Exploring the action landscape with trial world-lines

The Hamilton action principle, also known as the principle of least action, and Lagrange equations are an integral part of advanced undergraduate mechanics. At present, substantial efforts are ongoing to suitably incorporate the action principle in introductory physics courses. Although the Hamilton principle is oft stated as "the action for any nearby trial world-line is greater than the action for the classical world-line", the landscape of action in the space of world-lines is rarely explored. Here, for three common problems in introductory physics - a free particle, a uniformly accelerating particle, and a simple harmonic oscillator - we present families of trial world-lines, characterized by a few parameters, that evolve continuously from their respective classical world-lines. With explicit analytical expressions available for the action, they permit a graphical visualization of the action landscape in the space of nearby world-lines. Although these trial world-lines form only a subset of the space of all nearby world-lines, they provide a pedagogical tool that complements the traditional Lagrange equation approach and is well-suited for advanced undergraduate students.Comment: 9 pages, 6 figures, significant structural revisio

Emergency department triage nurse initiated pain management

Objectives: 1) To determine the time difference to analgesia administration for patients with painful limb conditions using an emergency triage nurse initiated pain management protocol versus analgesia administration by emergency doctors after consultation. 2) To determine the frequency of adverse events following such a protocol implementation. Methods: For emergency department patients with isolated limb injury or inflammation, a triage nurse initiated pain management policy was implemented in 2004. The protocol did not require the triage nurse to consult a physician. The triage nurse would record the chief complaint, past medical history, allergy, medication, vital signs, and pain severity using a combination of 0 to 10 numerical and face pain scales. Unless contraindicated, the triage nurse would offer intramuscular ketorolac to patients with pain score ≥5. Medical charts of patients fulfilling the inclusion criteria were reviewed from 1 to 30 September 2004. Results: Two hundred seventy-three patients were reviewed, of whom 73.3% were men and the overall mean age was 40.1 years (standard deviation SD 19.5). Two hundred and nine patients (76.6%) had pain score recorded at triage, and the median was 6. One hundred and five patients (38.5%) received analgesia, of which 69 were given by triage nurses and 36 by physicians. The mean time interval for analgesia given by triage nurse was 2.5 minutes (SD 8.9) and that for physician was significantly longer (p<0.0001) at 68.2 minutes (SD 59.5). There was no adverse drug reaction observed in patients who received intramuscular ketorolac given by triage nurses. Conclusion: The time interval for pain relief of emergency department patients with painful limb conditions was reduced when the triage nurse initiated pain management

Processing of ultrafine-size particulate metal matrix composites by advanced shear technology

Copyright @ 2009 ASM International. This paper was published in Metallurgical & Materials Transactions A 40A(3) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Lack of efficient mixing technology to achieve a uniform distribution of fine-size reinforcement within the matrix and the high cost of producing components have hindered the widespread adaptation of particulate metal matrix composites (PMMCs) for engineering applications. A new rheo-processing method, the melt-conditioning high-pressure die-cast (MC-HPDC) process, has been developed for manufacturing near-net-shape components of high integrity. The MC-HPDC process adapts the well-established high shear dispersive mixing action of a twin-screw mechanism to the task of overcoming the cohesive force of the agglomerates under a high shear rate and high intensity of turbulence. This is followed by direct shaping of the slurry into near-net-shape components using an existing cold-chamber die-casting process. The results indicate that the MC-HPDC samples have a uniform distribution of ultrafine-sized SiC particles throughout the entire sample in the as-cast condition. Compared to those produced by conventional high-pressure die casting (HPDC), MC-HPDC samples have a much improved tensile strength and ductility.EP-SR

Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells

Uroplakins (UPs) are major differentiation products of urothelial umbrella cells and play important roles in forming the permeability barrier and in the expansion/stabilization of the apical membrane. Further, UPIa serves as a uropathogenic Escherichia coli receptor. Although it is understood that UPs are delivered to the apical membrane via fusiform vesicles (FVs), the mechanisms that regulate this exocytic pathway remain poorly understood. Immunomicroscopy of normal and mutant mouse urothelia show that the UP-delivering FVs contained Rab8/11 and Rab27b/Slac2-a, which mediate apical transport along actin filaments. Subsequently a Rab27b/Slp2-a complex mediated FV–membrane anchorage before SNARE-mediated and MAL-facilitated apical fusion. We also show that keratin 20 (K20), which forms a chicken-wire network ∼200 nm below the apical membrane and has hole sizes allowing FV passage, defines a subapical compartment containing FVs primed and strategically located for fusion. Finally, we show that Rab8/11 and Rab27b function in the same pathway, Rab27b knockout leads to uroplakin and Slp2-a destabilization, and Rab27b works upstream from MAL. These data support a unifying model in which UP cargoes are targeted for apical insertion via sequential interactions with Rabs and their effectors, SNAREs and MAL, and in which K20 plays a key role in regulating vesicular trafficking

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Association of Common SIX6 Polymorphisms With Peripapillary Retinal Nerve Fiber Layer Thickness: The Singapore Chinese Eye Study

PURPOSE. Recently the common SIX6 missense variant rs33912345 was found to be highly associated with glaucoma. The aim of this study was to investigate the association between this SIX6 variant and peripapillary retinal nerve fiber layer (RNFL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) in a population setting. METHODS. Study subjects were enrolled from the Singapore Chinese Eye Study (SCES), a population-based survey of Singaporean Chinese aged 40 years or older. Subjects underwent a comprehensive ocular examination. Spectral-domain OCT was used to measure RNFL thicknesses. Genotyping of SIX6 rs33912345 (Asn141His) was performed using HumanExome BeadChip. RESULTS. A total of 2129 eyes from 1243 SCES subjects (mean age: 55.0 6 7.4 years) with rs33912345 genotype data and SD-OCT images were included for the analysis. Of these, 26 eyes of 21 subjects had glaucoma. The frequency of rs33912345 risk variant C (His141) was 80% in the study subjects. Each rs33912345 C allele was associated with a decrease of 1.44 lm in RNFL thickness after adjusting for age, sex, genetic principal components, and axial length (P ¼ 0.001). These associations remained similar in 2096 nonglaucoma eyes in which each C allele was associated with a decrease of 1.39 lm in RNFL thickness (P ¼ 0.001). The strongest association was observed in the superior RNFL sector (a decrease of 2.83 lm per risk allele, P < 0.001) followed by the inferior RNFL sector (a decrease of 2.24 lm per risk allele, P ¼ 0.003), while the association did not reach significance in the nasal and temporal sectors. CONCLUSIONS. Nonglaucomatous individuals with the SIX6 missense variant have reduced RNFL thickness in regions known to be particularly affected in those with glaucoma. This may be the primary mechanism for increased risk of POAG in individuals who carry the SIX6 His141 risk variant

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Reliability of Rapid Diagnostic Tests in Diagnosing Pregnancy-Associated Malaria in North-Eastern Tanzania.

Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen™) or HRP-2 only (Paracheck Pf® and ParaHIT®f), microscopy and nested Plasmodium species diagnostic PCR. From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 -1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool