Wave Mechanics and General Relativity: A Rapprochement

Using exact solutions, we show that it is in principle possible to regard waves and particles as representations of the same underlying geometry, thereby resolving the problem of wave-particle duality

Potential benefits of minimum unit pricing for alcohol versus a ban on below cost selling in England 2014: modelling study

Objective To evaluate the potential impact of two alcohol control policies under consideration in England: banning below cost selling of alcohol and minimum unit pricing. Design Modelling study using the Sheffield Alcohol Policy Model version 2.5. Setting England 2014-15. Population Adults and young people aged 16 or more, including subgroups of moderate, hazardous, and harmful drinkers. Interventions Policy to ban below cost selling, which means that the selling price to consumers could not be lower than tax payable on the product, compared with policies of minimum unit pricing at £0.40 (€0.57; $0.75), 45p, and 50p per unit (7.9 g/10 mL) of pure alcohol. Main outcome measures Changes in mean consumption in terms of units of alcohol, drinkers’ expenditure, and reductions in deaths, illnesses, admissions to hospital, and quality adjusted life years. Results The proportion of the market affected is a key driver of impact, with just 0.7% of all units estimated to be sold below the duty plus value added tax threshold implied by a ban on below cost selling, compared with 23.2% of units for a 45p minimum unit price. Below cost selling is estimated to reduce harmful drinkers’ mean annual consumption by just 0.08%, around 3 units per year, compared with 3.7% or 137 units per year for a 45p minimum unit price (an approximately 45 times greater effect). The ban on below cost selling has a small effect on population health—saving an estimated 14 deaths and 500 admissions to hospital per annum. In contrast, a 45p minimum unit price is estimated to save 624 deaths and 23 700 hospital admissions. Most of the harm reductions (for example, 89% of estimated deaths saved per annum) are estimated to occur in the 5.3% of people who are harmful drinkers. Conclusions The ban on below cost selling, implemented in the England in May 2014, is estimated to have small effects on consumption and health harm. The previously announced policy of a minimum unit price, if set at expected levels between 40p and 50p per unit, is estimated to have an approximately 40-50 times greater effect

Advancing biological understanding and therapeutics discovery with small-molecule probes

Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery

Occurrence, Distribution and Polymerase Chain Reaction-Based detection of resistance to Sterol Demethylation Inhibitor Fungicides in populations of Blumeriella jaapii in Michigan.

The intensive use of site-specific fungicides in agricultural production provides a potent selective mechanism for increasing the frequency of fungicide-resistant isolates in pathogen populations. Practical resistance occurs when the frequency and levels of resistance are great enough to limit the effectiveness of disease control in the field. Cherry leaf spot (CLS), caused by the fungus Blumeriella jaapii, is a major disease of cherry trees in the Great Lakes region. The site-specific sterol demethylation inhibitor fungicides (DMIs) have been used extensively in the region. In 2002, CLS control failed in a Michigan orchard that had used the DMI fenbuconazole exclusively for 8 years. That control failure and our observations from around the state suggested that practical resistance had developed in B. jaapii. Field trial data covering 1989 to 2005 for the DMIs fenbuconazole and tebuconazole supported observations of reduced efficacy of DMIs for controlling CLS. To verify the occurrence of fungicideresistant B. jaapii, monoconidial isolates were collected in two surveys and tested using a fungicide-amended medium. In one survey, 137 isolates from sites with different DMI histories (no known history, mixed or alternated with other fungicides, and exclusive use) were tested against 12 concentrations of fenbuconazole, tebuconazole, myclobutanil, and fenarimol. Isolates from sites with no prior DMI use were DMI sensitive (DMIS = no colony growth at 0.2 \u3bcg/ml a.i.) whereas the isolates from the site with prior exclusive use showed growth at DMI concentrations 3 to >100 times higher, and were rated as DMI resistant (DMIR). A second survey examined 1,530 monoconidial isolates, including 1,143 from 62 orchard sites in Michigan, where DMIs had been used to control CLS. Resistance to fenbuconazole was detected in 99.7% of the orchard isolates. All isolates from wild cherry trees were sensitive and isolates from feral and dooryard trees showed a range of sensitivities. A polymerase chain reaction (PCR)-based detection method for identifying B. jaapii and DMIR was developed and tested. The species-specific primer pair (Bj- F and Bj-R) based on introns in the CYP51 gene of B. jaapii, and the DMIR-specific primer pair (DMI-R-Bj-F and DMI-R-Bj-R) based on an insert found upstream of CYP51 in all DMIR isolates, provided an accurate and rapid method for detecting DMIR B. jaapii. The PCR-based identification method will facilitate timely decision making and continued monitoring of DMIR subpopulations in response to management programs

Integration of Copper based and Reduced-Risk Fungicides for Control of Blumeriella jaapii on Sour Cherry

Practical resistance to sterol demethylation inhibitor (DMI) fungicides among populations of Blumeriella jaapii, the cherry leaf spot (CLS) pathogen, was documented in 2005. In the present study, strategies to reduce selection for DMI-resistant strains of B. jaapii and adapt to possible restrictions on the use of chlorothalonil are described. Ten field trials were conducted on the sour cherry cultivars Balaton and Montmorency to test the efficacy of integrating respiration-inhibitor and copper-based fungicides into spray programs. Programs that included up to three sprays of copper-based fungicides were among the most effective for controlling CLS, although leaf phytotoxicity was sometimes observed. Under high disease pressure, eliminating chlorothalonil compromised CLS control. \u2018Balaton\u2019 and \u2018Montmorency\u2019 did not differ in the percentage of leaves with CLS or defoliation resulting from CLS. The physical modes of action of representative DMI, QoI, and copper-based fungicides were evaluated in a leaf disk assay. Trifloxystrobin, a QoI fungicide, provided the best protection against infection by B. jaapii. All fungicides were more effective than water when applied 46 h postinfection, although differences were not statistically significant in one of two trials. Tebuconazole, a DMI, was the only fungicide that was more effective than water in preventing resporulation from existing lesions in both trials. Isolates of B. jaapii, which varied in DMI-sensitivity, all were sensitive to copper in vitro