Long-range seed dispersal enables almost stationary patterns in a model for dryland vegetation

Spatiotemporal patterns of vegetation are a ubiquitous feature of semi-arid ecosystems. On sloped terrain, vegetation patterns occur as stripes perpendicular to the contours. Field studies report contrasting long-term dynamics between different observation sites; some observe slow uphill migration of vegetation bands while some report stationary patterns. In this paper, we show that long-range seed dispersal provides a mechanism that enables the occurrence of both migrating and stationary patterns. We utilise a nonlocal PDE model in which seed dispersal is accounted for by a convolution term. The model represents vegetation patterns as periodic travelling waves and numerical continuation shows that both migrating and almost stationary patterns are stable if seed dispersal distances are sufficiently large. We use a perturbation theory approach to obtain analytical confirmation of the existence of almost stationary patterned solutions and provide a biological interpretation of the phenomenon

An integrodifference model for vegetation patterns in semi-arid environments with seasonality

Vegetation patterns are a characteristic feature of semi-deserts occurring on all continents except Antarctica. In some semi-arid regions, the climate is characterised by seasonality, which yields a synchronisation of seed dispersal with the dry season or the beginning of the wet season. We reformulate the Klausmeier model, a reaction-advection-diffusion system that describes the plant-water dynamics in semi-arid environments, as an integrodifference model to account for the temporal separation of plant growth processes during the wet season and seed dispersal processes during the dry season. The model further accounts for nonlocal processes involved in the dispersal of seeds. Our analysis focusses on the onset of spatial patterns. The Klausmeier partial differential equations (PDE) model is linked to the integrodifference model in an appropriate limit, which yields a control parameter for the temporal separation of seed dispersal events. We find that the conditions for pattern onset in the integrodifference model are equivalent to those for the continuous PDE model and hence independent of the time between seed dispersal events. We thus conclude that in the context of seed dispersal, a PDE model provides a sufficiently accurate description, even if the environment is seasonal. This emphasises the validity of results that have previously been obtained for the PDE model. Further, we numerically investigate the effects of changes to seed dispersal behaviour on the onset of patterns. We find that long-range seed dispersal inhibits the formation of spatial patterns and that the seed dispersal kernel's decay at infinity is a significant regulator of patterning

<i>Bacillus subtilis</i> extracellular protease production incurs a context-dependent cost

Rosazza T, Eigentler L, Earl C, Davidson FA, Stanley-Wall NR. Bacillus subtilis extracellular protease production incurs a context-dependent cost. Molecular Microbiology. 2023.Microbes encounter a wide range of polymeric nutrient sources in various environmental settings, which require processing to facilitate growth. Bacillus subtilis, a bacterium found in the rhizosphere and broader soil environment, is highly adaptable and resilient due to its ability to utilise diverse sources of carbon and nitrogen. Here, we explore the role of extracellular proteases in supporting growth and assess the cost associated with their production. We provide evidence of the essentiality of extracellular proteases when B. subtilis is provided with an abundant, but polymeric nutrient source and demonstrate the extracellular proteases as a shared public good that can operate over a distance. We show that B. subtilis is subjected to a public good dilemma, specifically in the context of growth sustained by the digestion of a polymeric food source. Furthermore, using mathematical simulations, we uncover that this selectively enforced dilemma is driven by the relative cost of producing the public good. Collectively, our findings reveal how bacteria can survive in environments that vary in terms of immediate nutrient accessibility and the consequent impact on the population composition. These findings enhance our fundamental understanding of how bacteria respond to diverse environments, which has importance to contexts ranging from survival in the soil to infection and pathogenesis scenarios

Founder cell configuration drives competitive outcome within colony biofilms

Bacteria can form dense communities called biofilms, where cells are embedded in a self-produced extracellular matrix. Exploiting competitive interactions between strains within the biofilm context can have potential applications in biological, medical, and industrial systems. By combining mathematical modelling with experimental assays, we reveal that spatial structure and competitive dynamics within biofilms are significantly affected by the location and density of the founder cells used to inoculate the biofilm. Using a species-independent theoretical framework describing colony biofilm formation, we show that the observed spatial structure and relative strain biomass in a mature biofilm comprising two isogenic strains can be mapped directly to the geographical distributions of founder cells. Moreover, we define a predictor of competitive outcome that accurately forecasts relative abundance of strains based solely on the founder cells’ potential for radial expansion. Consequently, we reveal that variability of competitive outcome in biofilms inoculated at low founder density is a natural consequence of the random positioning of founding cells in the inoculum. Extension of our study to non-isogenic strains that interact through local antagonisms, shows that even for strains with different competition strengths, a race for space remains the dominant mode of competition in low founder density biofilms. Our results, verified by experimental assays using Bacillus subtilis, highlight the importance of spatial dynamics on competitive interactions within biofilms and hence to related applications

Adjuvant low-dose interferon α2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis

Background: More than half of patients with melanoma that has spread to regional lymph nodes develop recurrent disease within the first 3 years after surgery. The aim of the study was to improve disease-free survival (DFS) and overall survival (OS) with interferon (IFN) α2a with or without dacarbazine (DTIC) compared with observation alone. Patients and methods: A total of 444 patients from 42 centers of the German Dermatologic Cooperative Oncology Group who had received a complete lymph node dissection for pathologically proven regional node involvement were randomized to receive either 3 MU s.c. of IFNα2a three times a week for 2 years (Arm A) or combined treatment with same doses of IFNα2a plus DTIC 850 mg/m2 every 4-8 weeks for 2 years (Arm B) or to observation alone (Arm C). Treatment was discontinued at first sign of relapse. Results: A total of 441 patients were eligible for intention-to-treat analysis. Kaplan-Meier 4-year OS rate of those who had received IFNα2a was 59%. For those with surgery alone, survival was 42% (A versus C, P = 0.0045). No improvement of survival was found for the combined treatment Arm B with 45% survival rate (B versus C, P = 0.76). Similarly, DFS rates showed significant benefit for Arm A, and not for Arm B. Multivariate Cox model confirmed that Arm A has an impact on OS (P = 0.005) but not Arm B (P = 0.34). Conclusions: 3 MU interferon α2a given s.c. three times a week for 2 years significantly improved OS and DFS in patients with melanoma that had spread to the regional lymph nodes. Interestingly, the addition of DTIC reversed the beneficial effect of adjuvant interferon α2a therap

Radiofrequency antenna concepts for human cardiac MR at 14.0 T

OBJECTIVE: To examine the feasibility of human cardiac MR (CMR) at 14.0 T using high-density radiofrequency (RF) dipole transceiver arrays in conjunction with static and dynamic parallel transmission (pTx). MATERIALS AND METHODS: RF arrays comprised of self-grounded bow-tie (SGBT) antennas, bow-tie (BT) antennas, or fractionated dipole (FD) antennas were used in this simulation study. Static and dynamic pTx were applied to enhance transmission field (B(1)(+)) uniformity and efficiency in the heart of the human voxel model. B(1)(+) distribution and maximum specific absorption rate averaged over 10 g tissue (SAR(10g)) were examined at 7.0 T and 14.0 T. RESULTS: At 14.0 T static pTx revealed a minimum B(1)(+)(ROI) efficiency of 0.91 μT/√kW (SGBT), 0.73 μT/√kW (BT), and 0.56 μT/√kW (FD) and maximum SAR(10g) of 4.24 W/kg, 1.45 W/kg, and 2.04 W/kg. Dynamic pTx with 8 kT points indicate a balance between B(1)(+)(ROI) homogeneity (coefficient of variation  1.11 µT/√kW) at 14.0 T with a maximum SAR(10g) < 5.25 W/kg. DISCUSSION: MRI of the human heart at 14.0 T is feasible from an electrodynamic and theoretical standpoint, provided that multi-channel high-density antennas are arranged accordingly. These findings provide a technical foundation for further explorations into CMR at 14.0 T

Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma

BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks). CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla)

PURPOSE: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla). METHODS: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs. RESULTS: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV. DISCUSSION: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care