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AimsSurgical costs are a major component of healthcare expenditures in the USA. Intraoperative communication is a key factor contributing to patient outcomes. However, the effectiveness of communication is only partially determined by the surgeon, and understanding how non-surgeon personnel affect intraoperative communication is critical for the development of safe and cost-effective staffing guidelines. Operative efficiency is also dependent on high-functioning teams and can offer a proxy for effective communication in highly standardized procedures like primary total hip and knee arthroplasty. We aimed to evaluate how the composition and dynamics of surgical teams impact operative efficiency during arthroplasty.MethodsWe performed a retrospective review of staff characteristics and operating times for 112 surgeries (70 primary total hip arthroplasties (THAs) and 42 primary total knee arthroplasties (TKAs)) conducted by a single surgeon over a one-year period. Each surgery was evaluated in terms of operative duration, presence of surgeon-preferred staff, and turnover of trainees, nurses, and other non-surgical personnel, controlling cases for body mass index, presence of osteoarthritis, and American Society of Anesthesiologists (ASA) score.ResultsTurnover among specific types of operating room staff, including the anaesthesiologist (p = 0.011), circulating nurse (p = 0.027), and scrub nurse (p = 0.006), was significantly associated with increased operative duration. Furthermore, the presence of medical students and nursing students were associated with improved intraoperative efficiency in TKA (p = 0.048) and THA (p = 0.015), respectively. The presence of surgical fellows (p > 0.05), vendor representatives (p > 0.05), and physician assistants (p > 0.05) had no effect on intraoperative efficiency. Finally, the presence of the surgeon’s 'preferred' staff did not significantly shorten operative duration, except in the case of residents (p = 0.043).ConclusionOur findings suggest that active management of surgical team turnover and composition may provide a means of improving intraoperative efficiency during THA and TKA.Cite this article: Bone Joint J2021;103-B(2):347–352.

Computational biology is enabling an explosive growth in our understanding of stem cells and our ability to use them for disease modeling, regenerative medicine, and drug discovery. We discuss four topics that exemplify applications of computation to stem cell biology: cell typing, lineage tracing, trajectory inference, and regulatory networks. We use these examples to articulate principles that have guided computational biology broadly and call for renewed attention to these principles as computation becomes increasingly important in stem cell biology. We also discuss important challenges for this field with the hope that it will inspire more to join this exciting area.

Sexually violent predator (SVP) statutes are unique in that these laws allow for the indefinite civil psychiatric commitment of sex offenders after their criminal sentences have been served. In addition to the high cost of psychiatric hospitalization, recently observed low base rates of sexual recidivism of sex offenders released from custody suggest that, in select SVP cases, a collaborative justice model of outpatient placement may be feasible in lieu of lengthy and costly placement in state hospitals. Given its position as one of the states with a large number of SVP commitments, California offers an opportunity to implement a collaborative justice model for adult sex offenders found to meet SVP criteria. In this article, a template for such a model is suggested. Admittedly, this model faces multiple obstacles, both within the judicial system and in the public arena. Nonetheless, public concerns may be mitigated through high-control parole plus additional treatment and controls, interim halfway house placement, and community prosocial support systems. [ABSTRACT FROM AUTHOR]

Pediatric practice increasingly involves providing care for children with medical complexity. Telehealth offers a strategy for providers and health care systems to improve care for these patients and their families. However, lack of awareness related to the unintended negative consequences of telehealth on vulnerable populations--coupled with failure to intentional design best practices for telehealth initiatives--implies that these novel technologies may worsen health disparities in the long run. This article reviews the positive and negative implications of telehealth. In addition, to achieve optimal implementation of telehealth, it discusses 10 considerations to promote optimal care of children using these technologies.

(Abstracted from Birth2022;49:805–811Meconium-stained amniotic fluid (MSAF) occurs in up to 52% of postterm pregnancies, 25% of term pregnancies, and 5% of pregnancies <37 weeks of gestation. As a sign of fetal maturity, MFAS may also help signal fetal distress.

Introduction:Terrorism remains a major threat and concern in many countries around the world. Children represent approximately 30% of the world population and in the event of a terrorist attack can either be primary targets, to include the possibility of abduction, or unintended victims. Children are unique in their vulnerabilities and therefore, require special consideration.Method:This study is a semi-quantitative epidemiological analysis of all terrorism-related pediatric fatalities and injuries sustained between 1970-2019. Data collection was performed using a retrospective database search through the Global Terrorism Database (GTD). Summaries of events including search terms associated with children were individually reviewed and those describing the deaths, injuries, or abduction of children were tallied.Results:Of the over 200,000 terror events, 2,302 events met inclusion criteria. This represented 1.14% of total events which involved death, injury, or abduction of children. Of 2,032 events a total of 2,275 pediatric fatal injuries (FI) were recorded, as well as 2,280 pediatric non-fatal injuries (NFI). The most common weapons used in all attacks involving the pediatric population were explosives (1539[66.8%]), firearms (543 [23.5%]), other (169 [7.3%]) and melee (83 [3.6%]). 275 of the 2,032 were related to abductions, with 71 cases involving the abduction of ten children or more.Conclusion:Pediatric casualties in terrorist events represent a small proportion of overall victims, however, they have unique vulnerabilities, and when directly impacted by terrorism, can have long term physical and psychosocial sequelae, as well as a devastating emotional impact on the community.

Abstract:There is an emerging discussion of whether or not antisemitism, especially its Nazi form, can be said to be metaphysical in nature. The supposed metaphysical quality is intended to explain the peculiar intensity of Jew hatred. Robert Wistrich, David Patterson, and others have held that antisemitism is metaphysical; I say that it is not. Instead, I argue that the intensity of Nazi antisemitism arose from its role in Nazism as a political religion and revolutionary movement. The concept of sacrifice is also examined. I conclude that to explain the magnitude and cruelty of the Holocaust, or catastrophes that may be in some respects comparable, it is not helpful to invoke metaphysics—the rise of modern political religions and the individual sociopathy of many of their leaders are more appropriate determining factors.

Acute kidney injury (AKI) is a major risk factor for long-term adverse outcomes, including chronic kidney disease. In mouse models of AKI, maladaptive repair of the injured proximal tubule (PT) prevents complete tissue recovery. However, evidence for PT maladaptation and its etiological relationship with complications of AKI is lacking in humans. We performed single-nucleus RNA sequencing of 120,985 nuclei in kidneys from 17 participants with AKI and seven healthy controls from the Kidney Precision Medicine Project. Maladaptive PT cells, which exhibited transcriptomic features of dedifferentiation and enrichment in pro-inflammatory and profibrotic pathways, were present in participants with AKI of diverse etiologies. To develop plasma markers of PT maladaptation, we analyzed the plasma proteome in two independent cohorts of patients undergoing cardiac surgery and a cohort of marathon runners, linked it to the transcriptomic signatures associated with maladaptive PT, and identified nine proteins whose genes were specifically up- or down-regulated by maladaptive PT. After cardiac surgery, both cohorts of patients had increased transforming growth factor–β2 (TGFB2), collagen type XXIII-α1 (COL23A1), and X-linked neuroligin 4 (NLGN4X) and had decreased plasminogen (PLG), ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6), and protein C (PROC). Similar changes were observed in marathon runners with exercise-associated kidney injury. Postoperative changes in these markers were associated with AKI progression in adults after cardiac surgery and post-AKI kidney atrophy in mouse models of ischemia-reperfusion injury and toxic injury. Our results demonstrate the feasibility of a multiomics approach to discovering noninvasive markers and associating PT maladaptation with adverse clinical outcomes.

Background: There are limited data on the impact of chronic moderate or severe anaemia on the clinical outcomes of patients with acute coronary syndrome undergoing coronary angiography or percutaneous coronary intervention.Methods: We retrospectively compared two groups of consecutive patients with acute coronary syndrome according to their haemoglobin level on admission. The research group (n=89) had a haemoglobin level of 10.9 g/dl or less and a control group (n=79) of age-matched patients had a haemoglobin level greater than 10.9 g/dl. We studied drug therapy before, during and after intervention, and performed 1-year follow-up of bleeding complications according to the Bleeding Academic Research Consortium criteria, all-cause mortality and re-infarction, as well as haemoglobin level on discharge, 6 and 12 months after admission.Results: Compared to controls, a haemoglobin level less than 10.9 g\dl on admission is associated with a higher rate of major bleeding: 26 patients (32%) versus none in the control group (P<0.001); and the use of packed red blood cell (RBC) transfusion: nine patients (11.7%) versus none in the control group (P=0.003) within the first 6 months post-catheterisation. However, the re-infarction rate and mortality were similar in the study and control groups: 9.2% versus 9.7% (P=0.915) and 12.6% versus 8.9% (P=0.434), accordingly.Conclusions: Chronic moderate or severe anaemia in patients with acute coronary syndrome undergoing coronary angiography or percutaneous coronary intervention is associated with a substantially increased risk of bleeding in the first 6 months. However, rates of mortality and re-infarction were similar.

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.

The organization and expression of Pseudomonas stutzeriST-9 genes related to toluene catabolism and porin synthesis was investigated. Toluene-degrading genes were found to be localized in the chromosome close to a phage-type integrase. A regulatory gene and 21 genes related to an aromatics degradation pathway are organized as a putative operon. These proteins are upregulated in the presence of toluene. Fourteen outer membrane proteins were identified as porins in the ST-9 genome. The identified porins showed that the main detected porins are related to the OmpA and OprD superfamilies. The percentage of porins in the outer membrane protein fraction, as determined by mass spectrometry, was 73% and 54% when the cells were cultured with toluene and with glucose, respectively. Upregulation of OmpA and downregulation of OprD occurred in the presence of toluene. A porin fraction (90% OprD) from both cultures was isolated and examined as a toluene uptake system using the liposome-swelling assay. Liposomes were prepared with the porin fraction from a culture that was grown on toluene (T-proteoliposome) or glucose (G-proteoliposome). There was no significant difference in the permeability rate of the different solutes through the T-proteoliposome and the G-proteoliposome.

Introduction:In 2022, the Harvard/Beth Israel Deaconess Disaster Medicine Fellowship conducted a full-scale exercise (FSX) with the dual mission of 1) training Disaster Medicine Fellows (DMFs) in exercise design, planning, and execution, and 2) expanding local first responder experience with pediatric casualties in a mixed-method terrorist attack.Method:Project PUNCH (Preparedness for Uncertain and Novel Chemical Hazards) was planned in two stages. A tabletop exercise in the form of a facilitated discussion was conducted in March 2022 with stakeholders from Fire, Emergency Medical Services (EMS), and the Massachusetts HazMat Team. A FSX simulating a combined blast and chemical attack on a family gathering was held in June 2022 at Anna Maria College in Paxton, MA.Results:Fire, EMS, HazMat, LifeFlight, local Police, MA State Police, a local Medical Reserve Corps, and over 40 volunteer victims including 16 pediatric volunteers participated in the FSX. The FSX was a two-hour exercise with a simulated explosion and a secondary drone-deployed dummy-opioid aerosol release. This was the first FSX for the Paxton Region since the coronavirus pandemic began. Planning was conducted by the DMFs between January and June 2022 with the aid of Fellowship faculty and local stakeholders following Homeland Security Exercise and Evaluation Program guidelines. Local and Fellowship leadership with Pediatric expertise were engaged to plan pediatric specific considerations, precautions and safety measures. COVID precaution guidelines were followed. These efforts are detailed in the forthcoming field report. Educational guides for toxidromes and triage and resuscitation of pediatric victims were distributed to first responders.Conclusion:The end outcome was a FSX that trained DMFs in exercise design, planning, and execution, and increased experience of local first responders with the concepts of asymmetric terrorist attacks and comfort with pediatric disaster victims. Multi-agency disaster drills remain an important training tool for preparedness and response to mass casualty events.

The purpose of this study is to examine whether an overlap between compensation and audit committee memberships in firms affects earnings quality. We use a sample of 625 firm-year observations comprising data collected from Australian publicly listed firms between 2004 and 2010. Four measures of earnings quality are utilised to test our hypothesis. We find that firms with compensation and audit committee overlap exhibit higher earnings quality. Such sub-committee overlap is also more effective when overlapped members are independent and financial experts. Additional findings also indicate that female overlapped members are effective in reducing extreme earnings management. Findings have clear practical and regulatory implications in terms of the efficacy of sub-committee overlap.

Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients. Single-cell analysis shows that following engraftment in the bone marrow niche, these engineered HSCs further specify to a hybrid cell type, in which distinct gene regulatory networks of hematopoietic stem/progenitors and differentiated hematopoietic lineages are co-expressed. Our work demonstrates engineering of fully functional HSCs via modulation of genetic programs that govern self-renewal and lineage priming.

Burst-forming unit erythroid progenitors (BFU-Es) are so named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of “bursts” of smaller erythroid colonies derived from the later colony-forming unit erythroid progenitor erythropoietin (Epo)–dependent progenitors. “Early” BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do “late” BFU-Es forming small colonies, but the mechanism underlying this heterogeneity remains unknown. We show that the type III transforming growth factor β (TGF-β) receptor (TβRIII) is a marker that distinguishes early and late BFU-Es. Transient elevation of TβRIII expression promotes TGF-β signaling during the early BFU-E to late BFU-E transition. Blocking TGF-β signaling using a receptor kinase inhibitor increases early BFU-E cell self-renewal and total erythroblast production, suggesting the usefulness of this type of drug in treating Epo-unresponsive anemias.

The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs). In murine cells, LIN28A and LIN28B facilitate conversion from naive to primed pluripotency. Proteomic and metabolomic analysis highlighted roles for LIN28 in maintaining the low mitochondrial function associated with primed pluripotency and in regulating one-carbon metabolism, nucleotide metabolism, and histone methylation. LIN28 binds to mRNAs of proteins important for oxidative phosphorylation and modulates protein abundance. Thus, LIN28A and LIN28B play cooperative roles in regulating reprogramming, naive/primed pluripotency, and stem cell metabolism.

Mutations in the PARN gene (encoding poly(A)-specific ribonuclease) cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita, but how PARN deficiency impairs telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem cells (iPSCs) from patients with dyskeratosis congenita with PARN mutations, we show that PARN is required for the 3′-end maturation of the telomerase RNA component (TERC). Patient-derived cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3′ termini shows that PARN is required for removal of post-transcriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results demonstrate a new role for PARN in the biogenesis of TERC and provide a mechanism linking PARN mutations to telomere diseases.

Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of the CM maturation that is subsequently required to generate adult myocytes remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs), which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStatCMthat indexes CM maturation status. MatStatCMreveals that pluripotent-stem-cell-derived CMs mature early in culture but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation.