To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Agreements about reciprocal recognition of patent rights between nations were at the heart of discussions at the International Union for the Protection of Industrial Property held in Paris in 1883. Yet while some treat the so-called “Paris Union” as a starting point for the subsequent globalization in patent rights, the context of early attempts at patent law harmonization was international tension and disagreements. Divergences in patent laws have their roots in the strong heterogeneity manifest among national patent systems developing before 1883. The sheer diversity of patent systems available was indeed highlighted by those critics who sought the abolition of patents rights. The project of harmonization should thus be seen as a defensive response to critics of patenting per se, rather than as the advent of a natural process of legislative convergence. In looking at the 1883 Convention in this light, we see that negotiations there can only be understood in terms of a strong rivalry between the French and German models. Such rivalries continued to characterize the membership of the Paris Union even into the interwar period, raising major doubts about whether the project of harmonization could ever be completed.
Stretchable electronics fabrication generally relies on fine-tuning adhesion forces, putting some restrictions on what the carrier layer can be. In contrast to adhesion, mechanical tangling makes more kinds of carrier materials available. Antibacterial, conductive, heat-responsive and other functions can be brought in by fiber networks as long as they are compatible with the highly selective silicon etch process. Mechanical grippers can also bring electronic contacts from one side of a mesh to the other, which is difficult to do on continuous thin films of other soft materials like silicone or polyimide. Our solution uses mechanical strain to produce large arrays of redundant grippers from planar thin-film designs.
Une économie politique critique de la science s’est récemment développée pour analyser le tournant néo-libéral qui la caractérise. Ce courant tend pourtant à négliger la longue durée de l’histoire économique des sciences qui permet de comprendre les évolutions récentes. Cet article montre, à travers l’étude de l’entreprise scientifique de Louis Pasteur, comment la question du partage de la valeur du travail scientifique se pose dès l’essor du capitalisme industriel au xixe siècle. Il étudie la manière dont Pasteur défend sa propriété scientifique, manifestant une forme de revendication sur le contrôle de ses découvertes. L’étude du lien entre le développement de la science industrielle et le capitalisme permet d’abord de comprendre la logique d’action au cœur de l’entreprise scientifique pasteurienne qui s’affirme dès le début de sa carrière, aux prises avec le capitalisme nordiste. Cette logique se renforce ensuite dans les années 1860, alors que la distinction entre science et industrie est formalisée sur le plan juridique. Elle est un moyen, pour Pasteur, de faire valoir sa propriété scientifique et ses droits, autant économiques que scientifiques, sur les fruits de son travail. Est enfin examinée la façon dont ces derniers sont réinvestis, soit pour créer une société commerciale, soit pour fonder l’Institut éponyme. L’entreprise pasteurienne apparaît ainsi comme un processus d’accumulation qui se nourrit de cette ambivalence créatrice.
Terrorism and natural catastrophes have made disaster preparedness a critical issue. Despite the documented vulnerabilities of children during and following disasters, gaps remain in health care systems regarding pediatric disaster preparedness. This research study examined changes in knowledge acquisition of pediatric disaster preparedness among medical and non-medical personnel at a children’s hospital who completed an online training course of five modules: planning, triage, age-specific care, disaster management, and hospital emergency code response.
A multi-disciplinary team within the Pediatric Disaster Resource and Training Center at Children’s Hospital Los Angeles (Los Angeles, California USA) developed an online training course. Available archival course data from July 2009 to August 2012 were analyzed through linear growth curve multi-level modeling, with module total score as the outcome (0 to 100 points), attempt as the Level 1 variable (any module could be repeated), role in the hospital (medical or non-medical) as the Level 2 variable, and attempt by role as the cross-level effect.
A total of 44,115 module attempts by 5,773 course participants (3,686 medical personnel and 2,087 non-medical personnel) were analyzed. The average module total score upon first attempt across all participants ranged from 60.28 to 80.11 points, and participants significantly varied in how they initially scored. On average in the planning, triage, and age-specific care modules: total scores significantly increased per attempt across all participants (average rate of change ranged from 0.59 to 1.84 points) and medical personnel had higher total scores initially and through additional attempts (average difference ranged from 13.25 to 16.24 points). Cross-level effects were significant in the disaster management and hospital emergency code response modules: on average, total scores were initially lower among non-medical personnel compared to medical personnel, but non-medical personnel increased their total scores per attempt by 3.77 points in the disaster management module and 6.40 points in the hospital emergency code response module, while medical personnel did not improve their total scores through additional attempts.
Medical and non-medical hospital personnel alike can acquire knowledge of pediatric disaster preparedness. Key content can be reinforced or improved through successive training in an online course.
PhamPK, BeharSM, BergBM, UppermanJS, NagerAL. Pediatric Online Disaster Preparedness Training for Medical and Non-Medical Personnel: A Multi-Level Modeling AnalysisPrehosp Disaster Med.2018;33(4):349–354.
A lack of standardized clinical research coordinator (CRC) training programs requires determining appropriate approaches for content delivery. The purpose of this study was to assess CRCs preferred training delivery methods related to the 8 designated Joint Task Force Clinical Trial Competency domains.
Repeated measures analysis of variance and split-plot analysis of variance were adopted to compare the group means among 5 training delivery methods by 8 competency content domains and to examine whether demographic variables caused different preference patterns on the training delivery methods.
Participants reported a preference for online video; mentoring/coaching was the least preferred. Significant training delivery method preferences were reported for 3 content domains: participant safety considerations, medicines development and regulation, and clinical trials operations.
Observed statistical differences in the training delivery methods by the content domains provides guidance for program development. Ensuring that standardized educational training is aligned with the needs of adult learners may help ensure that CRCs are appropriately prepared for the workforce.
OBJECTIVES/SPECIFIC AIMS: Astroglial glutamine synthetase (GS), which metabolizes glutamate and ammonia to glutamine, is critical for the detoxification of brain ammonia, clearance of synaptic glutamate, and production of brain glutamine. Perturbations in the expression and activity of GS are thought to play a causative role in the pathogenesis of several conditions of abnormal neurotransmission. Although the long-term consequences of GS inhibition on amino acid homeostasis in the brain are unknown, it is thought that amino acid influx in the brain is tightly coupled with glutamine efflux via the L-type amino acid transporter. Both glutamine and leucine serve many critical functions in the brain including protein synthesis, gene expression, insulin regulation, and immune signaling. The objective of this study was to determine the effects of chronic GS inhibition with methionine sulfoximine (MSO) on glutamine and leucine homeostasis in the brain. METHODS/STUDY POPULATION: In total, 12 rats were surgically implanted with microdialysis guide cannulas in the bilateral dentate gyrus. Rats were randomly divided for surgical implantation of either a MSO (n=6) or phosphate buffer saline (PBS; n=6) pump in the right dentate gyrus. After 7 days, bilateral microdialysis probes were placed under brief isoflurane anesthesia, and microdialysis flow was established by infusing 0.5 µL/min of artificial extracellular fluid. Dialysate samples were collected every 30 minutes for the duration of the experiment. A 113 mM 15N-Leucine (3.6 mL/h) and 2 M 2–13C-sodium acetate (0.0633 μL/g/min for t=0–5 min, 0.0316 μL/g/min for t=5–10 min, and 0.0253 μL/g/min for t>10 min) solution was infused intravenously for 300 minutes. The EZ:Faast Free Amino Acid analysis kit and ultra-performance liquid chromatography/tandem mass spectrometry was used for quantification of amino acids in the dialysate fluid. RESULTS/ANTICIPATED RESULTS: At baseline (t=0 h), the concentrations of glutamine were significantly lower in MSO-treated rats (p<0.001) in the ipsilateral (GS-inhibited) hippocampus. There were no differences in glutamine concentrations between MSO and PBS-treated rats in the contralateral hippocampus. In PBS-treated rats, there was a significant increase in 15N-leucine between t=0 hour and t=5 hour in the contralateral (p<0.05) and ipsilateral (p<0.05) hippocampus. In MSO-treated rats, there was a significant increase in 15N-leucine between t=0 and t=5 hours in the contralateral (p<0.05) hippocampus, but not in the ipsilateral hippocampus (p=ns.). DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrated for the first time that basal glutamine concentrations are low in areas of the brain where GS is acutely inhibited, and that leucine uptake in these brain areas are markedly decreased. Perturbations in glutamine and leucine homeostasis have been implicated in several disease processes including diabetes, obesity, liver disease, immune system dysfunction, epilepsy, and cancer, and the glutamine-dependent leucine influx in the brain may be a novel and important therapeutic target to treat these conditions.
OBJECTIVES/SPECIFIC AIMS: To evaluate the NIH-sponsored Best Practices for Social and Behavioral Research e-learning course. METHODS/STUDY POPULATION: Four universities partnered in a pilot study to evaluate this new course. Outcomes from 294 participants completing the course included efficient progress through the training, perceived relevance of the course to current work, level of engagement with the course material, intent to work differently as a result of the course, and downloading digital resources. RESULTS/ANTICIPATED RESULTS: Participants rated the course as relevant and engaging (6.4 and 5.8 on a 7-point Likert scale) and 96% of respondents said they would recommend the course to colleagues. Qualitative analysis of participant testimonials suggested that most respondents had a readiness to change in the way they worked as a result of the course. Overall, results suggest participants completed the course efficiently, perceived outcomes positively and worked differently after the training. DISCUSSION/SIGNIFICANCE OF IMPACT: These results will inform new guidelines for future participants (e.g., average time to complete, expectations for knowledge checks in the training). Future studies should include larger samples and closer coordination and communication between study sites.
The Best Practices in Social and Behavioral Research Course was developed to provide instruction on good clinical practice for social and behavioral trials. This study evaluated the new course.
Participants across 4 universities took the course (n=294) and were sent surveys following course completion and 2 months later. Outcomes included relevance, how engaging the course was, and working differently because of the course. Open-ended questions were posed to understand how work was impacted.
Participants rated the course as relevant and engaging (6.4 and 5.8/7 points) and reported working differently (4.7/7 points). Participants with less experience in social and behavioral trials were most likely to report working differently 2 months later.
The course was perceived as relevant and engaging. Participants described actions taken to improve rigor in implementing trials. Future studies with a larger sample and additional participating sites are recommended.
Reactions to the brutal Syrian War from European governments and Europe's Muslims have been diverse and subject to many shifts over the past few years. This paper focuses on how Albanian political and Islamic religious figures living in the Balkans have come to interpret the war. I focus on discourse, the ways in which these different agents communicate with their audience, and the wider contexts they evoke. Government sources and religiously themed lectures delivered by prominent imams on the social networking site YouTube are used to assess these trends. The most obvious aspect of these debates is the ways in which these agents use the war to press their own agendas, the government to affirm their commitment to the “West” and an ethnicized view of Islam, while Islamic religious leaders use it to reconnect their audiences to a more cosmopolitan vision of their past. War thus becomes a catalyst for a resurgent contestation between different groups vying for control over what it means to be “Albanian” and “Muslim” in the twenty-first century.
Inherited optic neuropathies are a heterogeneous group of disorders characterized by mild to severe visual loss, colour vision deficit, central or paracentral visual field defects and optic disc pallor. Optic atrophies can be classified into isolated or non-syndromic and syndromic forms. While multiple modes of inheritance have been reported, autosomal dominant optic atrophy and mitochondrial inherited Leber's hereditary optic neuropathy are the most common forms. Optic atrophy type 1, caused by mutations in the OPA1 gene is believed to be the most common hereditary optic neuropathy, and most patients inherit a mutation from an affected parent. In this study we used whole-exome sequencing to investigate the genetic aetiology in a patient affected with isolated optic atrophy. Since the proband was the only affected individual in his extended family, and was a product of consanguineous marriage, homozygosity mapping followed by whole-exome sequencing were pursued. Exome results identified a novel de novo OPA1 mutation in the proband. We conclude, that though de novo OPA1 mutations are uncommon, testing of common optic atrophy-associated genes such as mitochondrial mutations and OPA1 gene sequencing should be performed first in single individuals presenting with optic neuropathy, even when dominant inheritance is not apparent.
Whole-exome sequencing for clinical applications is now an integral part of medical genetics practice. Though most studies are performed in order to establish diagnoses in individuals with rare and clinically unrecognizable disorders, due to the constantly decreasing costs and commercial availability, whole-exome sequencing has gradually become the initial tool to study patients with clinically recognized disorders when more than one gene is responsible for the phenotype or in complex phenotypes, when variants in more than one gene can be the cause for the disease. Here we report a patient presenting with a complex phenotype consisting of severe, adult-onset, dilated cardiomyopathy, hearing loss and developmental delay, in which exome sequencing revealed two genetic variants that are inherited from a healthy mother: a novel missense variant in the CASK gene, mutations in which cause a spectrum of neurocognitive manifestations, and a second variant, in MYBPC3, that is associated with hereditary cardiomyopathy. We conclude that although the potential for co-occurrence of rare diseases is higher when analyzing undefined phenotypes in consanguineous families, it should also be given consideration in the genetic evaluation of complex phenotypes in non-consanguineous families.
In the framework of the European Research Council-funded project, “Reconstructing Ancient (Biblical) Israel: The Exact and Life Sciences Perspective,” we carried out multiple analyses on iron and bronze objects from provenanced contexts in Israel, as well as on previously unidentified metallurgical remains from the production of both metals. In addition, we counted anew iron and bronze objects from well-stratified contexts and studied metalworking sequences at major sites, which included those that had undergone the bronze/iron transition. This enabled us to clarify some of the issues related to the bronze/iron transition in the southern Levant. Using this evidence, we showed that iron was not used for utilitarian purposes before the Iron I (late 12th century BCE) and that iron only became dominant concurrently with the beginning of its systematic production during the Iron IIA (10th–9th centuries BCE). A strong correlation between iron and bronze production suggests that during the Iron I local independent bronzesmiths adopted the new iron technology. Under local administrations that developed during the Iron IIA, workshops that previously produced bronze turned to iron production, although they continued to manufacture bronze items as a secondary venture. Significantly, at some of the major urban centers iron production was an independent industry that included the entire operational sequence, including the on-site smelting of the ore. This development appears to have been a major contributor to the transition to systematic production of iron.
Close examination of John Adams's oeuvre reveals that symmetry is one of the predominant features of his music. Three common types of symmetry are encountered in Adams's works: reflection, translation and rotation. This article investigates these symmetries and tracks their development throughout Adams's compositional career. An analysis of selected works from the 1970s (China Gates and Phrygian Gates), 1980s (Grand Pianola Music and Fearful Symmetries) and 1990s (the Violin Concerto and Century Rolls) highlights the most pervasive symmetry in each decade and shows a shift from preconceived overarching symmetries that frame entire musical structures to smaller-level symmetries that affect the music at a level of phrase and motivic structure.
A clean hot-water drill was used to gain access to Subglacial Lake Whillans (SLW) in late January 2013 as part of the Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project. Over 3 days, we deployed an array of scientific tools through the SLW borehole: a downhole camera, a conductivity–temperature–depth (CTD) probe, a Niskin water sampler, an in situ filtration unit, three different sediment corers, a geothermal probe and a geophysical sensor string. Our observations confirm the existence of a subglacial water reservoir whose presence was previously inferred from satellite altimetry and surface geophysics. Subglacial water is about two orders of magnitude less saline than sea water (0.37–0.41 psu vs 35 psu) and two orders of magnitude more saline than pure drill meltwater (<0.002 psu). It reaches a minimum temperature of –0.55~C, consistent with depression of the freezing point by 7.019 MPa of water pressure. Subglacial water was turbid and remained turbid following filtration through 0.45 µm filters. The recovered sediment cores, which sampled down to 0.8 m below the lake bottom, contained a macroscopically structureless diamicton with shear strength between 2 and 6 kPa. Our main operational recommendation for future subglacial access through water-filled boreholes is to supply enough heat to the top of the borehole to keep it from freezing.
During disasters, the needs of victims outstrip available resources. Rapid assessment of patients must be performed; however, language barriers can be an impediment to efficient patient assessment, especially if interpreter resources are limited. Dependency on interpretive services requiring technology such a telephones, cell phones, and video conferencing may be inefficient, as they may be unavailable during disaster conditions. A low-tech, portable tool that aids in communication with non-English speakers would be beneficial. The medical emergency communication (MEC) book, developed at Children's Hospital Los Angeles, has the potential to be a useful tool in this capacity.
The goal of this pilot study was to compare the accuracy of a newly developed disaster-focused medical history obtained from Spanish-speaking patients or caregivers using the MEC book, compared to a control group with whom no book was used. Our hypothesis was that use of the MEC book improves accuracy of medical history taking between English-only speaking health care workers and Spanish-speaking patients better than a monolingual clinician trying to take a medical history without it. We anticipated a higher overall score in the group of subjects whose histories were taken using the MEC book than in the control group. Patient satisfaction with the MEC book also was measured. (Disaster Med Public Health Preparedness. 2013;0:1-6)
The Automated Meteorology–Ice/Indigenous species–Geophysics Observation System (AMIGOS) consists of a set of measurement instruments and camera(s) controlled by a single-board computer with a simplified Linux operating system and an Iridium satellite modem supporting two-way communication. Primary features of the system relevant to polar operations are low power requirements, daily data uploading, reprogramming, tolerance for low temperatures, and various approaches for automatic resets and recovery from low power or cold shutdown. Instruments include a compact weather station, single- or dual-frequency GPS, solar flux and reflectivity sensors, sonic snow gauges, simplified radio-echo sounder, and resistance thermometer string in the firn column. In the current state of development, there are two basic designs. One is intended for in situ observations of glacier conditions. The other supports a high-resolution camera for monitoring biological or geophysical systems from short distances (100 m to 20 km). The stations have been successfully used in several locations for operational support, monitoring rapid ice changes in response to climate change or iceberg drift, and monitoring penguin colony activity. As of August 2012, there are nine AMIGOS systems installed, all on the Antarctic continent or in the surrounding ocean.