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Background Calling germline SNP variants from bisulfite-converted sequencing data poses a challenge for conventional software, which have no inherent capability to dissociate true polymorphisms from artificial mutations induced by the chemical treatment. Nevertheless, SNP data is desirable both for genotyping and to understand the DNA methylome in the context of the genetic background. The confounding effect of bisulfite conversion however can be conceptually resolved by observing differences in allele counts on a per-strand basis, whereby artificial mutations are reflected by non-complementary base pairs. Results Herein, we present a computational pre-processing approach for adapting sequence alignment data, thus indirectly enabling downstream analysis on a per-strand basis using conventional variant calling software such as GATK or Freebayes. In comparison to specialised tools, the method represents a marked improvement in precision-sensitivity based on high-quality, published benchmark datasets for both human and model plant variants. Conclusion The presented “double-masking” procedure represents an open source, easy-to-use method to facilitate accurate variant calling using conventional software, thus negating any dependency on specialised tools and mitigating the need to generate additional, conventional sequencing libraries alongside bisulfite sequencing experiments. The method is available at https://github.com/bio15anu/revelioand an implementation with Freebayes is available at https://github.com/EpiDiverse/SNP

Background Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity. Chronic exposure to elevated intracranial pressure during spaceflight is hypothesized to be a contributing factor, however, the etiologic causes remain unknown. Purpose To investigate the intracranial effects of microgravity by measuring combined changes in intracranial volumetric parameters, pituitary morphologic structure, and aqueductal cerebrospinal fluid (CSF) hydrodynamics relative to spaceflight and to establish a comprehensive model of recovery after return to Earth. Materials and Methods This prospective longitudinal MRI study enrolled astronauts with planned long-duration spaceflight. Measures were conducted before spaceflight followed by 1, 30, 90, 180, and 360 days after landing. Intracranial volumetry and aqueductal CSF hydrodynamics (CSF peak-to-peak velocity amplitude and aqueductal stroke volume) were quantified for each phase. Qualitative and quantitative changes in pre- to postflight (day 1) pituitary morphologic structure were determined. Statistical analysis included separate mixed-effects models per dependent variable with repeated observations over time. Results Eleven astronauts (mean age, 45 years ± 5 [standard deviation]; 10 men) showed increased mean volumes in the brain (28 mL; P < .001), white matter (26 mL; P < .001), mean lateral ventricles (2.2 mL; P < .001), and mean summated brain and CSF (33 mL; P < .001) at postflight day 1 with corresponding increases in mean aqueductal stroke volume (14.6 μL; P = .045) and mean CSF peak-to-peak velocity magnitude (2.2 cm/sec; P = .01). Summated mean brain and CSF volumes remained increased at 360 days after spaceflight (28 mL; P < .001). Qualitatively, six of 11 (55%) astronauts developed or showed exacerbated pituitary dome depression compared with baseline. Average midline pituitary height decreased from 5.9 to 5.3 mm (P < .001). Conclusion Long-duration spaceflight was associated with increased pituitary deformation, augmented aqueductal cerebrospinal fluid (CSF) hydrodynamics, and expansion of summated brain and CSF volumes. Summated brain and CSF volumetric expansion persisted up to 1 year into recovery, suggesting permanent alteration. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lev in this issue.

Prehospital stroke code activation results in reduced pre- and in-hospital delays and triage and transport of stroke patients to the right centers. In Paraguay, data about acute reper fusion treatment are not available. Recently, a pilot prehospital stroke code program was implemented in the country in November 2016. In an observational, single-center cohort study with a before–after design, from April 2015 to July 2018, we found that 193/832 (23.1%) of stroke patients were stroke code activated, and from these, 54 (6.5%) were brought to hospital under the prehospital stroke code protocol. Fifty-eight patients (58 alteplase and 2 additional endovascular treatment) received reperfusion therapy. Prehospital stroke code patients had a lower mean door-to-CT time (24 vs. 33 min, p = 0.021) and lower mean door-to-needle time (35.3 vs.76.3 min, p

With increasing carbon emissions rising temperatures are likely to impact our economies and societies profoundly. In particular, it has been shown that heat stress can strongly reduce labor productivity. The resulting economic perturbations can propagate along the global supply network. Here we show, using numerical simulations, that output losses due to heat stress alone are expected to increase by about 24% within the next 20 years, if no additional adaptation measures are taken. The subsequent market response with rising prices and supply shortages strongly reduces the consumers’ purchasing power in almost all countries including the US and Europe with particularly strong effects in India, Brazil, and Indonesia. As a consequence, the producing sectors in many regions temporarily benefit from higher selling prices while decreasing their production in quantity, whereas other countries suffer losses within their entire national economy. Our results stress that, even though climate shocks may stimulate economic activity in some regions and some sectors, their unpredictability exerts increasing pressure on people’s livelihood.

Background Reports on sex differences in stroke outcome and risk factors are scarce in Latin America. Our objective was to analyze clinical and prognostic differences according to sex among participants in the LASE (Latin American Stroke Registry). Methods and Results Nineteen centers across Central and South America compiled data on demographics, vascular risk factors, clinical stroke description, ancillary tests, and functional outcomes at short‐term follow‐up of patients included from January 2012 to January 2017. For the present study, all these variables were analyzed according to sex at hospital discharge. We included 4788 patients with a median in‐hospital stay of 8 days (interquartile range, 5–8); 2677 were male (median age, 66 years) and 2111 female (median age, 60 years). Ischemic stroke occurred in 4293: 3686 as cerebral infarction (77%) and 607 as transient ischemic attack cases (12.7%); 495 patients (10.3%) corresponded to intracerebral hemorrhage. Poor functional outcome (modified Rankin scale, 3–6) was present in 1662 (34.7%) patients and 38.2% of women ( P P =0.01). Death and poor functional outcome for all‐type stroke showed a higher risk in female patients (hazard ratio, 1.3, P =0.03; and hazard ratio, 1.1, P =0.001, respectively). Conclusions A worse functional outcome and higher mortality rates occurred in women compared with men in the LASE , confirming sex differences issues at short‐term follow‐up.

IMPORTANCE: Astronauts on International Space Station missions demonstrate adverse neuro-ocular changes. Reversing a negative translaminar pressure gradient (TLPG) by modulating cerebral blood flow, decreasing intracranial pressure, or increasing intraocular pressure (IOP) has been proposed as potential intervention for spaceflight-associated neuro-ocular syndrome (SANS). OBJECTIVE: To examine whether exercise (resistance, moderate-intensity aerobic, and high-intensity aerobic) or artificially increasing IOP is associated with modulated cerebro-ocular hemodynamic and pressure changes during head-down tilt (HDT), an analogue of spaceflight, in healthy adults. DESIGN, SETTING, AND PARTICIPANTS: A single-center investigation was conducted at Johnson Space Center, Houston, Texas, from January 1, 2014, to December 31, 2016, in 20 healthy men. EXPOSURE: On 3 separate days, participants rested supine, were tilted to −15° HDT, and then completed 1 of 3 experimental exercise conditions (moderate-intensity aerobic, resistance, or high-intensity interval aerobic). A subset of 10 participants wore swimming goggles on all days. MAIN OUTCOMES AND MEASURES: Applanation rebound tonometry was used to noninvasively assess IOP, and compression sonography was used to assess internal jugular venous pressure (IJVP). Estimated TLPG was calculated as the difference between IOP and IJVP. Cerebral inflow and outflow were measured in extracranial arteries using color-coded duplex ultrasonography. RESULTS: Twenty men participated in the study (mean [SD] age, 36 [9] years). Compared with supine IOP (mean [SD], 19.3 [3.7] mm Hg), IJVP (mean [SD], 21.4 [6.0] mm Hg), and estimated TLPG (mean [SD], −2.1 [7.0] mm Hg), −15° HDT was associated with increased IOP (mean difference, 2.3 mm Hg; 95% CI, 1.4-3.3 mm Hg; P

Importance After long-duration spaceflight, morphological changes in the optic nerve head (ONH) and surrounding tissues have been reported. Objective To develop methods to quantify ONH and surrounding tissue changes using preflight and postflight optical coherence tomographic scans of the ONH region. Design, Setting, and Participants Two separate analyses were done on retrospective data, with the first comparing a preflight group with a control group, followed by preflight to postflight analysis. All astronaut data were collected on the same instrument and maintained by the National Aeronautics and Space Administration (NASA) Lifetime Surveillance of Astronaut Health. Control data were all collected at the University of Houston. Participants were 15 astronauts who had previously been on an approximately 6-month long-duration mission and had associated preflight and postflight ONH scans. The control group consisted of 43 individuals with no history of ocular pathology or microgravity exposure. Development of algorithms and data analysis were performed between 2012 and 2015. Main Outcomes and Measures The optical coherence tomography data were analyzed using custom MATLAB programs (MathWorks) in which the Bruch membrane opening (BMO) was manually delineated and used as a reference for all morphological measures. The retinal pigment epithelium (RPE) position 2 mm from the center of the BMO was used to calculate the BMO height. Global and quadrant total retinal thickness and retinal nerve fiber layer (RNFL) thickness were calculated for elliptical annular regions referenced to the BMO. The standard circumpapillary circular scan was used to quantify RNFL and choroidal thickness. Results Among 15 astronauts (mean [SD] age at preflight evaluation, 48.7 [4.0] years) in this retrospective study, the BMO was recessed in preflight astronauts compared with healthy controls and deepened after long-duration microgravity exposure (median change, −9.9 μm; 95% CI of difference, −16.3 to 3.7 μm; P = .03). After long-duration missions, there was an increase in total retinal thickness to 1000 μm and RNFL to 500 μm from the BMO. Circumpapillary RNFL thickness increased by a median of 2.9 μm (95% CI of difference, 1.1-4.4 μm; P P = .66). Conclusions and Relevance After long-duration microgravity exposure, there are disc edema–like changes in the morphology of the ONH and surrounding tissue. The methods developed to analyze the ONH and surrounding tissue can be useful for assessing longitudinal changes and countermeasures in astronauts, as well as potentially for terrestrial disc edema causes.

We greatly appreciate the opportunity to respond to the comments of Dr. Wostyn et al. Their theory focuses on a glymphatic flow imbalance mechanism at the optic nerve head that may, at least partially, explain the development of optic disc swelling in astronauts during long-duration space flight. Th

To describe the history, clinical findings, and possible pathogenic etiologies of the constellation of neuro-ophthalmic findings discovered in astronauts after long-duration space flight and to discuss the terrestrial implications of such findings.Retrospective review of published observational, longitudinal examination of neuro-ophthalmic findings in astronauts after long-duration space flight; analysis of postflight questionnaires regarding in-flight vision changes in approximately 300 additional astronauts; and hypothesis generating for developing possible future countermeasures and potential implications for neuro-ophthalmic disorders on Earth. Astronauts with neuro-ophthalmic findings, which were not present at the start of a space flight mission and only seen on return from long-duration space missions to the International Space Station, will be discussed.After 6 months of space flight, 7 astronauts had ophthalmic findings consisting of optic disc edema in 5, globe flattening in 5, choroidal folds in 5, cotton-wool spots in 3, nerve fiber layer thickening detected by optical coherence tomography in 6, and decreased near vision in 6. Five of 7 astronauts with near vision complaints had a hyperopic shift ≥+0.50 diopters (D) between pre-/post-mission spherical equivalent refraction in 1 or both eyes (range, +0.50 to +1.75 D). These 5 astronauts showed globe flattening on magnetic resonance imaging. A total of 6 lumbar punctures have been performed to date (4 in the originally described cohort) and documented opening pressures of 18, 22, 21, 21.5, 28, and 28.5 cm H2O. These were performed at 8, 66, 19, 7, 12, and 57 days after mission, respectively. The 300 postflight questionnaires documented that approximately 29% and 60% of astronauts on short-duration and long-duration missions, respectively, experienced a degradation in distant and near visual acuity. Some of these vision changes remain unresolved for years after flight. Several possible pathogenic mechanisms, as well as potential countermeasures and discussion of possible terrestrial implications, are described.We previously hypothesized that the optic nerve and ocular changes that we described in astronauts may be the result of orbital and cranial cephalad fluid shifts brought about by prolonged microgravity exposure. The findings we reported previously and continue to see in astronauts may represent parts of a spectrum of ocular and cerebral responses to extended microgravity exposure. Future investigations hopefully will lead to countermeasures that can be used to eliminate or lessen the magnitude of these potentially harmful findings before long-duration space flight including the possibility of a manned mission to Mars.

The detection of differentially methylated regions (DMRs) is a necessary prerequisite for characterizing different epigenetic states. We present a novel program, metilene, to identify DMRs within whole-genome and targeted data with unrivaled specificity and sensitivity. A binary segmentation algorithm combined with a two-dimensional statistical test allows the detection of DMRs in large methylation experiments with multiple groups of samples in minutes rather than days using off-the-shelf hardware. metilene outperforms other state-of-the-art tools for low coverage data and can estimate missing data. Hence, metilene is a versatile tool to study the effect of epigenetic modifications in differentiation/development, tumorigenesis, and systems biology on a global, genome-wide level. Whether in the framework of international consortia with dozens of samples per group, or even without biological replicates, it produces highly significant and reliable results. journal article research support, non-u.s. gov't 2016 Feb 2015 12 02 imported

The McMurdo Research Station medical facility functions at the level of a rural community hospital emergency department. Telehealth technology has played an increasingly important role in providing intercontinental tertiary healthcare consultations, particularly for assistance with diagnostically challenging cases or cases involving complicated medical management. The role of telehealth in Antarctica is vital given the harsh and remote environment. The following case discusses a real-time tele-ultrasound consultation between the station physician and a patient with pericarditis at the McMurdo Medical Clinic in Antarctica and a team of cardiology consultants at the University of Texas Medical Branch, Galveston, TX. The use of teleheath technologies prevented an unnecessary intercontinental medical evacuation and allowed the patient to receive treatment at the McMurdo Research Station. This case report demonstrates that real-time tele-ultrasound can serve as an important diagnostic resource in the delivery of healthcare to isolated populations in remote environments.

The increase of bodyplan complexity in early bilaterian evolution is correlates with the advent and diversification of microRNAs. These small RNAs guide animal development by regulating temporal transitions in gene expression involved in cell fate choices and transitions between pluripotency and differentiation. One of the two known microRNAs whose origins date back before the bilaterian ancestor is mir-100. In Bilateria, it appears stably associated in polycistronic transcripts with let-7 and mir-125, two key regulators of development. In vertebrates, these three microRNA families have expanded to form a complex system of developmental regulators. In this contribution, we disentangle the evolutionary history of the let-7 locus, which was restructured independently in nematodes, platyhelminths, and deuterostomes. The foundation of a second let-7 locus in the common ancestor of vertebrates and urochordates predates the vertebrate-specific genome duplications, which then caused a rapid expansion of the let-7 family.

To quantify the change in cerebral spinal fluid (CSF) production rate and maximum systolic velocity in astronauts before and after exposure to microgravity and identify any physiologic trend and/or risk factor related to intracranial hypertension.Following Institutional Review Board (IRB) approval, with waiver of informed consent, a retrospective review of 27 astronauts imaged at 3T was done. Qualitative analysis was performed on T2 -weighted axial images through the orbits for degree of flattening of the posterior globe according to the following grades: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. One grade level change postflight was considered significant for exposure to intracranial hypertension. CSF production rate and maximum systolic velocity was calculated from cine phase-contrast magnetic resonance imaging and compared to seven healthy controls.Fourteen astronauts were studied. The preflight CSF production rate in astronauts was similar to controls (P = 0.83). Six astronauts with significant posterior globe flattening demonstrated a 70% increase in CSF production rate postflight compared to baseline (P = 0.01). There was a significant increase in CSF maximum systolic velocity in the subgroup without posterior globe flattening (P = 0.01).The increased postflight CSF production rate in astronauts with positive flattening is compatible with the hypothesis of microgravity-induced intracranial hypertension inferring downregulation in CSF production in microgravity that is upregulated upon return to normal gravity. Increased postflight CSF maximum systolic velocity in astronauts with negative flattening suggests increased craniospinal compliance and a potential negative risk factor to microgravity-induced intracranial hypertension.

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas.

Background: The genome is pervasively transcribed but most transcripts do not code for proteins, constituting non-protein-coding RNAs. Despite increasing numbers of functional reports of individual long non-coding RNAs (lncRNAs), assessing the extent of functionality among the non-coding transcriptional output of mammalian cells remains intricate. In the protein-coding world, transcripts differentially expressed in the context of processes essential for the survival of multicellular organisms have been instrumental in the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identified lncRNAs expressed differentially in response to oncologically relevant processes and cell-cycle, p53 and STAT3 pathways, using tiling arrays. Results: We found that up to 80% of the pathway-triggered transcriptional responses are non-coding. Among these we identified very large macroRNAs with pathway-specific expression patterns and demonstrated that these are likely continuous transcripts. MacroRNAs contain elements conserved in mammals and sauropsids, which in part exhibit conserved RNA secondary structure. Comparing evolutionary rates of a macroRNA to adjacent protein-coding genes suggests a local action of the transcript. Finally, in different grades of astrocytoma, a tumor disease unrelated to the initially used cell lines, macroRNAs are differentially expressed. Conclusions: It has been shown previously that the majority of expressed non-ribosomal transcripts are non-coding. We now conclude that differential expression triggered by signaling pathways gives rise to a similar abundance of non-coding content. It is thus unlikely that the prevalence of non-coding transcripts in the cell is a trivial consequence of leaky or random transcription events.

We investigated the effects of a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m) on selected Ca2+ sequestration properties of sarcoplasmic reticulum (SR) calcium pump in vastus lateralis muscle. Muscle samples were obtained by biopsy from 5 male climbers (peak oxygen consumption, VO2peak = 52.3 +/- 2.1 mL.kg(-1).min(-1)) approximately 7 days prior to (PRE) and 4 days following (POST) the expedition. A comparison of PRE versus POST measures of maximal Ca2+-ATPase activities (117 +/- 8.5 vs. 97.6 +/- 5.6 nmol.mg protein(-1).min(-1)) and Ca2+-uptake (204 +/- 15 vs. 161 +/- 11 nmol.mg protein(-1).min(-1)) measured in crude homogenates obtained from pre-exercised muscle, indicated only an effect (p0.05) of the expedition on Ca2+-uptake. The reduction in Ca2+-ATPase activity, representing 16.6%, was not significant (p = 0.089). The sarco endoplasmic reticulum calcium (SERCA)-ATPase isoforms, measured using Western blotting techniques, revealed a small reduction (p0.05) in SERCA 1 (-4.6 +/- 1.9%), but not in SERCA 2a (+2.0 +/- 1.4%). Prior to the expedition, both Ca2+-ATPase activity and Ca2+-uptake were reduced (p0.05) by approximately 34 and 18%, respectively, following 40 min of a two-step continuous cycling task (20 min at 59% VO2peak and 20 min at 74% VO2peak). The exercise-induced reduction in Ca2+-ATPase activity was independent of fiber type. Only in the case of Ca2+-uptake was a lower exercise response (p0.05) observed following the expedition, an effect that was due to the lower resting value. It is concluded that acclimatization as experienced during a mountaineering expedition induces changes in the properties of the SR Ca2+-pump, and particularly to Ca2+-sequestering function.

To investigate the hypothesis that acclimatization to altitude would result in a downregulation in muscle Na+-K+-ATPase pump concentration, tissue samples were obtained from the vastus lateralis muscle of six volunteers (5 males and 1 female), ranging in age from 24 to 35 yr, both before and within 3 days after a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m). Na+-K+-ATPase, measured by the [3H]ouabain-binding technique, decreased by 13.8% [348 ± 12 vs. 300 ± 7.6 (SE) pmol/g wet wt; P< 0.05]. No changes were found in the maximal activities (mol ⋅ kg protein− 1 ⋅ h− 1) of the mitochondrial enzymes, succinic dehydrogenase (3.63 ± 0.20 vs. 3.25 ± 0.23), citrate synthase (4.76 ± 0.44 vs. 4.94 ± 0.44), and malate dehydrogenase (12.6 ± 1.8 vs. 12.7 ± 1.2). Similarly, the expedition had no effect on any of the histochemical properties examined, namely fiber-type distribution (types I, IIA, IIB, IC, IIC, IIAB), area, capillarization, and succinic dehydrogenase activity. Peak aerobic power (52.3 ± 2.1 vs. 50.6 ± 1.9 ml ⋅ kg− 1 ⋅ min− 1) and body mass (76.9 ± 3.7 vs. 75.5 ± 2.9 kg) were also unaffected. We concluded that acclimatization to altitude results in a downregulation in muscle Na+-K+-ATPase pump concentration, which occurs without changes in oxidative potential and other fiber-type histochemical properties.

Background: A large number of Antarctic stations do not utilize ultrasound for medical care. Regular use of ultrasound imaging at South Pole and McMurdo Stations first began in October 2002. To date, there has been no evaluation of medical events requiring ultrasound examination from this remote environment. Additionally, the importance of tele-ultrasound for clinical management in Antarctica has not yet been assessed. We therefore conducted a retrospective analysis of all ultrasound exams performed at South Pole and McMurdo Stations between October 2002 and October 2003.Radiology reports and patient charts were reviewed for pre- and post-ultrasound diagnosis and treatment.Sixty-six ultrasound exams were conducted on 49 patients. Of the exams, 94.0% were interpreted by the store-and-forward method, whereas 6.0% were interpreted in "real-time" format. Abdominal, genitourinary, and gynecology ultrasound exams accounted for 63.6% of exams. Ultrasound examination prevented an intercontinental aeromedical evacuation in 25.8% of cases, and had a significant effect on the diagnosis and management of illness in patients at South Pole and McMurdo research stations.These findings indicate that diagnostic ultrasound has significant benefits for medical care at Antarctic stations and that tele-ultrasound is a valuable addition to remote medical care for isolated populations with limited access to tertiary-healthcare facilities.

Motivation: Tiling arrays have been a mainstay of unbiased genome-wide transcriptomics over the last decade. Currently available approaches to identify expressed or differentially expressed segments in tiling array data are limited in the recovery of the underlying gene structures and require several parameters that are intensity-related or partly dataset-specific. Results: We have developed TileShuffle, a statistical approach that identifies transcribed and differentially expressed segments as significant differences from the background distribution while considering sequence-specific affinity biases and cross-hybridization. It avoids dataset-specific parameters in order to provide better comparability of different tiling array datasets, based on different technologies or array designs. TileShuffle detects highly and differentially expressed segments in biological data with significantly lower false discovery rates under equal sensitivities than commonly used methods. Also, it is clearly superior in the recovery of exon–intron structures. It further provides window z-scores as a normalized and robust measure for visual inspection. Availability: The R package including documentation and examples is freely available at http://www.bioinf.uni-leipzig.de/Software/TileShuffle/ Contact: joerg.hackermueller@ufz.de Supplementary information: Supplementary data are available at Bioinformatics online.

Despite rigorous health screening in astronaut crews, there are a number of conditions that may occur during long duration, exploration class spaceflight. The risk of abdominal conditions requiring surgical intervention is not clear, yet submarine and polar base experiences suggest contingency planning is warranted. While radio communication time delay is only 2 s to the international space station (ISS), a potential Mars mission would necessitate time delays of about 15 min. We sought to demonstrate the feasibility of remote expert guidance of diagnostic ultrasound followed by laparoscopic appendectomy in a simulated Mars environment. Research was deemed exempt by the institutional review board. A simulated Mars research environment was utilized on Devon Island in the Canadian Arctic. Electronic communications including audio and video were established between the Arctic base and Henry Ford Hospital serving as Mission Control and incorporated the 15-min communications lag into all communication. Ultrasound and laparoscopic capabilities were integrated into communications for remote guidance. Remote guidance methods and technology utilized has been previously published in communication with the ISS. A simulated scenario involving a young female astronaut developing right lower quadrant pain was developed and utilized for this demonstration. An anatomical appendectomy model was utilized for the ultrasound and laparoscopic portions. Reference aids describing background technical aspects were developed. A set of confirmation milestones was used to generate a hard stop and mandated remote review. The simulated appendectomy was successfully pursued on the first attempt with no delays or untoward events. Reference aids were appropriate for non-surgical personnel and hard stops for milestones with remote approval and go ahead were shown to be feasible. The appendicitis was appropriately diagnosed utilizing remote guidance of ultrasonography and the appendix removed laparoscopically using stapled technique with remote guidance as well. We report a successful remote guidance demonstration from a simulated mars environment with clinical control from a terrestrial base utilizing appropriate delay and consistent bandwidth and technology

The interaction of the nucleotide excision repair (NER) protein dimeric complex XPC-hHR23B, which is implicated in the DNA damage recognition step, with three Cy3.5 labeled 90-bp double-stranded DNA substrates (unmodified, with a central unpaired region, and cholesterol modified) and a 90-mer single-strand DNA was investigated in solution by fluorescence correlation spectroscopy. Autocorrelation functions obtained in the presence of an excess of protein show larger diffusion times (tau (d)) than for free DNA, indicating the presence of DNA-protein bound complexes. The fraction of DNA bound (theta), as a way to describe the percentage of protein bound to DNA, was directly estimated from FCS data. A significantly stronger binding capability for the cholesterol modified substrate (78% DNA bound) than for other double-stranded DNA substrates was observed, while the lowest affinity was found for the single-stranded DNA (27%). This is in accordance with a damage recognition role of the XPC protein. The similar affinity of XPC for undamaged and 'bubble' DNA substrates (58% and 55%, respectively) indicates that XPC does not specifically bind to this type of DNA substrate comprising a large (30-nt) central unpaired region.

To investigate the hypothesis that respiratory gas exchange and, in particular, the O2consumption (V˙o2) response to exercise is altered after a 21-day expedition to 6,194 m, five male climbers (age 28.2 ± 2 yr; weight 76.9 ± 4.3 kg; means ± SE) performed a progressive and prolonged two-step cycle test both before and 3–4 days after return to sea level. During both exercise tests, a depression ( P < 0.05) inV˙o2(l/min) and an increase ( P < 0.05) in minute ventilation (V˙e btps; l/min) and respiratory exchange ratio were observed after the expedition. These changes occurred in the absence of changes in CO2production (l/min). During steady-state submaximal exercise, net efficiency, calculated from the rates of the mechanical power output to the energy expended (V˙o2) above that measured at rest, increased ( P < 0.05) from 25.9 ± 1.6 to 31.3 ± 1.3% at the lighter power output and from 24.4 ± 1.3 to 29.5 ± 1.5% at the heavy power output. These changes were accompanied by a 4.5% reduction ( P< 0.05) in peak V˙o2(3.99 ± 0.17 vs. 3.81 ± 0.18 l/min). After the expedition, an increase ( P < 0.05) in hemoglobin concentration (15.0 ± 0.49 vs. 15.8 ± 0.41 g/100 ml) was found. It is concluded that, because resting V˙o2was unchanged, net efficiency is enhanced during submaximal exercise after a mountaineering expedition when the exercise is performed soon after return to sea level conditions.

BACKGROUND: A high incidence of epileptiform activity in the electroencephalogram (EEG) was reported in children undergoing mask induction of anaesthesia with administration of high doses of sevoflurane for 5 minutes and longer. This study was performed to investigate whether reducing the time of exposure to a high inhaled sevoflurane concentration would affect the incidence of epileptiform EEG activity. It was hypothesized that no epileptiform activity would occur, when the inhaled sevoflurane concentration would be reduced from 8% to 4% immediately after the loss of consciousness. METHODOLOGY/PRINCIPAL FINDINGS: 70 children (age 7-96 months, ASA I-II, premedication with midazolam) were anaesthetized with 8% sevoflurane in 100% oxygen via face mask. Immediately after loss of consciousness, the sevoflurane concentration was reduced to 4%. EEGs were recorded continuously and were later analyzed visually with regard to epileptiform EEG patterns. Sevoflurane at a concentration of 8% was given for 1.2 ± 0.4 min (mean ± SD). In 14 children (20%) epileptiform EEG patterns without motor manifestations were observed (delta with spikes (DSP), rhythmic polyspikes (PSR), epileptiform discharges (PED) in 10, 10, 4 children (14%, 14%, 6%)). 38 children (54%) had slow, rhythmic delta waves with high amplitudes (DS) appearing on average before DSP. CONCLUSIONS/SIGNIFICANCE: The hypothesis that no epileptiform potentials would occur during induction of anaesthesia with a reduction of the inspired sevoflurane concentration from 8% to 4% directly after LOC was not proved. Even if 8% sevoflurane is administered only briefly for induction of anaesthesia, epileptiform EEG activity may be observed in children despite premedication with midazolam.

The purpose of this investigation was to demonstrate the potential of remote, mobile telemedicine during a four-week, high-altitude mountaineering expedition to Mount Logan, Canada's highest summit. Using a mobile satellite terminal and a laptop computer (both powered by a photovoltaic solar panel), ECG tracings and blood pressure measurements, in addition to colour images, short-segment video and audio clips were transmitted during the course of the ascent. The data were transmitted via a mobile communications satellite to a ground station in Ottawa, a distance of over 4000 km. The data were then transferred to the publics witched data network and delivered to the University of Ottawa Heart Institute for analysis. Similarly, data were transmitted from the ground station to the expedition team on Mount Logan throughout the ascent. Using this technique, medical diagnosis and emergency care can be facilitated in extreme and isolated locations lacking a telecommunications infrastructure. Such technology has applications in developing countries, disaster response efforts, remote civilian and military operations, and in space operations.