The contagiousness and deadliness of COVID-19 have necessitated drastic social management to halt transmission. The immediate effects of a nationwide lockdown were investigated by comparing matched ...samples of New Zealanders assessed before (Nprelockdown = 1,003) and during the first 18 days of lockdown (Nlockdown = 1,003). Two categories of outcomes were examined: (a) institutional trust and attitudes toward the nation and government and (b) health and well-being. Applying propensity score matching to approximate the conditions of a randomized controlled experiment, the study found that people in the pandemic/lockdown group reported higher trust in science, politicians, and police, higher levels of patriotism, and higher rates of mental distress compared to people in the prelockdown prepandemic group. Results were confirmed in within-subjects analyses. The study highlights social connectedness, resilience, and vulnerability in the face of adversity and has applied implications for how countries face this global challenge.
Public Significance Statement
This study describes the immediate effects of the COVID-19 pandemic and nationwide lockdown on levels of institutional trust and attitudes toward the nation and government and health and well-being in New Zealand, with implications for other nations. Our results suggest that a strong national response to COVID-19 may bolster national attachment and increase trust in the bodies determining and enforcing lockdown guidelines. Against a backdrop of general resilience, small increases in psychological distress serve as a warning about potential psychological consequences of lockdown and isolation.
Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity.
Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies ...cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with ERBB2 (231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2.
The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly.
Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type 1 diabetes is an incurable chronic autoimmune disease. Although transplantation of pancreatic islets may serve as a surrogate source of insulin, recipients are subjected to a life of ...immunosuppression. Interleukin (IL)-21 is necessary for type 1 diabetes in NOD mice. We examined the efficacy of an IL-21-targeted therapy on prevention of diabetes in NOD mice, in combination with syngeneic islet transplantation. In addition, we assessed the role of IL-21 responsiveness in islet allograft rejection in mouse animal models.
NOD mice were treated with IL-21R/Fc, an IL-21-neutralizing chimeric protein. This procedure was combined with syngeneic islet transplantation to treat diabetic NOD mice. Survival of allogeneic islet grafts in IL-21R-deficient mice was also assessed.
Evidence is provided that IL-21 is continually required by the autoimmune infiltrate, such that insulitis was reduced and reversed and diabetes inhibited by neutralization of IL-21 at a late preclinical stage. Recovery from autoimmune diabetes was achieved by combining neutralization of IL-21 with islet transplantation. Furthermore, IL-21-responsiveness by CD8+ T-cells was sufficient to mediate islet allograft rejection.
Neutralization of IL-21 in NOD mice can inhibit diabetes, and when paired with islet transplantation, this therapeutic approach restored normoglycemia. The influence of IL-21 on a graft-mounted immune response was robust, since the absence of IL-21 signaling prevented islet allograft rejection. These findings suggest that therapeutic manipulation of IL-21 may serve as a suitable treatment for patients with type 1 diabetes.
This paper pushes beyond current debates over what is being called the science of reading to articulate a multidimensional complex conception of what is entailed in reading comprehension. Reading ...comprehension entails not only cognitive processes, but equally important is how issues of identity along multiple dimensions, perceptions of tasks and settings, social and emotional relationships intersect to shape effort and motivation to comprehend. The paper argues that a central problem in the typical teaching of reading comprehension in the K–12 sector is insufficient attention to processes or meaning making. Typical instruction focuses on the outcomes of comprehension, but not on how readers can/should go about trying to make sense of texts. Such instruction can be created by communities of teachers who examine the sources of text difficulty in texts they are teaching. The paper offers explicit criteria for evaluating sources of text complexity in informational and literary texts, and in so doing push beyond the boundaries of traditional Lexile scores.
Edited by a diverse group of expert collaborators, the Handbook of the Cultural Foundations of Learning is a landmark volume that brings together cutting-edge research examining learning as entailing ...inherently cultural processes. Conceptualizing culture as both a set of social practices and connected to learner identities, the chapters synthesize contemporary research in elaborating a new vision of the cultural nature of learning, moving beyond summary to reshape the field toward studies that situate culture in the learning sciences alongside equity of educational processes and outcomes. With the recent increased focus on culture and equity within the educational research community, this volume presents a comprehensive, innovative treatment of what has become one of the field’s most timely and relevant topics.
Relatively little is known about the differential impact of maternal and paternal perceptions of vaccine safety on children’s vaccination status in New Zealand. Using a sample of 68 couples from the ...New Zealand Attitudes and Values Study (NZAVS), the present study investigated the distinct influence of mothers’ and fathers’ confidence in the safety of childhood vaccinations following the national immunisation schedule on their reports of children’s vaccination status. Actor-Partner Interdependence Modelling revealed that mothers’, but not fathers’, vaccine confidence predicted children’s vaccination status, regardless of who reported their children’s vaccination status. Higher maternal vaccine confidence increased the likelihood of child full vaccination status, but paternal vaccine confidence showed no unique significant effects. As women tend to express lower vaccine confidence than men, it is imperative to further investigate the key drivers of their low confidence and develop target interventions accordingly. Encouraging fathers’ involvement in the vaccination decision-making process may also be beneficial in increasing the likelihood of childhood vaccination uptake.
Hepatocellular carcinoma (HCC) is a major global health problem and its treatment options have been limited. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor ...important for various cellular processes. Overexpression and constitutive activation of STAT3 have been frequently found in HCC and associated with poor prognosis. Ample evidence has shown that STAT3 plays pivotal roles in the initiation, progression, metastasis and immune suppression of HCC. Thus, STAT3 has attracted attention as a novel therapeutic target in HCC. Clinical trials have investigated STAT3-targeted therapeutics either as monotherapy or in combination with chemotherapeutic agents, immune checkpoint inhibitors and alternative targeted drugs. Some of these studies have yielded encouraging results. Particularly, napabucasin-a cancer stemness inhibitor targeting STAT3-driven gene transcription-has stood out with its promising clinical efficacy and safety profile. Nonetheless, clinical investigations of STAT3-targeted therapies in HCC are limited and more efforts are strongly urged to evaluate their clinical performance in HCC. Here, we provide a comprehensive review of the roles of STAT3 in HCC and follow by comprehensive analysis of STAT3 targeted strategies.
Despite extensive scientific evidence on the safety of standard vaccinations, some parents express skeptical attitudes towards the safety of childhood immunisations. This paper uses data from the ...2013/14 New Zealand Attitudes and Values Study (NZAVS) survey (N=16,642) to explore the distribution, and demographic and personality correlates of New Zealanders’ attitudes towards the safety of childhood vaccinations. Around two thirds (68.5%) of New Zealanders strongly agreed/were confident that “it is safe to vaccinate children following the standard New Zealand immunisation schedule,” 26% were skeptical and 5.5% were strongly opposed. Multiple regression analysis indicated that people lower on Conscientiousness and Agreeableness but higher on Openness to Experience expressed lower confidence about vaccine safety. Having higher subjective health satisfaction, living rurally, being Māori, single, employed and not a parent were all associated with lower confidence, while a higher income and educational attainment were associated with greater confidence. Our findings suggest that the majority of New Zealand adults trust in the safety of scheduled childhood vaccinations, but about one third do express some degree of concern. This finding highlights the importance of improving public education about the safety and necessity of vaccinations.
If schools are to prepare students to participate more productively in civic life, schools will need to ensure that they have opportunities to practice the skills of civic reasoning, argues Carol ...Lee. Yet schools are challenged by the limits in the curriculum and the difficulty of addressing the different types of prior knowledge that students bring to the classroom. Lee suggests that when schools build their content and pedagogy on current understandings of human learning, they will be better able to enable students from all backgrounds to practice building the understandings they need, now and in the future.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Here, we describe a protocol for the selection of human antibody fragments using repertoires displayed on filamentous bacteriophage. Antigen-specific clones are enriched by binding to immobilized ...antigen, followed by elution and repropagation of phage. After multiple rounds of binding selection, specific clones are identified by ELISA. This article provides an overview of phage display and antibody technology, as well as detailed protocols for the immobilization of antigen, the selection of repertoires on purified or complex antigens and the identification of binders.
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