New distinguished classes of spectral spaces: a survey

In the present survey paper, we present several new classes of Hochster's spectral spaces "occurring in nature", actually in multiplicative ideal theory, and not linked to or realized in an explicit way by prime spectra of rings. The general setting is the space of the semistar operations (of finite type), endowed with a Zariski-like topology, which turns out to be a natural topological extension of the space of the overrings of an integral domain, endowed with a topology introduced by Zariski. One of the key tool is a recent characterization of spectral spaces, based on the ultrafilter topology, given in a paper by C. Finocchiaro in Comm. Algebra 2014. Several applications are also discussed

Using reflexivity to enhance in-depth interviewing skills for the clinician researcher

<p>Abstract</p> <p>Background</p> <p>Primary health care clinicians are being encouraged to undertake qualitative research, however the in-depth interviewing skills required are not as straightforward as might be first supposed. While there are benefits and certain skills that clinicians can bring to interview-based research, there are important new skills to develop. To date there has been neither discussion about these new skills, nor any preparatory guidelines for clinicians entering into interview-based research in the qualitative research literature. In the absence of formal guidelines, we suggest the use of reflexivity throughout the interview process as a means to become more accomplished in this area. We present our own experiences as a novice general practitioner (GP) researcher undertaking a PhD study and her experienced supervisors. The PhD study used critical phenomenology through in-depth interviews to understand the experience of the patient-doctor relationship between same-sex attracted women and their usual GP in Australia.</p> <p>Results</p> <p>We used reflexivity to improve the rigour of the data collection. This enabled improved probing, fewer assumptions, avoidance of premature interpretation, and an accentuated sense of curiosity during interviews. We also enlisted reciprocity between interviewer and interviewee as a tool to improve engagement and trust, share interview control, and ultimately improve the depth of the interview content.</p> <p>Conclusion</p> <p>Preparatory recommendations for novice clinician research interviewers include the importance of recognising the multiple identities that they bring to the interview. In this setting in particular this involves acknowledging the clinician interviewer as a potential insider in relation to interviewees and negotiating shared understanding to avoid insider assumptions. Other essential requirements are having an experienced research supervisor, arranging pilot interviews that include active feedback on interviewing style from interviewees, and being reflexive during interviews. More formal guidelines for in-depth interviewing skills development are needed.</p

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR. METHODS: After conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of NTLA-2001 in six patients with hereditary ATTR amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study. RESULTS: Preclinical studies showed durable knockout of TTR after a single dose. Serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. Dose-dependent pharmacodynamic effects were observed. At day 28, the mean reduction from baseline in serum TTR protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram. CONCLUSIONS: In a small group of patients with hereditary ATTR amyloidosis with polyneuropathy, administration of NTLA-2001 was associated with only mild adverse events and led to decreases in serum TTR protein concentrations through targeted knockout of TTR. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051. opens in new tab.

Genome-Wide Identification of Ampicillin Resistance Determinants in Enterococcus faecium

Enterococcus faecium has become a nosocomial pathogen of major importance, causing infections that are difficult to treat owing to its multi-drug resistance. In particular, resistance to the β-lactam antibiotic ampicillin has become ubiquitous among clinical isolates. Mutations in the low-affinity penicillin binding protein PBP5 have previously been shown to be important for ampicillin resistance in E. faecium, but the existence of additional resistance determinants has been suggested. Here, we constructed a high-density transposon mutant library in E. faecium and developed a transposon mutant tracking approach termed Microarray-based Transposon Mapping (M-TraM), leading to the identification of a compendium of E. faecium genes that contribute to ampicillin resistance. These genes are part of the core genome of E. faecium, indicating a high potential for E. faecium to evolve towards β-lactam resistance. To validate the M-TraM results, we adapted a Cre-lox recombination system to construct targeted, markerless mutants in E. faecium. We confirmed the role of four genes in ampicillin resistance by the generation of targeted mutants and further characterized these mutants regarding their resistance to lysozyme. The results revealed that ddcP, a gene predicted to encode a low-molecular-weight penicillin binding protein with D-alanyl-D-alanine carboxypeptidase activity, was essential for high-level ampicillin resistance. Furthermore, deletion of ddcP sensitized E. faecium to lysozyme and abolished membrane-associated D,D-carboxypeptidase activity. This study has led to the development of a broadly applicable platform for functional genomic-based studies in E. faecium, and it provides a new perspective on the genetic basis of ampicillin resistance in this organism

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Italian network for obesity and cardiovascular disease surveillance: A pilot project

<p>Abstract</p> <p>Background</p> <p>Also in Mediterranean countries, which are considered a low risk population for cardiovascular disease (CVD), the increase in body mass index (BMI) has become a public health priority. To evaluate the feasibility of a CVD and obesity surveillance network, forty General Practitioners (GPs) were engaged to perform a screening to assess obesity, cardiovascular risk, lifestyle habits and medication use.</p> <p>Methods</p> <p>A total of 1,046 women and 1,044 men aged 35–74 years were randomly selected from GPs' lists stratifying by age decade and gender. Anthropometric and blood pressure measurements were performed by GPs using standardized methodologies. BMI was computed and categorized in normal weight (BMI 18.5–24.9 kg/m²), overweight (BMI 25.0–29.9 kg/m²) and obese (BMI ≥ 30 kg/m²). Food frequency (per day: fruits and vegetables; per week: meat, cheese, fish, pulses, chocolate, fried food, sweet, wholemeal food, rotisserie food and sugar drink) and physical activity (at work and during leisure time) were investigated through a questionnaire. CVD risk was assessed using the Italian CUORE Project risk function.</p> <p>Results</p> <p>The percentage of missing values was very low. Prevalence of overweight was 34% in women and 50% in men; prevalence of obesity was 23% in both men and women. Level of physical activity was mostly low or very low. BMI was inversely associated with consumption of pulses, rotisserie food, chocolate, sweets and physical activity during leisure time and directly associated with consumption of meat. Mean value of total cardiovascular risk was 4% in women and 11% in men. One percent of women and 16% of men were at high cardiovascular risk (≥ 20% in 10 years). Normal weight persons were four times more likely to be at low risk than obese persons.</p> <p>Conclusion</p> <p>This study demonstrated the feasibility of a surveillance network of GPs in Italy focusing on obesity and other CVD risk factors. It also provided information on lifestyle habits, such as diet and physical activity.</p