Using extended reality (XR) for medical training and real-time clinical support during deep space missions.

Medical events can affect space crew health and compromise the success of deep space missions. To successfully manage such events, crew members must be sufficiently prepared to manage certain medical conditions for which they are not technically trained. Extended Reality (XR) can provide an immersive, realistic user experience that, when integrated with augmented clinical tools (ACT), can improve training outcomes and provide real-time guidance during non-routine tasks, diagnostic, and therapeutic procedures. The goal of this study was to develop a framework to guide XR platform development using astronaut medical training and guidance as the domain for illustration. We conducted a mixed-methods study-using video conference meetings (45 subject-matter experts), Delphi panel surveys, and a web-based card sorting application-to develop a standard taxonomy of essential XR capabilities. We augmented this by identifying additional models and taxonomies from related fields. Together, this "taxonomy of taxonomies," and the essential XR capabilities identified, serve as an initial framework to structure the development of XR-based medical training and guidance for use during deep space exploration missions. We provide a schematic approach, illustrated with a use case, for how this framework and materials generated through this study might be employed.

Lung metastases treated with image-guided stereotactic body radiation therapy.

AIMS: To evaluate outcomes after treatment with image-guided stereotactic body radiation therapy (SBRT) using daily online cone beam computed tomography for malignancies metastatic to the lung. MATERIALS AND METHODS: Forty-seven lung metastases in 32 patients were treated with volumetrically guided SBRT. The median age was 62 years (21-87). Primaries included colorectal (n = 10), sarcoma (n = 4), head and neck (n = 4), melanoma (n = 3), bladder (n = 2), non-small cell lung cancer (n = 2), renal cell (n = 2), thymoma (n = 2), thyroid (n = 1), endometrial (n = 1) and oesophageal (n = 1). The number of lung metastases per patient ranged from one to three (68% single lesions). SBRT was prescribed to the edge of the target volume to a median dose of 60 Gy (48-65 Gy) in a median of four fractions (four to 10). Most lesions were treated using 12 Gy fractions (92%) to 48 or 60 Gy. RESULTS: The median follow-up was 27.6 months (7.6-57.1 months). The 1, 2 and 3 year actuarial local control rates for all treated lesions were 97, 92 and 85%, respectively. Two patients with colorectal primaries (four lesions in total) had local failure. The median overall survival was 40 months. The 1, 2 and 3 year overall survival from the time of SBRT completion was 83, 76 and 63%, respectively. There were no grade 4 or 5 toxicities. Grade 3 toxicities (one instance of each) included pneumonitis, dyspnoea, cough, rib fracture and pain. CONCLUSION: SBRT with daily online cone beam computed tomography for lung metastases achieved excellent local tumour control with low toxicity and encouraging 2 and 3 year survival.

Influenza vaccination can induce new-onset anticardiolipins but not ß2-glycoprotein-I antibodies among patients with systemic lupus erythematosus.

BACKGROUND: Antiphospholipid syndrome is characterized by autoantibodies against cardiolipins (aCL), lupus anticoagulant, and independent ß2-glycoprotein (ß2GPI). Controversy exists as to whether vaccination triggers the development of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (101) and matched controls (101) were enrolled from 2005-2009 and received seasonal influenza vaccinations. Sera were tested by ELISA for aCL at baseline, 2, 6, and 12 weeks after vaccination. Vaccine responses were ranked according to an overall anti-influenza antibody response index. Individuals with positive aCL were further tested for ß2GPI antibodies. RESULTS: Patients with SLE and healthy controls can develop new-onset aCL post vaccination, although at rates which do not differ between patients and controls (12/101 cases and 7/101 controls, OR 1.81, p = 0.34). New-onset moderate aCL are slightly enriched in African American SLE patients (5/36 cases; p = 0.094). The optical density measurements for aCL reactivity in patients were significantly higher than baseline at 2 weeks (p < 0.05), 6 weeks (p < 0.05), and 12 weeks (p < 0.05) post vaccination. No new ß2GPI antibodies were detected among patients with new aCL reactivity. Vaccine response was not different between patients with and without new-onset aCL reactivity (p = 0.43). CONCLUSIONS: This study shows transient increases in aCL, but not anti-ß2GPI responses, after influenza vaccination.

Nondepleting anti-CD40-based therapy prolongs allograft survival in nonhuman primates.

Costimulation blockade of the CD40/CD154 pathway has been effective at preventing allograft rejection in numerous transplantation models. This strategy has largely depended on mAbs directed against CD154, limiting the potential for translation due to its association with thromboembolic events. Though targeting CD40 as an alternative to CD154 has been successful at preventing allograft rejection in preclinical models, there have been no reports on the effects of CD40-specific agents in human transplant recipients. This delay in clinical translation may in part be explained by the presence of cellular depletion with many CD40-specific mAbs. As such, the optimal biologic properties of CD40-directed immunotherapy remain to be determined. In this report, we have characterized 3A8, a human CD40-specific mAb and evaluated its efficacy in a rhesus macaque model of islet cell transplantation. Despite partially agonistic properties and the inability to block CD40 binding of soluble CD154 (sCD154) in vitro, 3A8-based therapy markedly prolonged islet allograft survival without depleting B cells. Our results indicate that the allograft-protective effects of CD40-directed costimulation blockade do not require sCD154 blockade, complete antagonism or cellular depletion, and serve to support and guide the continued development of CD40-specific agents for clinical translation.

Ecological release in White Sands lizards.

Ecological opportunity is any change that allows populations to escape selection from competition and predation. After encountering ecological opportunity, populations may experience ecological release: enlarged population size, broadened resource use, and/or increased morphological variation. We identified ecological opportunity and tested for ecological release in three lizard colonists of White Sands, New Mexico (Sceloporus undulatus, Holbrookia maculata, and Aspidoscelis inornata). First, we provide evidence for ecological opportunity by demonstrating reduced species richness and abundance of potential competitors and predators at White Sands relative to nearby dark soils habitats. Second, we characterize ecological release at White Sands by demonstrating density compensation in the three White Sands lizard species and expanded resource use in White Sands S. undulatus. Contrary to predictions from ecological release models, we observed directional trait change but not increased trait variation in S. undulatus. Our results suggest that ecological opportunity and ecological release can be identified in natural populations, especially those that have recently colonized isolated ecosystems.

Male territoriality and 'sex confusion' in recently adapted lizards at White Sands.

The evolution of intersexual interactions, like mate choice, during ecological speciation has received widespread attention. However, changes in intrasexual interactions, like male territoriality, during ecological divergence are largely unexamined. We conducted field experiments with adaptively diverged populations of the eastern fence lizard (Sceloporus undulatus) to determine whether territorial males behaved differently towards ecologically similar vs. dissimilar intruders. We performed trials with light-coloured males from White Sands, New Mexico and dark-coloured males from the surrounding desert. We found that intruders from White Sands elicited more aggression than intruders from dark-soil habitat. We also documented a case of 'sex confusion' where white-sand males courted dark-soil intruders. We found population differences in signalling patch size that can explain both aggression bias and sex misidentification. We argue that direct selection (for population recognition or optimal signal transmission) and indirect selection (by-products of ecological adaptation) should influence both intersexual and intrasexual interactions during ecological speciation.

An evaluation of commercial DNA extraction kits for the isolation of bacterial spore DNA from soil.

AIMS: To evaluate six commercial DNA extraction kits for their ability to isolate PCR-quality DNA from Bacillus spores in various soil samples. METHODS AND RESULTS: Three soils were inoculated with various amounts of Bacillus cereus spores to simulate an outbreak or intentional release of the threat agent Bacillus anthracis. DNA was isolated from soil samples using six commercial DNA extraction kits. Extraction and purification efficiencies were assessed using a duplex real-time PCR assay that included an internal positive control. The FastDNA(®) SPIN kit for Soil showed the highest DNA extraction yield, while the E.Z.N.A.(®) Soil DNA and PowerSoil(®) DNA Isolation kits showed the highest efficiencies in removing PCR inhibitors from loam soil extracts. CONCLUSIONS: The results of this study suggest that commercially available extraction kits can be used to extract PCR-quality DNA from bacterial spores in soil. The selection of an appropriate extraction kit should depend on the characteristics of the soil sample and the intended downstream application. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study aid in the selection of an appropriate DNA extraction kit for a given soil sample. Its application could expedite sample processing for real-time PCR detection of a pathogen in soil.

Cardiovascular collapse during ethanol sclerotherapy in a pediatric patient.

Ethanol sclerotherapy is a first line management therapy for low flow vascular malformations. It is usually performed under general anesthesia because of the pain associated with ethanol injection. Ethanol sclerotherapy frequently produces minor local complications but may rarely produce catastrophic cardiopulmonary complications. This report describes the cardiovascular collapse associated with an ethanol sclerotherapy procedure in an 11-year- old child. The evidence for ethanol-induced cardiovascular derangements is discussed.

The position and volume of the small bowel during adjuvant radiation therapy for rectal cancer.

PURPOSE: The rate of small bowel toxicity from adjuvant pelvic radiation therapy (RT) for rectal cancer has been reported to be lower for patients treated preoperatively (Preop). This was probably due to a lesser volume of irradiated small bowel; however, studies of postoperative treatment reported that patients with an abdominoperineal resection (APR), who likely have the largest volume of small bowel in the pelvis, had less acute and chronic toxicity than those with a low anterior resection (LAR). In this study, three-dimensional treatment planning techniques were used to characterize the position and volume of small bowel in the pelvis and compare these to repeat studies obtained during the typical 5-week course of treatment to attempt to explain the above observations. METHODS AND MATERIALS: Treatment planning CT scans were obtained in 30 patients with rectal cancer (10 Preop, 10 LAR, 10 APR), including 12 patients with weekly CT scans during RT (65 scans). The position of the small bowel was measured by the distance to the nearest small bowel from the bones of the posterior pelvis and by the volume of small bowel within four anatomically defined regions of the pelvis. The motion of the small bowel was expressed as the standard deviation of the small bowel position measured with both the distance and the volume in the 12 patients with repeat studies. RESULTS: Contrast-containing small bowel was found an average 2.9 cm more anterior than small bowel without contrast below the sacral promontory. The position of the small bowel in Preop patients was significantly more anterior (p < or = 0.01) with less volume (p < or = 0.04) in the pelvis than postoperatively treated patients. The small bowel was also more anterior for patients with an LAR vs. APR (p < or = 0.03) but with similar volume in all pelvic regions. Small bowel motion, expressed as the standard deviation of the distance from the bones of the posterior pelvis to the closest small bowel, was 2.9 cm, 1.4 cm, and 0.2 cm for the Preop, LAR, and APR group, respectively. The LAR group had a considerable degree of motion in the posterior pelvis. Increased bladder volume was associated with reduced small bowel volumes, although this benefit decreased during treatment. CONCLUSION: Because treatment planning CT scans can detect small bowel that does not contain contrast, they may be more accurate than the traditional small bowel series. The Preop patients had significantly less pelvic small bowel supporting the clinical observation of better tolerance to therapy. The higher small bowel toxicity reported for LAR vs. APR patients may be explained by the greater variability of both the position and volume of the small bowel in the posterior pelvis for LAR patients. This finding suggests that a single planning study may not be accurate for the block design used for boost treatment of LAR patients. Bladder-filling techniques were useful for Preop and LAR but not APR patients, and decreased in benefit over time. This study suggested that treatment planning CT scans were more useful than a small bowel series and that more than one treatment planning CT may be obtained in any patient receiving > 45 Gy for rectal cancer. However, further research will be necessary to determine the optimal timing and total number of repeat studies.

Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer.

PURPOSE: The primary objective of this phase I trial was to determine the maximum-tolerated dose of radiation that could be delivered to the primary tumor concurrent with full-dose gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Thirty seven patients with unresectable (n = 34) or incompletely resected pancreatic cancer (n = 3) were treated. Gemcitabine was administered as a 30-minute intravenous infusion at a dose of 1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Radiation therapy was initiated on day 1 and directed at the primary tumor alone, without prophylactic nodal coverage. The starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in increments of 0.2 Gy, keeping the duration of radiation constant at 3 weeks. A second cycle of gemcitabine alone was intended after a 1-week rest. RESULTS: Two of six assessable patients experienced dose-limiting toxicity at the final planned dose level of the trial (42 Gy in 2.8-Gy fractions), one with grade 4 vomiting and one with gastric/duodenal ulceration. Two additional patients at this dose level experienced late gastrointestinal toxicity that required surgical management. CONCLUSION: The final dose investigated (42 Gy) is not recommended for further study considering the occurrence of both acute and late toxicity. However, a phase II trial of this novel gemcitabine-based chemoradiotherapy approach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on the basis of tolerance, patterns of failure, and survival data.

Annular abscesses in surgical endocarditis: anatomic, clinical, and operative features.

BACKGROUND: The aim of this study was to determine patterns of anatomic, clinical, and operative features in surgical endocarditis (SE) with annular abscess (AA). METHODS: The study consisted of a retrospective analysis of SE cases with AA between 1981 and 1997. RESULTS: A total of 41 cases with AA were found in 106 consecutive SE cases. There was a higher incidence of AA in aortic (37 of 71 [52%]) (p<0.01) compared to mitral (6 of 42 [14.3%]) or tricuspid (0 of 12) infections. However, the mitral abscesses had a greater tendency toward fistula or pseudoaneurysm formation (4 of 6 [67%]) than other valve abscess cavities (7 of 46 [15%]) (p<0.01). Severe heart failure (p<0.01), heart block (p<0.05), and fistula/pseudoaneurysm (p<0.001), were more often found in SE with AA than without. There were 46 separate aortic AA in 37 instances of aortic valve SE. Of these, 31 of 46 (67%) were less than 1 cm (group 1), 10 of 46 (22%) were large but confined to a given cusp annulus (group 2), 4 of 46 (8.6%) were large between multiple cusps (group 3), and 1 of 46 (2.2%) was circumferential (group 4). There were four instances of aortoventricular discontinuity. Group 1 abscesses were repaired by local closure without a patch significantly more often than the other groups. The mortality of SE with AA was significantly greater for larger AA (groups 3 and 4, 3 of 5 [60%]) than for smaller AA (groups 1 and 2, 0 of 36) (p<0.001). There were six separate mitral AA in six instances of mitral SE, five requiring patch repair. The 30-day operative mortality for AA cases was 3 of 41 (7.3%) compared to 2 of 65 (3.1%) without AA. All AA mortalities involved large AA in the aortic valve position. Of 35 mechanical valves placed for AA, only one required subsequent removal for prosthetic endocarditis. CONCLUSIONS: Annular abscesses are most frequent in aortic AA, but fistulas/pseudoaneurysms are more frequent in mitral AA. Small to moderate aortic AA can be managed by local closure without an increased mortality compared to SE without AA. Patients with large aortic AA have a higher operative mortality. Mechanical prostheses are safe and effective for the majority of patients with AA.

Adhesion of Salmonella enterica var Enteritidis strains lacking fimbriae and flagella to rat ileal explants cultured at the air interface or submerged in tissue culture medium.

Rat ileal air interface and submerged explant models were developed and used to compare the adhesion of Salmonella enterica var Enteritidis wild-type strains with that of their isogenic single and multiple deletion mutants. The modified strains studied were defective for fimbriae, flagella, motility or chemotaxis and binding was assessed on tissues with and without an intact mucus layer. A multiple afimbriate/aflagellate (fim-/fla-) strain, a fimbriate but aflagellate (fla-) strain and a fimbriate/flagellate but non-motile (mot-) strain bound significantly less extensively to the explants than the corresponding wild-type strains. With the submerged explant model this difference was evident in tissues with or without a mucus layer, whereas in the air interface model it was observed only in tissues with an intact mucus layer. A smooth swimming chemotaxis-defective (che-) strain and single or multiple afimbriate strains bound to explants as well as their corresponding wild-type strain. This suggests that under the present experimental conditions fimbriae were not essential for attachment of S. enterica var Enteritidis to rat ileal explants. However, the possession of active flagella did appear to be an important factor in enabling salmonellae to penetrate the gastrointestinal mucus layer and attach specifically to epithelial cells.

Pain factors associated with physical disability in a sample of community-dwelling senior citizens.

BACKGROUND: Little is known about the specific aspects of pain that may contribute to the association between pain and disability. This study investigated whether the presence of a physical disability is associated with specific aspects of musculoskeletal pain. METHODS: Questionnaires sent to a sample of community-dwelling seniors included detailed questions about pain; the topics covered pain intensity, frequency, duration and location, use of pain medication, cause of pain, physical disability, depressive symptoms, chronic conditions, and demographic information. RESULTS: Of the 885 respondents, 644 reported musculoskeletal pain (mean age = 75.85 years, SD = 5.83; 63.2% men vs 36.8% women). Multiple logistic regression analysis revealed that pain of severe or greater intensity was shown to be significantly associated with disability (odds ratio [OR] = 4.32, 95% confidence interval [CI] 2.01 and 9.01, respectively). Pain experienced all or nearly all of the time (OR = 2.00, 95% CI 1.07 and 3.72) and taking pain medication (OR = 1.64, 95% CI 1.08 and 2.5 1) were also shown to be associated with disability. The number of pain locations reported by the respondents was also shown to be significantly associated with disability. The OR for the mean number of pain locations (5.8 locations out of a possible 45) was calculated to be 2.12 (95% CI 1.43 and 3.16). CONCLUSION: A thorough pain evaluation and appropriate management of certain aspects of pain may aid in the independent functioning of elderly persons.

DO11.10 and OT-II T cells recognize a C-terminal ovalbumin 323-339 epitope.

The OVA323-339 epitope recognized by DO11.10 (H-2d) and OT-II (H-2b) T cells was investigated using amino- and carboxy-terminal truncations to locate the approximate ends of the epitopes and single amino acid substitutions of OVA323-339 to identify critical TCR contact residues of the OVA323-339 peptide. DO11.10 and OT-II T cells are both specific for a C-terminal epitope whose core encompasses amino acids 329-337. Amino acid 333 was identified as the primary TCR contact residue for both cells, and amino acid 331 was found to be an important secondary TCR contact residue; however, the importance of other secondary TCR contact residues and peptide flanking residues differ between the cells. Additional OVA323-339-specific clones were generated that recognized epitopes found in the N-terminal end or in the center of the peptide. These findings indicate that OVA323-339 can be presented by I-Ad in at least three binding registers. This study highlights some of the complexities of peptide Ags such as OVA323-339, which contain a nested set of overlapping T cell epitopes and MHC binding registers.

The value of patient feedback in the audit of TMJ arthroscopy.

AIM: This study assessed the patients' and clinicians' perception of the outcome of temporomandibular joint arthroscopy. METHOD: All patients who underwent TMJ arthroscopy for both diagnostic and therapeutic purposes over a 6-year period were sent a questionnaire that asked about various symptoms attributable to the TMJ. Additionally a review of the clinical notes was performed. RESULTS: 83 patients underwent arthroscopy to 127 temporomandibular joints. The mean follow up was 3.6 years. 55% of patients assessed their jaw function as being effective, jaw movement, pain control, and overall satisfaction were satisfactory in 37%, 57%, and 48% of cases respectively. The clinicians' assessment revealed that 45% of patients had no joint tenderness, 74% of patients were able to open to > 35 mm and 74% of patients were free of any joint noise. 66% of patients were prepared to undergo a second procedure if indicated. CONCLUSION: Overall, 50% of patients seemed to view arthroscopy favourably although many patients still felt that jaw opening was restricted. The outcome was not related to the position and reducibility of the disc at surgery and other variables may be responsible. The disparity between the clinical evaluation and the patients' perception of effectiveness emphasises the importance of patient feedback.

The effect of radiation on an ambulatory chemotherapy infusion pump.

BACKGROUND: Ambulatory infusion pumps are used to deliver concurrent chemotherapy with pelvic radiation therapy for patients with rectal carcinoma. The pump is worn around the waist and may be exposed to direct as well as scattered radiation, possibly leading to a complete malfunction, requiring a new pump, and/or changes in the pump timing, with clinically significant reductions in chemotherapy administration. METHODS: Two new ambulatory chemotherapy pumps were irradiated using a 6-megavolt linear accelerator. The first pump received gradually increasing doses to determine whether a complete malfunction were possible and the approximate dose. The second pump was irradiated with a single large dose of 20 Gray (Gy) followed by smaller doses of 2 Gy to characterize the dose better. After each dose of radiation was given to both pumps, an internal self-diagnostic test and an independent assessment of the pump timing were performed. RESULTS: The first pump malfunctioned completely at a cumulative dose of 38.6 Gy after receiving an individual dose of 20 Gy. The second pump tolerated the single dose of 20 Gy without difficulty and completely malfunctioned at doses of 40-42 Gy. The second pump exhibited a reduction in pump timing by 25% at a cumulative dose of 40 Gy, which resolved spontaneously by approximately 2 hours. CONCLUSIONS: Even if removed from the direct radiation beam, an individual pump could accumulate enough radiation for complete failure during the treatment of fewer than 20 patients. Prior to a complete malfunction, the flow rate of chemotherapy may decrease by 25% for a number of hours without detection. Additional work will be necessary to define further the nature of the reduction in pump timing observed.