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Lung cancer patients with interstitial lung disease (ILD) are prone for higher morbidity and mortality and their treatment is challenging. The purpose of this study is to investigate whether the survival of lung cancer patients is affected by the presence of ILD documented on CT. 146 patients with ILD at initial chest CT were retrospectively included in the study. 146 lung cancer controls without ILD were selected. Chest CTs were evaluated for the presence of pulmonary fibrosis which was classified in 4 categories. Presence and type of emphysema, extent of ILD and emphysema, location and histologic type of cancer, clinical staging and treatment were evaluated. Kaplan-Meier estimates and Cox regression models were used to assess survival probability and hazard of death of different groups. P value < 0.05 was considered significant. 5-year survival for the study group was 41% versus 48% for the control group (log-rank test p = 0.0092). No significant difference in survival rate was found between the four different categories of ILD (log-rank test, p = 0.195) and the different histologic types (log-rank test, p = 0.4005). A cox proportional hazard model was used including presence of ILD, clinical stage and age. The hazard of death among patients with ILD was 1.522 times that among patients without ILD (95%CI, p = 0.029). Patients with lung cancer and CT evidence of ILD have a significantly shorter survival compared to patients with lung cancer only. Documenting the type and grading the severity of ILD in lung cancer patients will significantly contribute to their challenging management.

Diamond has superlative material properties for a broad range of quantum and electronic technologies. However, heteroepitaxial growth of single crystal diamond remains limited, impeding integration and evolution of diamond-based technologies. Here, we directly bond single-crystal diamond membranes to a wide variety of materials including silicon, fused silica, sapphire, thermal oxide, and lithium niobate. Our bonding process combines customized membrane synthesis, transfer, and dry surface functionalization, allowing for minimal contamination while providing pathways for near unity yield and scalability. We generate bonded crystalline membranes with thickness as low as 10 nm, sub-nm interfacial regions, and nanometer-scale thickness variability over 200 by 200  μ m 2 areas. We measure spin coherence times T 2 for nitrogen vacancy centers in 150 nm-thick bonded membranes of up to 623 ± 21  μ s, suitable for advanced quantum applications. We demonstrate multiple methods for integrating high quality factor nanophotonic cavities with the diamond heterostructures, highlighting the platform versatility in quantum photonic applications. Furthermore, we show that our ultra-thin diamond membranes are compatible with total internal reflection fluorescence (TIRF) microscopy, which enables interfacing coherent diamond quantum sensors with living cells while rejecting unwanted background luminescence. The processes demonstrated herein provide a full toolkit to synthesize heterogeneous diamond-based hybrid systems for quantum and electronic technologies. Development of diamond-based quantum and electronic technologies requires heterogeneous integration, which has remained challenging. This work realizes direct bonding of single crystal diamond membranes to a broad range of technology-relevant substrates while maintaining quantum coherence for hosted qubits.

This paper uses the writings of European teachers and Chinese students at St. Stephen’s Girls’ College in Hong Kong—published in English periodicals of its school magazine and local English newspapers—to examine how the school tactically positioned itself as an educational site for the “useful women of China” during a period in Republican China that was simultaneously defined as a time of “cosmopolitan modernity” and “national rebuilding.” St. Stephen’s brand of usefulness responded to the “New Woman” phenomenon in Republican China, and it was defined through the narrative of science learning and a sense of service. Through its progressive science curriculum and social service branch, the school helped prepare a class of “career women” for China. It was in educating this class that St. Stephen’s, in resonance with the colonial state, envisioned its role in the shaping of modern China.

Background Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Newborn screening and timely galactose-restricted diet can resolve acute symptoms and decrease fatalities. However, despite this, significant chronic, progressive morbidities remain which have a real impact upon daily life. To better understand the burden of disease, 20 in-depth qualitative interviews were undertaken with adult patients (n = 12), and their caregivers (n = 8), enrolled in the ACTION-Galactosemia trial, part of a clinical program designed to investigate the safety and efficacy of AT-007 (govorestat) in reducing toxic galactitol and long-term clinical outcomes in Classic Galactosemia. Results Interviews revealed the substantial burden of Classic Galactosemia on patients and families. Most adults were not able to live independently, and all required support with day-to-day activities. Short- and long-term memory difficulties and tremors were identified as the most frequently experienced and challenging symptoms. Other difficulties such as fine motor skills and slow/slurred speech contribute to the significant impact on daily activities, affecting ability to communicate and interact with others. Symptoms were first noticed in early childhood and worsened with age. Classic Galactosemia impacted all areas of daily functioning and quality of life, leading to social isolation, anxiety, anger/frustration and depression. This demonstrates the significant burden of disease and challenges associated with Classic Galactosemia. Conclusions The impact on both patients and caregivers underscores the severity of the unmet medical need and the importance of pharmacological intervention to halt or prevent disease progression. Any treatment that could reduce symptoms or slow functional decline would ease the burden of this condition on patients and caregivers.

Background Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Living with the debilitating symptoms and long-term consequences of Classic Galactosemia creates a heavy burden on patients’ and their families’ lives. Objectives were to: (1) Evaluate the impact and burden of disease; (2) Qualitatively explore changes in patient symptoms following treatment; and (3) Document the meaningfulness of changes resulting from treatment with govorestat as assessed by the Caregiver Global Impression of Severity (CGIS) and Caregiver Global Impression of Change (CGIC) scales. Methodology The AT-007-1002 clinical trial involved a Phase 1/2 dose escalation component (Part A) followed by a Phase 3, randomized, double-blind, placebo-controlled long-term administration component (Part B) that evaluated potential clinical benefit. Exit Interviews were completed prior to unblinding of data. The in-depth, qualitative interviews were semi-structured, using a discussion guide, and conducted by either Zoom or GoToMeeting. Thirty-six caregiver interviews were conducted, capturing the experience of 37 pediatric patients (one caregiver had 2 patients enrolled in the study). Thematic analysis was undertaken to identify themes or patterns within the data. All analyses were conducted on blinded data. Following finalization of the analysis and report findings, post-hoc analysis of the unblinded data was then conducted to explore the meaningfulness of patients experience by treatment arm. Results This study confirms the substantial burden known to be associated with Classic Galactosemia in a pediatric population. The difficulties experienced were across multiple areas including cognitive function, behavior/social function, motor function, emotional function, communication, vision problems, ovarian insufficiency, sensory difficulties, and sleep problems. The interviews demonstrated that most patients (approximately two thirds) experienced an improvement in symptoms and impacts associated with classic galactosemia over the course of the trial. Nearly all caregivers reported that they perceived a 1-category change on the Caregiver Global Impression of Severity or Caregiver Global Impression of Change items, indicating severity and change respectively, was meaningful to them and the patient. Unblinded analysis of the exit interview data confirmed the patient experience reported by caregivers was different between the treatment arms, providing qualitative support for the treatment benefit of govorestat when compared to placebo. Furthermore, the qualitative data from caregivers provide in-depth insights of their unique lived experience that highlight the substantial impact that this improvement had on the caregiver’s and the patient’s quality of life. The improvements observed led to a reduction on the burden of Classic Galactosemia and may lead to a greater patient’s greater independence. Conclusions The exit interviews confirmed the burden of Classic Galactosemia disease across multiple domains. Qualitative investigation suggests that observed changes are meaningful to the patient and caregiver, and changes were more commonly reported in those receiving govorestat compared to placebo. Full clinical trial findings will be published separately.

Objectives Unlike in adult rheumatology, for most forms of juvenile idiopathic arthritis (JIA) no reliable biomarkers currently exist to assess joint and disease activity. However, electrophoresis is frequently found changed in active juvenile arthritis. The objective of this study was to evaluate the α2-fraction of serum electrophoresis and its main components as biomarkers for JIA, categories extended/persistent oligoarthritis and seronegative polyarthritis, in comparison with the conventionally used erythrocyte sedimentation rate and C-reactive protein. Methods Serum samples and clinical data from 181 patients with JIA were collected. Serum electrophoresis and α2-fraction and its components were determined using standard methods. Relationship between calculated α2-fraction of serum electrophoresis (CA2F) and its components, acute-phase parameters and cJADAS27 was assessed using Pearson’s correlation coefficient and linear regression modelling, adjusting for confounding effects. Results were confirmed in a second cohort with 223 serum samples from 37 patients, using a mixed model to account for repeated measures. Results Compared to ESR and CRP, CA2F showed higher correlation to cJADAS27, in particular for persistent oligoarthritis. Of the three components of the α2-fraction, haptoglobin showed the highest correlation to cJADAS27. Regression analysis demonstrated higher ability to predict cJADAS27 for CA2F, and especially for haptoglobin as a component thereof, than for CRP and ESR. Conclusion Compared to conventional methods, α2-fraction of serum electrophoresis and specifically, haptoglobin show higher correlations with disease activity in common subtypes of JIA, representing excellent candidates as biomarkers for disease activity. Further studies are necessary to determine diagnostic value and correlations in other subtypes.

Background Classic Galactosemia (CG) is a rare, autosomal recessive condition. Newborn screening and a timely galactose-restricted diet can resolve acute symptoms and decrease fatalities, but significant chronic, progressive morbidities remain and significantly impact daily life. The objective of this study was to better understand the burden of disease in children and adults with CGs and describe how morbidities evolve over time. Methods A total of 49 individuals with CG from the United States (US) were included in the qualitative surveys (13 adults [9 self-reported] and 36 pediatric patients). Fifteen follow-up interviews were conducted with 5 adults and 10 caregivers, discussing 17 individuals with CG overall (2 caregivers each discussed 2 children). Results Qualitative survey and interview data demonstrated the substantial burden of CG. Difficulties in a wide range of functions were experienced, which included: speech articulation; language and communication; cognition, memory and learning; emotions; and social interactions. Most difficulties appeared in childhood and persisted or worsened with age. Most adults did not live independently. Others lived semi-independently and experienced many daily challenges and required support. Caregivers also described the burden of caring for someone with CG and spoke about the impact this has on their day-to-day life, work, and relationships. Conclusions These findings demonstrate the pronounced and persistent burden of disease encountered by individuals with CG, and that the condition has a significant impact on the quality of life of caregivers.

BackgroundEnhanced recovery after caesarean delivery (ERAC) is a multidisciplinary, evidence-based bundle of interventions developed from Enhanced Recovery After Surgery principles, designed to improve patient outcomes, reduce complications and save healthcare resources. Despite these benefits, the implementation of ERAC within the Canadian healthcare context is unknown. In addition, previous ERAC studies typically excluded patients undergoing unplanned caesarean deliveries (CD). The objective of our study was to evaluate the results of a quality improvement initiative that implemented a comprehensive ERAC pathway for both planned and unplanned CD in a large Canadian obstetric unit, with a specific focus on patient-reported outcomes.MethodsA pre-implementation post implementation design was used. The primary outcomes were Obstetric Quality of Recovery Score (ObsQoR-10) and patient satisfaction at 6 weeks postpartum. Secondary outcomes included postpartum length of stay, postoperative pain and maternal infectious morbidity.InterventionAntenatal, intraoperative and postoperative ERAC bundles were developed with multidisciplinary input.Results513 patients were included: 290 pre-implementation (149 planned CD, 141 unplanned CD) and 223 post- implementation (128 planned CD, 95 unplanned CD). Baseline demographics were similar, except the post implementation groups had significantly higher median Body Mass Index (BMI). In planned CD, ObsQoR-10 scores were on average 3.4 points higher in the post-implementation group (95% CI (−0.19 to 6.99); p-value=0.063). Patient satisfaction assessed at 6 weeks postpartum was significantly improved by 12 points in the post-implementation group (95% CI (5.58 to 18.62); p-value<0.001). In unplanned CD, implementation was not associated with ObsQoR-10 (p-value=0.92) or patient satisfaction assessed at 6 weeks postpartum (p-value=0.43). Pain scores were higher in both post-implementation groups, but there were no differences in morphine milliequivalents or requirement for breakthrough opioids. Length of stay and maternal infectious morbidity were similar.DiscussionImplementation of ERAC in a large Canadian tertiary care obstetrics unit was feasible and resulted in improved recovery and increased satisfaction in patients undergoing planned CD. There were no differences in other outcomes, including infectious morbidity; however, the contribution of BMI needs to be explored. Patients undergoing unplanned CD face additional challenges related to outcomes, recovery and satisfaction and should be targeted in future studies.

Background Individuals with advanced cancer often experience high levels of distress for which there are few standardized treatment approaches. Our multidisciplinary team has combined existing evidence-based approaches into Psilocybin-assisted Existential, Attachment, and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose psilocybin session, and integration sessions, with important elements from evidence-based psychotherapies designed for patients with advanced cancer. Method This open-label, single-arm clinical trial will assess the acceptability, feasibility, and safety of PEARL therapy among 15 patients with advanced cancer, using qualitative and quantitative methodologies. Participants will complete self-report questionnaires at four time points pre- and post-intervention, as well as a qualitative interview one month after PEARL completion. Feasibility will be evaluated in terms of recruitment, retention, and adherence rates, while safety will be assessed based on the number of participants experiencing no serious adverse events. Discussion This study will yield important information about the acceptability and feasibility of PEARL therapy and contribute to growing research around the efficacy of psychedelic-assisted therapies. PEARL therapy has the potential to improve quality of life among those with advanced disease, and careful research is needed to guide public policy, legislation, therapist training, and clinical guidelines. Trial registration NCT06416085; 2024–07-16.

Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. This prospective cohort study examined children (aged <18 years) recruited from May 23, 2013, to March 31, 2017, at 12 Canadian pediatric academic health centers who were receiving 1 or more cisplatin infusion. Children whose estimated or measured glomerular filtration rate (GFR) was less than 30 mL/min/1.73 m2 or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. Cisplatin infusions. The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteria-based definition (stage 1 or higher). The secondary outcome was acute kidney injury defined by electrolyte criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1 or higher). Assessments occurred at early (first or second cycle) and late (last or second to last cycle) cisplatin infusions. A total of 159 children (mean [SD] age at early cisplatin infusion, 7.2 [5.3] years; 80 [50%] male) participated. The most common diagnoses were central nervous system tumors (58 [36%]), neuroblastoma (43 [27%]), and osteosarcoma (33 [21%]). Acute kidney injury (by serum creatinine level increase) occurred in 48 of 159 patients (30%) at early cisplatin infusions and 23 of 143 patients (16%) at late cisplatin infusions. Acute kidney injury (by electrolyte abnormalities) occurred in 106 of 159 patients (67%) at early cisplatin infusion and 100 of 143 patients (70%) at late cisplatin infusions. Neuroblastoma diagnosis and higher precisplatin GFR were independently associated with acute kidney injury (serum creatinine level increase) at early cisplatin infusions (adjusted odds ratio [aOR] for neuroblastoma vs other, 3.25; 95% CI, 1.18-8.95; aOR for GFR, 1.01; 95% CI, 1.00-1.03) and late cisplatin infusions (aOR for neuroblastoma vs other, 6.85; 95% CI, 1.23-38.0; aOR for GFR, 1.01; 95% CI, 1.00-1.03). Higher cisplatin infusion dose was also independently associated with acute kidney injury (serum creatinine level increase) at later cisplatin infusions (aOR, 1.05; 95% CI, 1.01-1.10). The findings suggest that acute kidney injury is common among children receiving cisplatin infusions and that rate and risk factors differ at earlier vs later infusions. These results may help with risk stratification with a goal of risk reduction.