Lipids with negative spontaneous curvature decrease the solubility of the cancer drug paclitaxel in liposomes.

Paclitaxel (PTX) is a hydrophobic small-molecule cancer drug that loads into the membrane (tail) region of lipid carriers such as liposomes and micelles. The development of improved lipid-based carriers of PTX is an important objective to generate chemotherapeutics with fewer side effects. The lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) show propensity for fusion with other lipid membranes, which has led to their use in lipid vectors of nucleic acids. We hypothesized that DOPE and GMO could enhance PTX delivery to cells through a similar membrane fusion mechanism. As an important measure of drug carrier performance, we evaluated PTX solubility in cationic liposomes containing GMO or DOPE. Solubility was determined by time-dependent kinetic phase diagrams generated from direct observations of PTX crystal formation using differential-interference-contrast optical microscopy. Remarkably, PTX was much less soluble in these liposomes than in control cationic liposomes containing univalent cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), which are not fusogenic. In particular, PTX was not substantially soluble in GMO-based cationic liposomes. The fusogenicity of DOPE and GMO is related to the negative spontaneous curvature of membranes containing these lipids, which drives formation of nonlamellar self-assembled phases (inverted hexagonal or gyroid cubic). To determine whether PTX solubility is governed by lipid membrane structure or by local intermolecular interactions, we used synchrotron small-angle X-ray scattering. To increase the signal/noise ratio, we used DNA to condense the lipid formulations into lipoplex pellets. The results suggest that local intermolecular interactions are of greater importance and that the negative spontaneous curvature-inducing lipids DOPE and GMO are not suitable components of liposomal carriers for PTX delivery.

Lipids with negative spontaneous curvature decrease the solubility of the cancer drug paclitaxel in liposomes.

Paclitaxel (PTX) is a hydrophobic small-molecule cancer drug that loads into the membrane (tail) region of lipid carriers such as liposomes and micelles. The development of improved lipid-based carriers of PTX is an important objective to generate chemotherapeutics with fewer side effects. The lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) show propensity for fusion with other lipid membranes, which has led to their use in lipid vectors of nucleic acids. We hypothesized that DOPE and GMO could enhance PTX delivery to cells through a similar membrane fusion mechanism. As an important measure of drug carrier performance, we evaluated PTX solubility in cationic liposomes containing GMO or DOPE. Solubility was determined by time-dependent kinetic phase diagrams generated from direct observations of PTX crystal formation using differential-interference-contrast optical microscopy. Remarkably, PTX was much less soluble in these liposomes than in control cationic liposomes containing univalent cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), which are not fusogenic. In particular, PTX was not substantially soluble in GMO-based cationic liposomes. The fusogenicity of DOPE and GMO is related to the negative spontaneous curvature of membranes containing these lipids, which drives formation of nonlamellar self-assembled phases (inverted hexagonal or gyroid cubic). We used synchrotron small-angle x-ray scattering to determine whether PTX solubility is governed by lipid membrane structure (condensed with DNA in pellet form) or by local intermolecular interactions. The results suggest that local intermolecular interactions are of greater importance and that the negative spontaneous curvature-inducing lipids DOPE and GMO are not suitable components of lipid carriers for PTX delivery regardless of carrier structure.

Feasibility of a Novel ECG Electrode Placement Method in Newborn Infants.

BACKGROUND: International newborn resuscitation guidelines recommend electrocardiogram (ECG) heart rate (HR) monitoring at birth. We evaluated the application time of pre-set ECG electrodes fixed to a polyethene patch allowing adhesive-free attachment to the wet skin of the newborn chest. OBJECTIVES: Using a three-electrode pre-set ECG patch configuration, application success was calculated using video analysis and measured at three time points, the time to (1) apply electrodes; (2) detect recognizable QRS complexes after application; and (3) display a HR after application. METHOD: A prospective observational study in two UK tertiary maternity units was undertaken with 71 newborns including 23 who required resuscitation. RESULTS: The median (IQR) time for ECG patch application was 8 (6-10) seconds, detection of recognizable QRS complexes 8 (2-12) seconds, and time to output HR was 23 (15-37) seconds. CONCLUSION: Pre-set ECG chest electrodes allow rapid HR information at birth without electrode detachment or compromising skin integrity.

Assessment of a Program for SARS-CoV-2 Screening and Environmental Monitoring in an Urban Public School District.

Importance: Scalable programs for school-based SARS-CoV-2 testing and surveillance are needed to guide in-person learning practices and inform risk assessments in kindergarten through 12th grade settings. Objectives: To characterize SARS-CoV-2 infections in staff and students in an urban public school setting and evaluate test-based strategies to support ongoing risk assessment and mitigation for kindergarten through 12th grade in-person learning. Design, Setting, and Participants: This pilot quality improvement program engaged 3 schools in Omaha, Nebraska, for weekly saliva polymerase chain reaction testing of staff and students participating in in-person learning over a 5-week period from November 9 to December 11, 2020. Wastewater, air, and surface samples were collected weekly and tested for SARS-CoV-2 RNA to evaluate surrogacy for case detection and interrogate transmission risk of in-building activities. Main Outcomes and Measures: SARS-CoV-2 detection in saliva and environmental samples and risk factors for SARS-CoV-2 infection. Results: A total of 2885 supervised, self-collected saliva samples were tested from 458 asymptomatic staff members (mean [SD] age, 42.9 [12.4] years; 303 women [66.2%]; 25 Black or African American [5.5%], 83 Hispanic [18.1%], 312 White [68.1%], and 35 other or not provided [7.6%]) and 315 students (mean age, 14.2 [0.7] years; 151 female students [48%]; 20 Black or African American [6.3%], 201 Hispanic [63.8%], 75 White [23.8%], and 19 other race or not provided [6.0%]). A total of 46 cases of SARS-CoV-2 (22 students and 24 staff members) were detected, representing an increase in cumulative case detection rates from 1.2% (12 of 1000) to 7.0% (70 of 1000) among students and from 2.1% (21 of 1000) to 5.3% (53 of 1000) among staff compared with conventional reporting mechanisms during the pilot period. SARS-CoV-2 RNA was detected in wastewater samples from all pilot schools as well as in air samples collected from 2 choir rooms. Sequencing of 21 viral genomes in saliva specimens demonstrated minimal clustering associated with 1 school. Geographical analysis of SARS-CoV-2 cases reported district-wide demonstrated higher community risk in zip codes proximal to the pilot schools. Conclusions and Relevance: In this study of staff and students in 3 urban public schools in Omaha, Nebraska, weekly screening of asymptomatic staff and students by saliva polymerase chain reaction testing was associated with increased SARS-CoV-2 case detection, exceeding infection rates reported at the county level. Experiences differed among schools, and virus sequencing and geographical analyses suggested a dynamic interplay of school-based and community-derived transmission risk. Collectively, these findings provide insight into the performance and community value of test-based SARS-CoV-2 screening and surveillance strategies in the kindergarten through 12th grade educational setting.

A tribute to Dr. Serge N. Timasheff, our mentor.

Dr. Serge N. Timasheff, our mentor and friend, passed away in 2019. This article is a collection of tributes from his postdoctoral fellows, friends, and daughter, who all have been associated with or influenced by him or his research. Dr. Timasheff is a pioneer of research on thermodynamic linkage between ligand interaction and macromolecular reaction. We all learned a great deal from Dr. Timasheff, not only about science but also about life.

Smartphone monitoring of in-ambulance vibration and noise.

Transferring sick premature infants between hospitals increases the risk of severe brain injury, potentially linked to the excessive exposure to noise, vibration and driving-related accelerations. One method of reducing these levels may be to travel along smoother and quieter roads at an optimal speed, however this requires mass data on the effect of roads on the environment within ambulances. An app for the Android operating system has been developed for the purpose of recording vibration, noise levels, location and speed data during ambulance journeys. Smartphone accelerometers were calibrated using sinusoidal excitation and the microphones using calibrated pink noise. Four smartphones were provided to the local neonatal transport team and mounted on their neonatal transport systems to collect data. Repeatability of app recordings was assessed by comparing 37 journeys, made during the study period, along an 8.5 km single carriageway. The smartphones were found to have an accelerometer accurate to 5% up to 55 Hz and microphone accurate to 0.8 dB up to 80 dB. Use of the app was readily adopted by the neonatal transport team, recording more than 97,000 km of journeys in 1 year. To enable comparison between journeys, the 8.5 km route was split into 10 m segments. Interquartile ranges for vehicle speed, vertical acceleration and maximum noise level were consistent across all segments (within 0.99 m . s-1, 0.13 m · s-2 and 1.4 dB, respectively). Vertical accelerations registered were representative of the road surface. Noise levels correlated with vehicle speed. Android smartphones are a viable method of accurate mass data collection for this application. We now propose to utilise this approach to reduce potential harmful exposure, from vibration and noise, by routing ambulances along the most comfortable roads.

Accurate neonatal heart rate monitoring using a new wireless, cap mounted device.

AIM: A device for newborn heart rate (HR) monitoring at birth that is compatible with delayed cord clamping and minimises hypothermia risk could have advantages over current approaches. We evaluated a wireless, cap mounted device (fhPPG) for monitoring neonatal HR. METHODS: A total of 52 infants on the neonatal intensive care unit (NICU) and immediately following birth by elective caesarean section (ECS) were recruited. HR was monitored by electrocardiogram (ECG), pulse oximetry (PO) and the fhPPG device. Success rate, accuracy and time to output HR were compared with ECG as the gold standard. Standardised simulated data assessed the fhPPG algorithm accuracy. RESULTS: Compared to ECG HR, the median bias (and 95% limits of agreement) for the NICU was fhPPG -0.6 (-5.6, 4.9) vs PO -0.3 (-6.3, 6.2) bpm, and ECS phase fhPPG -0.5 (-8.7, 7.7) vs PO -0.1 (-7.6, 7.1) bpm. In both settings, fhPPG and PO correlated with paired ECG HRs (both R2  = 0.89). The fhPPG HR algorithm during simulations demonstrated a near-linear correlation (n = 1266, R2  = 0.99). CONCLUSION: Monitoring infants in the NICU and following ECS using a wireless, cap mounted device provides accurate HR measurements. This alternative approach could confer advantages compared with current methods of HR assessment and warrants further evaluation at birth.

Finding Comfortable Routes for Ambulance Transfers of Newborn Infants.

Early inter-hospital ambulance transport of premature babies is associated with more severe brain injury. The mechanism is unclear, but they are exposed to excessive noise and vibration. Smart-routing may help minimise these exposure levels and potentially improve outcomes.An app for Android smartphones was developed to collect vibration, noise and location data during ambulance journeys. Four smartphones, with the app installed, were provided to the local neonatal transport group to attach to their incubator trolleys. An example of route comparison was performed on the roads used between Nottingham City Hospital (NCH) and Leicester Royal Infirmary (LRI).Almost 1,700 journeys were recorded over the space of a year. 39 of these journeys travelled from NCH to LRI, comprising of 9 different routes. Analysis was performed on all recorded data which travelled along each road. For routes from NCH to LRI, the route with least vibration was also the quickest. Noise levels, however, were found to increase with vehicle speed. Ambulance drivers in the study did not tend to take the quickest, smoothest or quietest route.Android smartphones are a practical method of gathering information about the in-ambulance environment. Routes were found to vary in vibration, noise and speed, suggesting these could be minimised. The next step is to combine recorded and clinical data to try and define an ideal neonatal comfort metric which can then be fed into the routing. Roll-out of the app around the UK is also planned.Clinical relevance-Transferring preterm neonatal infants to specialist units lead to worse outcomes. By reducing the levels of vibration and noise the infants are exposed to during transport, we hope to improve outcomes.

Growth Spectrum Complexity Dictates Aromatic Intensity in Coriander (Coriandrum sativum L.).

Advancements in availability and specificity of light-emitting diodes (LEDs) have facilitated trait modification of high-value edible herbs and vegetables through the fine manipulation of spectra. Coriander (Coriandrum sativum L.) is a culinary herb, known for its fresh, citrusy aroma, and high economic value. Studies into the impact of light intensity and spectrum on C. sativum physiology, morphology, and aroma are limited. Using a nasal impact frequency panel, a selection of key compounds associated with the characteristic aroma of coriander was identified. Significant differences (P < 0.05) were observed in the concentration of these aromatics between plants grown in a controlled environment chamber under the same photosynthetic photon flux density (PPFD) but custom spectra: red (100%), blue (100%), red + blue (RB, 50% equal contribution), or red + green + blue (RGB, 35.8% red: 26.4% green: 37.8% blue) wavelengths. In general, the concentration of aromatics increased with increasing numbers of wavelengths emitted alongside selective changes, e.g., the greatest increase in coriander-defining E-(2)-decenal occurred under the RGB spectrum. This change in aroma profile was accompanied by significant differences (P < 0.05) in light saturated photosynthetic CO2 assimilation, water-use efficiency (Wi), and morphology. While plants grown under red wavelengths achieved the greatest leaf area, RB spectrum plants were shortest and had the highest leaf:shoot ratio. Therefore, this work evidences a trade-off between sellable commercial morphologies with a weaker, less desirable aroma or a less desirable morphology with more intense coriander-like aromas. When supplemental trichromatic LEDs were used in a commercial glasshouse, the majority of compounds, with the exception of linalool, also increased showing that even as a supplement additional wavelength can modify the aromatic profile increasing its complexity. Lower levels of linalool suggest these plants may be more susceptible to biotic stress such as herbivory. Finally, the concentration of coriander-defining aromatics E-(2)-decenal and E-(2)-hexenal was significantly higher in supermarket pre-packaged coriander leaves implying that concentrations of aromatics increase after excision. In summary, spectra can be used to co-manipulate aroma profile and plant form with increasing spectral complexity leading to greater aromatic complexity and intensity. We suggest that increasing spectral complexity progressively stimulates signaling pathways giving rise to valuable economic traits.

PEGylation of Paclitaxel-Loaded Cationic Liposomes Drives Steric Stabilization of Bicelles and Vesicles thereby Enhancing Delivery and Cytotoxicity to Human Cancer Cells.

Poly(ethylene glycol) (PEG) is a polymer used widely in drug delivery to create "stealth" nanoparticles (NPs); PEG coatings suppress NP detection and clearance by the immune system and beneficially increase NP circulation time in vivo. However, NP PEGylation typically obstructs cell attachment and uptake in vitro compared to the uncoated equivalent. Here, we report on a cationic liposome (CL) NP system loaded with the hydrophobic cancer drug paclitaxel (PTX) in which PEGylation (i.e., PEG-CLPTX NPs) unexpectedly enhances, rather than diminishes, delivery efficacy and cytotoxicity to human cancer cells. This highly unexpected enhancement occurs even when the PEG-chains coating the NP are in the transition regime between the mushroom and brush conformations. Cryogenic transmission electron microscopy (TEM) of PEG-CLPTX NPs shows that PEG causes the proliferation of a mixture of sterically stabilized nanometer-scale vesicles and anisotropic micelles (e.g., bicelles). Remarkably, the onset of bicelles at sub-monolayer concentrations of the PEG coat has to our knowledge not been previously reported; it was previously thought that PEG-lipid in this composition regime was incorporated into vesicles but did not alter their shape. Confocal microscopy and flow cytometry reveal significantly greater PTX cell uptake from stabilized PEG-CLPTX NPs (vesicles and bicelles) in contrast to bare CLPTX NPs, which can aggregate in cell medium. This underscores the ability of steric stabilization to facilitate NP entry into cells via distinct size-dependent endocytic pathways, some of which cannot transport large NP aggregates into cells. This study highlights the value of understanding how PEGylation alters NP shape and structure, and thus NP efficacy, to design next-generation stealth drug carriers that integrate active cell-targeting strategies into NPs for in vivo delivery.

The impact of post-fall huddles on repeat fall rates and perceptions of safety culture: a quasi-experimental evaluation of a patient safety demonstration project.

BACKGROUND: Conducting post-fall huddles is considered an integral component of a fall-risk-reduction program. However, there is no evidence linking post-fall huddles to patient outcomes or perceptions of teamwork and safety culture. The purpose of this study is to determine associations between conducting post-fall huddles and repeat fall rates and between post-fall huddle participation and perceptions of teamwork and safety culture. METHODS: During a two-year demonstration project, we developed a system for 16 small rural hospitals to report, benchmark, and learn from fall events, and we trained them to conduct post-fall huddles. To calculate a hospital's repeat fall rate, we divided the total number of falls reported by the hospital by the number of unique medical record numbers associated with each fall. We used Spearman correlations with exact P values to determine the association between the proportion of falls followed by a huddle and the repeat fall rate. At study end, we used the TeamSTEPPS® Teamwork Perceptions Questionnaire (T-TPQ) to assess perceptions of teamwork support for fall-risk reduction and the Hospital Survey on Patient Safety Culture (HSOPS) to assess perceptions of safety culture. We added an item to the T-TPQ for respondents to indicate the number of post-fall huddles in which they had participated. We used a binary logistic regression with a logit link to examine the effect of participation in post-fall huddles on respondent-level percent positive T-TPQ and HSOPS scores. We accounted for clustering of respondents within hospitals with random effects using the GLIMMIX procedure in SAS/STAT. RESULT: Repeat fall rates were negatively associated with the proportion of falls followed by a huddle. As compared to hospital staff who did not participate in huddles, those who participated in huddles had more positive perceptions of four domains of safety culture and how team structure, team leadership, and situation monitoring supported fall-risk reduction. CONCLUSIONS: Post-fall huddles may reduce the risk of repeat falls. Staff who participate in post-fall huddles are likely to have positive perceptions of teamwork support for fall-risk reduction and safety culture because huddles are a team-based approach to reporting, adapting, and learning.

Evaluating the use of multiteam systems to manage the complexity of inpatient falls in rural hospitals.

OBJECTIVE: To evaluate the implementation and outcomes of evidence-based fall-risk-reduction processes when those processes are implemented using a multiteam system (MTS) structure. DATA SOURCES/STUDY SETTING: Fall-risk-reduction process and outcome measures from 16 small rural hospitals participating in a research demonstration and dissemination study from August 2012 to July 2014. Previously, these hospitals lacked a fall-event reporting system to drive improvement. STUDY DESIGN: A one-group pretest-posttest embedded in a participatory research framework. We required hospitals to implement MTSs, which we supported by conducting education, developing an online toolkit, and establishing a fall-event reporting system. DATA COLLECTION: Hospitals used gap analyses to assess the presence of fall-risk-reduction processes at study beginning and their frequency and effectiveness at study end; they reported fall-event data throughout the study. PRINCIPAL FINDINGS: The extent to which hospitals implemented 21 processes to coordinate the fall-risk-reduction program and trained staff specifically about the program predicted unassisted and injurious fall rates during the end-of-study period (January 2014-July 2014). Bedside fall-risk-reduction processes were not significant predictors of these outcomes. CONCLUSIONS: Multiteam systems that effectively coordinate fall-risk-reduction processes may improve the capacity of hospitals to manage the complex patient, environmental, and system factors that result in falls.

Antiviral activity of bone morphogenetic proteins and activins.

Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity. Correspondingly, BMP6 regulated a gene repertoire reminiscent of type I interferon (IFN) signalling, including upregulating interferon regulatory factors (IRFs) and downregulating an inhibitor of IFN signalling, USP18. Moreover, in BMP-stimulated cells, SMAD1 occupied loci across the genome, similar to those bound by IRF1 in IFN-stimulated cells. Functionally, BMP6 enhanced the transcriptional and antiviral response to IFN, but BMP6 and related activin proteins also potently blocked HCV replication independently of IFN. Furthermore, BMP6 and activin A suppressed growth of HBV in cell culture, and activin A inhibited Zika virus replication alone and in combination with IFN. The data establish an unappreciated important role for BMPs and activins in cellular antiviral immunity, which acts independently of, and modulates, IFN.

Debriefs: Teams learning from doing in context.

Debriefs are a type of work meeting in which teams discuss, interpret, and learn from recent events during which they collaborated. In a variety of forms, debriefs are found across a wide range of organizational types and settings. Well-conducted debriefs can improve team effectiveness by 25% across a variety of organizations and settings. For example, the U.S. military adopted debriefs decades ago to promote learning and performance across the various services. Subsequently, debriefs have been introduced in the medical field, the fire service, aviation, education, and in a variety of organizational training and simulation environments. After a discussion of various purposes for which debriefs have been used, we proceed with a historical review of development of the concepts and use in industries and contexts. We then review the psychological factors relevant to debrief effectiveness and the outcomes for individuals, teams, and organizations that deploy debriefs. Future directions of particular interest to team researchers across a variety of psychological disciplines are presented along with a review of how best to implement debriefs from a practical perspective. (PsycINFO Database Record

Forensic Analysis of Stains on Fabric Using Direct Analysis in Real-time Ionization with High-Resolution Accurate Mass-Mass Spectrometry.

A rapid technique using direct analysis in real-time (DART) ambient ionization coupled to a high-resolution accurate mass-mass spectrometer (HRAM-MS) was employed to analyze stains on an individual's pants suspected to have been involved in a violent crime. The victim was consuming chocolate ice cream at the time of the attack, and investigators recovered the suspect's pants exhibiting splatter stains. Liquid chromatography with mass spectral detection (LC-MS) and stereoscopic light microscopy (SLM) were also utilized in this analysis. It was determined that the stains on the pants contained theobromine and caffeine, known components of chocolate. A shard from the ceramic bowl that contained the victim's ice cream and a control chocolate ice cream sample were also found to contain caffeine and theobromine. The use of DART-HRAM-MS was useful in this case due to its rapid analysis capability and because of the limited amount of sample present as a stain.

Disease outcomes in a cohort of women in Ireland infected by hepatitis C-contaminated anti-D immunoglobulin during 1970s.

BACKGROUND & AIM: In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression. METHODS: We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression. RESULTS: Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n=374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR=4.9 [2.5-9.5]) and diabetes mellitus (aSHR=5.0 [2.9-8.8]). CONCLUSIONS: Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history. LAY SUMMARY: In the mid-1990s, a group of women were diagnosed with chronic hepatitis C virus (HCV) infection following receipt of contaminated anti-D immunoglobulin between 1977 and 1979 in Ireland. Seventy-two (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of high alcohol consumption.

Neonatal head and torso vibration exposure during inter-hospital transfer.

Inter-hospital transport of premature infants is increasingly common, given the centralisation of neonatal intensive care. However, it is known to be associated with anomalously increased morbidity, most notably brain injury, and with increased mortality from multifactorial causes. Surprisingly, there have been relatively few previous studies investigating the levels of mechanical shock and vibration hazard present during this vehicular transport pathway. Using a custom inertial datalogger, and analysis software, we quantify vibration and linear head acceleration. Mounting multiple inertial sensing units on the forehead and torso of neonatal patients and a preterm manikin, and on the chassis of transport incubators over the duration of inter-site transfers, we find that the resonant frequency of the mattress and harness system currently used to secure neonates inside incubators is [Formula: see text]. This couples to vehicle chassis vibration, increasing vibration exposure to the neonate. The vibration exposure per journey (A(8) using the ISO 2631 standard) was at least 20% of the action point value of current European Union regulations over all 12 neonatal transports studied, reaching 70% in two cases. Direct injury risk from linear head acceleration (HIC15) was negligible. Although the overall hazard was similar, vibration isolation differed substantially between sponge and air mattresses, with a manikin. Using a Global Positioning System datalogger alongside inertial sensors, vibration increased with vehicle speed only above 60 km/h. These preliminary findings suggest there is scope to engineer better systems for transferring sick infants, thus potentially improving their outcomes.

Anti-confocal assessment of middle ear inflammation.

To improve the diagnostic prediction of recurrence of otitis media with effusion after surgery, an anti-confocal system combined with spectroscopic measurements is proposed to reject unwanted signals from the eardrum and assess the blood content. The anti-confocal system was experimentally evaluated on both optical middle ear phantom and human skin. Results showed effective rejection of signals from the eardrum using a central stop replacing the confocal pinhole, while still detecting signals from the middle ear mucosa. The system is sensitive to changes in blood content, but scattering and absorption characteristics of the eardrum can distort the measurement. Confocal detection of eardrum properties was shown to be a promising approach to correct measurements.

Simultaneous Orthogonal Drug Detection Using Fully Integrated Gas Chromatography with Fourier Transform Infrared Detection and Mass Spectrometric Detection.

Analytes that co-elute and yield nearly identical electron ionization (EI) mass spectra, as well as analytes that yield non-specific EI fragmentation patterns, have been identified using fully integrated gas chromatography with direct deposit Fourier transform infrared detection and mass spectrometric detection (GC/FT-IR/MS). While the IR detector proved to be more selective for identifying analytes such as synthetic cannabinoids and weight loss drugs, it was limited by a relatively high detection limit of 8.4 parts per million (ppm) for non-targeted identification of sibutramine based on a single injection but was reduced to 840 parts per billion (ppb) for targeted identification of sibutramine by redepositing ten injections along the same track. The MS detector was less selective for identifying these analytes but yielded non-targeted and targeted detection limits of approximately 84 ppb and 8.4 ppb, respectively, which corresponded to a 100-fold advantage compared to the IR detector. Overall, the results of this study demonstrate that the advantages of each detector compensate for the limitations of the other, which allows a wider range of analytes and concentrations to be examined using a fully integrated GC/FT-IR/MS instrument compared to what can be examined using GC/IR or GC/MS independently. Not only does this approach reduce consumption of laboratory resources and time, it provides IR and MS information on the same sample, which is important for forensic analyses that require data from two or more orthogonal techniques to make an identification.