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BACKGROUND: Alzheimer's disease (AD) prevention trials require a large outreach and screening funnel to identify cognitively unimpaired adults who meet the study's inclusion criteria, such as certain clinical or demographic criteria, genetic risk factors, and/or biomarker evidence of the disease. OBJECTIVES: Describe tactics and strategies to identify and enroll cognitively unimpaired adults with one (heterozygotes [HT]) or two (homozygotes [HM]) copies of the APOE ε4 allele, a genetic risk factor for dementia due to AD, into the Alzheimer's Prevention Initiative (API) Generation Program, the largest and only prevention trials for late onset AD using this enrichment technique. DESIGN AND SETTING: The Generation Program was comprised of two global, randomized, double-blind, placebo-controlled, parallel group adaptive design with variable treatment duration clinical trials. Generation Study 1 randomized participants into one of two cohorts: Cohort 1 which evaluated CAD106 vs. placebo or Cohort 2 which evaluated umibecestat vs placebo. Generation Study 2 randomized participants into two doses of umibecestat vs. placebo. The Generation Program was terminated early in 2019, while enrollment was still occurring. PARTICIPANTS: Both Generation Study 1 and Generation Study 2 enrolled cognitively unimpaired APOE ε4 HMs aged 60-75; Generation Study 2 also enrolled APOE ε4 HTs ages 60-75 with elevated brain amyloid. METHODS AND MEASUREMENTS: Describe results of the centralized and localized outreach, recruitment, screening strategies and tactics as well as characteristics of sites successful at enrolling genetically eligible participants, with a particular focus on APOE ε4 HMs given the 2-3% prevalence of this genotype. RESULTS: At the time the trial program was terminated, 35,333 individuals had consented to the optional prescreening ICF1a/ICFA and provided a sample of DNA for APOE genotyping, 1,138 APOE ε4 HMs consented to screening for Generation Study 1 (ICF1b), and 1,626 APOE ε4 carriers were randomized into either Generation Study 1 or Generation Study 2. Genetic testing registries, partnerships with genetic testing/counseling companies, and the optional prescreening ICF1a/ICFA were the most successful strategies for identifying genetically eligible participants for screening. CONCLUSIONS: It is feasible to recruit, screen and randomize cognitively unimpaired APOE ε4 carriers, particularly APOE ε4 HMs for a global AD prevention trial. The Generation Program was on track to complete enrollment by end of 2019. Factors that were key to this success included: working with sites to develop customizable outreach, recruitment, and screening programs specific to their site needs, providing forums for sites to exchange best practices, and developing partnerships between the sponsor team and trial sites.
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Enfermedad de Alzheimer , Adulto , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/prevención & control , Heterocigoto , Apolipoproteína E4/genética , Distribución Aleatoria , GenotipoRESUMEN
Participatory approaches to science and decision making, including stakeholder engagement, are increasingly common for managing complex socio-ecological challenges in working landscapes. However, critical questions about stakeholder engagement in this space remain. These include normative, political, and ethical questions concerning who participates, who benefits and loses, what good can be accomplished, and for what, whom, and by who. First, opportunities for addressing justice, equity, diversity, and inclusion interests through engagement, while implied in key conceptual frameworks, remain underexplored in scholarly work and collaborative practice alike. A second line of inquiry relates to research-practice gaps. While both the practice of doing engagement work and scholarly research on the efficacy of engagement is on the rise, there is little concerted interplay among 'on-the-ground' practitioners and scholarly researchers. This means scientific research often misses or ignores insight grounded in practical and experiential knowledge, while practitioners are disconnected from potentially useful scientific research on stakeholder engagement. A third set of questions concerns gaps in empirical understanding of the efficacy of engagement processes and includes inquiry into how different engagement contexts and process features affect a range of behavioral, cognitive, and decision-making outcomes. Because of these gaps, a cohesive and actionable research agenda for stakeholder engagement research and practice in working landscapes remains elusive. In this review article, we present a co-produced research agenda for stakeholder engagement in working landscapes. The co-production process involved professionally facilitated and iterative dialogue among a diverse and international group of over 160 scholars and practitioners through a yearlong virtual workshop series. The resulting research agenda is organized under six cross-cutting themes: (1) Justice, Equity, Diversity, and Inclusion; (2) Ethics; (3) Research and Practice; (4) Context; (5) Process; and (6) Outcomes and Measurement. This research agenda identifies critical research needs and opportunities relevant for researchers, practitioners, and policymakers alike. We argue that addressing these research opportunities is necessary to advance knowledge and practice of stakeholder engagement and to support more just and effective engagement processes in working landscapes. Supplementary Information: The online version contains supplementary material available at 10.1007/s42532-022-00132-8.
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Conservation practices (CPs) are integral to maintaining the long-term viability of agro-ecological systems. Because farming systems and farmers' values and attitudes are heterogeneous, factors that consistently predict conservation behaviors remain elusive. Moreover, heterogeneity is present among studies regarding the type of CPs examined, and whether behavioral intentions or actual behaviors were measured. This study considers the characteristics of each CP, and whether a given study measured behavioral intention or actual behavior, to better understand farmers' adoption of CPs. We reviewed and analyzed 35 years (1982-2017) of quantitative conservation adoption literature in the United States. We categorized CPs based on their primary purpose, the type of benefit they provide, and whether they are operational or structural. We also examined the following five CPs: conservation tillage, buffers or borders, soil testing, grassed waterways, and cover crops. In our behavioral intention and actual behavior analysis, we found that attitudinal factors predicted both conservation intention and action (actual behavior), whereas current or previous use of practices only influenced actions, not stated conservation intentions. In our analysis focusing on CP characteristics, we found that having specific knowledge about and positive attitudes toward the CP, adoption of other CPs, seeking and using information, larger farm size, and vulnerable land predicted actual adoption across nearly all CP categorizations. Nuances emerge when comparing predictors of CPs that share a particular characteristic. For example, we found farm characteristics to be comparatively more important in predicting adoption of soil management CPs than nutrient and livestock management CPs, and farmers' stewardship identity to be more important for permanent practices than operational practices.
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Agricultura , Intención , Estados Unidos , Humanos , Encuestas y Cuestionarios , Agricultores , SueloRESUMEN
Background: The basivertebral nerve (BVN) has been a recently discovered target as a potential source for vertebrogenic chronic low back pain (CLBP). Prior randomized controlled trials have demonstrated safety and efficacy of BVN ablation for vertebrogenic CLBP, but minimal data exists regarding BVN ablation's clinical effectiveness with broader application outside of strict trial inclusion criteria. Methods: Prospective, single arm, open label effectiveness trial of 48 patients from community spine and pain practices treated with BVN ablation. Inclusion criteria required more than 6 months of CLBP and type 1 or 2 Modic changes on MRI to be enrolled. Patients were followed post procedure for 12 months using ODI, VAS, EQ-5D-5L and SF-36 patient reported outcome metrics.Results: 47 patients successfully received BVN ablation and 45 patients completed 12 months of follow up. Mean reduction in ODI at 12 months was 32.31 +/- 14.07 (p<0.001) with 88.89% (40/45) patients reporting a ≥15 point ODI decrease at 12 months. Mean VAS pain score decrease was 4.31+/-2.51 at 12 months (p<0.001) and more than 69% reported a 50% reduction in VAS pain scale. Similarly, SF-36 and EQ-5D-5L scores improved 26.27+/-17.19 and 0.22+/-0.15 (each p<0.001). Conclusions: This data supports the clinical effectiveness of BVN ablation in the community practice setting, with similar 12 month improvements in patient reported outcomes as seen in previously published randomized control trials.
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Iowa State University Extension and Outreach conducted an assessment of Iowa farm operators' perceptions of the barriers and motivators when considering retrofitting tractors with rollover protective structures (ROPS). A statewide sample of approximately 2,000 farm operators was surveyed in the 2017 Iowa Farm and Rural Life Poll. A series of questions was asked to evaluate the importance of potential barriers to decisions to not retrofit a tractor and potential motivators that could influence the decision to retrofit or purchase a tractor with ROPS. The survey received a 48% response rate (999 responses). Among the 76% of Iowa farm operators who reported at least one pre-1985 tractor, only 18.6% reported that all of those tractors had ROPS. The remaining 81.4% had at least one tractor that did not have ROPS. Iowa farm operators' perceptions of the barriers and motivators when considering retrofitting tractors with ROPS are shared. The results of Iowa farm operators' perceptions will be used as Iowa State University Extension and Outreach prepares to align efforts with the National Tractor Safety Coalition and participate in the National ROPS Rebate Program, with the goal of reducing tractor fatalities.
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Accidentes de Trabajo , Agricultura , Seguridad de Equipos , Agricultores/psicología , Accidentes de Trabajo/prevención & control , Humanos , Iowa , Percepción , Equipos de SeguridadRESUMEN
Potential climate-change-related impacts to agriculture in the upper Midwest pose serious economic and ecological risks to the U.S. and the global economy. On a local level, farmers are at the forefront of responding to the impacts of climate change. Hence, it is important to understand how farmers and their farm operations may be more or less vulnerable to changes in the climate. A vulnerability index is a tool commonly used by researchers and practitioners to represent the geographical distribution of vulnerability in response to global change. Most vulnerability assessments measure objective adaptive capacity using secondary data collected by governmental agencies. However, other scholarship on human behavior has noted that sociocultural and cognitive factors, such as risk perceptions and perceived capacity, are consequential for modulating people's actual vulnerability. Thus, traditional assessments can potentially overlook people's subjective perceptions of changes in climate and extreme weather events and the extent to which people feel prepared to take necessary steps to cope with and respond to the negative effects of climate change. This article addresses this knowledge gap by: (1) incorporating perceived adaptive capacity into a vulnerability assessment; (2) using spatial smoothing to aggregate individual-level vulnerabilities to the county level; and (3) evaluating the relationships among different dimensions of adaptive capacity to examine whether perceived capacity should be integrated into vulnerability assessments. The result suggests that vulnerability assessments that rely only on objective measures might miss important sociocognitive dimensions of capacity. Vulnerability indices and maps presented in this article can inform engagement strategies for improving environmental sustainability in the region.
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Agricultura/métodos , Cambio Climático , Clima , Ambiente , Agricultores , Geografía , Humanos , Medio Oeste de Estados Unidos , Modelos Estadísticos , Lluvia , Medición de Riesgo , Población Rural , Factores Socioeconómicos , Estados Unidos , Tiempo (Meteorología)RESUMEN
Loss of biodiversity and degradation of ecosystem services from agricultural lands remain important challenges in the United States despite decades of spending on natural resource management. To date, conservation investment has emphasized engineering practices or vegetative strategies centered on monocultural plantings of nonnative plants, largely excluding native species from cropland. In a catchment-scale experiment, we quantified the multiple effects of integrating strips of native prairie species amid corn and soybean crops, with prairie strips arranged to arrest run-off on slopes. Replacing 10% of cropland with prairie strips increased biodiversity and ecosystem services with minimal impacts on crop production. Compared with catchments containing only crops, integrating prairie strips into cropland led to greater catchment-level insect taxa richness (2.6-fold), pollinator abundance (3.5-fold), native bird species richness (2.1-fold), and abundance of bird species of greatest conservation need (2.1-fold). Use of prairie strips also reduced total water runoff from catchments by 37%, resulting in retention of 20 times more soil and 4.3 times more phosphorus. Corn and soybean yields for catchments with prairie strips decreased only by the amount of the area taken out of crop production. Social survey results indicated demand among both farming and nonfarming populations for the environmental outcomes produced by prairie strips. If federal and state policies were aligned to promote prairie strips, the practice would be applicable to 3.9 million ha of cropland in Iowa alone.
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Agricultura/métodos , Biodiversidad , Valores Sociales , Animales , Aves , Humanos , Insectos , Iowa , Suelo , Glycine max , Zea maysRESUMEN
Persistent above average precipitation and runoff and associated increased sediment transfers from cultivated ecosystems to rivers and oceans are due to changes in climate and human action. The US Upper Midwest has experienced a 37% increase in precipitation (1958-2012), leading to increased crop damage from excess water and off-farm loss of soil and nutrients. Farmer adaptive management responses to changing weather patterns have potential to reduce crop losses and address degrading soil and water resources. This research used farmer survey ( = 4778) and climate data (1971-2011) to model influences of geophysical context, past weather, on-farm flood and saturated soils experiences, and risk and vulnerability perceptions on management practices. Seasonal precipitation varied across six Upper Midwest subregions and was significantly associated with variations in management. Increased warm-season precipitation (2007-2011) relative to the past 40 yr was positively associated with no-till, drainage, and increased planting on highly erodible land (HEL). Experience with saturated soils was significantly associated with increased use of drainage and less use of no-till, cover crops, and planting on HEL. Farmers in counties with a higher percentage of soils considered marginal for row crops were more likely to use no-till, cover crops, and plant on HEL. Respondents who sell corn through multiple markets were more likely to have planted cover crops and planted on HEL in 2011.This suggests that regional climate conditions may not well represent individual farmers' actual and perceived experiences with changing climate conditions. Accurate climate information downscaled to localized conditions has potential to influence specific adaptation strategies.
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Agriculture is vulnerable to climate change and a source of greenhouse gases (GHGs). Farmers face pressures to adjust agricultural systems to make them more resilient in the face of increasingly variable weather (adaptation) and reduce GHG production (mitigation). This research examines relationships between Iowa farmers' trust in environmental or agricultural interest groups as sources of climate information, climate change beliefs, perceived climate risks to agriculture, and support for adaptation and mitigation responses. Results indicate that beliefs varied with trust, and beliefs in turn had a significant direct effect on perceived risks from climate change. Support for adaptation varied with perceived risks, while attitudes toward GHG reduction (mitigation) were associated predominantly with variation in beliefs. Most farmers were supportive of adaptation responses, but few endorsed GHG reduction, suggesting that outreach should focus on interventions that have adaptive and mitigative properties (e.g., reduced tillage, improved fertilizer management).
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Climate change has serious implications for the agricultural industry-both in terms of the need to adapt to a changing climate and to modify practices to mitigate for the impacts of climate change. In high-income countries where farming tends to be very intensive and large scale, it is important to understand farmers' beliefs and concerns about climate change in order to develop appropriate policies and communication strategies. Looking across six study sites-Scotland, Midwestern United States, California, Australia, and two locations in New Zealand-this paper finds that over half of farmers in each location believe that climate change is occurring. However, there is a wide range of beliefs regarding the anthropogenic nature of climate change; only in Australia do a majority of farmers believe that climate change is anthropogenic. In all locations, a majority of farmers believe that climate change is not a threat to local agriculture. The different policy contexts and existing impacts from climate change are discussed as possible reasons for the variation in beliefs. This study compared varying surveys from the different locations and concludes that survey research on farmers and climate change in diverse locations should strive to include common questions to facilitate comparisons.
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Adaptación Psicológica , Agricultura , Cambio Climático , Agricultores/psicología , Australia , California , Países Desarrollados , Humanos , Medio Oeste de Estados Unidos , Nueva Zelanda , Medición de Riesgo , Escocia , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
INTRODUCTION: De Garengeot hernia is a rare occurrence whereby an appendix is found in a femoral hernia sac. It is rarer still to find an acutely inflamed appendix manifesting itself as a strangulated femoral hernia. This case is important to report as it highlights the diagnostic difficulty this particular condition presents to an emergency surgeon. PRESENTATION OF CASE: We report the case of an 86 year old female who was found to have a De Garengeot hernia containing a necrotic appendix. A retrograde appendicectomy was performed to prevent peritoneal contamination. The hernia defect was repaired using a standard repair with non-absorbable suture. DISCUSSION: De Garengeot's hernia is a rare occurrence, is often unexpected and tends to be diagnosed intra-operatively. Pre-operative diagnosis remains difficult and it will often masquerade as a strangulated femoral hernia. In stable patients, where there is a diagnostic uncertainty CT scanning is a useful adjunct and may allow a laparoscopic approach to be undertaken in the absence of appendicitis. CONCLUSION: A De Garengeot's hernia should be considered as a differential diagnosis in patients presenting with clinical signs of a strangulated femoral hernia. It is often an incidental finding during an emergency operation. Although mesh repairs in the presence of appendicitis have been reported, the safest approach remains a primary suture repair.
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INTRODUCTION: The insulin-like growth factor type 1 (IGF-1) receptor contributes importantly to transformation and survival of tumor cells both in vitro and in vivo, and selective antagonists of the IGF-1 receptor (IGF-1R) activity represent an attractive experimental approach for human cancer therapy. METHODS: Using a phage display library, we identified several high-affinity fully human monoclonal antibodies with inhibitory activity against both human and rodent IGF.1Rs. RESULTS: These candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro. They also induced IGF-1R downregulation and catabolism following antibody-mediated endocytosis. These antibodies exhibited activity against human, primate, and rodent IGF-1Rs, and dose-dependently inhibited the growth of established human tumors in nude mice. CONCLUSION: These fully human antibodies therefore have the potential to provide an effective anti-tumor biological therapy in the human clinical setting.
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Anticuerpos Monoclonales/farmacología , Proliferación Celular/efectos de los fármacos , Receptor IGF Tipo 1/inmunología , Células 3T3 , Animales , Afinidad de Anticuerpos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Mapeo Epitopo , Humanos , Ratones , Ratones Desnudos , Receptor IGF Tipo 1/metabolismo , Transducción de Señal/efectos de los fármacos , Transfección , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patologíaRESUMEN
BACKGROUND: Conventional surgical management of insulinomas involves an open technique. The laparoscopic approach has advantages in terms of improved postoperative pain and recovery time. This retrospective study evaluated the laparoscopic management of pancreatic insulinomas. METHODS: Between December 2000 and March 2007, 23 patients were referred for consideration of laparoscopic insulinoma resection. Two patients were not deemed appropriate for the laparoscopic approach and were managed with open surgery. All surgery was performed by one experienced pancreatic surgeon. Laparoscopic intraoperative ultrasonography was not available for the first six procedures, but was used thereafter. RESULTS: Twenty-one patients (five men and 16 women, median age 46 (range 22-70) years) had a successful resection. All had single tumours, five in the head, nine in the body and seven in the tail of the pancreas. One conversion to open operation was performed in a patient with an insulinoma in the head of the pancreas who had dense adhesions resulting from pancreatitis. Three patients developed a postoperative pancreatic fistula. There has been no recurrence of symptoms in any patient. CONCLUSION: Laparoscopic management of insulinomas is feasible and safe. Laparoscopic intraoperative ultrasonography is a promising adjunct to the procedure, even after accurate preoperative localization.
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Insulinoma/cirugía , Laparoscopía , Neoplasias Pancreáticas/cirugía , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Estudios de Factibilidad , Femenino , Humanos , Insulinoma/diagnóstico , Masculino , Persona de Mediana Edad , Pancreatectomía/métodos , Fístula Pancreática/etiología , Neoplasias Pancreáticas/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Postoperative complications after laparoscopic choledochotomy are mainly related to the T tube. Both laparoscopic endobiliary stent placement with primary closure of the common bile duct (CBD) and primary closure of the CBD without drainage have been proposed as safe and effective alternatives to T tube placement. METHODS: This was a retrospective analysis of data collected prospectively on 53 consecutive patients suffering from proven choledocholithiasis who underwent laparoscopic CBD exploration through a choledochotomy between January 1999 and January 2003. In the early period a T tube was placed at the end of the procedure (n = 32). Biliary stent placement and primary CBD closure was performed from June 2001 (n = 21). RESULTS: There were no significant differences in epidemiological characteristics, preoperative factors or intraoperative findings between the groups. Seven patients developed complications, six in the T tube group and one in the stent group. Univariate analysis revealed a significantly lower morbidity rate and shorter postoperative hospital stay in the stent group. CONCLUSION: Placement of a biliary endoprosthesis after laparoscopic choledochotomy achieves biliary decompression, and avoids the complications of a T tube, leading to a shorter postoperative hospital stay. The method is a safe and effective alternative method of CBD drainage after laparoscopic choledochotomy.
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Colecistectomía Laparoscópica/métodos , Coledocolitiasis/cirugía , Coledocostomía/métodos , Complicaciones Posoperatorias/etiología , Stents , Anciano , Drenaje/instrumentación , Drenaje/métodos , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Binding of antibodies to oligomeric envelope glycoprotein of R5-tropic primary isolates of human immunodeficiency virus type 1 (HIV-1) was studied by flow cytometry using sera from HIV-1 vaccine recipients and clade B and C HIV-1-infected patients, and monoclonal and polyclonal antibodies to neutralizing epitopes of HIV-1. Vaccine recipients received recombinant canarypox virus vaccine expressing HIV-1 gene products, and SF-2 recombinant gp120 subunit vaccine. Anti-gp120 neutralizing antibodies including human monoclonal antibody 2G12 and goat polyclonal anti-serum to V3 loop peptide [peptide T1-SP10MN(A)] bound to HIV-1-infected cells. Sera from vaccine recipients bound to HIV-1-infected cells, but at levels lower than did infected patient sera.
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Vacunas contra el SIDA/inmunología , Anticuerpos Anti-VIH/metabolismo , Infecciones por VIH/inmunología , Linfocitos/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Virus de la Viruela de los Canarios/inmunología , Epítopos/inmunología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Productos del Gen env/metabolismo , Cabras/inmunología , Anticuerpos Anti-VIH/análisis , Proteína gp120 de Envoltorio del VIH/inmunología , Proteínas gp160 de Envoltorio del VIH/metabolismo , Humanos , Unión Proteica , Proteínas Recombinantes/metabolismo , Vacunas Sintéticas/inmunologíaRESUMEN
Previous reports have shown that unrecognized or incidental bile duct varices have been reported as being related to hazardous complications and difficulties during surgery or other interventional procedures. A 32-year-old Indian female patient with no previous symptoms and signs suggestive of portal hypertension was admitted for an elective laparoscopic cholecystectomy for biliary colic. Bile duct varices were incidentally recognized during the operation. For the sake of safety, the surgery was converted to a conventional approach. Postoperatively, a detailed history revealed catheterization of the umbilical vein during the newborn period. Subsequently, contrast-enhanced computer tomography scanning showed extrahepatic portal vein thrombosis and cavernous transformation, while an upper gastrointestinal tract endoscopy did not reveal any evidence of esophageal varices. Bile duct varices should be excluded in patients with symptoms and signs suggestive for portal hypertension. Moreover, the present case addresses the fact that bile duct varices should also be suspected in asymptomatic patients with a history suggestive for extrahepatic portal vein thrombosis. Intraoperative recognition of bile duct varices requires a careful anatomical approach to the hepatoduodenal ligament to avoid hazardous complications.
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Conductos Biliares/irrigación sanguínea , Várices/cirugía , Adulto , Femenino , Humanos , Hipertensión Portal/diagnóstico , Vena Porta , Procedimientos Quirúrgicos Operativos , Várices/etiología , Trombosis de la Vena/complicacionesRESUMEN
OBJECTIVE: To describe dietary patterns among men and women in the Australian population, and to explore how these varied according to socioeconomic status (SES). DESIGN: A cross-sectional self-report population survey, the 1995 Australian National Nutrition Survey (NNS), was used. SETTING: Private dwelling sample, covering urban and rural areas across Australia. SUBJECTS: Data provided by 6680 adults aged 18-64 who participated in the NNS were used in the analyses. METHODS: Factor analyses were used to analyse data from a Food Frequency Questionnaire (FFQ) completed by participants. Associations between SES and dietary pattens were assessed using ANOVA. RESULTS: Separate factor analyses of the FFQ data for men and women revealed 15 factors, accounting for approximately 50% of the variance in both men's and women's dietary patterns. Several gender and SES differences in food patterns were observed. Lower SES males more frequently consumed 'tropical fruits', 'protein foods', and 'offal and canned fish', while high SES males more often ate 'breakfast cereals' and 'wholemeal bread'. Lower SES females more often ate 'traditional vegetables', 'meat dishes' and 'pasta, rice and other mixed foods', while high SES females more frequently ate 'ethnic vegetables' and 'breakfast cereal/muesli'. CONCLUSIONS: These findings contribute to a better understanding of the dietary patterns that underscore gender-specific SES differences in nutrient intakes. Analyses of the type employed in this study will facilitate the development of interventions aimed at modifying overall eating patterns, rather than specific components of the diet.
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Dieta/estadística & datos numéricos , Conducta Alimentaria , Clase Social , Adolescente , Adulto , Australia , Estudios de Cohortes , Estudios Transversales , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Población Rural , Factores Sexuales , Encuestas y Cuestionarios , Población UrbanaRESUMEN
V(D)J recombination is instigated by the recombination-activating proteins RAG1 and RAG2, which catalyze site-specific DNA cleavage at the border of the recombination signal sequence (RSS). Although both proteins are required for activity, core RAG1 (the catalytically active region containing residues 384-1008 of 1040) alone displays binding specificity for the conserved heptamer and nonamer sequences of the RSS. The nonamer-binding region lies near the N terminus of core RAG1, whereas the heptamer-binding region has not been identified. Here, potential domains within core RAG1 were identified using limited proteolysis studies. An iterative procedure of DNA cloning, protein expression, and characterization revealed the presence of two topologically independent domains within core RAG1, referred to as the central domain (residues 528-760) and the C-terminal domain (residues 761-980). The domains do not include the nonamer-binding region but rather largely span the remaining relatively uncharacterized region of core RAG1. Characterization of macromolecular interactions revealed that the central domain bound to the RSS with specificity for the heptamer and contained the predominant binding site for RAG2. The C-terminal domain bound DNA cooperatively but did not show specificity for either conserved RSS element. This domain was also found to self-associate, implicating it as a dimerization domain within RAG1.
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Reordenamiento Génico/fisiología , Proteínas de Homeodominio/química , Animales , Sitios de Unión , ADN/metabolismo , ADN Nucleotidiltransferasas/metabolismo , Dimerización , Proteínas de Homeodominio/metabolismo , Ratones , Conformación Proteica , Estructura Terciaria de Proteína , Tripsina/metabolismo , VDJ RecombinasasRESUMEN
Vaccine-induced T-cell memory for human immunodeficiency virus type 1 (HIV-1) was assessed by measuring HIV-1 antigen-stimulated cytokine secretion in 72 HIV-1-uninfected subjects, of whom 52 received live recombinant canarypox virus vaccine expressing HIV-1 env, gag, and protease gene products (vCP205) with or without HIV-1(SF-2) recombinant gp120 (SF-2 rgp120) subunit vaccine, and 20 the control. The vCP205 vaccine induced secretion of the Th1 cytokine, interferon-gamma, by peripheral blood mononuclear cells (PBMC) after in vitro stimulation with HIV-1 p24 and envelope glycoprotein. Immunization schedules with both vCP205 and SF-2 rgp120 subunit vaccines induced secretion of Th1 and Th2 cytokines by PBMC to HIV-1 envelope glycoprotein. Hence, vCP205 and SF-2 rgp120 subunit vaccines given together and in a prime-boost sequence appeared to induce a broader cytokine response pattern than vCP205 vaccine given alone.