Preterm infants can be inadvertently exposed to high tidal volumes (V(T)) in the delivery room, causing lung inflammation and injury, but little is known about their effects on the brain. The aim of ...this study was to compare an initial 15 min of high V(T) resuscitation strategy to a less injurious resuscitation strategy on cerebral haemodynamics, inflammation and injury.
Preterm lambs at 126 d gestation were surgically instrumented prior to receiving resuscitation with either: 1) High V(T) targeting 10-12 mL/kg for the first 15 min (n = 6) or 2) a protective resuscitation strategy (Prot V(T)), consisting of prophylactic surfactant, a 20 s sustained inflation and a lower initial V(T) (7 mL/kg; n = 6). Both groups were subsequently ventilated with a V(T) 7 mL/kg. Blood gases, arterial pressures and carotid blood flows were recorded. Cerebral blood volume and oxygenation were assessed using near infrared spectroscopy. The brain was collected for biochemical and histologic assessment of inflammation, injury, vascular extravasation, hemorrhage and oxidative injury. Unventilated controls (UVC; n = 6) were used for comparison.
High V(T) lambs had worse oxygenation and required greater ventilatory support than Prot V(T) lambs. High V(T) resulted in cerebral haemodynamic instability during the initial 15 min, adverse cerebral tissue oxygenation index and cerebral vasoparalysis. While both resuscitation strategies increased lung and brain inflammation and oxidative stress, High V(T) resuscitation significantly amplified the effect (p = 0.014 and p<0.001). Vascular extravasation was evident in the brains of 60% of High V(T) lambs, but not in UVC or Prot V(T) lambs.
High V(T) resulted in greater cerebral haemodynamic instability, increased brain inflammation, oxidative stress and vascular extravasation than a Prot V(T) strategy. The initiation of resuscitation targeting Prot V(T) may reduce the severity of brain injury in preterm neonates.
Compulsory co-payments limit access and may compromise quality in primary care. Patient Chosen Gap Payments (PCGPs) allow patients to specify a (voluntary) out-of-pocket contribution, creating an ...incentive for patient-centred care without the need for complex outcomes-based funding formulae. It is not yet known if widespread use of PCGP services is consistent with consumer preferences. We conducted a discrete choice experiment (DCE) in a sample of the adult Australian general population (n = 1457) during April 2019 to simulate patient choice between alternative primary care services and describe preferences for PCGP services. Participants also completed a supplementary valuation task in which participants reported their intended PCGP contribution for PCGP services. Finally, we conducted policy-simulations to predict market shares when PCGP clinics operate alongside the two existing models of primary care funding in Australia. Results suggest that patients prefer shorter wait time, longer consults, lower compulsory copayments, services with higher patient satisfaction ratings, choice of doctor and $0 suggested voluntary contribution for PCGP services. Policy-simulations suggest that high-quality PCGP services could obtain market share of up to 39% and voluntary contributions of up to $25.36 per service (95%CI: $10.24, $40.47), potentially adding $1.48 billion AUD in revenues and funding for primary care at no cost to government. Low-quality PCGP services are unlikely to capture significant market share and PCGP contributions were lowest for low-quality PCGP services ($12.12, 95%CI: $2.09, $26.34). Further field testing is recommended where (i) patients make consequential choices (e.g. real payments for simulated services), and (ii) dynamic effects on quality of care and utilisation can be observed; particularly in vulnerable populations. We conclude that PCGP services aligned with patient preferences could capture significant market share and substantially increase revenue to general practice.
•Patient chosen gap payments are chosen by the patient, not fixed by the provider.•Quality and service design are important to patients when choosing healthcare.•PCGPs appear a viable alternative pricing model in the market for primary care.•PCGP clinics could capture 39% market share and add $1.48 billion AUD in revenue.
We examined multistate outbreaks attributed to raw tomatoes in the United States from 1990 to 2010. We summarized the demographic and epidemiological characteristics of 15 outbreaks resulting in 1959 ...illnesses, 384 hospitalizations, and three deaths. Most (80%) outbreaks were reported during 2000–2010; 73% occurred May–September. Outbreaks commonly affected adult (median age 34 years) women (median 58% of outbreak cases). All outbreaks were caused by Salmonella serotypes Newport (n = 6 outbreaks), Braenderup (n = 2), Baildon, Enteritidis, Javiana, Montevideo, Thompson, Typhimurium (n = 1 each); multiple serotypes (n = 1). Red, round (69% of outbreaks), Roma (23%), and grape (8%) tomatoes were implicated. Most (93%) outbreaks were associated with tomatoes served predominantly in restaurants. However, traceback investigations suggested that contamination occurred on farms, at packinghouses, or at fresh-cut processing facilities. Government agencies, academia, trade associations, and the fresh tomato industry should consider further efforts to identify interventions to reduce contamination of tomatoes during production and processing.
The Transient Receptor Potential Vanilloid 1 (TRPV1R) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. TRPV1Rs respond to a variety of noxious stimuli ...including capsaicin, intense heat and acid. These factors, combined with behavioral studies, show that TRPV1Rs are involved in nociception. The aim of our study was to determine whether TRPV1Rs play a role in the development and maintenance of inflammation and mechanical hyperalgesia by studying the development of unilateral joint inflammation in TRPV1R−/− mice. Knee joints of TRPV1R−/− or wild-type (WT) mice were injected with FCA (200 μg) under temporary anesthesia, and the resulting inflammation and hyperalgesia measured for 35 days. Histological analysis was performed on joints at the end of the study. TRPV1R−/− mice developed mild joint swelling which was significantly less than that obtained in WT mice (
P < 0.05, Mann–Whitney). The ratio of the weight distribution between the hind limbs in TRPV1R−/− mice was also significantly less than in WT mice (
P < 0.05, Mann–Whitney). Neither swelling nor hypersensitivity was completely absent in the knockout mice, indicating either that other mechanisms are involved or that a compensatory mechanism operates in TRPV1R−/− mice. These results suggest that TRPV1 receptors are important for the development of joint inflammation and the associated mechanical hypersensitivity observed in this model.
To perform well on any challenging task, it is necessary to evaluate your performance so that you can learn from errors. Recent theoretical and experimental work suggests that the neural sequellae of ...error commission in a dorsal anterior cingulate circuit index a type of contingency- or reinforcement-based learning, while activation in a rostral anterior cingulate circuit reflects appraisal of the affective or motivational significance of errors. Patients with schizophrenia show rigid, perseverative behaviour that is not optimally responsive to outcome. Findings of reduced anterior cingulate cortex (ACC) activity during error commission in schizophrenia suggest that difficulties in evaluating and modifying behaviour in response to errors may contribute to behavioural rigidity. Using event-related functional MRI and an antisaccade paradigm with concurrent monitoring of eye position, the present study examined error-related activation and its relation to task performance in the anatomic components of two ACC circuits that are theorized to make distinct contributions to error processing. Eighteen chronic-medicated schizophrenia patients and 15 healthy controls participated. Compared to controls, patients showed increased antisaccade error rates and decreased error-related activation in the reinforcement learning network—dorsal ACC, striatum and brainstem (possibly substantia nigra)—and also in the affective appraisal network—rostral ACC, insula and amygdala. These reductions remained when the effects of antipsychotic medication dose and error rate were statistically controlled. Activation in these networks was inversely related to error rate in both patient and control groups, but the slope of this relation was shallower in patients (i.e. across participants with schizophrenia, decrements in error rate were associated with smaller decrements in activation). This indicates that the blunted neural response to errors in schizophrenia was not simply a reflection of more frequent errors. Our findings demonstrate a blunted response to error commission that is associated with worse performance in two ACC circuits in schizophrenia. In the dACC circuit, the blunted response may reflect deficient modification of prepotent stimulus-response mappings in response to errors, and in the rACC network it may reflect diminished concern regarding behavioural outcomes. However, despite these deficits and in the absence of external feedback regarding errors, patients corrected their errors as frequently as controls suggesting intact error recognition and ability to institute corrective action. Impairments in evaluating and learning from errors in schizophrenia may contribute to behaviour that is rigid and perseverative rather than optimally guided by outcomes, and may compromise performance across a wide range of tasks.
Abstract
As the global climate warms, a key question is how increased leaf temperatures will affect tree physiology and the coupling between leaf and air temperatures in forests. To explore the ...impact of increasing temperatures on plant performance in open air, we warmed leaves in the canopy of two mature evergreen forests, a temperate Eucalyptus woodland and a tropical rainforest. The leaf heaters consistently maintained leaves at a target of 4 °C above ambient leaf temperatures. Ambient leaf temperatures (Tleaf) were mostly coupled to air temperatures (Tair), but at times, leaves could be 8–10 °C warmer than ambient air temperatures, especially in full sun. At both sites, Tleaf was warmer at higher air temperatures (Tair > 25 °C), but was cooler at lower Tair, contrary to the ‘leaf homeothermy hypothesis’. Warmed leaves showed significantly lower stomatal conductance (−0.05 mol m−2 s−1 or −43% across species) and net photosynthesis (−3.91 μmol m−2 s−1 or −39%), with similar rates in leaf respiration rates at a common temperature (no acclimation). Increased canopy leaf temperatures due to future warming could reduce carbon assimilation via reduced photosynthesis in these forests, potentially weakening the land carbon sink in tropical and temperate forests.
Graphical abstract
Undertaking recruitment for research in schools is an effective way to recruit young people for research participation but it is not without its challenges. Gaining access and coordinating many ...levels of different organisations and stakeholders whose cooperation and approval are crucial all add time and sometimes logistical challenges for the research team. In addition, recruiting around sensitive research topics can elicit additional barriers to successful research. The research team aimed to conduct a pragmatic cluster randomised controlled trial involving schools in a local government region in Victoria, Australia, to assess the effect of a vaccination-based educational card game called "Vaxcards" on vaccine consent returns. Schools were contacted via phone and email to determine which staff member would best be a contact point for a face-to-face meeting to discuss the methods and purpose of the study. Email follow-ups were scheduled to follow up non-responsive schools and consent forms. The minimum required sample size was 13. Of 31 eligible schools, 13 were recruited. The research team encountered several unanticipated challenges before achieving the recruitment target. The most common reasons for non-participation were being too busy with other commitments, concerns regarding the topic of vaccination being too sensitive, and concerns that key stakeholders in the school would not approve of the research topic of vaccination. One school required a review by a private research ethics board that rejected the study. Significant hesitancy and misinformation about vaccine science was observed that affected engagement with a small number of schools. This paper highlights the challenges of recruiting schools in the context of public anxieties about vaccines and has several important learning lessons for successful recruitment about sensitive topics. This includes navigating approval processes for research in schools, the importance of local champions, dealing with misinformation and the importance of strong relationships and organisational trust. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001753246 . Prospectively registered on 25 October 2018 8:24:21 AM.
Generation-integrated energy storage (GIES) systems store energy at some point along the transformation between the primary energy form and electricity. Instances exist already in natural hydro ...power, biomass generation, wave power, and concentrated solar power. GIES systems have been proposed for wind, nuclear power and they arise naturally in photocatalysis systems that are in development. GIES systems can compare very favourably in both performance and total cost against equivalent non-integrated systems comprising both generation and storage. Despite this, they have not hitherto been recognised as a discrete class of systems. Consequently policy decisions affecting development or demonstration projects and policy approaches concerning low-carbon generation are not fully informed. This paper highlights that policy structures exist militating against the development and introduction of GIES systems-probably to the detriment of overall system good.
•Current wisdom considers that energy storage and generation must be separate.•Integrating energy storage with generation lowers capital costs.•Integrating energy storage with generation reduces total energy losses.•Existing policies militate against such integrated systems being developed.
Arguments based on the biochemistry of photosynthesis predict a positive interaction between elevated atmospheric CO2 and temperature on photosynthesis as well as growth. In contrast, few long-term ...studies on trees find greater stimulation of photosynthesis in response to elevated CO2 at warmer compared with cooler temperatures. To test for CO2 × temperature interactions on leaf photosynthesis and whole-plant growth, we planted Eucalyptus globulus Labill. in climate-controlled chambers in the field at the Hawkesbury Forest Experiment research site, and investigated how photosynthetic enhancement changed across a range of seasonal temperatures. Trees were grown in a complete two-way factorial design with two CO2 concentrations (ambient and ambient + 240 ppm) and two temperatures (ambient and ambient + 3 °C) for 15 months until they reached ∼10 m height, after which they were harvested for biomass. There was significant enhancement of photosynthesis and growth with elevated CO2, with the photosynthetic stimulation varying with season, but there was no significant effect of warming. Photosynthetic enhancement was higher in summer (+46% at 28 °C) than in winter (+14% at 20 °C). Photosynthetic enhancement as a function of leaf temperature was consistent with theoretical expectations, but was strongly mediated by the intercellular CO2/ambient CO2 (Ci/Ca) ratio across seasons. Total tree biomass after 15 months was 66% larger in elevated CO2 (P = 0.017) with no significant warming effect detected. The fraction of biomass in coarse roots was reduced in warmed trees compared with ambient temperature controls, but there was no evidence of changed biomass allocation patterns in elevated CO2. We conclude that there are strong and consistent elevated CO2 effects on photosynthesis and biomass of E. globulus. It is crucial to consider stomatal conductance under a range of conditions to appraise the interactive effect of CO2 and temperature on photosynthetic enhancement and subsequent implications for tree growth and forest productivity in future climates.
This Letter presents measurements of the elliptic flow of charged particles as a function of pseudorapidity and centrality from Cu-Cu collisions at 62.4 and 200 GeV using the PHOBOS detector at the ...Relativistic Heavy Ion Collider. The elliptic flow in Cu-Cu collisions is found to be significant even for the most central events. For comparison with the Au-Au results, it is found that the detailed way in which the collision geometry (eccentricity) is estimated is of critical importance when scaling out system-size effects. A new form of eccentricity, called the participant eccentricity, is introduced which yields a scaled elliptic flow in the Cu-Cu system that has the same relative magnitude and qualitative features as that in the Au-Au system.