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Additive manufacturing is now being used to generate sand molds and cores with complex and customized geometries with binder jetting, which is one of the seven subprocesses within the additive [...]

Diabetes is one of the major diseases and concerns of public health systems that affects over 200 million patients worldwide. It is estimated that 90% of these patients suffer from diabetes type 2, while 10% present diabetes type 1. This type of diabetes and certain types of diabetes type 2, are characterized by dysregulation of blood glycemic levels due to the total or partial depletion of insulin-secreting pancreatic β-cells. Different approaches have been proposed for long-term treatment of insulin-dependent patients; amongst them, cell-based approaches have been the subject of basic and clinical research since they allow blood glucose level sensing and in situ insulin secretion. The current gold standard for insulin-dependent patients is on-demand exogenous insulin application; cell-based therapies aim to remove this burden from the patient and caregivers. In recent years, protocols to isolate and implant pancreatic islets from diseased donors have been developed and tested in clinical trials. Nevertheless, the shortage of donors, along with the need of immunosuppressive companion therapies, have pushed researchers to focus their attention and efforts to overcome these disadvantages and develop alternative strategies. This review discusses current tested clinical approaches and future potential alternatives for diabetes type 1, and some diabetes type 2, insulin-dependent patients. Additionally, advantages and disadvantages of these discussed methods

Contribution: This article provides evidence on the influence of serious games (SGs) in software engineering (SE) education on students’ scores, exam attendance, and chance of passing. It also highlights the impact of teachers’ experience with the implementation of SGs as a learning approach on the aforementioned metrics.Background: Although there are previous studies validating SGs in SE subjects, examining the effects that SGs and the expertise to implement them can have on students’ academic achievement by means of rigorous scientific methods is lacking.Research Questions: Do students achieve better academic results when SGs are used? Are the exam attendance and chance of passing higher among students enrolled in courses that use SGs compared to those following a traditional approach? Does the teachers’ expertise with SGs have an impact on students’ achievement? Are students satisfied using SGs in SE courses?Methodology: A controlled experiment was conducted on undergraduate students who were enrolled in an SE course during the years 2012/2013-2013/2014 and 2021/2022 to compare the effects of SGs with traditional teaching on students’ achievement in this subject. The students from the academic year 2012/2013 attended traditional lectures only, while the students from the academic years 2013/2014 and 2021/2022 had SGs incorporated within their lectures, led by teachers without and with expertise to deploy SGs, respectively.Findings: Students’ scores are higher when SGs are used compared to traditional teaching. Teachers’ experience and expertise are key factors to improve the chances of attending and passing the final exam when SGs are used.

This study explores how youth engage with literacy practices in the age of AI through the use of counter‐cartographies within the Nayah‐Irú curriculum. By critically examining digital platforms and the underlying algorithms, students embarked on a journey to understand and challenge the pervasive influence of artificial intelligence in their lives. The curriculum encouraged students to create alternative narratives (counter‐maps) that represent their unique experiences and perspectives, challenging the dominant discourses around technology and power. This process of counter‐mapping served as a powerful tool for fostering critical literacy and agency among the youth, enabling them to envision and advocate for transformative changes in their relationship with digital technologies. Educators played a key role in guiding these explorations, emphasizing the importance of a community‐centered approach to literacy that incorporates real‐world scenarios and addresses the socio‐cultural dynamics of AI. Through counter‐cartographies of AI literacy, students not only critiqued existing digital structures but also imagined new possibilities for engagement and resistance, highlighting the potential for youth to actively shape the discourse and practice of literacy practices in digital platforms. Starting with speculative literacies allow youth to imagine and understand the future impacts of societal injustice. The Counter Cartographies of AI Literacy framework then, continually envisions a vulnerable space that continually calls for the solidarity of youth to identify their struggles, develop alternative discourses, and continually determine actions that contribute to the well‐being of their communities. The Framework is an understanding of youth development in a world growing in its assimilation of AI practices.

Short sleep duration has been associated with an increased risk of childhood overweight and obesity in high-income countries, but data from low- and middle-income countries are scarce. Independently, short sleep and food insecurity may increase the risk of overweight/obesity, but it is unknown whether they concurrently affect it.

Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.

Inflammatory myopathies or myositis encompass diseases characterized by the presence of inflammatory cellular infiltrates, mainly polymorphonuclear cells and/or lymphocytes, in muscle. This is in contrast to most forms of muscle disease characterized by myodegeneration that results in macrophage infiltration. Inflammatory myopathies could have infectious or noninfectious causes. Noninfectious causes consist of primary (genetic, autoimmune) or acquired immune-mediated disease. Focal, multifocal or diffuse, acute or recurrent forms of disease can occur. This article will mainly review immune-mediated myopathies in horses. Myositis directly caused by infection such as Clostridiumspp and others will not be discussed here.

Improving the clinical translation of nanomedicine requires better knowledge about how nanoparticles interact with biological environments. As researchers are recognizing the importance of understanding the protein corona and characterizing how nanocarriers respond in biological systems, new tools and techniques are needed to analyze nanocarrier–protein interactions, especially for smaller size (<10 nm) nanoparticles like polyamidoamine (PAMAM) dendrimers. Here, we developed a streamlined, semiquantitative approach to assess dendrimer–protein interactions using a nondenaturing electrophoresis technique combined with mass spectrometry. With this protocol, we detect fluorescently tagged dendrimers and proteins simultaneously, enabling us to analyze when dendrimers migrate with proteins. We found that PAMAM dendrimers mostly interact with complement proteins, particularly C3 and C4a, which aligns with previously published data, verifying that our approach can be used to isolate and identify dendrimer–protein interactions.

AbstractObjective:To identify urinary catheter (UC)–associated urinary tract infection (CAUTI) incidence and risk factors.Design:A prospective cohort study.Setting:The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries.Participants:The study included 169,036 patients, hospitalized for 1,166,593 patient days.Methods:Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression.Results:Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower–middle-income countries (3.05); and with patients in public hospitals (5.89).The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P< .0001), female sex (aOR, 1.39; P< .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P< .0001), UC DU ratio (aOR, 1.09; P< .0001), public facilities (aOR, 2.24; P< .0001), and neurologic ICUs (aOR, 11.49; P< .0001).Conclusions:CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities.Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.

AbstractEntrepreneurial firms depend on knowledge variety and the ability to manage alliance-network learning for knowledge acquisition, which are both challenging. Some studies argue reliance on one key alliance partner is more effective for entrepreneurial firms with limited resources as it is less demanding than collaborations with multiple ones, while others demonstrate that alliances with different organizations significantly benefit them. Firm strategies and mechanisms of the alliance-network learning with multiple partners remain unclear, and illuminating this puzzle is relevant for understanding small and young firms creating innovations. Focusing on the early stages of human health biotech firms in Canada, this paper examines how they use the alliance-network to identify learning opportunities and pursue knowledge accumulation over their successive developmental stages. Adopting the multiple case study method and analyzing the focal firms’ collaborations and learning outcomes, this research advances a processual model of multiplicity of learning. The model identifies firm-specific strategies combining a variety of knowledge building mechanisms and multiple partners guided by organizational goals to innovate. The study contributes to the intersection of entrepreneurial development and alliance learning literatures with a novel view of early-stage firm learning strategies, and offers insights to entrepreneurs, small firms, and policymakers for innovation.

Findings on adaptive optics scanning light ophthalmoscopy foveal imaging for 54 individuals with choroideremia are reported. Three distinct phenotypes were observed. Foveal cone density is associated with structural and functional measures of disease severity.

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Through skating, Roberto and Diego formed friendship bonds with Preston Maigetter and Jake Phelps that lasted decades. At the loss of their two close friends, they decided to channel their [...]

TABLE OF CONTENTS I. Introduction 255 II. Background 257 A. The Telephone Consumer Protection Act of 1991 257 B. The FCC and the Courts Broaden Their Interpretation of the Scope [...]

•FXIII-A increases FXIII-B levels in plasma, but FXIII-A does not induce de novo FXIII-B synthesis or release from hepatocytes.•The FXIII-A and FXIII-B subunits exhibit reciprocal stabilization in plasma.

Host genetics shape immune responses and influence severity of infectious diseases. The HLA-B–21 M/T dimorphism tunes the functionality of natural killer (NK) cells expressing the inhibitory receptor NKG2A. NKG2A+NK cells have been reported to recognize SARS-CoV-2-infected cells, but it remains unclear whether the HLA-B–21 M/T dimorphism associates with COVID-19 severity. Here, we investigated the influence of the HLA-B–21 M/T dimorphism in a cohort of 230 unvaccinated patients hospitalized with COVID-19 and requiring respiratory support. We found that HLA-B–21 M/M genotypes were more prevalent in patients with moderate compared to severe COVID-19 (6.0% vs. 0.9%). Comparison of age- and sex-matched sub-groups revealed that patients with M/M genotypes required mechanical respiratory support less frequently (OR = 0.13, 95% CI = 0.01-0.76, P= 0.013). Furthermore, patients with M/M genotypes showed a coordinately shifted signature of clinical laboratory parameters, coinciding with elevated serum levels of the anti-viral cytokine IFN-γ. These findings demonstrate that HLA-Bvariants associate with COVID-19 severity and suggest that the robust functionality of NKG2A+NK cells in patients carrying the M/M genotype may contribute to protection from severe disease.

BackgroundCerebrospinal fluid (CSF)-venous fistulas (CVFs) are increasingly identified as a cause of spontaneous intracranial hypotension (SIH). Lateral decubitus digital subtraction myelography (LD-DSM) and CT myelography (LD-CTM) are mainly used for detection, but the most sensitive method is yet unknown.ObjectiveTo compare LD-DSM with LD-CTM for diagnostic yield of CVFs.MethodsPatients with SIH diagnosed with a CVF between January 2021 and December 2022 in which the area of CVF(s) was covered by both diagnostic modalities were included. LD-CTM immediately followed LD-DSM without repositioning the spinal needle, and the second half of the contrast agent was injected at the CT scanner. Patients were awake or mildly sedated. Retrospectively, two neuroradiologists evaluated data independently and blinded for the presence of CVF.ResultsTwenty patients underwent a total of 27 combined LD-DSM/LD-CTM examinations (4/20 with follow-up and 3/20 with bilateral examinations). Both raters identified significantly more CVFs with LD-CTM than with LD-DSM (rater 1: 39 vs 9, P<0.001; rater 2: 42 vs 12, P<0.001). Inter-rater agreement was substantial for LD-DSM (κ=0.732) and LD-CTM (κ=0.655). The results remained significant after considering the senior rating for cases of disagreement (39 vs 10; P<0.001), and no CVF detected on LD-DSM was missed on LD-CTM.ConclusionIn this study, LD-CTM has a higher diagnostic yield for the detection of CVFs than LD-DSM and should supplement LD-DSM, but further studies are needed. LD-CTM can be easily acquired in awake or mildly sedated patients with the second half of contrast injected just before CT scanning, or it may be considered as a stand-alone investigation.

Cu2O NPs were synthesized using aqueous extract of Psidium guajava.

Requirements engineering needs a good process and the right tool. Yet in many companies I observe unsuitable use of tools. Missing, wrong, and changing requirements are major failure points. Tools for requirements facilitate professional and efficient engineering throughout the lifecycle. We provide here an overview and evaluation of current requirements engineering tools. Hands-on guidance on tool selection and their usage facilitates selecting the right tool for your environment.—Christof Ebert

AbstractObjective:To identify central-line (CL)–associated bloodstream infection (CLABSI) incidence and risk factors in low- and middle-income countries (LMICs).Design:From July 1, 1998, to February 12, 2022, we conducted a multinational multicenter prospective cohort study using online standardized surveillance system and unified forms.Setting:The study included 728 ICUs of 286 hospitals in 147 cities in 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries.Patients:In total, 278,241 patients followed during 1,815,043 patient days acquired 3,537 CLABSIs.Methods:For the CLABSI rate, we used CL days as the denominator and the number of CLABSIs as the numerator. Using multiple logistic regression, outcomes are shown as adjusted odds ratios (aORs).Results:The pooled CLABSI rate was 4.82 CLABSIs per 1,000 CL days, which is significantly higher than that reported by the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC NHSN). We analyzed 11 variables, and the following variables were independently and significantly associated with CLABSI: length of stay (LOS), risk increasing 3% daily (aOR, 1.03; 95% CI, 1.03–1.04; P < .0001), number of CL days, risk increasing 4% per CL day (aOR, 1.04; 95% CI, 1.03–1.04; P < .0001), surgical hospitalization (aOR, 1.12; 95% CI, 1.03–1.21; P < .0001), tracheostomy use (aOR, 1.52; 95% CI, 1.23–1.88; P < .0001), hospitalization at a publicly owned facility (aOR, 3.04; 95% CI, 2.31–4.01; P <.0001) or at a teaching hospital (aOR, 2.91; 95% CI, 2.22–3.83; P < .0001), hospitalization in a middle-income country (aOR, 2.41; 95% CI, 2.09–2.77; P < .0001). The ICU type with highest risk was adult oncology (aOR, 4.35; 95% CI, 3.11–6.09; P < .0001), followed by pediatric oncology (aOR, 2.51;95% CI, 1.57–3.99; P < .0001), and pediatric (aOR, 2.34; 95% CI, 1.81–3.01; P < .0001). The CL type with the highest risk was internal-jugular (aOR, 3.01; 95% CI, 2.71–3.33; P < .0001), followed by femoral (aOR, 2.29; 95% CI, 1.96–2.68; P < .0001). Peripherally inserted central catheter (PICC) was the CL with the lowest CLABSI risk (aOR, 1.48; 95% CI, 1.02–2.18; P = .04).Conclusions:The following CLABSI risk factors are unlikely to change: country income level, facility ownership, hospitalization type, and ICU type. These findings suggest a focus on reducing LOS, CL days, and tracheostomy; using PICC instead of internal-jugular or femoral CL; and implementing evidence-based CLABSI prevention recommendations.

Purpose: This paper aims to address the limitations in designing educational approaches that apply critical approaches to data literacy, given the obscure nature of digital platforms, which leave youth unable to develop discourses that challenge dominant narratives about the role of data in their lives. The purpose of this study is to propose and evaluate a critical data literacy approach that empowers youth to engage with data from a sociocultural perspective using a speculative participatory research approach that affords opportunities to develop alternative discourses. Design/methodology/approach: This is a multiple-case study that involves five alternative schools in Uruguay which implemented the Nayah-Irú curriculum over ten weeks leading to the development of six distinct research projects about the materialization of data in youth lives. The curriculum incorporates an alternate reality game (ARG) to engage youth in critical data literacy, based on the principles of Youth Participatory Action Research (YPAR) epistemology and Speculative Civic Literacies. Findings: The findings of this study highlight the integration of speculative storytelling and real-life experiences in developing alternative discourses about datafication. The analysis revealed instances of discursive closure among the youth, but through the curriculum's speculative fiction elements, such as the narrative of Nayah-Irú, emotional connections were formed, leading to increased engagement, critical inquiry, and problem framing. Research limitations/implications: The study conducted on the Nayah-Irú curriculum shows its effectiveness in engaging youth and educators in critical data literacy by affording opportunities for youth to engage in the analysis of their personal data literacies in an alternative world. Bringing speculative approaches to data literacy can open new avenues for exploring data literacy with youth in ways that center their voices and help them overcome different forms of discursive closure. Originality/value: This study offers new insights into critical data literacy education blending youth participatory action research epistemologies with a speculative literacies framework to support youth in developing alternative discourses regarding the role of data in their lives.

Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA—potentially capable of being translated to produce viral proteins—persist in tissue as a ‘reservoir’. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.

Supplemental Digital Content is Available in the Text. A detailed retinal phenotype of three patients with Danon disease, a systemic disease with cardiovascular, muscular, cognitive, and ophthalmic manifestations, demonstrating age-dependent loss of near-infrared fundus autofluorescence signals and rod photoreceptor abnormalities in a pattern consistent with other primary retinal pigment epithelial or parallel retinal pigment epithelial and photoreceptor disease.

Deteriorated functioning is a part of the clinical-high risk (CHR) criteria for psychosis. Diminished social, educational and occupational functioning in the phase of late adolescence and early adulthood are associated with long-term social, economic and health consequences, which stresses the importance of early intervention to stimulate functioning. This pilot study examines the effectiveness and feasibility of the choose-get-keep model of Supported Education and Supported Employment (SEE) to improve educational and occupational functioning of individuals at CHR for a psychosis. A single blind randomized controlled pilot study combined SEE with treatment as usual (TAU) versus TAU among adolescents and early adults at CHR. School performance and job status as well as global functioning scales were assessed at twelve months. Of the 78 eligible participants, 20 individuals consented to participate in this study. At follow-up, participants in the intervention condition (n = 9) did not start an education more often than the participants in the control condition (n = 11) and the school results for both conditions were similar. However, in the intervention condition there were no school dropouts, more participants gained a job and worked longer hours. Two participants quit the intervention. This pilot study provides preliminary evidence that a SEE intervention is effective and feasible in sustaining and improving the level of both educational and occupational functioning of individuals at CHR for psychosis by supporting them in attaining, keeping and elaborating of their education or employment.

AbstractDrawing upon recent studies that empirically estimate both the benefits and costs of trade, this paper addresses a simple and important question: By how much do the benefits of increased global trade outweigh the costs? To the best of our knowledge, this is the first attempt to answer this question at global and World Bank income-grouping levels using empirically estimated relationships from the trade cost literature. Using a structural gravity model, we simulate changes in three primary trade constraints: a 10% reduction in tariff levels, a 10% reduction in effective distance, and a 10% increase in free trade agreement depth. The projection leads to a roughly 5% increase in global trade by value. Our model suggests that increased trade has an incredibly high benefit–cost ratio (BCR) for the developing world with an order-of-magnitude estimate for low- and lower–middle-income countries of 100 and for upper–middle-income countries of 50. However, the BCR for high-income countries is substantially lower, with a value closer to 5. Overall, the results suggest that free trade leads to substantial net benefits globally, generating US$ 700 billion in benefits (0.83% of global GDP) and US$ 100 billion in costs (0.12% of global GDP) in the first year, a differential that grows over time. Sensitivity analyses suggest that our BCRs are on the lower end of a plausible range. The results point to the incredible value of free trade, particularly for developing countries, and reiterate the importance of considering distributional impacts when implementing trade reforms.

After decades of research in the neurobiology of IGF-I, its role as a prototypical neurotrophic factor is undisputed. However, many of its actions in the adult brain indicate that this growth factor is not only involved in brain development or in the response to injury. Following a three-layer assessment of its role in the central nervous system, we consider that at the cellular level, IGF-I is indeed a bona fide neurotrophic factor, modulating along ontogeny the generation and function of all the major types of brain cells, contributing to sculpt brain architecture and adaptive responses to damage. At the circuit level, IGF-I modulates neuronal excitability and synaptic plasticity at multiple sites, whereas at the system level, IGF-I intervenes in energy allocation, proteostasis, circadian cycles, mood, and cognition. Local and peripheral sources of brain IGF-I input contribute to a spatially restricted, compartmentalized, and timed modulation of brain activity. To better define these variety of actions, we consider IGF-I a modulator of brain states. This definition aims to reconcile all aspects of IGF-I neurobiology, and may provide a new conceptual framework in the design of future research on the actions of this multitasking neuromodulator in the brain.

Supplemental Digital Content is Available in the Text. NPHP1-associated retinal degeneration can present as a cone–rod dystrophy with relative foveal preservation. This phenotype is increasingly recognized in other oculorenal ciliopathies, such as Bardet–Biedl and Alström syndromes, suggesting a common or intersecting mechanism of disease. This report also supports that there may be a consistent NPHP1-retinal phenotype rather than diversity.

We report on a phenomenon, where thin films sputter-deposited on single-crystalline Al2O3(0001) substrates exposed to borazine─a precursor commonly used for the synthesis of hexagonal boron nitride layers─are more highly oriented than those grown on bare Al2O3(0001) under the same conditions. We observed this phenomenon in face-centered cubic Pd, body-centered cubic Mo, and trigonal Ta2C thin films grown on Al2O3(0001). Interestingly, intermittent exposure to borazine during the growth of Ta2C thin films on Ta2C yields better crystallinity than direct deposition of monolithic Ta2C. We attribute these rather unusual results to a combination of both enhanced adatom mobilities on, and epitaxial registry with, surfaces exposed to borazine during the deposition. We expect that our approach can potentially help improve the crystalline quality of thin films deposited on a variety of substrates.

This is a first report of two siblings with confirmed BEST1-vitelliform macular dystrophy associated with bilateral angioid streak-like changes and multifocal vitelliform lesions.

Generation of H2and O2from untreated water sources represents a promising alternative to ultrapure water required in contemporary proton exchange membrane-based electrolysis. Bipolar membrane-based devices, often used in electrodialysis and CO2electrolysis, facilitate impure water electrolysis via the simultaneous mediation of ion transport and enforcement of advantageous microenvironments. Herein, we report their application in direct seawater electrolysis; we show that upon introduction of ionic species such as Na+and Cl−from seawater, bipolar membrane electrolyzers limit the oxidation of Cl−to corrosive OCl−at the anode to a Faradaic efficiency (FE) of 0.005%, while proton exchange membrane electrolyzers under comparable operating conditions exhibit up to 10% FE to Cl−oxidation. The effective mitigation of Cl−oxidation by bipolar membrane electrolyzers underpins their ability to enable longer-term seawater electrolysis than proton exchange membrane assemblies by a factor of 140, suggesting a path to durable seawater electrolysis.

IMPORTANCE: Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear. OBJECTIVE: To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022. EXPOSURES: Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets. MAIN OUTCOMES AND MEASURES: Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored. RESULTS: The study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose. CONCLUSIONS AND RELEVANCE: This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.

T-cell redirection therapy using chimeric antigen receptor (CAR) T cells and bispecific antibodies (BiAbs) has shown promising efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), leading to the approval of 2 CAR T-cell products and numerous BiAb trials. Data on the outcomes after relapse following BiAbs are urgently required to develop strategies for sequencing salvage therapies. We identified 58 patients progressing after a BiAb trial at Mount Sinai Hospital. Progression-free survival (PFS) to the first salvage (PFS1), second salvage therapy (PFS2), and overall survival (OS) were estimated using the Kaplan-Meier method. The median age of the patients was 67 years, and 78% had high-risk cytogenetics. They had a median of 6 prior therapy lines, 89% were triple-class refractory, and 44% were penta-drug refractory. After the BiAb trial, patients were followed for a median of 30.5 months and received a median of 2 additional salvage therapies (range, 1-9). The most common first salvage was T-cell redirection in 19 patients (10 BiAb and 9 CAR T cells). Ten patients underwent T-cell redirection as a second salvage treatment. T-cell redirection therapy as first or second salvage was feasible and associated with a median PFS1 of 28.9 months, PFS2 of 30.9 months, and an OS of 62% at 2 years. The sequential use of different T-cell redirection therapies is possible and may lead to deep and durable responses following the relapse after BiAb therapy in RRMM.

Objective The aim of this study was to describe coping strategies used by parents of children with cleft palate with or without a cleft (CP ± L) during the early development of their children in El Salvador.Design Qualitative interviews were completed with 16 parents of children born with CP ± L who were 6 months to 6 years old. Parents were questioned about their emotions and coping during eight time periods: prenatal, birth, social interaction before the first surgery, the beginning of surgeries, social interaction after the first surgery, early childhood education (ECE), speech–language therapy, and formal education. Thematic analysis (TA) was used to identify coping strategies as conceptualized by Lazarus and Folkman (1984).Results Four major themes emerged: (a) experienced emotions related to diagnosis, (b) interpretations related to the birth of a child with a cleft, (c) seeking and experiencing cleft treatment, and (d) social interaction of the children. During prenatal and birth stages, parents used emotion-focused strategies. A few hours to a week after birth, they used problem-focused strategies, which led them in search of treatment. Some parents used avoidance strategies during periods of social interaction before surgery, ECE, and formal education. Socioeconomic challenges impacted access to speech–language therapy. Sociocultural factors, such as discrimination, religion, and folk beliefs, appeared to influence some of the coping strategies used by parents.Conclusions Problem-focused strategies appear to be helpful in seeking surgical treatments. The emotion-focused strategy of avoidance seemed to have adverse effects in minimizing opportunities for social interaction prior to surgery and early education.

Previous research on innovation capabilities in emerging economies shows knowledge networks tied to Western multinationals and national governments focused on economic growth. Less understood is the innovation capability building of emerging economies to achieve ‘good health’, an important Sustainable Development Goal. Here, we present a longitudinal study of a public research organization in an emerging economy and examine how it builds innovation capabilities for creating vaccines, drugs, and diagnostics for diseases primarily affecting the poor. We study FIOCRUZ in Brazil using archival, patent, and interview data about invention of technologies for neglected tropical diseases. We contribute novel insights into the evolution of knowledge networks, as national policy integrates innovation and health goals. We found significant diversification of local and foreign knowledge sources, and substantial creation of networks with public, private, and non-governmental organizations enabling collective invention. These R&D networks attract many multinationals to collaborate on socially driven innovation projects previously non-existent in their portfolios. The public research organization leads collaborations with multinationals and diverse partners, harnessing distributed international knowledge. Our results indicate emerging economies’ capabilities depend on elevating policies to increase health access for the poor to drive innovation and promoting local R&D to generate solutions to improve health.