How do I initiate and maintain a mobile apheresis service in the era of cellular therapy.

BACKGROUND: Mobile delivery of apheresis services is an increasingly important component of health care equity, as patients should not have to transfer care providers or travel far distances to receive critical therapeutic apheresis procedures or cell therapy-based treatments. Therefore, the availability of such services should be expanded. STUDY DESIGN AND METHODS: In this "How Do I" article, we provide a detailed overview of the elements necessary to initiate and maintain a successful mobile apheresis service, including challenges and potential solutions. RESULTS: Safe and efficient operation of a mobile apheresis service must consider acquisition of physical assets, such as apheresis sites, personnel, equipment and supplies, communication devices, and transportation vehicles, and optimize organizational aspects, such as staff responsibilities, service partnerships, logistics management, case scheduling and triage, and billing. In the era of cellular therapy, additional critical considerations include regulatory compliance and facility accreditation. DISCUSSION: To our knowledge, no previous publication provides the extensive details described herein to set up and maintain a successful mobile apheresis service, and thus will be very helpful to those facilities wishing to initiate or expand mobile apheresis services.

Lung Cancer in the Non-smoker: A Patient View Focused on the Hopes and Challenges Facing the Non-smoker Population.

A patient view paper focused on hopes and challenges facing the never smoker lung cancer population - from lived experience, unexpected diagnosis, treatment and subsequent immersion in lung cancer research and patient advocacy over many years, citing examples, references and events organised to explore the subject by UK research institutions. MATERIAL/METHODS: Based on lived experience, invited patient perspective conference presentations including National Cancer Research Institute (NCRI) never smoker lung cancer research strategy event opening presentation and subsequent article, includes references to relevant papers/findings and points raised during research events/group discussions, alongside personal experiences and beliefs. RESULTS: Discussions with clinicians, events, surveys, meetings and virtual discussions all revealed a dearth of evidence available to identify the best way to deal with this patient cohort at almost every aspect of their experience - from missed/late diagnosis, to screening potential (non-existent), mutation driven treatments (what about those ineligible?), and psychosocial/psychological aspects given their different life stage from older traditional lung cancer patients. CONCLUSION: More effort and focus are needed to better understand what is driving these cases, how best to detect them sooner and respond/refer to treatments as well as developing screening methods alongside increased public and healthcare professional awareness raising and tools to support clinicians in earlier detection.

Credibility assessment of patient-specific biomechanical models to investigate proximal junctional failure in clinical cases with adult spine deformity using ASME V&V40 standard.

Computational models are increasingly used to assess spine biomechanics and support surgical planning. However, varying levels of model verification and validation, along with characterization of uncertainty effects limit the level of confidence in their predictive potential. The objective was to assess the credibility of an adult spine deformity instrumentation model for proximal junction failure (PJF) analysis using the ASME V&V40:2018 framework. To assess model applicability, the surgery, erected posture, and flexion movement of actual clinical cases were simulated. The loads corresponding to PJF indicators for a group of asymptomatic patients and a group of PJF patients were compared. Model consistency was demonstrated by finding PJF indicators significantly higher for the simulated PJF vs. asymptomatic patients. A detailed sensitivity analysis and uncertainty quantification were performed to further establish the model credibility.

Quantum graph model for rovibrational states of protonated methane.

We calculate the rovibrational states of the protonated methane molecular ion CH5 + for angular momenta up to J = 4. Our novel approach is based on a quantum graph description of the low-energy nuclear dynamics. Previous work on the quantum graph model neglected rotational degrees of freedom and so only described purely vibrational excitations. We extend this work significantly to give the first example of a full rovibrational quantum graph model. We compare our results to 7D variational calculations, finding good agreement for J ≤ 3. To the best of our knowledge, the J = 4 results are the first of their kind.

The association between oral examination findings and computed tomographic appearance of the equine temporomandibular joint.

BACKGROUND: The temporomandibular joint (TMJ) forms the junction between the maxilla and mandible. Movement of the jaw and resulting masticatory forces have been extensively studied in the horse; however, less is known about the inter-relationship between this joint and oral and dental pathology. OBJECTIVES: To determine the association between specific oral and dental pathologies and anatomical variations of the TMJ imaged with computed tomography (CT) in horses with asymptomatic TMJs. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Horses (n = 201) from three practices with a complete oral examination and skull or upper cervical CT study were reviewed. Age, breed, sex, clinical presentation, oral examination findings, slice width and practice were recorded. Alterations in contour and density of the mandibular condyle, mandibular fossa and intra-articular disc were also documented. Logistic regression, corrected for clustering by practice, was used to determine whether CT anatomical variations were significantly associated with the oral examination findings. RESULTS: Horses categorised as having abnormal TMJs were older than those with normal TMJ. Horses with periodontal disease were less likely to have abnormal TMJ findings compared with horses with no oral pathology. In contrast, horses with infundibular disease were more likely to have TMJ abnormalities. MAIN LIMITATIONS: Due to the cross-sectional nature of the study, it was difficult to establish whether oral pathology preceded TMJ abnormalities. CONCLUSIONS: Despite examining over 200 horses of varying ages, the biological significance of the observed associations between oral, or dental disease and anatomically appreciable temporomandibular joint disorders remains uncertain.

Transoesophageal ultrasound and computer tomographic assessment of the equine cricoarytenoid dorsalis muscle: Relationship between muscle geometry and exercising laryngeal function.

REASONS FOR PERFORMING STUDY: Early detection of recurrent laryngeal neuropathy (RLN) is of considerable interest to the equine industry. OBJECTIVES: To describe two imaging modalities, transoesophageal ultrasound (TEU) and computed tomography (CT) with multiplanar reconstruction to assess laryngeal muscle geometry, and determine the relationship between cricoarytenoid dorsalis (CAD) geometry and function. STUDY DESIGN: Two-phase study evaluating CAD geometry in experimental horses and horses with naturally occurring RLN. METHODS: Equine CAD muscle volume was determined from CT scan sets using volumetric reconstruction with LiveWire. The midbody and caudal dorsal-ventral thickness of the CAD muscle was determined using a TEU in the same horses; and in horses with a range of severity of RLN (n = 112). RESULTS: Transoesophageal ultrasound was able to readily image the CAD muscles and lower left:right CAD thickness ratios were observed with increasing disease severity. Computed tomography based muscle volume correlated very closely with ex vivo muscle volume (R2 = 0.77). CONCLUSIONS: Computed tomography reconstruction can accurately determine intrinsic laryngeal muscle geometry. A relationship between TEU measurements of CAD geometry and laryngeal function was established. These imaging techniques could be used to track the response of the CAD muscle to restorative surgical treatments such as nerve muscle pedicle graft, nerve anastomosis and functional electrical stimulation.

Mandibular osteopathy in a Hagerman horse, Equus simplicidens (Equidae, Mammalia), from Hagerman Fossil Beds National Monument (Idaho, USA).

Multimodality imaging, including computed tomography (CT) and digital radiography, was utilized to examine a fossilized hemimandible of a probable female Hagerman horse (Equus simplicidens) with a large, ventrally located, osseous deformation. Utilizing comparative pathology to the modern day horse, it was determined that the most likely etiology of the pathologic bony swelling along the ventral hemimandible was abnormal tooth development that led to chronic osteomyelitis and subsequent osseous proliferation, sclerosis and deformation.

Equine Odontoclastic Tooth Resorption and Hypercementosis: Histopathologic Features.

Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a painful progressive condition of older horses that involves multiple teeth, including canines and incisors. EOTRH is uncommonly recognized by veterinary pathologists and in some cases may be misdiagnosed as cementoblastoma. The cause is unknown. The goals of this study were to describe the histopathologic features of EOTRH in 17 affected horses from the United States and to increase awareness of this condition. Samples ranged from affected tooth to the entire rostral mandible and maxilla. Affected teeth exhibited cemental hyperplasia and lysis. The marked proliferation of cementum in severe cases caused bulbous enlargement of the intra-alveolar portions of affected teeth. Several teeth contained necrotic debris, bacteria, and plant material in the regions of cemental lysis. All horses exhibited dentinal lysis in at least affected tooth, and several contained necrotic debris in these regions. Endodontic disease was often present with inflammation, lysis, necrotic debris, fibrosis, and/or a thin rim of atubular mineralized tissue in the pulp cavity. Periodontal disease was a common feature that was primarily characterized by moderate lymphoplasmacytic inflammation. Resorption with secondary hypercementosis appears to begin on the external surface of the teeth rather than within the pulp cavity. Distinguishing EOTRH from other diseases requires a complete history that includes the number and location of affected teeth, a gross description of regional hard/soft tissue health, and radiographic findings.

A systematic review of the evidence on service user involvement in interpersonal skills training of mental health students.

Service user involvement has become a common feature of education programmes for mental health students. However, little is known about the effects of this type of education on the interpersonal skills of students taking part. This paper reports findings from a systematic review that formed part of a wider investigation into service user involvement in teaching interpersonal skills. The review aimed to locate and assess the quality of the published evidence relating to the effects of service user involvement on mental health students interpersonal skills and to synthesize results, using a definition of interpersonal skill that includes attitudes, empathy and skills as its key components. Results from this study indicate that the quality of evidence in this area is poor. However, sufficient synthesis of the evidence base was possible to allow conclusions and recommendations for both research and practice. Conclusions were that the involvement of service users in this area is both acceptable and valuable for students and had specific impacts on attitudes, empathy and skills. Some difficulties and reservations about the style of involvement are discussed. Recommendations for the conduct of future research are also made.

Biomechanical characterisation of equine laryngeal cartilage.

REASONS FOR PERFORMING THE STUDY: Upper airway obstruction is a common problem in the performance horse as the soft tissues of the larynx collapse into the airway, yet there is a paucity of information on biomechanical properties for the structural cartilage components. OBJECTIVE: To measure the geometry and compressive mechanical properties of the hyaline cartilage to improve understanding of laryngeal function and morphology. METHODS: A total of 11 larynges were harvested from Thoroughbred and Standardbred racehorses. During gross dissection, linear dimensions of the cricoid were obtained. From both the cricoid and arytenoid, specimens were cored to obtain 6 mm disc samples from 3 sites within the dorsal cricoid (caudal, middle and rostral) and 2 central sites in the arytenoids (inner, outer). The specimens were mechanically tested using radial confined compression to calculate the aggregate modulus and permeability of the tissue. The biomechanical data were analysed using a nested mixed effects model. RESULTS: Geometrically, the cricoid has relatively straight walls compared to the morphology of human, ovine and canine larynges. There were significant observations of higher modulus with increasing age (0.13 MPa per year; P = 0.007) and stiffer cricoid cartilage (2.29 MPa) than the arytenoid cartilage (0.42 MPa; P<0.001), but no difference was observed between the left and right sides. Linear contrasts showed that the rostral aspect (2.51 MPa) of the cricoid was 20% stiffer than the caudal aspect (2.09 MPa; P = 0.025), with no difference between the arytenoid sites. CONCLUSIONS: The equine larynx is a well supported structure due to both the geometry and material properties of the cricoid cartilage. The hyaline structure is an order of magnitude higher in compressive modulus compared to the arytenoids and other hyaline-composed tissues. POTENTIAL RELEVANCE: These characterisations are important to understand the biomechanics of laryngeal function and the mechanisms involved with surgical interventions.

Intra-articular stabilisation of the equine cricoarytenoid joint.

REASONS FOR PERFORMING STUDY: The success of laryngoplasty is limited by abduction loss in the early post operative period. OBJECTIVE: To determine the efficacy of polymethylmethacrylate (PMMA) in stabilising the cricoarytenoid joint (CAJ) and reducing the force on the laryngoplasty suture. HYPOTHESIS: Injection into the cricoarytenoid joint resists the forces produced by physiological laryngeal air flows and pressures thereby reducing the force experienced by the laryngoplasty suture. METHODS: Ten cadaver larynges were collected at necropsy and PMMA was injected into one CAJ at selected random. Each larynx was subjected to physiological conditions with with constant (static) or cycling (dynamic) flow. The specimens were tested sequentially in each of 4 conditions: 1) bilateral full abduction (Control 1); 2) transection of the suture on the side without PMMA; 3) bilateral abduction achieved by replacing the suture (Control 2); and 4) cutting the suture on the PMMA side. Tracheal pressure and flow and pressure in the flow chamber were recorded using pressure and flow transducers. The strain experienced by each suture during bilateral abduction (Controls 1 and 2) was measured. Statistical comparison of the 4 conditions was performed using a mixed effect model with Tukey's post hoc test for multiple comparisons. The strain gauge data were analysed by paired comparison of the regression slopes. RESULTS: In the static and dynamic states, tracheal pressure increased and tracheal flow decreased when the suture on the non-cement side was cut (P < 0.05). There was no significant difference in any outcome measure between PMMA injected into the CAJ and bilaterally abducted specimens (Controls 1 and 2) for either condition. The rate of increase in strain with increasing translaryngeal pressure was significantly less on the suture with PMMA placed in the CAJ (P = 0.03). CONCLUSIONS: These data provide strong evidence that injecting PMMA into the CAJ resists the collapsing effect of physiological airflows and pressures in vitro and reduces the force experienced by the laryngoplasty suture during maximal abduction. POTENTIAL RELEVANCE: Augmentation of prosthetic laryngoplasty with this technique may reduce arytenoid abduction loss in the early post operative period.

Merkel cell (neuroendocrine) carcinoma of the anal canal: report of a case.

Merkel cell tumors are rare neuroendocrine tumors typically found on sun-exposed areas such as extremities. We describe the case of a 42-year-old female with a Merkel cell tumor arising in the anal canal. The tumor was initially thought to represent a hemorrhoid arising during pregnancy and was excised locally after confirmation of extensive metastatic disease. The patient died 13 months after diagnosis with extensive metastatic disease involving the liver. In our search of the world literature there are several reports of neuroendocrine tumors in the rectum; however, no cases of documented Merkel cell tumors arising in the anal canal have been reported. These tumors seem to behave in a very aggressive manner when found in other atypical areas. The presentation symptoms were perianal discomfort and bleeding. Local excision may be the only surgical treatment necessary to control symptoms, given the propensity to early metastases and short life expectancy.

Dose to radiation therapists from activation at high-energy accelerators used for conventional and intensity-modulated radiation therapy.

The increased beam-on times which characterize intensity-modulated radiation therapy (IMRT) could lead to an increase in the dose received by radiation therapists due to induced activity. To examine this, gamma ray spectrometry was used to identify the major isotopes responsible for activation at a representative location in the treatment room of an 18 MV accelerator (Varian Clinac 21EX). These were found to be 28Al, 56Mn, and 24Na. The decay of the dose rate measured at this location following irradiation was analyzed in terms of the known half-lives to yield saturation dose rates of 9.6, 12.4, and 6.2 microSv/h, respectively. A formalism was developed to estimate activation dose (microSv/week) due to successive patient irradiation cycles, characterized by the number of 18 MV fractions per week, F, the number of MU per fraction, M, the in-room time between fractions, td (min), and the treatment delivery time t'r (min). The results are represented by the sum of two formulas, one for the dose from 28Al 1.8 x 10(-3) F M (1-e(-03t'(r))/t'r and one for the dose from the other isotopes approximately 1.1 x 10(-6) F(1.7) Mt(d). For conventional therapy doses are about 60 microSv/week for an 18 MV workload of 60,000 MU/week. Irradiation for QA purposes can significantly increase the dose. For IMRT as currently practiced, lengthy treatment delivery times limit the number of fractions that can be delivered per week and hence limit the dose to values similar to those in conventional therapy. However for an IMRT regime designed to maximize patient throughput, doses up to 330 microSv/week could be expected. To reduce dose it is recommended that IMRT treatments should be delivered at energies lower than 18 MV, that in multienergy IMRT, high-energy treatments should be scheduled in the latter part of the day, and that equipment manufacturers should strive to minimize activation in the design of high-energy accelerators.

Selection of patients for resection of hepatic metastases: improved detection of extrahepatic disease with FDG pet.

A rapidly emerging clinical application of positron emission tomography (PET) is the detection of tumor tissue at whole-body studies performed with the glucose analogue 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). High rates of recurrence after partial hepatic resection in patients with colorectal cancer liver metastases indicate that current presurgical imaging strategies are failing to show extrahepatic tumor deposits. Although FDG PET cannot match the anatomic resolution of conventional imaging techniques in the liver and the lungs, it is particularly useful for identification and characterization of extrahepatic disease. FDG PET can show foci of metastatic disease that may not be apparent at conventional anatomic imaging and can aid in the characterization of indeterminate soft-tissue masses. Several sources of benign and physiologic increased activity at FDG PET emphasize the need for careful correlation with findings of other imaging studies and clinical findings. FDG PET can improve the selection of patients for partial hepatic resection and thereby reduce the morbidity and mortality associated with inappropriate surgery.

Identification of amyloid-beta binding sites using an antisense peptide approach.

The amyloid-beta (A beta) peptide is a cytotoxic peptide implicated in the pathology of Alzheimer's disease (AD). Catalase and the endoplasmic reticulum A beta binding dehydrogenase (ERAB) are both inhibited by characterized fragments of the A beta peptide. In order to target such proteins it is essential to determine which components of these enzymes interact with A beta. This study reports the use of antisense peptide methodology to identify specific A beta-binding domains. Synthetic peptides corresponding to the regions of catalase and ERAB identified showed specific binding to A beta and also prevented A beta cytotoxicity. Antisense peptide methodology has identified A beta recognition sequences and may also be applied to the identification of novel A beta protein interactions to identify targets for use in the treatment of AD.

Value of double-contrast barium enema performed immediately after incomplete colonoscopy.

OBJECTIVE: The purpose of this study was to evaluate the ease, completeness, and clinical utility of double-contrast barium enema (DCBE) performed immediately after incomplete colonoscopy. SUBJECTS AND METHODS: During a 30-month period, a prospective study was performed in 103 patients (79 women, 24 men) to determine the ease and completeness of DCBE immediately after failed colonoscopy and any additional useful information provided by the enema. The ease with which DCBE was performed was graded from 1 (easy) to 10 (difficult). RESULTS: DCBE revealed the entire colon in 97 patients (94%). Incomplete DCBE was a result of obstruction and incontinence in three patients each. The mean score for ease of performing DCBE was 5.0. In 14 patients (14%), significant additional diagnostic information was provided by the immediate DCBE. In eight patients, abnormalities were identified on DCBE that had not been seen at colonoscopy (five malignant neoplasms, one diverticular mass, two extrinsic masses, and multiple strictures). In four patients, a suspected colonoscopic abnormality was excluded with DCBE findings; and in two patients, a colonoscopic abnormality was further characterized with DCBE. CONCLUSION: Immediate DCBE after incomplete colonoscopy allows complete colonic evaluation in most cases, often adds vital diagnostic information, and eliminates repeated bowel preparation and unnecessary delay in diagnosis.

Sedation and analgesia in adult patients: evaluation of a staged-dose system based on body weight for use in abdominal interventional radiology.

PURPOSE: To evaluate the safety and effectiveness of a systematic protocol for sedation and analgesia in interventional radiology. MATERIALS AND METHODS: Ninety-one adult patients underwent 113 abdominal interventional procedures. Fentanyl citrate and midazolam hydrochloride were administered in one to five steps (A, B, C, D, E) until the patient was drowsy and tranquil at the effective loading dose (ELD). Doses per step were as follows: A, fentanyl 1 microg per kilogram of body weight; B, midazolam 0.010-0.035 mg/kg; C, repeat dose in A; D, repeat half the dose in B; and E, midazolam 1-2-mg boluses (maximum, 0.15 mg/kg). RESULTS: The ELD was reached in no procedure after step A, in 70 after B, in 23 after C, and in 18 after D. Step E was needed in two procedures. The mean maximum pain score (scale of 0 to 10) was 3.4; pain scores in 85 (75%) procedures were 4 or less (discomforting). Severe pain occurred in seven (6%) procedures. Hypoxia (oxygen saturation < 90%) occurred in 11 (22%) procedures performed in patients breathing room air and four (6%) performed in those breathing supplemental oxygen (P: =.04). All patients responded to supplemental oxygen. CONCLUSION: This stepwise "ABCDE protocol" allows safe and effective sedation of patients. It is easy to use and may be useful in training radiology residents, staff, and nurses in the techniques of sedation and analgesia. Supplemental oxygen should be used routinely.

Detection of unsuspected colonic abnormalities using the pneumocolon technique during small bowel meal examination.

AIMS: The pneumocolon technique in small bowel meal examination is used to obtain double-contrast views of the distal ileum. The purpose of this study was to determine the proportion of cases in which an overhead pneumocolon radiograph demonstrated clinically relevant findings in the colon. METHODS: The overhead pneumocolon radiographs in 151 patients who underwent small bowel meals were evaluated retrospectively. A chart review was performed on those patients with positive colonic findings to determine if the suspected abnormalities affected patient management. RESULTS: Colonic abnormalities were identified in 34 of the 151 patients. One patient had a previously undiagnosed ascending colonic cancer; 17 had evidence of acute or chronic colitis; 13 had diverticulosis; one had a caecal polyp; one had an ileosigmoid fistula; one had a filling defect in the ascending colon. In 25 cases the colonic abnormality was visible only on the pneumocolon radiograph and not on the preceding single-contrast images. Management was altered by the colonic findings in seven cases. False-positive findings occurred in two cases. CONCLUSIONS: A routine overhead radiograph following use of the pneumocolon technique is a useful adjunct to small bowel meal examination as it can yield unsuspected and clinically significant colonic findings.Chou, S. (2000). Clinical Radiology55, 459-464.