Robert Terlevic

The choice of therapy for muscle-invasive bladder cancer (MIBC) could be influenced by the tumor’s molecular subtype. Currently, well-defined consensus subtypes are based on tumor microarray mRNA data. Clearly defined and easy-to-use surrogate molecular subtypes, based on immunohistochemistry (IHC) performed on whole slides, are needed to make subtyping cost-effective and useful in routine work and future research. To aid in the development of a simple immunohistochemical classifier, a retrospective single-center series of 92 cases of localized bladder cancer was identified. Routine IHC for GATA3, cytokeratins 5 and 6 (CK5/6), and p16 was performed on whole tissue blocks containing muscle-invasive disease. Electronic medical records were retrieved and searched for clinical variables, treatment, and survival data. The mean age was 69.6 years, and 73% were males. Conservative treatment was used in 55% of cases, while cystectomy with chemotherapy was used in 45%. GATA3 and CK5/6 expression divided cases into broad luminal and basal subtypes, respectively, while p16 expression was used to subclassify luminal cases into luminal papillary and luminal unstable types according to the consensus molecular classification. When subtyped in this way, GATA3 and CK5/6 negative cases showed worse overall survival. Molecular subtyping of MIBC on whole slides containing muscle-invasive tumor using only three commonly used, consensus-based antibodies, is a feasible and cost-effective method for detecting subtypes of invasive bladder cancer. Future work combining morphological analysis and IHC is needed to fully translate the consensus molecular classification into a comprehensive, cost-effective subtyping strategy.

Autops Case Rep, vol.8, n2, e2018018, 2018

The microgravity ocular syndrome (MOS) results in significant structural and functional ophthalmic changes during 6-mo spaceflight missions consistent with an increase in cerebrospinal fluid (CSF) pressure compared with the preflight upright position. A ground-based study was performed to assess two of the major hypothesized contributors to MOS, headward fluid shifting and increased ambient CO₂, on intracranial and periorbital CSF. In addition, lower body negative pressure (LBNP) was assessed as a countermeasure to headward fluid shifting. Nine healthy male subjects participated in a crossover design study with five head-down tilt (HDT) conditions: −6, −12, and −18° HDT, −12° HDT with −20 mmHg LBNP, and −12° HDT with a 1% CO₂ environment, each for 5 h total. A three-dimensional volumetric scan of the cranium and transverse slices of the orbita were collected with MRI, and intracranial CSF volume and optic nerve sheath diameter (ONSD) were measured after 4.5 h HDT. ONSD increased during −6° ( P < 0.001), −12° ( P < 0.001), and −18° HDT ( P < 0.001) and intracranial CSF increased during −12° HDT ( P = 0.01) compared with supine baseline. Notably, LBNP was able to reduce the increases in ONSD and intracranial CSF during HDT. The addition of 1% CO₂ during HDT, however, had no further effect on ONSD, but rather ONSD increased from baseline in a similar magnitude to −12° HDT with ambient air ( P = 0.001). These findings demonstrate the ability of LBNP, a technique that targets fluid distribution in the lower limbs, to directly influence CSF and may be a promising countermeasure to help reduce increases in CSF. NEW & NOTEWORTHY This is the first study to demonstrate the ability of lower body negative pressure to directly influence cerebrospinal fluid surrounding the optic nerve, indicating potential use as a countermeasure for increased cerebrospinal fluid on Earth or in space.

We investigated whether the perceived angular velocity following velocity steps of 80°/s in the dark decreased with the repetition of the stimulation in the same direction. The perceptual response to velocity steps in the opposite direction was also compared before and after this unidirectional habituation training. Participants indicated their perceived angular velocity by clicking on a wireless mouse every time they felt that they had rotated by 90°. The prehabituation perceptual response decayed exponentially with a time constant of 23.9 s. After 100 velocity steps in the same direction, this time constant was 12.9 s. The time constant after velocity steps in the opposite direction was 13.4 s, indicating that the habituation of the sensation of rotation is not direction specific. The peak velocity of the perceptual response was not affected by the habituation training. The differences between the habituation characteristics of self-motion perception and eye movements confirm that different velocity storage mechanisms mediate ocular and perceptual responses.

Participants on spaceflights and international scientific analog Mars missions can encounter medical incidents (accidents, illnesses) and psychological issues (e.g., stress, group interaction, sleep disturbance, emotions). The aim of this study was to examine these parameters in a field crew living in a desert environment similar to Mars (Group 1) and in Mission Support Center (MSC) personnel on "Earth" (Group 2) during a 4-week mission. Of the 107 medical interventions in the field, 73 mainly minor incidents together with four near accidents and 29 medical checkup interventions were recorded. Of the 32 medical interventions, medical treatments for 23 incidents of minor severity were necessary in Group 2. Injuries (Group 1: 1.4/100 h, Group 2: 0.1/100 h) were significantly increased in the field, and illnesses (Group 1: 0.3/100 h, Group 2: 3.0/100 h) in the MSC personnel. Causes of accidents and illnesses are described. Psychological results show that emotions and stress remained stable in both groups. Sympathy, social competence, teamwork, and leadership showed high scores. These scores were lower on "Earth" but significantly increased in the last weeks. The Sahara's nighttime coldness was reflected in an increased wake-up frequency, and a longer sleeping time peaked in the third week, probably as a result of overfatigue. MARS2013 was a successful mission with highly motivated participants and minor medical incidents. For future analog missions and possibly long-distance open-space missions, some recommendations in terms of medical and psychological preparedness are made to reduce risks for field crew members and MSC personnel.

On future human Mars missions, surface sojourn duration and resources will be limited. One possibility to approach a positive cost-benefit ratio of a human Mars mission will be to maximize the scientific research on the martian surface within the operational, environmental, and experimental limitations. Sophisticated mission operations and advanced planning strategies will be a basic requirement for Mars exploration and make operational methods an important research subject during current Mars analog missions conducted by the Austrian Space Forum. The Morocco Mars analog field simulation MARS2013, with a duration of 4 weeks and a simulated time delay of 10 min for communication between field and mission support, was the most advanced Mars analog mission conducted by the Austrian Space Forum so far. Due to these constraints, planning strategies based on real-time adjustments and ground control were not applicable, leading to the development of the "3-days-in-advance" planning strategy. Applying this methodology, 45.7% of the total EVA time was used for scientific experiments that satisfied 75.8% of the planned science goals. Taking into account all activities (donning of the suits included), the fraction of time used for scientific experiments made up only one-third of the total time, whereas it was planned to be above 50%. Here, we present details on the application of the 3-days-in-advance planning and on the results of the efficiency analysis of MARS2013.