A Unit-Concentration Method to Quantify Source Contribution.

Solute migration is typically simulated to describe and estimate the fate and transport of contaminants in groundwater. The unit-concentration approach is investigated here as a method to enable solute transport simulations to expand the capabilities of groundwater flow modeling. The unit-concentration method uses a concentration value of one to identify sources of water to be assessed and a concentration of zero for all other water sources. The distribution of concentration thus obtained, unlike particle tracking methods, provides a more intuitive and direct quantification of the contribution of sources reaching various sinks. The unit-concentration approach can be applied readily with existing solute transport software for a range of analyses including source allocation, well capture analysis, and mixing/dilution calculations. This paper presents the theory, method, and example applications of the unit-concentration approach for source quantification.

Quantifying biomarkers of axonal degeneration in early glaucoma to find the disc at risk.

To evaluate regional axonal-related parameters as a function of disease stage in primary open angle glaucoma (POAG) and visual field (VF) sensitivity. Spectral domain optical coherence tomography was used to acquire 20° scans of POAG (n = 117) or healthy control (n = 52) human optic nerve heads (ONHs). Region specific and mean nerve fibre layer (NFL) thicknesses, border NFL and peripapillary NFL, minimum rim width (MRW)/ area (MRA) and prelamina thickness; and volume were compared across POAG disease stages and with visual field sensitivity. Differences identified between early glaucoma (EG), preperimetric glaucoma (PG) and control (C) ONHs included thinner PG prelamina regions than in controls (p < 0.05). Mean border NFL was thinner in EG (p < 0.001) and PG (p = 0.049) compared to control eyes; and EG mean, and inferior and ST, border NFL was thinner than in PG (p < 0.01). Mean, superior and inferior PG peripapillary NFL were thinner than in controls (p < 0.05), and EG ST peripapillary NFL was thinner than in PG (p = 0.023). MRW differences included: PG SN and inferior less than in controls (p < 0.05); thinner EG mean regional, inferior, nasal, and ST MRW versus PG MRW (p < 0.05). Regional border NFL, peripapillary NFL, MRW, MRA, prelamina thickness (except centre, p = 0.127) and prelamina volume (p < 0.05) were significantly associated with VF mean deviation (MD). Novel axon-derived indices hold potential as biomarkers to detect early glaucoma and identify ONHs at risk.

[A critical carol : Being an essay on anemia, suffocation, starvation, and other forms of intensive care, after the manner of Dickens]. / Eine kritische Weihnachtsgeschichte : Essay über Anämie, Ersticken, Verhungern und andere Behandlungsverfahren der Intensivmedizin ­ im Stil von Dickens.

Somewhere in the USA, shortly before Christmas, tipsy Charlie Cratchit intends to cross a street but is hit by an oncoming city bus und suffers severe trauma: serial rib fracture, femoral fracture, fibula fracture, splenic, pancreatic and bowel ruptures. He is operated on in a maximum care hospital and then transferred to the critical care unit. From then on, an anonymous, very experienced physician continuously takes care of him. Four nights before Christmas, the ghost of the famous British physiologist Ernest Henry Starling appears at the patient's bed. The ghost involves the anonymous physician in a dialogue and is very interested in the inserted Swan-Ganz catheter, then he disappears. He repeats his visits the next 3 nights. On the first occasion he is displeased with Cratchit's low haematocrit, the second time he dislikes the mechanical ventilator settings, and on his final visit he is concerned with Cratchit's clinical nutrition. At first, the anonymous physician is indignant with the ghost's criticism and indoctrinations, but then recognizes that ultimately they are the key to Cratchit's convalescence and acts accordingly. Successfully! Following the ghost's proposals, he changes the ventilator settings, transfuses 3 units of packed red blood cells, and starts clinical nutrition. Shortly thereafter, Cratchit's trachea is extubated, and on New Year's Day he is ready to be discharged from the critical care unit. In this essay, Robert Bartlett transposed Charles Dickens' "Christmas Carol" into the world of critical care. Its intention is to encourage the intensivist to scrutinize common therapeutic measures, such as mechanical ventilation, haemodynamic interventions and transfusion of blood products. Background information and comments on the addressed problems of modern intensive care are provided subsequent to the essay.

Enhancing analytical accuracy of intravascular electrochemical oxygen sensors via nitric oxide release using S-nitroso-N-acetyl-penicillamine (SNAP) impregnated catheter tubing.

Implantable medical devices are an integral part of primary/critical care. However, these devices carry a high risk for blood clots, caused by platelet aggregation on a foreign body surface. This study focuses on the development of a simplified approach to create nitric oxide (NO) releasing intravascular electrochemical oxygen (O2) sensors with increased biocompatibility and analytical accuracy. The implantable sensors are prepared by embedding S-nitroso-N-acetylpenacillamine (SNAP) as the NO donor molecule in the walls of the catheter type sensors. The SNAP-impregnated catheters were prepared by swelling silicone rubber tubing in a tetrahydrofuran solution containing SNAP. Control and SNAP-impregnated catheters were used to fabricate the Clark-style amperometric PO2 sensors. The SNAP-impregnated sensors release NO under physiological conditions for 18 d as measured by chemiluminescence. The analytical response of the SNAP-impregnated sensors was evaluated in vitro and in vivo. Rabbit and swine models (with sensors placed in both veins and arteries) were used to evaluate the effects on thrombus formation and analytical in vivo PO2 sensing performance. The SNAP-impregnated PO2 sensors were found to more accurately measure PO2 levels in blood continuously (over 7 and 20 h animal experiments) with significantly reduced thrombus formation (as compared to controls) on their surfaces.

Rodent Skeletal Muscle Metabolomic Changes Associated With Static Cold Storage.

OBJECTIVE: The aim of this study was to evaluate the impact of static cold storage preservation on skeletal muscle metabolism using a rodent model. METHODS: Sixteen male Lewis rats (250 ± 25 g) were distributed into 4 groups, including naive control, warm ischemia for 2 hours, static warm storage for 6 hours, and static cold storage for 6 hours. Energy status, metabolomics profiling, and histopathology of the muscle were analyzed. RESULTS: In the warm ischemia and static warm storage groups, glycolytic pathway metabolites decreased, but the Krebs cycle metabolite of succinate and the purine degradation product of hypoxanthine accumulated. Increased succinate and hypoxanthine levels were associated with increased injury severity scores. During static cold storage, the glycolytic pathway activity and the energy status were preserved. Succinate and hypoxanthine levels showed no significant difference from the naive group. CONCLUSION: Warm ischemia results in reduced glycolysis and Krebs cycle metabolites. Static cold storage preserves the glycolytic pathway and represents a favorable contribution to cellular energy demand. Succinate and hypoxanthine might be used as novel potential biomarkers for the assessment of viability and injury severity.

Temporal Analysis of Factors Associated with EAT-10 in Outpatients with Oropharyngeal Dysphagia from a Tertiary Care Clinic.

Self-perception of disease is increasingly recognized as a determinant of health. The Eating Assessment Tool-10 (EAT-10) is a functional health status questionnaire that measures the symptomatic severity of dysphagia from the patient's perspective. The objective of this work was to identify factors (demographics, clinical variables, swallowing physiology, health-related quality of life) associated with longitudinal change in EAT-10 scores in outpatients with oropharyngeal dysphagia at a multi-disciplinary, tertiary care clinic. All patients with swallowing concerns that were included in the UW Madison Voice and Swallowing Outcomes database from 12/2012 to 04/2015 were invited to complete EAT-10 and a general health-related quality of life survey (SF-12v2) at their initial evaluation and six months later. Forty-two patients were included in analysis (n = 42). Weaning from a gastrostomy tube was significantly associated with EAT-10 improvement. Approximately 70% of the sample had mild dysphagia, and floor effects were observed for all EAT-10 items in this sample subset. Mean SF-12v2 Physical Component Summary score was substantially lower than that of the general population. Significant, weak-moderate correlations were found between EAT-10 and SF-12v2 scores for all comparisons except for Physical Health Composite at six months (rs = = 0.24 to - 0.43). Weaning from a feeding tube appears to meaningfully improve self-perceived symptoms of dysphagia. Given the floor effects observed, validity of EAT-10 for patients with mild dysphagia should be examined. Future research should address contributors to self-perceived symptom change across the range of dysphagia severity.

Cochlear implantation in Malawi: report of the first four cases.

OBJECTIVE: This paper reports on the first four cochlear implant cases in Malawi. CASE REPORTS: Three patients were deafened from infectious diseases and one from an unknown cause. They all had post-lingual deafness. Six months after the last implant, they are all progressing well. CONCLUSION: Despite significant practical difficulties, it has proved possible, with the right support, to carry out cochlear implantation in one of the world's poorest countries. The project has also raised awareness of deafness in Malawi and highlighted significant public health issues relating to the aetiology of deafness in developing countries.

[The old man and the I sea U : Essay on faith, fate and evidence - after the manner of Hemingway]. / Der alte Mann und die "I sea U" : Essay über Vertrauen, Schicksal und Evidenz ­ im Stil von Hemingway.

Robert Bartlett, emeritus Professor of surgery at the University of Michigan in Ann Arbor, USA, transformed classical works of world literature (Charles Dickens: A Christmas Carol, Lewis Carroll: Alice in Wonderland) into teaching aids for advanced training in intensive care medicine. He recently turned his hand to the well-known work of Ernest Hemingway: the Nobel Prize winning novel The Old Man and the Sea. Subsequent to Robert Bartlett's essay this article provides background information and comments on the current problems in modern intensive care medicine addressed in his essay.

Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment.

BACKGROUND: Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. METHODS: Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (RT-PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. RESULTS AND DISCUSSION: Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]ß1, alpha smooth muscle actin, interleukin-1ß, interleukin-17ß and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC-treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair.

Extracorporeal life support for acute respiratory distress syndrome due to severe Legionella pneumonia.

PURPOSE: Legionella is a common cause of community-acquired pneumonia (CAP) and is second only to Pneumococcal pneumonia as a cause of severe CAP that requires treatment in an intensive care unit. We report a case series of patients with severe Legionella pneumonia who developed the acute respiratory distress syndrome (ARDS), failed to improve with mechanical ventilation alone and required extracorporeal life support (ECLS). METHODS: We performed a retrospective study of all patients treated with ECLS at our institution for severe ARDS as a result of Legionella pneumonia from 1994 to 2006. RESULTS: A total of twelve patients with a diagnosis of Legionella pneumonia were treated with veno-venous (VV) ECLS over this time period. Nine of these twelve (75%) were successfully treated and weaned off ECLS and 8 patients (67%) survived to hospital discharge. Two (13%) died of multisystem organ failure, one patient (8%) died from global hypoxic encephalopathy and one (8%) was weaned from ECLS, but ultimately died of liver failure. Renal failure requiring some form of continuous dialysis occurred in seven patients (58%) and the survival for this sub-set of patients was 43%. CONCLUSIONS: Extracorporeal life support for severe ARDS associated with Legionella pneumonia is an effective treatment option when mechanical ventilation fails, especially when introduced early in the course.

Extension MRI is clinically useful in cervical myelopathy.

INTRODUCTION: Cervical spine MRI with the neck in extension has been well described over the last 10 years, but its clinical value remains unknown. METHODS: We performed extension imaging in 60 patients in whom the initial neutral study showed borderline cord compression. Images were assessed using a previously validated grading system for cord compression. Multiple linear and area measurements were also obtained. Images were scored blindly and randomly. Inter- and intra-rater variability were determined in a subset of 20 cases. Independent clinical assessment utilised the Ranwat criteria. RESULTS: For most parameters inter/intra-observer variance of kappa/ICC > 0.6 was highly satisfactory. Standard MR was poor at discriminating between patients with and without myelopathy (ROC analysis, area under the curve (AUC), 0.52). This was considerably improved with extension imaging (AUC, 0.60), or by using the change in compression score between neutral and extension studies. Most measurements were not helpful; however, the ratio of cord area/CSF area at the level of maximum compression on extended images was the best discriminator (AUC, 0.71), as well as the presence of T2 change in cord substance (AUC, 0.68). CONCLUSION: This is the first study to demonstrate added clinical value utilising extension MRI. In this cohort of difficult patients, when there was no T2 signal change in the cord, the presence of clinical myelopathy could only be predicted by utilising the data from extension imaging.

MRI of the cervical spine with neck extension: is it useful?

OBJECTIVES: Standard MRI of the cervical spine is performed in a different anatomical position to that utilised for traditional contrast myelography. Those well practised in myelography are familiar with the considerable changes in configuration of the bony and soft tissues of the cervical spine that may occur with changes in the degree of neck flexion and extension. We set out to compare the findings in a select group of patients with myeloradiculopathy who had undergone myelography and MRI in both standard and neck-extended positions. These findings were correlated with the clinical status. METHODS: 29 patients underwent myelography with CT (CTM) and MRI in neutral and neck-extended positions. The imaging was assessed for the degree of cord compression and neural foraminal narrowing, quantified using a simple grading scheme suitable for routine clinical practice. The degree of neck extension was assessed using an angular measurement. RESULTS: For both CTM and MRI, scanning with the neck extended significantly increases the severity of cord compression compared with the standard supine position, to a degree similar to that shown during conventional prone myelography. The degree of perceived cord compression is related to the degree of neck extension achieved. Correlation of standard MRI findings and the clinical level of radiculopathy is poor. This correlation improves when the neck is extended. CONCLUSIONS: The most appropriate position for routine MRI of the cervical spine in degenerative disease remains unknown, but in selected patients imaging with the neck extended may provide important additional information.

SU-E-J-124: Assessment of Intrafraction and Interfraction Motion in Cranial SRT Using Tomotherapy.

PURPOSE: Stereotactic radiotherapy delivers large doses of radiation to small volumes with steep dose gradients, and therefore requires accurate positioning and near complete immobilization throughout the delivery of treatment. This work assesses intra and interfraction patient motion for two immobilization devices for patients treated on Tomotherapy. METHODS: The study set consisted of 60 patients undergoing treatment for brain metastases over 5 fractions on MVCT imaged-guided Tomotherapy. Patients were immobilized using either the frameless Aktina PinPoint system or thermoplastic mask with bite block. To assess intrafraction motion, a scan was performed at the end of 2 treatment fractions. All MVCT Tomotherapy images were registered to the original kVCT in Amira 5.2 using a quasi- newton, normalized mutual information affine transformation. To assess the precision and accuracy of MVCT image acquisition, reconstruction and off́line Amira registration to kVCT, a phantom study was conducted. RESULTS: The phantom study demonstrated that the total error (noise floor) of the measurements and imaging/registration workflow was 0.11 ± 0.09 mm. The Aktina frameless immobilization device yielded an average displacement of 2.58 ± 2.29 mm for intrafraction patient motion and 2.54 ± 1.37 mm for interfraction patient setup differences, while mask immobilization yielded average intrafraction patient motion of 1.29 ± 1.18 mm and interfraction patient setup differences of 2.13 ± 1.49 mm. Finally, 95% of all intrafraction motion using mask immobilization fell within our clinically used 2 mm margin, as compared to 75% of Aktina immobilization over the same margin. A margin of 3.5 mm is necessary for Aktina immobilized patients to include 95% of intrafraction motion within the margin. CONCLUSIONS: Our data indicates that mask immobilization performed better at preventing intrafraction motion and reducing interfraction patient setup differences.

A simple technique to prevent limb ischemia during veno-arterial ECMO using the femoral artery: the posterior tibial approach.

Lower extremity ischemia is common when the femoral artery is used for veno-arterial extracorporeal membrane oxygenation (VA ECMO). We describe a new technique to reperfuse the extremity. The ipsilateral posterior tibial artery is exposed via a small incision behind the medial malleolus. The vessel is cannulated in a retrograde fashion and connected to the arterial limb of the ECMO circuit. Thirty-six patients received a posterior tibial reperfusion cannula: average flow was 155.8 ml/min and increased over the initial 24 hours. Fifty-eight percent received the posterior tibial cannula within 6 hours of ECMO initiation and none sustained permanent lower extremity injury. Of the remaining 42%, three required amputation or developed permanent neurologic injury. Overall survival was 41%. Cannulation of the posterior tibial artery is a simple technique to reperfuse the lower extremity during VA ECMO. The cannula should be inserted within 6 hours of ECMO initiation to avoid irreversible ischemic damage.

Current status of extracorporeal life support (ECMO) for cardiopulmonary failure.

Extracorporeal life support with artificial heart and lung for cardiopulmonary failure is commonly called extracorporeal membrane oxygenation (ECMO). ECMO can provide partial or total support, is temporary, and requires systemic anticoagulation. ECMO controls gas exchange and perfusion, stabilizes the patient physiologically, decreases the risk of ongoing iatrogenic injury, and allows ample time for diagnosis, treatment, and recovery from the primary injury or disease. ECMO is used in a variety of clinical circumstances and the results depend on the primary indication. ECMO provides life support but is not a form of treatment. Survival ranges from 30% in extracorporeal cardiopulmonary resuscitation to 95% for neonatal meconium aspiration syndrome. The major limitations to widespread applications are the need for anticoagulation and bleeding complications. However, nowadays, the new devices allow only minor bleeding that is rarely a fatal complication. Research on non-thrombogenic surfaces holds the promise of prolonged extracorporeal circulation without anticoagulation and without bleeding. The next decade may bring routine application of ECMO to all advanced Intensive Care Units where patients with profound respiratory and cardiac failure are treated.

Extracorporeal support: improves donor renal graft function after cardiac death.

Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4-6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min +/- 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min +/- 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h +/- 1.7). DCD-30 had lower CrCl (0.9 mL/min +/- 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI.