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ObjectiveBuilding on our previous study, showing a correlation between ferritin in serum and urine, we conducted a feasibility evaluation, measuring urinary ferritin as a potential noninvasive screening test for iron deficiency among NICU patients.Study designThis was a prospective analysis of paired serum/urine ferritin levels. We defined iron-limited erythropoiesis by a RET-He <5th percentile lower reference interval (<28 pg).ResultsWe obtained 49 paired serum/urine samples from neonates judged as at-risk for iron deficiency. Urine ferritin (“corrected” for urine creatinine and specific gravity) correlated with serum ferritin (correlation coefficient of log10-transformed values 0.44). A corrected urine ferritin <12 ng/mL had a sensitivity of 82% (95% CI, 67–93%) and a specificity of 100% (CI, 66–100%) for detecting iron-limited erythropoiesis, with a positive predictive value of 100% (CI, 89–100%).ConclusionsMeasuring urinary ferritin in NICU patients is feasible. Since low values identify iron-limitation, this could become a useful noninvasive screen.

The combination of LiDAR and optical remotely sensed data provides unique information about ecosystem structure and function. Here, we describe the development, validation and application of a new airborne system that integrates commercial off the shelf LiDAR hyperspectral and thermal components in a compact, lightweight and portable system. Goddard’s LiDAR, Hyperspectral and Thermal (G-LiHT) airborne imager is a unique system that permits simultaneous measurements of vegetation structure, foliar spectra and surface temperatures at very high spatial resolution (~1 m) on a wide range of airborne platforms. The complementary nature of LiDAR, optical and thermal data provide an analytical framework for the development of new algorithms to map plant species composition, plant functional types, biodiversity, biomass and carbon stocks, and plant growth. In addition, G-LiHT data enhance our ability to validate data from existing satellite missions and support NASA Earth Science research. G-LiHT’s data processing and distribution system is designed to give scientists open access to both low- and high-level data products (http://gliht.gsfc.nasa.gov), which will stimulate the community development of synergistic data fusion algorithms. G-LiHT has been used to collect more than 6,500 km2 of data for NASA-sponsored studies across a broad range of ecoregions in the USA and Mexico. In this paper, we document G-LiHT design considerations, physical specifications, instrument performance and calibration and acquisition parameters. In addition, we describe the data processing system and higher-level data products that are freely distributed under NASA’s Data and Information policy.

The utilization of remotely sensed observations for light use efficiency (LUE) and tower-based gross primary production (GPP) estimates was studied in a USDA cornfield. Nadir hyperspectral reflectance measurements were acquired at canopy level during a collaborative field campaign conducted in four growing seasons. The Photochemical Reflectance Index (PRI) and solar induced chlorophyll fluorescence (SIF), were derived. SIF retrievals were accomplished in the two telluric atmospheric oxygen absorption features centered at 688 nm (O2-B) and 760 nm (O2-A). The PRI and SIF were examined in conjunction with GPP and LUE determined by flux tower-based measurements. All of these fluxes, environmental variables, and the PRI and SIF exhibited diurnal as well as day-to-day dynamics across the four growing seasons. Consistent with previous studies, the PRI was shown to be related to LUE (r^2 = 0.54 with a logarithm fit), but the relationship varied each year. By combining the PRI and SIF in a linear regression model, stronger performances for GPP estimation were obtained. The strongest relationship (r^2 = 0.80, RMSE = 0.186 mg CO2/m^2/s) was achieved when using the PRI and SIF retrievals at 688 nm. Cross-validation approaches were utilized to demonstrate the robustness and consistency of the performance. This study highlights a GPP retrieval method based entirely on hyperspectral remote sensing observations.

Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat INS-1 β-cell and murine islet toxicity. These globally flexible, low order oligomers upregulate pro-inflammatory markers and induce reactive oxygen species. They do not bind 1-anilnonaphthalene-8-sulphonic acid and lack extensive β-sheet structure. Aromatic interactions modulate, but are not required for toxicity. Not all IAPP oligomers are toxic; toxicity depends on their partially structured conformational states. Some anti-amyloid agents paradoxically prolong cytotoxicity by prolonging the lifetime of the toxic species. The data highlight the distinguishing properties of toxic IAPP oligomers and the common features that they share with toxic species reported for other amyloidogenic polypeptides, providing information for rational drug design to treat IAPP induced β-cell death.

Background In the context of expanding digital health tools, the health system is ready for Learning Health System (LHS) models. These models, with proper governance and stakeholder engagement, enable the integration of digital infrastructure to provide feedback to all relevant parties including clinicians and consumers on performance against best practice standards, as well as fostering innovation and aligning healthcare with patient needs. The LHS literature primarily includes opinion or consensus-based frameworks and lacks validation or evidence of benefit. Our aim was to outline a rigorously codesigned, evidence-based LHS framework and present a national case study of an LHS-aligned national stroke program that has delivered clinical benefit. Main text Current core components of a LHS involve capturing evidence from communities and stakeholders (quadrant 1), integrating evidence from research findings (quadrant 2), leveraging evidence from data and practice (quadrant 3), and generating evidence from implementation (quadrant 4) for iterative system-level improvement. The Australian Stroke program was selected as the case study as it provides an exemplar of how an iterative LHS works in practice at a national level encompassing and integrating evidence from all four LHS quadrants. Using this case study, we demonstrate how to apply evidence-based processes to healthcare improvement and embed real-world research for optimising healthcare improvement. We emphasize the transition from research as an endpoint, to research as an enabler and a solution for impact in healthcare improvement. Conclusions The Australian Stroke program has nationally improved stroke care since 2007, showcasing the value of integrated LHS-aligned approaches for tangible impact on outcomes. This LHS case study is a practical example for other health conditions and settings to follow suit.

Psychological distress (PD) (mental ill-health) has a frequency between 5 and 25% in urban populations, and there is mounting evidence that access to green space might reduce its occurrence. Evidence suggests that the quality of green space is as important as accessibility in promoting mental well-being. A pilot study for EURO-URHIS 2 allowed investigation of access to green space in relation to PD in a deprived urban population in the UK. An adult urban health indicator questionnaire, including the GHQ-12 and validated questions on access to and quality of green space, was sent to a stratified random sample of 1680 adults drawn from one general practice list in Sandwell, UK. Multivariable logistic regression was used to determine associations between attributes of green space and PD adjusting for age, sex and levels of deprivation. There were 578 (35%) completed responses. The reported prevalence of PD [n = 131 (22.7%)] was significantly greater than national England and Wales estimates. As well as accessibility (OR = 0.58; 95% CI = 0.35, 0.96) and sufficiency (OR = 0.12; 95% CI = 0.39, 0.89) of green spaces, having the ability to use them for relaxation and recreation were significantly associated with reduced PD [OR = 0.13 (0.42, 0.94) and OR = 0.11 (0.34, 0.80), respectively]. In addition, a dose-response relationship between number of positive green space attributes and PD was identified (P < 0.05). This population-based study in a deprived urban UK population demonstrates an association, and some dose-response relationship, between access to and quality of green spaces with reduced PD. The cross-sectional design and use of subjective measures limit interpretation of causality. More knowledge is needed on how UK planning affects green spaces and the potential mental health consequences.

Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy. COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681. We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]). Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials. UK Medical Research Council, Merck KGaA.

Penetration testing remains one of the best ways to test the security of private, government, military and corporate computer networks. This book provides step-by-step instruction on how to use tools, available mostly for free, to perform effective penetration tests of today's computer networks. Covering basic and advanced tools and procedures, it categorizes tools according to their use within the standard testing framework. Readers will learn how to perform an organized and efficient penetration test as well as techniques used to bypass anti-virus software and capture keystrokes of remote systems.

The first European Space Agency (ESA) and NASA collaboration in an airborne campaign to support ESA's FLuorescence EXplorer (FLEX) mission was conducted in North Carolina, USA during September-October 2013 (FLEX-US 2013) at the Parker Tract Loblolly Pine (LP) Plantation (Plymouth, NC, USA). This campaign combined two unique airborne instrument packages to obtain simultaneous observations of solar-induced fluorescence (SIF), LiDAR-based canopy structural information, visible through shortwave infrared (VSWIR) reflectance spectra, and surface temperature, to advance vegetation studies of carbon cycle dynamics and ecosystem health. We obtained statistically significant results for fluorescence, canopy temperature, and tower fluxes from data collected at four times of day over two consecutive autumn days across an age class chronosequence. Both the red fluorescence (F685) and far-red fluorescence (F740) radiances had highest values at mid-day, but their fluorescence yields exhibited different diurnal responses across LP age classes. The diurnal trends for F685 varied with forest canopy temperature difference (canopy minus air), having a stronger daily amplitude change for young vs. old canopies. The Photochemical Reflectance Index (PRI) was positively correlated with this temperature variable over the diurnal cycle. Tower measurements from mature loblolly stand showed the red/far-red fluorescence ratio was linearly related to canopy light use efficiency (LUE) over the diurnal cycle, but performed even better for the combined morning/afternoon (without midday) observations. This study demonstrates the importance of diurnal observations for interpretation of fluorescence dynamics, the need for red fluorescence to understand canopy physiological processes, and the benefits of combining fluorescence, reflectance, and structure information to clarify canopy function versus structure characteristics for a coniferous forest.

Collection of 3D data in archaeology is a long-standing practice. Traditionally, the focus of these data has been visualization as opposed to analysis. Three-dimensional data are often recorded during archaeological excavations, with the provenience of deposits, features, and artefacts documented by a variety of methods. Simple analysis of 3D data includes calculating the volumes of bound entities, such as deposits and features, and determining the spatial relationships of artifacts within these. The construction of these volumes presents challenges that originate in computer-aided design (CAD) but have implications for how data are used in archaeological analysis. We evaluate 3D construction processes using data from Waitetoke, Ahuahu Great Mercury Island, Aotearoa, New Zealand. Point clouds created with data collected by total station, photogrammetry, and terrestrial LiDAR using simultaneous localization and mapping (SLAM) are compared, as well as different methods for generating surface area and volumes with triangulated meshes and convex hulls. The differences between methods are evaluated and assessed in relation to analyzing artifact densities within deposits. While each method of 3D data acquisition and modeling has advantages in terms of accuracy and precision, other factors such as data collection and processing times must be considered when deciding on the most suitable.