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Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Aims Treatment Escalation Plan (TEP) is essential for recognition of patients’ ceiling for care in the event of clinical deterioration. It should be clearly documented to ensure continuity of care, especially during Covid-19 pandemic. This audit aims to evaluate and improve the TEP filling rate for general surgical patients. Methods A prospective data collection was performed for one week in July 2020 in general surgical wards. Data on patients’ gender, age, presence of DNACPR form and date of TEP completion were collected from patients’ clinical notes. Data was analysed using SPSS statistic software. Educational posters were displayed in the ward and presentation was done to emphasise the importance of TEP documentation. Second audit cycle was done in August 2020 to assess for improvement in TEP filling rate. Results In the first cycle, 60 patients were included with a mean age of 60. Only 11.7% patients had TEP form filled in with a mean delay of 2.7 days since admission. In the second cycle, 57 patients were included with a mean age of 66. 28.1% patients had TEP form documented with a mean delay of 1.7 days. This has shown a 140% improvement in completion rate of TEP form and 59% reduction in the delay in TEP documentation. Conclusions TEP is essential to ensure that patients received optimal care when their condition deteriorate. Simple intervention such as educational posters will help to improve the TEP completion rate. However, continuous auditing is required to ensure improvement in TEP documentation for surgical patients.

This study aimed to examine association between perioperative uses of aspirin and long-term survival in patients undergoing CABG. A retrospective cohort study was performed in 9,584 consecutive patients receiving cardiac surgery from three tertiary hospitals. Of all the patients, 4,132 patients undergoing CABG met inclusion criteria and were divided into four groups: with or without preoperative or postoperative aspirin respectively. 30-day postoperative and long-term mortality were compared with the use of propensity scores and inverse probability weighting adjustment to reduce the treatment-selection bias. The patients taking preoperative aspirin presented significantly more with comorbidities. However, the results of this study showed that preoperative aspirin (vs. no preoperative aspirin) was associated with significantly reduced the risk of 30-day mortality in the patients undergoing CABG. Further, the results of long-term mortality showed that the patients taking preoperative aspirin and postoperative aspirin (vs. not taking) were associated with significantly reduced the risk of 4-year mortality (14.8% vs. 18.1%, RR: 0.82, 95% CI: 0.75–0.89, P = 0.005; 10.7% vs. 16.2%, RR: 0.66, 95% CI: 0.50–0.82, P = 0.003). In conclusion, this cohort study showed that perioperative (before and after surgery) use of aspirin was associated with significant reduction in 30-day mortality without significant bleeding complications, also improved long-term survival in patients undergoing CABG.

Because of the increased number of cameras employed in environmental sensing and the tremendous image output they produce, we have created a flexible, open-source software solution called EcoIP to help automatically determine different phenophases for different species from digital image sequences. Onset and ending dates are calculated through an iterative process: (1) training images are chosen and areas of interest identified, (2) separation of foreground and background is accomplished based on a naive Bayesian method, (3) a signal is created based on the separation model and (4) it is then fit to a sigmoid that contains the dates of interest. Results using different phenological events of different species indicate that estimated dates fall within a few days of the observed dates for most cases. Our experiments indicate that color separability and scene illumination are contributing factors to this error. EcoIP is implemented as an open platform that encourages anyone to execute, copy, distribute, study, change, and/or improve the application.

Within alpine environments the interactions of air temperature, solar irradiance, wind, surface albedo, microtopography, and biotic traits all influence patterns of soil and plant canopy temperatures. The resulting mosaic of surface temperatures has a profound impact on ecosystem processes, plant survival, and ecophysiological performance. Previous studies have documented large and persistent variations in microhabitat temperatures over mesoscale alpine terrains. We have used a novel mobile system to examine changes in soil and plant canopy surface temperatures at spatial scales of centimeters and temporal scales of minutes in an alpine fellfield habitat in the White Mountains of California. In the middle of a summer day, the mean surface temperature differences between points 2, 5, and 10 cm apart were 2.9, 5.4, and 9.0 °C, respectively, and extreme differences of 18 °C or more were found over distances of a few centimeters. These thermal patterns are due not only to substrate material but also ...

Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p

This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate (approved in the USA, August 2009) for adult patients with acutely exacerbated schizophrenia. The patients (N = 652) were randomly assigned (1:1:1:1) to paliperidone palmitate at 25, 100, or 150 mg eq. or placebo in this 13-week double-blind study. The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or gluteal [corrected] on day 8 and then once monthly (days 36 and 64). No oral supplementation was used. Target plasma levels were achieved by day 8 in all paliperidone palmitate groups. The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly (P or =2% of patients in any of the treatment groups) that occurred more frequently in the total paliperidone palmitate group versus the placebo group (with > or =1% difference) were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%). The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range (25, 100, or 150 mg eq.) in adult patients with acutely exacerbated schizophrenia.

Vieta E, Nuamah IF, Lim P, Yuen EC, Palumbo JM, Hough DW, Berwaerts J. A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 2010: 12: 230–243. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: To evaluate the antimanic efficacy and safety of paliperidone extended-release (ER) tablets in patients with bipolar I disorder. Methods: This study included a 3-week, double-blind, acute treatment phase (paliperidone ER versus placebo, with quetiapine as control), and a 9-week, double-blind, maintenance phase (paliperidone ER versus quetiapine). Patients [n = 493; Young Mania Rating Scale (YMRS) score ≥ 20] were randomized (2:2:1) to flexibly dosed paliperidone ER (3–12 mg/day), quetiapine (400–800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy. Results: Paliperidone ER was superior to placebo at the 3-week endpoint {primary outcome; least-squares mean difference in change from baseline in YMRS scores [95% confidence interval (CI)]: −5.5 (−7.57; −3.35); p

The characterization of the solar radiation environment under a forest canopy is important for both understanding temperature-dependent biological processes and validating energy balance models. A modified sinusoidal model of soil heat conductivity was used to estimate subsurface temperature and heat flux from the uneven but periodic solar heating of the soil surface due to sun flecks from a forest canopy. Using a mobile sensor platform with an infrared thermometer along an 11 m transect, a sunfleck model of soil surface temperature was tested using soil surface temperature maxima, air temperatures, and photodiodes placed on the soil surface to measure sunflecks. A pan-tilt-zoom digital camera on a 10 m tower above the site was then used to capture a time series of panoramic images of sunflecks reflected from the soil surface and to scale the sunfleck temperature model to a wide area. Finally, this image-based model of surface temperatures was combined with the modified sinusoidal model for heat conduction to estimate soil subsurface temperatures and heat flux over a wide area due to sunflecks from a forest canopy.

Neuropsychologic data are presented from a randomized, double-blind, placebo-controlled, multicenter study with placebo, topiramate 50 mg/day, and topiramate 100 mg/day. The Cambridge Neuropsychological Test Automated Battery (CANTAB) and cognitive adverse events were used to evaluate neurocognitive effects of topiramate. Topiramate 100 mg/day vs placebo was associated with slight statistically significant score increases, indicating slowing, from baseline vs placebo in three CANTAB measures: five-choice reaction time ( P = 0.028), pattern recognition memory mean correct latency ( P = 0.027), and rapid visual information processing mean latency ( P = 0.040). No other patterns related to topiramate treatment were observed in measurements of learning, memory, and visual information processing, except for potential improvement with topiramate 100 mg/day vs placebo in spatial span total errors (accuracy test) ( P = 0.040). The most common cognitive and neuropsychiatric adverse events with a higher incidence in the topiramate 50 and 100 mg/day groups vs placebo were anorexia (9% and 11% vs 3%), insomnia (9% and 3% vs 3%), fatigue (6% and 9% vs 6%), and dizziness (6% and 9% vs 0%). Thus, topiramate 100 mg/day was associated with modest increases in psychomotor reaction times. Learning, memory, and executive function were unchanged. The tolerability profile, including cognitive adverse events, appeared to be acceptable.

Summary Purpose: To assess the efficacy, safety, and tolerability of the investigational drug carisbamate as adjunctive treatment for partial-onset seizures (POS). Methods: Two identical, randomized, placebo-controlled, double-blind studies were conducted in adults with POS uncontrolled for ≥1 year. Therapy-refractory epilepsy patients (≥16 years) remained on stable doses of prescribed antiepileptic drugs (≤2) for an 8-week prospective baseline phase and were then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, for a 12-week double-blind phase. Primary efficacy end points were percent reduction in seizure frequency and responder rate (patients with ≥50% reduction in POS frequency) during the double-blind phase compared with the prospective baseline phase. Results: Of the 565 patients randomized in study 1, 93% completed the study; of the 562 randomized in study 2, 94% completed the study. Patient characteristics were similar across both studies and treatment arms: mean age, 35 years (study 1, range 16–75 years) and 36 years (study 2, range 16–74 years); approximately 50% were men. Treatment with carisbamate 400 mg/day resulted in significant improvement (p

Paliperidone palmitate is an investigational, injectable atypical antipsychotic. The safety and tolerability of initiating treatment with paliperidone palmitate via deltoid versus gluteal injections given once monthly, and of switching injection sites, in adults with stable schizophrenia were assessed. In this crossover trial, stable outpatients (N=252) were randomly assigned 1:1:1 to 3 dose groups (paliperidone palmitate 50, 75, or 100 mg eq.) and 2 treatment sequences (blinded to dose): deltoid muscle (period 1 [13 weeks]) followed by gluteal muscle (period 2 [12 weeks]) or the reverse. The intent-to-treat analysis set had 249 patients: mean age=43 (SD: 12.8) years; 57% men, 81% white, baseline mean Positive and Negative Syndrome Scale (PANSS) total score=56 (SD: 11.5). A total of 170 (68%) patients completed the study, with a similar proportion completing each treatment sequence. The incidence of systemic treatment-emergent adverse events (TEAEs) was similar between the 2 injection sites across doses during period 1 (deltoid [D]: 61% to 67%; gluteus [G]: 58% to 65%), and during the last 8 weeks of the 2 study periods (DG: 32% to 45% [period 1], 29% to 42% [period 2]; GD: 31% to 40% [period 1], 30% to 41% [period 2]). During the first treatment week, median plasma paliperidone concentrations were higher with treatment initiation in the deltoid muscle compared with the gluteal muscle. At apparent steady state, there was little difference in plasma paliperidone concentrations between the deltoid and gluteus sites for a given dose. Local tolerability was slightly better with gluteal injections. Patient preference for injection sites differed between geographical regions, e.g. patients from the US preferred deltoid to gluteal sites. The most common (>or=5% overall) TEAEs were: (period 1) insomnia, anxiety, headache, and agitation; and (period 2) insomnia, psychotic disorder, weight increased, and tachycardia. Paliperidone palmitate treatment was tolerated, irrespective of injection site, and thus could offer the choice of administration into either the deltoid or gluteal muscle to meet patient and physician preference.

Plant phenology relates strongly to primary productivity and the energy that enters into ecological food webs, and thus is vital in understanding ecosystem function and the effects of climate and climate change. The manual collection of phenological data is labor-intensive and not easily scalable, thus the ability to quantify leaf flush and other parameters at many locations requires innovative new methodologies such as the use of visible light digital cameras. Improved imaging performance was obtained by using a cabled, mobile camera system that allowed a repeated image census of branches of Rhododendron occidentale in the understory along a 30 m transect during leaf flush. Automatic division of acquired images into areas of interest (leaves) and background for calculating leaf area was accomplished by thresholding images in different color spaces. Transformation of the color space into the hue, saturation, and luminance (HSL) color space before thresholding resulted in a mean RMS error of 21.2 cm 2 compared to hand-counts of leaf area. Thresholding in the native red, green, and blue (RGB) color space to isolate leaves resulted in a larger error, as did using algebraic combinations of the color components or color ratios. Relating physiological function to images, as for sap flow for branches of R. occidentale , indicates that the greening and calculated leaf area of a species as detected by imagers requires additional meteorological sensor data for interpretation.

In many organisms, the geometry of encounter of haploid germ cells is arbitrary. In Saccharomyces cerevisiae , the resulting zygotes have been seen to bud asymmetrically in several directions as they produce diploid progeny. What mechanisms account for the choice of direction, and do the mechanisms directing polarity change over time? Distinct subgroups of cortical “landmark” proteins guide budding by haploid versus diploid cells, both of which require the Bud1/Rsr1 GTPase to link landmarks to actin. We observed that as mating pairs of haploid cells form zygotes, bud site specification progresses through three phases. The first phase follows disassembly and limited scattering of proteins that concentrated at the zone of cell contact, followed by their reassembly to produce a large medial bud. Bud1 is not required for medial placement of the initial bud. The second phase produces a contiguous bud(s) and depends on axial landmarks. As the titer of the Axl1 landmark diminishes, the third phase ultimately redirects budding toward terminal sites and is promoted by bipolar landmarks. Thus, following the initial random encounter that specifies medial budding, sequential spatial choices are orchestrated by the titer of a single cortical determinant that determines whether successive buds will be contiguous to their predecessors.

Despite significant advances in Personal Protective Equipment (PPE) and enhanced tactics, line of duty deaths (LODD) and injuries due to cardiovascular events in the emergency responder community, specifically fire service, remain at an unacceptably high level each year. To address the tragic loss of life and often debilitating injuries that are too prevalent in the fire service, the Department of Homeland Security, Science and Technology Directorate, has created a Physiological Health Assessment System for Emergency Responders (PHASER) program. PHASER is charged to develop and deploy innovative technology solutions based on the fundamental medical understanding of risk factors to enhance health and safety of emergency responders. One of the outcomes of the program is a low-cost secure networked system — PHASER-Net — capable of remote physiological monitoring, risk profiling, risk mitigation and guidance of the individual emergency responders. The PHASER-Net system has been deployed at multiple fire departments across the country, as well as academic research laboratories for validation, testing and enhancement. From the days of initial deployments, the system proved vital by identifying individuals with high risk of cardiovascular events and providing targeted training guidance for risk mitigation and prevention.

Data from 2 studies (phase 1 and phase 3) in infants

Development of inexpensive, automated ground methods is necessary to advance precision plant phenology monitoring across large spatial extents. We propose the use of free, publicly available, Internet-connected cameras, often associated with nonscientific monitoring, to monitor plant phenology at continental scales. We provide a methodology to detect changes in vegetation greenness and determine timing of spring and fall events from over 1100 public cameras across North America from February 2008 - 2009. Manual image segmentation facilitated spring detection for both deciduous and understory vegetation occurring within a single camera view. Deciduous spring green-up was highly correlated with visual ground truths, despite signal noise introduced by varying image exposure and automatic color correction. Compared to co-occurring satellite remote sensing products, public cameras had an equivalent or higher ability to detect spring with fewer days lost to cloud cover.

Plant phenology is highly sensitive to changes in environmental conditions and can vary widely across landscapes. Current observation methods are either manual for small-scale, high precision measurements or by satellite remote sensing for large-scale, low spatial resolution measurement. The development of inexpensive approaches is necessary to advance large scale, high precision phenology monitoring. The use of publicly available, Internet-connected cameras, often associated with airports, national parks, and roadway conditions, for detecting and monitoring plant phenology at a continental scale can augment existing ground and satellite-based methodologies. We collected twice-daily images from over 1100 georeferenced public cameras across North America from February 2008 to 2009. Using a test subset of these cameras, we compared modeled spring 'green-up' with that from co-occurring remote sensing products. Although varying image exposure and color correction introduced noise to camera measurements, we were able to correlate spring green-up across North America with visual validation from images and detect a latitudinal trend. Public cameras had an equivalent or higher ability to detect spring compared with satellite-based data for corresponding locations, with fewer numbers of poor quality days, shorter continuous bad data days, and significantly lower errors of spring estimates. Manual image segmentation into deciduous, evergreen, and understory vegetation allowed detection of spring and fall onset for multiple vegetation types. Additional advantages of a public camera-based monitoring system include frequent image capture (subdaily) and the potential to detect quantitative responses to environmental changes in organisms, species, and communities. Public cameras represent a relatively untapped and freely available resource for supporting large-scale ecological and environmental monitoring.

Networked embedded acoustic sensors and imagers allow scientists to observe biological and environmental phenomena at high sampling rates and multiple scales. Such sampling can create large data sets that often require some form of automated processing to extract useful information. However, to guarantee the accuracy of the data, the scientist must be included in the processing, rather than treating it as a black box, an approach we call interactive environmental sensing. In this paper we describe the challenges of such an approach and motivate it with several examples from bioacoustics, plant phenology and avian biology.

In clinically classic carpal tunnel syndrome (CTS) without symptoms or signs to suggest other disorders that can mimic CTS, it remains somewhat controversial as to whether performing nerve conduction studies is necessary or cost-effective. MR imaging reliably depicts normal carpal tunnel anatomy. It can also identify pathologic nerve compression and mass lesions, such as ganglion cysts, that compress nerves. Currently, MR imaging is most commonly used to image patients with ambiguous electrodiagnostic studies and clinical examinations. MR diffusion-weighted imaging of peripheral nerves might prove to be the most sensitive imaging sequence for the detection of early nerve dysfunction. Electrodiagnostic studies are likely to remain the pivotal diagnostic examination in patients with suspected CTS for the foreseeable future. With advances in both software and hardware, however, high-resolution MR imaging of peripheral nerves will become faster, cheaper, and likely more accurate, possibly paving the way for an expanded role in the diagnosis of this common syndrome.

The performance of a sensor network may be best judged by the quality of application specific information return. The actual sensing performance of a deployed sensor network depends on several factors which cannot be accounted at design time, such as environmental obstacles to sensing. We propose the use of mobility to overcome the effect of unpredictable environmental influence and to adapt to run time dynamics. Now, mobility with its dependencies such as precise localization and navigation is expensive in terms of hardware resources and energy constraints, and may not be feasible in compact, densely deployed and widespread sensor nodes. We present a method based on low complexity and low energy actuation primitives which are feasible for implementation in sensor networks. We prove how these primitives improve the detection capabilities with theoretical analysis, extensive simulations and real world experiments. The significant coverage advantage recurrent in our investigation justifies our own and other parallel ongoing work in the implementation and refinement of self-actuated systems.

The goal of this integrated and cross-campus project is to sense the environment from the leaf to the landscape level. Aspects of the project include, but are not limited to: (1) NIMS and fixed-camera technologies that allow the real-time and automated observation of plant phenological events: leaf flushes, flowering, herbivore attack, and pollination and flower-visitation events. (2) Embedded micro-sensors that include light sensors sensitive to photosynthetic photon flux (PPF; 400-700 nm wavelength) installed on leaf surfaces indicate leaf- and plant-level responses to changes in light conditions, sap flow sensors that measure the velocity at which the transpiration stream flows by the dissipation of heat within a branch, and micrometeorological sensors that monitor conditions that change the driving force for transpiration and affect water balance on a plant- and landscape-level. (3) Minirhizotron tubes enable the direct measurement of root growth and allow for the estimations of microbial activity in the soil.