A Dependent Type Theory with Abstractable Names

This paper describes a version of Martin-Löf's dependent type theory extended with names and constructs for freshness and name-abstraction derived from the theory of nominal sets. We aim for a type theory for computing and proving (via a Curry-Howard correspondence) with syntactic structures which captures familiar, but informal, ‘nameful’ practices when dealing with binders.Partially supported by the UK EPSRC program grant EP/K008528/1, Rigorous Engineering for Mainstream Systems (REMS). Supported by the UK EPSRC leadership fellowship (Peter Sewell) grant EP/H005633/1, Semantic Foundations for Real-World Systems.This is the final published version of the article. It was originally published in Electronic Notes in Theoretical Computer Science (Pitts AM, Matthiesen J, Derikx J, Electronic Notes in Theoretical Computer Science 2015, 312, 19–50, doi:10.1016/j.entcs.2015.04.003) http://dx.doi.org/10.1016/j.entcs.2015.04.00

Usefulness of CT scan as part of an institutional protocol for proactive leakage management after low anterior resection for rectal cancer

Purpose: Highly selective fecal diversion after low anterior resection (LAR) for rectal cancer requires a strict postoperative protocol for early detection of anastomotic leakage (AL). The purpose of this study was to evaluate C-reactive protein (CRP)–based CT imaging in diagnosis and subsequent management of AL. Methods: All patients that underwent a CT scan for suspicion of AL after transanal total mesorectal excision for rectal cancer in a university center (2015–2020) were included. Outcome parameters were diagnostic yield of CT and timing of CT and subsequent intervention. Results: Forty-four out of 125 patients underwent CT (35%) with an overall median interval of 5 h (IQR 3–6) from CRP measurement. The anastomosis was diverted in 7/44 (16%). CT was conclusive or highly suspicious for AL in 23, with confirmed AL in all those patients (yield 52%), and was false-negative in one patient (sensitivity 96%). CT initiated subsequent intervention after median 6 h (IQR 3–25). There was no or minor suspicion of AL on imaging in all 20 patients without definitive diagnosis of AL. After CT imaging on day 2, AL was confirmed in 0/1, and these proportions were 6/6 for day 3, 7/10 for day 4, 2/4 for day 5, and 9/23 beyond day 5. Conclusion: In the setting of an institutional policy of highly selective fecal diversion and pro-active leakage management, the yield of selective CT imaging using predefined CRP cut-off values was 52% with a sensitivity of 96%, enabling timely and tailored intervention after a median of 6 h from imaging.</p

Usefulness of CT scan as part of an institutional protocol for proactive leakage management after low anterior resection for rectal cancer

Purpose: Highly selective fecal diversion after low anterior resection (LAR) for rectal cancer requires a strict postoperative protocol for early detection of anastomotic leakage (AL). The purpose of this study was to evaluate C-reactive protein (CRP)–based CT imaging in diagnosis and subsequent management of AL. Methods: All patients that underwent a CT scan for suspicion of AL after transanal total mesorectal excision for rectal cancer in a university center (2015–2020) were included. Outcome parameters were diagnostic yield of CT and timing of CT and subsequent intervention. Results: Forty-four out of 125 patients underwent CT (35%) with an overall median interval of 5 h (IQR 3–6) from CRP measurement. The anastomosis was diverted in 7/44 (16%). CT was conclusive or highly suspicious for AL in 23, with confirmed AL in all those patients (yield 52%), and was false-negative in one patient (sensitivity 96%). CT initiated subsequent intervention after median 6 h (IQR 3–25). There was no or minor suspicion of AL on imaging in all 20 patients without definitive diagnosis of AL. After CT imaging on day 2, AL was confirmed in 0/1, and these proportions were 6/6 for day 3, 7/10 for day 4, 2/4 for day 5, and 9/23 beyond day 5. Conclusion: In the setting of an institutional policy of highly selective fecal diversion and pro-active leakage management, the yield of selective CT imaging using predefined CRP cut-off values was 52% with a sensitivity of 96%, enabling timely and tailored intervention after a median of 6 h from imaging.</p

Modelling Cyclic Walking in Femurs With Metastatic Lesions:Femur-Specific Accumulation of Plasticity

Introduction Clinical fracture risk assessment in metastatic bone disease is extremely difficult, but subject-specific finite element (FE) modelling may improve these assessments in the future [Derikx, 2015]. By coupling to musculoskeletal modelling, realistic loading conditions can be implemented in FE analysis. However, it is unknown whether such analyses require complex elastic-plastic material models, or whether a linear elastic calculation already provides a reasonable prediction of fracture. Moreover, plastic deformation may accumulate over time, which is ignored by linear elastic calculations. In this study we compared linear and non-linear fracture predictions under realistic loading conditions in two patients with metastatic bone disease. Methods Two patients (P1, P2) with lytic lesions were included. Patient-specific femoral geometry and bone density were retrieved from quantitative CT-scans; the latter was used for implementing element-specific material behaviour [Keyak, 2005]. Muscle forces and hip contact forces acting on the femur during walking were calculated using musculoskeletal modelling (one typical case, adapted from [Wesseling, 2014]), and subsequently normalized to the patient’s body weight. Muscle forces were applied to attachment points that were morphed onto the patient femurs. Hip contact forces were applied to a cup mimicking the acetabulum, via a control node in the hip joint centre. Two simulations were run for each patient: a linear elastic analysis simulating a single walk cycle and a non-linear elastic-plastic analysis simulating 10 subsequent walk cycles. The safety factor (SF; yield stress/Von Mises stress) and plasticity were studied as measures of femoral failure in the linear and non-linear simulations, respectively, and compared between patients. Results The volume of elements with SF<1 (Figure 1A) as well as the volume of elements that underwent plastic deformation (Figure 1B) was highest in the femur of P1. In P1 the volume of plastic deformation increased over the loading cycles and eventually exceeded the peak volume of elements with SF<1 in the linear analysis. In P2, the volume of plasticity more or less stabilized after two loading cycles, and eventually resembled the volume of elements with SF<1 in the linear analysis. Discussion These preliminary results suggest that accumulation of plasticity under cyclic loading is femur-specific. Due to the variable and local weakening of the bone strength by metastatic lesions, relatively small changes in magnitude or direction of loading may initiate local failure and catalyze progressive failure in subsequent loading cycles. Hence, in some cases a linear analysis is sufficient, while in others it is not. Non-linear material behaviour and cyclic loading conditions are therefore required to capture these phenomena

Real-Time In Vivo Imaging of Early Mucosal Changes during Ischemia-Reperfusion in Human Jejunum

BACKGROUND AND STUDY AIMS: Small intestinal ischemia-reperfusion (IR) is a frequent, potentially life threatening phenomenon. There is a lack of non-invasive diagnostic modalities. For many intestinal diseases, visualizing the intestinal mucosa using endoscopy is gold standard. However, limited knowledge exists on small intestinal IR-induced, early mucosal changes. The aims of this study were to investigate endoscopic changes in human jejunum exposed to IR, and to study concordance between endoscopic appearance and histology. PATIENTS AND METHODS: In 23 patients a part of jejunum, to be removed for surgical reasons, was isolated and selectively exposed to ischemia with 0, 30 or 120 minutes of reperfusion. In 3 patients, a videocapsule was inserted in the isolated segment before exposure to IR, to visualize the mucosa. Endoscopic view at several time points was related to histology (Heamatoxylin & Eosin) obtained from 20 patients. RESULTS: Ischemia was characterized by loss of villous structure, mucosal whitening and appearance of punctate lesions. This was related to appearance of subepithelial spaces and breaches in the epithelial lining in the histological view. Early during reperfusion, the lumen filled with IR-damaged, shed cells and VCE showed mucosal erosions, hemorrhage and intraluminal debris. At 60 minutes of reperfusion, the only remaining signs of IR were loss of villous structure and small erosions, indicating rapid mucosal healing. CONCLUSIONS: This study shows a unique, real-time in vivo endoscopic view of early mucosal changes during IR of the human small intestine. Future studies should evaluate its usefulness in diagnosis of patients suspected of IR

Rapid development of intestinal cell damage following severe trauma: a prospective observational cohort study

Introduction Loss of intestinal integrity has been implicated as an important contributor to the development of excessive inflammation following severe trauma. Thus far, clinical data concerning the occurrence and significance of intestinal damage after trauma remain scarce. This study investigates whether early intestinal epithelial cell damage occurs in trauma patients and, if present, whether such cell injury is related to shock, injury severity and the subsequent inflammatory response. Methods Prospective observational cohort study in 96 adult trauma patients. Upon arrival at the emergency room (ER) plasma levels of intestinal fatty acid binding protein (i-FABP), a specific marker for damage of differentiated enterocytes, were measured. Factors that potentially influence the development of intestinal cell damage after trauma were determined, including the presence of shock and the extent of abdominal trauma and general injury severity. Furthermore, early plasma levels of i-FABP were related to inflammatory markers interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP). Results Upon arrival at the ER, plasma i-FABP levels were increased compared with healthy volunteers, especially in the presence of shock (P < 0.01). The elevation of i-FABP was related to the extent of abdominal trauma as well as general injury severity (P < 0.05). Circulatory i-FABP concentrations at ER correlated positively with IL-6 and PCT levels at the first day (r2 = 0.19; P < 0.01 and r2 = 0.36; P < 0.001 respectively) and CRP concentrations at the second day after trauma (r2 = 0.25; P < 0.01). Conclusions This study reveals early presence of intestinal epithelial cell damage in trauma patients. The extent of intestinal damage is associated with the presence of shock and injury severity. Early intestinal damage precedes and is related to the subsequent developing inflammatory response

Plasma citrulline during the first 48 h after onset of necrotizing enterocolitis in preterm infants

Background: Levels of plasma citrulline (citrulline-P), a biomarker for enterocyte function, might be useful for the monitoring the course of necrotizing enterocolitis (NEC). Our aim was to evaluate whether citrulline-P levels during the first 48 h (h) after NEC onset were associated with need for surgery, survival, and intestinal recovery. Methods: In preterm infants with NEC (Bell's stage ≥2) we measured citrulline-P levels during the first 48 h after NEC onset. Categorizing the measurements into 0–8 h, 8–16 h, 16–24 h, 24–36 h, and 36–48 h, we determined the course of citrulline-P using linear regression analyses. Next, we analyzed whether citrulline-P levels measured at 0–24 h and 24–48 h differed between conservative and surgical treatment, survivors and nonsurvivors, and equal/below and above total group's median time to full enteral feeding (FEFt). Results: We included 48 infants, median gestational age 28.3 [IQR:26.0–31.4] weeks, birth weight 1200 [IQR:905–1524] grams. Citrulline-P levels decreased the first 48 h (B per time interval: -1.40 μmol, 95% CI, −2.73 to −0.07, p = 0.04). Citrulline-P was not associated with treatment, nor with survival. Citrulline-P at 0–24 h, but not 24–48 h, was higher in infants with FEFt ≤20 days than in infants with FEFt >20 days (20.7 [IQR:19.9–25.3] µmol/L (n = 13) vs. 11.1 [IQR:8.4–24.0] µmol/L (n = 11), p = 0.049), with a citrulline-P cut-off value of 12.3 μmol/L. Conclusion: Citrulline-P levels decreased the first 48 h after NEC onset, suggesting on-going intestinal injury. In survivors, measuring citrulline-P in the first 24 h after NEC onset may provide an indication for intestinal recovery rate

The Diagnostic Accuracy of Serum Alpha-Fetoprotein Levels in Follow-up for Recurrence of Sacrococcygeal Teratoma; a Nationwide Review of SCT Cases in the Netherlands

Background: Serum alpha-fetoprotein (AFP) is often used as tumour marker for recurrent sacrococcygeal teratoma (SCT). We aimed to assess the normal dynamics of serum AFP levels after initial resection and diagnostic accuracy of serum AFP levels the follow-up for recurrence in SCT. Methods: This retrospective study included 57 patients treated for SCT in the six pediatric surgical centers in the Netherlands from 1980 to 2018. Main results: 57 patients were included in the study of whom 19 children developed 20 recurrences at a median of 14.0 months after initial resection. No significant difference was found in serum AFP level dynamics between the recurrence and non-recurrence group after initial resection (p = 0.950). Serum AFP levels did not significantly increase before recurrence (p = 0.106) compared to serum AFP levels of children without recurrence at the same time. However, serum AFP levels did significantly increase in malignant recurrences (n = 7) (p = 0.03) compared to patients without recurrence. A cut-off value of 55 μg/L was found to be predictive for recurrent SCT with an Area Under the Curve (AUC) of 0.636 with sensitivity of 50% and specificity of 100%. Conclusion: Dynamics of serum AFP levels are not different between patients with and without recurrence after initial resection of SCT. Serum AFP levels are not predictive for mature or immature recurrent SCT and normal AFP levels do not rule out recurrent SCT. However, serum AFP levels exceeding 55 μg/L can indicate recurrent SCT, especially malignant recurrences.</p

Endotoxin Induced Chorioamnionitis Prevents Intestinal Development during Gestation in Fetal Sheep

Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis

Surgical Management of Pediatric Inguinal Hernia: A Systematic Review and Guideline from the European Pediatric Surgeons' Association Evidence and Guideline Committee

Introduction: Inguinal hernia repair represents the most common operation in childhood; however, consensus about the optimal management is lacking. Hence, recommendations for clinical practice are needed. This study assesses the available evidence and compiles recommendations on pediatric inguinal hernia. / Materials and Methods: The European Pediatric Surgeons' Association Evidence and Guideline Committee addressed six questions on pediatric inguinal hernia repair with the following topics: (1) open versus laparoscopic repair, (2) extraperitoneal versus transperitoneal repair, (3) contralateral exploration, (4) surgical timing, (5) anesthesia technique in preterm infants, and (6) operation urgency in girls with irreducible ovarian hernia. Systematic literature searches were performed using PubMed, MEDLINE, Embase (Ovid), and The Cochrane Library. Reviews and meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. / Results: Seventy-two out of 5,173 articles were included, 27 in the meta-analyses. Laparoscopic repair shortens bilateral operation time compared with open repair. In preterm infants, hernia repair after neonatal intensive care unit (NICU)/hospital discharge is associated with less respiratory difficulties and recurrences, regional anesthesia is associated with a decrease of postoperative apnea and pain. The review regarding operation urgency for irreducible ovarian hernia gained insufficient evidence of low quality. / Conclusion: Laparoscopic repair may be beneficial for children with bilateral hernia and preterm infants may benefit using regional anesthesia and postponing surgery. However, no definite superiority was found and available evidence was of moderate-to-low quality. Evidence for other topics was less conclusive. For the optimal management of inguinal hernia repair, a tailored approach is recommended taking into account the local facilities, resources, and expertise of the medical team involved