A Reproducible Technique for Arthroscopic Acromioclavicular Joint Excision

Arthroscopic acromioclavicular joint excision is a commonly performed but technically demanding procedure. Incomplete excision can leave residual symptoms. We present a simple, reproducible technique ensuring satisfactory excision of the joint.     

Accuracy and Precision of Acetabular Component Placement With Imageless Navigation in Obese Patients

Background

Obesity is a risk factor for acetabular component malposition when total hip arthroplasty is performed with manual techniques. The utility of imageless navigation in obese patients remains unknown. This study compared the accuracy and precision of imageless navigation for component orientation between obese and nonobese patients.

Low potential for evolutionary rescue from climate change in a tropical fish

Climate change is increasing global temperatures and intensifying the frequency and severity of extreme heat waves. How organisms will cope with these changes depends on their inherent thermal tolerance, acclimation capacity, and ability for evolutionary adaptation. Yet, the potential for adaptation of upper thermal tolerance in vertebrates is largely unknown. We artificially selected offspring from wild-caught zebrafish (Danio rerio) to increase (Up-selected) or decrease (Down-selected) upper thermal tolerance over six generations. Selection to increase upper thermal tolerance was also performed on warm-acclimated fish to test whether plasticity in the form of inducible warm tolerance also evolved. Upper thermal tolerance responded to selection in the predicted directions. However, compared to the control lines, the response was stronger in the Down-selected than in the Up-selected lines in which evolution toward higher upper thermal tolerance was slow (0.04 ± 0.008 °C per generation). Furthermore, the scope for plasticity resulting from warm acclimation decreased in the Up-selected lines. These results suggest the existence of a hard limit in upper thermal tolerance. Considering the rate at which global temperatures are increasing, the observed rates of adaptation and the possible hard limit in upper thermal tolerance suggest a low potential for evolutionary rescue in tropical fish living at the edge of their thermal limits.

Globally, both mean and extreme environmental temperatures are increasing due to climate change with mean temperatures predicted to increase by 0.3–4.8 °C by the end of the century (1, 2). Aquatic ectotherms are particularly vulnerable to rising temperatures as their body temperature closely tracks the environmental temperature (3). These organisms can avoid thermal stress by migrating to cooler waters, acclimating, and/or adapting genetically (4–6). For species with a limited dispersal ability (e.g., species from shallow freshwater habitats; ref. 7), acclimation and evolutionary adaptation are the only possible strategies. Furthermore, for ectotherms living at the edge of their upper thermal limits, an increase in extreme temperatures may generate temperature peaks that exceed physiological limits and cause high mortality (5, 8–10). Although this is expected to cause strong selection toward higher upper thermal tolerance, it is largely unknown, particularly within vertebrates, whether and at what rate organisms may adapt by evolving their thermal limits (11–14). These are important issues because constrained or limited evolvability (15) of upper thermal tolerance could lead to population extinctions as climate change increases the severity of heat waves.Ectotherms can also increase their thermal limits through physiological and biochemical adjustments, in a process known as thermal acclimation when they are exposed to elevated temperatures for a period of time (16, 17). Thermal acclimation, sometimes called thermal compensation, is here used interchangeably with the term physiological plasticity as outlined by Seebacher et al. (18). In the wild, individuals may experience days or weeks of warmer temperatures prior to a thermal extreme. Through physiological plasticity, the severity of an ensuing thermal extreme may be reduced, thus increasing the chance for survival (19). Furthermore, in some cases, adaptation can be accelerated by plasticity (20–22). This requires that the physiological mechanisms responsible for acclimation are also (at least partly) involved in the acute response; that is, that there is a positive genetic correlation between physiological plasticity and (acute) upper thermal tolerance. It is therefore crucial to quantify the evolutionary potential of upper thermal tolerance of fish populations threatened by climate change (23, 24) and to understand the link between the evolutionary response of upper thermal tolerance and physiological plasticity.Previously detected evolution of upper thermal tolerance generally points toward a slow process (12, 13, 25–31). However, estimates of the evolutionary potential in upper thermal tolerance mostly come from studies on Drosophila (12, 25, 27, 32), and empirical evidence in aquatic ectotherms and specifically vertebrates is limited. The few studies that have been performed on fish show disparate responses to selection on heat tolerance even within the same species. Baer and Travis (33) detected no response to selection yet Doyle et al. (34) and Klerks et al. (28) detected selection responses with heritabilities of 0.2 in killifish (Heterandria formosa). Despite the typical asymmetry of thermal performance curves (3, 35), studies in vertebrates are limited to unidirectional estimates of evolutionary potential (28, 31, 33) or do not account for the direction of evolution when estimating heritability in upper thermal tolerance from breeding designs (36, 37). Furthermore, while several studies have found that populations with different thermal histories have evolved different levels of heat tolerance (29–31), we still lack a good understanding of how physiological plasticity within a generation, in response to a short heat exposure, interacts with genetic changes during evolution of thermal tolerance.To investigate possible asymmetry in the evolutionary potential of upper thermal tolerance in a vertebrate species, we artificially selected offspring of wild-caught zebrafish (Danio rerio) to increase and decrease upper thermal tolerance for six generations. Furthermore, to disentangle the contribution of acclimation from the genetic response to increase upper thermal tolerance, we selected two lines that were exposed to a period of warm acclimation prior to a thermal challenge. The size (>20,000 phenotyped fish) and duration (six generations) of this study are unique in a vertebrate species for a climate change-relevant selection experiment, and the results provide critical and robust information on how tropical fish may adapt to a changing climate.Being a freshwater and tropical species, zebrafish are likely to be especially vulnerable to climate change (7, 38). In the wild, zebrafish can already be found living only a few degrees below their thermal limits (17, 39) and live in shallow streams and pools (40) that have the potential to rapidly warm during heat waves. Zebrafish therefore represent a species living at the edge of its thermal limit in which rapid adaptation of thermal tolerance would be particularly beneficial for its survival. Wild-caught zebrafish originating from different sites in West Bengal, India (17, 40), were used to maximize the genetic diversity of the parental population. These wild-caught zebrafish (n = 2,265) served as parents of the starting F₀ generation (n = 1,800) on which we selected upper thermal tolerance for six generations. Upper thermal tolerance was measured as the critical thermal maximum (CT_max), a commonly used measure of an organism’s acute upper thermal tolerance (16, 41). CT_max is defined as the temperature at which an individual loses equilibrium (i.e., uncontrolled and disorganized swimming in zebrafish; ref. 42) during thermal ramping. Measuring CT_max is rapid, repeatable, and does not appear to harm zebrafish (42). CT_max is ecologically relevant because it is highly correlated with both tolerance to slow warming (43) and to the upper temperature range boundaries of wild aquatic ectotherms (9).Our selection experiment consisted of four treatment groups (Up-selected, Down-selected, Acclimated Up-selected, and Control) with two replicate lines in each treatment. We established these lines by selecting fish on their CT_max in the F₀ generation with each line consisting of 150 individuals (see Methods for further details of F₀ generation). The offspring of those fish formed the F₁ generation that consisted of 450 offspring in each line. At each generation, the Up, Down, and Control lines were all held at optimal temperature (28 °C) (39), whereas the Acclimated Up-selected lines were acclimated to a supraoptimal temperature (32 °C) for 2 wk prior to selection (17). From the F₁ to F₆ generations, we measured CT_max for all 450 fish in each line and selected the 33% with the highest CT_max in the Up-selected and in the Acclimated Up-selected lines, and the 33% with the lowest CT_max in the Down-selected lines. In the Control lines, 150 fish were randomly selected, measured, and retained. Thus, CT_max was measured on a total of 3,000 fish per generation and 150 individuals remained in each of the eight lines after selection, forming the parents for the next generation. The nonselected lines (Control) represented a control for the Up-selected and Down-selected lines, while the Up-selected lines represented a control for the Acclimated Up-selected lines, because these two treatments solely differed by the acclimation period to which the latter were exposed before selection. Thus, differences in CT_max between Up-selected and Acclimated Up-selected lines represent the contribution of physiological plasticity to upper thermal tolerance. If the difference between these two treatments increases during selection, it would suggest that plasticity increases during adaptation to higher CT_max (i.e., the slope the reaction norm describing the relationship between CT_max and acclimation temperature would become steeper).After six generations of selection, upper thermal tolerance had evolved in both the Up-selected and the Down-selected lines (Fig. 1). In the Up-selected lines, upper thermal tolerance increased by 0.22 ± 0.05 °C ($\bar{x}$ ± 1 SE) compared to the Control lines whereas the Down-selected lines displayed a mean upper thermal tolerance 0.74 ± 0.05 °C lower than the Control (Fig. 1B; estimates for replicated lines combined). The asymmetry in the response to selection was confirmed by the estimated realized heritability, which was more than twice as high in the Down-selected lines (h² = 0.24; 95% CI: 0.19–0.28) than in the Up-selected lines (h² = 0.10; 95% CI: 0.05–0.14; Fig. 2).Open in a separate windowFig. 1.Upper thermal tolerance (CT_max) of wild-caught zebrafish over six episodes of selection. Duplicated lines were selected for increased (Up-selected, orange lines and triangles) and decreased (Down-selected, blue lines and squares) upper thermal tolerance. In addition, we had two Control lines (green dashed lines and diamonds). The Up, Down, and Control lines were all acclimated to a temperature of 28 °C. In addition, two lines were selected for increased upper thermal tolerance after 2 wk of warm acclimation at 32 °C (Acclimated Up-selected, red lines and circles). At each generation, the mean and 95% CIs of each line are shown (n ∼ 450 individuals per line). (A) Absolute upper thermal tolerance values. (B) The response to selection in the Up and Down lines centered on the Control lines (dashed green line). Difference between Up-selected and Acclimated-Up lines are shown in Fig. 3. The rate of adaptation (°C per generation) is reported for each treatment using estimates obtained from linear mixed effects models using the Control-centered response in the Up-selected and Down-selected lines and the absolute response for the Acclimated-Up lines (SE = ±0.01 °C in all lines).Open in a separate windowFig. 2.Realized heritability (h²) of upper thermal tolerance (CT_max) in wild-caught zebrafish. The realized heritability was estimated for each treatment as the slope of the regression of the cumulative response to selection on the cumulative selection differential using mixed effect models passing through the origin with replicate as a random effect. Slopes are presented with their 95% CIs (shaded area) for the Down-selected lines (blue) and Up-selected lines (orange). Data points represent the mean of each replicate line (n ∼ 450) over six generations of selection. Average selection differentials are 0.57 (Down) and 0.39 (Up), respectively, see SI Appendix, Table S1 for more information.At the start of the experiment (F₀), warm acclimation (32 °C) increased thermal tolerance by 1.31 ± 0.05 °C (difference in CT_max between the Up-selected and Acclimated Up-selected lines in Figs. 1A and ​and3),3), which translates to a 0.3 °C change in CT_max per 1 °C of warming. In the last generation, the effect of acclimation had decreased by 25%, with the Acclimated-Up lines having an average CT_max 0.98 ± 0.04 °C higher than the Up lines (Fig. 3). This suggests that, despite a slight increase in CT_max in the Acclimated Up-selected lines during selection, the contribution of plasticity decreased over the course of the experiment.Open in a separate windowFig. 3.Contribution of acclimation to the upper thermal tolerance in the Acclimated-Up selected lines at each generation of selection. The contribution of acclimation was estimated as the difference between the Up and Acclimated-Up selected lines. Points and error bars represent the estimates (±SE) from a linear mixed effects model with CT_max as the response variable; Treatment (factor with two levels: Up and Acclimated Up), Generation (factor with seven levels), and their interaction as the predictor variables; and replicate line as a random factor.During the experiment, the phenotypic variation of CT_max that was left-skewed at F₀ increased in the Down-selected lines and decreased in the Up-selected lines (Fig. 4). At the F₆ generation, phenotypic variance was four times lower in the Up-selected lines (0.09 ± 0.01 and 0.12 ± 0.02 °C²; variance presented for each replicate line separately and SE obtained by nonparametric bootstrapping) than in the Down-selected lines (0.41 ± 0.03 and 0.50 ± 0.04 °C²), which had doubled since the start of the experiment (F₀: 0.20 ± 0.01 °C², see SI Appendix, Fig. S1). In the Acclimated Up-selected lines, the phenotypic variance that was already much lower than the Control at the F₀ also decreased and reached 0.06 ± 0.01 °C² and 0.07 ± 0.01 °C² for the two replicates at the last generation (SI Appendix, Fig. S1).Open in a separate windowFig. 4.Distribution of upper thermal tolerance (CT_max) in selected lines. (A) Distribution for each line at each generation (F₀ to F₆). In the F₀ generation, histograms show the preselection distribution in gray for the nonacclimated fish, in dark green for the Control lines, and in red for the Acclimated-Up fish. In all subsequent generations the Down-selected lines are in blue, the Up-selected lines in yellow, the Control lines in dark green, and Acclimated-up lines in red. All treatments use two shades, one for each replicate line. Dashed lines represent the mean CT_max for each line (n ∼ 450 individuals). (B) Distribution of upper thermal tolerance at the start (F₀, in gray) and the end (F₆, in blue and yellow) of the experiment for the Up-selected and Down-selected lines. The dashed gray line represents the mean of the Up-selected and Down-selected lines in the F₀ generation preselection (n ∼ 900 individuals). Dashed blue and yellow lines represent the mean CT_max for Up and Down-selected lines for the F₆ generation (n ∼ 450 individuals).Together with the asymmetrical response to selection and the lower response of the Acclimated Up-selected lines, these changes in phenotypic variance suggest the existence of a hard-upper limit for thermal tolerance (e.g., major protein denaturation (44), similar to the “concrete ceiling” for physiological responses to warming (14)). Such a hard-upper limit is expected to generate a nonlinear mapping of the genetic and environmental effects on the phenotypic expression of CT_max. This nonlinearity will affect the phenotypic variance of CT_max when mean CT_max approaches its upper limit (SI Appendix, Fig. S2A). For example, with directional selection toward higher CT_max, genetic changes in upper thermal tolerance will translate into progressively smaller phenotypic changes. Similarly, warm acclimation that shifts CT_max upwards will also decrease phenotypic variation in CT_max (see differences in phenotypic variance between control and Acclimated lines at the F₀). This hard ceiling can also explain why an evolutionary increase in CT_max reduces the magnitude of physiological plasticity in CT_max achieved after a period of acclimation (Fig. 3 and see SI Appendix, Fig. S2B). If the sum of the genetic and plastic contributions to CT_max cannot exceed a ceiling value, this should generate a zero-sum gain between the genetic and plastic determinants of thermal tolerance. An increase in the genetic contribution to CT_max via selection should thus decrease the contribution of plasticity. Selection for a higher CT_max should therefore negatively affect the slope of the reaction norm of thermal acclimation because acclimation will increase CT_max more strongly at low than high acclimation temperature (SI Appendix, Fig. S2B).To test this hypothesis, we measured CT_max in all selected lines at the final generation (F₆) after acclimation to 24, 28, and 32 °C. At all three acclimation temperatures, the Acclimated-Up lines did not differ from the Up-selected lines (average difference 0.14 ± 0.08 °C; 0.12 ± 0.09 °C; 0.14 ± 0.09 °C; at 24, 28, and 32 °C respectively; Fig. 5). This suggests that warm acclimation prior to selection did not affect the response to selection. However, considering the within-treatment differences in CT_max between fish acclimated to 28 and 32 °C, we show that the gain in CT_max due to acclimation decreases in both the Up and Acclimated-Up treatments compared to the Control and Down treatments (SI Appendix, Fig. S3). This confirms a loss of thermal plasticity in both Up-selected treatments (Up and Acclimated-Up) at higher acclimation temperatures. Notably, the loss of thermal plasticity is not evident in fish acclimated to 24 and 28 °C, possibly because at these temperatures CT_max remains further away from its hard upper limit.Open in a separate windowFig. 5.Upper thermal tolerance (CT_max) of the selected lines measured at the last generation (F₆) after acclimation at 24, 28, and 32 °C. The response is calculated as the mean difference in upper thermal tolerance (CT_max) relative to the Control lines. Large points and whiskers represent mean ±1 SE for each treatment (n = 120 individuals): Up-selected (orange triangles), Down-selected (blue squares), Acclimated Up-selected (red circles), and Control (green diamonds). Smaller translucent points represent means of each replicate line (n = 60 individuals). See SI Appendix, Fig. S3 for absolute CT_max values and model estimates.Acclimated Up-selected lines are perhaps the most ecologically relevant in our selection experiment. In the wild, natural selection on upper thermal tolerance may not result from increasing mean temperatures but through rapid heating events such as heat waves (45). During heat waves, temperature may rise for days before reaching critical temperatures. This gives individuals the possibility to acclimate and increase their upper thermal tolerance prior to peak temperatures. Our results show that while warm acclimation allowed individuals to increase their upper thermal tolerance, it did not increase the magnitude or the rate of adaptation of upper thermal tolerance.For the past two decades it has been recognized that rapid evolution, at ecological timescales, occurs and may represent an essential mechanism for the persistence of populations in rapidly changing environments (24, 46, 47). Yet, in the absence of an explicit reference, rates of evolution are often difficult to categorize as slow or rapid (48). For traits related to thermal tolerance or thermal performance, this issue is complicated by the fact that the scale on which traits are measured (temperature in °C) cannot meaningfully be transformed to a proportional scale. This prevents us from comparing rates of evolution between traits related to temperature with other traits measured on different scales (49, 50). However, for thermal tolerance, the rate of increase in ambient temperature predicted over the next century represents a particularly meaningful standard against which the rate of evolution observed in our study can be compared.In India and surrounding countries where zebrafish are native, heat waves are predicted to increase in frequency, intensity, and duration, and maximum air temperatures in some regions are predicted to exceed 44 °C in all future climate scenarios (51). Air temperature is a good predictor of water temperature in shallow ponds and streams where wild zebrafish are found (17, 40, 52, 53). Thus, strong directional selection on the thermal limits of zebrafish is very likely to occur in the wild. At first sight, changes in the upper thermal tolerance observed in our study (0.04 °C per generation) as well as the heritability estimates (Down-selected: h² = 0.24, Up-selected: h² = 0.10) similar to those obtained in fruit flies (Drosophila melanogaster) selected for acute upper thermal tolerance (Down-selected: h² = 0.19, Up-selected: h² = 0.12; ref. 12), suggest that zebrafish may just be able to keep pace with climate change and acutely tolerate temperatures of 44 °C predicted by the end of the century. However, several cautions make such an optimistic prediction unlikely.First, such an extrapolation assumes a generation time of 1 y, which is likely for zebrafish but unrealistic for many other fish species. Second, such a rate of evolution is associated with a thermal culling of two-thirds of the population at each generation, a strength of selection that may be impossible to sustain in natural populations exposed to other selection pressures such as predation or harvesting. Third, the heritability and rate of adaptation toward higher upper thermal tolerance observed here may be considered as upper estimates because of the potentially high genetic variance harbored by our parental population where samples from several sites were mixed. While mixing of zebrafish populations often occurs in the wild during monsoon flooding (54, 55), there are likely to be some isolated populations that may have a lower genetic diversity and adaptation potential than our starting population. Finally, and most importantly, the reduced phenotypic variance and decreased acclimation capacity with increasing CT_max observed in our study suggest the existence of a hard-upper limit to thermal tolerance that will lead to an evolutionary plateau similar to those reached in Drosophila selected for increased heat resistance over many generations (12, 56). Overall, the rate of evolution observed in our study is likely higher than what will occur in the wild and, based on this, it seems unlikely that zebrafish, or potentially other tropical fish species, will be able to acutely tolerate temperatures predicted by the end of the century. It is possible that other fish species, especially those living in cooler waters and with wider thermal safety margins, will display higher rates of adaptation than the ones we observed here, and more studies of this kind in a range of species are needed to determine whether slow adaptation of upper thermal tolerance is a general phenomenon.Transgenerational plasticity (e.g., epigenetics) has been suggested to modulate physiological thermal tolerance (57). However, the progressive changes in CT_max observed across generations in our study indicate that these changes were primarily due to genetic changes because effects of transgenerational plasticity are not expected to accumulate across generations. Therefore, the effects of transgenerational plasticity in the adaptation of upper thermal tolerance may be insufficient to mitigate impacts of climate change on zebrafish, yet the potential contribution of transgenerational plasticity is still an open question.By phenotyping more than 20,000 fish over six generations of selection, we show that evolution of upper thermal tolerance is possible in a vertebrate over short evolutionary time. However, the evolutionary potential for increased upper thermal tolerance is low due to the slow rate of adaptation compared to climate warming, as well as the diminishing effect of acclimation as adaptation progresses. Our results thus suggest that fish populations, especially warm water species living close to their thermal limits, may struggle to adapt with the rate at which water temperatures are increasing.     

Current therapeutical strategies for allergic rhinitis

Introduction: Allergic rhinitis is a common condition with increasing prevalence and is associated with several comorbid disorders such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causal treatment option.

Areas covered: This review focuses on current treatments and the future outlook for allergic rhinitis. Pharmacotherapy includes mast cell stabilizers, antihistamines, glucocorticosteroids (GCSs), leukotriene receptor antagonists, and nasal decongestants. Nasal GCSs are currently regarded as the most effective treatment and are considered first-line therapy together with non-sedating antihistamines. The new formulation MP29-02 combines the nasal GCS fluticasone propionate with azelastine in one single spray and has achieved greater improvements than those under monotherapy with modern GCSs or antihistamines. Furthermore, this review discusses allergen immunotherapy alone and in combination with modern monoclonal antibodies.

Expert opinion: Despite the variety of medications for allergic rhinitis, ranging from general symptomatic agents like GCSs or decongestants, to more specific ones like histamine receptor or leukotriene blockers, to causal therapy like immunotherapy, many patients still experience treatment failures or unsatisfactory results. The ultimate goal may be to endotype every downstream pathway separately in order to offer patients individualized, targeted therapy with specific antibodies against the respective pathway.     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.     

The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence

BACKGROUND AND PURPOSE: There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed. MATERIAL AND METHODS: The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques. RESULTS: A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response). CONCLUSION: By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.     

Continuously moving table 3D MRI with lateral frequency-encoding direction.

A method is presented for 3D MRI in an extended field of view (FOV) based on continuous motion of the patient table and an efficient acquisition scheme. A gradient-echo MR pulse sequence is applied with lateral (left-right (L/R)) frequency-encoding direction and slab selection along the direction of motion. Compensation for the table motion is achieved by a combination of slab tracking and data alignment in hybrid space. The method allows fast k-space coverage to be achieved, especially when a short sampling FOV is chosen along the direction of table motion, as is desirable for good image quality. The method can be incorporated into different acquisitions schemes, including segmented k-space scanning, which allows for contrast variation with the use of magnetization preparation. Head-to-toe images of volunteers were obtained with good quality using 3D spoiled gradient-echo sequences. As an example of magnetization-prepared imaging, fat/water separated images were acquired using chemical shift selective (CHESS) presaturation pulses.     

Coronary Magnetic Resonance Angiography

Coronary magnetic resonance angiography (CMRA) is a technique in clinical evolution. Current clinical applications include assessment for coronary anomalies, aneurysms, bypass graft patency, and, in experienced centers, the exclusion of proximal and multivessel coronary artery disease (CAD). As local expertise increases and more extensive multicenter data become available, additional applications will be established. CMRA promises to supplement and in some cases obviate the need for X-ray contrast angiography, and to expand our understanding of the pathophysiology of CAD. Zusammenfassung Die Magnetresonanzangiographie der Koronargefäße (CMRA) ist eine sich ständig weiterentwickelnde Technik. Etablierte Anwendungen sind zurzeit die Beurteilung von koronaren Anomalien, Aneurysmen und der Durchgängigkeit von Bypasses. Auch der Ausschluss proximaler Koronarstenosen und einer koronaren Mehrgefäßerkrankung ist in einigen spezialisierten Zentren möglich. Mit zunehmender Erfahrung der jeweiligen Anwender und der Verfügbarkeit von Ergebnissen großer multizentrischer Studien können zukünftig weitere klinische Anwendungen etabliert werden. In der Zukunft könnte die CMRA ergänzende Informationen zur Indikationsstellung einer konventionellen Röntgenangiographie bringen und in einigen Fällen diese Untersuchung sogar ersetzen. Die CMRA wird unseren Einblick in die Pathophysiologie der koronaren Herzerkrankung sicher erweitern.     

Characterizing luminous efficiency functions for a simulated mesopic night driving task based on reaction time

The objective of this study is to test the luminous efficiency functions V(lambda), V'(lambda), V(10)(lambda) and their linear combinations on the basis of a data set gained from a simulated mesopic night-time driving experiment. Another aim is to provide 'real-world' data for the 'X framework' or 'linear combination model', and to find out its limits in a practical situation. Human performance was measured by the reaction time method. Results show that the single parameter of the linear combination of photopic and scotopic luminous efficiency functions can be determined analytically with little variation for a given mesopic background luminance level and a given visual target colour, but the computation leads to considerable deviations comparing all three target colours (red, green and blue) used in the experiment. The conclusion for the given experimental conditions is that the single parameter of the linear combination model has an increasing deviation for lower background luminance levels.