Implications Of The Caacb Virus Contamination In Biomanufacturing Project For Cell Therapy Manufacturers

Adventitious agent contamination of cell culture-based biomanufacturing operations for the production of protein and monoclonal antibody biotherapeutics are infrequent, but when they do occur, they are very costly, impact manufacturing operations, and can potentially impact patient safety and product supply. In response to this need, the MIT Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) began the confidential collection and analysis of industry-wide viral contamination data with an emphasis on “lessons learned”. This presentation will cover the learnings from this study, including identified industry risks and best practices to mitigate those risks. Some of the key findings which have significant implications to the emerging cell therapy industry are: 1) Raw materials, including non-animal-based raw materials, may be a potential source of viral contamination and stringent raw material testing and vendor selection and auditing programs are critical. 2) Traditional viral tests, including in vitro testing and PCR, have contributed to false-positive events, which may take extended times to resolve prior to release of raw materials, process intermediates, or final product. 3) The time frames needed for viral testing in general, and for investigation of positive viral tests, can range from weeks to months, and are not compatible with the requirements for near real-time release testing for some cell therapy products. 4) Viral testing programs, and potential investigations of positive results, are quite expensive, and application to the autologous cell therapy space will be challenging

Recruitment, growth and mortality of an Antarctic hexactinellid sponge, Anoxycalyx joubini.

Polar ecosystems are sensitive to climate forcing, and we often lack baselines to evaluate changes. Here we report a nearly 50-year study in which a sudden shift in the population dynamics of an ecologically important, structure-forming hexactinellid sponge, Anoxycalyx joubini was observed. This is the largest Antarctic sponge, with individuals growing over two meters tall. In order to investigate life history characteristics of Antarctic marine invertebrates, artificial substrata were deployed at a number of sites in the southern portion of the Ross Sea between 1967 and 1975. Over a 22-year period, no growth or settlement was recorded for A. joubini on these substrata; however, in 2004 and 2010, A. joubini was observed to have settled and grown to large sizes on some but not all artificial substrata. This single settlement and growth event correlates with a region-wide shift in phytoplankton productivity driven by the calving of a massive iceberg. We also report almost complete mortality of large sponges followed over 40 years. Given our warming global climate, similar system-wide changes are expected in the future

Comptel observations of the quasar PKS 0528+134

During Phase I and Phase II of the CGRO‐mission, the quasar PKS 0528+134 was in the field of view of the COMPTEL instrument during several viewing periods. The quasar was detected by COMPTEL mainly at energies above 10 MeV. Below 10 MeV there is evidence for the source during some CGRO viewing periods, while below 3 MeV no signal is detected. The detections and non‐detections during different viewing periods follow the trend seen by EGRET, thereby indicating a time‐variable MEV‐flux of the quasar. The COMPTEL spectral results together with the simultaneously measured EGRET spectrum, indicate a spectral break in the upper part of the COMPTEL energy range at energies between 10 MeV and 30 MeV

Search for gamma‐ray emission from AGN with COMPTEL

The COMPTEL data (∼0.7–30 MeV) were searched for emission from AGN. Four sources have been detected so far: the quasars 3C 273, 3C 279, PKS 0528+134, and the radio galaxy Centaurus A. 3C 273 and 3C 279 were detected in CGRO observation period 3 with quite different spectral shapes. There is also evidence for 3C 273 at a weak flux level in observation period 11. The quasar PKS 0528+134 was detected above 3 MeV as part of a search for AGN already observed by EGRET. Cen A was seen up to 3 MeV by combining data from different observation periods

Low Back Pain in the Emergency Medicine Department: A Flipped Classroom Module.

IntroductionCurrent residency didactic schedules that are built upon hour-long, lecture-based presentations are incongruous with adult learning theory and the needs of millennial generation residents. An alternative to the traditional lecture, the flipped classroom involves viewing a short video lecture at home, followed by an active discussion during class time. This module was developed for emergency medicine residents and rotating medical students without previous training on the subject.MethodsThe at-home portion of the module was designed to be delivered at home, while the in-class discussion was designed to be carried out over 30-45 minutes during a regularly scheduled didactic time. Small-group size may be determined by faculty availability, though groups of five are optimal. There is no requirement for faculty preparation prior to the in-class session. Associated materials include objectives, the at-home video, a discussion guide for faculty facilitators, a case-based handout for students and residents, and assessment questions. We assessed our module with a pretest, immediate posttest, and the posttest again after 90 days.ResultsThe mean pretest score was 66%, mean posttest score 76%, and mean retention test score 66%. There was an immediate increase of 10%, which did not remain at 90 days.DiscussionWe developed a flipped classroom module that can be implemented in any emergency medicine residency or clerkship. It addresses the theoretical challenges posed to traditional conference didactics by increasing the focus on problem solving and self-directed learning

MARGIE: A gamma-ray burst ultra-long duration balloon mission

We are designing MARGIE as a 100 day ULDB mission to: a) detect and localize gamma-ray bursts; and b) survey the hard X-ray sky. MARGIE will consist of one small field-of-view (FOV) and four large FOV coded mask modules mounted on a balloon gondola. The burst position will be calculated onboard and disseminated in near-real time, while information about every count will be telemetered to the ground for further analysis. In a 100-day mission we will localize ∼40 bursts with peak photon fluxes from 0.14 to ∼5 ph cm−2 s−1 using 1 s integrations; the typical localization resolution will be better than ∼2 arcminutes

Minute-of-Arc Resolution Gamma ray Imaging Experiment—MARGIE

MARGIE (Minute-of-Arc Resolution Gamma-ray Imaging Experiment) is a large area(∼104 cm2), wide field-of-view (∼1 sr), hard X-ray/gamma-ray (∼20–600 keV) coded-mask imaging telescope capable of performing a sensitive survey of both steady and transient cosmic sources. MARGIE has been selected for a NASA mission-concept study for an Ultra Long Duration (100 day) Balloon flight. We describe our program to develop the instrument based on new detector technology of either cadmium zinc telluride (CZT) semiconductors or pixellated cesium iodide (CsI) scintillators viewed by fast-timing bi-directional charge-coupled devices (CCDs). The primary scientific objectives are to image faint Gamma-Ray Bursts (GRBs) in near-real-time at the low intensity (high-redshift) end of the logN-logS distribution, thereby extending the sensitivity of present observations, and to perform a wide field survey of the Galactic plane

Coccidioidomycosis in pregnancy: Case report and literature review of associated placental lesions

AbstractBackgroundCoccidioidomycosis is an endemic fungal infection found most commonly in the Southwestern United States, Northwestern Mexico, and parts of Central and South America. Although infection is relatively uncommon during pregnancy, it is imperative to have an index of suspicion in order to diagnose and begin timely treatment to prevent dissemination and dire consequences.Case reportA 33-year-old Hispanic female was evaluated after she was involved in an automobile accident. Radiographic evaluation showed a 3.2×3.2cm cavitary thick-walled lesion. A biopsy was negative for malignancy. Evaluation was positive for coccidioidomycosis by complement fixation reaction. Four months later, the patient presented 7weeks into a pregnancy with massive hemoptysis. Bronchoscopy revealed bleeding from the right upper lobe and emergency embolization was performed. The patient had a spontaneous abortion 9days after admission. The right upper and middle lobes of the lung were resected due to continuous bleeding. A subsequent pregnancy was un-eventful. Coccidioidomycosis titers remained negative throughout the second pregnancy.DiscussionThis case demonstrates the potential for severe pulmonary coccidioidomycosis and vascular strain of pregnancy-associated vascular expansion in the first trimester of pregnancy and the possibility of a favorable pregnancy outcome in subsequent pregnancies after appropriate treatment. The route of feto-maternal transmission and placental lesions in coccidioidomycosis are discussed

Initial results from COMPTEL—an overview

COMPTEL is presently completing the first full sky survey in MeV gamma‐ray astronomy (0.7 to 30 MeV). An overview of initial results from the survey is given: among these are the observations of the Crab and Vela pulsars with unprecedented accuracy, the observation of the black hole candidates Cyg X‐1 and Nova Persei 1992, an analysis of the diffuse Galactic continuum emission from the Galactic center region, the broad scale distribution of the 1.8 MeV line from radioactive 2 6Al, upper limits on gamma‐ray line emission from SN 1991T, observations of the three quasars 3C273, 3C279 and PKS 0528+134 and the radio galaxy Cen A, measurements of energy spectra, time histories and locations of a number of cosmic gamma‐ray bursts, and gamma‐ray and neutron emission from solar flares

(μ-Piperazine-1,4-dicarbodithio­ato-κ4 S 1,S 1′:S 4,S 4′)bis­[bis­(triphenyl­phos­phane-κP)gold(I)] chloro­form disolvate

In the title compound, [Au2(C6H8N2S4)(C18H15P)4]·2CHCl3, the digold complex resides on a crystallographic inversion center and co-crystallizes with two mol­ecules of chloro­form solvent. The piperazine-1,4-dicarbodithio­ate linker has an almost ideal chair conformation. The geometry about the gold atoms is severely distorted tetra­hedral punctuated by a very acute S—Au—S bite angle