(RS)-2-(3,4-Methylenedioxyphenyl)-5-phenyl-3,6-dihydro-2H-pyran

The title compound, C18H16O3, crystallizes with one molecule in the asymmetric unit. The conformation of the dihydropyran ring features puckering of the O atom by 0.612 (2) Å from the least-squares plane defined by the five C atoms [maximum deviation 0.1025 (12) Å]

Understanding cost of care for patients on renal replacement therapy: looking beyond fixed tariffs.

BACKGROUND: In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. METHODS: Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. RESULTS: Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. CONCLUSIONS: Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service.<br/

Testing the role of multicopy plasmids in the evolution of antibiotic resistance

Multicopy plasmids are extremely abundant in prokaryotes but their role in bacterial evolution remains poorly understood. We recently showed that the increase in gene copy number per cell provided by multicopy plasmids could accelerate the evolution of plasmid-encoded genes. In this work, we present an experimental system to test the ability of multicopy plasmids to promote gene evolution. Using simple molecular biology methods, we constructed a model system where an antibiotic resistance gene can be inserted into Escherichia coli MG1655, either in the chromosome or on a multicopy plasmid. We use an experimental evolution approach to propagate the different strains under increasing concentrations of antibiotics and we measure survival of bacterial populations over time. The choice of the antibiotic molecule and the resistance gene is so that the gene can only confer resistance through the acquisition of mutations. This "evolutionary rescue" approach provides a simple method to test the potential of multicopy plasmids to promote the acquisition of antibiotic resistance. In the next step of the experimental system, the molecular bases of antibiotic resistance are characterized. To identify mutations responsible for the acquisition of antibiotic resistance we use deep DNA sequencing of samples obtained from whole populations and clones. Finally, to confirm the role of the mutations in the gene under study, we reconstruct them in the parental background and test the resistance phenotype of the resulting strains

Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

National Institutes of Health grants GM-38765 and P50-DE016191 (C.N.S.), Welcome Trust Programme grant 086867/Z/08/Z (R.J.F. and M.P.) and Project grant 085903/Z/08 (R.J.F.) and Arthritis Research Campaign UK fellowships 18445 and 18103 (to L.V.N. and D.C., respectively). M.S. received a National Research Service Award from the NHLBI (HL087526)

Suppression of Lung Adenocarcinoma Progression by Nkx2-1

Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma development4. Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limitsmetastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga2. Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051

A simulation study of diagnostics for bias in non-probability samples

A non-probability sampling mechanism is likely to bias estimates of parameters with respect to a target population of interest. This bias poses a unique challenge when selection is \u27non-ignorable\u27, i.e. dependent upon the unobserved outcome of interest, since it is then undetectable and thus cannot be ameliorated. We extend a simulation study by Nishimura et al. [International Statistical Review, 84, 43--62 (2016)], adding a recently published statistic, the so-called \u27standardized measure of unadjusted bias\u27, which explicitly quantifies the extent of bias under the assumption that a specified amount of non-ignorable selection exists. Our findings suggest that this new sensitivity diagnostic is considerably correlated with, and more predictive of, the true, unknown extent of selection bias than other diagnostics, even when the underlying assumed level of non-ignorability is incorrect

Telemonitoring for Patients With COVID-19:Recommendations for Design and Implementation

Despite significant efforts, the COVID-19 pandemic has put enormous pressure on health care systems around the world, threatening the quality of patient care. Telemonitoring offers the opportunity to carefully monitor patients with a confirmed or suspected case of COVID-19 from home and allows for the timely identification of worsening symptoms. Additionally, it may decrease the number of hospital visits and admissions, thereby reducing the use of scarce resources, optimizing health care capacity, and minimizing the risk of viral transmission. In this paper, we present a COVID-19 telemonitoring care pathway developed at a tertiary care hospital in the Netherlands, which combined the monitoring of vital parameters with video consultations for adequate clinical assessment. Additionally, we report a series of medical, scientific, organizational, and ethical recommendations that may be used as a guide for the design and implementation of telemonitoring pathways for COVID-19 and other diseases worldwide