High-efficiency vertically emitting coupler facilitated by three wave interaction gratings.

We designed a grating coupler optimized for normal incidence and numerically demonstrate near-unity coupling in a standard 220-nm-thick silicon-on-insulator (SOI) technology. Our design breaks the vertical symmetry within the grating region by implementing three scattering sites per local period. This technique removes the need for bottom reflectors or additional material layers and can be realized using only two lithography masks. Using adjoint method-based optimization, we engineer the coupling spectrum of the grating, balancing the trade-off between peak efficiency and bandwidth. Using this technique, we simulate three devices with peak coupling efficiencies ranging between 93.4 (-0.3 dB) and 98.6% (-0.06 dB) with corresponding 1 dB bandwidths between 48 and 8 nm all centered around 1.55 µm.

Ebola Virus Uses Tunneling Nanotubes as an Alternate Route of Dissemination.

Ebola virus (EBOV) disease is marked by rapid virus replication and spread. EBOV enters the cell by macropinocytosis and replicates in the cytoplasm, and nascent virions egress from the cell surface to infect neighboring cells. Here, we show that EBOV uses an alternate route to disseminate: tunneling nanotubes (TNTs). TNTs, an actin-based long-range intercellular communication system, allows for direct exchange of cytosolic constituents between cells. Using live, scanning electron, and high-resolution quantitative 3-dimensional microscopy, we show that EBOV infection of primary human cells results in the enhanced formation of TNTs containing viral nucleocapsids. TNTs promote the intercellular transfer of nucleocapsids in the absence of live virus, and virus could replicate in cells devoid of entry factors after initial stall. Our studies suggest an alternate model of EBOV dissemination within the host, laying the groundwork for further investigations into the pathogenesis of filoviruses and, importantly, stimulating new areas of antiviral design.

Are medical procedures that induce coughing or involve respiratory suctioning associated with increased generation of aerosols and risk of SARS-CoV-2 infection? A rapid systematic review.

BACKGROUND: The risk of transmission of SARS-CoV-2 from aerosols generated by medical procedures is a cause for concern. AIM: To evaluate the evidence for aerosol production and transmission of respiratory infection associated with procedures that involve airway suctioning or induce coughing/sneezing. METHODS: The review was informed by PRISMA guidelines. Searches were conducted in PubMed for studies published between January 1st, 2003 and October 6th, 2020. Included studies examined whether nasogastric tube insertion, lung function tests, nasendoscopy, dysphagia assessment, or suctioning for airway clearance result in aerosol generation or transmission of SARS-CoV-2, SARS-CoV, MERS, or influenza. Risk of bias assessment focused on robustness of measurement, control for confounding, and applicability to clinical practice. FINDINGS: Eighteen primary studies and two systematic reviews were included. Three epidemiological studies found no association between nasogastric tube insertion and acquisition of respiratory infections. One simulation study found low/very low production of aerosols associated with pulmonary lung function tests. Seven simulation studies of endoscopic sinus surgery suggested significant increases in aerosols but findings were inconsistent; two clinical studies found airborne particles associated with the use of microdebriders/drills. Some simulation studies did not use robust measures to detect particles and are difficult to equate to clinical conditions. CONCLUSION: There was an absence of evidence to suggest that the procedures included in the review were associated with an increased risk of transmission of respiratory infection. In order to better target precautions to mitigate risk, more research is required to determine the characteristics of medical procedures and patients that increase the risk of transmission of SARS-CoV-2.

Transportation capacity for patients with highly infectious diseases in Europe: a survey in 16 nations.

Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. In most European Union member states specialized isolation facilities are responsible for the management of such cases. Ground ambulances are often affiliated with those facilities because rapid relocation of patients is most desirable. To date, no pooled data on the accessibility, technical specifications and operational procedures for such transport capacities are available. During 2009, the 'European Network for HIDs' conducted a cross-sectional analysis of hospitals responsible for HID patients in Europe including an assessment of (a) legal aspects; (b) technical and infrastructure aspects; and (c) operational procedures for ground ambulances used for HID transport. Overall, 48 isolation facilities in 16 European countries were evaluated and feedback rates ranged from 78% to 100% (n = 37 to n = 48 centres). Only 46.8% (22/47) of all centres have both national and local guidelines regulating HID patient transport. If recommended, specific equipment is found in 90% of centres (9/10), but standard ambulances in only 6/13 centres (46%). Exclusive entrances (32/45; 71%) and pathways (30/44; 68.2%) for patient admission, as well as protocols for disinfection of ambulances (34/47; 72.3%) and equipment (30/43; 69.8%) exist in most centres. In conclusion, the availability and technical specifications of ambulances broadly differ, reflecting different preparedness levels within the European Union. Hence, regulations for technical specifications and operational procedures should be harmonized to promote patient and healthcare worker safety.

Injectional anthrax at a Scottish district general hospital.

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

Guidance on the use of respiratory and facial protection equipment.

Infectious micro-organisms may be transmitted by a variety of routes, and some may be spread by more than one route. Respiratory and facial protection is required for those organisms that are usually transmitted via the droplet/airborne route, or when airborne particles have been artificially created, such as during 'aerosol-generating procedures'. A range of personal protective equipment that provides different degrees of facial and respiratory protection is available. It is apparent from the recent experiences with severe acute respiratory syndrome and pandemic (H1N1) 2009 influenza that healthcare workers may have difficulty in choosing the correct type of facial and respiratory protection in any given clinical situation. To address this issue, the Scientific Development Committee of the Healthcare Infection Society established a short-life working group to develop guidance. The guidance is based upon a review of the literature, which is published separately, and expert consensus.

Sequencing and phylogenetic characterisation of a fatal Crimean - Congo haemorrhagic fever case imported into the United Kingdom, October 2012.

A patient with fever, and haemorrhagic symptoms was admitted to a hospital in Glasgow on 2 October 2012. Since he had returned from Afghanistan, serum samples were sent for diagnosis at the Rare and Imported Pathogens Laboratory, where a real-time reverse transcriptase-PCR diagnosis of Crimean ­ Congo haemorrhagic fever was made within 3 hrs after receipt of the sample. Hereafter the patient was transferred to a high-security infectious diseases unit in London but died on 6 October.

The Early External Cephalic Version (ECV) 2 Trial: an international multicentre randomised controlled trial of timing of ECV for breech pregnancies.

OBJECTIVE: To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section. DESIGN: An unblinded multicentred randomised controlled trial. SETTING: A total of 1543 women were randomised from 68 centres in 21 countries. POPULATION: Women with a singleton breech fetus at a gestational age of 33(0/7) weeks (231 days) to 35(6/7) weeks (251 days) of gestation were included. METHODS: Participants were randomly assigned to having a first ECV procedure between the gestational ages of 34(0/7) (238 days) and 35(6/7) weeks of gestation (early ECV group) or at or after 37(0/7) (259 days) weeks of gestation (delayed ECV group). MAIN OUTCOME MEASURES: The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth. RESULTS: Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P=0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P=0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P=0.07) between groups. CONCLUSION: External cephalic version at 34-35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth.

Identification from a bitemark in a wad of chewing gum.

A wad of used chewing gum recovered from the scene of a burglary contained impressions of human teeth. Casts of these impressions displayed unique morphological characteristics which were found to show concordance with corresponding features present on casts of the posterior teeth of a suspect.

The gel microdrop secretion assay: Identification of a low productivity subpopulation arising during the production of human antibody in CHO cells.

The long-term stability of high-level expression is the mostimportant factor to consider when choosing cell lines for the expression of recombinant proteins. Declining volumetricyields in large-scale fermentation can be caused by changes affecting the cell population as a whole such as loss in viability, depletion of nutrients or accumulation of metabolites affecting cell growth. Alternatively, geneticinstability may lead to the outgrowth of a less productive,metabolically favored sub-population. Currently a variety ofparameters are measured to monitor the condition of cells infermenters including glucose uptake, lactate accumulation andoxygen consumption; in addition, periodic viable cell countsallow the determination of the growth rate and viability of the population. All of these methods measure the condition ofthe cell population as a whole and changes must involve a significantly large proportion of the total culture in orderto be detectable. Here we report on a method that allows theevaluation of the productivity of individual cells. Using the gel microdrop secretion assay, we detected the appearance ofa sub-population of cells with lower productivity. Subsequentanalysis of the culture confirmed the existence of lower productivity cells with a lower vector copy number. Therefore,the single cell secretion assay proved to be a rapid method todetect and isolate a low productivity variant of the producer cell line.

Prosaposin, a neurotrophic factor: presence and properties in milk.

The presence of prosaposin, the precursor of the sphingolipid activator proteins (saposins A, B, C, and D), was investigated in bovine milk. The milk proteins were resolved by SDS-PAGE, blotted onto nitrocellulose sheets, and immunostained. Each of three appropriate antibodies defined a band from milk that matched in mobility the reference prosaposin from human milk at a relative molecular mass of 66,000. Evidence of mature saposins was not found. Prosaposin was detected in milk of other species chimpanzee, rhesus, goat, and rat) and was consistently observed in samples of retail milk and from individual cows. Prosaposin was not associated with particulate matter (fat globules, casein micelles, membrane fragments, and somatic cells) in either human or bovine milk. Rather, prosaposin was located exclusively in the milk serum (whey), existing in monomeric form, as revealed by nondenaturing PAGE. A commercial whey protein concentrate (75% protein) appeared to retain milk prosaposin quantitatively. Properties that were useful in the isolation of prosaposin from milk were its binding to concanavalin A, retention by anion-exchange cellulose, and resistance to precipitation by heating. The possibility that bovine milk prosaposin nutritionally benefits the humans who consume it is enhanced by the fact that only part of its saposin C segment is required for neurotrophic activity.

Experimenting with feasibility of telemedicine in Alaska: successes and lessons learned.

Alaska may be ideally suited as a test site for telemedicine. It is by far the nation's largest state, with a population of only 550,000 clustered around a few cities and towns or widely spread across an area almost two and a half times as large as Texas. Its ratio of doctors to patients is the second lowest in the nation, and the cost of medical care exceeds that in the lower 48 states by 90%. Almost half of its residents are affiliated with the federal government in some way. Active duty and retired members of the military and their families (including children) represent 70,000 of the state's residents, and another 160,000 are affiliated with the Coast Guard, the Indian Health Service, and the Department of Veteran Affairs. In 1995, a telemedicine initiative was launched under the auspices of the 3rd Medical Center at Elmendorf Air Force Base. Its mission was to integrate video conferencing and store-and-forward technology into patient care. Brief but well-documented efforts yielded many valuable lessons on how relatively simple, low-bandwidth technology can be effectively used and its limitations. In addition, unexpected changes were observed in the way health care was delivered. This experience should provide valuable lessons for those embarking on this path to health care delivery.

Prosaposin and prosaptide, a peptide from prosaposin, induce an increase in ganglioside content on NS20Y neuroblastoma cells.

Prosaposin has been recently identified as a neurotrophic factor eliciting differentiation in neuronal cultured cells (NS20Y). In this paper we investigate whether prosaposin and its active peptide (prosaptide) may modify the ganglioside pattern in neuroblastoma cells. The analysis by high performance thin layer chromatography did not reveal qualitative changes in the ganglioside pattern of NS20Y cells incubated in the presence of prosaposin, compared to control cells, but it did reveal an increase of the content of all three major resorcinol positive bands (GM3, GM2, GD1a). Cytofluorimetric and immunofluorescence microscopic analysis revealed that the increase of the ganglioside content was at the plasma membrane level. These findings suggest that the neurotrophic activity of prosaposin on NS20Y neuroblastoma cells might be mediated in part by the increase of cell surface gangliosides.

Identification of the neurotrophic factor sequence of prosaposin.

Prosaposin, recently identified as a neurotrophic factor (1), is the precursor of saposins A, B, C, and D. The neurotrophic activity of prosaposin resides in the saposin C domain. We have pinpointed the active sequence to a linear 12-mer located in the NH2-terminal sequence of saposin C (LIDNNKTEKEIL). Nanomolar concentrations of a 22-mer peptide encompassing this region stimulated neurite outgrowth and choline acetyltransferase activity, and prevented cell death in neuroblastoma cells. In primary cerebellar granule cells, the 22-mer also stimulated neurite outgroth. Studies of the neuroblastoma line NS20Y using a radiolabeled 18-mer from the neurotrophic region identified a high-affinity (Kd = 70 pM) binding site indicative of receptor-ligand interaction. The 22-mer stimulated protein phosphorylation of several proteins, some of which were tyrosine-phosphorylated after brief exposure similar to saposin C. Circular dichroism studies demonstrated that the 22-mer was converted from a random to a helical structure by addition of ganglioside GM1. The results are consistent with receptor-ligand binding by the peptide initiating a signal transduction cascade and resulting in neuronal differentiation.

Identification of prosaposin as a neurotrophic factor.

Prosaposin was identified as a neurotrophic factor stimulating neurite outgrowth in murine neuroblastoma (NS20Y) cells and choline acetyltransferase (ChAT) activity in human neuroblastoma (SK-N-MC) cells. The four naturally occurring saposins, which are derived by proteolytic processing of prosaposin, were tested for activity. Saposin C was found to be active, whereas saposins A, B, and D were inactive as neurotrophic factors. Dose-response curves demonstrated that nanomolar concentrations of prosaposin and saposin C stimulated neurite outgrowth and increased ChAT activity. Prosaposin and saposin C exerted activity by a mechanism independent of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3. Binding assays utilizing saposin C as a ligand gave two saturable binding constants, a high-affinity (Kd = 19 pM) and a low-affinity (Kd = 1 nM) constant, with 2000 and 15,000 sites per NS20Y cell, respectively. Phosphorylation stimulation experiments demonstrated that brief treatment with prosaposin or saposin C enhanced phosphorylation of a variety of proteins, some of which contained phosphorylated tyrosine(s). Since both cell lines were also stimulated by ciliary neurotrophic factor (CNTF) as well as prosaposin, inhibition was tested by utilizing an anti-gp130 monoclonal antibody, which specifically inhibited CNTF stimulation; this antibody did not inhibit prosaposin or saposin C stimulation. These results indicate that prosaposin and saposin C are neurotrophic factors which initiate signal transduction by binding to a high-affinity receptor that induces protein phosphorylation.

Radiologic diagnosis of traumatic occipitovertebral dissociation: 1. Normal occipitovertebral relationships on lateral radiographs of supine subjects.

OBJECTIVE: The objective of this study was to establish a reliable method of determining the normal occipitovertebral relationship seen on lateral radiographs of the cervical spine in supine subjects in order to recognize alterations of normal that characterize occipitovertebral dissociation. MATERIALS AND METHODS: We define the rostral extension of the posterior cortex of the axis body as the posterior axial line, the distance between the basion (tip of the clivus) and the posterior axial line as the basion-axial interval, and the distance between the basion and the rostral tip of the dens as the basion-dental interval. The basion-axial interval was measured on horizontal-beam lateral radiographs of the cervical spine obtained at a 40-in. (1-m) target-film distance in 400 adults who had no occipitovertebral abnormalities. The basion-dental interval was measured in 374 (94%) of the same cohort of adults in whom the superior cortex of the dens could be identified. All radiographs were obtained with the subjects supine. The excursion of the basion referable to the posterior axial line was determined on lateral flexion and extension radiographs of 25 of the same cohort of adults. The basion-axial interval only was measured on radiographs of 50 children 2-13 years old who had no occipitovertebral abnormalities. RESULTS: In 392 (98%) of the 400 adults, the basion-axial interval did not exceed 12 mm. In eight adults (2%), the basion was situated 1-4 mm posterior to the posterior axial line. The excursion of the basion in flexion and extension ranged from 0 to 10 mm, but did not exceed the 12-mm limit of normal. The basion translated posterior to the posterior axial line in six (24%) of the 25 adults in whom excursion was measured. Of the 400 adults, the basion-dental interval ranged from 2 to 15 mm (mean, 7.5 +/- 4.3 mm [2 SD]); the 95% accuracy range was 11.8 mm. In all 50 children (100%), the basion was within the normal basion-axial interval of 12 mm, and in no instance was the basion posterior to the posterior axial line. CONCLUSION: In adults, the occipitovertebral junction can be considered normal when both the basion-axial interval and basion-dental interval are 12 mm or less. In children less than 13 years old, the basion-dental interval is not reliable because of the variable age at which complete ossification and fusion of the dens occur. The normal basion-axial interval in children did not exceed 12 mm. This simple, anatomically based method of recognizing normal occipitovertebral relationships facilitates identification of occipitovertebral dissociation.

Radiologic diagnosis of traumatic occipitovertebral dissociation: 2. Comparison of three methods of detecting occipitovertebral relationships on lateral radiographs of supine subjects.

OBJECTIVE: The purpose of this study was to describe a method for recognizing acute traumatic occipitoatlantal dissociation that uses the basion-axial interval and basion-dental interval and to compare the accuracy of this method with the accuracies of two other methods: the Powers ratio and the x-line method. MATERIALS AND METHODS: Lateral radiographs of the cervical spine of 37 patients in whom the diagnosis of occipitoatlantal dissociation had been made on the basis of the relationship of the basion to the tip of the dens, the Powers ratio, and/or the x-line method were reviewed. Retrospectively, the occipitoatlantal junction of each was reassessed by using the the Powers ratio, the x-line, and the basion-axial interval-basion-dental interval methods. Independently, the neurologic findings at admission and the final neurologic diagnosis at discharge were obtained from the hospital records and were compared with the radiologic findings to determine the degree of radiologic-clinical correlation. RESULTS: Three groups of patients were identified by analyzing the basion-axial and basion-dental intervals of the occipitovertebral junction and related clinical findings. Twenty-three patients (group 1) had frank occipitoatlantal dislocation. Eight patients (group 2) had incomplete occipitoatlantal dissociation, which was defined as occipitoatlantal subluxation. The remaining six patients (group 3) had normal radiologic and clinical findings. Four patterns of occipitovertebral dissociation were identified: purely anterior (4/31, 13%), purely distracted (6/31, 19%), concomitantly anterior and distracted (20/31, 65%), and purely posterior (1/31, 3%). Regardless of the magnitude or direction of occipitoatlantal dissociation, the basion-axial interval-basion-dental interval method correctly identified the abnormality and the type of each. Positive clinical correlation was found in 13 (57%) of the 23 patients in group 1 and in 100% of the eight and six patients in groups 2 and 3, respectively. Neither the Powers ratio nor the x-line method could be applied in 17 (46%) of 37 cases, either because the opisthion could not be detected on the radiographs or because fusion of the posterior arch of C1 had not occurred. In the remaining 20 patients in whom the Powers ratio and the x-line method were applicable, the type of occipitoatlantal dissociation was correctly identified by the Powers ratio in 12 (60%) and by the x-line method in four (20%). Neither the Powers ratio nor the x-line method was applicable in three (50%) of the six patients in whom analysis by the basion-axial interval-basion-dental interval method and clinical findings showed no occipitoatlantal abnormality. Normal occipitovertebral anatomy was correctly identified by the Powers ratio in the remaining three patients (50%) and by the x-line method in two (33%). CONCLUSION: Direct measurement of occipitovertebral skeletal relationships altered by occipitoatlantal dissociation using the basion-axial and basion-dental intervals provides the most accurate radiologic assessment of this injury.

Occurrence of prosaposin as a neuronal surface membrane component.

Prosaposin is a precursor of four saposins that are required for the lysosomal hydrolysis of sphingolipids by specific hydrolases. Besides its precursor role, prosaposin also exists as a secreted protein. The present investigation reveals that prosaposin also exists as an integral component of the surface membranes of neuronal cells. Subcellular fractionation studies demonstrate that the membrane-bound prosaposin occurs specifically in plasma membranes of NS20Y rat neuroblastoma cells. An immunohistochemical study of the neuroblastoma cells using rat prosaposin-specific antibodies also showed that a portion of prosaposin is located on the surface of neurites as well as on cell bodies. Similar histochemical studies with antibodies that specifically recognized human prosaposin revealed the presence of prosaposin in dendrites, axons, and cell bodies of subcortical and spinal cord neurons in both human adult brain and in fetal brain (24-wk gestation). These findings suggest an important role of prosaposin in neuronal development.