Z' studies at the LHC: an update

We reanalyse the potential of the LHC to discover new $Z'$ gauge bosons and to discriminate between various theoretical models. Using a fast LHC detector simulation, we have investigated how well the characteristics of $Z'$ bosons from different models can be measured. For this analysis we have combined the information coming from the cross section measurement, which provides also the $Z'$ mass and total width, the forward-backward charge asymmetries on- and off-peak, and the $Z'$ rapidity distribution, which is sensitive to its $u \bar{u}$ and $d \bar{d}$ couplings. We confirm that new $Z'$ bosons can be observed in the process $pp \to Z' \to l^+ l^-$, up to masses of about 5 TeV for an integrated luminosity of 100 fb$^{-1}$. The off- and on-resonance peak forward-backward charge asymmetries $A_{\rm FB}^{l}$ show that interesting statistical accuracies can be obtained up to $Z'$ masses of the order of 2 TeV. We then show how the different experimental observables allow for a diagnosis of the $Z'$ boson and the distinction between the various considered models.Comment: 14 pages, latex, 6 figure

Single-stranded heteroduplex intermediates in λ Red homologous recombination

<p>Abstract</p> <p>Background</p> <p>The Red proteins of lambda phage mediate probably the simplest and most efficient homologous recombination reactions yet described. However the mechanism of dsDNA recombination remains undefined.</p> <p>Results</p> <p>Here we show that the Red proteins can act via full length single stranded intermediates to establish single stranded heteroduplexes at the replication fork. We created asymmetrically digestible dsDNA substrates by exploiting the fact that Redα exonuclease activity requires a 5' phosphorylated end, or is blocked by phosphothioates. Using these substrates, we found that the most efficient configuration for dsDNA recombination occurred when the strand that can prime Okazaki-like synthesis contained both homology regions on the same ssDNA molecule. Furthermore, we show that Red recombination requires replication of the target molecule.</p> <p>Conclusions</p> <p>Hence we propose a new model for dsDNA recombination, termed 'beta' recombination, based on the formation of ssDNA heteroduplexes at the replication fork. Implications of the model were tested using (i) an <it>in situ </it>assay for recombination, which showed that recombination generated mixed wild type and recombinant colonies; and (ii) the predicted asymmetries of the homology arms, which showed that recombination is more sensitive to non-homologies attached to 5' than 3' ends. Whereas beta recombination can generate deletions in target BACs of at least 50 kb at about the same efficiency as small deletions, the converse event of insertion is very sensitive to increasing size. Insertions up to 3 kb are most efficiently achieved using beta recombination, however at greater sizes, an alternative Red-mediated mechanism(s) appears to be equally efficient. These findings define a new intermediate in homologous recombination, which also has practical implications for recombineering with the Red proteins.</p

The nitrogen problem of epiphytic lichens – a synthesis

Der starke Anstieg von nitrophytischen Flechten während der letzten 15 Jahren in landwirtschaftlich genutzten und städtischen Bereichen hat die Frage aufgeworfen, welche Stickstoffverbindung dafür verantwortlich sind, welche physiologischen Probleme diese machen, wo diese herkommen, welche Auswirkungen sie auf die Flechten haben, was mit dem Stickstoff in den Flechten passiert, wie sich Feinstaub und trockene Deposition auswirken und wieso Nitrophyten auch in unbelasteten Gebieten dominieren. Nach den Ergebnissen zahlreicher Einzelstudien, die hier mit neuen Daten ergänzt werden, ist Ammoniak die relevante Stickstoffquelle. Dieser wird als Ammoniumnitrat speziell in Form von trockener Deposition von den Flechten aufgenommen. Da Ammoniumnitrat ein Salz ist, haben Nitrophyten höhere osmotische Werte, weswegen sie in belasteten Gebieten konkurrenzkräftiger sind. Dies erlaubt Nitrophyten gleichzeitig die Existenz in Trockengebieten auch ohne Stickstoffemissionen, weswegen sie nicht unbedingt Stickstoffzeiger sondern auch Trockenzeiger sind. Der anfallende Stickstoff wird in Form von Aminosäuren in der Flechte passiv gespeichert, weswegen Nitrophyten nicht nitrophil sondern nitrotolerant, halotolerant und xerophytisch sind. Die momentane Temperaturerhöhung und die damit verbundene erhöhte Verdunstung sowie die Zunahme trockener Deposition (Feinstaubbelastung) führen zur Zeit trotz sinkender Gesamtstickstoffbelastung zu einem weiteren Anstieg der nitrophytischen Flechten.The strong increase of nitrophytic lichens in Central Europe during the past fifteen years in urban regions and regions with intensive agriculture poses the question, which nitrogen compounds are responsible, where they come from, which effects they have on lichens, what happens with the nitrogen in lichens, how particulate matter and dry deposition influence lichens und why nitrophytic lichens dominate also in regions with no or low nitrogen emissions. According to several studies, which are complete by new data, ammonia is the relevant source of nitrogen. It is taken up by lichens as ammoniumnitrate as dry deposition. Ammoniumnitrate, however, is a salt. Accordingly nitrophytic lichens have higher osmotic values. This enables nitrophytic lichens to survive in drier regions as compared with other epiphytic lichens, where they are more competitive, even without nitrogen emissions. Therefore nitrophytic lichens are not nitrophilous but halotolerant and xerophytic. The present increase of temperatures, which raises the evaporation, and the increase of dry deposition (particulate matter) cause an increase of nitrophytic lichens in spite of decrease total nitrogen emissions

Effect of novel endoscope cleaning brush on duodenoscope contamination

Background and aims:Current duodenoscope reprocessing protocols are insufficient to prevent contamination and require adaptations to prevent endoscopy-associated infections (EAI). This study aimed to investigate the effect of a new endoscope cleaning brush on the contamination rate of ready-to-use duodenoscopes. Methods:This retrospective before-and-after intervention study collected duodenoscope surveillance culture results from March 2018 to June 2022. Contamination was defined as ≥1 colony-forming units of gastrointestinal or oral microorganisms (MGO). In December 2020, an endoscope cleaning brush with a sweeper design was introduced as the intervention in the manual cleaning of duodenoscopes. A logistic mixed effects model was used to study the effects of the intervention. Results:Data were collected from 176 culture sets before the new brush's introduction and 81 culture sets after. Pre-introduction, culture sets positive with MGO comprised 45.5% (95% CI: 38.3%-52.8%, 80/176), decreasing to 17.3% (95% CI: 10.6%-26.9%, 14/81) after implementing the new brush. Compared to the former brush, duodenoscopes cleaned with the new brush had lower odds of contamination with MGO (aOR=0.25, 95% CI: 0.11-0.58, p=0.001).Conclusions:Use of the new brush in manual cleaning reduced contamination with MGO and is expected to prevent EAIs. These findings should be confirmed in future prospective randomized studies.</p

Reported barriers to evaluation in chronic care: experiences in six European countries.

INTRODUCTION: The growing movement of innovative approaches to chronic disease management in Europe has not been matched by a corresponding effort to evaluate them. This paper discusses challenges to evaluation of chronic disease management as reported by experts in six European countries. METHODS: We conducted 42 semi-structured interviews with key informants from Austria, Denmark, France, Germany, The Netherlands and Spain involved in decision-making and implementation of chronic disease management approaches. Interviews were complemented by a survey on approaches to chronic disease management in each country. Finally two project teams (France and the Netherlands) conducted in-depth case studies on various aspects of chronic care evaluation. RESULTS: We identified three common challenges to evaluation of chronic disease management approaches: (1) a lack of evaluation culture and related shortage of capacity; (2) reluctance of payers or providers to engage in evaluation and (3) practical challenges around data and the heterogeity of IT infrastructure. The ability to evaluate chronic disease management interventions is influenced by contextual and cultural factors. CONCLUSIONS: This study contributes to our understanding of some of the most common underlying barriers to chronic care evaluation by highlighting the views and experiences of stakeholders and experts in six European countries. Overcoming the cultural, political and structural barriers to evaluation should be driven by payers and providers, for example by building in incentives such as feedback on performance, aligning financial incentives with programme objectives, collectively participating in designing an appropriate framework for evaluation, and making data use and accessibility consistent with data protection policies

Genomic history of coastal societies from eastern South America

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr bp) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr bp from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr bp, corroborating evidence of cultural change

Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life

OBJECTIVE: The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes. DESIGN: We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies. RESULTS: We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population. CONCLUSION: In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies

Detection of novel recombinases in bacteriophage genomes unveils Rad52, Rad51 and Gp2.5 remote homologs

Homologous recombination is a key in contributing to bacteriophages genome repair, circularization and replication. No less than six kinds of recombinase genes have been reported so far in bacteriophage genomes, two (UvsX and Gp2.5) from virulent, and four (Sak, Redβ, Erf and Sak4) from temperate phages. Using profile–profile comparisons, structure-based modelling and gene-context analyses, we provide new views on the global landscape of recombinases in 465 bacteriophages. We show that Sak, Redβ and Erf belong to a common large superfamily adopting a shortcut Rad52-like fold. Remote homologs of Sak4 are predicted to adopt a shortcut Rad51/RecA fold and are discovered widespread among phage genomes. Unexpectedly, within temperate phages, gene-context analyses also pinpointed the presence of distant Gp2.5 homologs, believed to be restricted to virulent phages. All in all, three major superfamilies of phage recombinases emerged either related to Rad52-like, Rad51-like or Gp2.5-like proteins. For two newly detected recombinases belonging to the Sak4 and Gp2.5 families, we provide experimental evidence of their recombination activity in vivo. Temperate versus virulent lifestyle together with the importance of genome mosaicism is discussed in the light of these novel recombinases. Screening for these recombinases in genomes can be performed at http://biodev.extra.cea.fr/virfam

The influence of age, gender and socio-economic status on multimorbidity patterns in primary care. first results from the multicare cohort study

Background: Multimorbidity is a phenomenon with high burden and high prevalence in the elderly. Our previous research has shown that multimorbidity can be divided into the multimorbidity patterns of 1) anxiety, depression, somatoform disorders (ADS) and pain, and 2) cardiovascular and metabolic disorders. However, it is not yet known, how these patterns are influenced by patient characteristics. The objective of this paper is to analyze the association of socio-demographic variables, and especially socio-economic status with multimorbidity in general and with each multimorbidity pattern. Methods: The MultiCare Cohort Study is a multicentre, prospective, observational cohort study of 3.189 multimorbid patients aged 65+ randomly selected from 158 GP practices. Data were collected in GP interviews and comprehensive patient interviews. Missing values have been imputed by hot deck imputation based on Gower distance in morbidity and other variables. The association of patient characteristics with the number of chronic conditions is analysed by multilevel mixed-effects linear regression analyses. Results: Multimorbidity in general is associated with age (+0.07 chronic conditions per year), gender (-0.27 conditions for female), education (-0.26 conditions for medium and -0.29 conditions for high level vs. low level) and income (-0.27 conditions per logarithmic unit). The pattern of cardiovascular and metabolic disorders shows comparable associations with a higher coefficient for gender (-1.29 conditions for female), while multimorbidity within the pattern of ADS and pain correlates with gender (+0.79 conditions for female), but not with age or socioeconomic status. Conclusions: Our study confirms that the morbidity load of multimorbid patients is associated with age, gender and the socioeconomic status of the patients, but there were no effects of living arrangements and marital status. We could also show that the influence of patient characteristics is dependent on the multimorbidity pattern concerned, i.e. there seem to be at least two types of elderly multimorbid patients. First, there are patients with mainly cardiovascular and metabolic disorders, who are more often male, have an older age and a lower socio-economic status. Second, there are patients mainly with ADS and pain-related morbidity, who are more often female and equally distributed across age and socio-economic groups

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS &gt;5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p&lt;0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice