Cultivating Comadrerismo for Collective Liberation

In this paper, we draw from our positionality, respective roles on campus, and experience with developing the UndocuScholars Research Methods class. We argue that despite learning to navigate during a pandemic and dealing with the coexistence of grief and joy, transformation in the academy is possible when seeds are planted through building community, vulnerability, and the creation of an equitable and student-centered curriculum. At the same time, transformation in the academy occurs among faculty and staff through the development of comadrerismo, which is a bond that extends beyond collegiality, as it seeks to foster a sisterhood that honors, supports, and validates people’s journeys, roles, and goals in life. In the end, we all benefit from the harvest by reimagining spaces as locations where we can experience healing, transformation, and eventually, collective liberation. It is within our line of work that we can envision, change, and benefit from altering the institutional practices that move us to radically shift from individualistic to communal joy

Developing a Web-Based App to Assess Mental Health Difficulties in Secondary School Pupils: Qualitative User-Centered Design Study.

BACKGROUND: Secondary schools are an ideal setting to identify young people experiencing mental health difficulties such as anxiety or depression. However, current methods of identification rely on cumbersome paper-based assessments, which are lengthy and time-consuming to complete and resource-intensive for schools to manage. Artemis-A is a prototype web app that uses computerized adaptive testing technology to shorten the length of the assessment and provides schools with a simple and feasible solution for mental health assessment. OBJECTIVE: The objectives of this study are to coproduce the main components of the Artemis-A app with stakeholders to enhance the user interface, to carry out usability testing and finalize the interface design and functionality, and to explore the acceptability and feasibility of using Artemis-A in schools. METHODS: This study involved 2 iterative design feedback cycles-an initial stakeholder consultation to inform the app design and user testing. Using a user-centered design approach, qualitative data were collected through focus groups and interviews with secondary school pupils, parents, school staff, and mental health professionals (N=48). All transcripts were thematically analyzed. RESULTS: Initial stakeholder consultations provided feedback on preferences for the user interface design, school administration of the assessment, and outcome reporting. The findings informed the second iteration of the app design and development. The unmoderated usability assessment indicated that young people found the app easy to use and visually appealing. However, school staff suggested that additional features should be added to the school administration panel, which would provide them with more flexibility for data visualization. The analysis identified four themes relating to the implementation of the Artemis-A in schools, including the anticipated benefits and drawbacks of the app. Actionable suggestions for designing mental health assessment apps are also provided. CONCLUSIONS: Artemis-A is a potentially useful tool for secondary schools to assess the mental health of their pupils that requires minimal staff input and training. Future research will evaluate the feasibility and effectiveness of Artemis-A in a range of UK secondary schools.Medical Research Council Confidence in Concept award (MC_PC_18042)

Measurement of psychological entitlement in 28 countries

This article presents the cross-cultural validation of the Entitlement Attitudes Questionnaire, a tool designed to measure three facets of psychological entitlement: active, passive, and revenge entitlement. Active entitlement was defined as the tendency to protect individual rights based on self-worthiness. Passive entitlement was defined as the belief in obligations to and expectations toward other people and institutions for the fulfillment of the individual’s needs. Revenge entitlement was defined as the tendency to protect one’s individual rights when violated by others and the tendency to reciprocate insults. The 15-item EAQ was validated in a series of three studies: the first one on a general Polish sample (N = 1,900), the second one on a sample of Polish students (N = 199), and the third one on student samples from 28 countries (N = 5,979). A three-factor solution was confirmed across all samples. Examination of measurement equivalence indicated partial metric invariance of EAQ for all national samples. Discriminant and convergent validity of the EAQ was also confirmed

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Cas9 gRNA engineering for genome editing, activation and repression

We demonstrate that by altering the length of Cas9-associated guide RNA(gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein.National Human Genome Research Institute (U.S.) (P50 HG005550)United States. Department of Energy (DE-FG02-02ER63445)Wyss Institute for Biologically Inspired EngineeringUnited States. Army Research Office (DARPA W911NF-11-2-0054)National Science Foundation (U.S.)United States. National Institutes of Health (5R01CA155320-04)United States. National Institutes of Health (P50 GM098792)National Cancer Institute (U.S.) (5T32CA009216-34)Massachusetts Institute of Technology. Department of Biological EngineeringHarvard Medical School. Department of GeneticsDefense Threat Reduction Agency (DTRA) (HDTRA1-14-1-0006

Enhanced therapeutic effect using sequential administration of antigenically distinct oncolytic viruses expressing oncostatin M in a Syrian hamster orthotopic pancreatic cancer model

The limited efficacy of current treatments against pancreatic cancer has prompted the search of new alternatives such as virotherapy. Activation of the immune response against cancer cells is emerging as one of the main mechanisms of action of oncolytic viruses (OV). Direct oncolysis releases tumor antigens, and viral replication within the tumor microenvironment is a potent danger signal. Arming OV with immunostimulatory transgenes further enhances their therapeutic effect. However, standard virotherapy protocols do not take full advantage of OV as cancer vaccines because repeated viral administrations may polarize immune responses against strong viral antigens, and the rapid onset of neutralizing antibodies limits the efficacy of redosing. An alternative paradigm based on sequential combination of antigenically distinct OV has been recently proposed

Mining of nickel laterites – towards more environmentally responsible operations

Primary mining of technology metal ores is needed to enable effective decarbonisation. The use of nickel in rechargeable batteries is expected to increase global demand for nickel rapidly over the coming years. Over 60% of annual global nickel production originates from nickel laterites, with Indonesia and the Philippines leading the market. Mining of nickel laterite ore can adversely affect the environment through the release of CO2 and potentially hazardous elements (PHE), such as hexavalent chromium, or asbestiform minerals. Through our better understanding of the social and environmental impacts of mining operations and the availability of technologies that can potentially mitigate adverse impact, it is paramount to aim for more responsible mining and metal recovery operations. This study focuses on the Sta Cruz nickel laterite deposit in the Philippines. Through a multi-scale and multi-technique analytical programme and drawing on existing knowledge1,2, we appraise the deposit holistically, focusing on (i) the geochemistry and mineralogy of major commodities and trace metals, such as the platinum group elements; (ii) carbonate forming metals, e.g. magnesium and (iii) the presence and ecotoxicity of PHE and minerals. We use this understanding to assess the potential for a circular economy in mining, via complete utilisation of the ore to maximise the metal output and minimise the waste produced. This includes the removal of CO2 through the formation of carbonate minerals (mineral carbonation). We also investigate the potential of carbonates to immobilise chromium crystallographically alongside the CO2. This aspect of mineral carbonation is currently poorly understood. We have carried out laboratory synthesis of chromium-doped carbonates at ambient P-T conditions, which indicates that the most common magnesium carbonates do not readily accommodate chromium. However, other carbonate-bearing minerals, including those belonging to layered double hydroxides, present a viable alternative. The combined PHE-CO2 mineral carbonation, when implemented at different stages of metal recovery, from ore extraction to processing, could lead to a reduction of the volume and toxicity of waste, collectively contributing to the mitigation of the adverse environmental impact of nickel laterite mining. [1] Acquino et al (2022) Minerals, 12(3) [2] Bacuta et al (1990) Journal of Geochem.Exploration, 3

Comparison of geometric morphometric outline methods in the discrimination of age-related differences in feather shape

BACKGROUND: Geometric morphometric methods of capturing information about curves or outlines of organismal structures may be used in conjunction with canonical variates analysis (CVA) to assign specimens to groups or populations based on their shapes. This methodological paper examines approaches to optimizing the classification of specimens based on their outlines. This study examines the performance of four approaches to the mathematical representation of outlines and two different approaches to curve measurement as applied to a collection of feather outlines. A new approach to the dimension reduction necessary to carry out a CVA on this type of outline data with modest sample sizes is also presented, and its performance is compared to two other approaches to dimension reduction. RESULTS: Two semi-landmark-based methods, bending energy alignment and perpendicular projection, are shown to produce roughly equal rates of classification, as do elliptical Fourier methods and the extended eigenshape method of outline measurement. Rates of classification were not highly dependent on the number of points used to represent a curve or the manner in which those points were acquired. The new approach to dimensionality reduction, which utilizes a variable number of principal component (PC) axes, produced higher cross-validation assignment rates than either the standard approach of using a fixed number of PC axes or a partial least squares method. CONCLUSION: Classification of specimens based on feather shape was not highly dependent of the details of the method used to capture shape information. The choice of dimensionality reduction approach was more of a factor, and the cross validation rate of assignment may be optimized using the variable number of PC axes method presented herein

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study

Background: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2.77 (95% confidence interval, 1.66–4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. Conclusion: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19