Bad Practice in Erosion Management: The Southern Sicily Case Study

This case study from Sicily illustrates a common sequence of events where one unwise action was countered with another, which in turn created additional problems. The situation arose through strong political interference and ignorance (or lack of concern) regarding the environmental impacts of human interventions on the shoreline and by the public perception that government has a duty to protect private property. The poor design and location of ports and harbours produced infilling problems and huge updrift accretion with concomitant downdrift erosion. The human-induced coastal retreat was counteracted by the progressive emplacement of breakwaters creating a “domino” effect. On many occasions these were constructed to protect unplanned and illegal (in the sense that they do not conform to planning regulations) beachfront summer houses. Without the presence of these structures, there would have been no need for publicly funded intervention. Furthermore, only a narrow coastal belt close to the shoreline is used by bathers on the wide beaches formed updrift of ports and harbours and in the lee of breakwaters, most of the accreted beach being unused or partially occupied by tourist developments. Thus beach users and municipalities acquired some benefits from beach accretion at specific sites, the opposite being true in eroding areas

Dutch home-based pre-reading intervention with children at familial risk of dyslexia

Children (5 and 6 years old, n = 30) at familial risk of dyslexia received a home-based intervention that focused on phoneme awareness and letter knowledge in the year prior to formal reading instruction. The children were compared to a no-training at-risk control group (n = 27), which was selected a year earlier. After training, we found a small effect on a composite score of phoneme awareness (d = 0.29) and a large effect on receptive letter knowledge (d = 0.88). In first grade, however, this did not result in beneficial effects for the experimental group in word reading and spelling. Results are compared to three former intervention studies in The Netherlands and comparable studies from Denmark and Australia

Biodiversity modelling in practice - predicting bird and woody plant species richness on farmlands

In light of decreasing species richness on farmland and an increasing awareness of biodiversity issues among customers and food companies, concepts and models to evaluate and enhance farmland biodiversity are greatly needed. It is important that the models are easy to apply as they have to be utilized by practitioners such as farmers and their consultants. In this study, simple but valid predictors were identified to rapidly assess the species richness of birds and woody plants in hedgerows, an important farmland landscape element. Hedgerows were sampled in seven agricultural landscapes throughout Germany. By means of automatic model selection procedures, linear regression models were estimated to predict bird and woody plant species richness. Cross validation procedures were carried out in order to visualize model selection uncertainty and estimate the prediction error. Due to a rather high prediction error, the model for plants can only be recommended for use when field work is not feasible. The model for birds, however, explained 70.8% of the variance in species numbers. It may help farmers, food companies and nature conservation agencies to rapidly evaluate bird species richness in hedgerows on farmland and to identify potentials and appropriate measures for enhancing it

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes

BACKGROUND: Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours. METHODS: Tumour samples from an olaparib maintenance monotherapy trial (Study 19, D0810C00019; NCT00753545) were analysed. Analyses included classification of mutations in genes involved in homologous recombination repair (HRR), BRCA1 promoter methylation status, measurement of BRCA1 protein and Myriad HRD score. RESULTS: Patients with BRCAm tumours gained most benefit from olaparib; a similar treatment benefit was also observed in 21/95 patients whose tumours were BRCAwt but had loss-of-function HRR mutations compared to patients with no detectable HRR mutations (58/95). A higher median Myriad MyChoice® HRD score was observed in BRCAm and BRCAwt tumours with BRCA1 methylation. Patients without BRCAm tumours derived benefit from olaparib treatment vs placebo although to a lesser extent than BRCAm patients.CONCLUSIONS: Ovarian cancer patients with tumours harbouring loss-of-function mutations in HRR genes other than BRCA1/2 may constitute a small, molecularly identifiable and clinically relevant population who derive treatment benefit from olaparib similar to patients with BRCAm

“Microbiota, symbiosis and individuality summer school” meeting report

How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on “Microbiota, symbiosis and individuality: conceptual and philosophical issues” (July 2019), which was supported by a European Research Council starting grant project “Immunity, DEvelopment, and the Microbiota” (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota and highlights the value of incorporating into meetings experts from other disciplines, such as philosophy and history of science

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

Coherence and recurrency: maintenance, control and integration in working memory

Working memory (WM), including a ‘central executive’, is used to guide behavior by internal goals or intentions. We suggest that WM is best described as a set of three interdependent functions which are implemented in the prefrontal cortex (PFC). These functions are maintenance, control of attention and integration. A model for the maintenance function is presented, and we will argue that this model can be extended to incorporate the other functions as well. Maintenance is the capacity to briefly maintain information in the absence of corresponding input, and even in the face of distracting information. We will argue that maintenance is based on recurrent loops between PFC and posterior parts of the brain, and probably within PFC as well. In these loops information can be held temporarily in an active form. We show that a model based on these structural ideas is capable of maintaining a limited number of neural patterns. Not the size, but the coherence of patterns (i.e., a chunking principle based on synchronous firing of interconnected cell assemblies) determines the maintenance capacity. A mechanism that optimizes coherent pattern segregation, also poses a limit to the number of assemblies (about four) that can concurrently reverberate. Top-down attentional control (in perception, action and memory retrieval) can be modelled by the modulation and re-entry of top-down information to posterior parts of the brain. Hierarchically organized modules in PFC create the possibility for information integration. We argue that large-scale multimodal integration of information creates an ‘episodic buffer’, and may even suffice for implementing a central executive