Chapter Six – Individual Trait Variation and Diversity in Food Webs

In recent years, there has been a renewed interest in the ecological consequences of individual trait variation within populations. Given that individual variability arises from evolutionary dynamics, to fully understand eco-evolutionary feedback loops, we need to pay special attention to how standing trait variability affects ecological dynamics. There is mounting empirical evidence that intra-specific phenotypic variation can exceed species-level means, but theoretical models of multi-trophic species coexistence typically neglect individual-level trait variability. What is needed are multispecies datasets that are resolved at the individual level that can be used to discriminate among alternative models of resource selection and species coexistence in food webs. Here, using one the largest individual-based datasets of a food web compiled to date, along with an individual trait-based stochastic model that incorporates Approximate Bayesian computation methods, we document intra-population variation in the strength of prey selection by different classes or predator phenotypes which could potentially alter the diversity and coexistence patterns of food webs. In particular, we found that strongly connected individual predators preferentially consumed common prey, whereas weakly connected predators preferentially selected rare prey. Such patterns suggest that food web diversity may be governed by the distribution of predator connectivity and individual trait variation in prey selection. We discuss the consequences of intra-specific variation in prey selection to assess fitness differences among predator classes (or phenotypes) and track longer term food web patterns of coexistence accounting for several phenotypes within each prey and predator species.

Trastuzumab treatment beyond progression in advanced breast cancer: patterns of care in six Swiss breast cancer centers.

BACKGROUND Trastuzumab is an established treatment for HER2-positive breast cancer (BC). We analyzed Swiss patterns of care in patients with HER2-positive BC after disease progression on trastuzumab-containing therapy for metastatic BC (MBC). PATIENTS AND METHODS A retrospective analysis was performed in six Swiss BC centers. Patients with HER2-positive MBC treated with at least one infusion of trastuzumab for advanced disease between January 2006 and December 2007 were identified. Treatment patterns in first and further lines were analyzed. RESULTS All of the 72 identified patients received trastuzumab as their first palliative anti-HER2 therapy, either as monotherapy (n = 23) or in combination with chemotherapy (typically taxane or vinorelbine; n = 49). Median time to progression was 8.1, 8.0 and 7.9 months in the monotherapy, trastuzumab-taxane and trastuzumab-vinorelbine cohorts, respectively. After progression on first-line anti-HER2 therapy, trastuzumab was continued in 67 of 68 patients who received further therapy. One patient received second-line lapatinib plus capecitabine. The median duration of anti-HER2 therapy was 20 months. Patients received a median of 4 lines of anti-HER2 therapy. CONCLUSIONS Durable responses were achieved with repeated exposure to anti-HER2 therapy. In a selected patient population, trastuzumab monotherapy appears to be a reasonable first-line treatment option.

Collecting Societies - Not Yet 'Six Feet Under'

Despite ubiquitous digitisation and the advent of Digital Rights Management Systems, it seems that collecting societies are not quite yet six feet under. Even in a world of rapid technological developments collecting societies will keep providing services to authors, users and the public facilitating the management of rights and performing additionally certain important social and cultural functions. However, agreeing on the future of collecting societies and on the particular design of both individual and collective rights administration is not an easy task and the opinions of the major stakeholders are diverse and often conflicting.

Comparative enzymology of 11beta-hydroxysteroid dehydrogenase type 1 from six species.

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1), catalyzing the intracellular activation of cortisone to cortisol, is currently considered a promising target to treat patients with metabolic syndrome; hence, there is considerable interest in the development of selective inhibitors. For preclinical tests of such inhibitors, the characteristics of 11beta-HSD1 from the commonly used species have to be known. Therefore, we determined differences in substrate affinity and inhibitor effects for 11beta-HSD1 from six species. The differences in catalytic activities with cortisone and 11-dehydrocorticosterone were rather modest. Human, hamster and guinea-pig 11beta-HSD1 displayed the highest catalytic efficiency in the oxoreduction of cortisone, while mouse and rat showed intermediate and dog the lowest activity. Murine 11beta-HSD1 most efficiently reduced 11-dehydrocorticosterone, while the enzyme from dog showed lower activity than those from the other species. 7-ketocholesterol (7KC) was stereospecifically converted to 7beta-hydroxycholesterol by recombinant 11beta-HSD1 from all species analyzed except hamster, which showed a slight preference for the formation of 7alpha-hydroxycholesterol. Importantly, guinea-pig and canine 11beta-HSD1 displayed very low 7-oxoreductase activities. Furthermore, we demonstrate significant species-specific variability in the potency of various 11beta-HSD1 inhibitors, including endogenous compounds, natural chemicals and pharmaceutical compounds. The results suggest significant differences in the three-dimensional organization of the hydrophobic substrate-binding pocket of 11beta-HSD1, and they emphasize that species-specific variability must be considered in the interpretation of results obtained from different animal experiments. The assessment of such differences, by cell-based test systems, may help to choose the appropriate animal for safety and efficacy studies of novel potential drug candidates.

Lepton Flavor Violation in the Standard Model with general Dimension-Six Operators

We study lepton flavor observables in the Standard Model (SM) extended with all dimension-6 operators which are invariant under the SM gauge group. We calculate the complete one-loop predictions to the radiative lepton decays μ → eγ, τ → μγ and τ → eγ as well as to the closely related anomalous magnetic moments and electric dipole moments of charged leptons, taking into account all dimension-6 operators which can generate lepton flavor violation. Also the 3-body flavor violating charged lepton decays τ ± → μ ± μ + μ −, τ ± → e ± e + e −, τ ± → e ± μ + μ −, τ ± → μ ± e + e −, τ ± → e ∓ μ ± μ ±, τ ± → μ ∓ e ± e ± and μ ± → e ± e + e − and the Z 0 decays Z 0 → ℓ+iℓ−j are considered, taking into account all tree-level contributions.

Assessment of patient setup errors in IGRT in combination with a six degrees of freedom couch

PURPOSE The range of patient setup errors in six dimensions detected in clinical routine for cranial as well as for extracranial treatments, were analyzed while performing linear accelerator based stereotactic treatments with frameless patient setup systems. Additionally, the need for re-verification of the patient setup for situations where couch rotations are involved was analyzed for patients treated in the cranial region. METHODS AND MATERIALS A total of 2185 initial (i.e. after pre-positioning the patient with the infrared system but before image guidance) patient setup errors (1705 in the cranial and 480 in the extracranial region) obtained by using ExacTrac (BrainLAB AG, Feldkirchen, Germany) were analyzed. Additionally, the patient setup errors as a function of the couch rotation angle were obtained by analyzing 242 setup errors in the cranial region. Before the couch was rotated, the patient setup error was corrected at couch rotation angle 0° with the aid of image guidance and the six degrees of freedom (6DoF) couch. For both situations attainment rates for two different tolerances (tolerance A: ± 0.5mm, ± 0.5°; tolerance B: ± 1.0 mm, ± 1.0°) were calculated. RESULTS The mean (± one standard deviation) initial patient setup errors for the cranial cases were -0.24 ± 1.21°, -0.23 ± 0.91° and -0.03 ± 1.07° for the pitch, roll and couch rotation axes and 0.10 ± 1.17 mm, 0.10 ± 1.62 mm and 0.11 ± 1.29 mm for the lateral, longitudinal and vertical axes, respectively. Attainment rate (all six axes simultaneously) for tolerance A was 0.6% and 13.1% for tolerance B, respectively. For the extracranial cases the corresponding values were -0.21 ± 0.95°, -0.05 ± 1.08° and -0.14 ± 1.02° for the pitch, roll and couch rotation axes and 0.15 ± 1.77 mm, 0.62 ± 1.94 mm and -0.40 ± 2.15 mm for the lateral, longitudinal and vertical axes. Attainment rate (all six axes simultaneously) for tolerance A was 0.0% and 3.1% for tolerance B, respectively. After initial setup correction and rotation of the couch to treatment position a re-correction has to be performed in 77.4% of all cases to fulfill tolerance A and in 15.6% of all cases to fulfill tolerance B. CONCLUSION The analysis of the data shows that all six axes of a 6DoF couch are used extensively for patient setup in clinical routine. In order to fulfill high patient setup accuracies (e.g. for stereotactic treatments), a 6DoF couch is recommended. Moreover, re-verification of the patient setup after rotating the couch is required in clinical routine.

Circumferential distribution of the neointima at six-month and two-year follow-up after a bioresorbable vascular scaffold implantation: a substudy of the ABSORB Cohort B Clinical Trial

Aims: To investigate the extent and the circumferential distribution of the neointima tissue developed following an Absorb bioresorbable vascular scaffold (BVS) implantation. Methods and results: Twenty-three patients who were treated with the Absorb BVS and had optical coherence tomographic examination after scaffold implantation, at six-month and at two-year follow-up, were included in the current analysis. The lumen and the scaffold borders were detected and the circumferential thickness of the neointima was measured at one degree intervals. The symmetry of the neointima was defined as: minimum/maximum thickness. The lumen area was decreased at six months compared to baseline but it did not change between six-month and two-year follow-up (baseline: 7.49 [6.13-8.00] mm2, six months: 6.31 (4.75-7.06) mm2, two years: 6.01 [4.67-7.11] mm2, p=0.373). However, the mean neointima thickness (six months: 189 [173-229] μm, two years: 258 [222-283] μm, p<0.0001) and the symmetry index of the neointima (six months: 0.06 [0.02-0.09], two years: 0.27 [0.24-0.36], p<0.0001) were increased at two years. Full circumferential coverage of the vessel wall by neointima tissue was seen in 91% of the studied frames at two years. Conclusions: This study demonstrates that after an Absorb BVS implantation neointima tissue develops that covers almost the whole circumference of the vessel wall. In contrast to the metallic stents, the neointima tissue does not compromise the luminal dimensions. Further research is required to evaluate the neointimal characteristics and assess the potential value of the device in passivating high-risk plaques.

Six-month results following treatment of aggressive periodontitis with antimicrobial photodynamic therapy or amoxicillin and metronidazole.

OBJECTIVE The use of antibacterial photodynamic therapy (aPDT) additionally to scaling and root planing (SRP) has been shown to positively influence the clinical outcomes. However, at present, it is unknown to what extent aPDT may represent a potential alternative to the use of systemic antibiotics in nonsurgical periodontal therapy in patients with aggressive periodontitis (AP). The aim of this study was to evaluate the outcomes following nonsurgical periodontal therapy and additional use of either aPDT or amoxicillin and metronidazole (AB) in patients with AP. MATERIAL AND METHODS Thirty-six patients with AP displaying at least three sites with pocket depth (PD) ≥6 mm were treated with SRP and either systemic administration of AB for 7 days or with two episodes of aPDT. The following clinical parameters were evaluated at baseline and at 6 months: plaque index (PI), bleeding on probing (BOP), PD, gingival recession (GR) and clinical attachment level (CAL). RESULTS Thirty-five patients have completed the 6-month evaluation. At 6 months, mean PD was statistically significantly reduced in both groups (from 5.0 ± 0.8 to 3.0 ± 0.6 mm with AB and from 5.1 ± 0.5 to 3.9 ± 0.8 mm with aPDT (p < 0.001)). AB yielded statistically significantly higher improvements in the primary outcome parameter PD (p < 0.001) when compared to aPDT. The number of pockets ≥7 mm was reduced from 141 to 3 after AB (p < 0.001) and from 137 to 45 after aPDT (p = 0.03). Both therapies resulted in statistically significant reductions in all parameters compared to baseline. CONCLUSION While both treatments resulted in statistically significant clinical improvements, AB showed statistically significantly higher PD reduction and lower number of pockets ≥7 mm compared to aPDT. CLINICAL RELEVANCE In patients with AP, the two times application of aPDT in conjunction with nonsurgical periodontal therapy cannot be considered an alternative to the systemic use of amoxicillin and metronidazole.

Exercise capacity, physical activity patterns and outcomes six years after cardiac rehabilitation in patients with heart failure.

OBJECTIVE To determine the short- and long-term effects of an intensive, concentrated rehabilitation programme in patients with chronic heart failure. DESIGN Randomized controlled trial, with one-month and six-year evaluations. SETTING Residential rehabilitation centre in Switzerland. SUBJECTS Fifty patients with chronic heart failure, randomized to exercise or control groups. INTERVENTIONS A rehabilitation programme lasting one month, including educational sessions, a low-fat diet, and 2 hours of individually prescribed exercise daily. MAIN MEASURES Exercise test responses, health outcomes and physical activity patterns. RESULTS Peak Vo(2) increased 21.4% in the exercise group during the rehabilitation programme (P<0.05), whereas peak Vo(2) did not change among controls. After the six-year follow-up period, peak Vo(2) was only slightly higher than that at baseline in the trained group (7%, NS), while peak Vo(2) among controls was unchanged. During long-term follow-up, 9 and 12 patients died in the exercise and control groups, respectively (P = 0.63). At six years, physical activity patterns tended to be higher in the exercise group; the mean energy expenditure values over the last year were 2,704 +/- 1,970 and 2,085 +/- 1,522 kcal/week during recreational activities for the exercise and control groups, respectively. However, both groups were more active compared to energy expenditure prior to their cardiac event (P<0.001). CONCLUSIONS Six years after participation in a residential rehabilitation programme, patients with chronic heart failure had slightly better outcomes than control subjects, maintained exercise capacity and engaged in activities that exceed the minimal amount recommended by guidelines for cardiovascular health.

Relationship between depressive symptoms and acute low back pain at first medical consultation, three and six weeks of primary care

Background: Aim of the study was to test lagged reciprocal effects of depressive symptoms and acute low back pain (LBP) across the first weeks of primary care. Methods: In a prospective inception cohort study, 221 primary care patients with acute or subacute LBP were assessed at the time of initial consultation and then followed up at three and six weeks. Key measures were depressive symptoms (modified Zung Self-Rating Depression Scale) and LBP (sensory pain, present pain index and visual analogue scale of the Short-Form McGill Pain Questionnaire). Results: When only cross-lagged effects of six weeks were tested, a reciprocal positive relationship between LBP and depressive symptoms was shown in a cross-lagged structural equation model (β = .15 and .17, p < .01). When lagged reciprocal paths at three- and six-week follow-up were tested, depressive symptoms at the time of consultation predicted higher LBP severity after three weeks (β = .23, p < .01). LBP after three weeks had in turn a positive cross-lagged effect on depression after six weeks (β = .27, p < .001). Conclusions: Reciprocal effects of depressive symptoms and LBP seem to depend on time under medical treatment. Health practitioners should screen for and treat depressive symptoms at the first consultation to improve the LBP treatment.

The relation of secondary student's career choice readiness to a six-phase model of career decision-making

Based on common aspects of recent models of career decision-making (CDM) a sixphase model of CDM for secondary students is presented and empirically evaluated. The study tested the hypothesis that students who are in later phases possess more career choice readiness and consider different numbers of career alternatives. 266 Swiss secondary students completed measures tapping phase of CDM, career choice readiness, and number of considered career options. Career choice readiness showed an increase with phase of CDM. Later phases were generally associated with a larger increase in career choice readiness. Number of considered career options showed a curve-linear development with fewer options considered at the beginning and at the end of the process. Male students showed a larger variability in their distribution among the process with more male than female students in the first and last phase of the process. Implications for theory and practice are presented.

The effects of erythritol air-polishing powder on microbiologic and clinical outcomes during supportive periodontal therapy: Six-month results of a randomized controlled clinical trial.

OBJECTIVES To characterize the physical characteristics of a new low abrasive erythritol powder (EPAP) and to evaluate its influence on the clinical and microbiologic parameters over a period of 6 months in patients undergoing supportive periodontal therapy (SPT). METHOD AND MATERIALS Prior to the clinical application, the particle size and abrasion level of EPAP were compared to glycine air-polishing powder (GPAP) ex vivo. Subsequently, 40 chronic periodontitis patients previously enrolled in SPT were randomly assigned into two groups for the treatment with subgingival EPAP or repeated scaling and root planing (SRP). At baseline (BL), bleeding on probing positive (BOP+) sites with probing pocket depth (PPD) of ≥ 4 mm but no detectable calculus were defined as study sites. During SPT, these sites were either treated by EPAP or SRP at BL, 3, and 6 months (3M, 6M). When indicated, additional SRP was provided. Plaque Index, BOP, PPD, clinical attachment level (CAL), and subgingival plaque were evaluated at BL and 6M. RESULTS EPAP yielded lower abrasiveness and smaller particle sizes when compared to GPAP. In 38 patients completing the study, EPAP and SRP resulted in significant reductions of BOP% (EPAP, 40.45%; SRP, 42.53%), PPD (EPAP, -0.67; SRP, -0.68), and increase of CAL (EPAP, 0.48; SRP, 0.61) while at 6M no statistically significant between-group differences were observed (P > .05). Microbiologic evaluation revealed minor shifts in the composition of the subgingival biofilm without influence on periodontopathogenic bacteria. CONCLUSION The subgingival use of EPAP by means of an air-polishing device may be considered safe and may lead to comparable clinical and microbiologic outcomes to those obtained with SRP. CLINICAL RELEVANCE The subgingival use of EPAP appears to represent a promising modality for the removal of subgingival biofilm during SPT.