Developing the Quantitative Histopathology Image Ontology : A case study using the hot spot detection problem

Interoperability across data sets is a key challenge for quantitative histopathological imaging. There is a need for an ontology that can support effective merging of pathological image data with associated clinical and demographic data. To foster organized, cross-disciplinary, information-driven collaborations in the pathological imaging field, we propose to develop an ontology to represent imaging data and methods used in pathological imaging and analysis, and call it Quantitative Histopathological Imaging Ontology – QHIO. We apply QHIO to breast cancer hot-spot detection with the goal of enhancing reliability of detection by promoting the sharing of data between image analysts

Conversations About Everything

Conversations about Everything is based on a three way conversation about a performative educational project called Mapping Strange Assemblages. This was a part of UAL/London College of Communication‘s contribution the 2018 London Design Festival and the Design School’s Public Programme. It rhizomatically maps out the interventions by a group of students and alumni who where named the Band of Animateurs (BOAs). As an assemblages it attempts to create a visual and narrative affect that mirrored the performances during the Exhibition, Everything Happens So Much’

A Comparative Finite-Element Analysis of Bone Failure and Load Transfer of Osseointegrated Prostheses Fixations

An alternative solution to conventional stump–socket prosthetic limb attachment is offered by direct skeletal fixation. This study aimed to assess two percutaneous trans-femoral implants, the OPRA system (Integrum AB, Göteborg, Sweden), and the ISP Endo/Exo prosthesis (ESKA Implants AG, Lübeck, Germany) on bone failure and stem–bone interface mechanics both early post-operative (before bony ingrowth) and after full bone ingrowth. Moreover, mechanical consequences of implantation of those implants in terms of changed loading pattern within the bone and potential consequences on long-term bone remodeling were studied using finite-element models that represent the intact femur and implants fitted in amputated femora. Two experimentally measured loads from the normal walking cycle were applied. The analyses revealed that implantation of percutaneous prostheses had considerable effects on stress and strain energy density levels in bone. This was not only caused by the implant itself, but also by changed loading conditions in the amputated leg. The ISP design promoted slightly more physiological strain energy distribution (favoring long-term bone maintenance), but the OPRA design generated lower bone stresses (reducing bone fracture risk). The safety factor against mechanical failure of the two percutaneous designs was relatively low, which could be improved by design optimization of the implants

Ipilimumab augments antitumor activity of bispecific antibody-armed T cells

BACKGROUND: Ipilimumab is an antagonistic monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4) that enhances antitumor immunity by inhibiting immunosuppressive activity of regulatory T cells (Treg). In this study, we investigated whether inhibiting Treg activity with ipilimumab during ex vivo T cell expansion could augment anti-CD3-driven T cell proliferation and enhance bispecific antibody (BiAb)-redirected antitumor cytotoxicity of activated T cells (ATC). METHODS: PBMC from healthy individuals were stimulated with anti-CD3 monoclonal antibody with or without ipilimumab and expanded for 10-14 days. ATC were harvested and armed with anti-CD3 x anti-EGFR BiAb (EGFRBi) or anti-CD3 x anti-CD20 BiAb (CD20Bi) to test for redirected cytotoxicity against COLO356/FG pancreatic cancer cell line or Burkitt’s lymphoma cell line (Daudi). RESULTS: In PBMC from healthy individuals, the addition of ipilimumab at the initiation of culture significantly enhanced T cell proliferation (p = 0.0029). ATC grown in the presence of ipilimumab showed significantly increased mean tumor-specific cytotoxicity at effector:target (E:T) ratio of 25:1 directed at COLO356/FG and Daudi by 37.71% (p < 0.0004) and 27.5% (p < 0.0004), respectively, and increased the secretion of chemokines (CCL2, CCL3, CCL4,CCL5, CXCL9, and granulocyte-macrophage colony stimulating factor(GM-CSF)) and cytokines (IFN-γ, IL-2R, IL-12, and IL-13), while reducing IL-10 secretion. CONCLUSIONS: Expansion of ATC in the presence of ipilimumab significantly improves not only the T cell proliferation but it also enhances cytokine secretion and the specific cytotoxicity of T cells armed with bispecific antibodies

Parental Psychosocial Factors Moderate Opioid Administration Following Children’s Surgery

BACKGROUND: This investigation aimed to examine the impact of parental psychosocial variables on the administration of opioids to young children experiencing postoperative pain. METHODS: Participants in this longitudinal analysis were children ages 2–12 undergoing tonsillectomy with or without adenoidectomy and their parents. Parents completed validated instruments assessing trait anxiety, perceived stress, and coping style before surgery, and children and parents completed instruments assessing pain and administration of opioids and acetaminophen on days 1, 2, 3, and 7 at home after surgery. The structure of the data was such that parents and children completed multiple data assessments making the data multilevel (ie, days of data within dyads). To address this issue of data structure, multilevel modeling was used to analyze the dataset. RESULTS: Participants included 173 parent-child dyads (mean child age = 5.99 ± 2.51) recruited between 2012 and 2017. We found that parent-related psychosocial variables, such as trait anxiety, stress, and coping style, moderated the relationship between the child’s pain and postoperative medication administration. Specifically, when predicting hydrocodone, the interactions between anxiety and pain and stress and pain were significant; when child pain was high, high-anxiety and high-stressed parents gave their children 19% and 12% more hydrocodone, respectively, compared to low-anxiety and low-stressed parents. When predicting acetaminophen, the interactions between anxiety and pain, a blunting coping style and pain, and a monitoring coping style and pain were significant. CONCLUSIONS: These results suggest the need to identify parents who experience high levels of perceived stress and trait anxiety and use appropriate interventions to manage stress and anxiety. This may ensure children receive optimal amounts of pain medication following surgery

Evaluating Opioid Dispensing Rates among Pediatrics and Young Adults based on CURES Data Reporting in California from 2015–2019

Background Receipt of opioid prescriptions in pediatric and young adult patients may be a risk factor for future opioid misuse. Data from prescription drug monitoring programs provide insight on outpatient opioid use. In our study, we analyzed the opioid dispensing rates for pediatrics and young adults in California. Methods A secondary analysis was performed from 2015–2019 using Controlled Utilization Review and Evaluation System data. This database provides dispensing data of controlled substances in California. Patients younger than 25 years who were prescribed opiates were analyzed by county. We further divided them into two groups (children: ≤14 years; adolescents and young adult: 15–24 years). Descriptive statistics and heat maps were used to illustrate the trends in opioid usage among different age groups. Results The overall percentages for the number of opioids being dispensed to patients aged \u3c25 years have decreased over the past four years. In 2015, 6 out of 58 counties in California were considered “high-rate” with \u3e2.9% of opioids dispensed to patients younger than 25 years old; in 2019, this number reduced to zero. Patients 25 and older received a higher proportion of opioids compared to younger populations; in 2019, 35.91% of opioids were dispensed to patients 45–64, and 8.92% to patients younger than 25. Conclusion Pediatric opioid prescriptions have declined over the recent years. However, a high degree of variability of prescription rates between demographic counties was noted. More studies are warranted in order to understand this discrepancy in opioid prescribing among pediatric and young adult patients

Racial and Ethnic Disparities in Opioid Use for Adolescents at US Emergency Departments

Background Racial/ethnic disparities in the use of opioids to treat pain disorders have been previously reported in the emergency department (ED). Further research is needed to better evaluate the impact race/ethnicity may have on the use of opioids in adolescents for the management of pain disorders in the ED. Methods This was a cross-sectional study using data from the National Hospital Ambulatory Medical Care Survey from 2006 to 2016. Multivariate models were used to evaluate the role of race/ethnicity in the receipt of opioid agonists while in the ED. All ED visits with patients aged 11–21 years old were analyzed. Races/ethnicities were stratified as non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. In addition to race, statistical analysis included the following covariates: pain score, pain diagnosis, age, region, sex, and payment method. Results There was a weighted total of 189,256,419 ED visits. Those visits involved 109,826,315 (58%) non-Hispanic Whites, 46,314,977 (24%) non-Hispanic Blacks, and 33,115,127 (18%) Hispanics, with 21.6% (95% CI, 21.1%-22.1), 15.2% (95% CI, 14.6–15.9%), and 17.4% (95% CI, 16.5–18.2%) of those visits reporting use of opioids, respectively. Regardless of age, sex, and region, non-Hispanic Whites received opioids at a higher rate than non-Hispanic Blacks and Hispanics. Based on diagnosis, non-Hispanic Whites received opioids at a higher rate in multiple pain diagnoses. Additionally, non-Hispanic Blacks and Hispanics were less likely to receive an opioid when reporting moderate pain (aOR = 0.738, 95% CI 0.601–0.906, aOR = 0.739, 95% CI 0.578–0.945, respectively) and severe pain (aOR = 0.580, 95% CI 0.500–0.672, aOR = 0.807, 95% CI 0.685–0.951, respectively) compared to non-Hispanic Whites. Conclusions Differences in the receipt of opioid agonists in EDs among the races/ethnicities exist, with more non-Hispanic Whites receiving opioids than their minority counterparts. Non-Hispanic Black women may be an especially marginalized population. Further investigation into sex-based and regional differences are needed

An anatomical investigation of rare upper limb neuropathies due to the Struthers’ ligament or arcade: a meta-analysis

Background: The Struthers’ ligament (SL) is a fibrous band that originates fromthe supracondylar humeral process and inserts into the medial humeral epicondyle, potentially compressing both the median nerve and brachial artery. The controversial Struthers’ arcade (SA) is a musculotendinous band found in the distal end of the arm that might compress the ulnar nerve. This study aimed to evaluate the pooled prevalence estimate of the SL and SA, and their anatomical features. Materials and methods: A meticulous search of major electronic medical databases was carried out regarding both structures. Applicable articles (and all relevant references) were analysed. Data from the eligible articles was extracted and evaluated. The quality and the potential risk of bias in the included studies were assessed using the AQUA tool. Results: The arcade was reported in 13 studies (510 arms), whereas the ligament in 6 studies (513 arms). The overall pooled prevalence estimate of the ligament was 1.8%, and 52.6% for the arcade. Most frequently, the ulnar nerve was covered by a tendinous arcade (42.2%). In all cases, the ligament inserted into the medial humeral epicondyle, but had various origins. Only 1 study reported compression of the median nerve by the ligament, whilst another contradicted this view. Conclusions: Although the SL is rare, and the SA is a valid anatomical entity (though with a variable presentation), clinically meaningful neurovascular entrapments caused by these structures are infrequent. Nonetheless, a better understanding of each may be beneficial for the best patient outcomes

Evaluating the 0–10 Point Pain Scale on Adolescent Opioid Use in US Emergency Departments

Objective: To evaluate trends in national emergency department (ED) adolescent opioid use in relation to reported pain scores. Methods: A retrospective, cross-sectional analysis on National Hospital Ambulatory Medical Care Survey (NHAMCS) data was conducted on ED visits involving patients aged 11–21 from 2008–2017. Crude observational counts were extrapolated to weighted estimates matching total population counts. Multivariate models were used to evaluate the role of a pain score in the reported use of opioids. Anchors for pain scores were 0 (no pain) and 10 (worst pain imaginable). Results: 31,355 observations were captured, which were extrapolated by the NHAMCS to represent 162,515,943 visits nationwide. Overall, patients with a score of 10 were 1.35 times more likely to receive an opioid than patients scoring a 9, 41.7% (CI95 39.7–43.8%) and 31.0% (CI95 28.8–33.3%), respectively. Opioid use was significantly different between traditional pain score cutoffs of mild (1–3) and moderate pain (4–6), where scores of 4 were 1.76 times more likely to receive an opioid than scores of 3, 15.5% (CI95 13.7–17.3%) and 8.8% (CI95 7.1–10.6%), respectively. Scores of 7 were 1.33 times more likely to receive opioids than scores of 6, 24.7% (CI95 23.0–26.3%) and 18.5% (CI95 16.9–20.0%), respectively. Fractures had the highest likelihood of receiving an opioid, as 49.2% of adolescents with a fracture received an opioid (CI95 46.4–51.9%). Within this subgroup, only adolescents reporting a fracture pain score of 10 had significantly higher opioid use than adjacent pain scores, where fracture patients scoring a 10 were 1.4 times more likely to use opioids than those scoring 9, 82.2% (CI95 76.1–88.4%) and 59.8% (CI95 49.0–70.5%), respectively. Conclusions: While some guidelines in the adult population have revised cut-offs and groupings of the traditional tiers on a 0–10 point pain scale, the adolescent population may also require further examination to potentially warrant a similar adjustment

White Blood Cells and Blood Pressure: A Mendelian Randomization Study

Background: High blood pressure (BP) is a risk factor for cardiovascular morbidity and mortality. While BP is regulated by the function of kidney, vasculature, and sympathetic nervous system, recent experimental data suggest that immune cells may play a role in hypertension. Methods: We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and used Mendelian randomization (MR) analyses using the ≈750 000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies to examine which leukocyte populations may be causally linked to BP. Results: A positive association between quintiles of lymphocyte, monocyte, and neutrophil counts, and increased systolic BP, diastolic BP, and pulse pressure was observed (eg, adjusted systolic BP mean±SE for 1st versus 5th quintile respectively: 140.13±0.08 versus 141.62±0.07 mm Hg for lymphocyte, 139.51±0.08 versus 141.84±0.07 mm Hg for monocyte, and 137.96±0.08 versus 142.71±0.07 mm Hg for neutrophil counts; all P<10-50). Using 121 single nucleotide polymorphisms in MR, implemented through the inverse-variance weighted approach, we identified a potential causal relationship of lymphocyte count with systolic BP and diastolic BP (causal estimates: 0.69 [95% CI, 0.19-1.20] and 0.56 [95% CI, 0.23-0.90] of mm Hg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings. These inverse-variance weighted estimates were consistent with other robust MR methods. The exclusion of rs3184504 SNP in the SH2B3 locus attenuated the magnitude of the signal in some of the MR analyses. MR in the reverse direction found evidence of positive effects of BP indices on counts of monocytes, neutrophils, and eosinophils but not lymphocytes or basophils. Subsequent MR testing of lymphocyte count in the context of genetic correlation with renal function or resting and postexercise heart rate demonstrated a positive association of lymphocyte count with urine albumin-to-creatinine ratio. Conclusions: Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with systolic BP and diastolic BP