Prognostic implications of the seventh edition of the international union against cancer classification for patients with gastric cancer: the Western experience of patients treated in a single-center European institution

PURPOSE Validity of the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems for gastric cancer has been evaluated in several studies, mostly in Asian patient populations. Only few data are available on the prognostic implications of the new classification system on a Western population. Therefore, we investigated its prognostic ability based on a German patient cohort. PATIENTS AND METHODS Data from a single-center cohort of 1,767 consecutive patients surgically treated for gastric cancer were classified according to the seventh edition and were compared using the previous TNM/UICC classification. Kaplan-Meier analyses were performed for all TNM stages and UICC stages in a comparative manner. Additional survival receiver operating characteristic analyses and bootstrap-based goodness-of-fit comparisons via Bayesian information criterion (BIC) were performed to assess and compare prognostic performance of the competing classification systems. RESULTS We identified the UICC pT/pN stages according to the seventh edition of the AJCC/UICC guidelines as well as resection status, age, Lauren histotype, lymph-node ratio, and tumor grade as independent prognostic factors in gastric cancer, which is consistent with data from previous Asian studies. Overall survival rates according to the new edition were significantly different for each individual's pT, pN, and UICC stage. However, BIC analysis revealed that, owing to higher complexity, the new staging system might not significantly alter predictability for overall survival compared with the old system within the analyzed cohort from a statistical point of view. CONCLUSION The seventh edition of the AJCC/UICC classification was found to be valid with distinctive prognosis for each stage. However, the AJCC/UICC classification has become more complex without improving predictability for overall survival in a Western population. Therefore, simplification with better predictability of overall survival of patients with gastric cancer should be considered when revising the seventh edition.

The influence of recent major crater impacts on the surrounding surfaces of (21) Lutetia

We present 3-D simulations of impacts into Asteroid 21 Lutetia, the subject of a fly-by by the European Space Agency's Rosetta mission to Comet 67P/Churyumov-Gerasimenko. Using a 3-D shape model of the asteroid, impacts of sizes sufficient to reproduce the observed craters in Lutetia's North Polar Crater Cluster (NPCC) as observed by the OSIRIS experiment have been simulated using the Smoothed Particle Hydrodynamics technique. The asteroid itself has been modelled both as a homogeneous body and as a body with an iron core.

Measurements of a water potential and water content in unsaturated crystalline rock

A water desaturation zone develops around a tunnel in water-saturated rock when the evaporative water loss at the rock surface is larger than the water flow from the surrounding saturated region of restricted permeability. We describe the methods with which such water desaturation processes in rock materials can be quantified. The water retention characteristic theta(psi) of crystalline rock samples was determined with a pressure membrane apparatus. The negative water potential, identical to the capillary pressure, psi, below the tensiometric range (psi < -0.1 MPa) can be measured with thermocouple psychrometers (TP), and the volumetric water contents, theta, by means of time domain reflectometry (TDR). These standard methods were adapted for measuring the water status in a macroscopically unfissured granodiorite with a total porosity of approximately 0.01. The measured water retention curve of granodiorite samples from the Grimsel test site (central Switzerland) exhibits a shape which is typical for bimodal pore size distributions. The measured bimodality is probably an artifact of a large surface ratio of solid/voids. The thermocouples were installed without a metallic screen using the cavity drilled into the granodiorite as a measuring chamber. The water potentials observed in a cylindrical granodiorite monolith ranged between -0.1 and -3.0 MPa; those near the wall in a ventilated tunnel between -0.1 and -2.2 MPa. Two types of three-rod TDR Probes were used, one as a depth probe inserted into the rock, the other as a surface probe using three copper stripes attached to the surface for detecting water content changes in the rock-to-air boundary. The TDR signal was smoothed with a low-pass filter, and the signal length determined based on the first derivative of the trace. Despite the low porosity of crystalline rock these standard methods are applicable to describe the unsaturated zone in solid rock and may also be used in other consolidated materials such as concrete.

Statistical characterization and development of summary measures of non-normal distributions of nuclear morphometry data from prostate cancer cells for use as prognostic indicators

Nuclear morphometry (NM) uses image analysis to measure features of the cell nucleus which are classified as: bulk properties, shape or form, and DNA distribution. Studies have used these measurements as diagnostic and prognostic indicators of disease with inconclusive results. The distributional properties of these variables have not been systematically investigated although much of the medical data exhibit nonnormal distributions. Measurements are done on several hundred cells per patient so summary measurements reflecting the underlying distribution are needed.^ Distributional characteristics of 34 NM variables from prostate cancer cells were investigated using graphical and analytical techniques. Cells per sample ranged from 52 to 458. A small sample of patients with benign prostatic hyperplasia (BPH), representing non-cancer cells, was used for general comparison with the cancer cells.^ Data transformations such as log, square root and 1/x did not yield normality as measured by the Shapiro-Wilks test for normality. A modulus transformation, used for distributions having abnormal kurtosis values, also did not produce normality.^ Kernel density histograms of the 34 variables exhibited non-normality and 18 variables also exhibited bimodality. A bimodality coefficient was calculated and 3 variables: DNA concentration, shape and elongation, showed the strongest evidence of bimodality and were studied further.^ Two analytical approaches were used to obtain a summary measure for each variable for each patient: cluster analysis to determine significant clusters and a mixture model analysis using a two component model having a Gaussian distribution with equal variances. The mixture component parameters were used to bootstrap the log likelihood ratio to determine the significant number of components, 1 or 2. These summary measures were used as predictors of disease severity in several proportional odds logistic regression models. The disease severity scale had 5 levels and was constructed of 3 components: extracapsulary penetration (ECP), lymph node involvement (LN+) and seminal vesicle involvement (SV+) which represent surrogate measures of prognosis. The summary measures were not strong predictors of disease severity. There was some indication from the mixture model results that there were changes in mean levels and proportions of the components in the lower severity levels. ^

Quantifying uncertainty in cost effectiveness analyses

This study compared four alternative approaches (Taylor, Fieller, percentile bootstrap, and bias-corrected bootstrap methods) to estimating confidence intervals (CIs) around cost-effectiveness (CE) ratio. The study consisted of two components: (1) Monte Carlo simulation was conducted to identify characteristics of hypothetical cost-effectiveness data sets which might lead one CI estimation technique to outperform another. These results were matched to the characteristics of an (2) extant data set derived from the National AIDS Demonstration Research (NADR) project. The methods were used to calculate (CIs) for data set. These results were then compared. The main performance criterion in the simulation study was the percentage of times the estimated (CIs) contained the “true” CE. A secondary criterion was the average width of the confidence intervals. For the bootstrap methods, bias was estimated. ^ Simulation results for Taylor and Fieller methods indicated that the CIs estimated using the Taylor series method contained the true CE more often than did those obtained using the Fieller method, but the opposite was true when the correlation was positive and the CV of effectiveness was high for each value of CV of costs. Similarly, the CIs obtained by applying the Taylor series method to the NADR data set were wider than those obtained using the Fieller method for positive correlation values and for values for which the CV of effectiveness were not equal to 30% for each value of the CV of costs. ^ The general trend for the bootstrap methods was that the percentage of times the true CE ratio was contained in CIs was higher for the percentile method for higher values of the CV of effectiveness, given the correlation between average costs and effects and the CV of effectiveness. The results for the data set indicated that the bias corrected CIs were wider than the percentile method CIs. This result was in accordance with the prediction derived from the simulation experiment. ^ Generally, the bootstrap methods are more favorable for parameter specifications investigated in this study. However, the Taylor method is preferred for low CV of effect, and the percentile method is more favorable for higher CV of effect. ^

Robust estimates of climate-induced hydrological change in a temperate mountainous region

A sustainable water resources management depends on sound information about the impacts of climate change. This information is, however, not easily derived because natural runoff variability interferes with the climate change signal. This study presents a procedure that leads to robust estimates of magnitude and Time Of Emergence (TOE) of climate-induced hydrological change that also account for the natural variability contained in the time series. Firstly, natural variability of 189 mesoscale catchments in Switzerland is sampled for 10 ENSEMBLES scenarios for the control (1984–2005) and two scenario periods (near future: 2025–2046, far future: 2074–2095) applying a bootstrap procedure. Then, the sampling distributions of mean monthly runoff are tested for significant differences with the Wilcoxon-Mann–Whitney test and for effect size with Cliff’s delta d. Finally, the TOE of a climate change induced hydrological change is determined when at least eight out of the ten hydrological projections significantly differ from natural variability. The results show that the TOE occurs in the near future period except for high-elevated catchments in late summer. The significant hydrological projections in the near future correspond, however, to only minor runoff changes. In the far future, hydrological change is statistically significant and runoff changes are substantial. Temperature change is the most important factor determining hydrological change in this mountainous region. Therefore, hydrological change depends strongly on a catchment’s mean elevation. Considering that the hydrological changes are predicted to be robust in the near future highlights the importance of accounting for these changes in water resources planning.

Variability in Accumulation Rates from GPR Profiling on the West Antarctic Plateau

lsochronal layers in firn detected with ground-penetrating radar (GPR) and dated using results from ice-core analyses are used to calculate accumulation rates along a 100 km across-flow profile in West Antarctica. Accumulation rates are shown to be highly variable over short distances. Elevation measurements from global positioning system surveys show that accumulation rates derived from shallow horizons correlate well with surface undulations, which implies that wind redistribution of snow is the leading cause of this variability. Temporal changes in accumulation rate over 25-185 year intervals are smoothed to along-track length scales comparable to surface undulations in order to identify trends in accumulation that are likely related to changes in climate. Results show that accumulation rates along this profile have decreased in recent decades, which is consistent with core-derived time series of annual accumulation rates measured at the two ends of the radar profile. These results suggest that temporal variability observed in accumulation-rate records from ice cores and GPR profiles can be obscured by spatial influences, although it is possible to resolve temporal signals if the effects of local topography and ice flow are quantified and removed.

Basal Melting Along the Floating Part of Byrd Glacier

A mass balance calculation was made for the floating part of Byrd Glacier, using 1978-79 ice elevation and velocity data, over the 45 km of Byrd Glacier from its grounding line to where it leaves its fjord and merges with the Ross Ice Shelf. Smoothed basal melting rates were relatively uniform over this distance and averaged 12 +/- 2 m yr(-1).

Stacking of discontinuous regional palaeoclimate records: Chironomid-based summer temperatures from the Alpine region

Since multi-site reconstructions are less affected by site-specific climatic effects and artefacts, regional palaeotemperature reconstructions based on a number of sites can provide more robust estimates of centennial- to millennial-scale temperature trends than individual, site-specific records. Furthermore, reconstructions based on multiple records are necessary for developing continuous climate records over time scales longer than covered by individual sequences. Here, we present a procedure for developing such reconstructions based on relatively short (centuries to millennia), discontinuously sampled records as are typically developed when using biotic proxies in lake sediments for temperature reconstruction. The approach includes an altitudinal correction of temperatures, an interpolation of individual records to equal time intervals, a stacking procedure for sections of the interval of interest that have the same records available, as well as a splicing procedure to link the individual stacked records into a continuous reconstruction. Variations in the final, stacked and spliced reconstruction are driven by variations in the individual records, whereas the absolute temperature values are determined by the stacked segment based on the largest number of records. With numerical simulations based on the NGRIP δ18O record, we demonstrate that the interpolation and stacking procedure provides an approximation of a smoothed palaeoclimate record if based on a sufficient number of discontinuously sampled records. Finally, we provide an example of a stacked and spliced palaeotemperature reconstruction 15000–90 calibrated 14C yr BP based on six chironomid records from the northern and central Swiss Alps and eastern France to discuss the potential and limitations of this approach.

The positive effects of protean career attitude for self-initiated expatriates: Cultural adjustment as a mediator

Purpose – The authors sought to explain why and how protean career attitude might influence self‐initiated expatriates' (SIEs) experiences positively. A mediation model of cultural adjustment was proposed and empirically evaluated. Design/methodology/approach – Data from 132 SIEs in Germany containing measures of protean career attitude, cultural adjustment, career satisfaction, life satisfaction, and intention to stay in the host country were analysed using path analysis with a bootstrap method. Findings – Empirical results provide support for the authors' proposed model: the positive relations between protean career attitude and the three expatriation outcomes (career satisfaction, life satisfaction and intention to stay in the host country) were mediated by positive cross‐cultural adjustment of SIEs. Research limitations/implications – All data were cross‐sectional from a single source. The sample size was small and included a large portion of Chinese participants. The study should be replicated with samples in other destination countries, and longitudinal research is suggested. Practical implications – By fostering both a protean career attitude in skilled SIE employees and their cultural adjustment, corporations and receiving countries could be able to retain this international workforce better in times of talent shortage. Originality/value – This study contributes to the scarce research on the conceptual relatedness of protean career attitude and SIEs, as well as to acknowledging the cultural diversity of the SIE population.

Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

Metastases in normal-sized pelvic lymph nodes: detection with diffusion-weighted MR imaging

PURPOSE To prospectively assess the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging in the detection of pelvic lymph node metastases in patients with prostate and/or bladder cancer staged as N0 with preoperative cross-sectional imaging. MATERIALS AND METHODS This study was approved by an independent ethics committee. Written informed consent was obtained from all patients. Patients with no enlarged lymph nodes on preoperative cross-sectional images who were scheduled for radical resection of the primary tumor and extended pelvic lymph node dissection were enrolled. All patients were examined with a 3-T MR unit, and examinations included conventional and DW MR imaging of the entire pelvis. Image analysis was performed by three independent readers blinded to any clinical information. Metastases were diagnosed on the basis of high signal intensity on high b value DW MR images and morphologic features (shape, border). Histopathologic examination served as the standard of reference. Sensitivity and specificity were calculated, and bias-corrected 95% confidence intervals (CIs) were obtained with the bootstrap method. The Fleiss and Cohen κ and median test were applied for statistical analyses. RESULTS A total of 4846 lymph nodes were resected in 120 patients. Eighty-eight lymph node metastases were found in 33 of 120 patients (27.5%). Short-axis diameter of these metastases was less than or equal to 3 mm in 68, more than 3 mm to 5 mm in 13, more than 5 mm to 8 mm in five; and more than 8 mm in two. On a per-patient level, the three readers correctly detected metastases in 26 (79%; 95% CI: 64%, 91%), 21 (64%; 95% CI: 45%, 79%), and 25 (76%; 95% CI: 60%, 90%) of the 33 patients with metastases, with respective specificities of 85% (95% CI: 78%, 92%), 79% (95% CI: 70%, 88%), and 84% (95% CI: 76%, 92%). Analyzed according to hemipelvis, lymph node metastases were detected with histopathologic examination in 44 of 240 pelvic sides (18%); the three readers correctly detected these on DW MR images in 26 (59%; 95% CI: 45%, 73%), 19 (43%; 95% CI: 27%, 57%), and 28 (64%; 95% CI: 47%, 78%) of the 44 cases. CONCLUSION DW MR imaging enables noninvasive detection of small lymph node metastases in normal-sized nodes in a substantial percentage of patients with prostate and bladder cancer diagnosed as N0 with conventional cross-sectional imaging techniques.

Determinanten kognitiver Angstmanifestation während schulischer Tests: Eine Längsschnittstudie

Theoretischer Hintergrund und Fragestellung: Schulische Tests dienen der Feststellung von Wissen und Können. Wie jede Messung kann auch diese durch Störvariablen verzerrt werden. Während Tests erlebte Angst ist ein solcher potentieller Störeinfluss: Angst kann Testleistungen beinträchtigen, da sie sich hinderlich auf die Informationsverarbeitung auswirken kann (Störung des Wissensabrufs und des Denkens; Zeidner, 1998). Dieser kognitiven Angstmanifestation (Rost & Schermer, 1997) liegt die angstbedingte automatische Aufmerksamkeitsorientierung auf aufgaben-irrelevante Gedanken während der Testbearbeitung zugrunde (Eysenck, Derakshan, Santos & Calvo, 2007). Es hat sich allerdings gezeigt, dass Angst nicht grundsätzlich mit Testleistungseinbußen einhergeht (Eysenck et al., 2007). Wir gehen davon aus, dass die Kapazität zur Selbstkontrolle bzw. Aufmerksamkeitsregulation (Baumeister, Muraven & Tice, 2000; Schmeichel & Baumeister, 2010) ein Faktor ist, der bedingt, wie stark kognitive Angstmanifestation während Tests und damit zusammenhängende Leistungseinbußen auftreten. Ängstliche Lernende mit höherer Aufmerksamkeitsregulationskapazität sollten ihrer automatischen Aufmerksamkeitsorientierung auf aufgaben-irrelevante Gedanken erfolgreicher entgegensteuern und ihre Aufmerksamkeit weiterhin auf die Aufgabenbearbeitung richten können. Dem entsprechend sollten sie trotz Angst weniger kognitive Angstmanifestation während Tests erleben als ängstliche Lernende mit geringerer Aufmerksamkeitsregulationskapazität. Auch die Selbstwirksamkeitserwartung und das Selbstwertgefühl sind Variablen, die in der Vergangenheit mit der Bewältigung von Angst und Stress in Verbindung gebracht wurden (Bandura, 1977; Baumeister, Campbell, Krueger & Vohs, 2003). Daher wurden diese Variablen als weitere Prädiktoren berücksichtigt. Es wurde die Hypothese getestet, dass die dispositionelle Aufmerksamkeitsregulationskapazität über die dispositionelle Selbstwirksamkeitserwartung und das dispositionelle Selbstwertgefühl hinaus Veränderungen in der kognitiven Angstmanifestation während Mathematiktests in einer Wirtschaftsschülerstichprobe vorhersagt. Es wurde des Weiteren davon ausgegangen, dass eine indirekte Verbindung zwischen der Aufmerksamkeitsregulationskapazität und der Veränderung in den Mathematiknoten, vermittelt über die Veränderung in der kognitiven Angstmanifestation, besteht. Methode: Einhundertachtundfünfzig Wirtschaftsschüler bearbeiteten im September 2011 (T1) einen Fragebogen, der die folgenden Messungen enthielt:-Subskala Kognitive Angstmanifestation aus dem Differentiellen Leistungsangstinventar (Rost & Schermer, 1997) bezogen auf Mathematiktests (Sparfeldt, Schilling, Rost, Stelzl & Peipert, 2005); Alpha = .90; -Skala zur dispositionellen Aufmerksamkeitsregulationskapazität (Bertrams & Englert, 2013); Alpha = .88; -Skala zur Selbstwirksamkeitserwartung (Schwarzer & Jerusalem, 1995); Alpha = .83; -Skala zum Selbstwertgefühl (von Collani & Herzberg, 2003); Alpha = .83; -Angabe der letzten Mathematikzeugnisnote. Im Februar 2012 (T2), also nach 5 Monaten und kurz nach dem Erhalt des Halbjahreszeugnisses, gaben die Schüler erneut ihre kognitive Angstmanifestation während Mathematiktests (Alpha = .93) und ihre letzte Mathematikzeugnisnote an. Ergebnisse: Die Daten wurden mittels Korrelationsanalyse, multipler Regressionsanalyse und Bootstrapping ausgewertet. Die Aufmerksamkeitsregulationskapazität, die Selbstwirksamkeitserwartung und das Selbstwertgefühl (alle zu T1) waren positiv interkorreliert, r= .50/.59/.59. Diese Variablen wurden gemeinsam als Prädiktoren in ein Regressionsmodell zur Vorhersage der kognitiven Angstmanifestation zu T2 eingefügt. Gleichzeitig wurde die kognitive Angstmanifestation zu T1 konstant gehalten. Es zeigte sich, dass die Aufmerksamkeitsregulationskapazität erwartungskonform die Veränderungen in der kognitiven Angstmanifestation vorhersagte, Beta = -.21, p= .02. Das heißt, dass höhere Aufmerksamkeitsregulationskapazität zu T1 mit verringerter kognitiver Angstmanifestation zu T2 einherging. Die Selbstwirksamkeitserwartung, Beta = .12, p= .14, und das Selbstwertgefühl, Beta = .05, p= .54, hatten hingegen keinen eigenen Vorhersagewert für die Veränderungen in der kognitiven Angstmanifestation. Des Weiteren ergab eine Mediationsanalyse mittels Bootstrapping (bias-corrected bootstrap 95% confidence interval, 5000 resamples; siehe Hayes & Scharkow, in press), dass die Aufmerksamkeitsregulationskapazität (T1), vermittelt über die Veränderung in der kognitiven Angstmanifestation, indirekt mit der Veränderung in der Mathematikleistung verbunden war (d.h. das Bootstrap-Konfidenzintervall schloss nicht die Null ein; CI [0.01, 0.24]). Für die Selbstwirksamkeitserwartung und das Selbstwertgefühl fand sich keine analoge indirekte Verbindung zur Mathematikleistung. Fazit: Die Befunde verweisen auf die Bedeutsamkeit der Aufmerksamkeitsregulationskapazität für die Bewältigung kognitiver Angstreaktionen während schulischer Tests. Losgelöst von der Aufmerksamkeitsregulationskapazität scheinen positive Erwartungen und ein positives Selbstbild keine protektive Wirkung hinsichtlich der leistungsbeeinträchtigenden kognitiven Angstmanifestation während Mathematiktests zu besitzen.

Range-based Weighted-likelihood Particle Filter for RSS-based Indoor Tracking

Attractive business cases in various application fields contribute to the sustained long-term interest in indoor localization and tracking by the research community. Location tracking is generally treated as a dynamic state estimation problem, consisting of two steps: (i) location estimation through measurement, and (ii) location prediction. For the estimation step, one of the most efficient and low-cost solutions is Received Signal Strength (RSS)-based ranging. However, various challenges - unrealistic propagation model, non-line of sight (NLOS), and multipath propagation - are yet to be addressed. Particle filters are a popular choice for dealing with the inherent non-linearities in both location measurements and motion dynamics. While such filters have been successfully applied to accurate, time-based ranging measurements, dealing with the more error-prone RSS based ranging is still challenging. In this work, we address the above issues with a novel, weighted likelihood, bootstrap particle filter for tracking via RSS-based ranging. Our filter weights the individual likelihoods from different anchor nodes exponentially, according to the ranging estimation. We also employ an improved propagation model for more accurate RSS-based ranging, which we suggested in recent work. We implemented and tested our algorithm in a passive localization system with IEEE 802.15.4 signals, showing that our proposed solution largely outperforms a traditional bootstrap particle filter.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND  Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS  A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS  Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS  We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.