Inter-facility transfers for emergency obstetrical and neonatal care in rural Madagascar: a cost-effectiveness analysis.

CONTEXT: There is a substantial lack of inter-facility referral systems for emergency obstetrical and neonatal care in rural areas of sub-Saharan Africa. Data on the costs and cost-effectiveness of such systems that reduce preventable maternal and neonatal deaths are scarce. SETTING: We aimed to determine the cost-effectiveness of a non-governmental organisation (NGO)-run inter-facility referral system for emergency obstetrical and neonatal care in rural Southern Madagascar by analysing the characteristics of cases referred through the intervention as well as its costs. DESIGN: We used secondary NGO data, drawn from an NGO's monitoring and financial administration database, including medical and financial records. OUTCOME MEASURES: We performed a descriptive and a cost-effectiveness analysis, including a one-way deterministic sensitivity analysis. RESULTS: 1172 cases were referred over a period of 4 years. The most common referral reasons were obstructed labour, ineffective labour and eclampsia. In total, 48 neonates were referred through the referral system over the study period. Estimated cost per referral was US$336 and the incremental cost-effectiveness ratio (ICER) was US$70 per additional life-year saved (undiscounted, discounted US$137). The sensitivity analysis showed that the intervention was cost-effective for all scenarios with the lowest ICER at US$99 and the highest ICER at US$205 per additional life-year saved. When extrapolated to the population living in the study area, the investment costs of the programme were US$0.13 per person and annual running costs US$0.06 per person. CONCLUSIONS: In our study, the inter-facility referral system was a very cost-effective intervention. Our findings may inform policies, decision-making and implementation strategies for emergency obstetrical and neonatal care referral systems in similar resource-constrained settings.

A cross-sectional analysis of the effectiveness of a nutritional support programme for people with tuberculosis in Southern Madagascar using secondary data from a non-governmental organisation.

BACKGROUND: There is a strong, bi-directional link between tuberculosis (TB) and undernutrition: TB often causes undernutrition, and undernourished people are more likely to contract TB and experience worse outcomes. Globally, several TB nutritional support programmes exist; however, evidence on their effectiveness is limited and contested. This study evaluates the effect of a nutritional support programme implemented for people with TB in the Atsimo-Andrefana region, Madagascar in 2022. Within this programme, undernourished people with TB [with a body mass index (BMI) of < 18.5 kg/m2] receive 0.6 L of vegetable oil and 6.0 kg of a soy-wheat blend per month throughout their TB treatment. METHODS: We analysed secondary non-governmental organisation data collected between January and November 2022 in the Atsimo-Andrefana region, Southern Madagascar, including information on an individual's medical conditions (e.g., type of TB, treatment outcomes) and nutritional status measured prior to, during, and after completion of treatment (e.g., height, weight, mid-upper arm circumference). We conducted descriptive analyses of patient baseline characteristics and outcomes to assess the impact of the provided nutritional support on the BMI of people with TB. RESULTS: A total of 1310 people with TB were included in the study [9.9% (130) children under the age of 5, 32.1% (420) children between 5 and 18 years, 58.0% (760) adults]. 55.4% of children under 5, 28.1% of children between ages 5 and 18, and 81.3% of adults were undernourished at treatment initiation. 42.3% (55/130) of children under 5 experienced severe acute malnutrition at treatment uptake. While the average BMI of adults with TB receiving food support increased over time, from 17.1 kg/m2 (interquartile range: 15.8-18.3, range: 10.3-22.5) to 17.9 kg/m2 (interquartile range: 16.6-19.1, range: 11.9-24.1), most adults remained undernourished even after completing TB treatment. CONCLUSIONS: The current TB nutritional support programme falls short of sufficiently increasing the BMI of people with TB to overcome malnutrition. There is an urgent need to revise the nutritional support available for people with TB, particularly for children under 5.

Listening to the Voices of Health Care Workers During the COVID-19 Pandemic: A Qualitative Study Providing In-Depth Insights Into Ethical and Individual Challenges.

In their daily practice, health care workers (HCWs) experience the effects of tensions between professional ethos and work realities, which can lead to ethical dilemmas. We aim to explore the ethical dilemmas that affected HCWs in Germany during the COVID-19 pandemic and to understand these in the context of the German health system. Between April and December 2022, we interviewed HCWs from various levels of care and key informants responsible for decisions related to HCWs in Germany. Three themes were identified in the data analyzed from 78 participants. The first highlighted the potency of pre-existing health system problems during the COVID-19 pandemic. The second captured the ethical dilemmas that were described as having arisen due to the tension between professional ethos and structural constraints. The third included factors related to increasing or diminishing the implications of ethical dilemmas. A lack of opportunities for HCWs to participate in political and managerial decisions was suggested to result in policies that do not meet the needs of HCWs and patients. Positive interpersonal interactions were described as helpful when coping with dilemmatic decision-making situations. In order to avoid negative consequences caused by unresolved ethical dilemmas, including moral distress, among HCWs, staff shortages and decision-making in the German health system urgently need to be addressed. HCWs' working conditions regularly evoke ethical dilemmas, particularly during public health emergencies. Together with HCWs, decision-makers must develop new models for working in health care settings that are in line with HCWs' professional ethos.

Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease.

BACKGROUND: Patients with steroid-refractory acute graft-versus-host disease (aGvHD) not tolerating/responding to ruxolitinib (RR-aGvHD) have a dismal prognosis. METHODS: We retrospectively assessed real-world outcomes of RR-aGvHD treated with the random-donor allogeneic MSC preparation MSC-FFM, available via Hospital Exemption in Germany. MSC-FFM is provided as frozen cell dispersion for administration as i.v. infusion immediately after thawing, at a recommended dose of 1-2 million MSCs/kg body weight in 4 once-weekly doses. 156 patients, 33 thereof children, received MSC-FFM; 5% had Grade II, 40% had Grade III, and 54% had Grade IV aGvHD. Median (range) number of prior therapies was 4 (1-10) in adults and 7 (2-11) in children. RESULTS: The safety profile of MSC-FFM was consistent with previous reports for MSC therapies in general and MSC-FFM specifically. The overall response rate at Day 28 was 46% (95% confidence interval [CI] 36-55%) in adults and 64% (45-80%) in children; most responses were durable. Probability of overall survival at 6, 12 and 24 months was 47% (38-56%), 35% (27-44%) and 30% (22-39%) for adults, and 59% (40-74%), 42% (24-58%) and 35% (19-53%) for children, respectively (whole cohort: median OS 5.8 months). CONCLUSION: A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, respectively (median 28 days). Our data thus suggest effectiveness of MSC-FFM in RR-aGvHD.

Usability and acceptance of a mobile health wallet for pregnancy-related healthcare: A mixed methods study on stakeholders' perceptions in central Madagascar.

BACKGROUND: Several sub-Saharan African countries use digital financial services to improve health financing, especially for maternal and child health. In cooperation with the Malagasy Ministry of Health, the NGO Doctors for Madagascar is implementing a mobile health wallet for maternal health care in public-sector health facilities in Madagascar. Our aim was to explore the enabling and limiting factors related to the usability and acceptance of the Mobile Maternal Health Wallet (MMHW) intervention during its implementation. METHODS: We conducted a cross-sectional, mixed methods study with mothers and pregnant women and facility- (FBHWs) and community-based (CHWs) health workers from public-sector health facilities in three districts of the Analamanga region in Madagascar. We used a convergent design in collecting and analyzing quantitative and qualitative data. We performed one-stage proportional sampling of women who had signed up for the MMHW. All FBHWs and CHWs at primary care facilities in the intervention area were eligible to participate. RESULTS AND SIGNIFICANCE: 314 women, 76 FBHWs, and 52 CHWs were included in the quantitative survey. Qualitative data were extracted from in-depth interviews with 12 women and 12 FBHWs and from six focus group discussions with 39 CHWSs. The MMHW intervention was accepted and used by health workers and women from different socioeconomic backgrounds. Main motivations for women to enroll in the intervention were the opportunity to save money for health (30.6%), electronic vouchers for antenatal ultrasound (30.2%), and bonus payments upon reaching a savings goal (27.9%). Main motivation for health workers was enabling pregnant women to save for health, thus encouraging facility-based deliveries (57.9%). Performance-based payments had low motivational value for health workers. Key facilitators were community sensitization, strong women-health worker relationship, decision making at the household level, and repetitive training on the use of the MMHW. Key barriers included limited phone ownership, low level of digital literacy, disinformation concerning the effects of the intervention, and technical problems like slow payout processes.

Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis.

Impaired proinsulin-to-insulin processing in pancreatic ß-cells is a key defective step in both type 1 diabetes and type 2 diabetes (T2D) (refs. 1,2), but the mechanisms involved remain to be defined. Altered metabolism of sphingolipids (SLs) has been linked to development of obesity, type 1 diabetes and T2D (refs. 3-8); nonetheless, the role of specific SL species in ß-cell function and demise is unclear. Here we define the lipid signature of T2D-associated ß-cell failure, including an imbalance of specific very-long-chain SLs and long-chain SLs. ß-cell-specific ablation of CerS2, the enzyme necessary for generation of very-long-chain SLs, selectively reduces insulin content, impairs insulin secretion and disturbs systemic glucose tolerance in multiple complementary models. In contrast, ablation of long-chain-SL-synthesizing enzymes has no effect on insulin content. By quantitatively defining the SL-protein interactome, we reveal that CerS2 ablation affects SL binding to several endoplasmic reticulum-Golgi transport proteins, including Tmed2, which we define as an endogenous regulator of the essential proinsulin processing enzyme Pcsk1. Our study uncovers roles for specific SL subtypes and SL-binding proteins in ß-cell function and T2D-associated ß-cell failure.

Selective ablation of P53 in pancreatic beta cells fails to ameliorate glucose metabolism in genetic, dietary and pharmacological models of diabetes mellitus.

OBJECTIVE: Beta cell dysfunction and death are critical steps in the development of both type 1 and type 2 diabetes (T1D and T2D), but the underlying mechanisms are incompletely understood. Activation of the essential tumor suppressor and transcription factor P53 (also known as TP53 and Trp53 in mice) was linked to beta cell death in vitro and has been reported in several diabetes mouse models and beta cells of humans with T2D. In this article, we set out to determine the beta cell specific role of P53 in beta cell dysfunction, cell death and development of diabetes in vivo. METHODS: We generated beta cell specific P53 knockout (P53BKO) mice and used complementary genetic, dietary and pharmacological models of glucose intolerance, beta cell dysfunction and diabetes development to evaluate the functional role of P53 selectively in beta cells. We further analyzed the effect of P53 ablation on beta cell survival in isolated pancreatic islets exposed to diabetogenic stress inducers ex vivo by flow cytometry. RESULTS: Beta cell specific ablation of P53/Trp53 failed to ameliorate glucose tolerance, insulin secretion or to increase beta cell numbers in genetic, dietary and pharmacological models of diabetes. Additionally, loss of P53 in beta cells did not protect against streptozotocin (STZ) induced hyperglycemia and beta cell death, although STZ-induced activation of classical pro-apoptotic P53 target genes was significantly reduced in P53BKO mice. In contrast, Olaparib mediated PARP1 inhibition protected against acute ex vivo STZ-induced beta cell death and islet destruction. CONCLUSIONS: Our study reveals that ablation of P53 specifically in beta cells is unexpectedly unable to attenuate beta cell failure and death in vivo and ex vivo. While during development and progression of diabetes, P53 and P53-regulated pathways are activated, our study suggests that P53 signaling is not essential for loss of beta cells or beta cell dysfunction. P53 in other cell types and organs may predominantly regulate systemic glucose homeostasis.

Crossing the Last Mile of TB Care in Rural Southern Madagascar: A Multistakeholder Initiative.

Despite a free TB care policy, access to TB care in rural Madagascar is limited due to a markedly underfunded health care system. The World Health Organization estimated the yearly TB incidence in Madagascar at 238 cases per 100,000 people in 2020; only half of the patients with TB are being notified and treated. We describe the development, implementation, and lessons learned of an intervention to improve TB care services in a remote, rural district in southern Madagascar. We involved national, regional, and local stakeholders in assessing the multifaceted challenges in a remote, rural area and codesigning activities to address them. The overarching principles of the intervention were to (1) promote national TB guidelines, (2) build on best practices, and (3) prioritize low-cost activities to enable scale-up. An in-depth assessment of challenges in accessing and delivering TB care resulted in the following prioritization of activities: (1) fostering community engagement, (2) decentralizing service provision, (3) improving quality of care, (4) providing nutritional support, and (5) ensuring staff support and supervision. The intervention was launched in September 2019 and is ongoing as of October 2022. During mobile TB clinics conducted between September 2019 and December 2020, 4,982 presumptive patients were screened and 1,706 (34.2%) have been diagnosed with TB. Based on 2010-2020 official TB notification data, we calculated trend-adjusted additional TB notifications during the intervention, resulting in a 2.6-fold increase in cases in 2019-2020. The intervention district's TB notification rate increased from 178 cases per 100,000 people in 2018 to 424 cases per 100,000 people in 2020. Involving stakeholders from all levels of care was perceived as a key to success. The unexpected increase in the number of patients with TB in the intervention district overburdened the current paper-based TB notification system and emphasized the need for expanded diagnostics and social support services.

Individual and organizational resilience-Insights from healthcare providers in Germany during the COVID-19 pandemic.

We explored the effects of resilience in the healthcare setting during the COVID-19 pandemic in Germany. Our study sheds light on the cross-level effects of resilience in hospitals and thus responds to calls to research this empirically. In a cross-sectional study design, the perceptions of resilience of employees in hospitals and of transformations at the individual, team, and organizational level were analyzed. An online survey was conducted in summer 2020 in Germany in which 1,710 healthcare workers completed a self-report questionnaire. Results indicate that resilience is both a highly interrelated construct on the individual and organizational level and also positively linked to perceptions of transformation as an indicator for demonstration of resilience. We also found a partial mediation effect of organizational resilience and team efficacy, respectively, on the relationship between individual resilience and perceived transformation on the individual and organizational level as well as a full mediation on the team level. The study highlights the interdependence of individual and organizational resilience (which is mediated by team efficacy) and its impact on perceived transformation in German hospitals during the COVID-19 pandemic. Whereas team efficacy is crucial for performance in regular work operations, during a pandemic the organizational level becomes more relevant. Theoretical and practical implications are discussed.

Detection rate with routine postoperative renal ultrasound to identify urinary tract injury after gynecological surgery.

PURPOSE: The aim of this study was to establish the rate at which routine postoperative renal ultrasonography is able to detect urinary tract injury following gynecological surgery. METHODS: A retrospective analysis was carried out for the study period 2015-2019 of all patients who had undergone subtotal or total hysterectomy, or radical hysterectomy or salpingectomy, salpingo-oophorectomy, or oophorectomy, and subsequently had a urinary tract injury. RESULTS: In a total of 2068 patients, 25 urinary tract injuries occurred (1.21%), including 21 urinary bladder lesions (1.02%) and four ureteral injuries (0.19%). The incidence of urinary tract injuries was 3% in oncologic procedures and 0.86% in procedures for benign disease. Nineteen injuries (76%) were diagnosed intraoperatively, and six injuries (24%) were clinically diagnosed after surgery. All of the patients had uneventful postoperative renal ultrasound examinations. CONCLUSION: Routine postoperative renal ultrasonography was not capable of diagnosing urinary tract injuries after gynecologic surgery. Routine postoperative renal ultrasound examinations should, therefore, not be performed after gynecologic operations.

Metaphorical expressions originating from human senses: Psycholinguistic and affective norms for German metaphors for internal state terms (MIST database).

Internal states, e.g., emotions, cognitive states, or desires, are often verbalized by figurative means, in particular by embodied metaphors involving human senses, such as touch, taste, and smell. The present paper presents a database for German metaphorical expressions conveying internal states with human senses as their source domains. 168 metaphorical expressions from the source domains of vision, hearing, smell, taste, touch, and temperature combined with literal equivalents were collected and rated by 643 adults. The agreement between the metaphor and an equivalent literal expression, as well as emotional valence, arousal, and familiarity values were assessed using a 7-point Likert scale. Between the metaphorical expressions and their equivalents, familiarity, but not valence or arousal differed significantly while agreement ratings indicated high similarity in meaning. The novel database offers carefully controlled stimuli that can be used in both empirical metaphor research and research on internal state language. Using part of the stimuli in a sentence completion experiment revealed a significant preference for literal over metaphorical expressions that cannot be attributed to higher familiarity levels.

Direct and Base Excision Repair-Mediated Regulation of a GC-Rich cis-Element in Response to 5-Formylcytosine and 5-Carboxycytosine.

Stepwise oxidation of the epigenetic mark 5-methylcytosine and base excision repair (BER) of the resulting 5-formylcytosine (5-fC) and 5-carboxycytosine (5-caC) may provide a mechanism for reactivation of epigenetically silenced genes; however, the functions of 5-fC and 5-caC at defined gene elements are scarcely explored. We analyzed the expression of reporter constructs containing either 2'-deoxy-(5-fC/5-caC) or their BER-resistant 2'-fluorinated analogs, asymmetrically incorporated into CG-dinucleotide of the GC box cis-element (5'-TGGGCGGAGC) upstream from the RNA polymerase II core promoter. In the absence of BER, 5-caC caused a strong inhibition of the promoter activity, whereas 5-fC had almost no effect, similar to 5-methylcytosine or 5-hydroxymethylcytosine. BER of 5-caC caused a transient but significant promoter reactivation, succeeded by silencing during the following hours. Both responses strictly required thymine DNA glycosylase (TDG); however, the silencing phase additionally demanded a 5'-endonuclease (likely APE1) activity and was also induced by 5-fC or an apurinic/apyrimidinic site. We propose that 5-caC may act as a repressory mark to prevent premature activation of promoters undergoing the final stages of DNA demethylation, when the symmetric CpG methylation has already been lost. Remarkably, the downstream promoter activation or repression responses are regulated by two separate BER steps, where TDG and APE1 act as potential switches.

The 4MOTHERS trial of the impact of a mobile money-based intervention on maternal and neonatal health outcomes in Madagascar: study protocol of a cluster-randomized hybrid effectiveness-implementation trial.

BACKGROUND: Mobile money-a service enabling users to receive, store, and send electronic money using mobile phones-has been widely adopted across low- and middle-income economies to pay for a variety of services, including healthcare. However, evidence on its effects on healthcare access and health outcomes are scarce and the possible implications of using mobile money for financing and payment of maternal healthcare services-which generally require large one-time out-of-pocket payments-have not yet been systematically assessed in low-resource settings. The aim of this study is to determine the impact on health outcomes, cost-effectiveness, feasibility, acceptability, and usefulness of mobile phone-based savings and payment service, the Mobile Maternal Health Wallet (MMHW), for skilled healthcare during pregnancy and delivery among women in Madagascar. METHODS: This is a hybrid effectiveness-implementation type-1 trial, determining the effectiveness of the intervention while evaluating the context of its implementation in Madagascar's Analamanga region, containing the capital, Antananarivo. Using a stratified cluster randomized design, 61 public-sector primary-care health facilities were randomized within 6 strata to either receive the intervention or not (29 intervention vs. 32 control facilities). The strata were defined by a health facility's antenatal care visit volume and its capacity to offer facility-based deliveries. The registered pre-specified primary outcomes are (i) delivery at a health facility, (ii) antenatal care visits, and (iii) total healthcare expenditure during pregnancy, delivery, and neonatal period. The registered pre-specified secondary outcomes include additional health outcomes, economic outcomes, and measurements of user experience and satisfaction. Our estimated enrolment number is 4600 women, who completed their pregnancy between July 1, 2020, and December 31, 2021. A series of nested mixed-methods studies will elucidate client and provider perceptions on feasibility, acceptability, and usefulness of the intervention to inform future implementation efforts. DISCUSSION: A cluster-randomized, hybrid effectiveness-implementation design allows for a robust approach to determine whether the MMHW is a feasible and beneficial intervention in a resource-restricted public healthcare environment. We expect the results of our study to guide future initiatives and health policy decisions related to maternal and neonatal health and universal healthcare coverage through technology in Madagascar and other countries in sub-Saharan Africa. TRIAL REGISTRATION: This trial was registered on March 12, 2021: Deutsches Register Klinischer Studien (German Clinical Trials Register), identifier: DRKS00014928 . For World Health Organization Trial Registration Data Set see Additional file 1.

A longitudinal study on symptom duration and 60-day clinical course in non-hospitalised COVID-19 cases in Berlin, Germany, March to May, 2020.

BackgroundDetailed information on symptom duration and temporal course of patients with mild COVID-19 was scarce at the beginning of the COVID-19 pandemic.AimWe aimed to determine the longitudinal course of clinical symptoms in non-hospitalised COVID-19 patients in Berlin, Germany.MethodsBetween March and May 2020, 102 confirmed COVID-19 cases in home isolation notified in Berlin, Germany, were sampled using total population sampling. Data on 25 symptoms were collected during telephone consultations (a maximum of four consultations) with each patient. We collected information on prevalence and duration of symptoms for each day of the first 2 weeks after symptom onset and for day 30 and 60 after symptom onset.ResultsMedian age was 35 years (range 18-74), 57% (58/102) were female, and 37% (38/102) reported having comorbidities. During the first 2 weeks, most common symptoms were malaise (94%, 92/98), headache (71%, 70/98), and rhinitis (69%, 68/98). Malaise was present for a median of 11 days (IQR 7-14 days) with 35% (34/98) of cases still reporting malaise on day 14. Headache and muscle pain mostly occurred during the first week, whereas dysosmia and dysgeusia mostly occurred during the second week. Symptoms persisted in 41% (39/95) and 20% (18/88) of patients on day 30 and 60, respectively.ConclusionOur study shows that a significant proportion of non-hospitalised COVID-19 cases endured symptoms for at least 2 months. Further research is needed to assess the frequency of long-term adverse health effects in non-hospitalised COVID-19 patients.

Regulation of GC box activity by 8-oxoguanine.

The oxidation-induced DNA modification 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was recently implicated in the activation and repression of gene transcription. We aimed at a systematic characterisation of the impacts of 8-oxodG on the activity of a GC box placed upstream from the RNA polymerase II core promoter. With the help of reporters carrying single synthetic 8-oxodG residues at four conserved G:C base pairs (underlined) within the 5'-TGGGCGGAGC-3' GC box sequence, we identified two modes of interference of 8-oxodG with the promoter activity. Firstly, 8-oxodG in the purine-rich (but not in the pyrimidine-rich) strand caused direct impairment of transcriptional activation. In addition, and independently of the first mechanism, 8-oxodG initiated a decline of the gene expression, which was mediated by the specific DNA glycosylase OGG1. For the different 8-oxodG positions, the magnitude of this effect reflected the excision preferences of OGG1. Thus, 8-oxodG seeded in the pyrimidine-rich strand was excised with the highest efficiency and caused the most pronounced decrease of the promoter activity. Conversely, 8-oxodG in the symmetric position within the same CpG dinucleotide, was poorly excised and induced no decline of the gene expression. Of note, abasic lesions caused gene silencing in both positions. By contrast, an uncleavable apurinic lesion in the pyrimidine-rich strand enhanced the GC box activity, suggesting that the AP endonuclease step provides a switch between the active versus repressed promoter states during base excision repair.

Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q).

Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide. Genome-wide DNA methylation analysis using Illumina 450k methylation arrays was performed on n=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets.

The Elephant in the Room: A Systematic Review of Stimulus Control in Neuro-Measurement Studies on Figurative Language Processing.

The processing of metaphors and idioms has been the subject of neuroscientific research for several decades. However, results are often contradictory, which can be traced back to inconsistent terminology and stimulus control. In this systematic review of research methods, we analyse linguistic aspects of 116 research papers which used EEG, fMRI, PET, MEG, or NIRS to investigate the neural processing of the two figurative subtypes metaphor and idiom. We critically examine the theoretical foundations as well as stimulus control by performing a systematic literature synthesis according to the PRISMA guidelines. We explicitly do not analyse the findings of the studies but instead focus on four primary aspects: definitions of figurative language and its subtypes, linguistic theory behind the studies, control for factors influencing figurative language processing, and the relationship between theoretical and operational definitions. We found both a lack and a broad variety in existing definitions and operationalisation, especially in regard to familiarity and conventionality. We identify severe obstacles in the comparability and validation potential of the results of the papers in our review corpus. We propose the development of a consensus in fundamental terminology and more transparency in the reporting of stimulus design in the research on figurative language processing.

Severe Acute Respiratory Syndrome Coronavirus 2 Outbreak Related to a Nightclub, Germany, 2020.

We report an outbreak of coronavirus disease with 74 cases related to a nightclub in Germany in March 2020. Staff members were particularly affected (attack rate 56%) and likely caused sustained viral transmission after an event at the club. This outbreak illustrates the potential for superspreader events and corroborates current club closures.