The Simons Observatory: A large-diameter truss for a refracting telescope cooled to 1 K.

We present the design and measured performance of a new carbon fiber strut design that is used in a cryogenically cooled truss for the Simons Observatory small aperture telescope. The truss consists of two aluminum 6061 rings separated by 24 struts. Each strut consists of a central carbon fiber tube fitted with two aluminum end caps. We tested the performance of the strut and truss by (i) cryogenically cycling and destructively pull-testing strut samples, (ii) non-destructively pull-testing the final truss, and (iii) measuring the thermal conductivity of the carbon fiber tubes. We found that the strut strength is limited by the mounting fasteners and the strut end caps, not the epoxy adhesive or the carbon fiber tube. This result is consistent with our numerical predictions. Our thermal measurements suggest that the conductive heat load through the struts (from 4 to 1 K) will be less than 1 mW. This strut design may be a promising candidate for use in other cryogenic support structures.

Lower Interobserver Reliability for Nondimensional Intracystic Features Among Abdominal Radiologists for Characterizing Intraductal Papillary Mucinous Neoplasms Using Magnetic Resonance Imaging.

OBJECTIVES: Current guidelines recommend magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) for risk stratification of intraductal papillary mucinous neoplasms (IPMNs). We assessed the interobserver agreement among radiologists in evaluating and risk stratifying IPMNs. METHODS: This single-center study evaluated 30 patients with IPMNs who had undergone MRI/MRCP, endoscopic ultrasound, and/or surgical resection. Six abdominal radiologists evaluated the MRI/MRCPs to document multiple parameters. The analysis applied Landis and Koch κ interpretation for categorical variables and intraclass correlation coefficient (r) for continuous variables. RESULTS: Radiologists demonstrated almost perfect agreement for location (κ = 0.81, 95% confidence interval [CI], 0.74-0.87), size (r = 0.95; 95% CI, 0.89-0.98), and main pancreatic duct diameter (r = 0.98; 95% CI, 0.96-0.99). Substantial agreement was observed for communication with the main pancreatic duct (κ = 0.66; 95% CI, 0.57-0.75) and classification of IPMN subtype (κ = 0.77; 95% CI, 0.67-0.86). Presence of intracystic nodules (κ = 0.31; 95% CI, 0.21-0.42) and wall thickening (κ = 0.09; 95% CI, -0.01 to 0.18) reached only fair and slight agreement, respectively. CONCLUSIONS: Although MRI/MRCP is excellent in the evaluation of spatial aspects, there is lower reliability for nondimensional characteristics of IPMNs. These data support guideline-recommended complementary evaluation of IPMNs with MRI/MRCP and endoscopic ultrasound.

Simons Observatory: characterizing the Large Aperture Telescope Receiver with radio holography.

We present near-field radio holography measurements of the Simons Observatory Large Aperture Telescope Receiver optics. These measurements demonstrate that radio holography of complex millimeter-wave optical systems comprising cryogenic lenses, filters, and feed horns can provide detailed characterization of wave propagation before deployment. We used the measured amplitude and phase, at 4 K, of the receiver near-field beam pattern to predict two key performance parameters: 1) the amount of scattered light that will spill past the telescope to 300 K and 2) the beam pattern expected from the receiver when fielded on the telescope. These cryogenic measurements informed the removal of a filter, which led to improved optical efficiency and reduced sidelobes at the exit of the receiver. Holography measurements of this system suggest that the spilled power past the telescope mirrors will be less than 1%, and the main beam with its near sidelobes are consistent with the nominal telescope design. This is the first time such parameters have been confirmed in the lab prior to deployment of a new receiver. This approach is broadly applicable to millimeter and submillimeter instruments.

The Simons Observatory: modeling optical systematics in the Large Aperture Telescope.

We present geometrical and physical optics simulation results for the Simons Observatory Large Aperture Telescope. This work was developed as part of the general design process for the telescope, allowing us to evaluate the impact of various design choices on performance metrics and potential systematic effects. The primary goal of the simulations was to evaluate the final design of the reflectors and the cold optics that are now being built. We describe nonsequential ray tracing used to inform the design of the cold optics, including absorbers internal to each optics tube. We discuss ray tracing simulations of the telescope structure that allow us to determine geometries that minimize detector loading and mitigate spurious near-field effects that have not been resolved by the internal baffling. We also describe physical optics simulations, performed over a range of frequencies and field locations, that produce estimates of monochromatic far-field beam patterns, which in turn are used to gauge general optical performance. Finally, we describe simulations that shed light on beam sidelobes from panel gap diffraction.

Small duodenal carcinoids: a case series comparing endoscopic resection and autoamputation with band ligation.

GOALS: We sought to compare the efficacy and safety of endoscopic ultrasound-guided endoscopic resection (ER) and endoscopic band ligation (EBL) for autoamputation of small duodenal carcinoids. BACKGROUND: The ideal management of small duodenal carcinoid tumors remains unclear. STUDY: A retrospective review of duodenal carcinoids over a 10-year period (2002 to 2012) was performed at our tertiary-care teaching hospital. All patients with duodenal carcinoids ≤10 mm in size treated with either ER or EBL were included. The main outcome measurements were the efficacy and safety of endotherapy. RESULTS: A total of 37 patients with 39 subcentimeter duodenal carcinoids were identified. In the EBL group, the mean (SD) tumor size was 6.7±2.1 mm compared with 6.7±1.7 mm in the ER group (P=0.943). The mean Ki-67 index was ≤2% in specimens available for histologic analysis in both groups (16/23 EBL and 15/16 ER). The positive deep margin rate in the ER group was 68.8%. Residual carcinoid tumor cells were detected on follow-up biopsies in 1 patient after EBL, and 2 patients after ER. All underwent subsequent successful endotherapy. No adverse events occurred in the EBL group compared with an 18.8% adverse event rate in the ER group (P=0.066). CONCLUSIONS: Endoscopic ultrasound-guided EBL is a safe, effective method for removal of small superficial duodenal carcinoids and seems to be a lower risk alternative to conventional ER with cautery.

Issues in hypertriglyceridemic pancreatitis: an update.

Hypertriglyceridemia (HTG) is a well-established but underestimated cause of acute pancreatitis and recurrent acute pancreatitis. The clinical presentation of HTG-induced pancreatitis (HTG pancreatitis) is similar to other causes. Pancreatitis secondary to HTG is typically seen in the presence of one or more secondary factors (uncontrolled diabetes, alcoholism, medications, pregnancy) in a patient with an underlying common genetic abnormality of lipoprotein metabolism (familial combined hyperlipidemia or familial HTG). Less commonly, a patient with rare genetic abnormality (familial chylomicronemic syndrome) with or without an additional secondary factor is encountered. The risk of acute pancreatitis in patients with serum triglycerides >1000 and >2000 mg/dL is ∼ 5% and 10% to 20%, respectively. It is not clear whether HTG pancreatitis is more severe than when it is due to other causes. Clinical management of HTG pancreatitis is similar to that of other causes. Insulin infusion in diabetic patients with HTG can rapidly reduce triglyceride (TG) levels. Use of apheresis is still experimental and better designed studies are needed to clarify its role in the management of HTG pancreatitis. Diet, lifestyle changes, and control of secondary factors are key to the treatment, and medications are useful adjuncts to the long-term management of TG levels. Control of TG levels to 500 mg/dL or less can effectively prevent recurrences of pancreatitis.

A nerve clamp electrode design for indirect stimulation of skeletal muscle.

A nerve clamp electrode was developed to indirectly stimulate skeletal muscle innervated by α motor neurons as an alternative to conventional electrodes. The stimulating electrode device consists of a spring coil-activated nerve clamp mounted inside a 1-mL syringe barrel. Supramaximal pulses were generated by a Grass stimulator and delivered to the nerve segment via the nerve clamp electrode. The salient feature of the electrode is its ability to produce muscle contractions indirectly through stimulation of the attached nerve. Indirect muscle stimulation is critical for studying the paralytic actions of presynaptic-acting toxins such as botulinum neurotoxins (BoNT), a potent inhibitor of acetylcholine (ACh) release from α motor neurons. This device enables stimulation of muscle contraction indirectly as opposed to contraction from direct muscle stimulation. The electrode is able to stimulate indirect muscle contraction when tested on ex vivo preparations from rodent phrenic nerve-hemidiaphragm muscle in similar fashion to conventional electrodes. In addition, the electrode stimulated external intercostal nerve-muscle preparations. This was confirmed after applying BoNT serotype A, a potent inhibitor of ACh release, to induce muscle paralysis. Alternative methods, including suction and bipolar loop electrodes, were unsuccessful in stimulating indirect muscle contraction. Therefore, this novel electrode is useful for physiological assessment of nerve agents and presynaptic actions of toxins that cause muscle paralysis. This electrode is useful for stimulating nerve-muscle preparations for which the length of nerve is a concern.

Unique features of esophagogastric junction pressure topography in hiatus hernia patients with dysphagia.

BACKGROUND: Our aim was to assess pressure dynamics within the esophagogastric junction (EGJ) in sliding hiatus hernia (HH) during normal peristalsis and to compare the pressure profiles of HH patients with gastroesophageal reflux disease (GERD) symptoms (HH-GERD) to HH patients with dysphagia (HH-dysphagia). METHODS: High-resolution manometry studies in 230 consecutive patients and 68 controls were reviewed. HH patients were defined by a >or=1.5 cm separation between the lower esophageal sphincter (LES) and crural diaphragm (CD) on pressure topography plots. The HH population was further culled to eliminate those patients with motor disorders or stricture. The study groups were composed of 18 HH patients with only reflux symptoms and 10 HH patients with only dysphagia. Analysis of the pressure dynamics within the EGJ was performed at rest and after swallowing to independently quantify the LES and CD contributions to residual EGJ pressure, as well as the magnitude and genesis of distal esophageal intrabolus pressure (IBP). Differences among study groups were analyzed with analysis of variance. RESULTS: After swallows, HH-dysphagia patients had greater residual CD pressure (9 mmHg; standard deviation [SD], 4) and IBP pressure (19 mmHg; SD, 4) compared to HH-GERD patients (5 mmHg; SD, 2; and 12 mmHg; SD, 2, respectively; P<.001) or normal subjects (NA; 11 mmHg; SD, 3; P<.001). CONCLUSION: Sliding HH alters the pressure dynamics through the EGJ and can lead to a functional obstruction. Patients with HH and dysphagia have greater pressures through the CD compared to HH patients with GERD symptoms, supporting the hypothesis that sliding HH in and of itself may be responsible for dysphagia.

Functional esophagogastric junction obstruction with intact peristalsis: a heterogeneous syndrome sometimes akin to achalasia.

BACKGROUND: Some patients with suspected achalasia are found on manometry to have preserved peristalsis, thereby excluding that diagnosis. This study evaluated a series of such patients with functional esophagogastric junction (EGJ) obstruction. METHODS: Among 1,000 consecutive high-resolution manometry studies, 16 patients had functional EGJ obstruction characterized by impaired EGJ relaxation and intact peristalsis. Eight patients with post-fundoplication dysphagia and similarly impaired EGJ relaxation were studied as a comparator group with mechanical obstruction. Intrabolus pressure (IBP) was measured 1 cm proximal to the EGJ. Sixty-eight normal controls were used to define normal IBP. Patients' clinical features were evaluated. RESULTS: Functional EGJ obstruction patients presented with dysphagia (96%) and/or chest pain (42%). IBP was significantly elevated in idiopathic and post-fundoplication dysphagia patients versus controls. Among the idiopathic EGJ obstruction group treated with pneumatic dilation, BoTox(TM), or Heller myotomy, only the three treated with Heller myotomy responded well. Among the post-fundoplication dysphagia patients, three of four responded well to redo operations. CONCLUSION: Functional EGJ obstruction is characterized by pressure topography metrics demonstrating EGJ outflow obstruction of magnitude comparable to that seen with post-fundoplication dysphagia. Affected patients experience dysphagia and/or chest pain. In some cases, functional EGJ obstruction may represent an incomplete achalasia syndrome.

Inflammatory bowel disease: complications and extraintestinal manifestations.

Inflammatory bowel disease (IBD) is a disorder driven by immune dysregulation, characterized by a relapsing-remitting pattern which is punctuated by flares associated with abdominal pain and bloody diarrhea. Management in general is guided by potent immunosuppressive regimens, often with equally potent associated toxicities. Treatment of refractory disease has been revolutionized by biologic therapies. Surgery remains an important part of the overall treatment plan, especially in patients presenting with acute mechanical complications and for prophylactic total colectomy in certain patients at high risk for colorectal cancer (CRC). IBD is associated with a host of intestinal disease-related complications such as intestinal stricture and fistula formation, small bowel obstruction, toxic megacolon, CRC and malnutrition. In addition to these complications there exist a myriad of extraintestinal manifestations that affect almost every organ system, such as primary sclerosing cholangitis, ankylosing spondylitis, pyoderma gangrenosum and uveitis.

Celiac disease.

Celiac disease is an autoimmune disorder caused by the continued ingestion of gluten, a protein found in wheat, barley and rye, by predisposed individuals. With the development of highly sensitive serologic tests, this has become an increasingly recognized disease with prevalence as high as 1% in certain patient populations, such as Caucasian females. Almost all celiac patients carry the human leukocyte antigen DQ2/DQ8 gene. Much has recently been discovered about the role of the innate immune system in exposing genetically vulnerable patients to the pathogenic gliadin fraction of gluten. The "classical" presentation of chronic diarrhea and malabsorption is now a rarity. Due to earlier detection and increased awareness, celiac disease now presents with a myriad of "atypical" signs and symptoms such as iron-deficiency anemia and osteoporosis. Associated conditions include T-cell lymphoma, dermatitis herpetiformis, autoimmune thyroiditis and type 1 diabetes. Diagnosis requires serologic confirmation with either antiendomysial or antitransglutaminase antibodies as well as histologic confirmation from endoscopic small bowel biopsy. The only effective treatment necessitates a lifelong, continual adherence to a gluten-free diet.

Molecular identification of the biowarfare simulant Serratia marcescens from a 50-year-old munition buried at Fort Detrick, Maryland.

Serratia marcescens are Gram-negative bacteria that were often used by the U.S. military and others to track movement of bacteria in the environment. As part of ongoing construction at Fort Detrick, Maryland, what appeared to be a small bomblet was found buried in the ground at the site of an old test grid. A sample of a clear, straw-colored liquid was aseptically removed from the plastic reservoir; the results of routine cultures on standard bacteriological media were negative. DNA was extracted from the sample and found to be 99% identical to S. marcescens. These results demonstrate the ability to identify the contents of a biological munition that had been buried for approximately 50 years.

Conversion of a mouse Fab into a whole humanized IgG antibody for detecting botulinum toxin.

Antibodies serve as the gold standard in most immunodiagnostic assays. Recent advances in recombinant DNA technology have offered the production of antibody fragments or Fabs as promising alternatives. However, the lack of the Fc region of the antibody can be difficult in many standard diagnostic platforms. Therefore we sought to convert a murine Fab into a whole humanized IgG. The variable regions from an anti-botulinum Fab were cloned into human IgG heavy and light chain vectors and produced in myeloma cells. Purified humanized IgG demonstrated conversion to human IgG with no traces of mouse Fab as determined by Western blot analysis. In addition, the humanized IgG performed better as both a detection and capture reagent in an ELISA format and detected the botulinum toxoid at a lower concentration than the parental murine Fab. This technique offers the ability to convert various species of antibodies or antibody fragments into humanized antibodies with improved characteristics in immunodiagnostic assays, for use as human controls in serological assays, or for possible therapeutic benefit.

Predictors of assistive technology use: the importance of personal and psychosocial factors.

OBJECTIVE: To validate an assistive technology (AT) baseline and outcomes measure and to quantify the measure's value in determining the best match of consumer and AT considering consumer ratings of their subjective quality of life, mood, support from others, motivation for AT use, program/therapist reliance, and self-determination/self-esteem. DESIGN: Prospective multi-cohort study. SETTING: Vocational rehabilitation offices and community. PARTICIPANTS: Over 150 vocational rehabilitation counselors in 25 U.S. states with one consumer each receiving new AT. INTERVENTIONS: Counselor training in the Matching Person and Technology (MPT) Model and consumer completion of the MPT measure, Assistive Technology Device Predisposition Assessment (ATD PA). MAIN OUTCOME MEASURES: Total and subscale scores on the ATD PA as well as counselor-completed questionnaires. RESULTS: ATD PA items differentiated consumer predispositions to AT use as well as AT and user match. There were no significant differences due to gender, physical locality, or age within this sample of working-age adult consumers. Vocational rehabilitation counselors exposed to training in the MPT Model achieved enhanced AT service delivery outcomes. CONCLUSIONS: The ATD PA is a valid measure of predisposition to use an AT and the subsequent match of AT and user. Rehabilitation practitioners who use the ATD PA will achieve evidence-based practice and can expect to see enhanced AT service delivery outcomes.

Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates.

Four serotypes of monovalent live attenuated dengue virus vaccine candidates were tested for reactogenicity and immunogenicity in 49 flavivirus non-immune adult human volunteers. The four monovalent candidates were then combined into a tetravalent formulation and given to another 10 volunteers. Neutralizing antibody seroconversion rates after a single-dose monovalent vaccination ranged from 53% to 100%. Solicited reactogenicity was scored by each volunteer. A composite index, the Reactogenicity Index, was derived by these self-reported scores. Reactogenicity differed among the four serotype candidates with serotype-1 associated with the most vaccine related side effects. A second dose of monovalent vaccines at either 30 days or 90 days was much less reactogenic but did not significantly increase seroconversion rates. Seroconversion rates in the 10 volunteers who received a single dose of tetravalent vaccine ranged from 30% to 70% among the four serotypes. Similar to the monovalent vaccines, a second dose of the tetravalent vaccine at one month was less reactogenic and did not increase seroconversion. A third dose of the tetravalent vaccine at four months resulted in three of four volunteers with trivalent or tetravalent high-titer neutralizing antibody responses.