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This study set out to examine pre-analytical factors affecting the frequency of positive results in newborn screening for biotinidase deficiency. This investigation was prompted by an increase in the annual screen positive rate for biotinidase deficiency in Ontario from 2.65x10

Across Australia’s Wet Tropics region, populations of rainforest-dependent birds have declined because of climate change. Reforestation and regenerating secondary forest on abandoned agricultural land may help bolster species’ populations by expanding and connecting habitat. However, little is known about the value of these habitats for rainforest birds, or the impacts of climate change on secondary forests and their fauna compared with primary forests. At a 62-ha, mid-elevation property with primarily secondary forest cover on the Atherton Tablelands, in the Wet Tropics region, Queensland, we examined changes in bird species reporting rates on weekly lists between 2000–2005 and 2014–2019. Reporting rates of grassland and eucalypt-forest species decreased as expected because the area of ungrazed pasture was reduced over time, while the area occupied by tree plantings and naturally regenerating forest increased and matured. Reporting rates of most mixed-forest (61%) and nearly half (47%) of rainforest-dependent bird species also decreased significantly between the two time periods, despite the quality of rainforest habitat improving at the site. We infer that climate change is the cause of these declines. Five of the rainforest-dependent bird species whose reporting rates decreased in this study are known to have moderately increased in abundance in mid-elevation primary forest. Hotter, drier secondary forests may not be as well buffered as primary forest from the impacts of climate change, reducing their suitability as habitat for many bird species such as these. However, further studies are needed in secondary forests to investigate this.

The bare-nosed wombat (Vombatus ursinus) is a fossorial, herbivorous, Australian marsupial, renowned for its cubic feces. However, the ability of the wombat's soft intestine to sculpt flat faces and sharp corners in feces is poorly understood. In this combined experimental and numerical study, we show one mechanism for the formation of corners in a highly damped environment. Wombat dissections show that cubes are formed within the last 17 percent of the intestine. Using histology and tensile testing, we discover that the cross-section of the intestine exhibits regions with a two-fold increase in thickness and a four-fold increase in stiffness, which we hypothesize facilitates the formation of corners by contractions of the intestine. Using a mathematical model, we simulate a series of azimuthal contractions of a damped elastic ring composed of alternating stiff and soft regions. Increased stiffness ratio and higher Reynolds number yield shapes that are more square. The corners arise from faster contraction in the stiff regions and relatively slower movement in the center of the soft regions. These results may have applications in manufacturing, clinical pathology, and digestive health.

Colorectal cancer is the third most frequently encountered cancer worldwide. While current chemotherapeutics help to manage the disease to some extent, they have eluded achieving complete remission and are limited by their severe side effects. This warrants exploration of novel agents that are efficacious with anticipation of minimal adverse effects. In the current study, casticin, a tetramethoxyflavone, was tested for its ability to inhibit the viability of three human colorectal cancer cells: adenocarcinoma (DLD-1, Caco-2 cell lines) and human colorectal carcinoma cells (HCT116 cell line). Casticin showed potent inhibition of viability of DLD-1 and HCT116 cells. Clonogenic assay performed in DLD-1 cells revealed that casticin impeded the colony-forming efficiency of the cells, suggesting its impact on the proliferation of these cells. Further, a sustained effect of the inhibitory action upon withdrawal of the treatment was observed. Elucidation of the mechanism of action revealed that casticin impacted the extrinsic programmed cell death pathway, leading to an increase in apoptotic cells. Further, Bcl-2, the key moiety of cell survival, was affected. Notably, a significant number of cells were arrested in the G2/M phase of the cell cycle in DLD-1 cells. Due to the multifaceted action of casticin, we envision that treatment with casticin could provide an efficacious treatment option for colorectal adenocarcinomas with minimal side effects.

The new transdisciplinary nature of industrial product design should be appropriately addressed by post-secondary institutions and engineering schools in their curricula to ensure high quality of engineering design education and its applicability to industrial demands. To achieve this, a new transdisciplinary teaching methodology is required. This paper presents the results of a pilot trial of a new transdisciplinary teaching approach to engineering design education based on Bloom’s Taxonomy and a comparitive analysis of the cognitive game task performed by both professors and fours groups of students to investigate the differences in their design thinking. The approach included the knowledge component in the form of a lecture, a cognitive game task developed to map the design thinking of engineers, and administration of a modified sample design problem. The knowledge components consisted of a guest lecture on transdisciplinary engineering design and disciplinary differences. The cognitive task involved the formation of design activities and their placement along a general design process. The modification of the sample design problem involved the application of action verbs of Bloom’s Taxonomy to create guiding steps to guide students’ thinking while solving the problem. The results revealed a strong relation between engineering design activity and cognitive mental activity in both students and professors. The course instructors who piloted the new approach provided positive feedback finding it to be a “useful element” for the introduction of transdisciplinarity as well as for students’ reflection on their design thinking. In addition, the application of Bloom’s Taxonomy in design problems suggested potential improvements in students’ performance on design tasks. The results of this study are applicable for the development of engineering design courses and transdisciplinary projects.

As bias estimation methods are developed, it becomes necessary to obtain the bound on bias estimation for more complex bias and sensor models. Three-dimensional (3-D) sensors, such as radars commonly used in applications, contain both scale and additive biases in sine space which result in a nonlinear estimation problem that may have poor observability and accuracy depending on the geometry of the sensors. By converting the sine space and range measurements to Cartesian using an unbiased conversion, it is possible, via creation of pseudomeasurements, to eliminate the need to estimate the target's state thereby reducing the sensor bias estimator complexity. The present paper evaluates the Cramer–Rao lower bound (CRLB) for estimating scale and additive biases in sine space for 3-D sensors and compares it with a maximum likelihood formulation implemented via iterated least squares, which is thereby shown to be statistically efficient. Additionally, the importance of measurement diversity is investigated with respect to the CRLB.

New free electron lasers, such as SLAC’s LCLS-II, will provide unique scientific imaging opportunities. In order to fully utilize these facilities, we need to develop detectors with shallow entrance windows that will enable detection of soft x-rays from 250eV-1.5KeV. Achieving adequately shallow entrance windows is challenging because the high temperature anneal needed to activate the dopant for the diode termination also drives the dopant profile deeper, growing the region that is insensitive to soft x-rays. A new microwave annealing technology provides an efficient way to achieve shallow entrance windows in fully depleted high-resistivity silicon sensors. The micro-wave anneal technique can activate dopants at low substrate temperature, with minimal dopant diffusion, and can be used to fabricate both n-type and p-type entrance windows. SRP and SIMS measurements were used to verify dopant activation with negligible dopant diffusion. We then applied the microwave anneal process to a planar sensor device wafer, using the new process to create the backside diode contact. Electrical test of the resulting sensors shows good reverse bias diode characteristics. The sensors have been bump-bonded to a read-out ASIC and used successfully to measure an Fe-55 x-ray spectrum. Process and device simulations were performed to characterize the quantum efficiency of the entrance window for soft x-rays. This technique is useful for other sensor applications requiring a shallow entrance window, including detectors for UV photons, low energy ions and low energy electrons.

In track-to-truth assignment applications there are tracks present which are ambiguous and appear to originate from several different truth objects. These tracks can significantly affect intermediate processes that are involved in the assignment of tracks such as bias estimation, where an incorrect track-to-truth assignment would result in a incorrect bias estimate. Gating the ambiguous tracks out of the scenario and using exclusively clear unambiguous tracks within the intermediate process enables track-to-truth assignment to be more accurate afterwards. In this work a switching probability metric is proposed that reports the ambiguity of a track report by calculating the probability of the track report switching from one truth object to another. The use of this metric for gating tracks is shown to be accurate for finding tracks and reporting ambiguity. In addition it is shown to improve bias estimation consistency when applied to track-to-truth assignment.

Background The Canadian Inherited Metabolic Diseases Research Network (CIMDRN) is a pan-Canadian practice-based research network of 14 Hereditary Metabolic Disease Treatment Centres and over 50 investigators. CIMDRN aims to develop evidence to improve health outcomes for children with inherited metabolic diseases (IMD). We describe the development of our clinical data collection platform, discuss our data quality management plan, and present the findings to date from our data quality assessment, highlighting key lessons that can serve as a resource for future clinical research initiatives relating to rare diseases. Methods At participating centres, children born from 2006 to 2015 who were diagnosed with one of 31 targeted IMD were eligible to participate in CIMDRN’s clinical research stream. For all participants, we collected a minimum data set that includes information about demographics and diagnosis. For children with five prioritized IMD, we collected longitudinal data including interventions, clinical outcomes, and indicators of disease management. The data quality management plan included: design of user-friendly and intuitive clinical data collection forms; validation measures at point of data entry, designed to minimize data entry errors; regular communications with each CIMDRN site; and routine review of aggregate data. Results As of June 2019, CIMDRN has enrolled 798 participants of whom 764 (96%) have complete minimum data set information. Results from our data quality assessment revealed that potential data quality issues were related to interpretation of definitions of some variables, participants who transferred care across institutions, and the organization of information within the patient charts (e.g., neuropsychological test results). Little information was missing regarding disease ascertainment and diagnosis (e.g., ascertainment method – 0% missing). Discussion Using several data quality management strategies, we have established a comprehensive clinical database that provides information about care and outcomes for Canadian children affected by IMD. We describe quality issues and lessons for consideration in future clinical research initiatives for rare diseases, including accurately accommodating different clinic workflows and balancing comprehensiveness of data collection with available resources. Integrating data collection within clinical care, leveraging electronic medical records, and implementing core outcome sets will be essential for achieving sustainability.

Passive sensor target tracking has the challenge to 3-D tracking applications in that the raw angle-only measurements cannot be converted into Cartesian measurements. Multi-sensor methods can be used to convert the raw measurements into Cartesian measurements by finding the intersection of the two lines of sight. Examples include triangulation, law of sines, and maximum likelihood estimation. However, many of these methods can have an inherent bias present in the conversion as a result of its nonlinearity. In long range applications this can cause significant error. This paper investigates the conversion of passive sensor angle-only measurements into Cartesian coordinates and evaluates the conversion bias present in triangulation.

Bias estimation is a significant problem in target tracking applications and passive sensors present additional challenges in this field. Biases in passive sensors are commonly represented as unknown rotations of the sensor coordinate frame and it is necessary to correct for such errors. Many methods have used simultaneous target state and bias estimation to register the sensors, however it may be advantageous to decouple state and bias estimation to simplify the estimation problem. This way bias estimation can be done for any arbitrary target motion. If measurements are converted into Cartesian coordinates and differenced then it is possible to isolate the effects of the biases. This bias pseudo-measurement approach has been used in bias estimation for many types of biases and sensors and this paper applies this method to 3D passive sensors with rotational biases. The Cram´er-Rao Lower Bound for the bias estimates is evaluated and it is shown to be attained, i.e., the bias estimates are statistically efficient.

As is always the case, patient needs are the priority. Risk management involves implementing strategies for patient care. Risk management strategies reduce the possibility of an adverse outcome, injury, or loss. Good risk management improves the quality of patient care and decreases the probability of poor treatment results or a medical malpractice claim. Such strategies include identifying risks, minimizing those risks, and reducing the impact of injury or loss when untoward outcomes do occur.

In order to support the high luminosity upgrades at ATLAS and CMS, thinned silicon sensors for hybrid pixel detectors are critical to improve radiation hardness, reduce detector mass, and address high occupancy rates. Because silicon wafer processing tools are not equipped to handle thin wafers, the thinning step cannot be performed until the after the majority of the processing steps are complete, requiring post-processing to create the doped region that constitutes the diode contact at the backside of the wafer. This is challenging, because the high temperature anneal required to activate the dopant after ion implantation would be damaging to the existing front side structures. Current techniques for solving this problem, such as using Silicon-on-insulators wafers, are very expensive. A new microwave annealing technology has been developed which can activate the backside implant at low temperature, without damaging the frontside structures. We have verified this approach on a prototype sensor that was bump-bonded to a readout ASIC and used successfully to measure an Fe-55 x-ray spectrum

Free electron lasers, such as SLAC’s LCLS-II, will provide unique scientific imaging opportunities. In order to fully utilize these facilities, we need to develop detectors with shallow entrance windows that will enable detection of soft x-rays from 250eV-1.5KeV. Achieving adequately shallow entrance windows is challenging because the high temperature anneal used to active the dopant for the diode termination also drives the dopant profile deeper, growing the region that is insensitive to soft x-rays. A new microwave annealing technology provides an efficient way to achieve shallow entrance windows in fully depleted high-resistivity silicon sensors. The new technique can activate dopants at low substrate temperature, with minimal dopant diffusion. We implanted test wafers with low energy (10KeV) Arsenic implant, followed by microwave annealing with the new technique. SRP and SIMS measurements were used to verify dopant activation with negligible dopant diffusion. We then applied the microwave anneal process to a planar sensor device wafer, using the new process to create the backside diode contact. Electrical test of the resulting sensors shows good reverse bias diode characteristics. The sensors have been bump-bonded to a read-out ASIC and used successfully to measure an Fe-55 x-ray spectrum.

In order to carry out data fusion, it is crucial to account for the imprecision of sensor measurements due to systematic errors. This requires estimation of the sensor measurement biases. In this paper, we consider a 3D multisensor multitarget bias estimation approach for both additive and multiplicative biases in the measurements. Multiplicative biases can more accurately represent real biases in many sensors, however, they increase the complexity of the estimation problem. By converting biased measurements into pseudo-measurements of the biases it is possible to estimate biases separately from target state estimation. The conversion of the spherical measurements to Cartesian measurements, which has to be done using the unbiased conversion, is the key that allows estimation of the sensor biases without having to estimate the states of the targets of opportunity. The measurements provided by these sensors are assumed time-coincident (synchronous) and perfectly associated. We evaluate the Cram´er-Rao Lower Bound (CRLB) on the covariance of the bias estimates, which serves as a quantification of the available information about the biases.

The issue of the oversight of intelligence and security services is playing an increasing role in the debate on global security issues both among specialists and the broader public. Beyond theoretical debates on intelligence and surveillance ten practical approaches to advance oversight are being developed. Core ideas address the implications of the political supremacy of oversight, the need for revisiting the focus of oversight as well as the possibilities of the proliferation of best oversight practices. Furthermore, suggestions are made regarding the integration of ethics in security research and the creation of space for applied ethics for intelligence practitioners.

Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Administration of NSCs into the cerebrospinal fluid (CSF) offers a nontraumatic transplantation method into the brain. However, cell survival and intraparenchymal migration of the transplants are limited. Furthermore, CSF was recently reported to be an important milieu for controlling stem cell processes in the brain. We studied the effects of adult human leptomeningeal CSF on the behavior of fetal rat NSCs. CSF increased survival of NSCs compared with standard culture media during stem cell maintenance and differentiation. The presence of CSF enhanced NSC differentiation, leading to a faster loss of self-renewal capacity and faster and stronger neurite outgrowth. Some of these effects (mainly cell survival, neurite brancing) were blocked by addition of the bone morphogenic protein (BMP) inhibitor noggin. After differentiation in CSF, significantly fewer MAP2ab+ neurons were found, but there were more GFAP+ astroglia compared with standard media. By RT-PCR analysis, we determined a decrease of mRNA of the NSC marker gene Nestin but an increase of Gfap mRNA during differentiation up to 72 hr in CSF compared with standard media. Our data demonstrate that adult human leptomeningeal CSF enhances cell survival of fetal rat NSCs during proliferation and differentiation. Furthermore, CSF provides a stimulus for gliogenesis but inhibits neurogenesis from fetal NSCs. Our data suggest that CSF contains factors such as BMPs regulating NSC behavior, and we hypothesize that fast differentiation of NSCs in CSF leads to a rapid loss of migration capacity of intrathecally transplanted NSCs. © 2009 Wiley-Liss, Inc.

What are the sources of political myths? Useful starting points for answering this question can be found in the fiction of Cervantes and the political philosophies of Machiavelli, Erasmus, and Leo Strauss. These writers, who sought to defuse clashes of custom and of religion, emphasized the need to pay attention to the consequences of false belief, without lapsing into cynicism. In this, they were the ultimate idealists, whose insights might temper the dogmas of the modern ideologue.

We present an application of Ant Colony Optimisation (ACO) to simulate socio-cognitive features of a population. We incorporated perspective taking ability to generate three different proportions of ant colonies: Control Sample, High Altercentricity Sample, and Low Alter-centricity Sample. We simulated their performances on the Travelling Salesman Problem and compared them with the classic ACO. Results show that all three ‘cognitively enabled’ ant colonies require less time than the classic ACO. Also, though the best solution is found by the classic ACO, the Control Sample finds almost as good a solution but much faster. This study is offered as an example to illustrate an easy way of defining inter-individual interactions based on stigmergic features of the environment.

As Underwater Acoustic Networks (UANs) become more commonly utilized, it is crucial to research security against interference and jamming as the networks are based in an exposed environment. We have identified some of the key communication vulnerabilities across underwater networks using basic jamming techniques. Three commercial modems from the United States were analyzed in our tests, particularly LinkQuest, AquaSeNT and Benthos modems, which use DSSS, OFDM and MFSK transmission schemes. We observed that each modem has a preamble that contains a packet that is vulnerable to a shorter, more efficient targeted jam. Each modem is also vulnerable to single tone jamming at certain frequencies in the bandwidth, and can be reliably but less efficiently jammed with frequency sweeps.

Summary The antiepileptic drug valproic acid (VPA) has shown neuroprotective effects in different cell types including mesencephalic neural primary cultures. Furthermore, an influence on neural differentiation and neurite outgrowth has been described. Nevertheless, results in this regard are contradictory and data on long term expanded neural stem cells are missing. This is why we investigated possible neuroprotective effects of VPA on fetal mesencephalic neural stem cells (fmNSCs) in vitro, using the neurotoxic agent 1-methyl-4-phenyl-pyridin (MPP+). We also examined potential VPA effects on cell expansion and differentiation and the underlying signaling pathways. In our study, we could exclude any relevant toxic effects of 100 μg/ml and 200 μg/ml VPA on fmNSCs during expansion and differentiation for up to 96 h. MPP+ treatment in concentrations of 30 and 60 μM MPP+ significantly decreased the survival rate of fmNSCs during expansion and differentiation. In all used concentrations, VPA did neither reverse these MPP+ effects when applied simultaneously with MPP+ nor after pre-treatment with VPA for 24 h. In contrast, MPP+ effects were emphasized by VPA pretreatment for 24 h when applied during cell expansion. Concerning the self-renewing capacity of fmNSCs, measured by BrdU and Ki67 staining, we did not find any significant influence of VPA. Additionally there was no significant influence of therapeutic VPA dosages on astroglial (GFAP), oligodendroglial (GalC) and neuronal (MAP2) differentiation, measured by immunostaining after 10 days of differentiation. Summing up, we did not find any neuroprotective effects of VPA on fmNSCs in vitro, neither during expansion nor during cell differentiation. Also the self-renewing and differentiation potential of the used fmNSCs was not altered. These findings have implications for the large community of patients having to take VPA on a chronic base, especially in the light of knowledge that a regular cell replacement out of hippocampal adult stem cells is mandatory for the maintenance of normal cognition through adulthood.

BackgroundNeural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existingin vitrostudies focused on embryonic cell lines and embryonic CSF. We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).ResultsAdult CSF increased the survival rate of adult human NSCs compared to standard serum free culture media during both stem cell maintenance and differentiation. The presence of CSF promoted differentiation of NSCs leading to a faster loss of their self-renewal capacity as it is measured by the proliferation markers Ki67 and BrdU and stronger cell extension outgrowth with longer and more cell extensions per cell. After differentiation in CSF, we found a larger number of GFAP+astroglial cells compared to differentiation in standard culture media and a lower number of β-tubulin III+neuronal cells.ConclusionsOur data demonstrate that adult human leptomeningeal CSF creates a beneficial environment for the survival and differentiation of adult human NSCs. Adult CSF isin vitroa strong glial differentiation stimulus and leads to a rapid loss of stem cell potential.

Historisch gewachsene Produktzuordnungen zu einzelnen Produktionsstandorten, eine unklare oder nicht vorhandene Produktionsstrategie oder auch Preisdruck von der Marktseite her sind oft Grunde dafur, dass Unternehmen Probleme mit ihren Ertragen bekommen und aufgrund einer ungunstigen Kostensituation in einigen Bereichen nicht mehr wettbewerbsfahig sind. Gerade in der chemischen Industrie oder in anderen reifen Industrien, die mit ihren Produkten im Produktlebenszyklus weit fortgeschritten sind, ist ein effizientes Produktionsnetzwerk unabdingbar, um am Markt bestehen und auch mit Commodityprodukten uberdurchschnittliche Deckungsbeitrage erzielen zu konnen. Hierbei stehen haufig folgende Fragen im Vordergrund

Die Qualitatsstrategie fur ein Produkt beginnt bereits am ersten Tag der Produktentwicklung.

Die pharmazeutischen Fayencen des Deutschen Apotheken- Museums in Heidelberg. Die Verfasser erklären wie die Sammlung von pharmazeutischer Keramik des Museums von Heidelberg geschichtlich erstellt wurde und nach welchen Kriterien sie gezeigt wird. Sie geben den geographischen und zeitlichen Ursprung der Fayencen an., Pharmaceutical faience in the German Pharmacy Museum in Heidelberg. The authors give an account of both the historic development of the ceramic pharmaceutical collection in the Heidelberg Museum, and the criteria for its presentation. They also indicate its division by geographic provenance and by period., Kowalski Michael, Müller-Jahncke Wolf Dieter. Les faïences de pharmacie au Musée allemand de la pharmacie, à Heidelberg. In: Revue d'histoire de la pharmacie, 79ᵉ année, n°291, 1991. pp. 431-441.