may potentially preserve pristine magmatic Li element and isotope compositions, while areas with extensive groundmass crystallisation reveal Li enrichments in phenocrysts. Plagioclases in slowly cooled parts of the deposit record a two-fold increase in Li contents compared to plagioclase found in glassy counterparts, along with evidence of open-system degassing marked by heavier bulk Li isotope compositions and lower bulk Li contents of the crystallised lava portions (avg. δ7Li = +7.2 ± 0.1 and 7 ± 0.8 µg/g Li) relative to bulk glassy lithologies (avg. δ7Li = +4.1 ± 0.1 and 28 ± 2 µg/g Li). Partition coefficients derived from IDDP-1 cuts successfully predict Li inventories in vitrophyres of rhyolites on the surface of the KVS. Lithium isotope compositions of the crystal-rich IDDP-1 cuts are significantly heavier (avg. δ7Li = +7.2 ± 0.2) than lavas and IDDP-1 obsidian cuts, casting doubt on the notion that the IDDP-1 rhyolitic magma could result from the melting of felsite lenses in the KVS. Lithium contents in groundmass glasses within IDDP-1 crystal-rich cuts show higher Li contents (avg. 55.1-60.7 µg/g), correlating with the higher crystal content and an increase in other incompatible elements (avg. 250 µg/g Rb) relative to obsidian cuttings (avg. 75 µg/g Rb). Supplementary Information: The online version contains supplementary material available at 10.1007/s00410-024-02119-y.
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Of the estimated 35.3 million refugees around the world (UNHCR, Figures at a Glance, 2022), approximately 50% are children under the age of 18. Refugee adolescents represent a unique group as they navigate developmental tasks in an unstable and often threatening environment or in resettlement contexts in which they often face marginalization. In addition to physiological, social, and psychological changes that mark adolescence, refugee youth often face traumatic experiences, acculturative stress, discrimination, and a lack of basic resources. In this consensus statement, we examine research on refugee adolescents' developmental tasks, acculturative tasks, and psychological adjustment using Suárez-Orozco and colleague's integrative risk and resilience model for immigrant-origin children and youth proposed by Suárez-Orozco et al. Finally, we discuss recommendations-moving from proximal to more distal contexts.
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Emigrantes e Imigrantes , Refugiados , Criança , Humanos , Adolescente , Refugiados/psicologia , Ajustamento Emocional , Aculturação , Desenvolvimento do AdolescenteRESUMO
Brownfield redevelopment is a complex process often involving a wide range of stakeholders holding differing priorities and opinions. The use of digital systems and products for decision making, modelling, and supporting discussion has been recognised throughout literature and industry. The inclusion of stakeholder preferences is an important consideration in the design and development of impactful digital tools and decision support systems. In this study, we present findings from stakeholder consultation with professionals from the UK brownfield sector with the aim of informing the design of future digital tools and systems. Our research investigates two broad themes; digitalisation and the use of digital tools across the sector; and perceptions of key brownfield challenge areas where digital tools could help better inform decision-makers. The methodology employed for this study comprises the collection of data and information using a combination of interviews and an online questionnaire. The results from these methods were evaluated both qualitatively and quantitatively. Findings reveal a disparity in levels of digital capability between stakeholder groups including between technical stakeholder types, and that cross-discipline communication of important issues may be aided by the development of carefully designed digital tools. To this end, we present seven core principles to guide the design and implementation of future digital tools for the brownfield sector. These principles are that future digital tools should be: (1) Stakeholder driven, (2) Problem centred, (3) Visual, (4) Intuitive, (5) Interactive, (6) Interoperable, and (7) Geospatial data driven.
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Comunicação , IndústriasRESUMO
This research evaluates a novel decision support system (DSS) for planning brownfield redevelopment. The DSS is implemented within a web-based geographical information system that contains the spatial data informing three modules comprising land use suitability, economic viability, and ground risk. Using multi-criteria decision analysis, an evaluation was conducted on 31,942 ha of post-industrial land and around Liverpool, UK. The representativeness and credibility of the DSS outputs were evaluated through user trials with fifteen land-use planning and development stakeholders from the Liverpool City Region Comined Authority. The DSS was used to explore land use planning scenarios and it could be used to support decision making. Our research reveals that the DSS has the potential to positively inform the identification of brownfield redevelopment opportunities by offering a reliable, carefully curated, and user-driven digital evidence base. This expedites the traditionally manual process of conducting assessments of land suitability and viability. This research has important implications for assessing the impact of current and future planning policy and the potential for the use of digital tools for land use planning and sustainability in the UK and globally.
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Sistemas de Informação Geográfica , Indústrias , Poder PsicológicoRESUMO
PURPOSE: Immigrant mental health is closely linked to the context of reception in the receiving society, including discrimination; past research has examined this relationship only cross-sectionally. This longitudinal study examines the relationships between discrimination and mental health among Somali immigrants living in North America from 2013 to 2019. METHODS: Data for 395 participants (mean age 21 years at Time 1) were collected through the four-wave Somali Youth Longitudinal Study in four cities: Boston, MA, Minneapolis, MN, Lewiston/Portland, ME, and Toronto, ON. Latent linear and quadratic growth models were used to predict mental health symptoms over time and discrimination's role in these changes. RESULTS: PTSD and anxiety symptoms decreased from 2013 to 2015 and subsequently increased. Depression was static from 2013 to 2015, worsening thereafter. Increases in discrimination predicted increases in mental health symptomatology at all timepoints. CONCLUSION: This study provides support for discrimination's toxic impact on mental health and suggests that recent increases in discrimination may have contributed to worsening mental health among Somali immigrants living in North America.
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Emigrantes e Imigrantes , Saúde Mental , Adolescente , Adulto , Depressão , Humanos , Estudos Longitudinais , América do Norte , Somália , Adulto JovemRESUMO
Refugees are disproportionally impacted by trauma and its negative sequelae. Even after being resettled in the United States, refugees face disparities in accessing services due to the stigma attached to mental health symptoms and the paucity of culturally and linguistically accessible services. Thus, there is a great need to develop methods that facilitate the engagement of refugee communities. Community-Based Participatory Research recommends the forming of equal and equitable partnerships with communities and stakeholders to enhance community capacity and ownership of the research process and outcomes (Israel et al., 1998). The present article shares one approach to operationalizing these principles with the Somali refugee community. It provides a road map of best practices in collaborating with communities and the importance of colearning and cultural humility to a successful partnership. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Transtornos Mentais , Refugiados , Pesquisa Participativa Baseada na Comunidade , Humanos , Saúde Mental , Refugiados/psicologia , Somália , Estados UnidosRESUMO
Objectives: Understanding how immigrant young adults engage with civic society over time is critical to understanding and fostering healthy development and healthy democracies. The present study examines how civic engagement and antisocial attitudes/behavior of Somali young adult immigrants (ages 18-30, N = 498) in four North American regions co-occur, and change over time. Method: Using latent transition analyses, we examine latent classes of young adult males and females in relation to political and nonpolitical civic engagement and dimensions of antisocial attitudes/behavior and stability of these classes over 1 year. Results: Distinct latent classes were identified that remained consistent over time. Rates and patterns in latent class transitions varied along civically engaged/antisocial dimensions and also by gender. Conclusions: Antisocial attitudes/behavior can coexist with civic engagement. For males, sense of belonging to both Somali and American/Canadian communities was associated with lower levels of antisocial attitudes/behavior. Movement away from, or into, antisocial attitudes/behavior differs by gender and can happen either in the presence or absence of civic engagement. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Emigrantes e Imigrantes , Política , Adolescente , Adulto , Atitude , Canadá , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: It has been proposed that the frequent ingestion of baked hen's egg or cow's milk accelerates the resolution of hen's egg or cow's milk allergy. This practice is being introduced into clinical practice. OBJECTIVE: To systematically review the evidence to determine whether the introduction of baked hen's egg or cow's milk into the diet of children with hen's egg or cow's milk allergies respectively leads to a larger proportion of children outgrowing these allergies than expected. METHODS: A systematic review of the literature was conducted in Medline, Embase and CINAHL. The inclusion criteria were as follows: randomized control trials, case-control or cohort studies; children aged 0-18 years with hen's egg or cow's milk allergy; baked hen's egg or cow's milk intervention with or without a comparator; and resolution of the hen's egg or cow's milk allergy as determined by food challenge as the outcome. Studies were critically appraised using the quality assessment tool for quantitative studies. PROSPERO reference CRD42015026029. RESULTS: We identified 851 and 2816 hen's egg and cow's milk articles respectively. Only three hen's egg and three cow's milk studies fulfilled our pre-specified inclusion criteria. The studies concluded that baked products either increased the likelihood of the resolution of allergy or accelerated resolution. However, when critiqued, all studies were classified as weak because they were observational, lacking an appropriate control group; this brings into doubt the study's conclusions. There were a number of examples of severe reactions to baked products. CONCLUSION: There is little evidence to address the hypothesis that the ingestion of baked hen's egg or cow's milk results in more patients outgrowing their hen's egg or cow's milk allergy respectively. Data are required from a trial comparing the resolution rates of baked-tolerant participants who are randomized to ingest or avoid baked products to assess the accuracy of this hypothesis.
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Culinária , Dieta , Hipersensibilidade a Ovo , Hipersensibilidade a Leite , HumanosRESUMO
BACKGROUND: The aim of this study was to identify characteristics with independent predictive value for bowel cancer for use in the clinical assessment of patients attending colorectal outpatient clinics. METHODS: This was a 22-year (1986-2007) retrospective cohort analysis of data collected prospectively from patients who attended colorectal surgical outpatient clinics in Portsmouth. The data set was split randomly into two groups of patients to generate and validate a predictive model. Multivariable logistic regression was used to create and validate a system to predict outcome. Receiver operating characteristic (ROC) curves and Hosmer-Lemeshow test were used to evaluate the model's predictive capability. The likelihood of bowel cancer was expressed as the odds ratio (OR). RESULTS: Data from 29 005 patients were analysed. Discrimination of the model for bowel cancer was high in the development (C-statistic 0·87, 95 per cent c.i. 0·85 to 0·88) and validation (C-statistic 0·86, 0·84 to 0·87) groups. The most important co-variables in the final model were: age (OR 3·17-27·10), rectal (OR 31·48) or abdominal (OR 1·83-8·45) mass, iron deficiency anaemia (IDA) (OR 4·42-8·38), rectal bleeding and change in bowel habit in combination (OR 5·37), change in bowel habit without rectal bleeding, with or without abdominal pain (OR 2·12-2·52), and rectal bleeding with no perianal symptoms and without change in bowel habit (OR 2·91). Some 91·5 per cent of bowel cancers presented with these characteristics, 40·4 per cent with a mass and/or IDA. In patients with at least one of these characteristics the overall risk of having cancer was 10·0 (range 6·5-50·4) per cent, compared with 1·1 (0·3-2·3) per cent in patients without them. CONCLUSION: A clinical assessment that systematically identifies or excludes four symptom-age combinations, a mass and IDA (SAMI) stratifies patients as having a low and higher risk of having bowel cancer. This could improve patient selection for referral and investigation.
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Neoplasias Colorretais/diagnóstico , Medição de Risco/métodos , Dor Abdominal/etiologia , Adulto , Fatores Etários , Anemia Ferropriva/etiologia , Defecação , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Reto , Estudos Retrospectivos , Fatores de Risco , Redução de PesoRESUMO
Most mental health services for trauma-exposed children and adolescents were not originally developed for refugees. Information is needed to help clinicians design services to address the consequences of trauma in refugee populations. We compared trauma exposure, psychological distress, and mental health service utilization among children and adolescents of refugee-origin, immigrant-origin, and U.S.-origin referred for assessment and treatment by U.S. providers in the National Child Traumatic Stress Network (NCTSN). We used propensity score matching to compare trauma profiles, mental health needs, and service use across three groups. Our sample comprised refugee-origin youth (n = 60, 48.3% female, mean age = 13.07 years) and propensity-matched samples of immigrant-origin youth (n = 143, 60.8% female, mean age = 13.26 years), and U.S.-origin youth (n = 140, 56.1% female, mean age = 12.11 years). On average, there were significantly more types of trauma exposure among refugee youth than either U.S.-origin youth (p < .001) or immigrant youth (p ≤ .001). Compared with U.S.-origin youth, refugee youth had higher rates of community violence exposure, dissociative symptoms, traumatic grief, somatization, and phobic disorder. In contrast, the refugee group had comparably lower rates of substance abuse and oppositional defiant disorder (ps ranging from .030 to < .001).This clinic-referred sample of refugee-origin youth presented with distinct patterns of trauma exposure, distress symptoms, and service needs that merit consideration in services planning.
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Emigrantes e Imigrantes/estatística & dados numéricos , Exposição à Violência/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Refugiados/estatística & dados numéricos , Adolescente , Criança , Emigrantes e Imigrantes/psicologia , Exposição à Violência/psicologia , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Refugiados/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
Mixed leukocyte (white blood cells [WBCs]) trafficking using positron emission tomography (PET) is receiving growing interest to diagnose and monitor inflammatory conditions. PET, a high sensitivity molecular imaging technique, allows precise quantification of the signal produced from radiolabelled moieties. We have evaluated a new method for radiolabelling WBCs with either zirconium-89 ((89) Zr) or copper-64 ((64) Cu) for PET imaging. Chitosan nanoparticles (CNs) were produced by a process of ionotropic gelation and used to deliver radiometals into WBCs. Experiments were carried out using mixed WBCs freshly isolated from whole human blood. WBCs radiolabelling efficiency was higher with [(89) Zr]-loaded CN (76.8 ± 9.6% (n = 12)) than with [(64) Cu]-loaded CN (26.3 ± 7.0 % (n = 7)). [(89) Zr]-WBCs showed an initial loss of 28.4 ± 5.8% (n = 2) of the radioactivity after 2 h. This loss was then followed by a plateau as (89) Zr remains stable in the cells. [(64) Cu]-WBCs showed a loss of 85 ± 6% (n = 3) of the radioactivity after 1 h, which increased to 96 ± 6% (n = 3) loss after 3 h. WBC labelling with [(89) Zr]-loaded CN showed a fast kinetic of leukocyte association, high labelling efficiency and a relatively good retention of the radioactivity. This method using (89) Zr has a potential application for PET imaging of inflammation.
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Marcação por Isótopo/métodos , Leucócitos/metabolismo , Tomografia por Emissão de Pósitrons , Radioisótopos , Zircônio , Quitosana/química , Radioisótopos de Cobre , Desferroxamina/química , Humanos , Inflamação/diagnóstico por imagem , Nanopartículas/químicaRESUMO
BACKGROUND: Acetabular dysplasia is a major predisposing factor for development of hip osteoarthritis (OA), and may result from alterations to chondrolabral loading. Subject-specific finite element (FE) modeling can be used to evaluate chondrolabral mechanics in the dysplastic hip, thereby providing insight into mechanics that precede OA. OBJECTIVE: To evaluate chondrolabral contact mechanics and congruency in dysplastic hips and normal hips using a validated approach to subject-specific FE modeling. METHODS: FE models of ten subjects with normal acetabula and ten subjects with dysplasia were constructed using a previously validated protocol. Labrum load support, and labrum and acetabular cartilage contact stress and contact area were compared between groups. Local congruency was determined at the articular surface for two simulated activities. RESULTS: The labrum in dysplastic hips supported 2.8-4.0 times more of the load transferred across the joint than in normal hips. Dysplastic hips did not have significantly different congruency in the primary load-bearing regions than normal hips, but were less congruent in some unloaded regions. Normal hips had larger cartilage contact stress than dysplastic hips in the few regions that had significant differences. CONCLUSIONS: The labrum in dysplastic hips has a far more significant role in hip mechanics than it does in normal hips. The dysplastic hip is neither less congruent than the normal hip, nor subjected to elevated cartilage contact stresses. This study supports the concept of an outside-in pathogenesis of OA in dysplastic hips and that the labrum in dysplastic hips should be preserved during surgery.
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Acetábulo/fisiopatologia , Cartilagem Articular/fisiopatologia , Luxação do Quadril/fisiopatologia , Acetábulo/diagnóstico por imagem , Acetábulo/patologia , Adulto , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Estudos de Casos e Controles , Feminino , Análise de Elementos Finitos , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/patologia , Humanos , Masculino , Modelos Biológicos , Estresse Mecânico , Tomografia Computadorizada por Raios X , Suporte de Carga/fisiologia , Adulto JovemRESUMO
Chronic widespread pain (CWP), including fibromyalgia, is a highly prevalent condition with a range of disabling symptoms, both physical and psychological. The British Pain Society (BPS) is supporting the treatment of this group of patients through a care pathway and this article describes the rationale and discussion points relevant to the CWP and fibromyalgia pathway. There are several aims in producing this pathway: to reduce variation in the standards of care, to reduce delays at all stages of care, and in particular, to enable clinicians to help patients accept a diagnosis of CWP. This diagnosis should be based on the presence and distribution of symptoms in the absence of another defined pathological process: the features in the history or clinical examination are generally more important than laboratory investigations. There is an emphasis on addressing all aspects of symptomatology (physical, psychological, social, and personal needs) without an overemphasis on any one treatment modality. The pathway has focused on the potential pitfalls in the use of long-term opioids and the rationale is provided why these are not recommended. Patients with CWP value explanation and education and although clinicians may be unfamiliar with the condition, the majority of clinicians have generic skills in managing long-term conditions which can be supplemented by the interventions and actions detailed in this pathway.
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Dor Crônica/terapia , Fibromialgia/terapia , Analgesia , Analgésicos Opioides/uso terapêutico , Terapia Cognitivo-Comportamental , Humanos , Atenção Primária à Saúde , Encaminhamento e Consulta , Fatores de RiscoRESUMO
Various techniques exist for quantifying articular contact stress distributions, an important class of measurements in the field of orthopaedic biomechanics. In situations where the need for dynamic recording has been paramount, the approach of preference has involved thin-sheet multiplexed grid-array transducers. To date, these sensors have been used to study contact stresses in the knee, shoulder, ankle, wrist, and spinal facet joints. Until now, however, no such sensor had been available for the human hip joint due to difficulties posed by the deep, bi-curvilinear geometry of the acetabulum. We report here the design and development of a novel sensor capable of measuring dynamic contact stress in human cadaveric hip joints (maximum contact stress of 20 MPa and maximum sampling rate 100 readings/s). Particular emphasis is placed on issues concerning calibration, and on the effect of joint curvature on the sensor's performance. The active pressure-sensing regions of the sensors have the shape of a segment of an annulus with a 150-deg circumferential span, and employ a polar/circumferential "ring-and-spoke" sensel grid layout. There are two sensor sizes, having outside radii of 44 and 48 mm, respectively. The new design was evaluated in human cadaver hip joints using two methods. The stress magnitudes and spatial distribution measured by the sensor were compared to contact stresses measured by pressure sensitive film during static loading conditions that simulated heel strike during walking and stair climbing. Additionally, the forces obtained by spatial integration of the sensor contact stresses were compared to the forces measured by load cells during the static simulations and for loading applied by a dynamic hip simulator. Stress magnitudes and spatial distribution patterns obtained from the sensor versus from pressure sensitive film exhibited good agreement. The joint forces obtained during both static and dynamic loading were within ±10% and ±26%, respectively, of the forces measured by the load cells. These results provide confidence in the measurements obtained by the sensor. The new sensor's real-time output and dynamic measurement capabilities hold significant advantages over static measurements from pressure sensitive film.
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Acetábulo/fisiologia , Fêmur/fisiologia , Articulação do Quadril/fisiologia , Manometria/instrumentação , Transdutores , Adulto , Cadáver , Desenho de Equipamento , Análise de Falha de Equipamento , Fricção , Humanos , Masculino , Amplitude de Movimento Articular/fisiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estresse Mecânico , Propriedades de SuperfícieRESUMO
Women and children returning from areas formerly controlled by the Islamic State typically have experienced high levels of trauma and indoctrination, further complicating politically fraught efforts at reintegration and resettlement. Consequently, countries around the world are grappling with how best to manage the return of these women and children. To help better understand which types of programming can contribute to the successful, non-violent reintegration of these individuals, we incorporated ideas from existing Repatriation and Rehabilitation (R&R) literature, field practitioners, R&R subject matter experts, and literature from adjacent fields (e.g., refugee resettlement, criminal justice, psychological resilience) into a recommended best practice approach to supporting returning women and children. We propose a shift from "R&R" programming to what we call the "5R" framework: Repatriation/ Resettlement, Reintegration, Rehabilitation, and Resilience. This shift provides conceptual clarity related to how different program elements target proximal goals (e.g., wellbeing and personal safety, belonging and opportunity, non-violence, and dignity), and how programming can shift from more centrally- and government-held services to informal and community-based supports.
RESUMO
This rapid review used a systematic approach to examine the available literature on rehabilitation and reintegration (R&R) programs for women and children returning from contexts of violent extremism, examining common assumptions, inputs, activities and outcomes across diverse settings. Fifty-one documents including peer reviewed articles and grey literature were included in the analysis. The most common program activities identified included mental health services, community level social programs, promoting school and vocational enrollment, regular health services, and parenting training & education, though there was a lack of consensus around core program components. The analysis points to the need for a robust set of inputs and resources to implement R&R programs including government officials, child welfare, mental health professionals, teachers, law enforcement, healthcare, community leaders, and extended family. The review also uncovered a number of gaps. This includes the need to create clear and analytically distinct definitions of rehabilitation and reintegration that are applicable and relevant to key stakeholders, delineating age-appropriate activities and outcomes for young children, youth, and adults, defining frameworks for service delivery and coordination of stakeholders, and placing R&R programs within existing domains of public safety and restorative justice.
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An emerging strategy for the treatment of monogenic diseases uses genetic engineering to precisely correct the mutation(s) at the genome level. Recent advancements in this technology have demonstrated therapeutic levels of gene correction using a zinc-finger nuclease (ZFN)-induced DNA double-strand break in conjunction with an exogenous DNA donor substrate. This strategy requires efficient nucleic acid delivery and among viral vectors, recombinant adeno-associated virus (rAAV) has demonstrated clinical success without pathology. However, a major limitation of rAAV is the small DNA packaging capacity and to date, the use of rAAV for ZFN gene delivery has yet to be reported. Theoretically, an ideal situation is to deliver both ZFNs and the repair substrate in a single vector to avoid inefficient gene targeting and unwanted mutagenesis, both complications of a rAAV co-transduction strategy. Therefore, a rAAV format was generated in which a single polypeptide encodes the ZFN monomers connected by a ribosome skipping 2A peptide and furin cleavage sequence. On the basis of this arrangement, a DNA repair substrate of 750 nucleotides was also included in this vector. Efficient polypeptide processing to discrete ZFNs is demonstrated, as well as the ability of this single vector format to stimulate efficient gene targeting in a human cell line and mouse model derived fibroblasts. Additionally, we increased rAAV-mediated gene correction up to sixfold using a combination of Food and Drug Administration-approved drugs, which act at the level of AAV vector transduction. Collectively, these experiments demonstrate the ability to deliver ZFNs and a repair substrate by a single AAV vector and offer insights for the optimization of rAAV-mediated gene correction using drug therapy.
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Antineoplásicos/farmacologia , Dependovirus/genética , Endonucleases/genética , Vetores Genéticos , Transdução Genética , Dedos de Zinco , Células 3T3 , Animais , Reparo do DNA , Células HEK293 , Humanos , Camundongos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transformação Genética/efeitos dos fármacos , Estados Unidos , United States Food and Drug AdministrationRESUMO
BACKGROUND: A contributory factor to hip osteoarthritis (OA) is abnormal cartilage mechanics. Acetabular retroversion, a version deformity of the acetabulum, has been postulated to cause OA via decreased posterior contact area and increased posterior contact stress. Although cartilage mechanics cannot be measured directly in vivo to evaluate the causes of OA, they can be predicted using finite element (FE) modeling. OBJECTIVE: The objective of this study was to compare cartilage contact mechanics between hips with normal and retroverted acetabula using subject-specific FE modeling. METHODS: Twenty subjects were recruited and imaged: 10 with normal acetabula and 10 with retroverted acetabula. FE models were constructed using a validated protocol. Walking, stair ascent, stair descent and rising from a chair were simulated. Acetabular cartilage contact stress and contact area were compared between groups. RESULTS: Retroverted acetabula had superomedial cartilage contact patterns, while normal acetabula had widely distributed cartilage contact patterns. In the posterolateral acetabulum, average contact stress and contact area during walking and stair descent were 2.6-7.6 times larger in normal than retroverted acetabula (P ≤ 0.017). Conversely, in the superomedial acetabulum, peak contact stress during walking was 1.2-1.6 times larger in retroverted than normal acetabula (P ≤ 0.044). Further differences varied by region and activity. CONCLUSIONS: This study demonstrated superomedial contact patterns in retroverted acetabula vs widely distributed contact patterns in normal acetabula. Smaller posterolateral contact stress in retroverted acetabula than in normal acetabula suggests that increased posterior contact stress alone may not be the link between retroversion and OA.
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Acetábulo/anormalidades , Cartilagem Articular/fisiopatologia , Articulação do Quadril/fisiopatologia , Osteoartrite do Quadril/etiologia , Acetábulo/patologia , Acetábulo/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Análise de Elementos Finitos , Articulação do Quadril/patologia , Humanos , Masculino , Modelos Anatômicos , Atividade Motora/fisiologia , Osteoartrite do Quadril/patologia , Osteoartrite do Quadril/fisiopatologia , Fatores de Risco , Estresse Mecânico , Caminhada/fisiologia , Adulto JovemRESUMO
Lacewing larvae are generalist predators that are commercially available for aphid control on a variety of crops in both Europe and North America. Although lacewings are known for their symbiotic association with yeasts and bacteria, there are few reports of microsporidia in these natural enemies. An undescribed microsporidium was found in Chrysoperla carnea (Stephens) during the routine examination of specimens that were obtained from a commercial insectary for biological pest control. The objective of this study was to describe the pathogen by means of ultrastructure, molecular characterization and tissue pathology. All stages of the microsporidium were diplokaryotic and developed in direct contact with the host cell cytoplasm. Merogony and sporogony were not observed. Mature spores measured 3.49±0.10×1.52±0.05µm and had an isofilar polar filament with 8-10 coils that were frequently arranged in a single row, although double rows were also observed. Spores contained a lamellar polaroplast and a relatively small and inconspicuous polar vacuole was observed in the posterior region of about half of the spores that were examined. Tubular structures, similar in appearance to those in Nosema granulosis were observed in both sporonts and in spores. A cluster of small tubules was also observed in the posterior region of some spores. Microsporidian spores were observed in cells of the proventriculus, diverticulum and in epithelial cells of the posterior midgut. The Malpighian tubules, ileum, and rectum were heavily infected. Spores were also observed in the fat body, peripheral region of the ganglia, within and between the flight muscles, and beneath the cuticle. Although the tissues adjacent to the ovaries were heavily infected, microsporidian spores were not observed within the developing eggs. Pathogen transmission was not studied directly because it was difficult to maintain microsporidia-infected C. carnea in the laboratory. The presence of microsporidian spores in the alimentary canal suggests that the pathogen is transmitted per os and horizontal transmission may occur when infected larvae or adults are cannibalized by uninfected larvae. Molecular analysis of the microsporidian genome showed that the pathogen described in this study was 99% similar to Nosema bombycis, N. furnacalis, N. granulosis and N. spodopterae. Based on information gained during this study, we propose that the microsporidium in C. carnea be given the name Nosema chrysoperlae sp. nov.
Assuntos
Insetos/microbiologia , Nosema/ultraestrutura , Controle Biológico de Vetores , Animais , DNA Fúngico/química , Genoma Fúngico , Insetos/crescimento & desenvolvimento , Larva/microbiologia , Nosema/genética , Nosema/isolamento & purificação , Análise de Sequência de DNA , Esporos Fúngicos/genéticaRESUMO
Acculturation styles have important associations with future adjustment among immigrants and refugees, yet less is known about the individual and interpersonal factors that influence the strategy an individual adopts. High rates of discrimination may signal the receiving community's rejection of one's ethnic group, increasing pressure to assimilate and suppress one's heritage identity. Within a sample of Somali young adults (18-30, N = 185) resettled in North America, this study tested whether two acculturation styles (assimilation and integration) longitudinally mediate the relation between discrimination and three mental health outcomes (i.e., anxiety, depression, and posttraumatic stress disorder), and whether gender moderated these relations. Discrimination had a direct, positive relation with future mental health symptoms for females, which was not mediated by acculturation strategy. By contrast, the association between discrimination and mental health outcomes for males was fully mediated by increased endorsement of assimilation, but not integration. Experiences of marginalization may erode connections to both the Somali community and to the nation of resettlement, which have been identified as particularly strong protective forces within this community. Interventions targeted at the receiving community to reduce the rates of discrimination toward immigrants and refugees and interventions to strengthen youth's sense of belonging in both the predominant culture and their culture of origin may improve transdiagnostic mental health outcomes.