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We present an analysis of a three-layered structure used for both launching and detecting picosecond acoustic waves. To enhance the optical sensitivity to the acoustic disturbances, a cavity is designed, which acts as a Fabry–Perot interferometer. We use analytic modeling based on dual optical and acoustic transfer matrix formalism to analyze the coupled optical and acoustic wave propagation. Assuming a three-layer transducer made of an optical cavity sandwiched between two thin metallic layers, the model allows for mastering of the coupled optical and acoustic responses, which leads to an optimum design of the structure, and it highlights the various acoustic contributions to the reflectivity changes. The sensitivity of this three-layered structure to acoustic disturbances is compared to the numerical predictions we performed for the standard opto-acoustic transducer made of a single metallic layer.

Abstract A second autologous stem‐cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti‐CD38 and immunotherapy, its role remains debated. We conducted a real‐life study in 10 French centers (1996–2017) involving 267 RMM patients receiving ASCT2. The median age was 61 years, with 49% females. Most patients received melphalan 200 mg/m² before ASCT2, with low early mortality (1%). Very good partial response or better (VGPR+) rate post ASCT2 was 78%. Post ASCT2, 48% received consolidation therapy and 40% maintenance therapy. Median event‐free survival (EFS) after ASCT2 was 2.6 years (95% confidence interval [CI]: 2.3–2.8), and 2‐year EFS estimate was 63% (95% CI: 57–70). Median overall survival (OS) was 8.1 years (95% CI: 5.9–NA), and 2‐year OS estimate was 92% (95% CI: 88–95). Multivariate analysis revealed that VGPR+ status and maintenance therapy post ASCT2 were associated with better EFS (hazard ratio [HR]: 0.6; 95% CI: 0.3–0.9, p = 0.012 and HR: 0.4; 95% CI: 0.3–0.6, p

ObjectiveProviding the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM.MethodsAn integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04).ResultsThe primary endpoint was met, with VRD demonstrating a noninferior rate of at least very good partial response (≥ VGPR) after induction vs VTD. GEM comparison demonstrated improvement in the ≥ VGPR rate after induction for VRD vs VTD (66.3% vs 51.2%; P = .00281) that increased after transplant (74.4% vs 53.5%). Undetectable minimal residual disease rates post induction (46.7% vs 34.9%) and post transplant (62.4% vs 47.3%) support the benefit of VRD vs VTD. Treatment-emergent adverse events leading to study and/or treatment discontinuation were less frequent with VRD (3%, GEM2012; 6%, IFM 2009) vs VTD (11%, IFM 2013-04).ConclusionThese results supported the benefit of VRD over VTD for induction in transplant-eligible patients with NDMM. The trials included are registered with ClinicalTrials.gov (NCT01916252, NCT01191060, NCT00461747, and NCT01971658).

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood–brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

BackgroundBoth light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis are types of cardiac amyloidosis (CA) that require accurate prognostic stratification to plan therapeutic strategies and follow-ups. Cardiac biomarkers, e.g., N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (Hs-cTnT), remain the cornerstone of the prognostic assessment. An increased level of soluble suppression of tumorigenesis-2 (sST2) is predictive of adverse events [all-cause death and heart failure (HF) hospitalizations] in patients with HF. This study aimed to evaluate the prognostic value of circulating sST2 levels in AL-CA and ATTR-CA.MethodsWe carried out a multicenter study including 133 patients with AL-CA and 152 patients with ATTR-CA. During an elective outpatient visit for the diagnosis of CA, Mayo Clinic staging [NT-proBNP, Hs-cTnT, differential of free light chains (DFLCs)] and sST2 were assessed for all AL patients. Gillmore staging [including estimated glomerular filtration rate (eGFR), NT-proBNP] and Grogan staging (including NT-proBNP and Hs-cTnT) were assessed for TTR-CA patients.ResultsThe median age was 73 years [interquartile range (IQR) 61–81], and 53% were men. The endpoint was the composite of all-cause death or first HF-related hospitalization. The median follow-up was 20 months (IQR 3–34) in AL amyloidosis and 33 months (6–45) in TTR amyloidosis. The primary outcome occurred in 70 (53%) and 99 (65%) of AL and TTR patients, respectively. sST2 levels were higher in patients with AL-CA than in patients with ATTR-CA: 39 ng/L (26–80) vs. 32 ng/L (21–46), p

Abstract Chimeric antigen receptor T cells (CAR‐T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigated their phenotype and capacity to generate functional CAR‐T directed against CS1 or B Cell Maturation antigen. We found a decrease in naive T cells and elevated frequencies of exhaustion markers in T cells from treated MM patients. Interestingly, individuals treated with daratumumab display elevated ratios of central memory T cells. CAR‐T derived from patients at relapse show reduced in vitro expansion and cytotoxic capacities in response to MM cells compared to those produced at diagnosis. Of note, CAR‐T from daratumumab treated patients display intermediate defects. Reduced anti‐myeloma activity of CAR T cells from treated patients was also observed in a mouse model. Our findings suggest that T cell defects in MM patients, specifically during relapse, have a major impact on their capacity to generate efficient therapeutic CAR‐T. Selecting naive or central memory T cell subsets to generate therapeutic T cells could improve the CAR‐T therapy for MM.

Abstract Background CAR-T cell (chimeric antigen receptor T) therapy has emerged as an effective treatment of refractory hematological malignancies. Intensive care management is intrinsic to CAR-T cell therapy. We aim to describe and to assess outcomes in critically ill CAR-T cell recipients. Study design and methods Hospital-wide retrospective study. Consecutive CAR-T cell recipients requiring ICU admission from July 2017 and December 2020 were included. Results 71 patients (median age 60 years [37–68]) were admitted to the ICU 6 days [4–7] after CAR-T cell infusion. Underlying malignancies included diffuse large B cell lymphoma (n = 53, 75%), acute lymphoblastic leukemia (17 patients, 24%) and multiple myeloma (n = 1, 1.45%). Performance status (PS) was 1 [1–2]. Shock was the main reason for ICU admission (n = 40, 48%). Isolated cytokine release syndrome (CRS) was the most common complication (n = 33, 46%), while 21 patients (30%) had microbiologically documented bacterial infection (chiefly catheter-related infection). Immune effector cell-associated neurotoxicity syndrome was reported in 26 (37%) patients. At ICU admission, vasopressors were required in 18 patients (25%) and invasive mechanical ventilation in two. Overall, 49 (69%) and 40 patients (56%) received tocilizumab or steroids, respectively. Determinant of mortality were the reason for ICU admission (disease progression vs. sepsis or CRS (HR 4.02 [95%CI 1.10–14.65]), Performance status (HR 1.97/point [95%CI 1.14–3.41]) and SOFA score (HR 1.16/point [95%CI 1.01–1.33]). Conclusions Meaningful survival could be achieved in up to half the CAR-T cell recipients. The severity of organ dysfunction is a major determinant of death, especially in patients with altered performance status or disease progression.

Background The aim of this study was to assess the risk factors for atrophic progression of patients with papilloedema secondary to intracranial hypertension, using optical coherence tomography parameters.Methods A retrospective study was conducted at Marseille University Hospitals’ Ophthalmology departments between December 2015 and December 2021. All patients with papilloedema resulting from elevated intracranial hypertension at the initial presentation were included. Ophthalmological evaluations included analysing retinal nerve fibre layer (RNFL), ganglion cell layer (GCL) and total peripapillary retinal thickness (RT).Results The study included 222 eyes from 113 patients. The main aetiologies of intracranial hypertension were idiopathic intracranial hypertension (49/113), intracranial tumours (33/113) and cerebral venous thrombosis (15/113). The initial RNFL and RT showed significant correlations with optic atrophy. The mean RNFL was 199.63 µm in the ‘no atrophy’ group and 365.28 µm in the ‘atrophy’ group (p

CD73 is an ectonucleotidase overexpressed on tumor cells that suppresses anti-tumor immunity. Accordingly, several CD73 inhibitors are currently being evaluated in the clinic, including in large randomized clinical trials. Yet, the tumor cell-intrinsic impact of CD73 remain largely uncharacterized. Using metabolomics, we discovered that CD73 significantly enhances tumor cell mitochondrial respiration and aspartate biosynthesis. Importantly, rescuing aspartate biosynthesis was sufficient to restore proliferation of CD73-deficient tumors in immune deficient mice. Seahorse analysis of a large panel of mouse and human tumor cells demonstrated that CD73 enhanced oxidative phosphorylation (OXPHOS) and glycolytic reserve. Targeting CD73 decreased tumor cell metabolic fitness, increased genomic instability and suppressed poly ADP ribose polymerase (PARP) activity. Our study thus uncovered an important immune-independent function for CD73 in promoting tumor cell metabolism, and provides the rationale for previously unforeseen combination therapies incorporating CD73 inhibition.

In this article we first present the foundations of ultrafast photoacoustics, a technique where the acoustic wavelength in play can be considerably shorter than the optical wavelength. The physics primarily involved in the conversion of short light pulses into high frequency sound is described. The mechanical disturbances following the relaxation of hot electrons in metals and other processes leading to the breaking of the mechanical balance are presented, and the generation of bulk shear-waves, of surface and interface waves and of guided waves is discussed. Then, efforts to overcome the limitations imposed by optical diffraction are described. Next, the principles behind the detection of the so generated coherent acoustic phonons with short light pulses are introduced for both opaque and transparent materials. The striking instrumental advances, in the detection of acoustic displacements, ultrafast acquisition, frequency and space resolution are discussed. Then secondly, we introduce picosecond opto-acoustics as a remote and label-free novel modality with an excellent capacity for quantitative evaluation and imaging of the cell’s mechanical properties, currently with micron in-plane and sub-optical in depth resolution. We present the methods for time domain Brillouin spectroscopy in cells and for cell ultrasonography. The current applications of this unconventional means of addressing biological questions are presented. This microscopy of the nanoscale intra-cell mechanics, based on the optical monitoring of coherent phonons, is currently emerging as a breakthrough method offering new insights into the supra-molecular structural changes that accompany cell response to a myriad of biological events.

The ubiquitous nature of emotional intelligence, as a central theme in every aspect of our lives—be it at work, school, or home—coupled with the growing prevalence of digital interactions, makes it fundamental to develop our understanding of emotional intelligence in a digital world. However, the digital world represents more than just a contextual factor to consider, as interactions in digital environments require digital competence. The objective of this paper is to conceptualize “digital emotional intelligence” as the integration of both emotional intelligence and digital competence. The model we propose posits that trait emotional intelligence predicts attitudes toward digital competence, while digital ability emotional intelligence is predicted by digital competence skills and digital competence knowledge. Using a self-reported questionnaire on 503 respondents, a structural equation model highlights a positive relationship between trait emotional intelligence and attitudes toward digital competence.

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37–82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3–12). The median number of BM cycles administered was three (range, 1–22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population.

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy. Methods We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as “good” if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome. Results We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was “good” in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response. Conclusions We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids.

Background The scarcity of blood donors has always been a major concern for blood banks globally. Lack of eligibility by potential blood donors to donate blood called blood donor deferral is associated with the unsustainable and inadequate amount of blood collected by blood banks worldwide. However, there is limited information on blood donor deferral rates and causes reported from the Limbe Regional Hospital blood bank. This study was aimed at determining the blood donor deferral rate and associated causes at Limbe Regional hospital's blood bank center. Methods A hospital-based cross-sectional study was carried out that lasted from January 2021 to July 2021 at Limbe Regional Hospital's blood bank. Blood donors’ data were collected using structured questionnaires, and donors were screened following the National Policy for blood donor selection criteria in Cameroon. Data were entered into Excel version 2013 and transferred to SPSS version 20 for analysis. The level of significance alpha of 5% at a 95% confidence interval was considered. Results The blood donor deferral rate was 13.6% and no association was observed between type of donor and donor acceptance status as well as between type of donor and deferral status (P value>0.05). Hepatitis B surface antigen positive (66.7%), hypertension (22.2%), and diabetic (11.1%) were the causes of permanent deferrals whereas low haemoglobin concentration (71.4%), low weight (14.3%) and donation interval less than the specified periods (14.3%) were the causes of temporal deferrals. Conclusion The blood donor deferral rate is high at the Limbe Regional hospital blood bank and donor deferral is not dependent on the type of donor also donor type does not influence the deferral status. HBsAg positive was the leading cause of permanent deferrals and low haemoglobin concentration was the leading cause of temporal deferrals. Communities should be educated on the criteria for blood donor selection.

Abstract Objective As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta‐analysis compares the efficacy of first‐line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used. Methods Studies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first‐line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first‐line immunosuppression had to be available, calculable, or provided by the authors. Results We gathered data from 919 NMO patients (232 RTX‐, 294 MMF‐, and 393 AZA‐treated patients). The risk of first relapse after first‐line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA. Interpretation The findings suggest that RTX is more efficient than MMF as a first‐line therapy. Even if the results of our meta‐analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX.

Abstract The assessment of both thromboembolic and haemorrhagic risks and their management in systemic amyloidosis have been poorly emphasized so far. This narrative review summarizes main evidence from literature with clinical perspective. The rate of thromboembolic events is as high as 5–10% amyloidosis patients, at least in patients with cardiac involvement, with deleterious impact on prognosis. The most known pro‐thrombotic factors are heart failure, atrial fibrillation, and atrial myopathy. Atrial fibrillation could occur in 20% to 75% of systemic amyloidosis patients. Cardiac thrombi are frequently observed in patients, particularly in immunoglobulin light chains (AL) amyloidosis, up to 30%, and it is advised to look for them systematically before cardioversion. In AL amyloidosis, nephrotic syndrome and the use of immunomodulatory drugs also favour thrombosis. On the other hand, the bleeding risk increases because of frequent amyloid digestive involvement as well as factor X deficiency, renal failure, and increased risk of dysautonomia‐related fall.

Abstract Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to

In January 1980, during exceptional cyclonic rainfall, an atypical landslide, called déboulé, rapidly generated the permanent 700 m-long gully of the Ravine de l’Eglise on an inhabited plateau in Reunion Island (Indian Ocean). Retrieving the initial conditions that led to this historical process is both challenging and necessary for understanding the mechanism of gully incision and providing pointers for improving risk mitigation in relation to this phenomenon. In this study, we reconstruct the pre- and post-failure topographies using SFM (structure from motion) applied on archive aerial photographs. Based on the comparison of these digital elevation models, we estimate the volume of material eroded to be ca. 0.63 Mm3. Groundwater level increase, part of the triggering mechanism, is hindcast in the catchment of the gully using a lumped hydrological model. This model shows that in only a fortnight the groundwater level probably rose by 36 m, which could have caused a progressive increase in pore pressure and triggered formation of the gully by retrogressive landslides. We test this hypothesis by considering the pre-failure topography and the hindcast groundwater level in a deterministic model based on limit equilibrium equations to explore ground stability. The evolution of ground stability with a rise in the water table shows that the gully may have extended in a headward direction by retrogressive landslides. This is the first quantitative reconstruction of an exceptional historical event affecting the territory of Reunion Island. The methods used to investigate the Ravine de L’Eglise incision thus offer new complementary insights and challenges for understanding the mechanism and the temporality of gully formation.

This paper explores the question of how predictive uncertainty methods perform in practice in Natural Language Processing, specifically multi-class and multi-label text classification. We conduct benchmarking experiments with 1-D convolutional neural networks and pre-trained transformers on six real-world text classification datasets in which we empirically investigate why popular scalable uncertainty estimation strategies (Monte-Carlo Dropout, Deep Ensemble) and notable extensions (Heteroscedastic, Concrete Dropout) underestimate uncertainty. We motivate that uncertainty estimation benefits from combining posterior approximation procedures, linking it to recent research on how ensembles and variational Bayesian methods navigate the loss landscape. We find that our proposed method combination of Deep Ensemble with Concrete Dropout, by analysis of in- domain calibration, cross-domain classification, and novel class robustness, demonstrates superior performance, even at a smaller ensemble size. Our results corroborate the importance of fine-tuning dropout rate to the text classification task at hand, which individually and as an ensemble impacts model robustness. We observe in ablation that pre-trained transformers severely underperform in novelty detection, limiting the applicability of transfer learning when distribution shift from novel classes can be expected.

Genetic engineering of the type I polyketide synthases (PKSs) to produce desirable analogous remains largely inefficient. Here, the authors leverage multiple approaches to delete seven internal modules from the stambomycin PKS and generate 37-membered mini-stambomycin macrolactones.

Habitat loss and fragmentation are of concern to conservation biologists worldwide. However, not all organisms are affected equally by these processes; thus, it is important to study the effects of living in fragmented habitats on species that differ in lifestyle and habitat requirements. In this study, we examined the dispersal and connectivity patterns of rodents, one endemic (Eliurus myoxinus) and one invasive (Rattus rattus), in two landscapes containing forest fragments and adjacent continuous forest patches in northwestern Madagascar. We generated genetic (RADseq) data for 66 E. myoxinus and 81 R. rattus individuals to evaluate differences in genetic diversity as well as inbreeding and connectivity in two landscapes. We found higher levels of inbreeding and lower levels of genetic diversity in E. myoxinus compared with R. rattus. We observed related dyads both within and between habitat patches and positive spatial autocorrelation at lower distance classes for both species, with a stronger pattern of spatial autocorrelation in R. rattus. Across each site, we identified contrasting migration rates for each species, but these did not correspond to habitat–matrix dichotomies. The relatively low genetic diversity in the endemic E. myoxinus suggests ecological constraints that require further investigation.

Hyperviscosity syndrome (HVS) is a rare complication of newly diagnosed multiple myeloma (NDMM) related to high tumour burden. Studies about the prognosis of HVS in modern-era therapy for NDMM are missing. We investigated a retrospective cohort study of NDMM with HVS between 2011-2021. Thirty-nine NDMM patients with HVS were included. HVS presentation was heterogeneous, with asymptomatic, mild, and neurological forms in 23%, 59%, and 18% of cases, respectively. No thrombosis or major bleeding was observed. Therapeutic plasma exchanges were used in 92% of patients, which were effective and well tolerated. No rebound effect was observed. All patients except one had at least one CRAB criterion. Most of the patients received bortezomib and high-dose steroids (95%) associated with an immunomodulatory drug (43%) or alkylating agents (42%). HVS in NDMM patients had dismal overall survival matched to multiple myeloma patient controls (without HVS) in our center (median: 3.6 vs. 7.7 years, p=0.01), as confirmed by multivariate analysis. Early deaths (in the first two months) occurred in 21% of older patients (>65 years). HVS in NDMM patients is a rare but life-threatening complication associated with high lethality in older patients and be a potential dismal prognosis factor in the modern treatment era.

African literature has suffered a great deal of scathing criticism, especially from western critics and scholars, who believe that Black African writers and critics have repeatedly focused on trite themes and subject matters of colonial/postcolonial nature at the expense of the global environmental crises. This paper then, which is partly a response to this criticism, focuses on two novels, namely, Azasu’s The Slave Raiders (2004) and Gyasi’s Homegoing (2016), texts that yield themselves to postcolonial ecocritical reflections. Situated in the postcolonial ecocritical theory and using content analysis, the paper reveals that colonization and slavery, as the two texts show, have left some incontestable damage to the natural landscape of colonized Gold Coast, now Ghana. The wilderness has disappeared and the specimens of animal species are trafficked leading to some considerable damage to the ecosystems. However, these ecological hazards are subordinated in postcolonial thematic issues such as resistance to slavery, trauma, memory, and healing. The paper contributes to scholarship on the emerging discipline of postcolonial ecocriticism in the African context.

Abstract Background To evaluate the cost-effectiveness of six diagnostic strategies involving magnetic resonance imaging (MRI) targeted biopsy for diagnosing prostate cancer in initial and repeat biopsy settings from the Singapore healthcare system perspective. Methods A combined decision tree and Markov model was developed. The starting model population was men with mean age of 65 years referred for a first prostate biopsy due to clinical suspicion of prostate cancer. The six diagnostic strategies were selected for their relevance to local clinical practice. They comprised MRI targeted biopsy following a positive pre-biopsy multiparametric MRI (mpMRI) [Prostate Imaging – Reporting and Data System (PI-RADS) score ≥ 3], systematic biopsy, or saturation biopsy employed in different testing combinations and sequences. Deterministic base case analyses with sensitivity analyses were performed using costs from the healthcare system perspective and quality-adjusted life years (QALY) gained as the outcome measure to yield incremental cost-effectiveness ratios (ICERs). Results Deterministic base case analyses showed that Strategy 1 (MRI targeted biopsy alone), Strategy 2 (MRI targeted biopsy ➔ systematic biopsy), and Strategy 4 (MRI targeted biopsy ➔ systematic biopsy ➔ saturation biopsy) were cost-effective options at a willingness-to-pay (WTP) threshold of US$20,000, with ICERs ranging from US$18,975 to US$19,458. Strategies involving MRI targeted biopsy in the repeat biopsy setting were dominated. Sensitivity analyses found the ICERs were affected mostly by changes to the annual discounting rate and prevalence of prostate cancer in men referred for first biopsy, ranging between US$15,755 to US$23,022. Probabilistic sensitivity analyses confirmed Strategy 1 to be the least costly, and Strategies 2 and 4 being the preferred strategies when WTP thresholds were US$20,000 and US$30,000, respectively. Limitations and conclusions This study found MRI targeted biopsy to be cost-effective in diagnosing prostate cancer in the biopsy-naïve setting in Singapore.

Streptomyces bacteria have a linear chromosome, with core genes located in the central region and gene clusters for specialized metabolite biosynthesis found in the ‘arms’. Here, Lioy et al. show that such chromosome structure correlates with genetic compartmentalization, and the onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture.