Search Results (23)

Early mammalian embryos are highly sensitive to environmental, metabolic, hormonal, and genomic stress, yet embryo assessment during In Vitro Fertilization (IVF) relies largely on morphology and ploidy for embryo assessment, but these tests incompletely predict miscarriage. We present a transcriptomics based framework to classify and quantify lineage-specific stress in early embryos by benchmarking human preimplantation embryos against dose-, time-, and quality-dependent stress programs defined in Embryonic and placental Trophoblast Stem Cells (ESCs, TSCs) from the implanting blastocyst. Human embryos and stressed ESCs and TSCs are screened using transcriptomic markers from eleven biologically distinct stress Gene Ontology (GO) groups that define functional stress states and enable quantification of pathway presence and upregulation, pathway activity, and downstream outcomes. This framework determines whether the Integrated Stress Response (ISR), once initiated, resolves to enable the Developmentally Associated Stress Response (DASR). High-throughput screening (HTS) titrates stress to define increasingly risky yet biologically equivalent doses for levels of diminished stem cell growth across mechanistically diverse stressors. Then bulk RNA seq derives lineage specific transcriptomic markers putatively respond to common levels of diminished growth and that distinguish weak vs. strong stress and resolved vs. unresolved ISR. These stem cell transcriptomic signatures are applied to bulk RNA seq data from IVF embryos graded for morphology or adhesion, enabling quantitative inference of stress burden, lineage vulnerability, and developmental trajectory. Full article

Sexual dysfunction is a prevalent and often under-addressed concern among prostate cancer survivors, significantly affecting quality of life for patients and their partners. The True North Sexual Health and Rehabilitation eClinic (SHAReClinic) is a virtual, biopsychosocial intervention developed to improve access to sexual health support for prostate cancer survivors and their partners. This study used a qualitative descriptive design to examine barriers and facilitators influencing the integration of SHAReClinic into oncology care across nine Canadian health care centres. Semi-structured interviews were conducted with 17 knowledge users, including health care providers and institutional leaders. Data were analyzed using a hybrid deductive–inductive thematic approach guided by the Consolidated Framework for Implementation Research (CFIR) 2.0. Participants described SHAReClinic as a much-needed resource, particularly in the absence of standardized sexual health pathways in oncology care. The virtual format was seen as accessible and well suited to addressing sensitive topics. However, limited funding, lack of institutional support, and workflow integration challenges emerged as primary barriers to implementation. Findings offer practical, theory-informed guidance for integrating SHAReClinic into oncology care and highlight key considerations for developing sustainable and scalable survivorship care models. Full article

Although child-centred care is increasingly referred to within the nursing literature, a clear definition of child-centred care and clarity around the concept is yet to be achieved. The objectives of this review were to examine the following: (1) What constitutes the concept of child-centred care in healthcare? (2) How has the concept of child-centred care developed? (3) What is the applicability of child-centred care and what are its limitations? (4) How does the concept of child-centred care benefit and inform children’s healthcare? In total, 2984 papers were imported for screening, and, following the removal of duplicates and screening, 21 papers were included in the scoping review. The findings suggest that child-centred care is an emerging, ambiguous poorly defined concept; no clear consensus exists about what constitutes child-centred care. Although it seems antithetical to argue against child-centred care, little robust evidence was identified that demonstrates the impact and benefit of child-centred care. If child-centred care is to be a sustainable, convincing model to guide practice and compete with other models of care, it needs to establish robust evidence of its effectiveness, the impact on children and their families, as well as the wider impacts on the healthcare system. Full article

Introduction: Whether a combined anterior–posterior (AP) approach offers additional benefits over the posterior-only (P) approach in adult spinal deformity (ASD) surgery remains unknown. In a cohort of patients undergoing ASD surgery, we compared the combined AP vs. the P-only approach in: (1) preoperative/perioperative variables, (2) radiographic measurements, and (3) postoperative outcomes. Methods: A single-institution, retrospective cohort study was performed for patients undergoing ASD surgery from 2009 to 2021. Inclusion criteria were ≥5-level fusion, sagittal/coronal deformity, and 2-year follow-up. The primary exposure was the operative approach: a combined AP approach or P alone. Postoperative outcomes included mechanical complications, reoperation, and minimal clinically important difference (MCID), defined as 30% of patient-reported outcome measures (PROMs). Multivariable linear regression was controlled for age, BMI, and previous fusion. Results: Among 238 patients undergoing ASD surgery, 34 (14.3%) patients underwent the AP approach and 204 (85.7%) underwent the P-only approach. The AP group consisted mostly of anterior lumbar interbody fusion (ALIF) at L5/S1 (73.5%) and/or L4/L5 (38.0%). Preoperatively, the AP group had more previous fusions (64.7% vs. 28.9%, p < 0.001), higher pelvic tilt (PT) (29.6 ± 11.6° vs. 24.6 ± 11.4°, p = 0.037), higher T1 pelvic angle (T1PA) (31.8 ± 12.7° vs. 24.0 ± 13.9°, p = 0.003), less L1-S1 lordosis (−14.7 ± 28.4° vs. −24.3 ± 33.4°, p < 0.039), less L4-S1 lordosis (−25.4 ± 14.7° vs. 31.6 ± 15.5°, p = 0.042), and higher sagittal vertical axis (SVA) (102.6 ± 51.9 vs. 66.4 ± 71.2 mm, p = 0.005). Perioperatively, the AP approach had longer operative time (553.9 ± 177.4 vs. 397.4 ± 129.0 min, p < 0.001), more interbodies placed (100% vs. 17.6%, p < 0.001), and longer length of stay (8.4 ± 10.7 vs. 7.0 ± 9.6 days, p = 0.026). Radiographically, the AP group had more improvement in T1PA (13.4 ± 8.7° vs. 9.5 ± 8.6°, p = 0.005), L1-S1 lordosis (−14.3 ± 25.6° vs. −3.2 ± 20.2°, p < 0.001), L4-S1 lordosis (−4.7 ± 16.4° vs. 3.2 ± 13.7°, p = 0.008), and SVA (65.3 ± 44.8 vs. 44.8 ± 47.7 mm, p = 0.007). These outcomes remained statistically significant in the multivariable analysis controlling for age, BMI, and previous fusion. Postoperatively, no significant differences were found in mechanical complications, reoperations, or MCID of PROMs. Conclusions: Preoperatively, patients undergoing the combined anterior–posterior approach had higher PT, T1PA, and SVA and lower L1-S1 and L4-S1 lordosis than the posterior-only approach. Despite increased operative time and length of stay, the anterior–posterior approach provided greater sagittal correction without any difference in mechanical complications or PROMs. Full article

Recently, our in vitro study on the effects of plasma-activated simulated seawater (PASW) demonstrated its potential as a novel, alternative disinfectant in oyster depuration. In this current study, PASW’s physicochemical and antimicrobial properties were identified and its effects on oyster quality were observed. Simulated seawater (SS) activated by plasma for 10 min (PASW10) increased in temperature, oxidation reduction potential, and electrical conductivity with a decrease in those parameters after 1:1 dilution with SS (PASW10 (1:1)). The pH decreased immediately after plasma activation and subsequently increased after dilution. Nitrate and nitrite concentrations were higher in PASW10 (1:1) compared to PASW10 (3:1). No free available chlorine was detected in undiluted PASW10. Processing using SS and PASW10 (1:1) depuration and refrigeration of E. coli-bioaccumulated oysters was observed. Significantly higher reductions in total coliform and E. coli were noted for PASW10 (1:1) treated oyster samples after 24 h compared to refrigerated samples. No significant differences in values for condition index or biting force of oyster meats were observed for the processed samples after 24 h. Overall, the novel and environment-friendly PASW could be used as an alternative antimicrobial disinfectant in oyster depuration systems because it does not negatively affect an oyster’s viability or quality. Full article

Despite projected global rises in chicken consumption, growing environmental and welfare challenges threaten the future of commercial poultry production. Though some of these challenges, such as biosecurity, sourcing, pollution, and waste, have been thoroughly researched, the open-ended, complex, and interrelated nature of the sector means that it is difficult for poultry producers to know how to change. Design may offer a new way to analyse and reframe these challenges, to speculate on a range of different solutions for these complex systems of production. This paper reflects on the research-by-design methods applied to reimagine environmentally sustainable, high-welfare poultry housing futures. The paper is based on an eighteen-month long, multidisciplinary research project with a large U.K.-based poultry farming integrator, a poultry house ventilation and equipment supplier, and academic partners with expertise in research-by-design and bird welfare. After contextualising challenges faced by the poultry sector, the paper outlines a three-step, iterative approach within which design methods were applied, beginning with (1) a baseline analysis of farm inputs, outputs, actors, and networks, and then (2) a consolidation of themes and scenarios, leading to the development of (3) a compendium of ideas for the future of poultry farming. The Results section presents three design propositions, each imagining different futures by recreating the farm as a system of “closed-loop” flows, reframing the “chicken as client” and challenging current centralised models of production to connect consumers to food provenance and impact. These propositions function as vehicles to test design methods, such as designing for resource flows challenging actor hierarchies and hacking stakeholder networks. While some interesting ideas are presented, the paper highlights the complexity of the challenge and reflects on the value of design to reframe these challenges to collaboratively foster new perspectives and mindsets. Full article

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood–brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored. Full article

We updated the anthropogenic emissions inventory in NOAA’s operational Global Ensemble Forecast for Aerosols (GEFS-Aerosols) to improve the model’s prediction of aerosol optical depth (AOD). We used a methodology to quickly update the pivotal global anthropogenic sulfur dioxide (SO₂) emissions using a speciated AOD bias-scaling method. The AOD bias-scaling method is based on the latest model predictions compared to NASA’s Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA2). The model bias was subsequently applied to the CEDS 2019 SO₂ emissions for adjustment. The monthly mean GEFS-Aerosols AOD predictions were evaluated against a suite of satellite observations (e.g., MISR, VIIRS, and MODIS), ground-based AERONET observations, and the International Cooperative for Aerosol Prediction (ICAP) ensemble results. The results show that transitioning from CEDS 2014 to CEDS 2019 emissions data led to a significant improvement in the operational GEFS-Aerosols model performance, and applying the bias-scaled SO₂ emissions could further improve global AOD distributions. The biases of the simulated AODs against the observed AODs varied with observation type and seasons by a factor of 3~13 and 2~10, respectively. The global AOD distributions showed that the differences in the simulations against ICAP, MISR, VIIRS, and MODIS were the largest in March–May (MAM) and the smallest in December–February (DJF). When evaluating against the ground-truth AERONET data, the bias-scaling methods improved the global seasonal correlation (r), Index of Agreement (IOA), and mean biases, except for the MAM season, when the negative regional biases were exacerbated compared to the positive regional biases. The effect of bias-scaling had the most beneficial impact on model performance in the regions dominated by anthropogenic emissions, such as East Asia. However, it showed less improvement in other areas impacted by the greater relative transport of natural emissions sources, such as India. The accuracies of the reference observation or assimilation data for the adjusted inputs and the model physics for outputs, and the selection of regions with less seasonal emissions of natural aerosols determine the success of the bias-scaling methods. A companion study on emission scaling of anthropogenic absorbing aerosols needs further improved aerosol prediction. Full article

Stroke service delivery in rural areas in Australia lacks evidence-based, best practice care protocols as a result of limited resources and opportunity. Healthcare redesign is an approach to improving health services by understanding barriers and enablers to service provision and work with users to develop solutions for improvement. This research aimed to qualitatively evaluate stroke care in rural Tasmania using a person-centered approach, as part of a larger healthcare redesign initiative to improve acute stroke care. Semi-structured interviews, aimed at gaining insight into experiences of healthcare staff and users, were conducted. Thematic analysis revealed three global themes (communication, holistic care, and resourcing) that demonstrated some consistency between healthcare staff and user experience, highlighting that some needs and expectations were not being met. Results of this experiential study provide important perspectives for delivering needs-based improvements in service provision for acute stroke care. Overall, this study showed that systems of stroke care in rural areas could be improved by utilizing a redesign approach including healthcare staff and users in the development of solutions for health service improvement. Full article

In order to determine the impact of COVID-19 on the treatment and outcomes in patients with proximal femoral fracture’s (PFF), we analyzed a national US sample. This is a retrospective review of American College of Surgery’s (ACS) National Surgical Quality Improvement Program (NSQIP) for patients with proximal femoral fractures. A total of 26,830 and 26,300 patients sustaining PFF and undergoing surgical treatment were sampled during 2019 and 2020, respectively. On multivariable logistic regression, patients were less likely to have ‘presence of non-healing wound’ (p < 0.001), functional status ‘independent’ (p = 0.012), undergo surgical procedures of ‘hemiarthroplasty’(p = 0.002) and ‘ORIF IT, Peritroch, Subtroch with plates and screws’ (p < 0.001) and to be ‘alive at 30-days post-op’ (p = 0.001) in 2020 as compared to 2019. Patients were more likely to have a case status ‘emergent’, ‘loss of ≥10% body weight’, discharge destination of ‘home’ (p < 0.001 for each) or ‘leaving against medical advice’ (p = 0.026), postoperative ‘acute renal failure (ARF)’ (p = 0.011), ‘myocardial infarction (MI)’ (p = 0.006), ‘pulmonary embolism (PE)’ (p = 0.047), and ‘deep venous thrombosis (DVT)’ (p = 0.049) in 2020 as compared to 2019. Patients sustaining PFF and undergoing surgical treatment during pandemic year 2020 differed significantly in preoperative characteristics and 30-day postoperative complications when compared to patients from the previous year. Full article

Cultural practices and development level can influence a population’s household structures and mixing patterns. Within some populations, households can be organized across multiple dwellings. This likely affects the spread of infectious disease through these communities; however, current demographic data collection tools do not record these data. Methods: Between June and October 2018, the Contact And Mobility Patterns in remote Aboriginal Australian communities (CAMP-remote) pilot study recruited Aboriginal mothers with infants in a remote northern Australian community to complete a monthly iPad-based contact survey. Results: Thirteen mother–infant pairs (participants) completed 69 study visits between recruitment and the end of May 2019. Participants reported they and their other children slept in 28 dwellings during the study. The median dwelling occupancy, defined as people sleeping in the same dwelling on the previous night, was ten (range: 3.5–25). Participants who completed at least three responses (n = 8) slept in a median of three dwellings (range: 2–9). Each month, a median of 28% (range: 0–63%) of the participants travelled out of the community. Including these data in disease transmission models amplified estimates of infectious disease spread in the study community, compared to models parameterized using census data. Conclusions: The lack of data on mixing patterns in populations where households can be organized across dwellings may impact the accuracy of infectious disease models for these communities and the efficacy of public health actions they inform. Full article

Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes’ coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84–1.27 and OR: 1.08, 95% CI: 0.86–1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use. Full article

(1) Background: Jersey Shore University Medical Center (JSUMC) is a 646-bed tertiary medical center located in central New Jersey. Over the past several years, development and maturation of tertiary services at JSUMC has resulted in tremendous growth, with the inpatient volume increasing by 17% between 2016 and 2018. As hospital floors functioned at maximum capacity, the medical center was frequently forced into crisis mode with substantial increases in emergency department (ED) waiting times and a paradoxical increase in-hospital length of stay (hLOS). Prolonged hLOS can contribute to worse patient outcomes and satisfaction, as well as increased medical costs. (2) Methods: A root cause analysis was conducted to identify the factors leading to delays in providing in-hospital services. Four main bottlenecks were identified by the in-hospital phase sub-committee: incomplete orders, delays in placement to rehabilitation facilities, delays due to testing (mainly imaging), and delays in entering the discharge order. Similarly, the discharge process itself was analyzed, and obstacles were identified. Specific interventions to address each obstacle were implemented. Mean CMI-adjusted hospital LOS (CMI-hLOS) was the primary outcome measure. (3) Results: After interventions, CMI-hLOS decreased from 2.99 in 2017 to 2.84 and 2.76 days in 2018 and 2019, respectively. To correct for aberrations due to the COVID pandemic, we compared June–August 2019 to June–August 2020 and found a further decrease to 2.42 days after full implementation of all interventions. We estimate that the intervention led to an absolute reduction in costs of USD 3 million in the second half of 2019 and more than USD 7 million in 2020. On the other hand, the total expenses, represented by salaries for additional staffing, were USD 2,103,274, resulting in an estimated net saving for 2020 of USD 5,400,000. (4) Conclusions: At JSUMC, hLOS was found to be a complex and costly issue. A comprehensive approach, starting with the identification of all correctable delays followed by interventions to mitigate delays, led to a significant reduction in hLOS along with significant cost savings. Full article

The role and timing of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based regimens is unclear. However, the ability to achieve a complete response for metastatic renal cell carcinoma likely requires a nephrectomy at some point during treatment. Here we present a case series of three patients with metastatic clear-cell renal-cell carcinoma who received front-line immunotherapy-based treatment and subsequently underwent a cytoreductive nephrectomy. All three patients had a complete response to therapy and have subsequently remained off systemic therapy for a median of 531 days (range, 476–602). We also review the limited literature in this setting and highlight ongoing clinical trials. Although the role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based treatment is uncertain, a subset of patients will benefit from either an immediate or deferred cytoreductive nephrectomy. Ongoing trials are underway to further determine how to incorporate cytoreductive nephrectomy into the treatment paradigm for patients with metastatic renal cell carcinoma. Full article

Randomised controlled trials of ovarian cancer (OC) screening have not yet demonstrated an impact on disease mortality. Meanwhile, the screening data from clinical trials represents a rich resource to understand the performance of modalities used. We report here on incidence screening in the ultrasound arm of UKCTOCS. 44,799 of the 50,639 women who were randomised to annual screening with transvaginal ultrasound attended annual incidence screening between 28 April 2002 and 31 December 2011. Transvaginal ultrasound was used both as the first and the second line test. Participants were followed up through electronic health record linkage and postal questionnaires. Out of 280,534 annual incidence screens, 960 women underwent screen-positive surgery. 113 had ovarian/tubal cancer (80 invasive epithelial). Of the screen-detected invasive epithelial cancers, 37.5% (95% CI: 26.9–49.0) were Stage I/II. An additional 52 (50 invasive epithelial) were diagnosed within one year of their last screen. Of the 50 interval epithelial cancers, 6.0% (95% CI: 1.3–16.5) were Stage I/II. For detection of all ovarian/tubal cancers diagnosed within one year of screen, the sensitivity, specificity, and positive predictive values were 68.5% (95% CI: 60.8–75.5), 99.7% (95% CI: 99.7–99.7), and 11.8% (95% CI: 9.8–14) respectively. When the analysis was restricted to invasive epithelial cancers, sensitivity, specificity and positive predictive values were 61.5% (95% CI: 52.6–69.9); 99.7% (95% CI: 99.7–99.7) and 8.3% (95% CI: 6.7–10.3), with 12 surgeries per screen positive. The low sensitivity coupled with the advanced stage of interval cancers suggests that ultrasound scanning as the first line test might not be suitable for population screening for ovarian cancer. Trial registration: ISRCTN22488978. Registered on 6 April 2000. Full article