The use of an intermittent schedule of reinforcement to evaluate detection dogs' generalization from smokeless-powder.

Odor generalization is essential for detection dogs. Regardless of its importance, limited research is available on detection dog odor generalization. The objectives of this study were (1) evaluate the use of an intermittent schedule of reinforcement to assess generalization in dogs and (2) evaluate olfactory generalization from a single exemplar of smokeless powder (SP). Dogs (N = 5) were trained to detect SP in an automated olfactometer under an intermittent schedule of reinforcement where only 60% of correct responses were reinforced. After training, eight non-reinforced probe trials were inserted within a session. A total of 15 testing odors were evaluated across 15 consecutive sessions (one odor/session). Six of the testing odors were control and the remaining testing odors were objects indirectly exposed to SP, objects that contained or were directly exposed to SP, single-base SP and diphenylamine (the main volatile present in the headspace of SP). Dogs' response rate to all testing odors except for the cotton gauzes and t-shirt cloths exposed to the headspace of SP, the simulated IED, and Getxent tubes exposed to direct contact with SP were statistically lower than their response rate of actual SP. The response rate to SP was not different across all 15 testing sessions suggesting that the intermittent schedule of reinforcement, maintained dog motivation and performance. Data show that the outlined method is a good approach to study generalization in detection dogs. These results also highlight dog generalization to SP varieties and associated odors.

Stem cell therapy for preventing neonatal diseases in the 21st century: Current understanding and challenges.

Diseases of the preterm newborn such as bronchopulmonary dysplasia, necrotizing enterocolitis, cerebral palsy, and hypoxic-ischemic encephalopathy continue to be major causes of infant mortality and long-term morbidity. Effective therapies for the prevention or treatment for these conditions are still lacking as recent clinical trials have shown modest or no benefit. Stem cell therapy is rapidly emerging as a novel therapeutic tool for several neonatal diseases with encouraging pre-clinical results that hold promise for clinical translation. However, there are a number of unanswered questions and facets to the development of stem cell therapy as a clinical intervention. There is much work to be done to fully elucidate the mechanisms by which stem cell therapy is effective (e.g., anti-inflammatory versus pro-angiogenic), identifying important paracrine mediators, and determining the timing and type of therapy (e.g., cellular versus secretomes), as well as patient characteristics that are ideal. Importantly, the interaction between stem cell therapy and current, standard-of-care interventions is nearly completely unknown. In this review, we will focus predominantly on the use of mesenchymal stromal cells for neonatal diseases, highlighting the promises and challenges in clinical translation towards preventing neonatal diseases in the 21st century.

Pediatric Colorectal Surgery: A Collaborative Approach From a Single Institution.

BACKGROUND: Inflammatory bowel disease encompasses relapsing gastrointestinal disorders commonly presenting in pediatric patients, with 25% of diagnoses made before age 20 and 4% before age 5. Considering the need for life-long surgical follow-up, a collaborative system involving both pediatric and colorectal surgeons could improve overall patient experiences. We hypothesized that cases performed in collaboration with both pediatric and adult colorectal surgeons may lead to better outcomes. METHODS: Data were gathered retrospectively for 116 patients 18 y old or younger who underwent colorectal resections for inflammatory bowel disease between 2010 and 2017 at our institution. Data included patient demographics, type of procedure, surgical approach, specimen extraction site, surgeon involvement (pediatric, colorectal, or collaborative), operative time, and estimated blood loss. We analyzed days until passage of flatus and bowel movement, length of stay, type of surgical procedure, and surgical complications. RESULTS: Our data showed that days until flatus (2.27 ± 0.47, P = 0.049), first bowel movement (2.64 ± 0.67, P = 0.006), and length of stay (4.45 ± 1.51, P = 0.006) were the shortest in the collaborative group. We also found that single-incision laparoscopic surgery was significantly more common in the collaborative group (77.8%, P = 0.002). We did not see a difference in surgical complication rates among any of the groups. CONCLUSIONS: Our study showed short-term beneficial outcomes in a single institution associated with the collaboration of pediatric surgeons and colorectal surgeons on pediatric colorectal cases in comparison to those performed by pediatric surgeons or adult colorectal surgeons alone.

Examining the Effect of Threatened Masculinity on Gun Violence.

Gun violence is considered a national epidemic in the United States. In 2020, approximately 45,000 people were killed due to firearm-related injuries in the United States alone. However, research has struggled to identify a comprehensive list of risk factors associated with gun violence. One such risk factor could be threatened masculinity. This study aims to examine the effect of threatened masculinity on gun violence. As such a 2 (intervention x 3 (time) mixed design will be used. Each participant will be given a baseline assessment of their masculinity, using the Masculinity Contingency Scale. Using a variation of the hot sauce paradigm, participants will be asked to answer the Heinz Dilemma, and told that another participant will read their response, and then give the first participant an audio recording about what they think of their response. At this point, participants will be randomly assigned to one of two conditions. They will either have their masculinity threatened or be assigned to a control group. Following this, participants will be asked to play a game involving an online voodoo doll where they will be asked to pretend the voodoo doll is the person from the recording, and to shoot the voodoo doll. It is predicted that those in the experimental group will shoot the voodoo doll more than the control group.

Real-World Data: Applications and Relevance to Cancer Clinical Trials.

Randomized controlled trials (RCTs) are the gold standard for comparative-effectiveness research (CER). Since the 1980s, there has been a rise in the creation and utilization of large national cancer databases to provide readily accessible "real-world data" (RWD). This review article discusses the role of RCTs in oncology, and the role of RWD from the national cancer database in CER. RCTs remain the preferred study type for CER because they minimize confounding and bias. RCTs have challenges to conduct, including extensive time and resources, but these factors do not impact the internal validity of the result. Generalizability and external validity are potential limitations of RCTs. RWD is ideal for studying cancer epidemiology, patterns of care, disparities in care delivery, quality-of-care evaluation, and applicability of RCT data in specific populations excluded from RCTs. However, retrospective databases with RWD have limitations in CER due to unmeasured confounders and are often suboptimal in identifying causal treatment effects.

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer.

PURPOSE: Accelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation. METHODS AND MATERIALS: This was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period. RESULTS: From 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience. CONCLUSIONS: APBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.

Variation in acute fluid resuscitation among pediatric burn centers.

BACKGROUND: Accurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates. METHODS: Five pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received. RESULTS: Differences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers' resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35ml/kg/% TBSA, p<0.001), (4.90 versus 6.35ml/kg/TBSA, p=0.002) and (3.38 versus 6.35ml/kg/TBSA, p<0.0001). CONCLUSIONS: This variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.

Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC) is a leading cause of death in premature infants. Breast feeding decreases the incidence of NEC but, even with aggressive promotion of nursing in Neonatal Intensive Care Units, morbidity and mortality remain high. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) purified from mouse and rat stem cells can protect the intestines from NEC. The aim of this study was to determine whether human breast milk (BM)-derived EVs could prevent NEC. METHODS: EVs were purified from human donor breast milk. NEC was induced in premature rat pups by exposure to asphyxia/hypothermia/hypercaloric feeds. Pups were randomized to: (1) breast fed, no injury, (2) NEC, (3) NEC + BM-derived EVs once intraperitoneally (IP), (4) NEC + BM-derived EVs enterally (PO) with each feed. Intestinal tracts were examined for histologic damage. Additionally, the effect of BM-derived EVs on intestinal epithelial cells (IEC) subjected to hypoxia/reoxygenation injury in vitro was examined. RESULTS: NEC incidence was 0% in breast-fed pups and 62% in pups subjected to NEC. IP administration of BM-derived EVs decreased NEC incidence to 29% and enteral administration further decreased NEC incidence to 11.9%. (p < 0.05). BM-derived EVs significantly increased cell proliferation and decreased apoptosis in IEC in vitro. CONCLUSION: Breast milk-derived EVs delivered either IP or enterally significantly decrease the incidence and severity of experimental NEC, protect IEC from injury in vitro, and may represent an innovative therapeutic option for NEC in the future. TYPE OF STUDY: Basic science study. LEVEL OF EVIDENCE: N/A.

Potential role of stem cells in disease prevention based on a murine model of experimental necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating disease of newborns, and despite years of research, there is no known cure. The mortality rate of infants with NEC remains as high as 20%-30%. Babies who survive NEC frequently have long term complications including short gut syndrome, developmental delays and neurological sequelae. Unfortunately, despite much research over the past years, the precise pathogenesis of the disease is still not completely understood. METHODS: Our laboratory has focused on identifying novel therapies to prevent the disease, including the use of stem cells (SC), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and recently, stem cell derived-exosomes, a type of nanovesicle, to combat this illness. RESULTS: We have outlined the major SC lines and data suggesting potential benefit as a curative or preventive approach for NEC as well as describing several new therapeutic strategies, including stem cell derived- exosomes and HB-EGF for decreasing the incidence and severity of this disease in rat models in our lab. CONCLUSION: Overall, our lab has demonstrated that these different types of SC equivalently reduce the incidence and severity of NEC and equally preserve intestinal barrier function during NEC. We have previously demonstrated that AF-MSC can protect the intestines from intestinal injury and may therefore hold strong therapeutic potential for the prevention of NEC. Most recently, our work with stem cell derived-exosomes has shown them to be equivalent to their derived SC lines in decreasing the incidence of this disease.