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Unchecked antimicrobial resistance is lethal and carries a high economic burden on the global economy. Primary care is central to the success of health service antibiotic stewardship programmes, as most of these infections are managed in the community. This article examines a pioneering programme that aims to reduce resistance to antibiotics commonly used to treat lower urinary tract infections. [ABSTRACT FROM AUTHOR]

This study examines filmic (mis)use of monstrous sharks as metaphors for exploring prey and predation, and how these films have incorporated postfeminist discourses around a symbolic overcoming of gendered violence. Research methods deployed include framing analysis of film narratives, dialogue and visual elements, including the key phrases and images used in the theatrical release posters and other promotional materials of shark attack horror films. The evolving shark horror film subgenre relies on common carefully constructed metaphors, narrative parallels, genre conventions and stylistic processes which not only convey gendered ideologies but build an entire contrived nightmare universe around human‐shark interactions. [ABSTRACT FROM AUTHOR]

There are concerns that sotrovimab has reduced efficacy at reducing hospitalisation risk against the BA.2 sub‐lineage of the Omicron SARS‐CoV‐2 variant. We performed a retrospective cohort (n = 8850) study of individuals treated with sotrovimab in the community, with the objective of assessing whether there were any differences in risk of hospitalisation of BA.2 cases compared with BA.1. We estimated that the hazard ratio of hospital admission with a length of stay of 2 days or more was 1.17 for BA.2 compared with BA.1 (95%CI 0.74–1.86). These results suggest that the risk of hospital admission was similar between the two sub‐lineages. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?How does the interaction between posture and gravity affect the stresses on the lung, particularly in highly inflated gravitationally non‐dependent regions, which are potentially vulnerable to increased mechanical stress and injury?What is the main finding and its importance?Changes in stress attributable to gravity are not well characterized between postures. Using a new metric of gravitational stress, we show that regions of the lung near maximal inflation have the greatest gravitational stresses while supine, but not while prone. In simulations of increased lung weight consistent with severe pulmonary oedema, the prone lung has lower gravitational stress in vulnerable, non‐dependent regions, potentially protecting them from overinflation and injury. Prone posture changes the gravitational vector, and potentially the stress induced by tissue deformation, because a larger lung volume is gravitationally dependent when supine, but non‐dependent when prone. To evaluate this, 10 normal subjects (six male and four female; age, means ± SD = 27 ± 6 years; height, 171 ± 9 cm; weight, 69 ± 13 kg; forced expiratory volume in the first second/forced expiratory volume as a percentage of predicted, 93 ± 6%) were imaged at functional residual capacity, supine and prone, using magnetic resonance imaging, to quantify regional lung density. We defined regional gravitational stress as the cumulative weight, per unit area, of the column of lung tissue below each point. Gravitational stress was compared between regions of differing inflation to evaluate differences between highly stretched, and thus potentially vulnerable, regions and less stretched lung. Using reference density values for normal lungs at total lung capacity (0.10 ± 0.03 g/ml), regions were classified as highly inflated (density < 0.13 g/ml, i.e., close to total lung capacity), intermediate (0.13 ≤ density < 0.16 g/ml) or normally inflated (density ≥ 0.16 g/ml). Gravitational stress differed between inflation categories while supine (−1.6 ± 0.3 cmH2O highly inflated; −1.4 ± 0.3 cmH2O intermediate; −1.1 ± 0.1 cmH2O normally inflated; P = 0.05) but not while prone (−1.4 ± 0.2 cmH2O highly inflated; −1.3 ± 0.2 cmH2O intermediate; −1.3 ± 0.1 cmH2O normally inflated; P = 0.39), and increased more with height from dependent lung while supine (−0.24 ± 0.02 cmH2O/cm supine; −0.18 ± 0.04 cmH2O/cm prone; P = 0.05). In simulated severe pulmonary oedema, the gradient in gravitational stress increased in both postures (all P < 0.0001), was greater in the supine posture than when prone (−0.57 ± 0.21 cmH2O/cm supine; −0.34 ± 0.16 cmH2O/cm prone; P = 0.0004) and was similar to the gradient calculated from supine computed tomography images in a patient with acute respiratory distress syndrome (−0.51 cmH2O/cm). The non‐dependent lung has greater gravitational stress while supine and might be protected while prone, particularly in the presence of oedema. [ABSTRACT FROM AUTHOR]

Key points: The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions.We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients.Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients.Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology. Many factors affect the distribution of pulmonary perfusion, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. An example is following the Fontan procedure, where pulmonary perfusion is passive, and heterogeneity may be increased because of the underlying pathophysiology leading to Fontan palliation, remodelling, or increased gravitational gradients from low flow. Another is pulmonary arterial hypertension (PAH), where gravitational gradients may be reduced secondary to high pressures, but remodelling may increase perfusion heterogeneity. We evaluated regional pulmonary perfusion in Fontan patients (n = 5), healthy young controls (Fontan control, n = 5), patients with PAH (n = 6) and healthy older controls (PAH control) using proton magnetic resonance imaging. Regional perfusion was measured using arterial spin labelling. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Mean perfusion was similar (Fontan = 2.50 ± 1.02 ml min−1 ml−1; Fontan control = 3.09 ± 0.58, PAH = 3.63 ± 1.95; PAH control = 3.98 ± 0.91, P = 0.26), and the slopes of gravitational gradients were not different (Fontan = −0.23 ± 0.09 ml min−1 ml−1 cm−1; Fontan control = −0.29 ± 0.23, PAH = −0.27 ± 0.09, PAH control = −0.25 ± 0.18, P = 0.91) between groups. Perfusion relative dispersion was greater in both Fontan and PAH than controls (Fontan = 1.46 ± 0.18; Fontan control = 0.99 ± 0.21, P = 0.005; PAH = 1.22 ± 0.27, PAH control = 0.91 ± 0.12, P = 0.02) but similar between patient groups (P = 0.13). These findings persisted after removing contributions from large blood vessels and gravitational gradients (all P < 0.05). We conclude that patients with Fontan physiology and PAH have increased pulmonary perfusion heterogeneity that is not explained by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects the effects of remodelling in PAH and possibly in Fontan physiology. Key points: The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions.We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients.Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients.Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Do highly trained male endurance athletes who develop exercise‐induced arterial hypoxaemia (EIAH) demonstrate reduced peripheral chemoresponsiveness during exercise?What is the main finding and its importance?Those with the lowest arterial saturation during exercise have a smaller ventilatory response to hypercapnia during exercise. There was no significant relationship between the hyperoxic ventilatory response and EIAH. The findings suggest that peripheral chemoresponsiveness to hypercapnia during exercise could play a role in the development of EIAH. The findings improve our understanding of the mechanisms that contribute to EIAH. Exercise‐induced arterial hypoxaemia (EIAH) is characterized by a decrease in arterial oxygen tension and/or saturation during whole‐body exercise, which may in part result from inadequate alveolar ventilation. However, the role of peripheral chemoresponsiveness in the development of EIAH is not well established. We hypothesized that those with the most severe EIAH would have an attenuated ventilatory response to hyperoxia and hypercapnia during exercise. To evaluate this, on separate days, we measured ventilatory sensitivity to hyperoxia and separately hypercapnia at rest and during three different exercise intensities (25, 50% of V̇O2max and ventilatory threshold (∼67% of V̇O2max)) in 12 males cyclists (V̇O2max = 66.6 ± 4.7 ml kg−1 min−1). Subjects were divided into two groups based on their end‐exercise arterial oxygen saturation (ear oximetry, SpO2): a normal oxyhaemoglobin saturation group (NOS, SpO2 = 93.4 ± 0.4%, n = 5) and a low oxyhaemoglobin saturation group (LOS, SpO2 = 89.9 ± 0.9%, n = 7). There was no difference in V̇O2max (66.4 ± 2.9 vs. 66.8 ± 6.0 ml kg−1 min−1, respectively, P = 0.9), peak ventilation during maximal exercise (182 ± 15 vs. 197 ± 32 l min−1, respectively, P = 0.36) or ventilatory response to hyperoxia (P = 0.98) at any exercise intensity between NOS and LOS groups. However, those in the LOS group had a significantly lower ventilatory response to hypercapnia (P = 0.004, (η2 = 0.18). There was also a significant relationship between the mean hypercapnic response and end‐exercise SpO2 (r = 0.75, P = 0.009) but not between the mean hyperoxic response and end‐exercise SpO2 (r = 0.21, P = 0.51). A blunted hypercapnic ventilatory response may contribute to EIAH in highly trained men due to a failure to increase ventilation sufficiently to offset exercise‐induced gas exchange impairments. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion (V˙A/Q˙) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2‐dependent manner. Specific ventilation imaging data are acquired during five wash‐in/wash‐out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated‐SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙, and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p =.84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p =.04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p =.54); Deadspace was not significantly different (p =.54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p =.052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized. [ABSTRACT FROM AUTHOR]

Key points: Imaging techniques such as contrast echocardiography suggest that anatomical intra‐pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung.To evaluate this discrepancy, we compared anatomical shunt with 25‐µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET).Intra‐pulmonary shunt measured by 25‐µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt.A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange. The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra‐pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right‐to‐left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25‐µm microspheres and compared the results to contrast echocardiography and MIGET‐determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2 µg kg−1 min−1i.v. dopamine, (3) 10 µg kg−1 min−1i.v. dobutamine, and (4) following creation of an intra‐atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25‐µm microspheres recovered in systemic arterial blood. Ventilation–perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25‐µm microspheres. Across all conditions, anatomical shunt measured by 25‐µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3 ± 7.4%; MIGET: 2.6 ± 6.1%, P = 0.64). Saline contrast bubble score was associated with microsphere shunt (ρ = 0.60, P < 0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22–48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25‐µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange. Key points: Imaging techniques such as contrast echocardiography suggest that anatomical intra‐pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung.To evaluate this discrepancy, we compared anatomical shunt with 25‐µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET).Intra‐pulmonary shunt measured by 25‐µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt.A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange. [ABSTRACT FROM AUTHOR]

Key points: Precapillary gas exchange for oxygen has been documented in both humans and animals.It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET).We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1 cm proximal to the wedge position) and systemic artery.Some 12–19% of pulmonary gas exchange occurred within small (1.7 mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane.Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. Some pulmonary gas exchange is known to occur proximal to the pulmonary capillary, although the magnitude of this gas exchange is uncertain, and it is unclear whether oxygen and inert gases are similarly affected. This has implications for measuring shunt and associated gas exchange consequences. By measuring respiratory and inert gas levels in the proximal pulmonary artery (P), a distal pulmonary artery 1 cm proximal to the wedge position (using a 5‐F catheter) (D) and a systemic artery (A), we evaluated precapillary gas exchange in 27 paired samples from seven anaesthetized, ventilated canines. Fractional precapillary gas exchange (F) was quantified for each gas as F = (P – D)/(P – A). The lowest solubility inert gases, sulphur hexafluoride (SF6) and ethane were used because, with higher solubility gases, the P–A difference is sufficiently small that experimental error prevents accurate assessment of F. Distal samples (n = 12) with oxygen (O2) saturation values that were (within experimental error) equal to or above systemic arterial values, suggestive of retrograde capillary blood aspiration, were discarded, leaving 15 for analysis. D was significantly lower than P for SF6 (D/P = 88.6 ± 18.1%; P = 0.03) and ethane (D/P = 90.6 ± 16.0%; P = 0.04), indicating partial excretion of inert gas across small pulmonary arteries. Distal pulmonary arterial O2 saturation was significantly higher than proximal (74.1 ± 6.8% vs. 69.0 ± 4.9%; P = 0.03). Fractional precapillary gas exchange was similar for SF6, ethane and O2 (0.12 ± 0.19, 0.12 ± 0.20 and 0.19 ± 0.26, respectively; P = 0.54). Under these experimental conditions, 12–19% of pulmonary gas exchange occurs within the small pulmonary arteries and the extent is similar between oxygen and inert gases. Key points: Precapillary gas exchange for oxygen has been documented in both humans and animals.It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET).We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1 cm proximal to the wedge position) and systemic artery.Some 12–19% of pulmonary gas exchange occurred within small (1.7 mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane.Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. [ABSTRACT FROM AUTHOR]

Key points Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes., The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution., Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch., Abstract Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation-perfusion matching. Density-normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects ( n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non-dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice ( P = 0.10). The greatest expansion was seen in the dependent region ( P < 0.0001: dependent vs non-dependent, P < 0.0001: dependent vs middle) and RLL ( P = 0.0015: RLL vs RUL, P < 0.0001: RLL vs RML). Neither nDNP recruitment to RLL [+500 ml = −0.047(0.145), +1 litre = 0.018(0.096)] nor to dependent lung [+500 ml = −0.058(0.126), +1 litre = −0.023(0.106)] were found. Instead, redistribution was seen in decreased nDNP in the non-dependent [+500 ml = −0.075(0.152), +1 litre = −0.137(0.167)) and increased nDNP in the gravitational middle lung [+500 ml = 0.098(0.058), +1 litre = 0.093(0.081)] ( P = 0.01). However, there was no significant lobar redistribution ( P < 0.89). Contrary to our hypothesis, based on the comparison between gravitational and lobar perfusion data, perfusion was not redistributed to the regions of the most inflation. This suggests that either changes in hydrostatic pressure or transmural pressure distribution in the gravitational direction are implicated in the redistribution of perfusion away from the non-dependent lung. [ABSTRACT FROM AUTHOR]

The measurement of pulmonary perfusion (blood delivered to the capillary bed within a voxel) using arterial spin labeling (ASL) magnetic resonance imaging is often complicated by signal artifacts from conduit vessels that carry blood destined for voxels at a distant location in the lung. One approach to dealing with conduit vessel contributions involves the application of an absolute threshold on the ASL signal. While useful for identifying a subset of the most dominant high signal conduit image features, signal thresholding cannot discriminate between perfusion and conduit vessel contributions at intermediate and low signal. As an alternative, this article discusses a data-driven statistical approach based on statistical clustering for characterizing and discriminating between capillary perfusion and conduit vessel contributions over the full signal spectrum. An ASL flow image is constructed from the difference between a pair of tagged magnetic resonance images. However, when viewed as a bivariate projection that treats the image pair as independent measures (rather than the univariate quantity that results from the subtraction of the two images), the signal associated with capillary perfusion contributions is observed to cluster independently of the signal associated with conduit vessel contributions. Analyzing the observed clusters using a Gaussian mixture model makes it possible to discriminate between conduit vessel and capillary-perfusion-dominated signal contributions over the full signal spectrum of the ASL image. As a demonstration of feasibility, this study compares the proposed clustering approach with the standard absolute signal threshold strategy in a small number of test images. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The field of proton lung MRI is advancing on a variety of fronts. In the realm of functional imaging, it is now possible to use arterial spin labeling (ASL) and oxygen-enhanced imaging techniques to quantify regional perfusion and ventilation, respectively, in standard units of measurement. By combining these techniques into a single scan, it is also possible to quantify the local ventilation-perfusion ratio, which is the most important determinant of gas-exchange efficiency in the lung. To demonstrate potential for accurate and meaningful measurements of lung function, this technique was used to study gravitational gradients of ventilation, perfusion, and ventilation-perfusion ratio in healthy subjects, yielding quantitative results consistent with expected regional variations. Such techniques can also be applied in the time domain, providing new tools for studying temporal dynamics of lung function. Temporal ASL measurements showed increased spatial-temporal heterogeneity of pulmonary blood flow in healthy subjects exposed to hypoxia, suggesting sensitivity to active control mechanisms such as hypoxic pulmonary vasoconstriction, and illustrating that to fully examine the factors that govern lung function it is necessary to consider temporal as well as spatial variability. Further development to increase spatial coverage and improve robustness would enhance the clinical applicability of these new functional imaging tools. In the realm of structural imaging, pulse sequence techniques such as ultrashort echo-time radial k-space acquisition, ultrafast steady-state free precession, and imaging-based diaphragm triggering can be combined to overcome the significant challenges associated with proton MRI in the lung, enabling high-quality three-dimensional imaging of the whole lung in a clinically reasonable scan time. Images of healthy and cystic fibrosis subjects using these techniques demonstrate substantial promise for non-contrast pulmonary angiography and detailed depiction of airway disease. Although there is opportunity for further optimization, such approaches to structural lung imaging are ready for clinical testing. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: To validate a fast gradient echo sequence for rapid (9 s) quantitative imaging of lung water. Materials and Methods: Eleven excised pig lungs were imaged with a fast GRE sequence in triplicate, in the sagittal plane at 2 levels of inflation pressure (5 and 15 cm H [ABSTRACT FROM AUTHOR]

There is a gravitational influence on pulmonary perfusion, including in the most dependent lung, where perfusion is reduced, termed Zone 4. Studies using xenon-133 show Zone 4 behaviour, present in the dependent 4 cm at total lung capacity (TLC), affects the dependent 11 cm at functional residual capacity (FRC) and almost all the lung at residual volume (RV). These differences were ascribed to increased resistance in extra-alveolar vessels at low lung volumes although other mechanisms have been proposed. To further evaluate the behaviour of perfusion in dependent lung using a technique that directly measures pulmonary perfusion and corrects for tissue distribution by measuring regional proton density, seven healthy subjects (age = 38 ± 6 years, FEV= 104 ± 7% predicted) underwent magnetic resonance imaging in supine posture. Data were acquired in the right lung during breath-holds at RV, FRC and TLC. Arterial spin labelling quantified regional pulmonary perfusion, which was normalized for regional proton density measured using a fast low-angle shot technique. The height of the onset of Zone 4 behaviour was not different between lung volumes ( P= 0.23). There were no significant differences in perfusion (expressed as ml min g) between lung volumes in the gravitationally intermediate (RV = 8.9 ± 3.1, FRC = 8.1 ± 2.9, TLC = 7.4 ± 3.6; P= 0.26) and dependent lung (RV = 6.6 ± 2.4, FRC = 6.1 ± 2.1, TLC = 6.4 ± 2.6; P= 0.51). However, at TLC perfusion was significantly lower in non-dependent lung than at FRC or RV (3.6 ± 3.3, 7.7 ± 1.5, 7.9 ± 2.0, respectively; P < 0.001). These data suggest that the mechanism of the reduction in perfusion in dependent lung is unlikely to be a result of lung volume related increases in resistance in extra-alveolar vessels. In supine posture, the gravitational influence on perfusion is remarkably similar over most of the lung, irrespective of lung volume. The lung is subject to multiple influences that affect its function. In particular the effect of gravity has attracted considerable interest, especially as it relates to the distribution of blood flow. In the most gravitationally dependent part of the lung, blood flow is reduced, and this region is known as Zone 4. Zone 4 has been suggested to result from increased resistance in some of the blood vessels, and this effect is thought to be the smallest when the lung is at a high volume as the elastic structures of the lung hold the vessels open minimizing resistance. Using novel magnetic resonance imaging techniques to measure blood flow, this study shows that the distribution of blood flow in the dependent lung is unchanged when the lung volume is changed and suggests that the intrinsic structure of the vessels is a more likely explanation for this behaviour. [ABSTRACT FROM AUTHOR]

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the 'Slinky' effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed. J. Magn. Reson. Imaging 2010;32:1287-1301. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head-down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% ( p < 0.005). Head-down tilt significantly reduced the lognormal scale parameter ( p = 0.01) but not the shape parameter or GSD. The RD increased post-tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To evaluate lung water density at three different levels of lung inflation in normal lungs using a fast gradient echo sequence developed for rapid imaging. Materials and Methods Ten healthy volunteers were imaged with a fast gradient echo sequence that collects 12 images alternating between two closely spaced echoes in a single 9-s breathhold. Data were fit to a single exponential to determine lung water density and T [ABSTRACT FROM AUTHOR]

Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O2 transport in several different and potentially conflicting ways, we examined its effects on pulmonary and muscle gas exchange and acid–base status during cycle exercise at ∼30, 50 and 90% in normoxia and acute hypoxia . In a double-blind, order-balanced, crossover design, six healthy, trained men (normoxic = 59 ml kg−1 min−1) exercised at both values after ACZ (3 doses of 250 mg, 8 h apart) and placebo. One week later this protocol was repeated using the other drug (placebo or ACZ). We measured cardiac output , leg blood flow (LBF), and muscle and pulmonary gas exchange, the latter using the multiple inert gas elimination technique. ACZ did not significantly affect , , LBF or muscle gas exchange. As expected, ACZ led to lower arterial and venous blood [HCO3−], pH and lactate levels ( P < 0.05), and increased ventilation ( P < 0.05). In both normoxia and hypoxia, ACZ resulted in higher arterial PO2 and saturation and a lower alveolar–arterial PO2 difference (Aa DO2) due to both less mismatch and less diffusion limitation ( P < 0.05). In summary, ACZ improved arterial oxygenation during exercise, due to both greater ventilation and more efficient pulmonary gas exchange. However, muscle gas exchange was unaffected. [ABSTRACT FROM AUTHOR]

Women may experience greater pulmonary gas exchange impairment during exercise than men. To test this we used the multiple inert gas elimination technique to study eight women and seven men matched for age, height and VO2max (∼48 ml kg-1 min-1) during normoxic and hypoxic (inspired PO2 = 95 Torr) cycle exercise. Resting lung function was similar between the sexes, except for a lower carbon monoxide diffusing capacity (DLco) in women (P < 0.05). Arterial PO2, Pco2 and alveolar-arterial O2 difference (A-- aDO2) were not significantly different in men and women. Despite a lower diffusing capacity for O2 (DLO2) in women, the ratio DLO2/βQ (which estimates pulmonary end-capillary diffusion equilibrium) was similar between men and women and estimates of diffusion limitation during hypoxic exercise were not different between the sexes. Ventilation-perfusion inequality (described by the second moment of the perfusion distribution, logSDQ) increased during both normoxic and hypoxic exercise. Surprisingly, logSDQ values were slightly lower for women under all conditions (P < 0.05), but this did not significantly affect gas exchange. These data indicate that these active women, despite a lower DLco and DLo2, do not experience greater exercise-induced abnormalities in gas exchange than men matched for age, height, aerobic capacity and lung size. Possibly fitness level and lung size are more important in determining whether or not pulmonary gas exchange impairment occurs during exercise than sex per se. [ABSTRACT FROM AUTHOR]

A discussion of the legal aspects of female genital mutilation The purpose of this paper is to examine the position of the nurse/midwife in the United Kingdom when involved with the care of a woman or female child who has suffered genital mutilation, which is an illegal practice in this country and most other areas of the world. The types of circumcision commonly practised are introduced, the prevalent reasons for the continuation of the practice among certain ethnic groups are presented, and the range of issues to be considered by the nurse is examined. These include international and national legal aspects which do not exist in isolation and are considered in context with cultural, medical, human rights and gender issues. Nursing legal issues include child protection, consent, advocacy and confidentiality, which invoke the Code Of Professional Conduct of the United Kingdom Central Council for Nursing Midwifery & Health Visiting. Midwives and nurses working in the field of gynaecology have raised questions regarding possible courses of action to take when presented with this issue. Increased knowledge can help to inform those decisions. Therefore, implications for future practice are addressed, together with recommendations to assist nurses with decision making when faced with this scenario in the future. [ABSTRACT FROM AUTHOR]

Dietary cholesterol (CHL) and triglycerides (TG) can influence plasma, hepatic, and biliary lipid composition, but effects on lipids in these three compartments during the early stages of CHL gallstone formation have not been studied in parallel. We fed prairie dogs diets containing one of four tes oils (safflower, coconut, olive, or menhaden) at either 5 or 40% of calories, in the presence of 0 or 0.34% CHL, for 3 wk. In the absence of dietary CHL, increases in dietary TG produced 50–200% increases in the concentrations of biliary CHL and hepatic cholesteryl ester (CE), while the concentrations of hepatic free CHL (FC) as well as plasma FC and CE remained relatively unchanged. Increasing dietary CHL to 0.34% resulted in increases in hepatic FC of approximately 50% for all four fats regardless of whether they were supplied at 5 or 40% of calories. CHL supplementation caused more pronounced increases in biliary CHL (200–400%), hepatic CE (50–200%), plasma FC (up to 100%), and plasma CE (up to 150%), and these increases were exacerbated by concurrent supplementation of dietary fat and CHL (biliary CHL: 300–700%; hepatic CE: 100–250%; plasma FC: up to 165%; plasma CE: 100–350%). These results indicate that enhanced secretion of biliary CHL and, to a lesser extent, increased synthesis of hepatic CE, may be primary mechanisms for maintaining the hepatic FC pool. Furthermore, dietary CHL and high levels of fat intake are independent risk factors for increasing biliary CHL concentrations, and adverse effects on lipid concentrations in plasma and bile tend to be exacerbated by ingestion of diets rich in both fat and CHL. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion (V˙A/Q˙) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2‐dependent manner. Specific ventilation imaging data are acquired during five wash‐in/wash‐out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated‐SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙, and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p =.84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p =.04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p =.54); Deadspace was not significantly different (p =.54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p =.052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized. [ABSTRACT FROM AUTHOR]