Search results for: Kathryn R. Burke

Authors: Akunna Agunwah, Kevin Gallimore, Kathryn Kinnmond

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Entrepreneurship and project management are widely associated and seen as a vehicle for economic growth, but are studied separately. A few authors have considered the interconnectivity existing between these two fields, but relatively little empirical data currently exist in the literature. The purpose of the present empirical study is to explore whether successful entrepreneurs utilise project management approaches in enhancing enterprise growth by understanding the working practices and experiences of the entrepreneurs’ using the Theory of Planned Behaviour (TPB) as a lens. In order to understand those experiences, ten successful entrepreneurs in various business sectors in the North West of England were interviewed through a face-to-face semi-structured interview method. The collected audio tape-recorded data was transcribed and analysed using the deductive thematic technique (qualitative approach). The themes were viewed through the lens of Theory of Planned Behaviour to identify the three intentional antecedents (attitude, subjective norms, and perceived behavioural control) and to understand how they relate to the project management approaches (Planning, execution, and monitoring). The findings are twofold, the first evidence of the three intentional antecedents, which make up Theory of Planned Behaviour was present. Secondly, the analysis of project management approaches themes (planning, execution, and monitoring) using the lens of the theory of planned behaviour shows evidence of the three intentional antecedents. There were more than one intentional antecedents found in a particular project management theme, which indicates that the entrepreneur does utilise these approaches without categorising them into definite themes. However, the entrepreneur utilised these intentional antecedents as processes to enhanced business growth. In conclusion, the work presented here showed a way of understanding the interconnectivity between entrepreneurship and project management towards enhancing enterprise growth by examining the working practices and experiences of the successful entrepreneurs in the North-West England.

Keywords: business growth, entrepreneurship, project management approaches, theory of planned behaviour

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Authors: Kathryn Rooney, Kaitlyn Eddy, Evan Landers, Weihui Li

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The international mortality rate for neonates and infants has been declining at a disproportionally low rate when compared to the overall decline in child mortality in recent decades. A significant portion of infant deaths could be prevented with the implementation of low-cost and easy to use physiological monitoring devices, by enabling early identification of symptoms before they progress into life-threatening illnesses. The oral diagnostic device discussed in this paper serves to continuously monitor the key vital signs of body temperature, respiratory rate, heart rate, and oxygen saturation. The device mimics an infant pacifier, designed to be easily tolerated by infants as well as orthodontically inert. The fundamental measurements are gathered via thermistors and a pulse oximeter, each encapsulated in medical-grade silicone and wired internally to a microcontroller chip. The chip then translates the raw measurements into physiological values via an internal algorithm, before outputting the data to a liquid crystal display screen and an Android application. Additionally, a biological sample collection chamber is incorporated into the internal portion of the device. The movement within the oral chamber created by sucking on the pacifier-like device pushes saliva through a small check valve in the distal end, where it is accumulated and stored. The collection chamber can be easily removed, making the sample readily available to be tested for various diseases and analytes. With the vital sign monitoring and sample collection offered by this device, abnormal fluctuations in physiological parameters can be identified and appropriate medical care can be sought. This device enables preventative diagnosis for infants who may otherwise have gone undiagnosed, due to the inaccessibility of healthcare that plagues vast numbers of underprivileged populations.

Keywords: neonate mortality, infant mortality, low-cost diagnostics, vital signs, saliva testing, preventative care

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Authors: Andrea Parisi, Samantha Vilkins, Luis Furuya-Kanamori, John A. Crump, Benjamin P. Howden, Darren Gray, Kathryn Glass, Martyn Kirk

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Objectives: Salmonella is a leading cause of foodborne enterocolitis worldwide. Nontyphoidal Salmonella (NTS) infections that are Multi-Drug Resistant (MDR) (non-susceptible to ≥1 agent in ≥3 antimicrobial categories) may result in more severe outcomes, although these effects have not been systematically examined. We conducted a systematic review and meta-analysis to examine impacts of MDR NTS on health in high-income settings. Methods: We systematically reviewed the literature from scientific databases, including PubMed, Scopus and grey literature sources, using PRISMA guidelines. We searched for data from case-control studies, cohorts, outbreaks, reports and theses, imposing no language restriction. We included only publications from January 1990 to September 2016 from high income countries as classified by World Bank. We extracted data from papers on duration of illness, hospitalisation rates, morbidity and mortality for MDR and non-MDR NTS strains. Results: After removing duplicates, the initial search revealed 4258 articles. After further screening, we identified 16 eligible studies for the systematic review, and 9 of these were included in meta-analysis. NTS serotypes differed among the reported studies but serotype Typhimurium, Enteritidis, Newport and Heidelberg were among the most often reported as MDR pathogens. Salmonella infections that were MDR were associated with excess bloodstream infections (OR 1.63; 95%CI 1.18-2.26), excess hospitalisations (OR 2.77; 95%CI 1.47-5.21) and higher mortality (OR 3.54; 95%CI 1.10-11.40). Conclusions: MDR NTS infections are a serious public health concern. With the emergence of MDR Salmonella strains in the high-income countries, it is crucial to restrict the use of antimicrobials both in animals and humans, and intervene to prevent foodborne infections.

Keywords: Antimicrobial Resistance, Bloodstream Infection, Health Outcomes, Hospitalisation, Invasive Disease, Multi-Drug Resistance (MDR), Mortality, Nontyphoidal Salmonella

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Authors: F. Moghtaderi, M. Burke, J. Troelsen

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There has been a significant decline in active travel as well as the massive increase use of car-dependent travel mode in many countries during past two decades. Evidential risks for people’s physical and mental health problems are followed by this increased use of motorized travel mode. These problems range from overweight and obesity to increasing air pollution. In response to these rising concerns, local councils and other interested organizations around the world have introduced a variety of initiatives regarding reduce the dominance of cars for the daily journeys. However, the nature of these kinds of interventions, which related to the human behavior, make lots of complexities. People’s travel behavior and changing this behavior, has two different aspects. People’s attitudes and perceptions toward the sustainable and healthy modes of travel, and motorized travel modes (especially private car use) is one these two aspects. The other one related to people’s behavior change processes. There are no comprehensive model in order to guide policy interventions to increase the level of succeed of such interventions. A comprehensive theoretical framework is required in accordance to facilitate and guide the processes of data collection and analysis to achieve the best possible guidelines for policy makers. Regarding this gaps in the travel behavior change research, this paper attempted to identify and suggest a multidimensional framework in order to facilitate planning interventions. A structured mixed-method is suggested regarding the expand the scope and improve the analytic power of the result according to the complexity of human behavior. In order to recognize people’s attitudes, a theory with the focus on people’s attitudes towards a particular travel behavior was needed. The literature around the theory of planned behavior (TPB) was the most useful, and had been proven to be a good predictor of behavior change. Another aspect of the research, related to the people’s decision-making process regarding explore guidelines for the further interventions. Therefore, a theory was needed to facilitate and direct the interventions’ design. The concept of the transtheoretical model of behavior change (TTM) was used regarding reach a set of useful guidelines for the further interventions with the aim to increase active travel and sustainable modes of travel. Consequently, a combination of these two theories (TTM and TPB) had presented as an appropriate concept to identify and design implemented travel behavior change interventions.

Keywords: behavior change theories, theoretical framework, travel behavior change interventions, urban research

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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Authors: Tony Feng, Rea Thomson, Kathryn Greenslade, Ross Medine, Jennifer Easterbrook, Calum Arthur, Matilda Powell-bowns

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There are clear guidelines on taking group and screen samples (G&S) for elective arthroplasty and major trauma. However, there is limited guidance on blood grouping for other trauma patients. The purpose of this study was to review the level of blood grouping at a major trauma centre and validate a protocol that limits the expensive processing of G&S samples. After reviewing the national guidance on transfusion samples in orthopaedic patients, data was prospectively collected for all orthopaedic admissions in the Royal Infirmary of Edinburgh between January to February 2023. The cause of admission, number of G&S samples processed on arrival and need for red cells was collected using the hospital blood bank. A new protocol was devised based on a multidisciplinary meeting which limited the requirement for G&S samples only to presentations in “category X”, including neck-of-femur fractures (NOFs), pelvic fractures and major trauma. A re-audit was completed between April and May after departmental education and institution of this protocol. 759 patients were admitted under orthopaedics in the major trauma centre across two separate months. 47% of patients were admitted with presentations falling in category X (354/759) and patients in this category accounted for 88% (92/104) of those requiring post-operative red cell transfusions. Of these, 51% were attributed to NOFs (47/92). In the initial audit, 50% of trauma patients outwith category X had samples sent (116/230), estimated to cost £3800. Of these 230 patients, 3% required post-operative transfusions (7/230). In the re-audit, 23% of patients outwith category X had samples sent (40/173), estimated to cost £1400, of which 3% (5/173) required transfusions. None of the transfusions in these patients in either audit were related to their operation and the protocol achieved an estimated cost saving of £2400 over one month. This study highlights the importance of sending samples for patients with certain categories of orthopaedic trauma (category X) due to the high demand for post-operative transfusions. However, the absence of transfusion requirements in other presentations suggests over-testing. While implementation of the new protocol has markedly reduced over-testing, additional interventions are required to reduce this further.

Keywords: blood transfusion, quality improvement, orthopaedics, trauma

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Authors: Shirl H. Terrell

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In the telling of mythologies, stories of cultural and religious histories, the creative arts provide an archetypal lens through which the personal and collective unconscious are viewed, thus revealing mysteries of the unknown psyche. To that end, the author of this paper, using the hermeneutic approach, proves that Carlisle Floyd’s (1955) English language opera Susannah illuminates humanity’s instinctual nature and behaviors through music, libretto, and drama. While impressive musical works such as Wagner’s Ring Cycle and Webber’s Phantom of the Opera have received extensive Jungian analyses, critics and scholars often ignore lesser esteemed works, such as Susannah, notwithstanding the fact that they have been consistently performed on the theater circuit. Such pieces, when given notice, allow viewers to grasp the soul-making depth and timeless quality of productions which may otherwise go unrecognized as culturally or psychologically significant. Although Susannah has sometimes been described as unsophisticated and simple in scope, the author demonstrates why Floyd’s 'little' opera, set in New Hope Valley, Appalachia, a cultural region in the Eastern United States known for its prevailing myths and distortions of isolation, temperament, and the judgmentally conservative behavior of its inhabitants, belongs to opera’s hallmark works. Its approach to powerful underlying archetypal themes, which give rise to the poignant and haunting depictions of the darker and destructive side of the human soul, the Shadow, provides crucial significance to the work. The Shadow’s manifestation in the form of the scapegoating complex is central to the plot of Susannah; the church’s meting out of rules, judgment, and reparation for sins point to the foreboding aspects of human behavior that evoke their intrinsic nature. The scapegoating complex is highlighted in an eight-step process gleaned from the works of Kenneth Burke and Rene Girard. In summary, through depth psychological terms and mythological motifs, the author provides an insightful approach to perceiving instinctual behaviors as they play out in an American opera that has been staged over eight-hundred times, yet, unfortunately, remains in the shadows. Susannah’s timelessness is now.

Keywords: archetypes, mythology, opera, scapegoating, Shadow, Susannah

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Authors: Kathryn Nderitu, Atunga Nyachieo, Ezekiel Mecha

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Introduction: Solanum nigrum , also known as black nightshade, biosynthesizes various phytochemical compounds with various pharmacological activities, including treating cardiovascular diseases and type 2 diabetes, among others. Materials and Methods: To assess the anti-obesity effects of Solanum nigrum using high-fat-fed diet rats, Sprague Dawley male rats (n = 35) of weights 160–180 g were assigned randomly into seven groups comprising n = 5 rats each. Each group was fed for 11 weeks as follows: normal group (normal chow rat feed); high-fat diet control (HFD); HFD and standard drug (Orlistat 30 mg/kg bw); HFD and methanolic extract 150 mg/kgbw; HFD and methanolic extract 300 mg/kgbw; HFD and dichloromethane extract 150 mg/kgbw; HFD and dichloromethane extract 300 mg/kgbw. Body mass index and food intake were monitored per week, and an oral glucose tolerance test was measured in weeks 5 and 10. Lipid profiles, liver function tests, adipose tissue, liver weights, and phytochemical analysis of Solanum nigrum were later carried out. Results: High-fat diet control group rats exhibited a significant increase in body mass index (BMI), while rats administered with leaf extracts of Solanum nigrum showed a reduction in BMI. Both low doses of dichloromethane (150 mg/kgbw) and high doses of methanol extracts (300 mg/kgbw) showed a better reduction in BMI than the other treatment groups. A significant decrease (p <0.05) in low-density lipoprotein-cholesterol, triglycerides, and cholesterol was observed among the rats administered with Solanum nigrum extracts compared to those of HFD control. Moreover, the HFD control group significantly increased liver and adipose tissue weights compared to other treatment groups (p<0.05). Solanum nigrum also decreased glycemic levels and normalized the hepatic enzymes of HFD control. However, food intake among the groups showed no significant difference (p>0.05). Qualitative analysis of Solanum nigrum leaf extracts indicated the presence of various bioactive compounds associated with anti-obesity. Conclusion: These results validate the use of Solanum nigrum in controlling obesity.

Keywords: solanum nigrum, High fat diet, phytocompounds, obesity

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Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

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Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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Authors: Lauren Kathryn Stretch

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A study was conducted in the underprivileged setting of Nelson Mandela Bay, South Africa in order to monitor the progress of learners whose teachers receive training through the Early Inspiration Training Programme. Through tracking children’s growth & development, the effectiveness of the practitioner-training programme, which focuses on empowering women from underprivileged communities in South Africa, was analyzed. The aim was to identify impact & reach and to assess the effectiveness of this intervention programme through identifying impact on children’s growth and development. A Pre- and Post-Test was administered on about 850 young children in Pre-Grade R and Grade R classes in order to understand children’s ability level & the growth that would be evident as a result of effective teacher training. A pre-test evaluated the level of each child’s abilities, including physical-motor development, language, and speech development, cognitive development including visual perceptual skills, social-emotional development & play development. This was followed by a random selection of the classes of children into experimental and control groups. The experimental group’s teachers (practitioners) received 8-months of training & intervention, as well as mentorship & support. After the 8-month training programme, children from the experimental & control groups underwent post-assessment. The results indicate that the impact of effective practitioner training and enhancing a deep understanding of stimulation on young children, that this understanding is implemented in the classroom, highlighting the areas of growth & development in the children whose teachers received additional training & support, as compared to those who did not receive additional training. Monitoring & Evaluation systems not only track children’s ability levels, but also have a core focus on reporting systems, mentorship and providing ongoing support. As a result of the study, an Online Application (for Apple or Android Devices) was developed which is used to track children’s growth via age-appropriate assessments. The data is then statistically analysed to provide direction for relevant & impactful intervention. The App also focuses on effective reporting strategies, structures, and implementation to support organizations working with young children & maximize on outcomes.

Keywords: early childhood development, developmental child assessments, online application, monitoring and evaluating online

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Authors: Sara E. Baumann, Megan A. Rabin, Mary Hawk, Bhimsen Devkota, Kajol Upadhyaya, Guna Raj Shrestha, Brigit Joseph, Annika Agarwal, Jessica G. Burke

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In Nepal, prevailing sociocultural norms associated with menstruation prompt adherence to stringent rules that limit participation in daily activities. Chhaupadi is a specific menstrual tradition in Nepal in which women and girls segregate themselves and follow a series of restrictions during menstruation. Despite having numerous physical and mental health implications, extant interventions have yet to sustainably address the harms associated with chhaupadi. In this study, the authors describe insights garnered from a collaboration with community members in Dailekh district, who formulated their own approaches to mitigate the adverse facets of chhaupadi. Envisaged as an entry point to improve women’s menstrual health experiences, this investigation employed an approach that uses Human-centered Design and a community-engaged approach. The authors conducted a four-day design workshop which unfolded in two phases: The Discovery Phase, to uncover chhaupadi context and key stakeholders, and the Design Phase, to design contextually relevant interventions. Diverse community-members, including those with lived experience practicing chhaupadi, developed five intervention concepts: 1) harnessing Female Community Health Volunteers as role models, for counseling, and raising awareness; 2) focusing on mothers and mother’s groups to instigate behavioral shifts; 3) engaging the broader community in behavior change efforts; 4) empowering fathers to effect change in their homes through counseling and education; and 5) training and emboldening youth to advocate for positive change through advocacy in their schools and homes. This research underscores the importance of employing multi-level approaches tailored to specific stakeholder groups, given Nepal’s rich cultural diversity. The engagement of Female Community Health Volunteers emerged as a promising yet underexplored intervention concept for chhaupadi, warranting broader implementation. Crucially, it is also imperative for interventions to prioritize tackling deleterious aspects of the chhaupadi tradition, emphasizing safety considerations, all while acknowledging chhaupadi’s entrenched cultural history; for some, there are positive aspects of the tradition that women and girls wish to preserve.

Keywords: human-centered design, menstrual health, Nepal, community-engagement, intervention development, women's health, rural health

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Authors: Ankita Jadon, Sidi Souvi, Nathalie Girault, Denis Petitprez

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The interaction of fission products (FP) with sodium carbonate (Na₂CO₃) aerosols is of a high safety concern because of their potential role in the radiological source term mitigation by FP trapping. In a sodium-cooled fast nuclear reactor (SFR) experiencing a severe accident, sodium (Na) aerosols can be formed after the ejection of the liquid Na coolant inside the containment. The surface interactions between these aerosols and different FP species have been investigated using ab-initio, density functional theory (DFT) calculations using Vienna ab-initio simulation package (VASP). In addition, an improved thermodynamic model has been proposed to treat DFT-VASP calculated energies to extrapolate them to temperatures and pressures of interest in our study. A combined experimental and theoretical chemistry study has been carried out to have both atomistic and macroscopic understanding of the chemical processes; the theoretical chemistry part of this approach is presented in this paper. The Perdew, Burke, and Ernzerhof functional were applied in combination with Grimme’s van der Waals correction to compute exchange-correlational energy at 0 K. Seven different surface cleavages were studied of Ƴ-Na₂CO₃ phase (stable at 603.15 K), it was found that for defect-free surfaces, the (001) facet is the most stable. Furthermore, calculations were performed to study surface defects and reconstructions on the ideal surface. All the studied surface defects were found to be less stable than the ideal surface. More than one adsorbate-ligand configurations were found to be stable confirming that FP vapors could be trapped on various adsorption sites. The calculated adsorption energies (Eads, eV) for the three most stable adsorption sites for I₂ are -1.33, -1.088, and -1.085. Moreover, the adsorption of the first molecule of I₂ changes the surface in a way which would favor stronger adsorption of a second molecule of I2 (Eads, eV = -1.261). For HI adsorption, the most favored reactions have the following Eads (eV) -1.982, -1.790, -1.683 implying that HI would be more reactive than I₂. In addition to FP species, adsorption of H₂O was also studied as the hydrated surface can have different reactivity than the bare surface. One thermodynamically favored site for H₂O adsorption was found with an Eads, eV of -0.754. Finally, the calculations of hydrated surfaces of Na₂CO₃ show that a layer of water adsorbed on the surface significantly reduces its affinity for iodine (Eads, eV = -1.066). According to the thermodynamic model built, the required partial pressure at 373 K to have adsorption of the first layer of iodine is 4.57×10⁻⁴ bar. The second layer will be adsorbed at partial pressures higher than 8.56×10⁻⁶ bar; a layer of water on the surface will increase these pressure almost ten folds to 3.71×10⁻³ bar. The surface interacts with elemental Cs with an Eads (eV) of -1.60, while interacts even strongly with CsI with an Eads (eV) of -2.39. More results on the interactions between Na₂CO₃ (001) and cesium-based FP will also be presented in this paper.

Keywords: iodine uptake, sodium carbonate surface, sodium-cooled fast nuclear reactor, DFT calculations, fission products

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Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

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Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

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Authors: Kathryn McMillan

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A recent study of 8500 adult Australians aged 16 and over revealed 62% had experienced childhood maltreatment. In response to multiple recommendations by bodies such as the Australian Law Reform Commission, parliamentary reports and stakeholder input, a number of key initiatives have been developed to grapple with the difficulties of a federal-state system and to screen and triage high-risk families navigating their way through the court system. The Lighthouse Project (LHP) is a world-first initiative of the Federal Circuit and Family Courts in Australia (FCFOCA) to screen family law litigants for major risk factors, including family violence, child abuse, alcohol or substance abuse and mental ill-health at the point of filing in all applications that seek parenting orders. It commenced on 7 December 2020 on a pilot basis but has now been expanded to 15 registries across the country. A specialist risk screen, Family DOORS, Triage has been developed – focused on improving the safety and wellbeing of families involved in the family law system safety planning and service referral, and ¬ differentiated case management based on risk level, with the Evatt List specifically designed to manage the highest risk cases. Early signs are that this approach is meeting the needs of families with multiple risks moving through the Court system. Before the LHP, there was no data available about the prevalence of risk factors experienced by litigants entering the family courts and it was often assumed that it was the litigation process that was fueling family violence and other risks such as suicidality. Data from the 2022 FCFCOA annual report indicated that in parenting proceedings, 70% alleged a child had been or was at risk of abuse, 80% alleged a party had experienced Family Violence, 74 % of children had been exposed to Family Violence, 53% alleged through substance misuse by party children had caused or was at risk of causing harm to children and 58% of matters allege mental health issues of a party had caused or placed a child at risk of harm. Those figures reveal the significant overlap between child protection and family violence, both of which are under the responsibility of state and territory governments. Since 2020, a further key initiative has been the co-location of child protection and police officials amongst a number of registries of the FCFOCA. The ability to access in a time-effective way details of family violence or child protection orders, weapons licenses, criminal convictions or proceedings is key to managing issues across the state and federal divide. It ensures a more cohesive and effective response to family law, family violence and child protection systems.

Keywords: child protection, family violence, parenting, risk screening, triage.

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Authors: Avi Shrivastava

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Our world continues to grapple with a lot of social issues. Economic growth and scientific advancements have not completely eradicated poverty, homelessness, discrimination and bias, gender inequality, health issues, mental illness, addiction, and other social issues. So, how do we improve the human condition in a world driven by advanced technology? The answer is simple: we will have to leverage technology to address some of the most important social challenges of the day. AI, or artificial intelligence, has emerged as a critical tool in the battle against issues that deprive marginalized and disadvantaged groups of the right to enjoy benefits that a society offers. Social work professionals can transform their lives by harnessing it. The lack of reliable data is one of the reasons why a lot of social work projects fail. Social work professionals continue to rely on expensive and time-consuming primary data collection methods, such as observation, surveys, questionnaires, and interviews, instead of tapping into AI-based technology to generate useful, real-time data and necessary insights. By leveraging AI’s data-mining ability, we can gain a deeper understanding of how to solve complex social problems and change lives of people. We can do the right work for the right people and at the right time. For example, AI can enable social work professionals to focus their humanitarian efforts on some of the world’s poorest regions, where there is extreme poverty. An interdisciplinary team of Stanford scientists, Marshall Burke, Stefano Ermon, David Lobell, Michael Xie, and Neal Jean, used AI to spot global poverty zones – identifying such zones is a key step in the fight against poverty. The scientists combined daytime and nighttime satellite imagery with machine learning algorithms to predict poverty in Nigeria, Uganda, Tanzania, Rwanda, and Malawi. In an article published by Stanford News, Stanford researchers use dark of night and machine learning, Ermon explained that they provided the machine-learning system, an application of AI, with the high-resolution satellite images and asked it to predict poverty in the African region. “The system essentially learned how to solve the problem by comparing those two sets of images [daytime and nighttime].” This is one example of how AI can be used by social work professionals to reach regions that need their aid the most. It can also help identify sources of inequality and conflict, which could reduce inequalities, according to Nature’s study, titled The role of artificial intelligence in achieving the Sustainable Development Goals, published in 2020. The report also notes that AI can help achieve 79 percent of the United Nation’s (UN) Sustainable Development Goals (SDG). AI is impacting our everyday lives in multiple amazing ways, yet some people do not know much about it. If someone is not familiar with this technology, they may be reluctant to use it to solve social issues. So, before we talk more about the use of AI to accomplish social work objectives, let’s put the spotlight on how AI and social work can complement each other.

Keywords: social work, artificial intelligence, AI based social work, machine learning, technology

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Authors: Vera G. Dianova, Lori P. Montross, Charles M. Burke

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In the digital age, the widespread and frequently excessive use of mobile phones amongst university students is recognized as a significant distractor which interferes with their ability to enter a deep state of concentration during studies and diminishes their prospects of experiencing the enjoyable and instrumental state of flow, as defined and described by psychologist M. Csikszentmihalyi. This study has targeted 50 university students with the aim of teaching them to cultivate their ability to engage in deep work and to attain the state of flow, fostering more effective and enjoyable learning experiences. Prior to the start of the intervention, all participating students completed a comprehensive survey based on a variety of validated scales assessing their inclination toward lifelong learning, frequency of flow experiences during study, frustration tolerance, sense of agency, as well as their love of learning and daily time devoted to non-academic mobile phone activities. Several days after this initial assessment, students received a 90-minute lecture on the principles of flow and deep work, accompanied by a critical discourse on the detrimental effects of excessive mobile phone usage. They were encouraged to practice deep work and strive for frequent flow states throughout the semester. Subsequently, students submitted weekly surveys, including the 10-item CORE Dispositional Flow Scale, a 3-item agency scale and furthermore disclosed their average daily hours spent on non-academic mobile phone usage. As a final step, at the end of the semester students engaged in reflective report writing, sharing their experiences and evaluating the intervention's effectiveness. They considered alterations in their love of learning, reflected on the implications of their mobile phone usage, contemplated improvements in their tolerance for boredom and perseverance in complex tasks, and pondered the concept of lifelong learning. Additionally, students assessed whether they actively took steps towards managing their recreational phone usage and towards improving their commitment to becoming lifelong learners. Employing a mixed-methods approach our study offers insights into the dynamics of concentration, flow, mobile phone usage and attitudes towards learning among undergraduate and graduate university students. The findings of this study aim to promote profound contemplation, on the part of both students and instructors, on the rapidly evolving digital-age higher education environment. In an era defined by digital and AI advancements, the ability to concentrate, to experience the state of flow, and to love learning has never been more crucial. This study underscores the significance of addressing mobile phone distractions and providing strategies for cultivating deep concentration. The insights gained can guide educators in shaping effective learning strategies for the digital age. By nurturing a love for learning and encouraging lifelong learning, educational institutions can better prepare students for a rapidly changing labor market, where adaptability and continuous learning are paramount for success in a dynamic career landscape.

Keywords: deep work, flow, higher education, lifelong learning, love of learning

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Authors: Kathryn Ewing

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Safe and accessible public spaces are vital elements of our South African cities. Public spaces hold the potential to act as important, vibrant places for learning, exchange, and practice. Public walkways, however, are some of the most neglected and extremely dangerous public spaces experienced in the local neighborhood of Gugulethu in Cape Town. Walkways feel insignificant, being recognized as informal and undetermined or retain complex fragments of formal erven. They are generally out of sight connecting minor streets and informal settlements. Community residents refer to the walkways as unsafe and dirty spaces. Local authorities allocate minimal to no municipal budgets nor maintenance plans resulting in a lack of basic services, particularly lighting and green infrastructure. ‘The Walkway Project’ presents a series of urban stories collected from co-design workshops, emotional mapping exercises, and fieldwork, including urban walks and urban talks. The narrative interprets the socio-spatial practice and complexity of informal public space in Gugulethu, Cape Town. The Walkway Project research, interrelated to the Master of Urban Design teaching and design-research studio, has a strong focus on participatory and engaged learning and action research methodology within a deliberate pedagogy. A consolidated urban design implementation plan exposes the impact and challenges of waste and water, opening the debate on relevant local solutions for resilience and safety in Cape Town. A small and neglected passage connecting two streets, commonly referred to as iThemba Walkway, is presented as a case study to show-case strategic urban design intervention strategies for urban upgrading. The iThemba walkway is a community-driven project that demonstrates active and responsible co-design and participatory development opportunities. In March 2021, when visited on an urban walk, the public space was covered by rubble and solid waste. By April 2021, the community cleaned the walkway and created an accessible passage for the school children to pass. Numerous co-design workshops have taken place over the past year. The walkway has emerged as a public space upgrading project facilitated, motivated, and implemented by multiple local partners and residents. Social maps from urban walks and talks illustrate the transformation of iThemba Walkway into an inclusive, safe, resilient, and sustainable urban space, linked to Sustainable Development Goal number 11, sustainable cities and communities. The outcomes of the upgrading project facilitate a deeper understanding of co-design methods, urban upgrading processes, and monitoring of public space and informal urbanism.

Keywords: informal, public space, resilience, safety, upgrade, walkways

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Authors: Vladimir A. Basiuk, Laura J. Flores-Sanchez, Victor Meza-Laguna, Jose O. Flores-Flores, Lauro Bucio-Galindo, Elena V. Basiuk

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Noncovalent nanohybrid materials combining carbon nanotubes (CNTs) with phthalocyanines (Pcs) is a subject of increasing research effort, with a particular emphasis on the design of new heterogeneous catalysts, efficient organic photovoltaic cells, lithium batteries, gas sensors, field effect transistors, among other possible applications. The possibility of using unsubstituted Pcs for CNT functionalization is very attractive due to their very moderate cost and easy commercial availability. However, unfortunately, the deposition of unsubstituted Pcs onto nanotube sidewalls through the traditional liquid-phase protocols turns to be very problematic due to extremely poor solubility of Pcs. On the other hand, unsubstituted free-base H₂Pc phthalocyanine ligand, as well as many of its transition metal complexes, exhibit very high thermal stability and considerable volatility under reduced pressure, which opens the possibility for their physical vapor deposition onto solid surfaces, including nanotube sidewalls. In the present work, we show the possibility of simple, fast and efficient noncovalent functionalization of single-walled carbon nanotubes (SWNTs) with a series of 3d metal(II) phthalocyanines Me(II)Pc, where Me= Co, Ni, Cu, and Zn. The functionalization can be performed in a temperature range of 400-500 °C under moderate vacuum and requires about 2-3 h only. The functionalized materials obtained were characterized by means of Fourier-transform infrared (FTIR), Raman, UV-visible and energy-dispersive X-ray spectroscopy (EDS), scanning and transmission electron microscopy (SEM and TEM, respectively) and thermogravimetric analysis (TGA). TGA suggested that Me(II)Pc weight content is 30%, 17% and 35% for NiPc, CuPc, and ZnPc, respectively (CoPc exhibited anomalous thermal decomposition behavior). The above values are consistent with those estimated from EDS spectra, namely, of 24-39%, 27-36% and 27-44% for CoPc, CuPc, and ZnPc, respectively. A strong increase in intensity of D band in the Raman spectra of SWNT‒Me(II)Pc hybrids, as compared to that of pristine nanotubes, implies very strong interactions between Pc molecules and SWNT sidewalls. Very high absolute values of binding energies of 32.46-37.12 kcal/mol and the highest occupied and lowest unoccupied molecular orbital (HOMO and LUMO, respectively) distribution patterns, calculated with density functional theory by using Perdew-Burke-Ernzerhof general gradient approximation correlation functional in combination with the Grimme’s empirical dispersion correction (PBE-D) and the double numerical basis set (DNP), also suggested that the interactions between Me(II) phthalocyanines and nanotube sidewalls are very strong. The authors thank the National Autonomous University of Mexico (grant DGAPA-IN200516) and the National Council of Science and Technology of Mexico (CONACYT, grant 250655) for financial support. The authors are also grateful to Dr. Natalia Alzate-Carvajal (CCADET of UNAM), Eréndira Martínez (IF of UNAM) and Iván Puente-Lee (Faculty of Chemistry of UNAM) for technical assistance with FTIR, TGA measurements, and TEM imaging, respectively.

Keywords: carbon nanotubes, functionalization, gas-phase, metal(II) phthalocyanines

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Authors: Hannah R. Devens, Phillip L. Davidson, Dione Deaker, Kathryn E. Smith, Gregory A. Wray, Maria Byrne

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Marine invertebrate species with calcifying larvae are especially vulnerable to ocean acidification (OA) caused by rising atmospheric CO₂ levels. Acidic conditions can delay development, suppress metabolism, and decrease the availability of carbonate ions in the ocean environment for skeletogenesis. These stresses often result in increased larval mortality, which may lead to significant ecological consequences including alterations to the larval settlement, population distribution, and genetic connectivity. Importantly, many of these physiological and developmental effects are caused by genetic and molecular level changes. Although many studies have examined the effect of near-future oceanic pH levels on gene expression in marine invertebrates, little is known about the impact of OA on gene expression in a developmental context. Here, we performed mRNA-sequencing to investigate the impact of environmental acidity on gene expression across three developmental stages in the sea urchin Heliocidaris erythrogramma. We collected RNA from gastrula, early larva, and 1-day post-metamorphic juvenile sea urchins cultured at present-day and predicted future oceanic pH levels (pH 8.1 and 7.7, respectively). We assembled an annotated reference transcriptome encompassing development from egg to ten days post-metamorphosis by combining these data with datasets from two previous developmental transcriptomic studies of H. erythrogramma. Differential gene expression and time course analyses between pH conditions revealed significant alterations to developmental transcription that are potentially associated with pH stress. Consistent with previous investigations, genes involved in biomineralization and ion transport were significantly upregulated under acidic conditions. Differences in gene expression between the two pH conditions became more pronounced post-metamorphosis, suggesting a development-dependent effect of OA on gene expression. Furthermore, many differences in gene expression later in development appeared to be a result of broad downregulation at pH 7.7: of 539 genes differentially expressed at the juvenile stage, 519 of these were lower in the acidic condition. Time course comparisons between pH 8.1 and 7.7 samples also demonstrated over 500 genes were more lowly expressed in pH 7.7 samples throughout development. Of the genes exhibiting stage-dependent expression level changes, over 15% of these diverged from the expected temporal pattern of expression in the acidic condition. Through these analyses, we identify novel candidate genes involved in development, metabolism, and transcriptional regulation that are possibly affected by pH stress. Our results demonstrate that pH stress significantly alters gene expression dynamics throughout development. A large number of genes differentially expressed between pH conditions in juveniles relative to earlier stages may be attributed to the effects of acidity on transcriptional regulation, as a greater proportion of mRNA at this later stage has been nascent transcribed rather than maternally loaded. Also, the overall downregulation of many genes in the acidic condition suggests that OA-induced developmental delay manifests as suppressed mRNA expression, possibly from lower transcription rates or increased mRNA degradation in the acidic environment. Further studies will be necessary to determine in greater detail the extent of OA effects on early developing marine invertebrates.

Keywords: development, gene expression, ocean acidification, RNA-sequencing, sea urchins

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Authors: Alexandra Cheira

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Cultural appropriation has been theorised as a form of colonialism in which members of a dominant culture reduce cultural elements that are deeply meaningful to a minority culture to the category of the “exotic other” since they do not experience the oppression and discriminations faced by members of the minority culture. Yet, in the particular case of literature, writers such as Lionel Shriver and Bernardine Evaristo have argued that authors from a cultural majority have a right to write in the voice of someone from a cultural minority, hence attacking the idea that this is a form of cultural appropriation. By definition, Shriver and Evaristo claim, writers are supposed to write beyond their own culture, gender, class, and/ or race. In this light, this paper discusses the limits of cultural appropriation vis-à-vis the ethics of narrative empathy by addressing the mixed critical reception of Kathryn Stockett’s The Help (2009) and Jeanine Cummins’s American Dirt (2020). In fact, both novels were acclaimed as global eye-openers regarding the struggles of respectively South American migrants and African American maids. At the same time, both novelists have been accused of cultural appropriation by telling a story that is not theirs to tell, given the fact that they are white women telling these stories in what critics have argued is really an American voice telling a story to American readers.These claims will be investigated within the framework of Edward Said’s foundational examination of Orientalism in the field of postcolonial studies as a Western style for authoritatively restructuring the Orient. This means that Orientalist stereotypes regarding Eastern cultures have implicitly validated colonial and imperial pursuits, in the specific context of literary representations of African American and Mexican cultures by white writers. At the same time, the conflicted reception of American Dirt and The Help will be examined within the critical framework of narrative empathy as theorised by Suzanne Keen. Hence, there will be a particular focus on the way a reader’s heated perception that the author’s perspective is purely dishonest can result from a friction between an author’s intention and a reader’s experience of narrative empathy, while a shared sense of empathy between authors and readers can be a rousing momentum to move beyond literary response to social action.Finally, in order to assess that “the key question should not be who can write about whom, but how the writer tells the story”, the recent controversy surrounding Dutch author Marieke Lucas Rijneveld’s decision to resign the translation of American poet Amanda Gorman’s work into Dutch will be duly investigated. In fact, Rijneveld stepped out after journalist and activist Janice Deul criticised Dutch publisher Meulenhoff for choosing a translator who was not also Black, despite the fact that 22-year-old Gorman had selected the 29-year-old Rijneveld herself, as a fellow young writer who had likewise come to fame early on in life. In this light, the critical argument that the controversial reception of The Help reveals as much about US race relations in the early twenty-first century as about the complex literary transactions between individual readers and the novel itself will also be discussed in the extended context of American Dirt and white author Marieke Rijneveld’s withdrawal from the projected translation of Black poet Amanda Gorman.

Keywords: cultural appropriation, cultural stereotypes, narrative empathy, race relations

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Authors: Geraldine Macdonald, Oliver Perra, Nina O’Neill, Laura Neeson, Kathryn Higgins

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Background: Despite improvements in recent years, almost one in six children in Northern Ireland (NI) leaves primary school without achieving the expected level in English and Maths. By early adolescence, this ratio is one in five. In 2010-11, around 9000 pupils in NI had failed to achieve the required standard in literacy and numeracy by the time they left full-time education. This paper reports the findings of an experimental evaluation of a programmed designed to improve educational outcomes of a cohort of children starting primary school in areas of high social disadvantage in Northern Ireland. The intervention: ‘Ready to Learn’ comprised two key components: a literacy-rich After School programme (one hour after school, three days per week), and a range of activities and support to promote the engagement of parents with their children’s learning, in school and at home. The intervention was delivered between September 2010 and August 2013. Study aims and objectives: The primary aim was to assess whether, and to what extent, ‘Ready to Learn’ improved the literacy of socially disadvantaged children entering primary schools compared with children in schools without access to the programme. Secondary aims included assessing the programme’s impact on children’s social, emotional and behavioural regulation, and parents’ engagement with their children’s learning. In total, 505 children (almost all) participated in the baseline assessment for the study, with good retention over seven sweeps of data collection. Study design: The intervention was evaluated by means of a cluster randomized trial, with schools as the unit of randomization and analysis. It included a qualitative component designed to examine process and implementation, and to explore the concept of parental engagement. Sixteen schools participated, with nine randomized to the experimental group. As well as outcome data relating to children, 134 semi-structured interviews were conducted with parents over the three years of the study, together with 88 interviews with school staff. Results: Given the children’s ages, not all measures used were direct measures of reading. Findings point to a positive impact of “Ready to Learn” on children’s reading achievement (comprehension and fluency), as assessed by the York Assessment of Reading Comprehension (YARC) and decoding, assessed using the Word Recognition and Phonic Skills (WRaPS3). Effects were not large, but evidence suggests that it is unusual for an after school programme to clearly to demonstrate effects on reading skills. No differences were found on three other measures of literacy-related skills: British Picture Vocabulary Scale (BPVS-II), Naming Speed and Non-word Reading Tests from the Phonological Assessment Battery (PhAB) or Concepts about Print (CAP) – the last due to an age-related ceiling effect). No differences were found between the two groups on measures of social, emotional and behavioural regulation, and due to low levels of participation, it was not possible directly to assess the contribution of the parent component to children’s outcomes. The qualitative data highlighted conflicting concepts of engagement between parents and school staff. Ready to Learn is a promising intervention that merits further support and evaluation.

Keywords: after-school, education, literacy, parental engagement

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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