Unexpected and delayed fragmentation dynamics of the organometallic ferrocene induced by ion-collision.

We have investigated the fragmentation dynamics of the organometallic ferrocene molecule after interaction with multiply charged ions using multicoincidence mass spectrometry and quantum chemistry calculations. We observed unexpected fragmentation dynamics of the two-body breakup channels from ferrocene dications revealing a charge screening effect from the iron atom and delayed fragmentation dynamics. These observations are rationalized through the population of a specific long-lived excited state, where one positive charge is located on each cyclopentadienyl ring.

Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study.

This first-in-human study of AGN1 LOEP demonstrated that this minimally-invasive treatment durably increased aBMD in femurs of osteoporotic postmenopausal women. AGN1 resorption was coupled with new bone formation by 12 weeks and that new bone was maintained for at least 5-7 years resulting in substantially increased FEA-estimated femoral strength. INTRODUCTION: This first-in-human study evaluated feasibility, safety, and in vivo response to treating proximal femurs of postmenopausal osteoporotic women with a minimally-invasive local osteo-enhancement procedure (LOEP) to inject a resorbable triphasic osteoconductive implant material (AGN1). METHODS: This prospective cohort study enrolled 12 postmenopausal osteoporotic (femoral neck T-score ≤ - 2.5) women aged 56 to 89 years. AGN1 LOEP was performed on left femurs; right femurs were untreated controls. Subjects were followed-up for 5-7 years. Outcomes included adverse events, proximal femur areal bone mineral density (aBMD), AGN1 resorption, and replacement with bone by X-ray and CT, and finite element analysis (FEA) estimated hip strength. RESULTS: Baseline treated and control femoral neck aBMD was equivalent. Treated femoral neck aBMD increased by 68 ± 22%, 59 ± 24%, and 58 ± 27% over control at 12 and 24 weeks and 5-7 years, respectively (p < 0.001, all time points). Using conservative assumptions, FEA-estimated femoral strength increased by 41%, 37%, and 22% at 12 and 24 weeks and 5-7 years, respectively (p < 0.01, all time points). Qualitative analysis of X-ray and CT scans demonstrated that AGN1 resorption and replacement with bone was nearly complete by 24 weeks. By 5-7 years, AGN1 appeared to be fully resorbed and replaced with bone integrated with surrounding trabecular and cortical bone. No procedure- or device-related serious adverse events (SAEs) occurred. CONCLUSIONS: Treating femurs of postmenopausal osteoporotic women with AGN1 LOEP results in a rapid, durable increase in aBMD and femoral strength. These results support the use and further clinical study of this approach in osteoporotic patients at high risk of hip fracture.

Customised bi-compartmental knee arthroplasty shows encouraging 3-year results: findings of a prospective, multicenter study.

PURPOSE: The purpose of this study was to assess the clinical and patient-reported outcomes of a customised, individually made (CIM) bi-compartmental knee arthroplasty (BKA). METHODS: A prospectively recruited cohort of 79 patients was implanted with a CIM-BKA (patello-femoral plus either medial or lateral tibio-femoral, iDuo G2 system, Conformis, Billerica MA) at eight centres in the US and Germany. Patients were assessed for the 2011 KSS, KOOS, and ROM pre-operatively and at 2 weeks, 6 weeks, 12 weeks, 1 year, and 2 years post-operatively. RESULTS: The objective KSS score significantly improved from 69 at the pre-operative visit, to 94 at the 2-year post-operative time-point. Similar improvements were observed for the KSS function and satisfaction domains. Significant improvements from pre-operative levels were observed across all five domains of the KOOS. Two patients have undergone surgery to revise their CIM-BKA implant to total knees, resulting in a survivorship rate of 97.5% at an average follow-up of 2.6 years. CONCLUSIONS: CIM-BKA compares favourably to published scores as well as revision rates for previously available monolithic OTS-BKA implants. CIM-BKA implants provide surgeons with a viable and patient-specific monolithic implant solution as an option for patients presenting with bi-compartmental disease, who might, otherwise, be treated by performing uni-condylar + patello-femoral joint or bicruciate sparing TKA surgeries. Longer follow-up and higher numbers have to be awaited for further validation of these encouraging early results. LEVEL OF EVIDENCE: 3b (individual case-controlled study).

Multiple electron capture from isolated protein poly-anions in collision with slow highly charged ions.

Collisions of 375 keV Xe25+ ions with trapped mass/charge selected poly-anions of the cytochrome C protein (∼12.5 kDa) were studied by coupling a linear quadrupole ion trap with low-energy ion beam facility. Tandem mass spectra were recorded for the protein precursor charge states ranging from -9 to -17. The present work reports the first study of slow highly charged ion collisions with poly-anions. A high signal to noise ratio allowed the study of the intensity of single and multiple electron removal by a projectile, as well as associated neutral losses, as a function of the target charge state. Relative single and double electron detachment cross sections were found to increase with increasing charge state of the precursor anion. The experimental findings are supported by the calculations of the total electron capture cross sections, based on the classical over-the-barrier model, restricted to a simple uniformly charged linear protein structure and a near-end electron capture.

Fragmentation of pure and hydrated clusters of 5Br-uracil by low energy carbon ions: observation of hydrated fragments.

The fragmentation of the isolated 5-bromouracil (5BrU) molecule and pure and nano-hydrated 5BrU clusters induced by low energy 12C4+ ions has been studied. A comparison indicates that the environment, on the one hand, protects the system against the complete break-up into small fragments, but, on the other hand, triggers 'new' pathways for fragmentation, for example the loss of the OH group. The most striking result is the observation of several series of hydrated fragments in the hydrated cluster case, with water molecules bound to hydrophilic sites of 5BrU. This highlights the strong interaction between 5BrU and water molecules and the blocking of specific fragmentation pathways, such as the loss of the BrC2H group for example.

Intracellular LINGO-1 negatively regulates Trk neurotrophin receptor signaling.

Neurotrophins, essential regulators of many aspects of neuronal differentiation and function, signal via four receptors, p75, TrkA, TrkB and TrkC. The three Trk paralogs are members of the LIG superfamily of membrane proteins, which share extracellular domains consisting of leucine-rich repeat and C2 Ig domains. Another LIG protein, LINGO-1 has been reported to bind and influence signaling of p75 as well as TrkA, TrkB and TrkC. Here we examine the manner in which LINGO-1 influences the function of TrkA, TrkB and TrkC. We report that Trk activation promotes Trk association with LINGO-1, and that this association promotes Trk degradation by a lysosomal mechanism. This mechanism resembles the mechanism by which another LIG protein, LRIG1, promotes lysosomal degradation of receptor tyrosine kinases such as the EGF receptor. We present evidence indicating that the Trk/LINGO-1 interaction occurs, in part, within recycling endosomes. We show that a mutant form of LINGO-1, with much of the extracellular domain deleted, has the capacity to enhance TrkA signaling in PC12 cells, possibly by acting as an inhibitor of Trk down-regulation by full length LINGO-1. We propose that LINGO-1 functions as a negative feedback regulator of signaling by cognate receptor tyrosine kinases including TrkA, TrkB and TrkC.

Determination of Energy-Transfer Distributions in Ionizing Ion-Molecule Collisions.

The ionization and fragmentation of the nucleoside thymidine in the gas phase has been investigated by combining ion collision with state-selected photoionization experiments and quantum chemistry calculations. The comparison between the mass spectra measured in both types of experiments allows us to accurately determine the distribution of the energy deposited in the ionized molecule as a result of the collision. The relation of two experimental techniques and theory shows a strong correlation between the excited states of the ionized molecule with the computed dissociation pathways, as well as with charge localization or delocalization.

The diversification of Heliconius butterflies: what have we learned in 150 years?

Research into Heliconius butterflies has made a significant contribution to evolutionary biology. Here, we review our understanding of the diversification of these butterflies, covering recent advances and a vast foundation of earlier work. Whereas no single group of organisms can be sufficient for understanding life's diversity, after years of intensive study, research into Heliconius has addressed a wide variety of evolutionary questions. We first discuss evidence for widespread gene flow between Heliconius species and what this reveals about the nature of species. We then address the evolution and diversity of warning patterns, both as the target of selection and with respect to their underlying genetic basis. The identification of major genes involved in mimetic shifts, and homology at these loci between distantly related taxa, has revealed a surprising predictability in the genetic basis of evolution. In the final sections, we consider the evolution of warning patterns, and Heliconius diversity more generally, within a broader context of ecological and sexual selection. We consider how different traits and modes of selection can interact and influence the evolution of reproductive isolation.

Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies.

Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima.

Formation of H2 from internally heated polycyclic aromatic hydrocarbons: excitation energy dependence.

We have investigated the effectiveness of molecular hydrogen (H2) formation from Polycyclic Aromatic Hydrocarbons (PAHs) which are internally heated by collisions with keV ions. The present and earlier experimental results are analyzed in view of molecular structure calculations and a simple collision model. We estimate that H2 formation becomes important for internal PAH temperatures exceeding about 2200 K, regardless of the PAH size and the excitation agent. This suggests that keV ions may effectively induce such reactions, while they are unlikely due to, e.g., absorption of single photons with energies below the Lyman limit. The present analysis also suggests that H2 emission is correlated with multi-fragmentation processes, which means that the [PAH-2H](+) peak intensities in the mass spectra may not be used for estimating H2-formation rates.

Mobilisation of haemopoietic stem cells in teriparatide-treated patients.

Parathyroid hormone (PTH) is the predominant regulator of calcium/phosphate homeostasis in the human body. Beside this classical function, preclinical and clinical studies indicated a relevant role for PTH in mobilisation of bone marrow-derived cells into peripheral blood. In addition, recombinant PTH (teriparatide) was recently approved for the treatment of severe osteoporosis. Therefore, it was the aim of the present study to investigate the dynamics of haemopoietic stem cells and corresponding in peripheral blood of 13 patients with osteoporosis during treatment with teriparatide. We were able to show that administration of teriparatide is sufficient to mobilise haemopoietic stem cells into the bloodstream accompanied by an alteration of mobilising cytokines. In conclusion, teriparatide might be a useful tool in the context of stem cell mobilisation.

Fragmentation of anthracene C14H10, acridine C13H9N and phenazine C12H8N2 ions in collisions with atoms.

We report experimental total, absolute, fragmentation cross sections for anthracene C14H10, acridine C13H9N, and phenazine C12H8N2 ions colliding with He at center-of-mass energies close to 100 eV. In addition, we report results for the same ions colliding with Ne, Ar, and Xe at higher energies. The total fragmentation cross sections for these three ions are the same within error bars for a given target. The measured fragment mass distributions reveal significant contributions from both delayed (≫10(-12) s) statistical fragmentation processes as well as non-statistical, prompt (∼10(-15) s), single atom knockout processes. The latter dominate and are often followed by secondary statistical fragmentation. Classical Molecular Dynamics (MD) simulations yield separate cross sections for prompt and delayed fragmentation which are consistent with the experimental results. The intensity of the single C/N-loss peak, the signature of non-statistical fragmentation, decreases with the number of N atoms in the parent ion. The fragment intensity distributions for losses of more than one C or N atom are rather similar for C14H10 and C13H9N but differ strongly for C12H8N2 where weak C-N bonds often remain in the fragments after the first fragmentation step. This greatly increases their probability to fragment further. Distributions of internal energy remaining in the fragments after knockout are obtained from the MD simulations.

Absolute fragmentation cross sections in atom-molecule collisions: scaling laws for non-statistical fragmentation of polycyclic aromatic hydrocarbon molecules.

We present scaling laws for absolute cross sections for non-statistical fragmentation in collisions between Polycyclic Aromatic Hydrocarbons (PAH/PAH(+)) and hydrogen or helium atoms with kinetic energies ranging from 50 eV to 10 keV. Further, we calculate the total fragmentation cross sections (including statistical fragmentation) for 110 eV PAH/PAH(+) + He collisions, and show that they compare well with experimental results. We demonstrate that non-statistical fragmentation becomes dominant for large PAHs and that it yields highly reactive fragments forming strong covalent bonds with atoms (H and N) and molecules (C6H5). Thus nonstatistical fragmentation may be an effective initial step in the formation of, e.g., Polycyclic Aromatic Nitrogen Heterocycles (PANHs). This relates to recent discussions on the evolution of PAHNs in space and the reactivities of defect graphene structures.

Revealing biogenic sulfuric acid corrosion in sludge digesters: detection of sulfur-oxidizing bacteria within full-scale digesters.

Biogenic sulfuric acid corrosion (BSA) is a costly problem affecting both sewerage infrastructure and sludge handling facilities such as digesters. The aim of this study was to verify BSA in full-scale digesters by identifying the microorganisms involved in the concrete corrosion process, that is, sulfate-reducing (SRB) and sulfur-oxidizing bacteria (SOB). To investigate the SRB and SOB communities, digester sludge and biofilm samples were collected. SRB diversity within digester sludge was studied by applying polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) targeting the dsrB-gene (dissimilatory sulfite reductase beta subunit). To reveal SOB diversity, cultivation dependent and independent techniques were applied. The SRB diversity studies revealed different uncultured SRB, confirming SRB activity and H2S production. Comparable DGGE profiles were obtained from the different sludges, demonstrating the presence of similar SRB species. By cultivation, three pure SOB strains from the digester headspace were obtained including Acidithiobacillus thiooxidans, Thiomonas intermedia and Thiomonas perometabolis. These organisms were also detected with PCR-DGGE in addition to two new SOB: Thiobacillus thioparus and Paracoccus solventivorans. The SRB and SOB responsible for BSA were identified within five different digesters, demonstrating that BSA is a problem occurring not only in sewer systems but also in sludge digesters. In addition, the presence of different SOB species was successfully associated with the progression of microbial corrosion.

Evidence for strong van der Waals type Rydberg-Rydberg interaction in a thermal vapor.

We present evidence for Rydberg-Rydberg interaction in a gas of rubidium atoms above room temperature. Rabi oscillations on the nanosecond time scale to different Rydberg states are investigated in a vapor cell experiment. Analyzing the atomic time evolution and comparing to a dephasing model, we find a scaling with the Rydberg quantum number n that is consistent with van der Waals interaction. Our results show that the interaction strength can be larger than the kinetic energy scale (Doppler width), which is the requirement for realization of thermal quantum devices in the GHz regime.

Formations of dumbbell C118 and C119 inside clusters of C60 molecules by collision with α particles.

We report highly selective covalent bond modifications in collisions between keV alpha particles and van der Waals clusters of C(60) fullerenes. Surprisingly, C(119)(+) and C(118)(+) are the dominant molecular fusion products. We use molecular dynamics simulations to show that C(59)(+) and C(58)(+) ions--effectively produced in prompt knockout processes with He(2+)--react rapidly with C(60) to form dumbbell C(119)(+) and C(118)(+). Ion impact on molecular clusters in general is expected to lead to efficient secondary reactions of interest for astrophysics. These reactions are different from those induced by photons.

Ions colliding with clusters of fullerenes--decay pathways and covalent bond formations.

We report experimental results for the ionization and fragmentation of weakly bound van der Waals clusters of n C60 molecules following collisions with Ar(2+), He(2+), and Xe(20+) at laboratory kinetic energies of 13 keV, 22.5 keV, and 300 keV, respectively. Intact singly charged C60 monomers are the dominant reaction products in all three cases and this is accounted for by means of Monte Carlo calculations of energy transfer processes and a simple Arrhenius-type [C60]n(+) → C60(+)+(n-1)C60 evaporation model. Excitation energies in the range of only ~0.7 eV per C60 molecule in a [C60]13(+) cluster are sufficient for complete evaporation and such low energies correspond to ion trajectories far outside the clusters. Still we observe singly and even doubly charged intact cluster ions which stem from even more distant collisions. For penetrating collisions the clusters become multiply charged and some of the individual molecules may be promptly fragmented in direct knock-out processes leading to efficient formations of new covalent systems. For Ar(2+) and He(2+) collisions, we observe very efficient C119(+) and C118(+) formation and molecular dynamics simulations suggest that they are covalent dumb-bell systems due to bonding between C59(+) or C58(+) and C60 during cluster fragmentation. In the Ar(2+) case, it is possible to form even smaller C120-2m(+) molecules (m = 2-7), while no molecular fusion reactions are observed for the present Xe(20+) collisions.

[The clinical importance of the critical view of safety in laparoscopic cholecystectomy]. / Die klinische Bedeutung des "critical view of safety" in der laparoskopischen Gallenblasenchirurgie.

BACKGROUND: Injury of the bile duct during cholecystectomy (CHE) is a severe complication. The critical view of safety (CVS) can help to reduce the frequency of this complication during laparoscopic CHE. So far, no scoring of CVS images with a grading system is available. METHOD: The CVS images of 534 patients with laparoscopic CHE could be structurally analyzed and assessed with marks from 1 (very good) to 5 (insufficient). The CVS mark was correlated with the perioperative course. Additionally, the perioperative course of patients after laparoscopic CHE with and without a CVS image was investigated. RESULTS: In 534 patients 1 or more CVS images could be analyzed. The average CVS mark was 1.9, whereby 280 patients (52.4%) had a 1, 126 patients (23.6%) a 2, 114 (21.3%) a 3 and 14 patients (2.6%) a 4 or 5. Younger patients with elective laparoscopic CHE had CVS images significantly more frequently (p ≤ 0.04). The statistical examination with Pearson's χ2-test and the F­test (ANOVA) showed a significant correlation between improving CVS marks and reduction of surgery time (p < 0.01) and the hospitalization time (p < 0.01). For senior physicians the quota of CVS images ranged from 71% to 92% and the average marks from 1.5 to 2.2. The marks for the CVS images were significantly better for female than male patients (1.8 vs. 2.1, p < 0.01). DISCUSSION: There was a relatively broad distribution of marks for CVS images. Injuries of the bile duct can be avoided with a high degree of certainty with marks 1­2 for the CVS image. The CVS is not always adequately visualized in laparoscopic CHE.

[The COVID-19 pandemic had significant impact on duration of surgery and hospitalization time for patients after cholecystectomy]. / Die Auswirkungen der COVID-19 Pandemie führten zu signifikanten Veränderungen der Operations- und Liegezeiten bei Patienten nach Cholezystektomie.

BACKGROUND: The COVID-19 pandemic made substantial changes in medical care necessary. The aims of this study were to find out what influence the pandemic had on the perioperative course in patients with cholecystectomy (CHE) and to highlight possible residual consequences. METHOD: From 1 July 2018 to 31 December 2021 a total of 735 patients with CHE were analyzed. Up to 21 March 2020 patients were assigned to the regular patient group (Reg, n = 430), patients after this date (first lockdown 22 March 2020) to the Cov19 patient group (Cov19, n = 305) and the 2 groups were compared. RESULTS: The average age of all patients was 59 years and 63% were women. The average length of hospitalization (KrVD, time period between surgery and discharge) was 4.4 days. The patient groups Reg and Cov19 did not differ with respect to age, gender or KrVD. The total number of CHEs carried out was reduced by 21.4% in the Cov19 group. This affected elective and emergency CHE to the same extent. The length of surgery significantly increased in the Cov19 group from 64 min (SD 34 min) to 71 min (SD 38 min). The number of short and long hospital stays (KrVD 2 or >4 days) significantly increased in the Cov19 group from 4 % to 20 % (short stay, p < 0.01) and from 23 % to 27 % (long stay, p < 0.01). This was particularly observed for patients >70 years old with an increase in long stays from 43 % to 56 % in the Cov19 group. CONCLUSION: The COVID-19 pandemic led to a clear reduction in CHE both for elective and emergency interventions. Furthermore, a significant lengthening of the surgery and hospitalization times could be observed for older patients. The residual consequences of the pandemic could be shortened hospitalization times after uncomplicated CHE and more interventional treatment procedures in complex cases.

Biomolecular characterization of 3500-year-old ancient Egyptian mummification balms from the Valley of the Kings.

Ancient Egyptian mummification was practiced for nearly 4000 years as a key feature of some of the most complex mortuary practices documented in the archaeological record. Embalming, the preservation of the body and organs of the deceased for the afterlife, was a central component of the Egyptian mummification process. Here, we combine GC-MS, HT-GC-MS, and LC-MS/MS analyses to examine mummification balms excavated more than a century ago by Howard Carter from Tomb KV42 in the Valley of the Kings. Balm residues were scraped from now empty canopic jars that once contained the mummified organs of the noble lady Senetnay, dating to the 18th dynasty, ca. 1450 BCE. Our analysis revealed balms consisting of beeswax, plant oil, fats, bitumen, Pinaceae resins, a balsamic substance, and dammar or Pistacia tree resin. These are the richest, most complex balms yet identified for this early time period and they shed light on balm ingredients for which there is limited information in Egyptian textual sources. They highlight both the exceptional status of Senetnay and the myriad trade connections of the Egyptians in the 2nd millennium BCE. They further illustrate the excellent preservation possible even for organic remains long removed from their original archaeological context.