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David Foster Wallace’s writing has come to be synonymous with post-postmodernism. Strategies that are often singled out in this respect include the return to epic forms of storytelling; a post-ironic attitude towards its subject matter; a concern with empathy and affective generosity; and an ambiguous but reinvigorated relationship of language to ‘reality’. In this essay I consider some of these in the context of visual art. The aim is less to map one onto another, detailing how much they have in common, than it is to tease out some of the differences between them so as to pinpoint Wallace’s position on post-postmodernism’s cognitive map across the disciplines.

Accurate quantification of the water balance, in particular evapotranspiration, is fundamental in managing water resources, especially in semi-arid areas. The objective of this study was to compare evaporation from endemic vegetation - Renosterveld - and a dryland wheat/fallow cropping system. The study was carried out in the mid-reaches of the Berg River catchment (South Africa), characterised by dryland salinity. Measurements of total evaporation from these 2 land uses were carried out with large aperture scintillometers during window periods from 2005 to 2007. Total evaporation was measured to be higher in Renosterveld than in wheat during the rainy winter season. In the dry summer season, total evaporation from Renosterveld was limited by soil water supply, and vegetation was under water stress. Spatial variability of total evaporation from both wheat/fallow land and Renosterveld was estimated using the Surface Energy Balance Algorithm for Land (SEBAL) model for 3 climatically different years. The scintillometer measurements were used to determine basal crop coefficients for long-term (20 years) simulations with the HYDRUS-1D model to assess temporal variability in total evaporation. Long-term simulations indicated that well-established, deep-rooted Renosterveld uses 39% more water than the shallowrooted wheat/fallow system. A change in land use from Renosterveld to dryland annual crops could therefore affect the soil water balance, cause shallow saline groundwater tables and degradation of soil and water resources. [ABSTRACT FROM AUTHOR]

Abstract: Background. Glutamine synthetase (GS) is ubiquitously expressed in the human and plays a major role for many metabolic pathways. However, little is known about its role during the fetal period. Methods. Cultured skin fibroblasts derived from an aborted fetus deficient in GS activity due to a R324C exchange as well as fetal and mature controls were used to determine the level of GS-expression, apoptosis, and proliferation in presence or absence of exogenous glutamine. Results. Glutamine synthetase can be found at early gestational stages. Loss of GS activity either inherited or induced through l-methionine sulfoximine leads to an upregulation of the GS protein but not of the GS mRNA and results in a significant drop in the proliferation rate but has no effect on apoptosis. Exogenous glutamine does not influence the rate of apoptosis but increases proliferation rates of the fetal but not the mature fibroblasts. Conclusion. GS can be found during early human fetal stages when it displays a significant effect on cell proliferation. [Copyright &y& Elsevier]

Investigates the effect of the phenylpyrrole fungicide fludioxonil on basal and induced expression of BcatrB in fungicide-sensitive and resistant strains of Botrytis cinerea. Accumulation of the fungicide in various isolates of the fungus; Effect of fludioxonil and some other fungicides on expression of ATP-binding cassette and major facilitator superfamily genes.

Twenty isolates of Phytophthora infestans from potato and twenty-two from tomato, collected in Uganda and Kenya in 1995, were compared for dilocus allozyme genotype, mitochondrial DNA (mtDNA) haplotype, mating type and restriction fragment length polymorphism (RFLP) fingerprint using probe RG57. Based on RFLP fingerprint and mtDNA haplotype, all isolates were classified in the US-1 clonal lineage. Nonetheless, isolates from potato differed from isolates from tomato in several characteristics. Isolates from potato had the 86/100 glucose-6-phosphate isomerase (Gpi) genotype, while those from tomato were 100/100, which represents a variant of US-1 that had been identified previously as US-1.7. Furthermore, while pure cultures of the pathogen were acquired from infected potato leaflets by first growing the isolates on potato tuber slices, this approach failed with infected tomato tissue because the isolates grew poorly on this medium. Tomato isolates were eventually purified using a selective medium. Six isolates from each host were compared for the diameter of lesions they produced on three tomato and three potato cultivars in one or two detached-leaf assays (four isolates from the first test were repeated in the second). On potato leaflets, isolates from potato caused larger lesions than isolates from tomato. On tomato leaflets, isolates from that host caused larger lesions than did isolates from potato, but the difference was significant in only one test. The interaction between source of inoculum (potato or tomato) and inoculated host (potato or tomato) was significant in both tests. Isolates from tomato were highly biotrophic on tomato leaflets, producing little or no necrosis during the seven days following infection, even though abundant sporulation could be seen. In contrast, isolates from potato sporulated less abundantly on tomato leaflets and produced darkly pigmented lesions that were most visible on the adaxial side of the leaflets. Nonetheless, all isolates infected and sporulated on both hosts, indicating that host adaptation is not determined by an ability to cause disease but rather by quantitative differences in pathogenic fitness. Assessment of Gpi banding patterns, mtDNA haplotype and RFLP fingerprint of 39 isolates from potato collected in Uganda and Kenya in 1997 indicated that the population had not changed on this host. The population of P. infestans from Kenya and Uganda provides an interesting model for the study of quantitative host adaptation. [ABSTRACT FROM AUTHOR]

An abstract of the article "Apoptosis versus active gene transcription in skeletal muscle of chronic heart failure patients. The effect of exercise training," by V. Conraads and colleagues is presented.

An abstract of the study "Apoptosis Versus Active Gene Transcription in the Skeletal Muscle of Patients With Mild to Moderate Chronic Heart Failure. Relationship With Exercise Capacity," by V. Conraads and colleagues is presented.

Background: Variants in cardiomyopathy genes have been identified in patients with cancer therapy-related cardiac dysfunction (CTRCD), suggesting a genetic predisposition for the development of CTRCD. The diagnostic yield of genetic testing in a CTRCD population compared to a cardiomyopathy patient cohort is not yet known and information on which genes should be assessed in this population is lacking., Methods: We retrospectively included 46 cancer patients with a history of anthracycline induced CTRCD (defined as a decrease in left ventricular ejection fraction (LVEF) to < 50% and a ≥ 10% reduction from baseline by echocardiography). Genetic testing was performed for 59 established cardiomyopathy genes. Only variants of uncertain significance and (likely) pathogenic variants were included. Diagnostic yield of genetic testing was compared with a matched cohort of patients with dilated cardiomyopathy (DCM, n = 46) and a matched cohort of patients without cardiac disease (n = 111)., Results: Average LVEF at time of CTRCD diagnosis was 30.1 ± 11.0%. Patients were 52.9 ± 14.6 years old at time of diagnosis and 30 (65.2%) were female. Most patients were treated for breast cancer or lymphoma, with a median doxorubicin equivalent dose of 300 mg/m 2 [112.5-540.0]. A genetic variant, either pathogenic, likely pathogenic or of uncertain significance, was identified in 29/46 (63.0%) of patients with CTRCD, which is similar to the DCM cohort (34/46, 73.9%, p = 0.262), but significantly higher than in the negative control cohort (47/111, 39.6%, p = 0.018). Variants in TTN were the most prevalent in the CTRCD cohort (43% of all variants). All (likely) pathogenic variants identified in the CTRCD cohort were truncating variants in TTN. There were no significant differences in severity of CTRCD and in recovery rate in variant-harbouring individuals versus non-variant harbouring individuals., Conclusions: In this case-control study, cancer patients with anthracycline-induced CTRCD have an increased burden of genetic variants in cardiomyopathy genes, similar to a DCM cohort. If validated in larger prospective studies, integration of genetic data in risk prediction models for CTRCD may guide cancer treatment. Moreover, genetic results have important clinical impact, both for the patient in the setting of precision medicine, as for the family members that will receive genetic counselling., (© 2024. The Author(s).)

Introduction: Narcolepsy type 1 (NT1) is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the orexin neuropeptides in the lateral hypothalamus. Genetic and environmental factors strongly suggest the involvement of the immune system in the loss of orexin neurons. The cerebrospinal fluid (CSF), secreted locally and surrounding the central nervous system (CNS), represents an accessible window into CNS pathological processes., Methods: To gain insight into the biological and molecular changes in NT1 patients, we performed a comparative proteomics analysis of the CSF from 21 recent-onset NT1 patients and from two control groups: group 1 with somatoform disorders, and group 2 patients with hypersomnia other than NT1, to control for any potential effect of sleep disturbances on CSF composition. To achieve an optimal proteomic coverage analysis, the twelve most abundant CSF proteins were depleted, and samples were analyzed by nano-flow liquid chromatography tandem mass spectrometry (nano-LC-MS/MS) using the latest generation of hybrid Orbitrap mass spectrometer., Results and Discussion: Our study allowed the identification and quantification of up to 1943 proteins, providing a remarkably deep analysis of the CSF proteome. Interestingly, gene set enrichment analysis indicated that the complement and coagulation systems were enriched and significantly activated in NT1 patients in both cohorts analyzed. Notably, the lectin and alternative complement pathway as well as the downstream lytic membrane attack complex were congruently increased in NT1. Our data suggest that the complement dysregulation in NT1 patients can contribute to immunopathology either by directly promoting tissue damage or as part of local inflammatory responses. We therefore reveal an altered composition of the CSF proteome in NT1 patients, which points to an ongoing inflammatory process contributed, at least in part, by the complement system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ayoub, Dauvilliers, Barateau, Vermeulen, Mouton-Barbosa, Marcellin, Gonzalez-de-Peredo, Gross, Saoudi and Liblau.)

High-altitude (HA) hypoxia may alter the structural-functional integrity of the neurovascular unit (NVU). Herein, we compared male lowlanders (n = 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex-, age- and body mass index-matched healthy highlanders (n = 9) native to CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, in addition to free radicals and nitric oxide (NO). Regional cerebral blood flow (CBF) was examined in conjunction with cerebral substrate delivery, dynamic cerebral autoregulation (dCA), cerebrovascular reactivity to carbon dioxide (CVR CO2 ) and neurovascular coupling (NVC). Psychomotor tests were employed to examine cognitive function. Compared to lowlanders at SL, highlanders exhibited elevated basal plasma and red blood cell NO bioavailability, improved anterior and posterior dCA, elevated anterior CVR CO2 and preserved cerebral substrate delivery, NVC and cognition. In highlanders, S100B, neurofilament light-chain (NF-L) and T-tau were consistently lower and cognition comparable to lowlanders following chronic-HA. These findings highlight novel integrated adaptations towards regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia. KEY POINTS: High-altitude (HA) hypoxia has the potential to alter the structural-functional integrity of the neurovascular unit (NVU) in humans. For the first time, we examined to what extent chronic and lifelong hypoxia impacts multimodal biomarkers reflecting NVU structure and function in lowlanders and native Andean highlanders. Despite lowlanders presenting with a reduction in systemic oxidative-nitrosative stress and maintained cerebral bioenergetics and cerebrovascular function during chronic hypoxia, there was evidence for increased axonal injury and cognitive impairment. Compared to lowlanders at sea level, highlanders exhibited elevated vascular NO bioavailability, improved dynamic regulatory capacity and cerebrovascular reactivity, comparable cerebral substrate delivery and neurovascular coupling, and maintained cognition. Unlike lowlanders following chronic HA, highlanders presented with lower concentrations of S100B, neurofilament light chain and total tau. These findings highlight novel integrated adaptations towards the regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

It remains unclear whether psychotic depression (PD) compared to non-psychotic depression (non-PD) among older adults is associated with poorer cognitive performance. For inpatients (60+) with a major depressive episode, cognitive performance in PD and non-PD (categorical) were compared as well as the relationship between symptom severity for depression and psychosis (dimensional) and cognition. Of 90 participants (on average 72.7 years old; range 60-92), 64% were female. The severity of depressive- and psychotic symptoms are both negatively associated with cognitive functioning among older adults with depression. This is of relevance for the treatment of this vulnerable group of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide (WHO), with almost 60000 deaths annually. Pregnancy is a prothrombotic state with increased levels of several coagulation factors to protect the parturient from bleeding problems during delivery. Fibrinogen has a significant role in coagulation and bleeding. Studies have pointed out that lower fibrinogen levels before delivery, but also at the initiation of PPH, are predictive of major hemorrhage. Early, the goal-directed fibrinogen concentrate therapy might be very useful in a subgroup of patients with serious PPH. This review aims to summarize the current literature on fibrinogen during PPH., Competing Interests: Declaration of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The importance of genetic testing for cardiomyopathies has increased in the last decade. However, in heart transplant patients with former cardiomyopathy, genetic testing in retrospect is not routinely performed. We hypothesize that the yield of genetic testing in this population is considerable, and will have a major impact for both patients and relatives., Methods: Patients that underwent heart transplantation (HTx) between 1995 and 2020 and were still in follow-up, were offered genetic testing if the primary etiology was non-ischemic cardiomyopathy. Next generation sequencing (NGS) of known cardiomyopathy genes was performed and variants were classified as variant of unknown significance (class 3), likely pathogenic (class 4) or pathogenic (class 5) variant., Results: Of the 99 HTx patients in active follow-up, only 6 patients had a genetic diagnosis at the time of HTx. In this study, 31 selected patients with prior non-ischemic cardiomyopathy underwent genetic testing post HTx. 23/31 patients (74.2%) carried a variant that was classified as class 3 or higher. In 12/31 patients a class 4/5 variant (38.7%) was identified, and in 11/31 patients (35.5%) a class 3 variant. Class 5 Variants in TTN were the most prevalent (7/31), followed by class 5 variants in MYBPC3 (2/31). A positive family history was present in 21/31 (67.7%) and a second precipitating factor (e.g., alcohol abuse, pregnancy) was present in 17/31 patients (54.8%). Diagnostic yield of genetic testing was similar between patients with or without familial history and/or second hit. Through cascade screening 48 family members were screened for presence of a class 4/5 variant, of whom 19 (39.6%) were genotype positive, of whom 10 (52.6%) showed a cardiac phenotype. Appropriate follow-up was offered., Conclusions: Genetic testing for cardiomyopathy genes established a molecular diagnosis in 38.7% of patients post HTx. These results highlight the importance of genetic testing in this population as it is still often overlooked in patients that already underwent HTx in the past. Genetic testing is highly recommended, independent of family history or second precipitating factors, as it might identify relatives at risk., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. (2) Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free ( p = 0.040) and overall ( p = 0.022) survival. (4) Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.

Aims: Smoking is linked to disease and survival in the general and transplant population. We studied the smoking history, disease and survival of patients after heart transplantation., Methods: A total of 130 patients who underwent heart transplantation between 1995 and 2019 received a questionnaire to document their smoking history. We assessed patient characteristics, comorbidities and survival., Results: Sixty-five per cent of patients were active or former smokers prior to heart transplantation. All patients stopped smoking; 26% of the former smokers resumed smoking after transplantation. Patients who resumed smoking were younger at the time of transplantation, used fewer statins and were more likely to be treated with azathioprine after transplantation. The mean follow-up for all patients was 11 ± 5.5 years. Patients who resumed smoking were more likely to develop solid organ cancers (45%) compared to those who remained abstinent (23%) and those who never smoked (13%) ( p 0.014). A Cox proportional hazards regression analysis identified smoking resumption, with a RR of 2.31 (1.14-4.68, p 0.02), and age at transplantation, with a RR of 1.03 (1-1.06, p 0.034), as significant for survival. Patients resuming smoking after transplantation had a significantly higher risk of dying from solid organ cancer, with a RR of 2.54 (1.03, 6.28; p 0.04) with a short median survival time (25th-75th percentile) of (1 (0-5) months, p 0.007)., Conclusion: Patients who resume smoking after heart transplantation have worse survival and are at higher risk of dying from solid organ cancer. Implementing a smoking cessation plan throughout the post-transplant period is important.

When acute stroke care is organised using a "drip-and-ship" model, patients receive immediate treatment at the nearest primary stroke centre followed by transfer to a comprehensive stroke centre (CSC). When stroke care is further centralised into the "direct-to-mothership" model, patients with stroke symptoms are immediately brought to a CSC to further reduce treatment times and enhance stroke outcomes. We investigated the effects of the ongoing centralization in a Dutch urban setting on treatment times of patients with confirmed ischemic stroke in a 4-year period. Next, in a non-randomized controlled trial, we assessed treatment times of patients with suspected ischemic stroke, and treatment times of patients with neurologic disorders other than suspected ischemic stroke, before and after the intervention in the CSC and the decentralized hospitals, the intervention being the change from "drip and ship" into "direct-to-mothership". Our findings provide support for the ongoing centralization of acute stroke care in urban areas. Treatment times for patients with ischemic stroke decreased significantly, potentially improving functional outcomes. Improvements in treatment times for patients with suspected ischemic stroke were achieved without negative side effects for self-referrals with stroke symptoms and patients with other neurological disorders., Competing Interests: Declaration of Competing Interest All authors work in the study setting, except for Naomi van der Linden, who currently works at the University of Twente but was employed by AstraZeneca Netherlands, a pharmaceutical company, during this study. Crispijn van den Brand worked in the study setting and is currently employed by the Dutch Institute for Clinical Auditing.The authors declare that they have no competing interests, (Copyright © 2021. Published by Elsevier B.V.)