Role of the Binding Energy on Nondipole Effects in Single-Photon Ionization.

We experimentally study the influence of the binding energy on nondipole effects in K-shell single-photon ionization of atoms at high photon energies. We find that for each ionization event, as expected by momentum conservation, the photon momentum is transferred almost fully to the recoiling ion. The momentum distribution of the electrons becomes asymmetrically deformed along the photon propagation direction with a mean value of 8/(5c)(E_{γ}-I_{P}) confirming an almost 100 year old prediction by Sommerfeld and Schur [Ann. Phys. (N.Y.) 396, 409 (1930)10.1002/andp.19303960402]. The emission direction of the photoions results from competition between the forward-directed photon momentum and the backward-directed recoil imparted by the photoelectron. Which of the two counteracting effects prevails depends on the binding energy of the emitted electron. As an example, we show that at 20 keV photon energy, Ne^{+} and Ar^{+} photoions are pushed backward towards the radiation source, while Kr^{+} photoions are emitted forward along the light propagation direction.

Tracing Photoinduced Hydrogen Migration in Alcohol Dications from Time-Resolved Molecular-Frame Photoelectron Angular Distributions.

The recent implementation of attosecond and few-femtosecond X-ray pump/X-ray probe schemes in large-scale free-electron laser facilities has opened the way to visualize fast nuclear dynamics in molecules with unprecedented temporal and spatial resolution. Here, we present the results of theoretical calculations showing how polarization-averaged molecular-frame photoelectron angular distributions (PA-MFPADs) can be used to visualize the dynamics of hydrogen migration in methanol, ethanol, propanol, and isopropyl alcohol dications generated by X-ray irradiation of the corresponding neutral species. We show that changes in the PA-MFPADs with the pump-probe delay as a result of intramolecular photoelectron diffraction carry information on the dynamics of hydrogen migration in real space. Although visualization of this dynamics is more straightforward in the smaller systems, methanol and ethanol, one can still recognize the signature of that motion in propanol and isopropyl alcohol and assign a tentative path to it. A possible pathway for a corresponding experiment requires an angularly resolved detection of photoelectrons in coincidence with molecular fragment ions used to define a molecular frame of reference. Such studies have become, in principle, possible since the first XFELs with sufficiently high repetition rates have emerged. To further support our findings, we provide experimental evidence of H migration in ethanol-OD from ion-ion coincidence measurements performed with synchrotron radiation.

High-energy molecular-frame photoelectron angular distributions: a molecular bond-length ruler.

We present a study on molecular-frame photoelectron angular distributions (MFPADs) of small molecules using circularly polarized synchrotron light. We find that the main forward-scattering peaks of the MFPADs are slightly tilted with respect to the molecular axis. This tilt angle is directly connected to the molecular bond length by a simple, universal formula. We apply the derived formula to several examples of MFPADs of C 1s and O 1s photoelectrons of CO, which have been measured experimentally or obtained by means of ab initio modeling. In addition, we discuss the influence of the back-scattering contribution that is superimposed over the analyzed forward-scattering peak in the case of homo-nuclear diatomic molecules such as N2.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Familiarity influences social networks in dairy cows after regrouping.

Regrouping is common practice when managing dairy cow groups, and it is known to have disruptive effects on behavior and production. The presence of a small group of familiar cows upon regrouping may provide social support and mitigate some of the negative effects. In this study we investigated (1) how regrouping affects social relationships among familiar cows and (2) if cows prefer familiar individuals over unfamiliar ones as social partners after regrouping. We used 3 established groups of cows to create 2 new groups, each containing 14 cows, using subgroups of familiar animals (i.e., 4, 6, and 4 cows) from the original groups. The new groups were similar in respect to the age, parity, and sire of cows. The frequencies of grooming and displacements were determined in the walking alley, lying stalls, and feed bunk by observing 48 h of continuous video before regrouping, directly after regrouping, and 1 wk later. First, social network analysis was applied to investigate the effects of regrouping on the relationships within the subgroups of familiar cows. Second, we determined if familiar cows were more or less connected than would be expected by chance (i.e., assortment), considering displacement, grooming, and feed bunk neighbor networks (derived from electronic feeder data) after regrouping. Regrouping increased the number of displacements, especially in the walking alley. Within the subgroups of familiar cows, regrouping resulted in slightly more displacements, but the network structure did not change. The frequency of grooming among familiar cows remained stable across all observation periods, and the network structure was not affected by regrouping. We found positive assortment in grooming and feed bunk neighbor networks, thereby suggesting that cows preferred familiar individuals as grooming partners and feeding neighbors directly after regrouping and, to a smaller extent, 1 wk later. The effect of familiarity on displacements depended on the pen area. The weak assortment directly after regrouping at the feed bunk indicated that familiar cows displaced each other more than unfamiliar ones, possibly because they were neighbors more often. Our results indicated that a small group of familiar cows may provide ongoing social buffering after regrouping. Further research with multiple groups and larger group sizes is needed to determine whether similar effects are consistently present when groups of familiar cows are subjected to regrouping.

Continued treatment with secukinumab is associated with high retention or regain of response.

BACKGROUND: Conventional analyses present aggregate data, masking late responders and efficacy reductions. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows sustained efficacy in moderate-to-severe psoriasis. OBJECTIVES: To determine stability of response to secukinumab, changes in efficacy were assessed in individual patients. METHODS: This is a post hoc analysis of two phase III randomized controlled trials, FIXTURE (trial registration: NCT01358578) and CLEAR (trial registration: NCT02074982). Patients received secukinumab 300 mg (FIXTURE and CLEAR), etanercept 50 mg (FIXTURE) or ustekinumab 45 or 90 mg (CLEAR) over 52 weeks. Mutually exclusive response categories were defined: ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) ('excellent'), ≥ 75% improvement in PASI (PASI 75) and < PASI 90 ('good') and < PASI 75 ('insufficient'). Reductions in efficacy were defined as shifts from higher to lower response categories between two consecutive visits maintained for a third consecutive visit. Loss of efficacy was defined as a reduction of efficacy resulting in 'insufficient' response. All comparisons are descriptive. RESULTS: At 52 weeks, in CLEAR, 90·2% (303/336) of patients on secukinumab achieved stable efficacy without loss and 77·7% (261/336) showed stable efficacy without any reduction of response [74·3% (252/339) and 59·9% (203/339) of patients for ustekinumab]. In FIXTURE, 83·5% (273/327) and 66·4% (217/327) of patients on secukinumab had stable efficacy without loss or reduction of response [58·3% (190/326) and 42·6% (139/326) for etanercept]. Response was regained by continuing secukinumab treatment in 50% (8/16) of patients in CLEAR and 26% (9/34) in FIXTURE. Similar patterns were observed for other response definitions. CONCLUSIONS: Efficacy with secukinumab was stable over 52 weeks of treatment in most patients. Continued treatment with secukinumab resulted in regain of efficacy in some patients. Persistent loss of response was uncommon. What's already known about this topic? Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows significant and sustained efficacy in the treatment of moderate-to-severe psoriasis. Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood. What does this study add? To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories. Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon. Patient factors such as body weight may affect the likelihood of loss of efficacy.

Secukinumab is effective in treatment of moderate-to-severe plaque psoriasis: real-life effectiveness and safety from the PROSPECT study.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate-to-severe psoriasis. Trial protocols specify transition periods and prohibit concomitant psoriasis medication. Data are therefore needed on secukinumab effectiveness and safety in routine clinical practice. OBJECTIVES: The PROSPECT study assesses prior and concomitant psoriasis treatments and transition periods in subjects receiving secukinumab. Here, we report interim effectiveness and safety data for secukinumab in the context of prior and concomitant treatments. METHODS: PROSPECT is an ongoing 24-week, single-cohort, non-interventional study. Subjects with moderate-to-severe psoriasis with a decision to receive secukinumab 300 mg were included. RESULTS: Of 1988 subjects, 1238/1988 (62.4%) were male, and mean age was 48.1 ± 13.7 years. Mean baseline Psoriasis Area and Severity Index (PASI) score was 17.7 ± 12.5. 90.9% of subjects had prior systemic treatment. Concomitant treatment was recorded in 44.3% of subjects. Median duration of transition period was 14.0, 30.0 and 44.5 days from prior topical, conventional systemic and biologic treatments. At Week 24, PASI75/90/100 was reached by 86.1%, 68.5% and 39.7% of subjects who started secukinumab treatment at baseline. No unexpected safety signals were observed. CONCLUSION: PROSPECT provides a large prospective real-world analysis of secukinumab treatment and includes prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real-world setting. Secukinumab effectiveness and safety were comparable to that seen in the phase 2/3 secukinumab clinical trial programme.

Photon-Momentum-Induced Molecular Dynamics in Photoionization of N_{2} at hν=40 keV.

We investigate K-shell ionization of N_{2} at 40 keV photon energy. Using a cold target recoil ion momentum spectroscopy reaction microscope, we determine the vector momenta of the photoelectron, the Auger electron, and both N^{+} fragments. These fully differential data show that the dissociation process of the N_{2}^{2+} ion is significantly modified not only by the recoil momentum of the photoelectron but also by the photon momentum and the momentum of the emitted Auger electron. We find that the recoil energy introduced by the photon and the photoelectron momentum is partitioned with a ratio of approximately 30∶70 between the Auger electron and fragment ion kinetic energies, respectively. We also observe that the photon momentum induces an additional rotation of the molecular ion.

Recoil-Induced Asymmetry of Nondipole Molecular Frame Photoelectron Angular Distributions in the Hard X-ray Regime.

We investigate angular emission distributions of the 1s photoelectrons of N_{2} ionized by linearly polarized synchrotron radiation at hν=40 keV. As expected, nondipole contributions cause a very strong forward-backward asymmetry in the measured emission distributions. In addition, we observe an unexpected asymmetry with respect to the polarization direction, which depends on the direction of the molecular fragmentation. In particular, photoelectrons are predominantly emitted in the direction of the forward nitrogen atom. This observation cannot be explained via asymmetries introduced by the initial bound and final continuum electronic states of the oriented molecule. The present simulations assign this asymmetry to a novel nontrivial effect of the recoil imposed to the nuclei by the fast photoelectrons and high-energy photons, which results in a propensity for the ions to break up along the axis of the recoil momentum. The results are of particular importance for the interpretation of future experiments at x-ray free electron lasers operating in the few tens of keV regime, where such nondipole and recoil effects will be essential.

Automatic detection of feeding- and drinking-related agonistic behavior and dominance in dairy cows.

Accurate assessments of social behavior and dominance relationships in cattle can be time consuming. We investigated whether replacements at the feed bunk and water trough-one type of agonistic interaction-can be used to automatically assess dominance relationships. Our study set out to (1) validate a replacement detection algorithm using combined data from electronic feed and water bins, and (2) investigate the applicability of this algorithm to identify individual dominance scores and group-level social hierarchy in freestall-housed dairy cows. We used 4 groups of lactating cows kept in different group sizes (11 to 20 cows) located at 2 research facilities. In both facilities, feed and water were provided via automated feeding systems. A trained observer recorded all agonistic interactions in the pen over multiple days using video. Data from the electronic feed and water bins for the same days were analyzed using an algorithm to detect replacements (i.e., visits where a receiver cow was competitively replaced by an actor cow). Most agonistic interactions at the feed bunk were replacements. These replacements were associated with a brief interval between the time the receiver cow left the bin and the actor cow took her place; the optimal threshold to detect these replacements varied from 22 to 27 s between groups, independent of stocking density. The recall and precision of an algorithm based upon this threshold was high (on average >0.8), comparable to that of trained human observers. We improved data preparation by controlling for detection errors and included filtering to reduce false positives. This resulted in a >20% decrease in false positives and an increase in precision of 0.043. The dominance hierarchy based upon algorithm-detected replacements was similar to that based upon total agonistic interactions observed in the pen; the Spearman rank correlation coefficient between these hierarchies varied among the groups from 0.81 to 0.96. We conclude that data from electronic feed and water bins can accurately estimate agonistic behavior and dominance relationships among dairy cows.