Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer.

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40+ Th1-like cells and CD8+ memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.

Evaluating thromboprophylaxis in the sickle cell disease population: Navigating the evidence gap.

Sickle cell disease (SCD) arises from beta-globin gene mutations, with global estimates indicating around 500 000 affected neonates in 2021. In the United States, it is considered rare, impacting fewer than 200 000 individuals. The key pathogenic flaw lies in mutant haemoglobin S, prone to polymerization under low oxygen conditions, causing erythrocytes to adopt a sickled shape. This leads to complications like vascular occlusion, haemolytic anaemia, inflammation and organ damage. Beyond erythrocyte abnormalities however, there is a body of literature highlighting the hypercoagulable state that is likely a contributor to many of the complications we see in SCD. The persistent activation of the coagulation cascade results in thromboembolic events, notably venous thromboembolism (VTE) which is independently associated with increased mortality in both adults and children with SCD. While the increased risk of VTE in the SCD population seems well established, there is a lack of guidelines for thromboprophylaxis in this population. This Wider Perspective will describe the hypercoagulable state and increased thrombosis risk in the SCD population, as well as advocate for the development of evidence-based guidelines to aid in the prevention of VTE in SCD.

Hemostatic and thrombotic disorders in the pediatric patient.

This review focuses on significant advances in the field of pediatric hemostasis and thrombosis, with a focus on published studies within the past decade. The evaluation and management of patients with excessive bleeding remain cornerstones of consultative hematology. We will describe the development of validated bleeding assessment tools relevant to pediatric practice, laboratory advances in the evaluation of von Willebrand disease, and a shift in clinical practice regarding the interpretation of normal coagulation studies in patients with significant bleeding phenotypes. There have also been critical advances in the management of hemostatic disorders. This review highlights new treatment paradigms in hemophilia and the rise of multidisciplinary medical homes for women living with bleeding disorders. Given the continued increase in the incidence of thrombosis, particularly in the hospital setting, a full call to arms against pediatric venous thromboembolism is now essential. We will describe recently completed clinical trials of direct oral anticoagulants in children and adolescents and ongoing work to elucidate the appropriate duration of therapy for children with provoked thrombosis. Recent work regarding the prevention of pediatric venous thromboembolism is highlighted, including studies of thromboprophylaxis and the development of risk prediction models for hospital-acquired thrombosis. Finally, we review advances in our understanding of thrombotic sequelae and the need for continued refinement of our evaluation tools. Despite the significant advances in pediatric hemostasis and thrombosis over the past decade, many unanswered questions remain for the next generation of investigators.

The views of parents and carers on managing acute otitis media in urban Aboriginal and Torres Strait Islander children: a qualitative study.

OBJECTIVES: To explore the views of parents and carers regarding the management of acute otitis media in urban Aboriginal and Torres Strait Islander children who are at low risk of complications living in urban communities. STUDY DESIGN: Qualitative study; semi-structured interviews and short telephone survey. SETTING, PARTICIPANTS: Interviews: purposive sample of parents and carers of urban Aboriginal and Torres Strait Islander children (18 months - 16 years old) screened in Aboriginal medical services in Queensland, New South Wales, and Canberra for the WATCH study, a randomised controlled trial that compared immediate antibiotic therapy with watchful waiting for Aboriginal and Torres Strait Islander children with acute otitis media. SURVEY: parents and carers recruited for the WATCH trial who had completed week two WATCH surveys. RESULTS: We interviewed twenty-two parents and carers, including ten who had declined participation in or whose children were ineligible for the WATCH trial. Some interviewees preferred antibiotics for managing acute otitis media, others preferred watchful waiting, expressing concerns about side effects and reduced efficacy with overuse of antibiotics. Factors that influenced this preference included the severity, duration, and recurrence of infection, and knowledge about management gained during the trial and from personal and often multigenerational experience of ear disease. Participants highlighted the importance of shared decision making by parents and carers and their doctors. Parents and carers of 165 of 262 WATCH participants completed telephone surveys (63%); 81 were undecided about whether antibiotics should always be used for treating acute otitis media. Open-ended responses indicated that antibiotic use should be determined by clinical need, support for general practitioners' decisions, and the view that some general practitioners prescribed antibiotics too often. CONCLUSIONS: Parents and carers are key partners in managing acute otitis media in urban Aboriginal and Torres Strait Islander children. Our findings support shared decision making informed by the experience of parents and carers, which could also lead to reduced antibiotic use for managing acute otitis media.

SEMA3: A free smartphone platform for daily life surveys.

Traditionally, behavioral, social, and health science researchers have relied on global/retrospective survey methods administered cross-sectionally (i.e., on a single occasion) or longitudinally (i.e., on several occasions separated by weeks, months, or years). More recently, social and health scientists have added daily life survey methods (also known as intensive longitudinal methods or ambulatory assessment) to their toolkit. These methods (e.g., daily diaries, experience sampling, ecological momentary assessment) involve dense repeated assessments in everyday settings. To facilitate research using daily life survey methods, we present SEMA3 ( http://www.SEMA3.com ), a platform for designing and administering intensive longitudinal daily life surveys via Android and iOS smartphones. SEMA3 fills an important gap by providing researchers with a free, intuitive, and flexible platform with basic and advanced functionality. In this article, we describe SEMA3's development history and system architecture, provide an overview of how to design a study using SEMA3 and outline its key features, and discuss the platform's limitations and propose directions for future development of SEMA3.

Brief report: STING expressed in tumor and non-tumor compartments has distinct roles in regulating anti-tumor immunity.

Type I interferon-mediated activation of immune cells can facilitate the generation of productive tumor antigen-specific T cell responses in solid tumors. The cGAS/STING DNA sensing pathway is a critical upstream mediator of type I interferon production and is an important regulator of anti-tumor immunity. Numerous STING pathway agonists are now being tested in clinical trials, but the effectiveness of this approach is not yet clear and a better understanding of the relative importance of this pathway in various tumor settings is needed. We have evaluated syngeneic tumor models with different baseline inflammatory states to determine the contributions of STING activity in both tumor and non-tumor cellular compartments to anti-tumor immune responses. We find that productive anti-tumor immune responses in the poorly immunogenic B16F10 model show a strong dependence on STING expression in non-tumor cells. In the immunogenic MC38 model, constitutive STING activation in tumor cells can partially bypass the requirement for STING-dependent activity from immune cells. Our findings reveal multiple, context-dependent roles for STING activity in the regulation of anti-tumor immunity and the response to immunotherapy. In preclinical models where STING is basally active, checkpoint inhibition is more likely to have a therapeutic effect and removal of STING signaling from either the tumor or the non-tumor compartment has a minimal effect. Removal of STING signaling in both, however, diminishes the efficacy derived from checkpoint therapy. Further work is needed to understand the heterogeneity of STING signaling in patients, both in tumor cells and the tumor microenvironment, and the best means of harnessing this pathway to generate anti-tumor immunity and improve therapeutic outcomes.

The relationship between heavy menstrual bleeding, iron deficiency, and iron deficiency anemia.

For reproductive-aged women, the symptom of heavy menstrual bleeding is highly prevalent and a major contributor to iron deficiency and its most severe manifestation, iron deficiency anemia. It is recognized that these 2 clinical entities are not only highly prevalent, but their interrelationship is poorly appreciated and frequently normalized by society, healthcare providers, and affected girls and women themselves. Both heavy menstrual bleeding and iron deficiency, with or without anemia, adversely impact quality of life-heavy menstrual bleeding during the episodes of bleeding and iron deficiency on a daily basis. These combined issues adversely affect the lives of reproductive-aged girls and women of all ages, from menarche to menopause, and their often-insidious nature frequently leads to normalization. The effects on cognitive function and the related work and school absenteeism and presenteeism can undermine the efforts and function of women in all walks of life, be they students, educators, employers, or employees. There is also an increasing body of evidence that suggests that iron deficiency, even in early pregnancy, may adversely impact fetal neurodevelopment with enduring effects on a spectrum of cognitive and psychological disorders, critically important evidence that begs the normalization of iron stores in reproductive-aged women. The authors seek to raise individual, societal, and professional awareness of this underappreciated situation in a fashion that leads to meaningful and evidence-based changes in clinical guidance and healthcare policy directed at preventing, screening, diagnosing, and appropriately managing both disorders. This manuscript provides evidence supporting the need for action and describes the elements necessary to address this pervasive set of conditions that not only affect reproductive-aged girls and women but also the lives of children everywhere.

Pregnancy-related thromboembolism in women with sickle cell disease: An analysis of National Medicaid Data.

Pregnancy and sickle cell disease (SCD) both individually carry a risk of thromboembolism (TE). Pregnancy in people with SCD may further enhance the prothrombotic effect of the underlying disease. The objectives of this study were to determine the rate and risk factors for arterial and venous thrombosis in pregnant people with SCD. Administrative claims data from the United States Centers for Medicare and Medicaid Service Analytic eXtract from 2006 to 2018 were used. The study population included people with SCD from the start of their first identified pregnancy until 1 year postpartum and a control cohort of pregnant people without SCD of similar age and race. Outcomes of interest were identified with ICD-9 or 10 codes. Logistic regression analyses were used to analyze risk factors. We identified infant deliveries in 6388 unique people with SCD and 17 110 controls. A total of 720 venous thromboembolism (11.3%) and 335 arterial TE (5.2%) were observed in people with SCD compared to 202 (1.2%) and 95 (0.6%) in controls. People with SCD had an 8-11 times higher odds of TE compared to controls (p < .001). Within the SCD cohort, age, hemoglobin SS (HbSS) genotype, hypertension, and history of thrombosis were identified as independent risk factors for pregnancy-related TE. Pregnancy-specific factors (pre-eclampsia, eclampsia, multigestational pregnancy) were not associated with TE. In conclusion, the risk of pregnancy-related TE is considerably higher in people with SCD compared with controls without SCD. Hence, people with SCD, particularly those with multiple risk factors may be candidates for thromboprophylaxis during pregnancy and the postpartum period.

Clinicians' perspectives on barriers and facilitators to sperm banking in adolescent males with cancer: a mixed-methods study.

PURPOSE: To examine processes, barriers, and facilitators to sperm banking counseling and decision-making for adolescent males newly diagnosed with cancer from the perspective of clinicians who completed Oncofertility communication training. We also identify opportunities for improvement to inform future interventions and implementation. METHODS: A survey (N=104) and subsequent focus groups (N=15) were conducted with non-physician clinicians practicing in pediatric oncology who completed Oncofertility communication training. RESULTS: Most survey participants were confident in communicating about the impact of cancer on fertility (n=87, 83.7%) and fertility preservation options (n=80, 76.9%). Most participants reported never/rarely using a sperm banking decision tool (n=70, 67.3%), although 98.1% (n=102) said a decision tool with a family-centered approach would be beneficial. Primary themes in the subsequent focus groups included variable processes/workflows (inconsistent approaches to consult initiation; involvement of adolescents, caregivers, and various clinician types; assessment of puberty/sexual experience), structural and psychosocial barriers (cost and logistics, developmental, cultural, clinical acuity/prognosis), and facilitators (educational materials, alternative options for banking). Opportunities and strategies for improvement (including fertility preservation in existing research protocols; additional staffing/resources; oncologist education and buy-in; and development of decision tools) were informed by challenges identified in the other themes. CONCLUSION: Barriers to adolescent sperm banking remain, even among clinicians who have completed Oncofertility training. Although training is one factor necessary to facilitate banking, structural and psychosocial barriers persist. Given the complexities of offering sperm banking to pediatric populations, continued efforts are needed to mitigate structural barriers and develop strategies to facilitate decision-making before childhood cancer treatment.

A restatement of the natural science evidence base regarding the source, spread and control of Campylobacter species causing human disease.

Food poisoning caused by Campylobacter (campylobacteriosis) is the most prevalent bacterial disease associated with the consumption of poultry, beef, lamb and pork meat and unpasteurized dairy products. A variety of livestock industry, food chain and public health interventions have been implemented or proposed to reduce disease prevalence, some of which entail costs for producers and retailers. This paper describes a project that set out to summarize the natural science evidence base relevant to campylobacteriosis control in as policy-neutral terms as possible. A series of evidence statements are listed and categorized according to the nature of the underlying information. The evidence summary forms the appendix to this paper and an annotated bibliography is provided in the electronic supplementary material.

Peripherally inserted central catheters lead to a high risk of venous thromboembolism in children.

Venous thromboembolism (VTE) incidence in children has sharply increased with the majority of cases secondary to central venous catheters (CVCs). Among CVCs, the number of peripherally inserted central catheters (PICCs) placed has risen significantly. In this multicenter, prospective, observational cohort study, we enrolled patients aged 6 months to 18 years with newly placed PICCs or tunneled lines (TLs). We evaluated the incidence of VTE, central line-associated bloodstream infections (CLABSIs), and catheter malfunctions in PICCs and TLs, and risk factors of CVC-related VTE. A total of 1967 CVCs were included in the analysis. The incidence of CVC-related VTE was 5.9% ± 0.63%. The majority of the cases, 80%, were in subjects with PICCs, which had a significantly higher risk of catheter-related VTE than subjects with TLs (hazard ratio [HR] = 8.5; 95% confidence interval [CI], 3.1-23; P < .001). PICCs were significantly more likely to have a CLABSI (HR = 1.6; 95% CI, 1.2-2.2; P = .002) and CVC malfunction (HR = 2.0; 95% CI, 1.6-2.4; P < .001). Increased risk of CVC-related VTE was found in patients with a prior history of VTE (HR = 23; 95% CI, 4-127; P < .001), multilumen CVC (HR = 3.9; 95% CI, 1.8-8.9; P = .003), and leukemia (HR = 3.5; 95% CI, 1.3-9.0; P = .031). Children with PICCs had a significantly higher incidence of catheter-related VTE, CLABSI, and CVC malfunction over TLs. The results suggest that pause be taken prior to placing CVCs, especially PICCs, due to the serious complications they have been shown to cause.

Iron deficiency and fatigue among adolescents with bleeding disorders.

Iron deficiency anemia is associated with heavy menstrual bleeding (HMB) and, by extension, a bleeding disorder (BD). It is unknown if iron deficiency without anemia is associated with a BD in adolescents. Moreover, the threshold of ferritin associated with fatigue in adolescents with HMB is unclear. In this multicenter study, we enrolled adolescents with HMB without BD. Participants underwent BD and anemia work-up in Young Women's Hematology Clinics and completed the Peds QL™ fatigue scale. BDs were defined as von Willebrand Disease, platelet function defect, clotting factor deficiencies, and hypermobility syndrome. Two hundred and fifty consecutive adolescents were enrolled, of whom 196 met eligibility criteria. Overall, 43% (95% confidence interval: 36%-50%) were diagnosed with BD. A total of 61% (n = 119) had serum ferritin levels < 15 ng/mL, 23.5% (n = 46) had iron deficiency only, and 37% (n = 73) had iron deficiency anemia. Low ferritin or ferritin dichotomized as < 15 or ≥ 15 ng/mL was not associated with BD on univariable analysis (p = .24) or when accounting for age, race, ethnicity, body mass index, and hemoglobin (p = .35). A total of 85% had total fatigue score below the population mean of 80.5, and 52% (n = 102) were > 2 SD (or < 54) below the mean, the cut-off associated with severe fatigue. A ferritin threshold of < 6 ng/mL had a specificity of 79.8% but a sensitivity of 36% for severe fatigue. In conclusion, iron deficiency without anemia is not a predictor of BD in adolescents with HMB in a specialty setting. Severe fatigue, especially sleep fatigue, is prevalent in adolescents with BD. Ferritin of < 6 ng/mL has ~80% specificity for severe fatigue in adolescents with HMB.

Impact of hydroxyurea dose and adherence on hematologic outcomes for children with sickle cell anemia.

BACKGROUND: Hydroxyurea is the primary treatment for sickle cell anemia (SCA), yet real-world implementation in high-income settings is suboptimal. Variation in prescribed hydroxyurea dose and patient adherence in these settings can both affect actual exposure to hydroxyurea. Quantifying the contributions of hydroxyurea dose and medication adherence to the relationship between hydroxyurea exposure and hematologic parameters could inform strategies to optimize exposure and improve outcomes. PROCEDURE: We evaluated the relationship between hydroxyurea exposure, defined by average prescribed dose and adherence, and hematologic parameters using data from children with SCA who were enrolled in two prospective hydroxyurea adherence studies. Hydroxyurea adherence was assessed by video directly observed therapy or electronic pill bottle and medication administration record. Average prescribed dose was abstracted from prescriptions in patients' electronic medical record. Participants with a hydroxyurea exposure >20 mg/kg/day and ≤20 mg/kg/day were included in the higher and lower exposure groups, respectively. RESULTS: Forty-five participants were included in the analysis (56% male; median age 12 years [range 2-19]; 98% Black). Higher exposed participants (n = 23) were prescribed a higher dose (27.2 vs. 24.4 mg/kg/day, p = .002) and had better adherence (0.92 vs. 0.71, p ≤ .001) compared to lower exposed participants (n = 22). Higher exposure was associated with higher fetal hemoglobin (p = .04) and mean corpuscular volume (p = .02). CONCLUSIONS: Higher hydroxyurea exposure is associated with improved hematologic parameters in the high-income setting and is affected by both prescribed dose and adherence. Future studies are needed to optimize both adherence and hydroxyurea prescribing and confirm that increasing exposure improves clinical outcomes in this setting.

Cross-sectional household transmission study of Cryptosporidium shows that C. hominis infections are a key risk factor for spread.

BACKGROUND: Infection with the Cryptosporidium parasite causes over 4000 cases of diagnosed illness (cryptosporidiosis) in England and Wales each year. The incidence of sporadic disease has not been sufficiently established, and how frequently this arises from contact with other infected people is not well documented. This project aimed to explore potential transmission in the home and attempt to identify asymptomatic infections, which might play a role in transmission. Risk factors and characteristics associated with spread of infection in the home were described including any differences between Cryptosporidium species. METHODS: The study identified cryptosporidiosis cases from North West England and Wales over a year and invited them and their household to take part. Each household was sent a study pack containing study information and a questionnaire, and stool sample kits to provide samples from consenting household members. Cryptosporidium-positive stool samples, identified by immunofluorescence microscopy, were characterised using molecular methods to help describe any patterns of transmission. Characteristics of households with and without additional cases were described, and compared using odds ratios (OR) and a multivariable logistic regression identified independent risk factors for household transmission. Data collection ran for one year, beginning in September 2018 with an initial pilot phase. RESULTS: We enrolled 128 index cases and their households. Additional illness occurred in over a quarter of homes, each reporting an average of two additional cases. The majority of these were undiagnosed and unreported to surveillance. This burden was even greater in households where the index case was infected with C. hominis versus C. parvum, or the index case was under five years old, with mums and siblings most at risk of secondary infection. Only having an index case of C. hominis was independently associated with transmission in the multivariable model (OR 4.46; p = 0.01). CONCLUSIONS: Cryptosporidium was a considerable burden in the home. At-risk homes were those where the index was less than five years old and/or infected with C. hominis. Of particular risk were female caregivers and siblings. Hygiene advice should be specifically directed here. This work provides evidence for humans as sources of C. hominis infection and that person-person is a key pathway. We recommend that all stools submitted for the investigation of gastrointestinal pathogens are tested for Cryptosporidium to better capture cases, inclusion of speciation data in routine surveillance, and the consideration of specific clinical advice on prevention for high-risk homes.

Norovirus attribution study: Detection of norovirus from the commercial food preparation environment in outbreak and non-outbreak premises.

AIMS: Norovirus remains the most significant virological risk that is transmitted via food and the environment to cause acute gastroenteritis. This study aimed to investigate the hypothesis that the contamination of the commercial food production environment with norovirus will be higher in premises that have recently reported a foodborne norovirus outbreak than those that have not. METHODS: Sampling of commercial food production environments was carried out across a 16-month period between January 2015 and April 2016 in the South East and the North West of England by local authority environmental health departments as part of routine surveillance visits to premises. A total of 2982 samples, 2038 virological and 944 bacteriological, were collected from 256 premises. Sixteen of these premises, six from South East and ten from North West England, were sampled as part of a public health outbreak investigation. RESULTS & CONCLUSIONS: Overall, 2038 swabs were submitted for norovirus testing, with an average of eight swabs per premises (range 4 to 23) and a median of seven. Of the premises sampled, 11.7% (30/256) yielded at least one norovirus-positive sample (environmental, and/or food handler hand swab), and 2.5% of the swabs were positive for norovirus. A peak in the positivity rate was seen in the South East in April 2016. No associations were found between norovirus positivity and bacteriology indicators, or between bacteriology indicators and hygiene ratings. SIGNIFICANCE AND IMPACT OF STUDY: This study demonstrates that food premises and food handlers remain a potential source of norovirus transmission and outbreaks.

Sedation Practices for Lumbar Punctures in Patients With Acute Lymphoblastic Leukemia: A Multicenter Retrospective Study Using Pediatric Health Information Systems.

BACKGROUND: Sedation is often used to reduce pain and anxiety in pediatric patients with acute lymphoblastic leukemia (ALL) undergoing lumbar punctures (LPs). There is a potential for long-term effects on neurocognition with repeat sedative exposures in young children. The purpose of this study is to determine the practice habits regarding sedation for LPs in pediatric patients with ALL among multiple institutions. METHODS: This is a retrospective study of 48 hospitals in the Pediatric Health Information Systems (PHIS) between October 2015 and December 2019. Children 1 to 18 years old with ALL who received intrathecal chemotherapy in an outpatient setting were included. We analyzed the prevalence of anesthesia usage and the types of anesthetics used. RESULTS: Of the 16,785 encounters with documented use of anesthetic medications, intravenous and inhaled anesthetics were used in 16,486 (98.2%) and local anesthetics alone in 299 (1.8%). The most commonly used medications used for sedation were propofol (n=13,279; 79.1%), midazolam (n=4228; 25.2%), inhaled fluranes (n=3169; 18.9%), and ketamine (n=2100; 12.5%). CONCLUSION: The majority of children's hospitals in the United States use intravenous and inhaled anesthetics for routine therapeutic LPs in pediatric patients with ALL. Propofol is one of the most common medications used for sedation.

Can cases and outbreaks of norovirus in children provide an early warning of seasonal norovirus infection: an analysis of nine seasons of surveillance data in England UK.

BACKGROUND: Children are important transmitters of norovirus infection and there is evidence that laboratory reports in children increase earlier in the norovirus season than in adults. This raises the question as to whether cases and outbreaks in children could provide an early warning of seasonal norovirus before cases start increasing in older, more vulnerable age groups. METHODS: This study uses weekly national surveillance data on reported outbreaks within schools, care homes and hospitals, general practice (GP) consultations for infectious intestinal disease (IID), telehealth calls for diarrhoea and/or vomiting and laboratory norovirus reports from across England, UK for nine norovirus seasons (2010/11-2018/19). Lagged correlation analysis was undertaken to identify lead or lag times between cases in children and those in adults for each surveillance dataset. A partial correlation analysis explored whether school outbreaks provided a lead time ahead of other surveillance indicators, controlling for breaks in the data due to school holidays. A breakpoint analysis was used to identify which surveillance indicator and age group provided the earliest warning of the norovirus season each year. RESULTS: School outbreaks occurred 3-weeks before care home and hospital outbreaks, norovirus laboratory reports and NHS 111 calls for diarrhoea, and provided a 2-week lead time ahead of NHS 111 calls for vomiting. Children provided a lead time ahead of adults for norovirus laboratory reports (+ 1-2 weeks), NHS 111 calls for vomiting (+ 1 week) and NHS 111 calls for diarrhoea (+ 1 week) but occurred concurrently with adults for GP consultations. Breakpoint analysis revealed an earlier seasonal increase in cases among children compared to adults for laboratory, GP and NHS 111 data, with school outbreaks increasing earlier than other surveillance indicators in five out of nine surveillance years. CONCLUSION: These findings suggest that monitoring cases and outbreaks of norovirus in children could provide an early warning of seasonal norovirus infection. However, both school outbreak data and syndromic surveillance data are not norovirus specific and will also capture other causes of IID. The use of school outbreak data as an early warning indicator may be improved by enhancing sampling in community outbreaks to confirm the causative organism.

PACS downtime drill: testing departmental workflow with an enterprise imaging viewer and archive.

In today's workflow, radiologists rely on the picture archiving and communication system (PACS) to view images. Unplanned downtime causes significant delays in patient care and lengthy downtimes can have lasting effects on patient care and end-user confidence. The purpose of this manuscript is to describe the planning and implementation of a disaster drill where the departmental PACS was taken off-line and the hospital enterprise viewer was used for departmental image interpretation.

Creation of a Multi-vendor Image-Sharing Solution.

Transferring medical imaging studies from one institution to another is a common occurrence in today's medical practice. For the past two decades, radiology departments have relied on physical media (compact discs and digital video disks) and human couriers to accomplish image transfer. This mode of transfer is slow, prone to failure, and reliant on outdated technology. To address these shortcomings, multiple image-sharing vendors have created electronic, cloud-based solutions. While these solutions solve multiple problems, a new problem has been introduced: it is difficult to send or receive images across image-sharing platforms. In this work, we describe how we have developed a solution to share images across multiple vendor platforms.

Activity of tumor-associated macrophage depletion by CSF1R blockade is highly dependent on the tumor model and timing of treatment.

Tumor-associated macrophages (TAMs) are abundant in solid tumors where they exhibit immunosuppressive and pro-tumorigenic functions. Inhibition of TAM proliferation and survival through CSF1R blockade has been widely explored as a cancer immunotherapy. To further define mechanisms regulating CSF1R-targeted therapies, we systematically evaluated the effect of anti-CSF1R treatment on tumor growth and tumor microenvironment (TME) inflammation across multiple murine models. Despite substantial macrophage depletion, anti-CSF1R had minimal effects on the anti-tumor immune response in mice bearing established tumors. In contrast, anti-CSF1R treatment concurrent with tumor implantation resulted in more robust tumor growth inhibition and evidence of enhanced anti-tumor immunity. Our findings suggest only minor contributions of CSF1R-dependent TAMs to the inflammatory state of the TME in established tumors, that immune landscape heterogeneity across different tumor models can influence anti-CSF1R activity, and that alternative treatment schedules and/or TAM depletion strategies may be needed to maximize the clinical benefit of this approach.