Book chapters will be unavailable on Saturday 24th August between 8am-12pm BST. This is for essential maintenance which will provide improved performance going forwards. Please accept our apologies for any inconvenience caused.
To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Oxidative stress is implicated in the etiology of schizophrenia, and the antioxidant defense system may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain, and its correlates with clinical and demographic variables, in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r=-.46, p=.015), and a trend-level positive relationship between GSH and duration of illness (r=.34, p=.076).
Our findings are consistent with a possible compensatory upregulation of the antioxidant defense system with longer duration of illness, and suggests the antioxidant defense system may play a role in schizophrenia.
Introduction: Previous systematic reviews suggest early mobilization in the intensive care unit (ICU) population is feasible, safe, and may improve outcomes. Only one review investigated mobilization specifically in trauma ICU patients and failed to identify any relevant articles. The objective of the present systematic review was to conduct an up-to-date search of the literature to assess the effect of early mobilization in adult trauma ICU patients on mortality, length of stay (LOS) and duration of mechanical ventilation. Methods: We performed a systematic search of four electronic databases (Ovid MEDLINE, Embase, CINAHL, Cochrane Library) and the grey literature. To be included, studies must have compared early mobilization to delayed or no mobilization among trauma patients admitted to the ICU. Meta-analysis was performed to determine the effect of early mobilization on mortality, hospital LOS, ICU LOS, and duration of mechanical ventilation. Results: The search yielded 2,975 records from the 4 databases and 7 records from grey literature and bibliographic searches; of these, 9 articles met all eligibility criteria and were included in the analysis. There were 7 studies performed in the United States, 1 study from China and 1 study from Norway. Study populations included neurotrauma (3 studies), blunt abdominal trauma (2 studies), mixed injury types (2 studies) and burns (1 study). Cohorts ranged in size from 15 to 1,132 patients (median, 63) and varied in inclusion criteria. Most studies used some form of stepwise progressive mobility protocol. Two studies used simple ambulation as the mobilization measure, and 1 study employed upright sitting as their only intervention. Time to commencement of the intervention was variable across studies, and only 2 studies specified the timing of mobilization initiation. We did not detect a difference in mortality with early mobilization, although the pooled risk ratio (RR) was reduced (RR 0.90, 95% CI 0.74 to 1.09). Hospital LOS and ICU LOS were decreased with early mobilization, though this difference did not reach significance. Duration of mechanical ventilation was significantly shorter in the early mobilization group (mean difference −1.18. 95% CI −2.17 to −0.19). Conclusion: Our review identified few studies that examined mobilization of critically ill trauma patients in the ICU. On meta-analysis, early mobilization was found to reduce duration of mechanical ventilation, but the effects on mortality and LOS were not significant.
Introduction: Long-term immobility has detrimental effects for critically ill patients admitted to the intensive care unit (ICU) including ICU-acquired weakness. Early mobilization of patients admitted to ICU has been demonstrated to be a safe, feasible and effective strategy to improve patient outcomes. The optimal mobilization of trauma ICU patients has not been extensively studied. Our objective was to determine the impact of an early mobilization protocol on outcomes among trauma patients admitted to the ICU. Methods: We analyzed all adult trauma patients ( > 18 years old) admitted to ICU over a 2-year period prior to and following implementation of an early mobilization protocol, allowing for a 1-year transition period. Data were collected from the Nova Scotia Trauma Registry. We compared patient characteristics and outcomes (mortality, length of stay [LOS], ventilator days) between the pre- and post-implementation groups. Associations between early mobilization and clinical outcomes were estimated using binary and linear regression models. Results: Overall, there were 526 patients included in the analysis (292 pre-implementation, 234 post-implementation). The study population ranged in age from 18 to 92 years (mean age 49.0 ± 20.4 years) and 74.3% of all patients were male. The pre- and post-implementation groups were similar in age, sex, and injury severity. In-hospital mortality was reduced in the post-implementation group (25.3% vs. 17.5%; p = 0.031). In addition, there was a reduction in ICU mortality in the post-implementation group (21.6% vs. 12.8%; p = 0.009). We did not observe any difference in overall hospital LOS, ICU LOS, or ventilator days between the two groups. Compared to the pre-implementation period, trauma patients admitted to the ICU following protocol implementation were less likely to die in-hospital (OR = 0.52, 95% CI 0.30-0.91; p = 0.021) or in the ICU (OR = 0.40, 95% CI 0.21- 0.76, p = 0.005). Results were similar following a sensitivity analysis limited to patients with blunt or penetrating injuries. There was no difference between the pre- and post-implementation groups with respect to in-hospital LOS, ICU LOS, or the number of ventilator days. Conclusion: We found that trauma patients admitted to ICU during the post-implementation period had decreased odds of in-hospital mortality and ICU mortality. Ours is the first study to demonstrate a significant reduction in trauma mortality following implementation of an ICU mobility protocol.
Introduction: The Prehospital Evidence-Based Practice (PEP) program is an online, freely accessible, continuously updated Emergency Medical Services (EMS) evidence repository. This summary describes the research evidence for the identification and management of adult patients suffering from sepsis syndrome or septic shock. Methods: PubMed was searched in a systematic manner. One author reviewed titles and abstracts for relevance and two authors appraised each study selected for inclusion. Primary outcomes were extracted. Studies were scored by trained appraisers on a three-point Level of Evidence (LOE) scale (based on study design and quality) and a three-point Direction of Evidence (DOE) scale (supportive, neutral, or opposing findings based on the studies’ primary outcome for each intervention). LOE and DOE of each intervention were plotted on an evidence matrix (DOE x LOE). Results: Eighty-eight studies were included for 15 interventions listed in PEP. The interventions with the most evidence were related to identification tools (ID) (n = 26, 30%) and early goal directed therapy (EGDT) (n = 21, 24%). ID tools included Systematic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA) and other unique measures. The most common primary outcomes were related to diagnosis (n = 30, 34%), mortality (n = 40, 45%) and treatment goals (e.g. time to antibiotic) (n = 14, 16%). The evidence rank for the supported interventions were: supportive-high quality (n = 1, 7%) for crystalloid infusion, supportive-moderate quality (n = 7, 47%) for identification tools, prenotification, point of care lactate, titrated oxygen, temperature monitoring, and supportive-low quality (n = 1, 7%) for vasopressors. The benefit of prehospital antibiotics and EGDT remain inconclusive with a neutral DOE. There is moderate level evidence opposing use of high flow oxygen. Conclusion: EMS sepsis interventions are informed primarily by moderate quality supportive evidence. Several standard treatments are well supported by moderate to high quality evidence, as are identification tools. However, some standard in-hospital therapies are not supported by evidence in the prehospital setting, such as antibiotics, and EGDT. Based on primary outcomes, no identification tool appears superior. This evidence analysis can guide selection of appropriate prehospital therapies.
Introduction: Early and accurate diagnosis of critical conditions is essential in emergency medical services (EMS). Serum lactate testing may be used to identify patients with worse prognosis, including sepsis. Recently, the use of a point-of-care lactate (POCL) test has been evaluated in guiding treatment in patients with sepsis. Operating as part of the Prehospital Evidence Based Practice (PEP) Program, the authors sought to identify and describe the body of evidence for POCL use in EMS and the emergency department (ED) for patients with sepsis. Methods: Following PEP methodology, in May 2018, PubMed was searched in a systematic manner. Title and abstract screening were conducted by the program coordinator. These studies were collected, appraised and added to the existing body of literature contained within the PEP database. Evidence appraisal was conducted by two reviewers who assigned both a level of evidence (LOE) on a novel three tier scale and a direction of evidence (supportive, neutral or opposing; based on primary outcome). Data on setting and study design were also extracted. Results: Eight studies were included in our analysis. Three of these studies were conducted in the ED setting; each investigating the POCL test's ability to predict severe sepsis, ICU admission or death. All three studies found supportive results for POCL. A systematic review on the use of POCL in the ED determined that this test can also improve time to treatment. Five of the total 8 studies were conducted prehospitally. Two of these studies were supportive of POCL use in the prehospital setting; in terms of feasibility and the ability to predict sepsis. Both of these study sites used this early information as part of initiating a “sepsis alert” pathway. The other three prehospital studies provide neutral support for POCL. One study demonstrated moderate ability of POCL to predict severe illness. Two studies found poor agreement between prehospital POCL and serum lactate values. Conclusion: Limited low and moderate quality evidence suggest POCL may be feasible and helpful in predicting sepsis in the prehospital setting. However, there is sparse and inconsistent support for specific important outcomes, including accuracy.
Influenza and respiratory syncytial virus (RSV) are common causes of respiratory tract infections and place a burden on health services each winter. Systems to describe the timing and intensity of such activity will improve the public health response and deployment of interventions to these pressures. Here we develop early warning and activity intensity thresholds for monitoring influenza and RSV using two novel data sources: general practitioner out-of-hours consultations (GP OOH) and telehealth calls (NHS 111). Moving Epidemic Method (MEM) thresholds were developed for winter 2017–2018. The NHS 111 cold/flu threshold was breached several weeks in advance of other systems. The NHS 111 RSV epidemic threshold was breached in week 41, in advance of RSV laboratory reporting. Combining the use of MEM thresholds with daily monitoring of NHS 111 and GP OOH syndromic surveillance systems provides the potential to alert to threshold breaches in real-time. An advantage of using thresholds across different health systems is the ability to capture a range of healthcare-seeking behaviour, which may reflect differences in disease severity. This study also provides a quantifiable measure of seasonal RSV activity, which contributes to our understanding of RSV activity in advance of the potential introduction of new RSV vaccines.
X-ray diffraction topography is the name given to several x-ray diffraction techniques where large area x-ray beams diffracted from a crystal provide detailed information about the surface structure and internal perfection of crystal microstructures. Since x-ray topographic techniques are based on Bragg (reflection) or Laue (transmission) diffraction from a crystal lattice, they are extremely sensitive to any atomic lattice imperfections and strains. Alterations of the interplanar spacing as small as one part in ten thousand extending over a reasonable number of atomic ce11 lengths can be recorded as a corresponding change in the diffracted beam intensity. Line Modified-Asymmetric Crystal Topography (LM-ACT) is one such reflection technique that shows particular promise in Che field of microelectronics. The LM-ACT system is designed with low angular divergence in the x-ray beam probe. Low probe beam divergence allows details of device geometries on the order of microns to be resolved in the recorded x-ray intensity variation of the diffracted beam.
The LM-ACT system was applied here to the study of integrated circuits (IC) after specific processing steps were accomplished during IC fabrication and in the final product condition. Topographs obtained from specular crystal surfaces that were implanted through a patterned mask showed contrast variations between the implanted and non-implanted regions; details of the mask patterns have been resolved on the order of a few microns. LMACT topographs from annealed, and unannealed, Implanted specimens showed marked differences and as a result it is suggested that LM-ACT would be beneficial in optimizing the processing schedule for a particular wafer/electronic system. A significant feature of the LM-ACT technique is the capability for producing high resolution stereo-pair topographs that provide quantitative information through the depth of individual process layers in an integrated circuit.
The strength of ceramics or glasses can be increased by placing their surfaces into compression. Techniques include ion exchange, temperature glazing, surface chemical reactions and stress-induced phase transformations. Although most of these techniques are well recognized, little effort has been expended In experimentally determining the magnitude of the compressive stress, and in particular, to use experimental evidence to identify important material and process parameters that need to be controlled. The goal of this investigation was to determine some of the factors that effect the magnitude, profile and depth of the compressive layer introduced by a structural phase transformation. X-ray residual stress measurements were used to directly determine the state of the surface residual stress.
Mismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity (‘repetition positivity’; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity (‘deviant negativity’; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC).
Electroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains.
Compared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects.
MMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
Legionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.
During the 2009 influenza pandemic, a rapid assessment of disease severity was a challenge as a significant proportion of cases did not seek medical care; care-seeking behaviour changed and the proportion asymptomatic was unknown. A random-digit-dialling telephone survey was undertaken during the 2011/12 winter season in England and Wales to address the feasibility of answering these questions. A proportional quota sampling strategy was employed based on gender, age group, geographical location, employment status and level of education. Households were recruited pre-season and re-contacted immediately following peak seasonal influenza activity. The pre-peak survey was undertaken in October 2011 with 1061 individuals recruited and the post-peak telephone survey in March 2012. Eight hundred and thirty-four of the 1061 (78.6%) participants were successfully re-contacted. Their demographic characteristics compared well to national census data. In total, 8.4% of participants self-reported an influenza-like illness (ILI) in the previous 2 weeks, with 3.2% conforming to the World Health Organization (WHO) ILI case definition. In total, 29.6% of the cases reported consulting their general practitioner. 54.1% of the 1061 participants agreed to be re-contacted about providing biological samples. A population-based cohort was successfully recruited and followed up. Longitudinal survey methodology provides a practical tool to assess disease severity during future pandemics.
Significant increases in excess all-cause mortality, particularly in the elderly, were observed during the winter of 2014/15 in England. With influenza A(H3N2) the dominant circulating influenza A subtype, this paper determines the contribution of influenza to this excess controlling for weather. A standardised multivariable Poisson regression model was employed with weekly all-cause deaths the dependent variable for the period 2008–2015. Adjusting for extreme temperature, a total of 26 542 (95% CI 25 301–27 804) deaths in 65+ and 1942 (95% CI 1834–2052) in 15–64-year-olds were associated with influenza from week 40, 2014 to week 20, 2015. This is compatible with the circulation of influenza A(H3N2). It is the largest estimated number of influenza-related deaths in England since prior to 2008/09. The findings highlight the potential health impact of influenza and the important role of the annual influenza vaccination programme that is required to protect the population including the elderly, who are vulnerable to a severe outcome.
Nutritional management of pigs to optimise growth demands pig-specific, time-specific and place-specific determination and provision of nutritional requirement. These elements need to be incorporated into response prediction models that operate in a real-time (not retrospective) closed-loop control environment. This implies appropriate means for the on-line measurement of response to change in nutrient provision, and the simultaneous means for manipulation of feeding level and feed quality. The paper describes how response prediction modelling and response measurement may now be achieved. Optimisation may be pursued with mixed objectives, including those of production efficiency and environmental protection.
The intergenerational risk for mental illness is well established within diagnostic categories, but the risk is unlikely to respect diagnostic boundaries and may be reflected more broadly in early life vulnerabilities. We aimed to establish patterns of association between externalising and internalising vulnerabilities in early childhood and parental mental disorder across the full spectrum of diagnoses.
A cohort of Australian children (n = 69 116) entering the first year of school in 2009 were assessed using the Australian Early Development Census, providing measures of externalising and internalising vulnerability. Parental psychiatric diagnostic status was determined utilising record-linkage to administrative health datasets.
Parental mental illness, across diagnostic categories, was associated with all child externalising and internalising domains of vulnerability. There was little evidence to support interaction by parental or offspring sex.
These findings have important implications for informing early identification and intervention strategies in high-risk offspring and for research into the causes of mental illness. There may be benefits to focusing less on diagnostic categories in both cases.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The purpose of an integrated management system is to optimise both pig performance and environmental protection. A major impediment to this process has been the inability to measure and control the production process in real time, for specific and contemporary pig batches. Optimisation thus requires in-line measurement of pig growth performance, together with the means to change performance with adjustments to feed quantity and quality. This report deals with the use of visual image analysis (VIA) to provide the first of these; measurement of growth. VIA determines, continuously and in-line, the size and shape of the plan view of the pig as it stands at the feeder. Three seminal questions are here addressed. (i) can VIA be used to provide a reliable measure of pig weight, and (ii) how many days are required to elapse before a change in size can be reliably determined and how does the VIA system compare with daily weighing by a conventional weigh-scale, and (iii) can VIA sort pigs according to their shape?
The Molonglo Observatory Synthesis Telescope (MOST) is an 18000 m2 radio telescope located 40 km from Canberra, Australia. Its operating band (820–851 MHz) is partly allocated to telecommunications, making radio astronomy challenging. We describe how the deployment of new digital receivers, Field Programmable Gate Array-based filterbanks, and server-class computers equipped with 43 Graphics Processing Units, has transformed the telescope into a versatile new instrument (UTMOST) for studying the radio sky on millisecond timescales. UTMOST has 10 times the bandwidth and double the field of view compared to the MOST, and voltage record and playback capability has facilitated rapid implementaton of many new observing modes, most of which operate commensally. UTMOST can simultaneously excise interference, make maps, coherently dedisperse pulsars, and perform real-time searches of coherent fan-beams for dispersed single pulses. UTMOST operates as a robotic facility, deciding how to efficiently target pulsars and how long to stay on source via real-time pulsar folding, while searching for single pulse events. Regular timing of over 300 pulsars has yielded seven pulsar glitches and three Fast Radio Bursts during commissioning. UTMOST demonstrates that if sufficient signal processing is applied to voltage streams, innovative science remains possible even in hostile radio frequency environments.
We present the results from the Australian Long Baseline Array (LBA) observations of the ground- and excited-state OH masers at high resolutions towards the massive star-forming region G351.417+0.645 in 2012. We obtain the most accurate spatial gradient of magnetic fields at ground state transitions and verify the reliability of magnetic field strengths measured from previous lower resolution observations. In comparison with previous LBA observations in 2001 at 6.0 GHz, we identified several matched Zeeman pairs. We found that the OH maser features have no significant change of magnetic field strengths and directions with small internal proper motions, implying quite stable physical conditions. Additionally, we found that 1665- and 6035-MHz OH maser features reveal the same trend of reversal of magnetic fields. Moreover, we also analyzed the physical conditions at different locations from the coincidence of different OH maser transitions based on current OH maser models.
The class of radio transients called Fast Radio Bursts (FRBs) encompasses enigmatic single pulses, each unique in its own way, hindering a consensus for their origin. The key to demystifying FRBs lies in discovering many of them in order to identity commonalities – and in real time, in order to find potential counterparts at other wavelengths. The recently upgraded UTMOST in Australia, is undergoing a backend transformation to rise as a fast transient detection machine. The first interferometric detections of FRBs with UTMOST, place their origin beyond the near-field region of the telescope thus ruling out local sources of interference as a possible origin. We have localised these bursts to much better than the ones discovered at the Parkes radio telescope and have plans to upgrade UTMOST to be capable of much better localisation still.