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Early in a foodborne disease outbreak investigation, illness incubation periods can help focus case interviews, case definitions, clinical and environmental evaluations and predict an aetiology. Data describing incubation periods are limited. We examined foodborne disease outbreaks from laboratory-confirmed, single aetiology, enteric bacterial and viral pathogens reported to United States foodborne disease outbreak surveillance from 1998–2013. We grouped pathogens by clinical presentation and analysed the reported median incubation period among all illnesses from the implicated pathogen for each outbreak as the outbreak incubation period. Outbreaks from preformed bacterial toxins (Staphylococcus aureus, Bacillus cereus and Clostridium perfringens) had the shortest outbreak incubation periods (4–10 h medians), distinct from that of Vibrio parahaemolyticus (17 h median). Norovirus, salmonella and shigella had longer but similar outbreak incubation periods (32–45 h medians); campylobacter and Shiga toxin-producing Escherichia coli had the longest among bacteria (62–87 h medians); hepatitis A had the longest overall (672 h median). Our results can help guide diagnostic and investigative strategies early in an outbreak investigation to suggest or rule out specific etiologies or, when the pathogen is known, the likely timeframe for exposure. They also point to possible differences in pathogenesis among pathogens causing broadly similar syndromes.
The preservation of genetic diversity is an important aspect of conservation biology. Low genetic diversity within a population can lead to inbreeding depression and a reduction in adaptive potential, which may increase extinction risk. Here we report changes in genetic diversity over 12 years in a declining population of the Corncrake Crex crex, a grassland bird species of high conservation concern throughout Europe. Despite a twofold demographic decline during the same period, we found no evidence for a reduction of genetic diversity. The gradual genetic differentiation observed among populations of Corncrake across Europe suggests that genetic diversity is maintained in western populations by constant gene flow from the larger and more productive populations in eastern Europe and Asia. The maintenance of genetic diversity in this species is an opportunity that may help the implementation of effective conservation actions across the Corncrake’s European range.
Following publication, errors were discovered in the y-axis labels of the electron and hole concentration plots in the following figure panels: figure 4c, figure 4d, figure 5c, figure 5d, figure 6c, figure 6d, figure 8c and figure 8d. The error does not affect the description, analysis or conclusions. The correct representation of the figure panels are shown here.
Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.
Introduction: Point of care ultrasound has been reported to improve diagnosis in non-traumatic hypotensive ED patients. We compared diagnostic performance of physicians with and without PoCUS in undifferentiated hypotensive patients as part of an international prospective randomized controlled study. The primary outcome was diagnostic performance of PoCUS for cardiogenic vs. non-cardiogenic shock. Methods: SHoC-ED recruited hypotensive patients (SBP < 100 mmHg or shock index > 1) in 6 centres in Canada and South Africa. We describe previously unreported secondary outcomes relating to diagnostic accuracy. Patients were randomized to standard clinical assessment (No PoCUS) or PoCUS groups. PoCUS-trained physicians performed scans after initial assessment. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses including shock category were recorded at 0 and 60 minutes. Final diagnosis was determined by independent blinded chart review. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: 273 patients were enrolled with follow-up for primary outcome completed for 270. Baseline demographics and perceived category of shock were similar between groups. 11% of patients were determined to have cardiogenic shock. PoCUS had a sensitivity of 80.0% (95% CI 54.8 to 93.0%), specificity 95.5% (90.0 to 98.1%), LR+ve 17.9 (7.34 to 43.8), LR-ve 0.21 (0.08 to 0.58), Diagnostic OR 85.6 (18.2 to 403.6) and accuracy 93.7% (88.0 to 97.2%) for cardiogenic shock. Standard assessment without PoCUS had a sensitivity of 91.7% (64.6 to 98.5%), specificity 93.8% (87.8 to 97.0%), LR+ve 14.8 (7.1 to 30.9), LR- of 0.09 (0.01 to 0.58), Diagnostic OR 166.6 (18.7 to 1481) and accuracy of 93.6% (87.8 to 97.2%). There was no significant difference in sensitivity (-11.7% (-37.8 to 18.3%)) or specificity (1.73% (-4.67 to 8.29%)). Diagnostic performance was also similar between other shock subcategories. Conclusion: As reported in other studies, PoCUS based assessment performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test. However performance was similar to standard (non-PoCUS) assessment, which was excellent in this study.
Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.
Increasing evidence suggests that the presence of mobile ions in perovskite solar cells (PSCs) can cause a current–voltage curve hysteresis. Steady state and transient current–voltage characteristics of a planar metal halide CH3NH3PbI3 PSC are analysed with a drift-diffusion model that accounts for both charge transport and ion vacancy motion. The high ion vacancy density within the perovskite layer gives rise to narrow Debye layers (typical width ~2 nm), adjacent to the interfaces with the transport layers, over which large drops in the electric potential occur and in which significant charge is stored. Large disparities between (I) the width of the Debye layers and that of the perovskite layer (~600 nm) and (II) the ion vacancy density and the charge carrier densities motivate an asymptotic approach to solving the model, while the stiffness of the equations renders standard solution methods unreliable. We derive a simplified surface polarisation model in which the slow ion dynamics are replaced by interfacial (non-linear) capacitances at the perovskite interfaces. Favourable comparison is made between the results of the asymptotic approach and numerical solutions for a realistic cell over a wide range of operating conditions of practical interest.
The flow in a decelerating turbulent round jet is investigated using direct numerical simulation. The simulations are initialised with a flow field from a statistically stationary turbulent jet. Upon stopping the inflow, a deceleration wave passes through the jet, behind which the velocity field evolves towards a new statistically unsteady self-similar state. Assumption of unsteady self-similar behaviour leads to analytical relations concerning the evolution of the centreline mean axial velocity and the shapes of the radial profiles of the velocity statistics. Consistency between these predictions and the simulation data supports the use of the assumption of self-similarity. The mean radial velocity is predicted to reverse in direction near to the jet centreline as the deceleration wave passes, contributing to an approximately threefold increase in the normalised mass entrainment rate. The shape of the mean axial velocity profile undergoes a relatively small change across the deceleration transient, and this observation provides direct evidence in support of previous models that have assumed that the mean axial velocity profile, and in some cases also the jet spreading angle, remain approximately constant within unsteady jets.
Fluid residence time is a key concept in the understanding and design of chemically reacting flows. In order to investigate how turbulent mixing affects the residence time distribution within a flow, this study examines statistics of fluid residence time from a direct numerical simulation (DNS) of a statistically stationary turbulent round jet with a jet Reynolds number of 7290. The residence time distribution in the flow is characterised by solving transport equations for the residence time of the jet fluid and for the jet fluid mass fraction. The product of the jet fluid residence time and the jet fluid mass fraction, referred to as the mass-weighted stream age, gives a quantity that has stationary statistics in the turbulent jet. Based on the observation that the statistics of the mass fraction and velocity are self-similar downstream of an initial development region, the transport equation for the jet fluid residence time is used to derive a model describing a self-similar profile for the mean of the mass-weighted stream age. The self-similar profile predicted is dependent on, but different from, the self-similar profiles for the mass fraction and the axial velocity. The DNS data confirm that the first four moments and the shape of the one-point probability density function of mass-weighted stream age are indeed self-similar, and that the model derived for the mean mass-weighted stream-age profile provides a useful approximation. Using the self-similar form of the moments and probability density functions presented it is therefore possible to estimate the local residence time distribution in a wide range of practical situations in which fluid is introduced by a high-Reynolds-number jet of fluid.
Recent studies have improved our understanding of nearshore marine ecosystems surrounding Ascension Island (central Atlantic Ocean), but little is known about Ascension's benthic environment beyond its shallow coastal waters. Here, we report the first detailed physical and biological examination of the seabed surrounding Ascension Island at 100–1000 m depth. Multibeam swath data were used to map fine scale bathymetry and derive seabed slope and rugosity indices for the entire area. Water temperature and salinity profiles were obtained from five Conductivity, Temperature, Depth (CTD) deployments, revealing a spatially consistent thermocline at 80 m depth. A camera lander (Shelf Underwater Camera System; SUCS) provided nearly 400 images from 21 sites (100 m transects) at depths of 110–1020 m, showing high variability in the structure of benthic habitats and biological communities. These surveys revealed a total of 95 faunal morphotypes (mean richness >14 per site), complemented by 213 voucher specimens constituting 60 morphotypes collected from seven targeted Agassiz trawl (AGT) deployments. While total faunal density (maximum >300 m−2 at 480 m depth) increased with rugosity, characteristic shifts in multivariate assemblage structure were driven by depth and substratum type. Shallow assemblages (~100 m) were dominated by black coral (Antipatharia sp.) on rocky substrata, cup corals (Caryophyllia sp.) and sea urchins (Cidaris sp.) were abundant on fine sediment at intermediate depths (250–500 m), and shrimps (Nematocarcinus spp.) were common at greater depths (>500 m). Other ubiquitous taxa included serpulid and sabellid polychaetes and brittle stars (Ophiocantha sp.). Cold-water corals (Lophelia cf. pertusa), indicative of Vulnerable Marine Ecosystems (VMEs) and representing substantial benthic carbon accumulation, occurred in particularly dense aggregations at <350 m but were encountered as deep as 1020 m. In addition to enhancing marine biodiversity records at this locality, this study provides critical baseline data to support the future management of Ascension's marine environment.
Introduction: Point of care ultrasound (PoCUS) is an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). While PoCUS protocols have been shown to improve early diagnostic accuracy, there is little published evidence for any mortality benefit. We report the findings from our international multicenter randomized controlled trial, assessing the impact of a PoCUS protocol on survival and key clinical outcomes. Methods: Recruitment occurred at 7 centres in North America (4) and South Africa (3). Scans were performed by PoCUS-trained physicians. Screening at triage identified patients (SBP<100 or shock index>1), randomized to PoCUS or control (standard care and no PoCUS) groups. Demographics, clinical details and study findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. The primary outcome measure was 30-day/discharge mortality. Secondary outcome measures included diagnostic accuracy, changes in vital signs, acid-base status, and length of stay. Categorical data was analyzed using Fishers test, and continuous data by Student T test and multi-level log-regression testing. (GraphPad/SPSS) Final chart review was blinded to initial impressions and PoCUS findings. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no difference between groups for the primary outcome of mortality; PoCUS 32/129 (24.8%; 95% CI 14.3-35.3%) vs. Control 32/129 (24.8%; 95% CI 14.3-35.3%); RR 1.00 (95% CI 0.869 to 1.15; p=1.00). There were no differences in the secondary outcomes; ICU and total length of stay. Our sample size has a power of 0.80 (α:0.05) for a moderate effect size. Other secondary outcomes are reported separately. Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We did not find any mortality or length of stay benefits with the use of a PoCUS protocol, though a larger study is required to confirm these findings. While PoCUS may have diagnostic benefits, these may not translate into a survival benefit effect.
Introduction: Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for emergency department (ED) patients with undifferentiated non-traumatic hypotension. While PoCUS has been shown to improve early diagnosis, there is a minimal evidence for any outcome benefit. We completed an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key resuscitation markers in this group. We report diagnostic impact and mortality elsewhere. Methods: The SHoC-ED1 study compared the addition of PoCUS to standard care within the first hour in the treatment of adult patients presenting with undifferentiated hypotension (SBP<100 mmHg or a Shock Index >1.0) with a control group that did not receive PoCUS. Scans were performed by PoCUS-trained physicians. 4 North American, and 3 South African sites participated in the study. Resuscitation outcomes analyzed included volume of fluid administered in the ED, changes in shock index (SI), modified early warning score (MEWS), venous acid-base balance, and lactate, at one and four hours. Comparisons utilized a T-test as well as stratified binomial log-regression to assess for any significant improvement in resuscitation amount the outcomes. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no significant difference in mean total volume of fluid received between the control (1658 ml; 95%CI 1365-1950) and PoCUS groups (1609 ml; 1385-1832; p=0.79). Significant improvements were seen in SI, MEWS, lactate and bicarbonate with resuscitation in both the PoCUS and control groups, however there was no difference between groups. Conclusion: SHOC-ED1 is the first RCT to compare PoCUS to standard of care in hypotensive ED patients. No significant difference in fluid used, or markers of resuscitation was found when comparing the use of a PoCUS protocol to that of standard of care in the resuscitation of patients with undifferentiated hypotension.
Introduction: Point of care ultrasonography (PoCUS) is an established tool in the initial management of hypotensive patients in the emergency department (ED). It has been shown rule out certain shock etiologies, and improve diagnostic certainty, however evidence on benefit in the management of hypotensive patients is limited. We report the findings from our international multicenter RCT assessing the impact of a PoCUS protocol on diagnostic accuracy, as well as other key outcomes including mortality, which are reported elsewhere. Methods: Recruitment occurred at 4 North American and 3 Southern African sites. Screening at triage identified patients (SBP<100 mmHg or shock index >1) who were randomized to either PoCUS or control groups. Scans were performed by PoCUS-trained physicians. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. Final chart review was blinded to initial impressions and PoCUS findings. Categorical data was analyzed using Fishers two-tailed test. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. The perceived shock category changed more frequently in the PoCUS group 20/127 (15.7%) vs. control 7/125 (5.6%); RR 2.81 (95% CI 1.23 to 6.42; p=0.0134). There was no significant difference in change of diagnostic impression between groups PoCUS 39/123 (31.7%) vs control 34/124 (27.4%); RR 1.16 (95% CI 0.786 to 1.70; p=0.4879). There was no significant difference in the rate of correct category of shock between PoCUS (118/127; 93%) and control (113/122; 93%); RR 1.00 (95% CI 0.936 to 1.08; p=1.00), or for correct diagnosis; PoCUS 90/127 (70%) vs control 86/122 (70%); RR 0.987 (95% CI 0.671 to 1.45; p=1.00). Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We found that the use of PoCUS did change physicians’ perceived shock category. PoCUS did not improve diagnostic accuracy for category of shock or diagnosis.
Although most non-typhoidal Salmonella illnesses are self-limiting, antimicrobial treatment is critical for invasive infections. To describe resistance in Salmonella that caused foodborne outbreaks in the United States, we linked outbreaks submitted to the Foodborne Disease Outbreak Surveillance System to isolate susceptibility data in the National Antimicrobial Resistance Monitoring System. Resistant outbreaks were defined as those linked to one or more isolates with resistance to at least one antimicrobial drug. Multidrug resistant (MDR) outbreaks had at least one isolate resistant to three or more antimicrobial classes. Twenty-one per cent (37/176) of linked outbreaks were resistant. In outbreaks attributed to a single food group, 73% (16/22) of resistant outbreaks and 46% (31/68) of non-resistant outbreaks were attributed to foods from land animals (P < 0·05). MDR Salmonella with clinically important resistance caused 29% (14/48) of outbreaks from land animals and 8% (3/40) of outbreaks from plant products (P < 0·01). In our study, resistant Salmonella infections were more common in outbreaks attributed to foods from land animals than outbreaks from foods from plants or aquatic animals. Antimicrobial susceptibility data on isolates from foodborne Salmonella outbreaks can help determine which foods are associated with resistant infections.
I propose to concentrate on international humanitarian assistance that really lives up to its name. Accordingly, I will be confining my attention to well-meaning international interventions. To be sure, some interventions carried out under the banner of alleged humanitarian assistance are really attempts to grab power or to pursue national or institutional interests. Such interventions are not worthy of the name “humanitarian assistance.” I will limit my attention to the well-meaning cases. To be sure, as we will see, those who mean well may operate with blinkered or parochial or condescending ideas about what would assist others; but they do mean well, unlike those who use the appearance of humanitarianism to further their narrow self-interest. I will also limit my attention to interventions. Some well-meaning attempts to influence international affairs should not be counted as interventions. For example, offering asylum to people overseas because they seem to need exit from where they are, though intended to influence their situation, does not seem to interfere with them or with the nation in which they live. Again, I propose to focus my attention on well-meaning international interventions, of which international humanitarian assistance, properly so-called, is a special case.
Although the kind of example just given would complicate any analysis, an intervention is an action intended to alter another's life or activities. Since I will be focusing on interventions, I will not be directly concerning myself with attitudes such as arrogance or structural problems such as an absence of consultation mechanisms, except insofar as these give rise to problematic actions. Nonetheless, since I will analyze paternalism as a kind of action that is taken from a certain attitude, my account will help pinpoint relevant attitudes; and since structural problems can often be seen to tend to give rise to objectionable actions, my account could also indirectly help indicate what structural problems exacerbate or give rise to paternalist interventions.
Those engaged in international humanitarian assistance have become used to being called paternalistic – not only by those they are intending to aid but also by various third-party commentators. This is hardly a neutral description. As Michael N. Barnett observes, “[W]hereas in the nineteenth century being called a paternalist was not necessarily an insult, today it is.”