Accurate measures of changes in regional lung air volumes from chest x-rays of small animals.

Objective. To develop a robust technique for calculating regional volume changes within the lung from x-ray radiograph sequences captured during ventilation, without the use of computed tomography (CT).Approach. This technique is based on the change in transmitted x-ray intensity that occurs for each lung region as air displaces the attenuating lung tissue.Main results. Lung air volumes calculated from x-ray intensity changes showed a strong correlation (R2= 0.98) against the true volumes, measured from high-resolution CT. This correlation enables us to accurately convert projected intensity data into relative changes in lung air volume. We have applied this technique to measure changes in regional lung volumes from x-ray image sequences of mechanically ventilated, recently-deceased newborn rabbits, without the use of CT.Significance. This method is suitable for biomedical research studies,enabling quantitative regional measurement of relative lung air volumes at high temporal resolution, and shows great potential for future clinical application.

Antimicrobial resistance in enteric bacteria: current state and next-generation solutions.

Antimicrobial resistance is one of the largest threats to global health and imposes substantial burdens in terms of morbidity, mortality, and economic costs. The gut is a key conduit for the genesis and spread of antimicrobial resistance in enteric bacterial pathogens. Distinct bacterial species that cause enteric disease can exist as invasive enteropathogens that immediately evoke gastrointestinal distress, or pathobionts that can arise from established bacterial commensals to inflict dysbiosis and disease. Furthermore, various environmental reservoirs and stressors facilitate the evolution and transmission of resistance. In this review, we present a comprehensive discussion on circulating resistance profiles and gene mobilization strategies of the most problematic species of enteric bacterial pathogens. Importantly, we present emerging approaches toward surveillance of pathogens and their resistance elements as well as promising treatment strategies that can circumvent common resistance mechanisms.

Tuning behaviour of slotted vernier widely tunable lasers.

A detailed thermo-optic model combining the 1D transfer matrix method and a 3D finite element method is developed and used to simulate a widely tunable vernier laser based on surface etched slots. The model is used to investigate the experimentally observed tuning patterns. At low injection currents, carrier tuning dominates, while at high currents, thermal tuning is the dominant mechanism. These lasers are very simple to fabricate and have a wide tuning over 50 nm, but SMSR and linewidth performance is not yet optimised. Simulations give an insight into the observed tuning efficiency and linewidth performance of the lasers, with high carrier densities in the grating regions being identified as a key area, which is presently limiting these parameters.

The Delphi technique in radiography education research.

OBJECTIVES: To describe and review the Delphi technique as a tool for radiographers engaged in mixed-methods research whereby agreement is required on the proficiencies needed by educational programmes for pre- and post- registration radiographers. This is achieved through a description offering a brief history of the technique. Through a literature search, radiography education research using this technique is identified. A protocol for a research project using the technique is presented. Using this worked example, advantages and disadvantages of the method are explored including sampling of participants, sample size, number of rounds and methods of feedback. KEY FINDINGS: There are limited examples of the use of the Delphi technique in radiography literature including considerations on how to select experts and panel size. CONCLUSION: The Delphi technique is a suitable method for establishing collective agreement in the design of radiography educational interventions. Additional research is needed to deepen this evidence-based knowledge.

Athermal operation of multi-section slotted tunable lasers.

Two distinct athermal bias current procedures based on thermal tuning are demonstrated for a low-cost, monotlithic, three section slotted single mode laser, achieving mode-hop free wavelength stability of ± 0.04 nm / 5 GHz over a temperature range of 8-47 °C. This is the first time that athermal performance has been demonstrated for a three-section slotted laser with simple fabrication, and is well within the 50 GHz grid spacing specified for DWDM systems. This performance is similar to experiments on more complex DS-DBR lasers, indicating that strong athermal performance can be achieved using our lower-cost three section devices. An analytical model and thermoreflectance measurements provide further insight into the operation of multi-section lasers and lay the foundation for an accurate predictive tool for optimising such devices for athermal operation.

Reducing thermal crosstalk in ten-channel tunable slotted-laser arrays.

Given the tight constraints on the wavelength stability of sources in optical networks, the thermal crosstalk between operating devices in a ten-channel thermally-tunable slotted laser array for DWDM applications has been investigated. It was found experimentally the current standard thermal solution with the laser array chip mounted on an AlN carrier does not allow for wavelength stability of ± 25 GHz ( ± 2 K) with a temperature rise of 5 K measured in a device with 100 mA (CW) applied to a neighbouring laser (device spacing = 360 µm). A combined experimental/numerical approach revealed solid state submounts comprising diamond or highly ordered pyrolytic graphite are inadequate to reduce crosstalk below an allowable level. Numerical simulations of advanced cooling technologies reveal a microfluidic enabled substrate would reduce thermal crosstalk between operational devices on the chip to acceptable levels. Critically our simulations show this reduced crosstalk is not at the expense of device tunability as the thermal resistance of individual lasers remains similar for the base and microfluidic cases.

Portal vein embolization improves rate of resection of extensive colorectal liver metastases without worsening survival.

BACKGROUND: Most patients requiring an extended right hepatectomy (ERH) have an inadequate standardized future liver remnant (sFLR) and need preoperative portal vein embolization (PVE). However, the clinical and oncological impact of PVE in such patients remains unclear. METHODS: All consecutive patients presenting at the M. D. Anderson Cancer Center with colorectal liver metastases (CLM) requiring ERH at presentation from 1995 to 2012 were studied. Surgical and oncological outcomes were compared between patients with adequate and inadequate sFLRs at presentation. RESULTS: Of the 265 patients requiring ERH, 126 (47·5 per cent) had an adequate sFLR at presentation, of whom 123 underwent a curative resection. Of the 139 patients (52·5 per cent) who had an inadequate sFLR and underwent PVE, 87 (62·6 per cent) had a curative resection. Thus, the curative resection rate was increased from 46·4 per cent (123 of 265) at baseline to 79·2 per cent (210 of 265) following PVE. Among patients who underwent ERH, major complication and 90-day mortality rates were similar in the no-PVE and PVE groups (22·0 and 4·1 per cent versus 31 and 7 per cent respectively); overall and disease-free survival rates were also similar in these two groups. Of patients with an inadequate sFLR at presentation, those who underwent ERH had a significantly better median overall survival (50·2 months) than patients who had non-curative surgery (21·3 months) or did not undergo surgery (24·7 months) (P = 0·002). CONCLUSION: PVE enabled curative resection in two-thirds of patients with CLM who had an inadequate sFLR and were unable to tolerate ERH at presentation. Patients who underwent curative resection after PVE had overall and disease-free survival rates equivalent to those of patients who did not need PVE.

Induced magnetic moment of Eu(3+) ions in GaN.

Magnetic semiconductors with coupled magnetic and electronic properties are of high technological and fundamental importance. Rare-earth elements can be used to introduce magnetic moments associated with the uncompensated spin of 4f-electrons into the semiconductor hosts. The luminescence produced by rare-earth doped semiconductors also attracts considerable interest due to the possibility of electrical excitation of characteristic sharp emission lines from intra 4f-shell transitions. Recently, electroluminescence of Eu-doped GaN in current-injection mode was demonstrated in p-n junction diode structures grown by organometallic vapour phase epitaxy. Unlike most other trivalent rare-earth ions, Eu(3+) ions possess no magnetic moment in the ground state. Here we report the detection of an induced magnetic moment of Eu(3+) ions in GaN which is associated with the (7)F(2) final state of (5)D(0)→(7)F(2) optical transitions emitting at 622 nm. The prospect of controlling magnetic moments electrically or optically will lead to the development of novel magneto-optic devices.

Amygdala protein kinase C epsilon controls alcohol consumption.

Alcoholism is a progressive disorder that involves the amygdala. Mice lacking protein kinase C epsilon (PKCepsilon) show reduced ethanol consumption, sensitivity and reward. We therefore investigated whether PKCepsilon signaling in the amygdala is involved in ethanol consumption. Local knockdown of PKCepsilon in the amygdala reduced ethanol consumption and preference in a limited-access paradigm. Further, mice that are heterozygous for the PKCepsilon allele consume less ethanol compared with wild-type mice in this paradigm. These mice have a >50% reduction in the abundance of PKCepsilon in the amygdala compared with wild-type mice. We conclude that amygdala PKCepsilon is important for ethanol consumption in mice.

Dynamic measures of regional lung air volume using phase contrast x-ray imaging.

Phase contrast x-ray imaging can provide detailed images of lung morphology with sufficient spatial resolution to observe the terminal airways (alveoli). We demonstrate that quantitative functional and anatomical imaging of lung ventilation can be achieved in vivo using two-dimensional phase contrast x-ray images with high contrast and spatial resolution (<100 microm) in near real time. Changes in lung air volume as small as 25 microL were calculated from the images of term and preterm rabbit pup lungs (n = 28) using a single-image phase retrieval algorithm. Comparisons with plethysmography and computed tomography showed that the technique provided an accurate and robust method of measuring total lung air volumes. Furthermore, regional ventilation was measured by partitioning the phase contrast images, which revealed differences in aeration for different ventilation strategies.

Increased response to morphine in mice lacking protein kinase C epsilon.

The protein kinase C (PKC) family of serine-threonine kinases has been implicated in behavioral responses to opiates, but little is known about the individual PKC isozymes involved. Here, we show that mice lacking PKCepsilon have increased sensitivity to the rewarding effects of morphine, revealed as the expression of place preference and intravenous self-administration at very low doses of morphine that do not evoke place preference or self-administration in wild-type mice. The PKCepsilon null mice also show prolonged maintenance of morphine place preference in response to repeated testing when compared with wild-type mice. The supraspinal analgesic effects of morphine are enhanced in PKCepsilon null mice, and the development of tolerance to the spinal analgesic effects of morphine is delayed. The density of mu-opioid receptors and their coupling to G-proteins are normal. These studies identify PKCepsilon as a key regulator of opiate sensitivity in mice.

Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs.

Although increased lung expansion markedly alters lung growth and epithelial cell differentiation during fetal life, the effect of increasing lung expansion after birth is unknown. We hypothesized that increased basal lung expansion, caused by ventilating newborn lambs with a positive end-expiratory pressure (PEEP), would stimulate lung growth and alter alveolar epithelial cell (AEC) proportions and decrease surfactant protein mRNA levels. Two groups of lambs were sedated and ventilated with either 0 cmH(2)O PEEP (controls, n = 5) or 10 cmH(2)O PEEP (n = 5) for 48 h beginning at 15 +/- 1 days after normal term birth. A further group of nonventilated 2-wk-old lambs was used for comparison. We determined wet and dry lung weights, DNA and protein content, a labeling index for proliferating cells, surfactant protein mRNA expression, and proportions of AECs using electron microscopy. Although ventilating lambs for 48 h with 10 cmH(2)O PEEP did not affect total lung DNA or protein, it significantly increased the proportion of proliferating cells in the lung when compared with nonventilated 2-wk-old controls and lambs ventilated with 0 cmH(2)O PEEP (control: 2.6 +/- 0.5%; 0 PEEP: 1.9 +/- 0.3%; 10 PEEP: 3.5 +/- 0.3%). In contrast, no differences were observed in AEC proportions or surfactant protein mRNA levels between either of the ventilated groups. This study demonstrates that increases in end-expiratory lung volumes, induced by the application of PEEP, lead to increased lung growth in mechanically ventilated 2-wk-old lambs but do not alter the proportions of AECs.

VDUP1: a potential mediator of expansion-induced lung growth and epithelial cell differentiation in the ovine fetus.

The degree of fetal lung expansion is a critical determinant of fetal lung growth and alveolar epithelial cell (AEC) differentiation, although the mechanisms involved are unknown. As VDUP1 (vitamin D3-upregulated protein 1) can modulate cell proliferation, can induce cell differentiation, and is highly expressed in the lung, we have investigated the effects of fetal lung expansion on VDUP1 expression and its relationship to expansion-induced fetal lung growth and AEC differentiation in fetal sheep. Alterations in fetal lung expansion caused profound changes in VDUP1 mRNA levels in lung tissue. Increased fetal lung expansion significantly reduced VDUP1 mRNA levels from 100+/-8% in control fetuses to 37+/-4, 46+/-4, and 45+/-9% of control values at 2, 4, and 10 days of increased fetal lung expansion, respectively. Reduced fetal lung expansion increased VDUP1 mRNA levels from 100+/-16% in control fetuses to 162+/-16% of control values after 7 days. VDUP1 was localized to airway epithelium in small bronchioles, AECs, and some mesenchymal cells. Its expression was inversely correlated with cell proliferation during normal lung development (R2=0.972, P<0.002) as well as in response to alterations in fetal lung expansion (R2=0.956, P<0.001) and was positively correlated with SP-B expression during normal lung development (R2=0.803, P<0.0001) and following altered lung expansion (R2=0.817, P<0.001). We suggest that VDUP1 may be an important mediator of expansion-induced lung cell proliferation and AEC differentiation in the developing lung.

Dynamic imaging of the lungs using x-ray phase contrast.

High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice.

Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.

Changes in alveolar epithelial cell proportions during fetal and postnatal development in sheep.

Basal lung expansion is an important determinant of alveolar epithelial cell (AEC) phenotype in the fetus. Because basal lung expansion increases toward term and is reduced after birth, we hypothesized that these changes would be associated with altered proportions of AECs. AEC proportions were calculated with electron microscopy in fetal and postnatal sheep. Type I AECs increased from 4.8 +/- 1.3% at 91 days to 63.0 +/- 3.6% at 111 days of gestation, remained at this level until term, and decreased to 44.8 +/- 1.8% after birth. Type II AECs increased from 4.3 +/- 1.5% at 111 days to 29.6 +/- 4.1% at 128 days of gestation, remained at this level until term, and then increased to 52.9 +/- 1.5% after birth. Surfactant protein (SP)-A, -B and -C mRNA levels increased with increasing gestational age before birth, but the changes in SP expression after birth were inconsistent. Thus before birth type I AECs predominate, whereas after birth type II AECs predominate, possibly due to the reduction in basal lung expansion associated with the entry of air into the lungs.

Increased expansion of the lung stimulates calmodulin 2 expression in fetal sheep.

Obstruction of the fetal trachea causes the lungs to expand with accumulated liquid. Although this is a potent stimulus for lung growth, the mechanisms involved are unknown. Our aim was to identify genes that are differentially expressed as a result of increased fetal lung expansion. Using differential display RT-PCR, we isolated a cDNA fragment partially encoding calmodulin 2 (CALM2) and identified the remainder of the coding region by 5'-rapid amplification of cDNA ends. Differential expression of CALM2 was confirmed by Northern blot analysis; CALM2 mRNA levels were increased to 161 +/- 5% of control at 2 days of increased lung expansion, induced by tracheal obstruction (TO), and had returned to control levels at days 4 and 10. Using in situ hybridization analysis, we found that the proportion of CALM2-labeled cells increased from 10.3 +/- 1.0% to 21.4 +/- 6.8% by 2 days of TO. This increase in CALM2 expression was reflected by a tendency for calmodulin protein levels to increase from 122.7 +/- 17.3 to 156.5 +/- 17.7 at 2 days of TO. Thus increases in fetal lung expansion result in time-dependent changes in CALM2 mRNA levels, which closely parallels the changes in lung DNA synthesis rates. As calmodulin is essential for cell proliferation, increased CALM2 mRNA levels may reflect an important role for calmodulin in expansion-induced fetal lung growth.

Creation of a transrenal arteriovenous dialysis shunt: feasibility study in a swine model.

PURPOSE: To investigate the feasibility of percutaneous renal artery and vein access for the creation of a transrenal arteriovenous hemodialysis graft. MATERIALS AND METHODS: Renal-artery-to-ipsilateral-renal-vein conduits were constructed with use of entirely percutaneous techniques in seven swine. Renal artery and vein access was performed in six animals with use of a retrograde (inside-out) technique and in one animal with use of an antegrade (outside-in) technique. Modified 8-F sheaths were used in the first three animals and Wallgrafts were used in the final four animals to form the arterial and venous limbs of each shunt. The arterial and venous limbs were joined together by a subcutaneous segment of 6-mm reinforced polytetrafluoroethylene (PTFE) in five animals and by external conduits in two animals. Wallgrafts were deployed from the renal artery and vein into the segments of PTFE. The free ends of each conduit were tunneled and joined together to close the arteriovenous circuit. Post-shunt angiography was used in all animals to document successful shunt creation and demonstrate rapid arteriovenous shunting as a determinant of technical feasibility. Two of the seven animals received additional anticoagulation therapy and/or antiplatelet therapy to prevent shunt thrombosis during the follow-up period. The three initial animals were killed within 2 hours of shunt creation, and two of the remaining four animals returned for angiographic follow-up, one on day 2 and one on day 9. All animals underwent a complete necropsy to assess for potential complications including hemorrhage and vascular or bowel injury. RESULTS: Retrograde renal arterial and venous access was successful in all six animals in which it was attempted. Five of six arterial accesses and four of six venous accesses traversed the peritoneum with two arterial accesses and one venous access penetrating a loop of large bowel. Antegrade access was performed and successfully accomplished in the final animal. Brisk arteriovenous shunting was demonstrated on completion angiography in all animals. Graft occlusion was present in the two animals that returned for follow-up and two animals died before follow-up as a result of graft leakage and subsequent hemorrhage. Minimal perinephric and intrarenal hemorrhage was demonstrated at necropsy after shunt insertion in the remaining five animals. Renal infarction was present in all kidneys used for transrenal access. CONCLUSION: The transrenal approach for the creation of a percutaneous arteriovenous shunt is feasible after renal artery and vein access by either the retrograde or antegrade technique. Additional technical refinements of the procedure and the devices used will be necessary before follow-up studies are conducted.

Percutaneous closure of a subclavian artery injury after inadvertent catheterization.

Life-threatening complications of subclavian central venous access are rare. Herein a case of inadvertent subclavian artery catheterization and subsequent percutaneous arterial repair with use of the Prostar XL suture-mediated closure device and temporary balloon tamponade is reported. This approach obviated a complex surgical intervention that would have required medial clavicle resection.