42 research outputs found
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