A Rare Presentation of Crohn's Disease

Free peritoneal perforation is a rare complication of Crohn's disease with a report of only 100 cases in the literature. It needs an emergency exploration and an unaware general surgeon is confounded in intraoperative decision-making. We present our experience when this rarity struck us in a district hospital and briefly review the guidelines of optimal management of this complication of Crohn's disease

Study of Presentation, Management and Outcome of Esophageal Fistulas.

INTRODUCTION : Esophageal fistulas are a major cause of morbidity and mortality necessitating complex clinical evaluation and decision making for optimal management. It is best treated in a specialty tertiary care setting by a multidisciplinary team approach. Etiology of esophageal fistulas is multifactorial and the presentation can vary from simple external cervical esophageal fistulas to complex tracheoesophageal fistulas and esophagopleurocutaneous fistulas. Among patients with carcinoma esophagus, the development of airway-esophageal fistulas alters the natural history dramatically with rapid downhill course leading onto mortality in untreated cases. In acquired non-malignant causes of airway-esophageal fistulas, the patients suffer from significant morbidity due to recurrent pulmonary sepsis. These diseases are complex and mandates critical preoperative evaluation for optimal management. As we are tertiary surgical center for advanced gastrointestinal surgery, such difficult-to-manage patients are referred from all over the state. We ventured to collect the data of all these patients and analyze them in detail for better understanding of this uncommon disease. AIM : To study the various etiological factors and patterns of clinical presentation of esophageal fistulas. To study the modes of evaluation and treatment of esophageal fistula. To analyze the outcome of management of esophageal fistula Patients. MATERIALS AND METHODS : All patients diagnosed with esophageal fistulas during the study period from August 2010 to February 2013 were included in the study. The patients’ demographic data including Name, Age, Sex, place of origin and occupation were documented. An accurate history taking was done and recorded systematically. They were examined in detail and findings tabulated. Each patient’s clinical course was closely monitored and recorded. The etiology of the fistula, the investigative modalities undergone by the patient and treatment offered to each patient was noted. As part of the study, no special treatment was offered to the patient. Each patient’s natural course in the hospital is observed and analyzed. In general, patients with malignant tracheoesophageal fistula were taken up for endoscopic esophageal stent placement. Before stent placement, the site of the tracheoesophageal fistula (TEF) was assessed by upper gastrointestinal endoscopy which is performed with topical lidocaine spray. A guide wire was inserted through the endoscope and under fluoroscopic guidance, it is passed distal to the tumor and the site of the fistula and a covered metallic stent was placed. In the event of unavailability of stents, they were offered other treatment. For patients with acquired nonmalignant fistulas, each patient was individually assessed and treatment decisions taken by multidisciplinary team. CONCLUSION : In conclusion, we would like to state that esophageal fistulas are complex and heterogeneous disorders. The mode of clinical presentation varies depending on the etiology. With respect to malignant tracheoesophageal fistulas, stenting of the esophagus and/or the airway is the current standard of care. If the patient presents late in the course of the fistula with pulmonary sepsis, he shall be best managed with supportive care and no heroic measures should be tried. Surgical management of malignant TEF finds very little place in the modern endoscopic stenting era. With regards to acquired non-malignant esopahgorespiratory fistulas, majority of them are managed surgically with strict adherence to well-established principles of operative management. With careful preoperative preparation and diligent postoperative care, results are extremely satisfactory. We would like to emphasize that these disorders are best managed in tertiary care hospitals where multidisciplinary team management is possible and helps in achieving the best possible results

Vehicle sideslip angle estimation using Kalman filters: modelling and validation

The knowledge of the vehicle sideslip angle provides useful information about the state of the vehicle and it is often considered to increase the performance of the car as well as to develop safety systems, especially in the vehicle equipped with Torque Vectoring control systems. This paper describes two methods, based on the use of Kalman filters, to estimate the vehicle sideslip angle and the tire forces of a vehicle starting from the longitudinal and yaw velocity data. In particular, these data refer to on-track testing of a Range Rover Evoque performing ramp steer maneuvers at constant speed. The results of the sideslip estimation method are compared with the actual vehicle sideslip measured by a Datron sensor and are also used to estimate the tire lateral forces

BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.

T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs. In naive cells, this prevented TCR-driven induction of genes associated with terminal differentiation. Upon effector differentiation, reduced expression of BACH2 and its phosphorylation enabled unrestrained induction of TCR-driven effector programs

Stromal Interferon-γ Signaling and Cross-Presentation Are Required to Eliminate Antigen-Loss Variants of B Cell Lymphomas in Mice

To study mechanisms of T cell-mediated rejection of B cell lymphomas, we developed a murine lymphoma model wherein three potential rejection antigens, human c-MYC, chicken ovalbumin (OVA), and GFP are expressed. After transfer into wild-type mice 60–70% of systemically growing lymphomas expressing all three antigens were rejected; lymphomas expressing only human c-MYC protein were not rejected. OVA expressing lymphomas were infiltrated by T cells, showed MHC class I and II upregulation, and lost antigen expression, indicating immune escape. In contrast to wild-type recipients, 80–100% of STAT1-, IFN-γ-, or IFN-γ receptor-deficient recipients died of lymphoma, indicating that host IFN-γ signaling is critical for rejection. Lymphomas arising in IFN-γ- and IFN-γ-receptor-deficient mice had invariably lost antigen expression, suggesting that poor overall survival of these recipients was due to inefficient elimination of antigen-negative lymphoma variants. Antigen-dependent eradication of lymphoma cells in wild-type animals was dependent on cross-presentation of antigen by cells of the tumor stroma. These findings provide first evidence for an important role of the tumor stroma in T cell-mediated control of hematologic neoplasias and highlight the importance of incorporating stroma-targeting strategies into future immunotherapeutic approaches

Retinoic acid controls the homeostasis of pre-cDC–derived splenic and intestinal dendritic cells

Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)–derived splenic CD11b(+)CD8α(−)Esam(high) DCs and the developmentally related CD11b(+)CD103(+) subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC–derived CD11b(−)CD8α(+) and CD11b(−)CD103(+) nor monocyte-derived CD11b(+)CD8α(−)Esam(low) or CD11b(+)CD103(−) DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b(+)CD8α(−) subset, whereas transfer into vitamin A–deficient (VAD) hosts caused diversion to the CD11b(−)CD8α(+) lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II–restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC–derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation

Techno-economic Analysis of Charging and Heating Options for an Electric Bus Service in London

This study explores electric bus operations for a bus depot in London. Operational data about speed, GPS coordinates and electric motor performance are used to define accurate drive cycles and validate simulations. A validated vehicle simulation tool is used to estimate the power requirements of electric buses over the defined drive cycles. The performance requirements for a practical system are set and appropriate charging infrastructures for electrified bus operations are proposed. The number and location of charging points required within the area of service, their power transfer rates and the capacity of the on-board battery for each charging option are determined. The effects of diesel heating versus electric heating are also analysed. The power demands are calculated and a cost model is built to assess the financial viability of the proposals. It is shown that electrification of the two routes is technically feasible and financially viable when the Opportunity Charging approach is adopted. Such a system (electric bus operations for the bus depot) results in financial savings of approximately £1.7 million over a fourteen-year lifetime when compared to conventional diesel buses. The use of electric buses would result in aggregated CO2 savings of 48.2 kt between 2019 and 2050

A Data-Driven Model of Pedestrian Movement

We present a method for simulating individual pedestrian motion based on empirical data. Our model keeps track of the pedestrian’s position and body configuration (pose) and uses motion capture data to produce plausible motion. While our ultimate goal is creating 3D animations of crowds, our initial efforts focus on 2D simulations. In this paper, we present a 2D model for an able-bodied male. Using our approach, we could also capture data and build models for a heterogeneous population, including children, the elderly, pedestrians in wheelchairs, and people on crutches. We demonstrate the realism of our model with a small-scale test case and a larger crowd evacuation simulation.