Risk Factors for Infectious Complications following Endoscopic Retrograde Cholangiopancreatography in Liver Transplant Patients: A Single-Center Study.

Background: Liver transplant recipients often require endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications, which can lead to infections. This retrospective single-center study aimed to identify risk factors for infectious complications following ERCP in liver transplant patients. Methods: A retrospective analysis was conducted on 285 elective ERCP interventions performed in 88 liver transplant patients at a tertiary care center. The primary endpoint was the occurrence of an infection following ERCP. Univariable and multivariable regression analyses, Cox regression, and log-rank tests were employed to assess the influence of various factors on the incidence of infectious complications. Results: Among the 285 ERCP interventions, isolated anastomotic stenosis was found in 175 cases, ischemic type biliary lesion (ITBL) in 103 cases, and choledocholithiasis in seven cases. Bile duct interventions were performed in 96.9% of all ERCPs. Infections after ERCP occurred in 46 cases (16.1%). Independent risk factors for infection included male sex (OR 24.19), prednisolone therapy (OR 4.5), ITBL (OR 4.51), sphincterotomy (OR 2.44), cholangioscopy (OR 3.22), dilatation therapy of the bile ducts (OR 9.48), and delayed prophylactic antibiotic therapy (>1 h after ERCP) (OR 2.93). Additionally, infections following previous ERCP interventions were associated with an increased incidence of infections following future ERCP interventions (p < 0.0001). Conclusion: In liver transplant patients undergoing ERCP, male sex, prednisolone therapy, and complex bile duct interventions independently raised infection risks. Delayed antibiotic treatment further increased this risk. Patients with ITBL were notably susceptible due to incomplete drainage. Additionally, a history of post-ERCP infections signaled higher future risks, necessitating close monitoring and timely antibiotic prophylaxis.

Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis.

BACKGROUND: Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. AIM: The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. METHODS: Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. RESULTS: A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). CONCLUSIONS: Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.

Mitochondrial translocation of TFEB regulates complex I and inflammation.

TFEB is a master regulator of autophagy, lysosome biogenesis, mitochondrial metabolism, and immunity that works primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation. Proteomics analysis reveals extensive TFEB co-immunoprecipitation with several mitochondrial proteins, whose interactions are disrupted upon infection with S. Typhimurium. High resolution confocal microscopy and biochemistry confirms TFEB localization in the mitochondrial matrix. TFEB translocation depends on a conserved N-terminal TOMM20-binding motif and is enhanced by mTOR inhibition. Within the mitochondria, TFEB and protease LONP1 antagonistically co-regulate complex I, reactive oxygen species and the inflammatory response. Consequently, during infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines, contributing to innate immune pathogenesis.

Irrelevant interests? A qualitative study into how German family surrogates of persons living with dementia fulfill their legal role as advocates of an advance directive.

BACKGROUND AND OBJECTIVES: German legislation establishes advance directives (ADs) as legally binding instruments that all involved parties need to adhere to. This applies also to family members who have been authorized as official surrogates of the AD's author. As surrogates, they are expected to make sure that the AD is being implemented. Our study aims at uncovering how family members experience their legally assigned role as an advocate of an AD. RESEARCH DESIGN AND METHODS: We conducted 25 episodic interviews with family surrogates of persons living with dementia and used thematic analysis to make sense of our interview data. RESULTS: Family surrogates expressed skepticism towards ADs as instruments for planning end-of-life care. They did not necessarily followed the decisions expressed in the AD. We found cases in which family surrogates intentionally refrained from bringing the ADs to the attention of health care providers as well as cases in which the ADs conflicted with self-related interests of family surrogates. DISCUSSION AND IMPLICATION: Our findings lead us to critique the legal construction of family surrogates as advocates of the AD. Family members are directly and enduringly affected by the end-of-life care decisions that the AD sets out and are thus no neutral agents who have no stake in the matter. Expecting them to simply transmit decisions formulated in the AD means expecting them to render their own interests irrelevant - which, arguably, might be too much to ask.

Technical note: Influence of the drying position and time on the persistence of gunshot residues on fabrics.

The influence of the drying position and time on the persistence of gunshot residues (GSR) on fabrics was investigated. Powder tattooing from a 40 cm shooting distance on targeted fabrics were slightly wetted using a spray and dried for 3 h or 48 h in horizontal or vertical positions. The GSR particles were visualised using IR fluorescence with a Video Spectral Comparator (VSC) and automatically counted with a software before the wetting and after the drying stages. While a significant rate of GSR particles (up to 22%) were lost, it was mainly due to the wetting procedure rather than the drying stage. No statistically significant difference was observed between the drying positions, indicating that both drying positions can be used in practice to dry slightly wet fabrics. The drying time had no influence on the loss, and the GSR distribution was not significantly influenced by either factor (i.e., time and position).

Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons.

Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high-coverage whole-genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and interspecies gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes.

Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons.

Baboons (genus Papio ) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high coverage whole genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and inter-species gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal novel patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes. One-Sentence Summary: Genomic data for 225 baboons reveal novel sites of inter-species gene flow and local effects due to differences in admixture.

[Sex in infectious diseases-How sex differences influence the immune response to infections]. / Das Geschlecht in der Infektiologie ­ wie Geschlechtsunterschiede die Immunantwort auf Infektionen beeinflussen.

The humoral and cellular immune responses to antigen stimulation, vaccinations and infections differ between women and men. Genetic, epigenetic and hormonal factors contribute to the sex-specific immunity. The expression of genes on the X­chromosome and the effect of sex hormones substantially influence the immune defence against infections. Females show stronger cellular and humoral immune responses to infections than males, but the enhanced immune response often leads to aberrant inflammatory reactions and autoimmune diseases. Men are principally more prone to bacterial, viral and fungal infections and more often show severe disease courses. In contrast, a more reactive female immune system results in significantly more adverse reactions to vaccinations. In order to be able to better identify the multiple sex-specific that have an influence on the immune system, sex-specific differences should be investigated in a differentiated way. The better understanding of the sex-specific differences in the immune response will have a long-term influence on the prevention, diagnostics and treatment of infectious diseases, and will ultimately contribute to improving healthcare of both women and men.

Social disappointment and partner presence affect long-tailed macaque refusal behaviour in an 'inequity aversion' experiment.

Protest in response to unequal reward distribution is thought to have played a central role in the evolution of human cooperation. Some animals refuse food and become demotivated when rewarded more poorly than a conspecific, and this has been taken as evidence that non-human animals, like humans, protest in the face of inequity. An alternative explanation-social disappointment-shifts the cause of this discontent away from the unequal reward, to the human experimenter who could-but elects not to-treat the subject well. This study investigates whether social disappointment could explain frustration behaviour in long-tailed macaques, Macaca fascicularis. We tested 12 monkeys in a novel 'inequity aversion' paradigm. Subjects had to pull a lever and were rewarded with low-value food; in half of the trials, a partner worked alongside the subjects receiving high-value food. Rewards were distributed either by a human or a machine. In line with the social disappointment hypothesis, monkeys rewarded by the human refused food more often than monkeys rewarded by the machine. Our study extends previous findings in chimpanzees and suggests that social disappointment plus social facilitation or food competition effects drive food refusal patterns.

Inappropriate Involvement? Presenting Empirical Insight into the Preparation Phase of Advance Directives of Persons Living with Dementia Under German Legislation.

The scholarly debate on advance directives (ADs) in the context of dementia is mainly built around ethical arguments. Empirical studies that shed light into the realities of ADs of persons living with dementia are few and far between and too little is known about the effect of national AD legislation on such realities. This paper offers insight into the preparation phase of ADs according to German legislation in the context of dementia. It presents results from a document analysis of 100 ADs and from 25 episodic interviews with family members. Findings show that drafting an AD involves family members and different professionals in addition to the signatory, whose cognitive impairment differed considerably at the time of preparing the AD. The involvement of family members and professionals is at times problematic, which prompts the question of how much and what kind of involvement of others turns an AD of a person living with dementia into an AD about a person living with dementia. The results invite policy makers to critically review legislation on ADs from the perspective of cognitively impaired persons, who might find it difficult to protect themselves from inappropriate involvement when completing an AD.

Human and macaque pairs employ different coordination strategies in a transparent decision game.

Many real-world decisions in social contexts are made while observing a partner's actions. To study dynamic interactions during such decisions, we developed a setup where two agents seated face-to-face to engage in game-theoretical tasks on a shared transparent touchscreen display ('transparent games'). We compared human and macaque pairs in a transparent version of the coordination game 'Bach-or-Stravinsky', which entails a conflict about which of two individually-preferred opposing options to choose to achieve coordination. Most human pairs developed coordinated behavior and adopted dynamic turn-taking to equalize the payoffs. All macaque pairs converged on simpler, static coordination. Remarkably, two animals learned to coordinate dynamically after training with a human confederate. This pair selected the faster agent's preferred option, exhibiting turn-taking behavior that was captured by modeling the visibility of the partner's action before one's own movement. Such competitive turn-taking was unlike the prosocial turn-taking in humans, who equally often initiated switches to and from their preferred option. Thus, the dynamic coordination is not restricted to humans but can occur on the background of different social attitudes and cognitive capacities in rhesus monkeys. Overall, our results illustrate how action visibility promotes the emergence and maintenance of coordination when agents can observe and time their mutual actions.

To live with others is to make concessions. You may want to go to the movies tonight, but your partner may prefer the theatre: reaching a mutually desirable goal ­ that is, spending time together ­ requires adjusting your preferences to theirs. Many other social species also make such decisions, in particular monkeys that live in large groups. Conceptually, these interactions are known as coordination games. In such scenarios, two players must coordinate their actions to attain a coveted reward, but they must also resolve a conflict about who gets the larger share. This makes the joint strategy non-trivial, and different pairs of players might resort to different strategies. In the laboratory, coordination games are often tested in settings which do not allow participants to monitor each other's behaviors as they make these complex choices. In real life, however, individuals making a joint decision can often observe each other and receive immediate feedback. In response, Moeller et al. developed a new way to test coordination games that allows more realistic social interactions. In their setup, two participants face each other and use a shared see-through touchscreen to perform a task. This new design was used to test how humans and macaque monkeys solved a simplified version of the 'Bach or Stravinsky' coordination game, which involves choosing between a red and blue target on the screen. Players in a pair had been trained to 'prefer' opposite colors. In this game, collaboration is beneficial (both individuals get a better prize if they choose the same color) but also creates unfairness (the reward is higher for the participant whose 'favorite' color is selected). When paired up, both humans and monkeys learned to collaborate and to go for the same color (or, in some monkey pairs, the same side of the screen). However, only humans took turns selecting red or blue so that players could alternate getting the highest reward. Monkeys usually settled on one color throughout the game, unless they had learned the 'turn-taking' strategy from a human partner; in that case, the color chosen in each trial was typically determined by the monkey who was the faster to move. These experiments show how monkeys and humans use visual information about their partner's actions to coordinate their choices, paving the way for further decision-making studies that accurately reflect how interactions unfold in real life. Moeller et al. expect that this will help to understand how cooperation and competition emerge in these two species, including how direct face-to-face contact, or lack thereof in some aspects of our modern world, shapes our social behavior.

The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: a prospective observational study.

BACKGROUND: Multiple myeloma (MM) is the third most common hematologic malignancy with increasing importance due to improving treatment strategies and long-term outcomes in an aging population. This study aims to analyse influencing factors on health-related quality of life (HRQoL), such as treatment strategies, participation in a clinical trial and patient characteristics like anxiety, depression, gender, and age. A better understanding of the individual factors in context with HRQoL could provide a helpful instrument for clinical decisions. METHODS: In this prospective observational study, the HRQoL of MM patients with different therapies (first-line and relapse) was quantified by standardized questionnaires (EORTC QLQ-C30 and -MY20) in the context of sociodemographic data, individual anxiety and depressiveness (PHQ-4), and a selected number of clinical parameters and symptoms at defined time-points before, during, and after therapy. RESULTS: In total, 70 patients were included in the study. The median age of the study cohort was 62 years. 44% were female and 56% were male patients. More than half of the patients were fully active with an ECOG 0. Global health status was significantly higher in patients with first-line treatment and even increased after start of therapy, while the pain level decreased. In contrast, patients with relapsed MM reported a decreasing global health status and increasing pain. Additionally, there was a higher global health status in less anxious/depressive patients. HRQoL decreased significantly after start of chemotherapy in the parameters body image, side effects of treatment, and cognitive functioning. Tandem stem-cell transplantation was not found to be a risk factor for higher impairment of HRQoL. Participation in a clinical study led to an improvement of most aspects of HRQoL. Among others, increased anxiety and depression, female gender, older age, impaired performance status, and recurrent disease can be early indicators for a reduced HRQoL. CONCLUSION: This study showed the importance of regular longitudinal assessments of patient reported outcomes (PROs) in routine clinical care. For the first time, to our knowledge, we were able to demonstrate a potential impact between participation in clinical trials and HRQoL. However, due to frequently restrictive inclusion criteria for clinical trials, these MM patients might not be directly comparable with patients treated within standard therapy concepts. Further studies are needed to clarify the relevance of this preliminary data in order to develop an individualized, patient-centred, therapy concept.

Older Barbary macaques show limited capacity for self-regulation to avoid hazardous social interactions.

According to the Strength-and-Vulnerability-Integration (SAVI) model, older people are more motivated to avoid negative affect and high arousal than younger people. To explore the biological roots of this effect, we investigate communicative interactions and social information processing in Barbary macaques (Macaca sylvanus) living at 'La Forêt des Singes' in Rocamadour, France. The study combines an analysis of the production of (N = 8185 signals, 84 signallers) and responses to communicative signals (N = 3672 events, 84 receivers) with a field experiment (N = 166 trials, 45 subjects). Here we show that older monkeys are not more likely to specifically ignore negative social information or to employ avoidance strategies in stressful situations, although they are overall less sociable. We suggest that the monkeys have only a limited capacity for self-regulation within social interactions and rather rely on general avoidance strategies to decrease the risk of potentially hazardous social interactions.

Lessons for the AAC field: a tribute to Dr. David Beukelman.

On February 5, 2022, the field of augmentative and alternative communication (AAC) lost a giant when Dr. David "Dave" Beukelman passed away. As the readership of this journal is aware, Dave was one of the principal founders of the AAC field and devoted his career to providing a voice to those without one. Before AAC became a field, people who could not talk were invisible or seldom noticed, unless they were in the way. For more than 40 years, he was a catalyst for change in AAC clinical practice, research, dissemination, teaching, and public policy development. This tribute aims to honor Dave's lifelong mission of serving others by sharing some of his most timeless and valued lessons. Each lesson begins with one of Dave's most enduring quotes that is then followed by a brief synopsis of the lesson Dave hoped to convey.

The political presence of persons living with dementia in parliament. A qualitative study into the dementia representation work of German parliamentarians.

Parliamentary representation of persons living with dementia is important because it has the potential to enhance the lives of affected individuals. However, studies that take a closer look at the parliamentarization of dementia are few and far between. Drawing on recent advances in political science representation theory, this paper shows how parliamentary attention to persons living with dementia takes the form of representative claims. An interpretive analysis of 56 parliamentary documents revealed that German parliamentarians voiced what they considered to be the political wants and needs of persons living with dementia in different debates on a broad range of topics. They also created a political presence for persons living with dementia in representative claims about other groups - such as professional carers. Both types of claims were one-dimensional in nature: parliamentarians reduced persons living with dementia to their impairments, rendering them politically visible as vulnerable persons who need to be protected by the same society that their existence is putting a "burden" on. A more multi-dimensional political presence for persons living with dementia is required. In order to improve their dementia representation work, it is important that parliamentarians engage with persons living with dementia and understand how they wish to be engagedin parliament or otherwise.

Male-male social bonding, coalitionary support and reproductive success in wild Guinea baboons.

Male-male bonds may confer substantial fitness benefits. The adaptive value of these relationships is often attributed to coalitionary support, which aids in rank ascension and female defence, ultimately resulting in greater reproductive success. We investigated the link between male-male sociality and both coalitionary support and reproductive success in wild Guinea baboons. This species lives in a tolerant multi-level society with reproductive units comprising a male and 1-6 females at the core. Males are philopatric, form differentiated, stable and equitable affiliative relationships (strong bonds) with other males, and lack a clear rank hierarchy. Here, we analysed behavioural and paternity data for 30 males and 50 infants collected over 4 years in the Niokolo-Koba National Park, Senegal. Strongly bonded males supported each other more frequently during conflicts, but strong bonds did not promote reproductive success. Instead, males that spent less time socializing with other males were associated with a higher number of females and sired more offspring. Notably, reproductively active males still maintained bonds with other males, but adjusted their social investment in relation to life-history stage. Long-term data will be needed to test if the adaptive value of male bonding lies in longer male tenure and/or in promoting group cohesion.

How children revise their beliefs in light of reasons.

We investigate how the ability to respond appropriately to reasons provided in discourse develops in young children. In Study 1 (N = 58, Germany, 26 girls), 4- and 5-, but not 3-year-old children, differentiated good from bad reasons. In Study 2 (N = 131, Germany, 64 girls), 4- and 5-year-old children considered both the strength of evidence for their initial belief and the quality of socially provided reasons for an alternative view when deciding whether to change their minds. Study 3 (N = 80, the United States, 42 girls, preregistered) shows that 4- and 5-year-old children also consider meta-reasons (reasons about reasons) in their belief revision. These results suggest that by age 4, children possess key critical thinking capacities for participating in public discourse.