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The closure of school buildings due to COVID-19 created a challenge for parents and teachers supporting children's remote learning. This paper presents findings of a study that explored whether parents of children with special educational needs and disabilities (SEND) experienced an unusually challenging period and what obstacles they faced. An online survey was sent to parents during the first (March-June 2020) and second (January-March 2021) lockdowns in England: a total of 141 voluntary participants responded. Thematic data analysis identified three significant themes: Infrastructure (Quality and efficacy of resources; Access to school's virtual learning environment); Impact on parent (Perceived lack of ability or understanding; Relationships; Time; Mental health); Impact on child (Reduced stress and anxiety; Need for routine). Recommendations for schools include collaborating with parents to ensure children with SEND achieve greater equality and inclusivity in educational provision, by developing blended models for in-school and remote learning.

Participatory Research (PR), which places participants at the foreground, is an evolving field spanning several disciplines. This article critiques conceptual tensions surrounding the notion of participation itself and how PR tenets can be engaged with children (under 18). We propose an innovative heuristic framework to be used flexibly by the adult facilitator to aid decision-making when seeking balance between intervention and giving young participants room for expression. It serves as an aide memoire to facilitate cognisance of issues of control and directiveness that could potentially diminish children's voices, containing more explicit emphasis on the necessary movement between modes of adult facilitator involvement than existing PR models. Our proposed modes, 'organic and unbridled', 'organic yet enabling', 'enabled and shaping', are fleshed out and illustrated with reference to our own PR projects. We relate these modes to easily-called-to-mind notions, inspired by the metaphor of the choreography of dance: 'stepping-in'; 'stepping-out'; 'stepping-on-toes'.

Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. The Third International Conference of T21RS, held June 6-9, 2019, in Barcelona, Spain, brought together 429 scientists, families, and industry representatives to share the latest discoveries on underlying cellular and molecular mechanisms of T21, define cognitive and behavioral challenges and better understand comorbidities associated with Down syndrome, including Alzheimer's disease and leukemia. Presentation of cutting-edge results in neuroscience, neurology, model systems, psychology, cancer, biomarkers and molecular and phar-ma-cological therapeutic approaches demonstrate the compelling interest and continuing advancement in all aspects of understanding and ameliorating conditions associated with T21.

The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity. [ABSTRACT FROM AUTHOR]

This paper presents findings from a research study, which sought to illuminate the perceived notions of inclusion of four to five year old children in pedagogical activities, in the early years classes of two schools in the North of England. It employed a qualitative methodology to gather extensive data with forty children over a six-week period in each school. This included collecting fieldnotes; undertaking observations of children in pedagogical activities; and conducting group and individual interviews. Central to the research aim was the use of participative tools to engage with children's voices; these included photographs and drawings. Children's perceived notions of inclusion resonated with two dimensions: belonging and relationships (with practitioner and/or child) and democratic pedagogies. The findings advance the conceptualisation of the notion of inclusion and bring to the fore the voices of a young group of children that has not been studied before. Engaging with children in meaningful ways can enable practitioners to better understand young children's perceived, multi-faceted notions of inclusion as they experience it within pedagogical activities.

This paper presents a unique perspective into challenges faced by kindergarten teachers in engaging children in Science, Technology, Engineering, Arts and Mathematics (STEAM) education in Vietnam. It reports on teachers' perspectives of an adaptation of immersive learning experiences (ILE), to develop understanding of pedagogical approaches to STEAM education in real-world contexts. The study adopted a qualitative and interpretivist methodology, engaging 105 teachers in informal and collaborative activities. Their perceptions were gathered via participatory tools; photographic images recorded how they engaged with ILE. Data analysis occurred using de Freitas's four-dimensional framework. The study responds to evidence that STEAM education is not prevalent in Vietnamese schools, and reflects on the top-down siloed approach ubiquitous within its early childhood education (ECE) sector. Findings indicate the necessity for a prolonged period of training using ILE that enables teachers' development of pedagogical approaches to STEAM education. Significantly, it provides new insight for a variety of stakeholders (including teacher trainers and policy makers) into the under-researched field of Vietnamese teachers' pedagogical approaches in ECE, and extends its findings to countries adopting more formalised approaches to education.

Whilst the importance of engaging with children's voices is now more widely recognized, there is still a dearth of representation of younger children's voices specifically. Visual methodological tools, such as photo-elicitation and photo-voice are used in research; however, there remains a lack of clarity about what they mean, how they are used, and whether they are effective in providing valuable insights into younger children's everyday worlds. This paper draws on the findings of two research projects utilizing the tools to engage with the voices of 56 children aged four to five years, in the classes of three schools in the UK. It identifies the differences between photo-elicitation and photo-voice and appraises their advantages and limitations when engaging with child voice. It explores whether through careful, critical and conscientious application, these tools might advance understandings of younger children's perceptions of matters affecting them. The definition of photo-elicitation is the insertion of a photograph by the researcher into a research interview to evoke information, feelings, and memories due to the photograph's particular form of representation; photo-voice is defined as a technique that enables people to record their own photographs.

Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56+CD3- population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56+CD3- cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells.

In the digital era, we witness the increasing use of artificial intelligence (AI) to solve problems, while improving productivity and efficiency. Yet, inevitably costs are involved with delegating power to algorithmically based systems, some of whose workings are opaque and unobservable and thus termed the 'black box'. Central to understanding the 'black box' is to acknowledge that the algorithm is not mendaciously undertaking this action; it is simply using the recombination afforded to scaled computable machine learning algorithms. But an algorithm with arbitrary precision can easily reconstruct those characteristics and make life-changing decisions, particularly in financial services (credit scoring, risk assessment, etc.), and it could be difficult to reconstruct, if this was done in a fair manner reflecting the values of society. If we permit AI to make life-changing decisions, what are the opportunity costs, data trade-offs, and implications for social, economic, technical, legal, and environmental systems? We find that over 160 ethical AI principles exist, advocating organisations to act responsibly to avoid causing digital societal harms. This maelstrom of guidance, none of which is compulsory, serves to confuse, as opposed to guide. We need to think carefully about how we implement these algorithms, the delegation of decisions and data usage, in the absence of human oversight and AI governance. The paper seeks to harmonise and align approaches, illustrating the opportunities and threats of AI, while raising awareness of Corporate Digital Responsibility (CDR) as a potential collaborative mechanism to demystify governance complexity and to establish an equitable digital society., Author(s): Karen Elliott [sup.1] , Rob Price [sup.2] , Patricia Shaw [sup.3] , Tasos Spiliotopoulos [sup.1] , Magdalene Ng [sup.1] , Kovila Coopamootoo [sup.1] , Aad van Moorsel [sup.1] Author [...]

Minimally Invasive Karyotyping (MINK) was communicated in 2009 as a novel method for the non-invasive detection of fetal copy number anomalies in maternal plasma DNA. The original manuscript illustrated the potential of MINK using a model system in which fragmented genomic DNA obtained from a trisomy 21 male individual was mixed with that of his karyotypically normal mother at dilutions representing fetal fractions found in maternal plasma. Although it has been previously shown that MINK is able to non-invasively detect fetal microdeletions, its utility for aneuploidy detection in maternal plasma has not previously been demonstrated. The current study illustrates the ability of MINK to detect common aneuploidy in early gestation, compares its performance to other published third party methods (and related software packages) for prenatal aneuploidy detection and evaluates the performance of these methods across a range of sequencing read inputs. Plasma samples were obtained from 416 pregnant women between gestational weeks 8.1 and 34.4. Shotgun DNA sequencing was performed and data analyzed using MINK RAPIDR and WISECONDOR. MINK performed with greater accuracy than RAPIDR and WISECONDOR, correctly identifying 60 out of 61 true trisomy cases, and reporting only one false positive in 355 normal pregnancies. Significantly, MINK achieved accurate detection of trisomy 21 using just 2 million aligned input reads, whereas WISECONDOR required 6 million reads and RAPIDR did not achieve complete accuracy at any read input tested. In conclusion, we demonstrate that MINK provides an analysis pipeline for the detection of fetal aneuploidy in samples of maternal plasma DNA.

The paper seeks to extend the knowledge and understanding of how engaging with young children's voices in a meaningful way, can alter practitioners' pedagogical practice and thus create environments for learning that are more inclusive. It draws on the findings of a research study that explored practitioners' (teachers, nursery nurses and teaching assistants) views about engaging with young children's voices of perceived notions of inclusion in pedagogical activities in the early years classes of two schools in the North of England. It adopted a qualitative methodological approach that operates within constructivist and interpretivist paradigms. The study revealed that practitioners retain some resistance to responding to the voices of young children and that internal and external pressures influence their decision-making. Moreover, it signifies the necessity for greater emphasis on the importance of engaging with children's voices in the training of newly qualified teachers, and the ongoing professional development for all practitioners in early childhood education.

Background/objectiveThe non-invasive prenatal detection of fetal microdeletions becomes increasingly challenging as the size of the mutation decreases, with current practical lower limits in the range of a few megabases. Our goals were to explore the lower limits of microdeletion size detection via non-invasive prenatal tests using Minimally Invasive Karyotyping (MINK) and introduce/evaluate a novel statistical approach we recently developed called the GC Content Random Effect Model (GCREM).MethodsMaternal plasma was obtained from a pregnancy affected by a 4.2-Mb fetal microdeletion and three normal controls. Plasma DNA was subjected to capture an 8-Mb sequence spanning the breakpoint region and sequence. Data were analyzed with our published method, MINK, and a new method called GCREM.ResultsThe 8-Mb capture segment was divided into either 38 or 76 non-overlapping regions of 200 and 100 Kb, respectively. At 200 Kb resolution, using GCREM (but not MINK), we obtained significant adjusted p-values for all 20 regions overlapping the deleted sequence, and non-significant p-values for all 18 reference regions. At 100 Kb resolution, GCREM identified significant adjusted p-values for all but one 100-Kb region located inside the deleted region.ConclusionTargeted sequencing and GCREM analysis may enable cost effective detection of fetal microdeletions and microduplications at high resolution.

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.