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Abstract Golden‐winged Warblers (Vermivora chrysoptera) have become rare across much of their historic breeding range and response to conservation efforts is variable. Evidence from several recent studies suggests that breeding output is a primary driver explaining responses to conservation and it is hypothesized that differences in food availability may be driving breeding output disparity between two subpopulations of the warbler's Appalachian breeding range. Herein, we studied two subpopulations: central Pennsylvania (“central subpopulation”), where breeding productivity is relatively low, and eastern Pennsylvania (“eastern subpopulation”), where breeding productivity is relatively high. To test the food‐availability hypothesis in this system, we measured density of caterpillars, plasma lipid metabolites (triglycerides [TRIG; fat deposition] and glycerol [GLYC; fat breakdown]), body mass of adults males, and acquired body mass data for fledglings at 38 sites managed for nesting habitat. Consistent with our prediction, leaf‐roller caterpillar density, the group upon which Golden‐winged Warblers specialize, was 45× lower in the central subpopulation than the eastern subpopulation. TRIG concentrations were highest within the eastern subpopulation during breeding grounds arrival. The change in TRIG concentrations from the breeding‐grounds‐arrival stage to the nestling‐rearing stage was subpopulation dependent: TRIG decreased in the eastern subpopulation and was constant in the central subpopulation, resulting in similar concentrations during the nestling‐rearing stage. Furthermore, GLYC concentrations were higher in the eastern subpopulation, which suggests greater energy demands in this region. Despite this, adult male warblers in the eastern subpopulation maintained a higher average body mass. Finally, fledgling body mass was 16% greater in the eastern subpopulation than the central subpopulation before and after fledging. Collectively, our results suggest that poor breeding success of Golden‐winged Warblers in the central subpopulation could be driven by lower availability of primary prey during the breeding season (leaf‐roller caterpillars), and this, in turn, limits their response to conservation efforts.

This article has been created following a process of collaborative reflective dialogue and writing between members of the Kildare and Wicklow Education and Training Board Community Education Team. We reflected on the experience of providing community education during the COVID-19 pandemic and mapping the next steps as we navigated living with COVID-19. We explored the ways we supported and upskilled learners, tutors, and each other as a team, all while continuing to navigate our way forward in the reality of living with COVID-19 and the implications it might have for the future of community education.

This paper investigates, using a case study methodology, the impact of formative video feedback on the educational experiences of early childhood and primary pre-service teachers (PST) completing a pedagogically focused mathematics education unit in a fully online mode. Given the trend over the past 10 years towards the delivery of university mathematics education courses online, this research is important. It is particularly timely given the current world health crisis, where universities are hurriedly rolling out online courses. We argue, based on the findings of this initial pilot, that the use of regular, formative video feedback has a positive effect on PST learning, and on the way PSTs perceive and engage with the feedback provided in video form, and on the affective connection this platform provides between the PST and the lecturer. We suggest that these themes have the potential to positively impact on PSTs' knowledge of content and pedagogy in the context of university mathematics education.

ObjectiveReports of efficacy, effectiveness and harms of COVID-19 vaccines have not used key indicators from evidence-based medicine (EBM) that can inform policies about vaccine distribution. This study aims to clarify EBM indicators that consider baseline risks when assessing vaccines' benefits versus harms: absolute risk reduction (ARR) and number needed to be vaccinated (NNV), versus absolute risk of the intervention (ARI) and number needed to harm (NNH).MethodsWe used a multimethod approach, including a scoping review of the literature; calculation of risk reductions and harms from data concerning five major vaccines; analysis of risk reductions in population subgroups with varying baseline risks; and comparisons with prior vaccines.FindingsThe scoping review showed few reports regarding ARR, NNV, ARI and NNH; comparisons of benefits versus harms using these EBM methods; or analyses of varying baseline risks. Calculated ARRs for symptomatic infection and hospitalisation were approximately 1% and 0.1%, respectively, as compared with relative risk reduction of 50%-95% and 58%-100%. NNV to prevent one symptomatic infection and one hospitalisation was in the range of 80-500 and 500-4000. Based on available data, ARI and NNH as measures of harm were difficult to calculate, and the balance between benefits and harms using EBM measures remained uncertain. The effectiveness of COVID-19 vaccines as measured by ARR and NNV was substantially higher in population subgroups with high versus low baseline risks.ConclusionsPriorities for vaccine distribution should target subpopulations with higher baseline risks. Similar analyses using ARR/NNV and ARI/NNH would strengthen evaluations of vaccines' benefits versus harms. An EBM perspective on vaccine distribution that emphasises baseline risks becomes especially important as the world's population continues to face major barriers to vaccine access-sometimes termed 'vaccine apartheid'.

Greenspace may benefit sleep by enhancing physical activity, reducing stress or air pollution exposure. Studies on greenspace and childrens sleep are limited, and most use satellite-derived measures that do not capture ground-level exposures that may be important for sleep. We examined associations of street view imagery (SVI)-based greenspace with sleep in Project Viva, a Massachusetts pre-birth cohort. We used deep learning algorithms to derive novel metrics of greenspace (e.g., %trees, %grass) from SVI within 250m of participant residential addresses during 2007-2010 (mid-childhood, mean age 7.9 years) and 2012-2016 (early adolescence, 13.2y) (N = 533). In early adolescence, participants completed >5 days of wrist actigraphy. Sleep duration, efficiency, and time awake after sleep onset (WASO) were derived from actigraph data. We used linear regression to examine cross-sectional and prospective associations of mid-childhood and early adolescence greenspace exposure with early adolescence sleep, adjusting for confounders. We compared associations with satellite-based greenspace (Normalized Difference Vegetation Index, NDVI). In unadjusted models, mid-childhood SVI-based total greenspace and %trees (per interquartile range) were associated with longer sleep duration at early adolescence (9.4 min/day; 95%CI:3.2,15.7; 8.1; 95%CI:1.7,14.6 respectively). However, in fully adjusted models, only the association between %grass at mid-childhood and WASO was observed (4.1; 95%CI:0.2,7.9). No associations were observed between greenspace and sleep efficiency, nor in cross-sectional early adolescence models. The association between greenspace and sleep differed by racial and socioeconomic subgroups. For example, among Black participants, higher NDVI was associated with better sleep, in neighborhoods with low socio-economic status (SES), higher %grass was associated with worse sleep, and in neighborhoods with high SES, higher total greenspace and %grass were associated with better sleep time. SVI metrics may have the potential to identify specific features of greenspace that affect sleep.

Decrypting the rearrangements that drive mammalian chromosome evolution is critical to understanding the molecular bases of speciation, adaptation, and disease susceptibility. Using 8 scaffolded and 26 chromosome-scale genome assemblies representing 23/26 mammal orders, we computationally reconstructed ancestral karyotypes and syntenic relationships at 16 nodes along the mammalian phylogeny. Three different reference genomes (human, sloth, and cattle) representing phylogenetically distinct mammalian superorders were used to assess reference bias in the reconstructed ancestral karyotypes and to expand the number of clades with reconstructed genomes. The mammalian ancestor likely had 19 pairs of autosomes, with nine of the smallest chromosomes shared with the common ancestor of all amniotes (three still conserved in extant mammals), demonstrating a striking conservation of synteny for ∼320 My of vertebrate evolution. The numbers and types of chromosome rearrangements were classified for transitions between the ancestral mammalian karyotype, descendent ancestors, and extant species. For example, 94 inversions, 16 fissions, and 14 fusions that occurred over 53 My differentiated the therian from the descendent eutherian ancestor. The highest breakpoint rate was observed between the mammalian and therian ancestors (3.9 breakpoints/My). Reconstructed mammalian ancestor chromosomes were found to have distinct evolutionary histories reflected in their rates and types of rearrangements. The distributions of genes, repetitive elements, topologically associating domains, and actively transcribed regions in multispecies homologous synteny blocks and evolutionary breakpoint regions indicate that purifying selection acted over millions of years of vertebrate evolution to maintain syntenic relationships of developmentally important genes and regulatory landscapes of gene-dense chromosomes.

Abstract Background There is growing evidence that Technology Assisted Sexual Abuse (TASA) represents a serious problem for large numbers of children. To date, there are very few evidence-based interventions available to young people (YP) after they have been exposed to this form of abuse, and access to support services remains a challenge. Digital tools such as smartphones have the potential to increase access to mental health support and may provide an opportunity for YP to both manage their distress and reduce the possibility of further victimization. The current study explores the acceptability of a digital health intervention (DHI; the i-Minds app) which is a theory-driven, co-produced, mentalization-based DHI designed for YP aged 12–18 who have experienced TASA. Methods Semi-structured interviews were conducted with 15 YP recruited through Child and Adolescent Mental Health Services, a Sexual Assault Referral Centre and an e-therapy provider who had access to the i-Minds app as part of a feasibility clinical trial. Interviews focused on the acceptability and usability of i-Minds and were coded to themes based on the Acceptability of Healthcare Interventions framework. Results All participants found the i-Minds app acceptable. Many aspects of the app were seen as enjoyable and useful in helping YP understand their abuse, manage feelings, and change behavior. The app was seen as usable and easy to navigate, but for some participants the level of text was problematic and aspects of the content was, at times, emotionally distressing at times. Conclusions The i-Minds app is useful in the management of TASA and helping change some risk-related vulnerabilities. The app was designed, developed and evaluated with YP who had experienced TASA and this may account for the high levels of acceptability seen. Trial registration The trial was registered on the ISRCTN registry on the 12/04/2022 as i-Minds: a digital intervention for young people exposed to online sexual abuse (ISRCTN43130832).

Abstract Exposure to both oxidative and shear stress, a condition that the red blood cell (RBC) continuously experiences in the circulation in vivo can be mimicked in a Couette type viscometer and monitored by ektacytometry. RBCs maintain their deformation and orientation under shear stress and oxidative stress until a threshold is reached at which these conditions appear to overwhelm the elaborate and complex pathways that maintain a proper redox environment in the cell. Oxidative stress under shear alters the ability of the cell to deform, changes cell morphology, its orientation in the shear stress field, and appears to alter intracellular and membrane characteristics. The application of the RoxyScan technology allows the comparison of oxidant effects and the role of antioxidant systems. This provides the opportunity to study the ability of RBC to deal with oxidative stress in various conditions, including RBC disorders such as sickle cell disease (SCD).

Abstract Acute myeloid leukemia (AML) is a highly aggressive hematologic cancer with poor survival across a broad range of molecular subtypes. Development of efficacious and well-tolerable therapies encompassing the range of mutations that can arise in AML remains an unmet need. The bromo- and extra-terminal domain (BET) family of proteins represents an attractive therapeutic target in AML due to their crucial roles in many cellular functions, regardless of any specific mutation. Many BET inhibitors (BETi) are currently in pre-clinical and early clinical development, but acquisition of resistance continues to remain an obstacle for the drug class. Novel methods to circumvent this development of resistance could be instrumental for the future use of BET inhibitors in AML, both as monotherapy and in combination. To date, many investigations into possible drug combinations of BETi with CDK inhibitors have focused on CDK9, which has a known physical and functional interaction with the BET protein BRD4. Therefore, we wished to investigate possible synergy and additive effects between inhibitors of these targets in AML. Here, we describe combination therapy with the multi-CDK inhibitor dinaciclib and the BETi PLX51107 in pre-clinical models of AML. Dinaciclib and PLX51107 demonstrate additive effects in AML cell lines, primary AML samples, and in vivo. Further, we demonstrate novel activity of dinaciclib through inhibition of the canonical/β-catenin dependent Wnt signaling pathway, a known resistance mechanism to BETi in AML. We show dinaciclib inhibits Wnt signaling at multiple levels, including downregulation of β-catenin, the Wnt co-receptor LRP6, as well as many Wnt pathway components and targets. Moreover, dinaciclib sensitivity remains unaffected in a setting of BET resistance, demonstrating similar inhibitory effects on Wnt signaling when compared to BET-sensitive cells. Ultimately, our results demonstrate rationale for combination CDKi and BETi in AML. In addition, our novel finding of Wnt signaling inhibition could have potential implications in other cancers where Wnt signaling is dysregulated and demonstrates one possible approach to circumvent development of BET resistance in AML.

Lipin-1 is a member of the evolutionarily conserved family of proteins and is expressed predominantly in adipose tissue and skeletal muscle. On the one hand, lipin-1 is an enzyme that catalyzes the dephosphorylation of phosphatidic acid to diacylglycerol (DAG) and thus participates in the metabolic pathways of biosynthesis of storage lipids in the cell, membrane phospholipids, and intracellular signaling molecules. On the other hand, lipin-1 is able to be transported from the cytoplasm to the nucleus and is a coactivator of lipid metabolism gene transcription. It was shown, using the analysis of single nucleotide polymorphism (SNP) associations, that the lipin-1 coding gene (LPIN1) is a promising candidate gene for milk production traits in Holstein and Brown Swiss cows. However, it is unclear how much of its effect depends on the breed. The Yaroslavl dairy cattle breed was created in the 18–19 centuries in Russia by breeding northern Great Russian cattle, which were short and poor productive, but well adapted to local climatic conditions and bad food base. It was shown by whole genome genotyping and sequencing that the Yaroslavl breed has unique genetics compared to Russian and other cattle breeds. The aim of the study was to assess the frequency of alleles and genotypes of three SNPs in the LPIN1 gene and to study the association of these SNPs with milk production traits in Yaroslavl cows. Blood samples from 142 cows of the Yaroslavl breed were obtained from two farms in the Yaroslavl region. Genotyping of SNPs was carried out by polymerase chain reaction-restriction fragment length polymorphism method. Associations of SNPs with 305-day milk yield, fat yield, fat percentages, protein yield, and protein percentages were studied from the first to the fourth lactation. Statistical tests were carried out using a mixed linear model, taking into account the relationship between individuals. We identified three SNPs – rs110871255, rs207681322 and rs109039955 with a frequency of a rare allele of 0.042–0.261 in Yaroslavl cows. SNP rs110871255 was associated with fat yield during the third and fourth lactations. SNP rs207681322 was associated with milk yield for the second, third and fourth lactations, as well as protein yield for the third lactation. Thus, we identified significant associations of SNPs rs207681322 and rs110871255 in the LPIN1 gene with a number of milk production traits during several lactations in Yaroslavl cows.

Abstract To efficiently detect aquatic invasive species early in an invasion when control may still be possible, predictions about which locations are likeliest to be occupied are needed at fine scales but are rarely available. Occupancy modeling could provide such predictions given data of sufficient quality and quantity. We assembled a data set for the macroalga starry stonewort (Nitellopsis obtusa) across Minnesota and Wisconsin, USA, where it is a new and high-priority invader. We used these data to construct a multi-season, single-species spatial occupancy model that included biotic, abiotic, and movement-related predictors. Distance to the nearest access was an important occurrence predictor, highlighting the likely role boats play in spreading starry stonewort. Fetch and water depth also predicted occupancy. We estimated an average detection probability of 63% at sites with mean non-N. obtusa plant cover, declining to ~ 38% at sites with abundant plant cover, especially that of other Characeae. We recommend that surveyors preferentially search for starry stonewort in areas of shallow depth and high fetch close to boat accesses. We also recommend searching during late summer/early fall when detection is likelier. This study illustrates the utility of fine-scale occupancy modeling for predicting the locations of nascent populations of difficult-to-detect species.

Abstract Background Despite concerted efforts by policy developers, health professionals and lay groups, breastfeeding rates in Ireland remain one of the lowest in world, with 63.6% of mothers initiating breastfeeding at birth, dropping to 37.6% of mothers breastfeeding exclusively on hospital discharge. Nipple trauma and difficulties with baby latching are major contributors to the introduction of formula and discontinuation of breastfeeding. Research shows laid-back breastfeeding (LBBF) significantly reduces breast problems such as sore and cracked nipples, engorgement, and mastitis as well as facilitating a better latch. Although the benefits of LBBF are well documented, this position does not seem to be routinely suggested to mothers as an option when establishing breastfeeding. This study aims to determine midwives’ and student midwives’ knowledge, attitudes, and practices of using laid-back breastfeeding in Ireland. Method A cross-sectional descriptive survey distributed to midwives and student midwives in three maternity hospitals in Ireland and two online midwifery groups based in the Republic of Ireland, during June, July, and August 2021. Results Two hundred and fifty-three valid responses were received from nine maternity units. Most participants (81.4%) were aware of laid-back breastfeeding. However, only 6.8% of respondents cited it as the position they most frequently use. Over one-third (38.34%) had never used this position with mothers. Those more likely to suggest LBBF had personal experience of it, were lactation consultants or working towards qualification, or had participated in specific education about LBBF. Barriers included lack of education, confidence, time, and experience. Further issues related to work culture, a tendency to continue using more familiar positions and concerns about mothers’ anatomy and mothers’ unfamiliarity with LBBF. Conclusion Although there was a high level of awareness of laid-back breastfeeding among midwives and student midwives, there are challenges preventing its use in practice. Education specifically related to using LBBF in practice is required to overcome the barriers identified. A greater understanding of mothers’ and babies’ intrinsic feeding capacities may give midwives more confidence to recommend this method as a first choice, potentially leading to more successful breastfeeding establishment and maintenance.

Abstract Background The experience of Wish to Die is common in patients living with Advanced Disease. It has been studied worldwide and qualitative studies have contributed to the understanding of the complexity of the phenomenon of the WTD but a deeper understanding on the individual’s views is still needed. The objective of this study was to identify common characteristics of the experience of wish to die in advanced disease. Methods A phenomenological study was carried out with multicenter participation of patients with advanced disease who had expressed their wish to die to health professionals. Semi-structured interviews were employed to obtain an in-depth perspective of each patient’s lived experience. A phenomenological analysis of the data collected was performed to describe and explore the characteristic aspects of the phenomenon under study. Results Fourteen patients with advanced disease were interviewed. Most of them had cancer. In the analysis of the patients’ accounts of their experiences, three common characteristics were identified: a) experiencing a state of transience; b) the attempt to reconnect with oneself; and c) additional disease-related aspects that influence the wish to die. Patients expressed the need for a safe space to address the wish to die and the importance of receiving care that considers both ‘being’ and ‘doing’. Conclusions Patients with advanced disease and wish to die experience a state of transience where the patient lives and ephemeral state of existence. Interventions focused on reinforcing the intrinsic value of the individual emerge as essential components of a compassionate accompaniment of those facing the wish to die.

Convolutional Neural Networks (CNNs) have been utilised in many image and video processing applications. The convolution operator, also known as a spatial filter, is usually a linear operation, but this linearity compromises essential features and details inherent in the non-linearity present in many applications. However, due to its slow processing, the use of a nonlinear spatial filter is a significant bottleneck in many software applications. Further, due to their complexity, they are difficult to accelerate in FPGA or VLSI architectures. This paper presents novel FPGA implementations of linear and nonlinear spatial filters. More specifically, the arithmetic computations are carried out in custom floating-point, enabling a tradeoff of precision and hardware compactness, reducing algorithm development time. Further, we show that it is possible to process video at a resolution of 1080p with a frame rate of 60 frames per second, using a low-cost FPGA board. Finally, we show that using a domain-specific language will allow the rapid prototyping of image processing algorithms in custom floating-point arithmetic, allowing non-experts to quickly develop real-time video processing applications.

Objective: Metastatic spinal tumors represent a rare but concerning complication of primary thyroid carcinoma. We identified demographics, metastatic features, outcomes, and treatment strategies for these tumors in our institutional cohort. Materials and Methods: We retrospectively reviewed patients surgically treated for spinal metastases of primary thyroid carcinoma. Demographics, tumor characteristics, and treatment modalities were collected. The functional outcomes were quantified using Nurik, Modified Rankin, and Karnofsky Scores. Results: Twelve patients were identified who underwent 17 surgeries for resection of spinal metastases. The primary thyroid tumor pathologies included papillary (4/12), follicular (6/12), and Hurthle cell (2/12) subtypes. The average number of spinal metastases was 2.5. Of the primary tumor subtypes, follicular tumors averaged 2.8 metastases at the highest and Hurthle cell tumors averaged 2.0 spinal metastases at the lowest. Five patients (41.7%) underwent preoperative embolization for their spinal metastases. Seven patients (58.3%) received postoperative radiation. There was no significant difference in progression-free survival between patients receiving surgery with adjuvant radiation and surgery alone (P = 0.0773). Five patients (41.7%) experienced postoperative complications. Two patients (16.7%) succumbed to disease progression and two patients (16.7%) experienced tumor recurrence following resection. Postsurgical mean Nurik scores decreased 0.54 points, mean Modified Rankin scores decreased 0.48 points, and mean Karnofsky scores increased 4.8 points. Conclusion: Surgery presents as an important treatment modality in the management of spinal metastases from thyroid cancer. Further work is needed to understand the predictive factors for survival and outcomes following treatment.