A Novel Artificial Intelligence-Based Parameterization Approach of the Stromal Landscape in Merkel Cell Carcinoma: A Multi-Institutional Study.

Tumor-stroma ratio (TSR) has been recognized as a valuable prognostic indicator in various solid tumors. This study aimed to examine the clinicopathologic relevance of TSR in Merkel cell carcinoma (MCC) using artificial intelligence (AI)-based parameterization of the stromal landscape and validate TSR scores generated by our AI model against those assessed by humans. One hundred twelve MCC cases with whole-slide images were collected from 4 different institutions. Whole-slide images were first partitioned into 128 × 128-pixel "mini-patches," then classified using a novel framework, termed pre-tumor and stroma (Pre-TOAST) and TOAST, whose output equaled the probability of the minipatch representing tumor cells rather than stroma. Hierarchical random samplings of 50 minipatches per region were performed throughout 50 regions per slide. TSR and tumor-stroma landscape (TSL) parameters were estimated using the maximum-likelihood algorithm. Receiver operating characteristic curves showed that the area under the curve value of Pre-TOAST in discriminating classes of interest including tumor cells, collagenous stroma, and lymphocytes from nonclasses of interest including hemorrhage, space, and necrosis was 1.00. The area under the curve value of TOAST in differentiating tumor cells from related stroma was 0.93. MCC stroma was categorized into TSR high (TSR ≥ 50%) and TSR low (TSR < 50%) using both AI- and human pathology-based methods. The AI-based TSR-high subgroup exhibited notably shorter metastasis-free survival (MFS) with a statistical significance of P = .029. Interestingly, pathologist-determined TSR subgroups lacked statistical significance in recurrence-free survival, MFS, and overall survival (P > .05). Density-based spatial clustering of applications with noise analysis identified the following 2 distinct TSL clusters: TSL1 and TSL2. TSL2 showed significantly shorter recurrence-free survival (P = .045) and markedly reduced MFS (P < .001) compared with TSL1. TSL classification appears to offer better prognostic discrimination than traditional TSR evaluation in MCC. TSL can be reliably calculated using an AI-based classification framework and predict various prognostic features of MCC.

Evidence Synthesis for Complex Interventions Using Meta-Regression Models.

A goal of evidence synthesis for trials of complex interventions is to inform the design or implementation of novel versions of complex interventions by predicting expected outcomes with each intervention version. Conventional aggregate data meta-analyses of studies comparing complex interventions have limited ability to provide such information. We argue that evidence synthesis for trials of complex interventions should forgo aspirations of estimating causal effects and instead model the response surface of study results to 1) summarize the available evidence and 2) predict the average outcomes of future studies or in new settings. We illustrate this modeling approach using data from a systematic review of diabetes quality improvement (QI) interventions involving at least 1 of 12 QI strategy components. We specify a series of meta-regression models to assess the association of specific components with the posttreatment outcome mean and compare the results to conventional meta-analysis approaches. Compared with conventional approaches, modeling the response surface of study results can better reflect the associations between intervention components and study characteristics with the posttreatment outcome mean. Modeling study results using a response surface approach offers a useful and feasible goal for evidence synthesis of complex interventions that rely on aggregate data.

Diuretic Tolerance to Repeated-Dose Furosemide in Infants Born Very Preterm with Bronchopulmonary Dysplasia.

OBJECTIVES: To assess the presence and timing of furosemide diuretic tolerance in infants with bronchopulmonary dysplasia (BPD), and to determine if tolerance is modified by thiazide co-administration. STUDY DESIGN: We performed a retrospective cohort study among infants born very preterm with BPD exposed to repeated-dose furosemide for 72 hours, measuring net fluid balance (total intake minus total output) as a surrogate of diuresis in the 3 days before and after exposure. The primary comparison was the difference in fluid balance between the first and third 24 hours of furosemide exposure. We fit a general linear model for within-subject repeated measures of fluid balance over time, with thiazide co-administration as an interaction variable. Secondary analyses included an evaluation of weight trajectories over time. RESULTS: In 83 infants, median fluid balance ranged between + 43.6 and + 52.7 ml/kg/d in the 3 days prior to furosemide exposure. Fluid balance decreased to a median of + 29.1 ml/kg/d in the first 24 hours after furosemide, but then increased to +47.5 ml/kg/d by the third 24-hour interval, consistent with tolerance (P < .001). Thiazides did not modify the change in fluid balance during furosemide exposure for any time-period. Weight decreased significantly in the first 24 hours after furosemide and increased thereafter (P < .001). CONCLUSIONS: The net fluid balance response to furosemide decreases rapidly during repeated-dose exposures in infants with BPD, consistent with diuretic tolerance. Clinicians should consider this finding in the context of an infant's therapeutic goals. Further research efforts to identify safe and effective furosemide dosage strategies are needed.

PLAG1 dampens protein synthesis to promote human hematopoietic stem cell self-renewal.

Hematopoietic stem cell (HSC) dormancy is understood as supportive of HSC function and its long-term integrity. Although regulation of stress responses incurred as a result of HSC activation is recognized as important in maintaining stem cell function, little is understood of the preventive machinery present in human HSCs that may serve to resist their activation and promote HSC self-renewal. We demonstrate that the transcription factor PLAG1 is essential for long-term HSC function and, when overexpressed, endows a 15.6-fold enhancement in the frequency of functional HSCs in stimulatory conditions. Genome-wide measures of chromatin occupancy and PLAG1-directed gene expression changes combined with functional measures reveal that PLAG1 dampens protein synthesis, restrains cell growth and division, and enhances survival, with the primitive cell advantages it imparts being attenuated by addition of the potent translation activator, c-MYC. We find PLAG1 capitalizes on multiple regulatory factors to ensure protective diminished protein synthesis including 4EBP1 and translation-targeting miR-127 and does so independently of stress response signaling. Overall, our study identifies PLAG1 as an enforcer of human HSC dormancy and self-renewal through its highly context-specific regulation of protein biosynthesis and classifies PLAG1 among a rare set of bona fide regulators of messenger RNA translation in these cells. Our findings showcase the importance of regulated translation control underlying human HSC physiology, its dysregulation under activating demands, and the potential if its targeting for therapeutic benefit.

Radiotherapy concepts for spinal metastases-results from an online survey among radiation oncologists of the German Society for Radiation Oncology.

PURPOSE: Spinal metastases (SM) are a common radiotherapy (RT) indication. There is limited level I data to drive decision making regarding dose regimen (DR) and target volume definition (TVD). We aim to depict the patterns of care for RT of SM among German Society for Radiation Oncology (DEGRO) members. METHODS: An online survey on conventional RT and Stereotactic Body Radiation Therapy (SBRT) for SM, distributed via e­mail to all DEGRO members, was completed by 80 radiation oncologists between February 24 and April 29, 2022. Participation was voluntary and anonymous. RESULTS: A variety of DR was frequently used for conventional RT (primary: n = 15, adjuvant: n = 14). 30 Gy/10 fractions was reported most frequently. TVD in adjuvant RT was heterogenous, with a trend towards larger volumes. SBRT was offered in 65% (primary) and 21% (adjuvant) of participants' institutions. A variety of DR was reported (primary: n = 40, adjuvant: n = 27), most commonly 27 Gy/3 fractions and 30 Gy/5 fractions. 59% followed International Consensus Guidelines (ICG) for TVD. CONCLUSION: We provide a representative depiction of RT practice for SM among DEGRO members. DR and TVD are heterogeneous. SBRT is not comprehensively practiced, especially in the adjuvant setting. Further research is needed to provide a solid data basis for detailed recommendations.

Development and qualification of 3 L scale-down model for large scale vaccine process on vero cell culture using microcarriers.

Scale-down models (SDM) are pivotal tools for process understanding and improvement to accelerate the development of vaccines from laboratory research to global commercialization. In this study, a 3 L SDM representing a 50 L scale Vero cell culture process of a live-attenuated virus vaccine using microcarriers was developed and qualified based on the constant impeller power per volume principle. Both multivariate data analysis (MVDA) and the traditional univariate data analysis showed comparable and equivalent cell growth, metabolic activity, and product quality results across scales. Computational fluid dynamics simulation further confirmed similar hydrodynamic stress between the two scales.

Evaluating CD133 as a Radiotheranostic Target in Small-Cell Lung Cancer.

Despite decades of work, small-cell lung cancer (SCLC) remains a frustratingly recalcitrant disease. Both diagnosis and treatment are challenges: low-dose computed tomography (the approved method used for lung cancer screening) is unable to reliably detect early SCLC, and the malignancy's 5 year survival rate stands at a paltry 7%. Clearly, the development of novel diagnostic and therapeutic tools for SCLC is an urgent, unmet need. CD133 is a transmembrane protein that is expressed at low levels in normal tissue but is overexpressed by a variety of tumors, including SCLC. We previously explored CD133 as a biomarker for a novel autoantibody-to-immunopositron emission tomography (PET) strategy for the diagnosis of SCLC, work that first suggested the promise of the antigen as a radiotheranostic target in the disease. Herein, we report the in vivo validation of a pair of CD133-targeted radioimmunoconjugates for the PET imaging and radioimmunotherapy of SCLC. To this end, [89Zr]Zr-DFO-αCD133 was first interrogated in a trio of advanced murine models of SCLC─i.e., orthotopic, metastatic, and patient-derived xenografts─with the PET probe consistently producing high activity concentrations (>%ID/g) in tumor lesions combined with low uptake in healthy tissues. Subsequently, a variant of αCD133 labeled with the ß-emitting radiometal 177Lu─[177Lu]Lu-DTPA-A″-CHX-αCD133─was synthesized and evaluated in a longitudinal therapy study in a subcutaneous xenograft model of SCLC, ultimately revealing that treatment with a dose of 9.6 MBq of the radioimmunoconjugate produced a significant increase in median survival compared to a control cohort. Taken together, these data establish CD133 as a viable target for the nuclear imaging and radiopharmaceutical therapy of SCLC.

Impact of upfront adjuvant chemoradiation on survival in patients with molecularly defined oligodendroglioma: the benefits of PCV over TMZ.

PURPOSE: Oligodendroglioma is an adult-type diffuse glioma defined by 1p/19q codeletion and IDH1/2 mutation. Treatment includes surgery followed by observation alone in select low-grade tumors, or combination radiation and chemotherapy with procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ). While prospective studies investigating treatments for molecularly defined oligodendrogliomas are ongoing, this retrospective study analyzes the relationship between adjuvant regimens and progression-free survival (PFS). METHODS: Adults with IDH-mutant, 1p/19q codeleted oligodendroglioma (WHO grade 2 or 3) who underwent surgery between 2005 and 2021 were identified. Clinical data, disease characteristics, treatment, and outcomes were collected. RESULTS: A total of 207 patients with grade 2 and 70 with grade 3 oligodendrogliomas were identified. Median (IQR) follow-up was 57 (87) months. Patients with grade 3 tumors who received adjuvant radiation and PCV had longer median PFS (> 110 months) than patients who received radiation and TMZ (52 months, p = 0.008) or no adjuvant chemoradiation (83 months, p = 0.03), which was not seen in grade 2 tumors (p = 0.8). In multivariate analysis, patients who received PCV chemotherapy (Relative Risk [95% CI] = 0.24[0.05-1.08] and radiotherapy (0.46[0.21-1.02]) trended towards longer PFS, independently of grade. CONCLUSION: Adjuvant radiation and PCV are associated with improved PFS over radiation with TMZ in patients with grade 3 molecularly defined oligodendrogliomas, and all-grade patients treated with PCV trended towards decreased risk of recurrence and progression. These results highlight the importance of ongoing clinical trials investigating these treatments.

Intraoperative renal replacement therapy during liver transplantation in children: Safety, efficacy and impact on survival.

BACKGROUND: Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life-threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT. METHODS: We conducted a retrospective cohort study of all children requiring CRRT pre-OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post-LT outcomes were compared between those who received iCRRT and those who did not. RESULTS: Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24 h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One-year post-LT mortality rates were similar. CONCLUSION: ICRRT is safe in critically ill children with pre-LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource-intensive therapy to benefit this fragile population.

Changes in maternity care policies and practices that support breastfeeding as measured by the Ten Steps to Successful Breastfeeding - United States, 2018-2022.

BACKGROUND: Experiences during the birth hospitalization affect a family's ability to establish and maintain breastfeeding. The Ten Steps to Successful Breastfeeding (Ten Steps) describe evidence-based hospital policies and practices shown to improve breastfeeding outcomes. We aim to describe hospitals' implementation of the Ten Steps, changes over time, and hospitals' implementation of a majority (≥ 6) of the Ten Steps by hospital characteristics and state. METHODS: The biennial Maternity Practices in Infant Nutrition and Care (mPINC) survey assesses all hospitals in the United States (including the District of Columbia and territories) that routinely provide maternity care services. We analyzed data from 2018, 2020, and 2022 survey cycles to describe trends in the prevalence of hospitals implementing maternity care policies and practices that are consistent with the Ten Steps. Differences were calculated using the absolute difference in percentage-points between 2018 and 2022. RESULTS: Between 2018 and 2022, the percentage of hospitals that implemented Step 2: Staff Competency and Step 5: Support Mothers with Breastfeeding increased 12 and 8 percentage points, respectively. The percentage of hospitals that implemented Step 6: Exclusive Breastfeeding Among Breastfed Infants was 7 percentage points lower in 2022 than 2018. Implementation of the remaining seven steps did not change by more than 5 percentage points in either direction between 2018 and 2022. Nationally, the percentage of hospitals that implemented ≥ 6 of the Ten Steps increased from 44.0% in 2018 to 51.1% in 2022. Differences were seen when comparing implementation of ≥ 6 of the Ten Steps by hospital characteristics including state, hospital size, and highest level of neonatal care offered. CONCLUSIONS: Nationally, maternity care policies and practices supportive of breastfeeding continued to improve; however, certain practices lost progress. Differences in implementation of the Ten Steps were observed across states and by certain hospital characteristics, suggesting more work is needed to ensure all people receive optimal breastfeeding support during their delivery hospitalization.

Demographic changes in COVID-19 mortality during the pandemic: analysis of trends in disparities among workers using California's mortality surveillance system.

BACKGROUND: There is limited information on the extent and patterns of disparities in COVID-19 mortality throughout the pandemic. We aimed to examine trends in disparities by demographics over variants in the pre- and post-vaccine availability period among Californian workers using a social determinants of health lens. METHODS: Using death certificates, we identified all COVID-19 deaths that occurred between January 2020 and May 2022 among workers aged 18-64 years in California (CA). We derived estimates for at-risk worker populations using the Current Population Survey. The waves of COVID-19 mortality in the pre-vaccine availability period were March 2020-June 2020 (wave 1), and July 2020-November 2020 (wave 2), and in the post-vaccine availability period: December 2020-May 2021 (wave 3), June 2021-January 2022 (wave 4), and February 2022-May 2022 (wave 5). Poisson regression models with robust standard errors were used to determine wave-specific mortality rate ratios (MRRs). We examined the change in MRR across waves by including an interaction term between each demographic characteristic and wave period in different models. The role of potential misclassification of Race/ethnicity on death certificates was examined using probabilistic quantitative bias analysis as sensitivity analysis. RESULTS: Among the 24.1 million working age CA population included in the study, there were 26,068 COVID-19 deaths in the period between January 2020 and May 2022. Compared with their respective reference groups, workers who were 50-64 years old, male, Native Hawaiian, Latino, or African American, foreign-born; individuals who had lower education; and unmarried were disproportionately affected by COVID-19 mortality. While disparities by sex, race/ethnicity and foreign-born status narrowed in later waves (post-vaccine availability), disparities by age, education level and marital status did not change substantially across waves. CONCLUSION: Demographic disparities in COVID-19 mortality narrowed in the post-vaccine availability waves. However, the existence of disparities across all waves of the pandemic, even in an era of widespread vaccine coverage, could indicate remaining gaps in prevention and differential vulnerability. Addressing the underlying social, structural, and occupational factors that contribute to these disparities is critical for achieving health equity.

Anthropogenic lead pervasive in Canadian Arctic seawater.

Anthropogenic Pb is widespread in the environment including remote places. However, its presence in Canadian Arctic seawater is thought to be negligible based on low dissolved Pb (dPb) concentrations and proxy data. Here, we measured dPb isotopes in Arctic seawater with very low dPb concentrations (average ∼5 pmol ⋅ kg-1) and show that anthropogenic Pb is pervasive and often dominant in the western Arctic Ocean. Pb isotopes further reveal that historic aerosol Pb from Europe and Russia (Eurasia) deposited to the Arctic during the 20th century, and subsequently remobilized, is a significant source of dPb, particularly in water layers with relatively higher dPb concentrations (up to 16 pmol ⋅ kg-1). The 20th century Eurasian Pb is present predominantly in the upper 1,000 m near the shelf but is also detected in older deep water (2,000 to 2,500 m). These findings highlight the importance of the remobilization of anthropogenic Pb associated with previously deposited aerosols, especially those that were emitted during the peak of Pb emissions in the 20th century. This remobilization might be further enhanced because of accelerated melting of permafrost and ice along with increased coastal erosion in the Arctic. Additionally, the detection of 20th century Eurasian Pb in deep water helps constrain ventilation ages. Overall, this study shows that Pb isotopes in Arctic seawater are useful as a gauge of changing particulate and contaminant sources, such as those resulting from increased remobilization (e.g., coastal erosion) and potentially also those associated with increased human activities (e.g., mining and shipping).

Characterizing the presentation, management, and clinical outcomes of patients with intradural spinal chordomas: a systematic review.

OBJECTIVE: Chordomas are locally aggressive neoplasms of the spine or skull base that arise from embryonic remnants of the notochord. Intradural chordomas represent a rare subset of these neoplasms, and few studies have described intradural chordomas in the spine. This review evaluates the presentation, management, and outcomes of intradural spinal chordomas. METHODS: A systematic review of PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science was performed. Studies describing at least 1 case of intradural chordomas anywhere in the spine were included. Extracted details included presenting symptoms, radiological findings, treatment course, follow-up, and disease progression. RESULTS: Thirty-one studies, with a total of 41 patients, were included in this review. Seventy-six percent (31/41) of patients had primary intradural tumors, whereas 24% (10/41) presented with metastasis. The most common signs and symptoms were pain (n = 27, 66%); motor deficits (n = 20, 49%); sensory deficits (n = 17, 42%); and gait disturbance (n = 10, 24%). The most common treatment for intradural chordoma was resection and postoperative radiotherapy. Sixty-six percent (19/29) of patients reported improvement or complete resolution of symptoms after surgery. The recurrence rate was 37% (10/27), and the complication rate was 25% (6/24). The median progression-free survival was 24 months (range 4-72 months). Four patient deaths were reported. The median follow-up time was 12 months (range 13 days-84 months). CONCLUSIONS: Treatment of intradural spinal chordomas primarily involves resection and radiotherapy. A significant challenge and complication in management is spinal tumor seeding after resection, with 9 studies proposing seeding as a mechanism of tumor metastasis in 11 cases. Factors such as tumor size, Ki-67 positivity, and distant metastasis may correlate with worse outcomes and demonstrate potential as prognostic indicators for intradural spinal chordomas. Further research is needed to improve understanding of this tumor and develop optimal treatment paradigms for these patients.

Sibling support exchange in late adulthood moderates the long-term impact of childhood neglect on psychological outcomes.

Objectives: Sibling relationships are often the longest-lasting and serve as a source of support and comfort for many older adults. The current study examined the moderating effect of sibling support exchange in the association between childhood maltreatment and mental health outcomes.Method: Using data from the Wisconsin Longitudinal Study (WLS), we analyzed a sample of older adults whose selected sibling was alive across the three data collections (baseline N = 4,041). Longitudinal multilevel regression models were estimated.Results: Key results showed that a history of neglect was associated with decreased psychological well-being, and all three forms of childhood maltreatment were related to increased depressive symptoms. We also found that sibling support exchange mitigated the negative mental health effects of childhood neglect.Conclusion: Our findings suggest that siblings may be uniquely positioned to support older adults who grew up in a neglectful family environment. Older adults may be encouraged to promote resilience by strengthening their sibling relationships.

Epidemiologic Assessment of Craniosynostosis in Mississippi's Pediatric Population from 2015 to 2020.

OBJECTIVES: This study aimed to report geographic and demographic patterns of patients with craniosynostosis (CS) treated at Children's of Mississippi, the state's only American Cleft Palate-Craniofacial Association-approved craniofacial team. METHODS: Patients with CS were treated at a tertiary pediatric hospital cared for by craniofacial surgeons and neurosurgeons from 2015 to 2020. Demographic, geographic, and CS diagnosis details, including sex, gestational age, race, ethnicity, insurance status, and affected cranial suture type(s), number, and associated syndromic diagnosis were collected, including birth county and total live births from state data. Significant differences between prevalence of CS in four regions of Mississippi were examined using two-tailed t tests (P < 0.05). RESULTS: Among 222,819 live births in Mississippi between 2015 and 2020, 79 pediatric patients presented to Children's of Mississippi with CS, with an overall incidence of 0.355/1000 live births. Most cases were nonsyndromic CS (82%, n = 65) affecting a single major cranial suture (81%, n = 64). The overall incidence of CS was higher in the coastal and central regions compared with northeast Mississippi, at 0.333 and 0.527 vs 0.132/1000 live births (P = 0.012 and P = 0.004), respectively. CONCLUSIONS: Results from this study suggest regional patterns of CS in Mississippi, which may reflect actual incidence patterns or proximity to Children's of Mississippi. Further study could reveal regional differences in risk factors underlying CS incidence or access to specialized CS care for different regions in the state. This will lead to opportunities for institutional outreach to decrease the burden of CS care in Mississippi.

Posterior Vault Distraction in the Acute Setting.

ABSTRACT: Posterior vault distraction osteogenesis (PVDO) has been shown to resolve acute intracranial hypertension (AIH) while carrying an acceptable perioperative morbidity profile. PVDO has been associated with symptomatic improvement and fewer surgeries in those requiring ventriculoperitoneal shunts. The authors' experience using PVDO as an acute intervention is presented, demonstrating its safety and efficacy for management of AIH. Four cases of children with craniosynostosis that underwent PVDO in the acute setting are outlined. All patients presented with papilledema and symptoms of AIH. One patient with slit ventricle syndrome (SVS) presented with a nonfunctioning shunt following multiple shunt revisions. No intraoperative complications during distractor placement or removal were reported. Distraction protocol for all patients began on postoperative day 1 at 1-2 mm per day, resulting in an average total distraction of 30.25 mm. For the 3 cases with no shunt, the average length of stay was 7 days. As part of the planned treatment course, the patient with SVS required externalization of the shunt during distraction followed by early distractor removal and planned shunt replacement. One case of surgical site infection (in an immunocompromised patient) required premature distractor removal during the consolidation period. Computed tomography (CT) in all patients indicated increased intracranial volume following distraction, and symptomatic improvement was reported. Six-month follow-up showed resolution of papilledema in all patients. The authors' experience using PVDO in the acute setting is reported, alongside a review of current literature, in order to provide supporting evidence for the efficacy of PVDO as a tool for resolving AIH.

The therapist role in parent-led cognitive behavioral therapy for children after trauma: treating trauma from a distance.

This article examines the therapist experience of their role in providing Stepped Care Cognitive-Behavioral-Therapy for Children after Trauma (SC-CBT-CT), a semi-homebased, parent-led trauma-treatment for children (7-12). Previous research has documented that parent-led, therapist-assisted psychological interventions are an acceptable and effective type of service delivery. Yet, the therapist perspective on their role when providing parent-led treatments has received limited research attention. Attention is therefore directed to the therapist experience of engaging parents, establishing relationships, and working with children's trauma narratives from a distance-through the engagement of parents. The data material consists of semi-structured interviews with SC-CBT-CT therapists. To identify patterns of experience, thought, and viewpoints in the overall data, a stepwise thematic analysis approach was applied. Two core themes emerged: 1) Perceptions of therapeutic control and therapeutic presence when engaging parents to lead their own children through an exposure-based program; 2) Establishment and maintenance of therapeutic alliances with and between parents and children. Although parents are inherently well-positioned to engage with their own children about trauma, the article highlights that treatment adherence, progression, and perseverance is contingent upon systematic therapist guidance, monitoring, and availability for support and problem-solving.

Depiction of Homemade Infant Formula and Formula Hacks on Pinterest: An Unsafe and Unhealthy Pin for Infants?

PURPOSE: To examine Pinterest pins to discern the content, messaging and claims, and engagement with pins regarding formula hacking and homemade formula. BACKGROUND: The American Academy of Pediatrics and the Centers for Disease Control and Prevention discourage formula hacking (ie, preparing formula not according to directions to extend its use) and making homemade infant formula due to its associated health risks. Yet, caregivers are using social media platforms to find information on these topics. METHODS: This study conducted a content analysis of Pinterest pins related to formula hacking and homemade infant formula identified from the platform in January 2023 by using 14 search terms. RESULTS: A total of 63 pins were included in the sample. The topic of all (100.0%) pins was homemade formula. More than one-half (56.0%) of the 25 pins that provided a recipe included an unsafe ingredient, such as raw milk. The most frequently provided reasons to use homemade infant formula were in an emergency (38.2%) and when breastfeeding was not possible (38.2%). The most common claim was that homemade infant formula was healthy (59.6%). The total number of followers for the 63 pins was 861 636. CONCLUSIONS: Pinterest is widely used by caregivers to find feeding information for their infants. Credible organizations should utilize Pinterest to disseminate safe infant feeding practices supported by the Centers for Disease Control and Prevention and the American Academy of Pediatrics. IMPLICATIONS: The results will help nurses advocate for safe infant feeding and help them guide caregivers away from unsafe formula practices found on social media.

Cardiovascular events and risk in patients with systemic lupus erythematosus: Systematic literature review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that typically affects women aged 16-55 years. Cardiovascular disease (CVD) is a well-recognized complication of SLE. This systematic literature review and meta-analysis evaluated the relative risk (RR; compared with non-SLE controls), absolute risk (AR; as incidence proportion, n/N), and incidence rate (IR) of CVD events (including stroke, myocardial infarction [MI], and CVD [composite or undefined]) in adult patients with SLE. The RR of CV risk factors (including hypertension, diabetes, and metabolic syndrome [MetS]) was also examined. METHODS: PubMed and Embase were searched on September 10, 2020. Observational studies published between January 2010 and September 2020 that reported RR, AR, and/or IR of CVD events, or RR of CV risk factors, were eligible. Pooled risk estimates were calculated using a random-effects model. RESULTS: Forty-six studies (16 cross-sectional, 15 retrospective cohort, 14 prospective cohort, and 1 case-control) were included in meta-analyses. Most studies were considered high quality (Critical Appraisal Skills Programme checklists). Compared with adults without SLE, patients with SLE had statistically significantly higher RRs (95% CIs) of stroke (2.51 [2.03-3.10]; 12 studies), MI (2.92 [2.45-3.48]; 11 studies), CVD (2.24 [1.94-2.59]; 8 studies), and hypertension (2.70 [1.48-4.92]; 7 studies). RRs of diabetes (1.24 [0.78-1.96]; 3 studies) and MetS (1.49 [0.95-2.33]; 7 studies) were elevated but not significant. RRs of stroke and MI were generally higher in younger versus older patients with SLE. In patients with SLE, the pooled estimate of AR (95% CI) was 0.03 (0.02-0.05), 0.01 (0.00-0.02), and 0.06 (0.03-0.10) for stroke (7 studies), MI (6 studies), and CVD (8 studies), respectively. The pooled estimate of IR per 1000 person-years (95% CI) was 4.72 (3.35-6.32), 2.81 (1.61-4.32), and 11.21 (8.48-14.32) for stroke (10 studies), MI (6 studies), and CVD (8 studies), respectively. Although heterogeneity (based on I2 value) was high in most analyses, sensitivity analyses confirmed the robustness of the pooled estimates. CONCLUSIONS: This meta-analysis found an increased risk of stroke, MI, CVD, and hypertension in patients with SLE compared with the general population, despite substantial heterogeneity across the included studies.

Large carnivores avoid humans while prioritizing prey acquisition in anthropogenic areas.

Large carnivores are recovering in many landscapes where the human footprint is simultaneously growing. When carnivores encounter humans, the way they behave often changes, which may subsequently influence how they affect their prey. However, little research investigates the behavioural mechanisms underpinning carnivore response to humans. As a result, it is not clear how predator-prey interactions and their associated ecosystem processes will play out in the human-dominated areas into which carnivore populations are increasingly expanding. We hypothesized that humans would reduce predation risk for prey by disturbing carnivores or threatening their survival. Alternatively, or additionally, we hypothesized that humans would increase predation risk by providing forage resources that congregate herbivorous prey in predictable places and times. Using grey wolves Canis lupus in Jackson Hole, Wyoming, USA as a study species, we investigated 170 kill sites across a spectrum of human influences ranging from heavily restricted human activities on protected federal lands to largely unregulated activities on private lands. Then, we used conditional logistic regression to quantify how the probability of predation changed across varied types and amounts of human influences, while controlling for environmental characteristics and prey availability. Wolves primarily made kills in environmental terrain traps and where prey availability was high, but predation risk was significantly better explained with the inclusion of human influences than by environmental characteristics alone. Different human influences had different, and even converse, effects on the risk of wolf predation. For example, where prey were readily available, wolves preferentially killed animals far from motorized roads but close to unpaved trails. However, wolves responded less strongly to humans, if at all, where prey were scarce, suggesting they prioritized acquiring prey over avoiding human interactions. Overall, our work reveals that the effects of large carnivores on prey populations can vary considerably among different types of human influences, yet carnivores may not appreciably alter predatory behaviour in response to humans if prey are difficult to obtain. These results shed new light on the drivers of large carnivore behaviour in anthropogenic areas while improving understanding of predator-prey dynamics in and around the wildland-urban interface.