A NASA family of minicomputer systems, Appendix A

This investigation was undertaken to establish sufficient specifications, or standards, for minicomputer hardware and software to provide NASA with realizable economics in quantity purchases, interchangeability of minicomputers, software, storage and peripherals, and a uniformly high quality. The standards will define minicomputer system component types, each specialized to its intended NASA application, in as many levels of capacity as required

Leg-focused high-weight resistance training improves ventricular stroke volume, exercise capacity and strength in young patients with a Fontan circulation

INTRODUCTION: Effective therapy to improve exercise capacity in Fontan patients is lacking. Leg-focused high-weight resistance training might augment the peripheral muscle pump and thereby improve exercise capacity.METHODS: This randomized semi-cross-over controlled trial investigated effects of a 12-week leg-focused high-weight resistance training plus high-protein diet, on (sub)maximal exercise capacity, cardiac function (assessed with cardiovascular magnetic resonance), muscle strength and quality of life in pediatric Fontan patients.RESULTS: Twenty-eight pediatric Fontan patients were included, 27 patients, (median age 12.9 [10.5-15.7]), successfully completed the program. Peak oxygen uptake (PeakVO2) at baseline was reduced (33.3 ml/kg/min [27.1-37.4],73% [62-79] of predicted). After training PeakVO2/kg and Peak workload improved significantly with +6.2 ml/kg/min [95%CI: 3.4-9.0](+18%) p&lt;0.001 and +22 Watts [95%CI: 12-32](+18%) p&lt;0.001 respectively, compared to the control period. Indexed single ventricle stroke volume increased significantly (43 ml/beat/m2 [40-49] versus 46 [41-53], p=0.014), as did inferior vena cava flow (21 ml/beat/m2 [18-24] versus 23 [20-28], p=0.015), while superior vena cava flow remained unchanged. Strength of all measured leg muscles increased significantly compared to the control period. Self-reported quality of life improved on the physical functioning and change in health domains of the child health questionnaire, parent-reported quality of life improved on the bodily pain, general health perception, and change in health domains compared to the control period.CONCLUSION:In a relatively large group of 27 older Fontan children, 12-weeks of leg-focused high-weight resistance training improved exercise capacity, stroke volume, (sub)maximal exercise capacity, muscle strength, and domains of quality of life.</p

Intraoperative neurophysiological monitoring during scoliosis surgery in patients with Duchenne muscular dystrophy

PURPOSE: Little is known about the reliability and value of intraoperative neurophysiological monitoring (IONM) in patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction surgery. The aim of this study was to investigate the feasibility of IONM and the cortical excitability in these patients. METHODS: Fifteen patients with DMD and scoliosis and 15 patients with adolescent idiopathic scoliosis (AIS) underwent scoliosis correction surgery with the use of IONM. IONM consisted of transcranial electrical stimulation motor evoked potential (Tc-MEP) and somatosensory evoked potential (SSEP) monitoring. The highest Tc-MEP amplitudes were collected to test the feasibility. Preoperative compound muscle action potentials (CMAPs) and transcranial magnetic stimulation (TMS)-MEPs were recorded to test the cortical excitability. SSEPs were scored as elicitable or not elicitable. RESULTS: Tc-MEP amplitudes were significantly lower in the DMD group for both the gastrocnemius and tibialis anterior muscles. However, the abductor hallucis muscle had similar amplitudes in both the DMD as the AIS group. TMS/CMAP and Tc-MEP/CMAP ratios were similar in the DMD and AIS group (P = 0.126 and P = 0.792 respectively). CONCLUSIONS: Tc-MEP and SSEP monitoring is feasible, particularly when Tc-MEPs are recorded from the abductor hallucis muscle in patients with DMD. Similar TMS/CMAP and Tc-MEP/CMAP ratios show that there were no differences observed in cortical excitability between the groups. IONM seems a feasible and valuable neurophysiological tool to signal possible surgically induced damage to the spinal cord during scoliosis correction surgery in patients with DMD

The influence of depth of anesthesia and blood pressure on muscle recorded motor evoked potentials in spinal surgery. A prospective observational study protocol

For high-risk spinal surgeries, intraoperative neurophysiological monitoring (IONM) is used to detect and prevent intraoperative neurological injury. The motor tracts are monitored by recording and analyzing muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs). A mTc-MEP amplitude decrease of 50-80% is the most common warning criterion for possible neurological injury. However, these warning criteria often result in false positive warnings. False positives may be caused by inadequate depth of anesthesia and blood pressure on mTc-MEP amplitudes. The aim of this paper is to validate the study protocol in which the goal is to investigate the effects of depth of anesthesia (part 1) and blood pressure (part 2) on mTc-MEPs. Per part, 25 patients will be included. In order to investigate the effects of depth of anesthesia, a processed electroencephalogram (pEEG) monitor will be used. At pEEG values of 30, 40 and 50, mTc-MEP measurements will be performed. To examine the effect of blood pressure on mTc-MEPs the mean arterial pressure will be elevated from 60 to 100 mmHg during which mTc-MEP measurements will be performed. We hypothesize that by understanding the effects of depth of anesthesia and blood pressure on mTc-MEPs, the mTc-MEP monitoring can be interpreted more reliably. This may contribute to fewer false positive warnings. By performing this study after induction and prior to incision, this protocol provides a unique opportunity to study the effects of depths of anesthesia and blood pressure on mTc-MEPs alone with as little confounders as possible. Trial registration number NL7772

Groundwater geochemistry, hydrogeology and potash mineral potential of the Lake Woods region, Northern Territory, Australia

We collected 38 groundwater and two surface-water samples in the semi-arid Lake Woods region of the Northern Territory to better understand the hydrogeochemistry of this system, which straddles the Wiso, Tennant Creek and Georgina geological regions. Lake Woods is presently a losing waterbody feeding the underlying groundwater system. The main aquifers comprise mainly carbonate (limestone and dolostone), siliciclastic (sandstone and siltstone) and evaporitic units. The water composition was determined in terms of bulk properties (pH, electrical conductivity, temperature, dissolved oxygen, redox potential), 40 major, minor and trace elements, and six isotopes (δ18Owater, δ2Hwater, δ13CDIC, δ34SSO42–, δ18OSO42–, 87Sr/86Sr). The groundwater is recharged through infiltration in the catchment from monsoonal rainfall (annual average rainfall ∼600 mm) and runoff. It evolves geochemically mainly through evapotranspiration and water–mineral interaction (dissolution of carbonates, silicates and to a lesser extent sulfates). The two surface waters (one from the main creek feeding the lake, the other from the lake itself) are extraordinarily enriched in 18O and 2H isotopes (δ18O of +10.9 and +16.4‰ VSMOW, and δ2H of +41 and +93‰ VSMOW, respectively), which is interpreted to reflect evaporation during the dry season (annual average evaporation ∼3000 mm) under low humidity conditions (annual average relative humidity ∼40%). This interpretation is supported by modelling results. The potassium (K) relative enrichment (K/Cl– mass ratio over 50 times that of sea water) is similar to that observed in salt-lake systems worldwide that are prospective for potash resources. Potassium enrichment is believed to derive partly from dust during atmospheric transport/deposition, but mostly from weathering of K-silicates in the aquifer materials (and possibly underlying formations). Further studies of Australian salt-lake systems are required to reach evidence-based conclusions on their mineral potential for potash, lithium, boron and other low-temperature mineral system commodities such as uranium.This project was undertaken as part of the salt-lake mineral prospectivity project at Geoscience Australia during 2012–2013, which was supported by appropriation funding from the Commonwealth of Australi

Trends in community response and long term outcomes from paediatric cardiac arrest:A retrospective observational study

AIM: This study aimed to investigate trends over time in pre-hospital factors for pediatric out-of-hospital cardiac arrest (pOHCA) and long-term neurological and neuropsychological outcomes. These have not been described before in large populations.METHODS: Non-traumatic arrest patients, 1 day-17 years old, presented to the Sophia Children's Hospital from January 2002 to December 2020, were eligible for inclusion. Favorable neurological outcome was defined as Pediatric Cerebral Performance Categories (PCPC) 1-2 or no difference with pre-arrest baseline. The trend over time was tested with multivariable logistic and linear regression models with year of event as independent variable.FINDINGS: Over a nineteen-year study period, the annual rate of long-term favorable neurological outcome, assessed at a median 2·5 years follow-up, increased significantly (OR 1·10, 95%-CI 1·03-1·19), adjusted for confounders. Concurrently, annual automated external defibrillator (AED) use and, among adolescents, initial shockable rhythm increased significantly (OR 1·21, 95% CI 1·10-1·33 and OR 1·15, 95% CI 1·02-1·29, respectively), adjusted for confounders. For generalizability purposes, only the total intelligence quotient (IQ) was considered for trend analysis of all tested domains. Total IQ scores and bystander basic life support (BLS) rate did not change significantly over time.INTERPRETATION: Long-term favorable neurological outcome, assessed at a median 2·5 years follow-up, improved significantly over the study period. Total IQ scores did not significantly change over time. Furthermore, AED use (OR 1·21, 95%CI 1.10-1·33) and shockable rhythms among adolescents (OR1·15, 95%CI 1·02-1·29) increased over time.</p

Evaluation of Ac-Lys(0)(IRDye800CW)Tyr(3)-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma

PURPOSE: Meningioma recurrence rates can be reduced by optimizing surgical resection with the use of intraoperative molecular fluorescence guided surgery (MFGS). We evaluated the potential of the fluorescent tracer 800CW-TATE for MFGS using in vitro and in vivo models. It targets somatostatin receptor subtype 2 (SSTR(2)), which is overexpressed in all meningiomas. METHODS: Binding affinity of 800CW-TATE was evaluated using [(177)Lu] Lu-DOTA-Tyr(3)-octreotate displacement assays. Tumor uptake was determined by injecting 800CW-TATE in (SSTR(2)-positive) NCI-H69 or (SSTR(2)-negative) CH-157MN xenograft bearing mice and FMT2500 imaging. SSTR(2)-specific binding was measured by comparing tumor uptake in NCI-H69 and CH-157MN xenografts, blocking experiments and non-targeted IRDye800CW-carboxylate binding. Tracer distribution was analyzed ex vivo, and the tumor-to-background ratio (TBR) was calculated. SSTR(2) expression was determined by immunohistochemistry (IHC). Lastly, 800CW-TATE was incubated on frozen and fresh meningioma specimens and analyzed by microscopy. RESULTS: 800CW-TATE binding affinity assays showed an IC(50) value of 72 nM. NCI-H69 xenografted mice showed a TBR of 21.1. 800CW-TATE detection was reduced after co-administration of non-fluorescent DOTA-Tyr(3)-octreotate or administration of IRDye800CW. CH-157MN had no tumor specific tracer staining due to absence of SSTR(2) expression, thereby serving as a negative control. The tracer bound specifically to SSTR(2)-positive meningioma tissues representing all WHO grades. CONCLUSION: 800CW-TATE demonstrated sufficient binding affinity, specific SSTR(2)-mediated tumor uptake, a favorable biodistribution, and high TBR. These features make this tracer very promising for use in MFGS and could potentially aid in safer and a more complete meningioma resection, especially in high-grade meningiomas or those at complex anatomical localizations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-021-03739-1

Necrosis binding of Ac-Lys(0)(IRDye800CW)-Tyr(3)-octreotate:a consequence from cyanine-labeling of small molecules

BACKGROUND: There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery. RESULTS: Binding of 800CW-TATE could be blocked with DOTA0-Tyr3-octreotate (DOTA-TATE) on cultured SSTR2-positive U2OS cells and was absent in SSTR2 negative U2OS cells. However, strong binding was observed to dead cells, which could not be blocked with DOTA-TATE and was also present in dead SSTR2 negative cells. No SSTR2-mediated binding was observed in frozen tumor sections, possibly due to disruption of the cells in the process of sectioning the tissue before exposure to the contrast agent. DOTA-TATE blocking resulted in an incomplete reduction of 61.5 ± 5.8% fluorescence uptake by NCI-H69-tumors in mice. Near-infrared imaging and dead cell staining on paraffin sections from resected tumors revealed that fluorescence uptake persisted in necrotic regions upon blocking with DOTA-TATE. CONCLUSION: This study shows that labeling peptides with cyanines can result in dead cell binding. This does not hamper the ultimate purpose of fluorescence-guided surgery, as necrotic tissue appears in most solid tumors. Hence, the necrosis binding can increase the overall tumor uptake. Moreover, necrotic tissue should be removed as much as possible: it cannot be salvaged, causes inflammation, and is tumorigenic. However, when performing binding experiments to cells with disrupted membrane integrity, which is routinely done with nuclear probes, this dead cell-binding can resemble non-specific binding. This study will benefit the development of fluorescent contrast agents