Lower endothelium-dependent microvascular function in adult breast cancer patients receiving radiation therapy.

PURPOSE: Cancer patients with a history of radiotherapy are at an increased risk of ischemic heart disease. Preclinical animal studies demonstrate markedly impaired acetylcholine (ACh)-mediated endothelium-dependent vasorelaxation within days to weeks post-irradiation, however, whether microvascular function is affected in the intact human circulation during cancer radiation therapy has yet to be determined. MATERIALS AND METHODS: Using laser-Doppler flowmetry, microvascular endothelium-dependent and independent responses were evaluated through iontophoresis of acetylcholine (ACh) (part 1, n = 7) and sodium nitroprusside (SNP) (part 2, n = 8), respectively, in women currently receiving unilateral chest adjuvant radiation therapy for breast cancer. Measurements were performed at the site of radiation treatment and at a contralateral control, non-radiated site. Cutaneous vascular conductance (CVC) was calculated by normalizing for mean arterial pressure. RESULTS AND CONCULSIONS: In part 1, patients received an average radiation dose of 2104 ± 236 cGy. A significantly lower peak ACh-mediated endothelium-dependent vasodilation was observed within the radiated microvasculature when compared to non-radiated (radiated: 532 ± 167%, non-radiated 1029 ± 263%; P = 0.02). In part 2, the average radiation dose received was 2251 ± 196 cGy. Iontophoresis of SNP elicited a similar peak endothelium-independent vasodilator response in radiated and non-radiated tissue (radiated: 179 ± 58%, non-radiated: 310 ± 158; P = 0.2). The time to 50% of the peak response for ACh and SNP was similar between radiated and non-radiated microvasculature (P < 0.05). These data provide evidence of early endothelium-dependent microvascular dysfunction in cancer patients currently receiving chest radiation and provide the scientific premise for future work evaluating coronary endothelial function and vasomotor reactivity using more detailed and invasive procedures.

Quantifying the forces needed for ureteral stent removal: Initial evaluation of magnetic stent removal devices on benchtop and porcine models.

BACKGROUND: Indwelling ureteral stents are commonly used in pediatric surgeries for kidney stones and urinary tract obstruction, but often require instrumentation or anesthesia for removal. We evaluated the use of novel magnet devices to remove indwelling ureteral stents with a distally attached magnetic bead. Since the forces required for stent removal are unknown, we aimed to characterize and quantify the forces required for stent removal for future prototype testing. METHODS: A custom 3-D urinary tract model was used for benchtop testing, and 6 female porcine subjects were used for in vivo testing after obtaining institutional approval. A modified porcine urethral model that patterned the human female urethral anatomy with approximately 4.5 cm urethral length was used. A HF-10 digital force gauge measured the force required to remove stents with varying properties (stent size, presence of curl, and size of distal magnetic bead). These force measurements were compared to the quantified magnetic forces generated by external magnets and catheter tip magnets. Furthermore, the magnetic retrieval devices were tested with various magnetic beads on both benchtop and porcine models. RESULTS: The required force for removal of a 5 Fr x 14 cm double J stent was significantly higher in the benchtop model compared to the porcine model (4.7N v. 0.8N, p < 0.001). Forces of at least 1N were required from the external magnets to move the stent and bead across a 4-5 cm distance from the bladder neck to the urethral meatus. External magnets at a distance of 4-5 cm produced insufficient forces for removal, and thus they failed to remove the magnetic bead and stent from the bladder. The catheter-based retrieval device showed better success with a variety of different magnet pairs on the retrieval device and stent. Furthermore, the addition of saline to the bladder allowed for better retrieval rates of the smallest beads, even by the smallest magnetic tip catheters. CONCLUSIONS: The forces required for ureteral stent removal are <1N in the porcine model, and improved benchtop models that emulate such parameters will facilitate future stent removal device testing. Given this threshold, external magnets did not generate sufficient force for stent removal at the required distance of 4-5 cm, whereas catheter tip magnetic retrieval overcomes the minimum distance limitation and showed successful retrieval. While these results are encouraging, further studies will define the optimal combination of catheter magnetic tip size and stent magnetic bead size.

Comparing internal migration across the countries of Latin America: A multidimensional approach.

While considerable progress has been made in understanding the way particular aspects of internal migration, such as its intensity, age profile and spatial impact, vary between countries around the world, little attention to date has been given to establishing how these dimensions of migration interact in different national settings. We use recently developed measures of internal migration that are scale-independent to compare the overall intensity, age composition, spatial impact, and distance profile of internal migration in 19 Latin American countries. Comparisons reveal substantial cross-national variation but cluster analysis suggests the different dimensions of migration evolve systematically to form a broad sequence characterised by low intensities, young ages at migration, unbalanced flows and high friction of distance at lower levels of development, trending to high intensities, an older age profile of migration, more closely balanced flows and lower friction of distance at later stages of development. However, the transition is not linear and local contingencies, such as international migration and political control, often distort the migration-development nexus, leading to unique migration patterns in individual national contexts.

Systematic Review of the Association Between Laboratory- and Field-Based Exercise Tests and Lung Function in Patients with Chronic Obstructive Pulmonary Disease.

Introduction: Typical symptoms of chronic obstructive pulmonary disease (COPD) include breathlessness and reduced exercise capacity. Several laboratory- and field-based exercise tests are used to assess the exercise capacity of patients with COPD. It is unclear whether these exercise tests reflect the spirometric measures recommended for diagnosis of COPD. We therefore aimed to systematically assess the correlation between these exercise tests and common measures of lung function. Methods: A search of Embase™, MEDLINE® and The Cochrane Library identified primary publications in English that reported data on the correlations (Pearson's r or Spearman's rho) between the outcomes of exercise tests and the physiological measures of interest: forced expiratory volume in 1 second (FEV1), forced vital capacity, inspiratory capacity and arterial oxygen saturation. We included studies reporting on the following exercise tests: 6- and 12-minute walk tests (6MWT and 12 MWT), incremental and endurance shuttle walk tests, incremental and endurance cycle ergometer tests, and treadmill tests. Results: Of 1781 articles screened, 45 were ultimately deemed eligible for inclusion in this review. The most commonly reported lung function variable was FEV1 (reported by 39 studies); the most commonly reported exercise test was the 6-minute walk test (reported by 24 studies). FEV1 appears to correlate moderately-to-strongly with 6MWT and 12MWT; and moderately-to-very strongly with incremental cycle ergometer tests (ICET); evidence for other exercise tests was limited. Conclusion: There is evidence that 6MWT, 12MWT and ICET correlate with FEV1 to some degree; - evidence for associations of other exercise tests with measures of lung function in patients with COPD is limited. Clinicians must consider this when deciding to use these tests. Further comparisons of these tests must be made in order to assess which physiological and hemodynamic characteristics they reflect in patients with COPD.

Production of cold beams of ND3 with variable rotational state distributions by electrostatic extraction of He and Ne buffer-gas-cooled beams.

The measurement of the rotational state distribution of a velocity-selected, buffer-gas-cooled beam of ND3 is described. In an apparatus recently constructed to study cold ion-molecule collisions, the ND3 beam is extracted from a cryogenically cooled buffer-gas cell using a 2.15 m long electrostatic quadrupole guide with three 90° bends. (2+1) resonance enhanced multiphoton ionization spectra of molecules exiting the guide show that beams of ND3 can be produced with rotational state populations corresponding to approximately T(rot) = 9-18 K, achieved through manipulation of the temperature of the buffer-gas cell (operated at 6 K or 17 K), the identity of the buffer gas (He or Ne), or the relative densities of the buffer gas and ND3. The translational temperature of the guided ND3 is found to be similar in a 6 K helium and 17 K neon buffer-gas cell (peak kinetic energies of 6.92(0.13) K and 5.90(0.01) K, respectively). The characterization of this cold-molecule source provides an opportunity for the first experimental investigations into the rotational dependence of reaction cross sections in low temperature collisions.

Improved measures for the cross-national comparison of age profiles of internal migration.

We develop and demonstrate the application of a concise set of measures intended to encapsulate key features of the age profile of internal migration and highlight the significant differences that exist between nations in these profiles. Model schedules have been the most common method of comparing internal migration patterns but issues related to the estimation and interpretation of their parameters hinder their use for cross-national comparison. We demonstrate that the interpretation of exponential coefficients as rates of ascent and descent does not best reflect the slopes of migration age profiles, and we propose more consistent measures based on the rate of change in migration intensity. We demonstrate, through correlation and factor analysis, that most of the inter-country variance in migration age profiles is captured by the age at and intensity of peak migration. The application of these two indicators to 25 countries reveals significant differences between regions.

Systematic review: laparoscopic fundoplication for gastroesophageal reflux disease in partial responders to proton pump inhibitors.

AIM: To assess laparoscopic fundoplication (LF) in partial responders to proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD). METHODS: We systematically searched PubMed and Embase (1966-Dec 2011) for articles reporting data on LF efficacy in partial responders. Due to a lack of randomized controlled trials, observational studies were included. Of 558 articles screened, 17 were eligible for inclusion. Prevalence data for individual symptoms were collated across studies according to mutually compatible time points (before and/or after LF). Where suitable, prevalence data were presented as percentage of patients reporting symptoms of any frequency or severity. RESULTS: Due to a lack of standardized reporting of symptoms, the proportion of patients experiencing symptoms was recorded across studies where possible. After LF, the proportion of partial responders with heartburn was reduced from 93.1% (5 studies) to 3.8% (5 studies), with similar results observed for regurgitation [from 78.4% (4 studies) to 1.9% (4 studies)]. However, 10 years after LF, 35.8% (2 studies) of partial responders reported heartburn and 29.1% (1 study) reported regurgitation. The proportion using acid-suppressive medication also increased, from 8.8% (4 studies) in the year after LF to 18.2% (2 studies) at 10 years. In the only study comparing partial responders to PPI therapy with complete responders, higher symptom scores and more frequent acid-suppressive medication use were seen in partial responders after LF. CONCLUSION: GERD symptoms improve after LF, but subsequently recur, and acid-suppressive medication use increases. LF may be less effective in partial responders than in complete responders.

Blackbody-mediated rotational laser cooling schemes in MgH+, DCl+, HCl+, LiH and CsH.

Ensembles of ultra-cold atoms, molecules and ions (both atomic and molecular) can be held in traps for increasingly long periods of time. While these trapped species remain translationally cold, for molecules the absorption of ambient black-body radiation can result in rapid thermalisation of the rotational (and vibrational) degrees of freedom. At 300 K, internal state purity is lost typically on the order of tens of seconds, inhibiting the study of quantum state selected reactions. In this paper a theoretical model is used to investigate laser-driven, blackbody-mediated, rotational cooling schemes for several (1)Σ and (2)Π diatomic species. The rotational cooling is particularly effective for DCl(+) and HCl(+), for which 92% and >99% (respectively) of the population can be driven into the rovibrational ground state. For the other systems a broadband optical pumping source (simultaneously exciting up to four transitions) is found to enhance the population that can be accumulated in the rovibrational ground state by up to 29% over that achieved when exciting a single transition. The influence of the rotational constant, dipole moments and electronic state of the diatomics on the rotational cooling achievable is also considered. An extension to polyatomic species is discussed and a combination of cold trap environments (at 77 K) and optical pumping schemes is proposed.

Cold chemistry with electronically excited Ca+ Coulomb crystals.

Rate constants for chemical reactions of laser-cooled Ca(+) ions and neutral polar molecules (CH(3)F, CH(2)F(2), or CH(3)Cl) have been measured at low collision energies (/k(B)=5-243 K). Low kinetic energy ensembles of (40)Ca(+) ions are prepared through Doppler laser cooling to form "Coulomb crystals" in which the ions form a latticelike arrangement in the trapping potential. The trapped ions react with translationally cold beams of polar molecules produced by a quadrupole guide velocity selector or with room-temperature gas admitted into the vacuum chamber. Imaging of the Ca(+) ion fluorescence allows the progress of the reaction to be monitored. Product ions are sympathetically cooled into the crystal structure and are unambiguously identified through resonance-excitation mass spectrometry using just two trapped ions. Variations of the laser-cooling parameters are shown to result in different steady-state populations of the electronic states of (40)Ca(+) involved in the laser-cooling cycle, and these are modeled by solving the optical Bloch equations for the eight-level system. Systematic variation of the steady-state populations over a series of reaction experiments allows the extraction of bimolecular rate constants for reactions of the ground state ((2)S(1/2)) and the combined excited states ((2)D(3/2) and (2)P(1/2)) of (40)Ca(+). These results are analyzed in the context of capture theories and ab initio electronic structure calculations of the reaction profiles. In each case, suppression of the ground state rate constant is explained by the presence of a submerged or real barrier on the ground state potential surface. Rate constants for the excited states are generally found to be in line with capture theories.

Interaction between muscle temperature and contraction velocity affects mechanical efficiency during moderate-intensity cycling exercise in young and older women.

The effect of elevated muscle temperature on mechanical efficiency was investigated during exercise at different pedal frequencies in young and older women. Eight young (24 +/- 3 yr) and eight older (70 +/- 4 yr) women performed 6-min periods of cycling at 75% ventilatory threshold at pedal frequencies of 45, 60, 75, and 90 rpm under control and passively elevated local muscle temperature conditions. Mechanical efficiency was calculated from the ratio of energy turnover (pulmonary O(2) uptake) and mechanical power output. Overall, elevating muscle temperature increased (P < 0.05) mechanical efficiency in young (32.0 +/- 3.1 to 34.0 +/- 5.5%) and decreased (P < 0.05) efficiency in older women (30.2 +/- 5.6 to 27.9 +/- 4.1%). The different effect of elevated muscle temperature in young and older women reflects a shift in the efficiency-velocity relationship of skeletal muscle. These effects may be due to differences in recruitment patterns, as well as sarcopenic and fiber-type changes with age.

Ion-molecule chemistry at very low temperatures: cold chemical reactions between Coulomb-crystallized ions and velocity-selected neutral molecules.

The recent development of a range of techniques for producing cold atoms and molecules at very low translational temperatures T < or = 1 K has provided the opportunity to investigate collisional processes in a new physical regime. We have recently presented a new experimental method to study low-temperature reactive collisions between translationally cold ions and neutral molecules (S. Willitsch et al., Phys. Rev. Lett. 2008, 100, 043203). Our technique relies on the combination of a quadrupole-guide velocity selector for the generation of translationally cold neutral molecules with a facility to produce ordered structures of cold ions (Coulomb crystals) by laser cooling in a linear quadrupole ion trap. The strong localisation of the ions in the trap in combination with the high sensitivity of laser-induced-fluorescence detection enabled us to study chemical reactions on the single-particle level, down to temperatures of T approximately 1 K. In the current paper, we present a detailed characterisation of the scope and limitations of this method based on our study of the reaction between laser-cooled Ca+ ions and velocity-selected CH3F molecules. The properties of our cold-neutrals source and the dependence of the measured rate constant on the shape of the Coulomb crystals, trapping and laser-cooling parameters are discussed. An extension of our technique for the study of low-temperature reactions with sympathetically cooled molecular ions (translational temperature T > 10 mK) is presented and first results on the charge-transfer reaction between OCS+ and ND3 are discussed. Finally, perspectives for further developments of our method are explored.

Chemical applications of laser- and sympathetically-cooled ions in ion traps.

Ensembles of cold atomic and molecular ions in ion traps prepared at millikelvin temperatures by laser and sympathetic cooling have recently found considerable interest in both physics and chemistry. At very low temperatures the ions form ordered structures in the trap also known as "Coulomb crystals". Ion Coulomb crystals exhibit a range of intriguing properties which render them attractive systems for novel experiments in chemical dynamics, ultrahigh-resolution spectroscopy and quantum-information processing. In this article we review the methods used to prepare atomic and molecular ion Coulomb crystals and discuss some recent studies in mass spectrometry, low-temperature chemistry and precision spectroscopy to illustrate their scientific potential for chemical applications. Finally, we conclude with an outlook on outstanding challenges and prospective further developments in the field.

Cold Reactive Collisions between laser-cooled ions and velocity-selected neutral molecules.

We report a new experimental method to study reactive ion-molecule collisions at very low temperatures. A source of laser-cooled ions in a linear Paul trap has been combined with a quadrupole-guide velocity selector to investigate the reaction of Ca+ with CH3F at collision energies E[over](coll)/k(B)> or =1 K with single-particle sensitivity. The technique represents a general approach to study reactive collisions between ions and polar molecules over a wide temperature range down to the cold regime.

Modulation of spontaneous baroreflex control of heart rate and indexes of vagal tone by passive calf muscle stretch during graded metaboreflex activation in humans.

We examined whether spontaneous baroreflex modulation of heart rate and other indexes of cardiac vagal tone could be altered by passive stretch of the human calf muscle during graded concurrent activation of the muscle metaboreflex. Ten healthy subjects performed four trials: a control trial, resting for 1.5 min (0% trial); or 1.5 min of one-legged isometric plantar flexor exercise at 30, 50, and 70% maximal voluntary contraction. The incremental increases in blood pressure (BP) caused were then partially sustained by subsequent local circulatory occlusion (CO). After 3.5 min of CO alone, sustained calf stretch and CO were applied for 3 min. Spontaneous baroreflex sensitivity (SBRS) was progressively decreased with increasing exercise intensity (P < 0.05). During CO, stretch decreased SBRS and increased BP similarly in all trials (P < 0.05). Within 15 s of stretch onset, heart rate (HR) increased by 6 +/- 1, 6 +/- 1, 8 +/- 1, and 6 +/- 2 beats/min in the 0, 30, 50, and 70% trials, respectively (P < 0.05), and root mean square of successive differences was decreased from CO-alone levels (P < 0.05). During the second and third minutes of stretch, HR fell back but remained significantly above CO levels, and common coefficient of variance of R-R interval decreased progressively with increasing prior exercise intensity (P < 0.05; 70% trial). This suggests that passive stretch of the human calf muscles decreases cardiac vagal outflow irrespective of the levels of BP increase caused by muscle metaboreflex activation and implies that central modulation of baroreceptor input, mediated by the actions of stretch-activated mechanoreceptive muscle afferent fibers, continues.

Cardiovascular responses to human calf muscle stretch during varying levels of muscle metaboreflex activation.

The purpose of the present study was to investigate the cardiovascular responses to muscle metaboreflex- and concurrent muscle stretch-induced mechanoreflex activation. Eight subjects (7 males, 1 female) performed 90 s of isometric calf plantarflexion at 0, 30, 50 and 70% of maximum voluntary contraction. During exercise and for 3.5 min postexercise, circulatory occlusion (PECO) was ensured by inflation of a thigh cuff. After 90 s of PECO the calf muscle was stretched for 60 s (Stretch). Heart rate (HR; assessed from ECG), blood pressure (BP; Finapres) and phase of respiratory cycle were recorded. Exercise increased diastolic BP (DBP) from rest by 1+/-0.8, 14+/-2.5, 29+/-3.9 and 35+/-3.6 mmHg, during the 0, 30, 50 and 70% conditions, respectively (ANOVA rest versus exercise, P<0.05). During PECO DBP remained elevated, by 2+/-0.4, 8+/-0.3, 12+/-0.3 and 13+/-0.9 mmHg, respectively. Stretch produced a further increase in DBP that was not different between conditions (3+/-1.4, 2+/-0.8, 3+/-1.0 and 3+/-0.9 mmHg, for the 0, 30, 50 and 70%, respectively). HR increased during exercise but returned to baseline during PECO. HR increased at Stretch onset in all conditions. No EMG was detected from the gastrocnemius and soleus during Stretch. Our data show that the cardiovascular responses to human calf Stretch are independent of the level of concurrent muscle metaboreflex activation.

Cardiovascular responses to external compression of human calf muscle vary during graded metaboreflex stimulation.

This study investigated the cardiovascular response to a standard external muscle compression during concomitant muscle metaboreflex stimulation of varying intensity in human calf muscle. Eleven healthy male subjects (mean (s.d.) age, 26 (5.6) years; height, 177 (5) cm; weight, 74.3 (6.8) kg) were seated in an isometric dynamometer with the angle of the knee at 90 deg, and the angle of the ankle at 85 deg. After a 150-s rest period, subjects were asked to either perform isometric plantar flexion at 20, 30, 40, 50, 60, 70 or 80% of previously determined maximum isometric contractile force (MVC) for 90 s, or to sit at rest for this period. A thigh cuff maintained circulatory occlusion throughout the exercise period and for 180 s post exercise. After 60 s of post-exercise circulatory occlusion (PECO), a calf cuff was inflated to 300 mmHg for 60 s followed by a further 60 s of PECO alone after which the thigh cuff was deflated. During PECO the mean arterial pressure (MAP) increase from rest was dependent upon the preceding exercise intensity (P < 0.001). Compression elicited a further significant change in MAP, and the magnitude of this change from the PECO baseline was also dependent upon the preceding exercise intensity (P < 0.01). These results are compatible with activation of a metabolically sensitised population of mechanoreceptive afferents in human muscle during external compression.

Clarifying the relationships between health and residential mobility.

Health-selective migration within countries has been implicated as one of the mechanisms by which spatial disadvantage is created and maintained. However, there is conflicting evidence on the nature of the relationship between health and mobility, caused in part by diverse definitions, and age and sex differences. This paper uses the first two waves of data for the middle-aged cohort (aged 45-50 in 1996) of the Australian Longitudinal Study on Women's Health to investigate the relationship between four sets of health variables with subsequent local moves (within the same postcode), longer distance moves (between postcodes) and inter-regional migration from rural and remote areas 'up' the urban hierarchy. After adjusting for socio-economic and marital status, short and longer distance mobility among these middle-aged Australian women was positively associated with long-term and chronic poor health and being a smoker. Moves between postcodes and rural-to-urban migration were positively associated with multiple recent visits to a medical specialist. Our findings are consistent with UK and US studies that have found mobility to be more strongly associated with poor health than good health in mature adults. As the population ages, the health of receiving areas may be adversely affected by relatively unhealthy in-migrants seeking amenities not provided in their former place of residence.

The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anesthesia.

UNLABELLED: Sevoflurane anesthesia in young children has been associated with an increased incidence of emergence agitation compared with halothane. Postoperative pain may be an etiologic factor. We designed a study to compare the incidence of emergence agitation after halothane and sevoflurane anesthesia in children whose pain was managed with caudal analgesia. Eighty children undergoing inguinal hernia repair between the ages of 12 mo and 6 yr were randomly assigned to receive either halothane or sevoflurane anesthesia. Baseline preoperative anxiety was assessed with the Yale Preoperative Anxiety Scale. The children were sedated with oral midazolam, underwent a mask induction, and had a caudal block placed for postoperative analgesia. After surgery, the children's behavior was assessed with a four-point agitation scale. At 5 min after arrival in the postanesthesia care unit (PACU), sevoflurane was associated with a greater incidence of emergence agitation than halothane (26% vs 6%; P < 0.05), but not during the remainder of the PACU stay. Higher levels of preoperative anxiety were associated with difficult mask induction, agitation on admission to the PACU, and more severe agitation episodes. Emergence agitation appears to be an early and transient phenomenon after sevoflurane anesthesia in children with effective postoperative analgesia. IMPLICATIONS: Effective postoperative analgesia may reduce the incidence of emergence agitation reported with sevoflurane anesthesia. The Yale Preoperative Anxiety Scale appears to be helpful in identifying young children who are at risk for developing emergence agitation.