Pre-Flight Calibration of the Mars 2020 Rover Mastcam Zoom (Mastcam-Z) Multispectral, Stereoscopic Imager.

The NASA Perseverance rover Mast Camera Zoom (Mastcam-Z) system is a pair of zoomable, focusable, multi-spectral, and color charge-coupled device (CCD) cameras mounted on top of a 1.7 m Remote Sensing Mast, along with associated electronics and two calibration targets. The cameras contain identical optical assemblies that can range in focal length from 26 mm ( 25.5 ∘ × 19.1 ∘ FOV ) to 110 mm ( 6.2 ∘ × 4.2 ∘ FOV ) and will acquire data at pixel scales of 148-540 µm at a range of 2 m and 7.4-27 cm at 1 km. The cameras are mounted on the rover's mast with a stereo baseline of 24.3 ± 0.1  cm and a toe-in angle of 1.17 ± 0.03 ∘ (per camera). Each camera uses a Kodak KAI-2020 CCD with 1600 × 1200 active pixels and an 8 position filter wheel that contains an IR-cutoff filter for color imaging through the detectors' Bayer-pattern filters, a neutral density (ND) solar filter for imaging the sun, and 6 narrow-band geology filters (16 total filters). An associated Digital Electronics Assembly provides command data interfaces to the rover, 11-to-8 bit companding, and JPEG compression capabilities. Herein, we describe pre-flight calibration of the Mastcam-Z instrument and characterize its radiometric and geometric behavior. Between April 26 t h and May 9 t h , 2019, ∼45,000 images were acquired during stand-alone calibration at Malin Space Science Systems (MSSS) in San Diego, CA. Additional data were acquired during Assembly Test and Launch Operations (ATLO) at the Jet Propulsion Laboratory and Kennedy Space Center. Results of the radiometric calibration validate a 5% absolute radiometric accuracy when using camera state parameters investigated during testing. When observing using camera state parameters not interrogated during calibration (e.g., non-canonical zoom positions), we conservatively estimate the absolute uncertainty to be < 10 % . Image quality, measured via the amplitude of the Modulation Transfer Function (MTF) at Nyquist sampling (0.35 line pairs per pixel), shows MTF Nyquist = 0.26 - 0.50 across all zoom, focus, and filter positions, exceeding the > 0.2 design requirement. We discuss lessons learned from calibration and suggest tactical strategies that will optimize the quality of science data acquired during operation at Mars. While most results matched expectations, some surprises were discovered, such as a strong wavelength and temperature dependence on the radiometric coefficients and a scene-dependent dynamic component to the zero-exposure bias frames. Calibration results and derived accuracies were validated using a Geoboard target consisting of well-characterized geologic samples. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-021-00795-x.

A comparison of Landsat 8, RapidEye and Pleiades products for improving empirical predictions of satellite-derived bathymetry.

Satellite derived bathymetry (SDB) enables rapid mapping of large coastal areas through measurement of optical penetration of the water column. The resolution of bathymetric mapping and achievable horizontal and vertical accuracies vary but generally, all SDB outputs are constrained by sensor type, water quality and other environmental conditions. Efforts to improve accuracy include physics-based methods (similar to radiative transfer models e.g. for atmospheric/vegetation studies) or detailed in-situ sampling of the seabed and water column, but the spatial component of SDB measurements is often under-utilised in SDB workflows despite promising results suggesting potential to improve accuracy significantly. In this study, a selection of satellite datasets (Landsat 8, RapidEye and Pleiades) at different spatial and spectral resolutions were tested using a log ratio transform to derive bathymetry in an Atlantic coastal embayment. A series of non-spatial and spatial linear analyses were then conducted and their influence on SDB prediction accuracy was assessed in addition to the significance of each model's parameters. Landsat 8 (30 m pixel size) performed relatively weak with the non-spatial model, but showed the best results with the spatial model. However, the highest spatial resolution imagery used - Pleiades (2 m pixel size) showed good results across both non-spatial and spatial models which suggests a suitability for SDB prediction at a higher spatial resolution than the others. In all cases, the spatial models were able to constrain the prediction differences at increased water depths.

Bioimpedance spectroscopy measurements of phase angle and height for age are predictive of outcome in children following surgery for congenital heart disease.

OBJECTIVE: Children with congenital heart disease (CHD) are often growth restricted (low weight- and/or height-for-age) which may increase risk of poor post operative resilience. Bioelectrical impedance spectroscopy (BIS) has been used to determine body composition in different clinical settings and has been shown to mark differences in nutritional state and clinical outcome. In disease conditions were fluid is not normally distributed it is proposed that raw impedance values and BIS derived phase-angle may serve as prognostic indicators of clinical outcome. We sought to describe the relationship between nutritional status, phase-angle and post-operative outcomes in children with congenital heart disease. DESIGN: Single centre prospective cohort study. SETTING: Paediatric Intensive Care Unit (PICU), Southampton Children's Hospital. PATIENTS: 122 children with CHD following cardiac surgery (March 2015-April 2016). Outcome variables included growth, mechanical-ventilation, PICU length of stay (PICU-LOS) and phase-angle at 50 Hz. MEASUREMENTS AND MAIN RESULTS: BIS measurements were taken before and on the day of surgery (day 0), day 2 post-operatively and on discharge from hospital. Pre-operative moderate malnutrition defined as height-for-age-z-score (HAZ) ≤-2 was observed in 28.5% of infants and 20.6% of children. Regression analysis was used to investigate the relationship between phase-angle, HAZ and clinical outcomes. Moderate-malnutrition (HAZ ≤-2) was associated with an increased PICU-LOS (odds ratios (OR) with 95% confidence interval: 1.8; 1.1-2.7, p = 0.008) whilst a low phase-angle (≤2.7° on day 2 was associated with longer PICU-LOS (OR 7.8; 2.7-22.45, p < 0.001)); When the model was adjusted for age, known risk factors and length of surgery, HAZ ≤-2 and phase-angle ≤2.7° on day 2 were associated with longer PICU-LOS (p = 0.001 and p = 0.04 respectively) and together explained 81.7% of the variability in PICU-LOS. CONCLUSIONS: Moderate malnutrition (HAZ ≤-2) in infants and children undergoing cardiac surgery is associated with longer PICU-LOS. Post-operative measures of BIS phase angle may further improve our ability to identifying hose children with an increased risk of prolonged PICU-LOS compared to using pre-operative anthropometry alone.

Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making.

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

Clinical and molecular characteristics of 1qter microdeletion syndrome: delineating a critical region for corpus callosum agenesis/hypogenesis.

BACKGROUND: Patients with a microscopically visible deletion of the distal part of the long arm of chromosome 1 have a recognisable phenotype, including mental retardation, microcephaly, growth retardation, a distinct facial appearance and various midline defects including corpus callosum abnormalities, cardiac, gastro-oesophageal and urogenital defects, as well as various central nervous system anomalies. Patients with a submicroscopic, subtelomeric 1qter deletion have a similar phenotype, suggesting that the main phenotype of these patients is caused by haploinsufficiency of genes in this region. OBJECTIVE: To describe the clinical presentation of 13 new patients with a submicroscopic deletion of 1q43q44, of which nine were interstitial, and to report on the molecular characterisation of the deletion size. RESULTS AND CONCLUSIONS: The clinical presentation of these patients has clear similarities with previously reported cases with a terminal 1q deletion. Corpus callosum abnormalities were present in 10 of our patients. The AKT3 gene has been reported as an important candidate gene causing this abnormality. However, through detailed molecular analysis of the deletion sizes in our patient cohort, we were able to delineate the critical region for corpus callosum abnormalities to a 360 kb genomic segment which contains four possible candidate genes, but excluding the AKT3 gene.

Activated signal transducer and activator of transcription-3 (STAT3) is a poor regulator of tumour necrosis factor-alpha production by human monocytes.

Signal transducer and activator of transcription-3 (STAT3) activation has been associated with suppressed inflammatory processes in experimental animals, murine myeloid cells and macrophage cell lines. Manipulation of STAT3 activity may therefore be a focus for pharmacological intervention of inflammatory diseases in humans. However, the ability of STAT3 to reduce the production of inflammatory mediators by activated human monocytes and macrophages has been characterized inadequately. To establish this, we used a recently optimized adenoviral approach to study the effect of overexpressed STAT3 or a transcriptionally inactive mutant STAT3 in lipopolysaccharide (LPS)-stimulated human monocytes. STAT3 activated by LPS did not directly regulate inhibitor of kappa B alpha (IkappaBalpha) activation or tumour necrosis factor (TNF)-alpha production, a process dependent on the transcriptional activity of nuclear factor kappa B (NFkappaB), although the transcriptional activity of STAT3 contributed to the mechanism by which interleukin (IL)-10 suppressed LPS-induced TNF-alpha levels. This contrasted with the efficient block in IL-10 induction of suppressor of cytokine signalling-3 (SOCS3) in monocytes infected with an adenovirus expressing mutant STAT3. These results indicate that STAT3 activation cannot directly regulate LPS-signalling in human monocytes and represents only part of the mechanism by which IL-10 suppresses TNF-alpha production by activated human monocytes. This study concludes that pharmacological manipulation of STAT3 transcriptional activity alone would be insufficient to control NFkappaB-associated inflammation in humans.

High speed optically sectioned fluorescence lifetime imaging permits study of live cell signaling events.

We present a time domain optically sectioned fluorescence lifetime imaging (FLIM) microscope developed for high-speed live cell imaging. This single photon excited system combines wide field parallel pixel detection with confocal sectioning utilizing spinning Nipkow disc microscopy. It can acquire fluorescence lifetime images of live cells at up to 10 frames per second (fps), permitting high-speed FLIM of cell dynamics and protein interactions with potential for high throughput cell imaging and screening applications. We demonstrate the application of this FLIM microscope to real-time monitoring of changes in lipid order in cell membranes following cholesterol depletion using cyclodextrin and to the activation of the small GTP-ase Ras in live cells using FRET.

Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients.

MECP2 mutations are identifiable in approximately 80% of classic Rett syndrome (RTT), but less frequently in atypical RTT. We recruited 110 patients who fulfilled the diagnostic criteria for Rett syndrome and were referred to Cardiff for molecular analysis, but in whom an MECP2 mutation was not identifiable. Dosage analysis of MECP2 was carried out using multiplex ligation dependent probe amplification or quantitative fluorescent PCR. Large deletions were identified in 37.8% (14/37) of classic and 7.5% (4/53) of atypical RTT patients. Most large deletions contained a breakpoint in the deletion prone region of exon 4. The clinical phenotype was ascertained in all 18 of the deleted cases and in four further cases with large deletions identified in Goettingen. Five patients with large deletions had additional congenital anomalies, which was significantly more than in RTT patients with other MECP2 mutations (2/193; p<0.0001). Quantitative analysis should be included in molecular diagnostic strategies in both classic and atypical RTT.

Pulmonary vein stenosis: initial experience with cutting balloon angioplasty.

OBJECTIVE: To determine the safety and effectiveness of cutting balloon angioplasty for pulmonary vein stenosis (PVS). DESIGN AND SETTING: Retrospective review of case notes and cardiac catheterisation data at the Royal Brompton Hospital. MAIN OUTCOME MEASURES: Diameter of pulmonary vein, tricuspid regurgitant jet velocity on echocardiogram, and percutaneous oxygen saturation before and after cutting balloon angioplasty. RESULTS: Three patients had congenital PVS and three had PVS associated with total anomalous pulmonary venous drainage. A total of 27 PVSs were treated during 12 catheterisation procedures. Median patient age at the time of procedure was 12.5 months (range 1.5-36 months) and weight was 7.1 kg (range 2.8-11.1 kg). Minimum pulmonary vein diameter increased significantly on angiography after cutting balloon angioplasty, from mean (SD) 2.3 (0.7) mm to 4.2 (1.9) mm, mean of differences 1.9 mm (95% confidence interval (CI) 0.9 to 2.9 mm, p = 0.0013). Mean (SD) oxygen saturation rose from 79.6 (12.9)% to 83.9 (9.0)%, mean of differences 4.3% (95% CI 0.7% to 8.0%, p = 0.0238). All children's symptoms improved subjectively. Tricuspid regurgitant jet velocity did not change significantly. The longest time interval before repeat intervention was six months. There were no acute deaths; one patient had a small pulmonary haemorrhage and developed a small aneurysm adjacent to the site of angioplasty. CONCLUSION: Cutting balloon angioplasty is safe in the palliation of PVS in children. It gives some acute relief but often needs to be repeated, as improvement is rarely sustained.

The MTT assays of bovine retinal pericytes and human microvascular endothelial cells on DLC and Si-DLC-coated TCPS.

MTT (Tetrazolium)-assay suggests that diamond-like carbon (DLC) and silicon-doped DLC (Si-DLC) films obtained under appropriate deposition parameters are not toxic to bovine retinal pericytes, and human microvascular endothelial cells (HMEC). The observed frequency distributions of the optical density (OD) values indicative of cell viability are near Gaussian-normal distribution. One-way ANOVA indicates that at 0.05 levels the population means are not significantly different for the coated and control samples. The observed OD values depend on the cell line (cell growth/metabolic rate), possibly cell cycle stage, the deposition parameters-bias voltage, ion energy, pressure, argon precleaning, and the dopant. For colored thin films like DLC with room temperature photoconductivity and photoelectric effects, it is important to account for the OD contribution from the coating itself. MTT assay, not surprisingly, seems not to be highly sensitive to interfacial cellular interaction resulting from the change in the film's nanostructure, because the tetrazolium metabolism is mainly intracellular and not interfacial. The thin films were synthesized by 13.56 MHz RF-PECVD using argon and acetylene as source gases, with tetramethylsilane (TMS) vapor introduced for silicon doping. This study could be relevant to biomedical application of the films in the eye, peri-vascular, vascular compartments, and for cell-tissue engineering.

A review of cochlear implantation in mitochondrial sensorineural hearing loss.

OBJECTIVE: Mitochondrial sensorineural hearing loss (SNHL) may be nonsyndromic (occurring in isolation), associated with the A1555G mutation in the MTRNR1 gene. Mitochondrial SNHL may also be syndromic, associated with the A3243G point mutation in the MTTL1 gene. In syndromic cases-mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS), maternally inherited diabetes and deafness, Kearns-Sayre syndrome, and chronic progressive external ophthalmoplegia-the SNHL compounds already existing disabilities. The genetic basis for mitochondrial SNHL and postulated sites of pathologic changes are discussed. DATA SOURCES: Sources used were relevant clinical and basic science publications. STUDY SELECTION: A search of the entire databases of Medline and Web of Science, using various subject headings and free-text terms, was used to identify patients with mitochondrial disease having cochlear implants. DATA EXTRACTION: The data from publications were critically reviewed and tabulated to assess implantation outcomes. DATA SYNTHESIS: The data were not amenable to formal meta-analysis or valid data summarization, other than descriptive statistics. CONCLUSIONS: There is an increasing awareness of the prevalence of mitochondrial SNHL and its progressive nature. High-risk candidates warrant genetic testing and family screening. Correlating the data for mitochondrial SNHL as a treatable entity is important, and the authors present an overview of these patients successfully rehabilitated by cochlear implantation.

Follow up of fetal outcome in cases of maternal phenylketonuria in Northern Ireland.

BACKGROUND: Maternal phenylketonuria (PKU) can result in multiple congenital anomalies. In Northern Ireland, the prevalence of PKU is relatively high at 1 in 4000. OBJECTIVE: To assess the outcome of 39 pregnancies in 20 mothers. RESULTS: Dietary control was established before conception in 17 pregnancies (44%). Five mothers with hyperphenylalaninaemia had 11 pregnancies. There were no congenital anomalies in this group, and all appear to be developing normally. Fifteen women with classical PKU had 28 pregnancies. One pregnancy ended in a first trimester miscarriage. Twelve out of 27 (44%) completed pregnancies produced babies with a congenital anomaly and/or developmental delay. CONCLUSIONS: Most problems occurred when dietary control was not established until after the 2nd trimester. As the cohort of young women with treated PKU is growing steadily, maternal PKU is going to become an even greater cause for concern.

The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody.

BACKGROUND: Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis. METHODS: This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks. RESULTS: The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P =.002). A physician's global assessment of excellent (>75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P =.0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 +/- 7.5 (placebo) and 10.9 +/- 8.4 (0.3 mg/kg) (P <.0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P =.004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur. CONCLUSIONS: Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.

Transcatheter coil occlusion of the arterial duct; results of the European Registry.

AIMS: To report on the data, collected by the Association for European Paediatric Cardiology (AEPC) Registry, on transcatheter coil occlusion of the arterial duct. METHODS AND RESULTS: A retrospective study was conducted of intention-to-treat data from 30 European and Middle Eastern tertiary referral centres which included an analysis of causes of suboptimal outcome. Since 1994, reports have been made on 1291 attempted coil occlusions of the arterial duct in 1258 patients. Median age at procedure was 4 years (range 0.1-52) and median weight was 29 kg (range 1.8-100). Following coil implantation, the immediate occlusion rate was 59%, which rose to 95% at 1 year. A suboptimal outcome occurred on 129 occasions (10% of procedures) and was defined as coil embolization, an abandoned procedure, persistent haemolysis, residual leak requiring a further procedure, flow impairment in adjacent structures and duct re-canalization. A number of clinical factors were chosen but only increasing duct size [odds ratio of 2.6:1 (CI 2-3.2)] and the presence of a tubular shaped duct [odds ratio 2.4:1 (CI 1.4-4)] were positively associated with an unfavourable outcome. CONCLUSION: The results of the European Registry support the view that transcatheter coil occlusion of the persistent arterial duct is a safe and effective procedure. Unfavourable outcomes are more likely when closing larger and/or tubular shaped ducts.

Requirement for capsule in colonization by Streptococcus pneumoniae.

Nasopharyngeal colonization is a necessary first step in the pathogenesis of Streptococcus pneumoniae. Using isolates containing defined mutations in the S. pneumoniae capsule locus, we found that expression of the capsular polysaccharide is essential for colonization by the type 2 strain D39 and the type 3 strains A66 and WU2. Nonencapsulated derivatives of each of these strains were unable to colonize BALB/cByJ mice. Similarly, type 3 mutants that produced < 6% of the parental amounts of capsule could not colonize. Capsule production equivalent to that of the parent strain was not required for efficient colonization, however, as type 3 mutants producing approximately 20% of the parental amounts of capsule colonized as effectively as the parent. This 80% reduction in capsule level had only a minimal effect on intraperitoneal virulence but caused a significant reduction in virulence via the intravenous route. In the X-linked immunodeficient CBA/N mouse, the type 3 mutant producing ~20% of the parental amount of capsule (AM188) was diminished in its ability to cause invasive disease and death following intranasal inoculation. Following intravenous or intraperitoneal challenge, however, only extended survival times were observed. Our results demonstrate an additional role for capsule in the pathogenesis of S. pneumoniae and show that isolates producing reduced levels of capsule can remain highly virulent.