New Formulation of Paraquat: A Step Forward but in the Wrong Direction?

The author discusses whether the new paraquat formulation introduced in Sri Lanka is a step forward in reducing deaths from paraquat self-poisoning

A PROTEOMIC ANALYSIS OF NEOPLASTIC PROGRESSION IN BREAST CANCER

The utilization of high-throughput -omics strategies, such as proteomics, in the analysis of breastcancer will function to define central molecular characteristics across a disease that is associatedwith a high degree of molecular heterogeneity. Data reported herein details the investigation ofkey subjects in breast cancer biology focused on the characterization of endogenous andexperimentally-induced disease biology characteristics utilizing the application of LC-MS basedproteomic analyses of both in vitro models of breast cancer as well as primary clinical samples.Results include a combined global and functional proteomic strategy to identify governingfunctional roles for mutually, differentially abundant proteins observed across three divergentcell line models of breast cancer. Further, evidence is presented which provides insights into theregulatory activity of the breast cancer-associated microRNA (miR-145) in several cell linemodels of breast cancer in which expression of this microRNA has been restored. Lastly, robustanalyses are detailed focused on the identification of differential protein characteristics indicativeof disease stage as well as of recurrent disease in breast cancer derived from proteomic analysisof formalin-fixed, paraffin embedded (FFPE) clinical samples. These studies contribute to thefield of proteomics in the form of 1) providing robust experimental workflows directed towardsinvestigation of functional themes and associated functional targets in large protein data sets 2)detailing strategies for navigating the application of proteomic analysis to microRNA targetdiscovery and 3) further development and utilization of methodologies towards the proteomicanalysis of clinical, FFPE tissue samples. Furthermore, these studies benefit the breast cancercommunity on several fronts including 1) the elucidation of provocative protein candidateswhich warrant further investigation for their role in regulating disease mechanisms underlyingvbreast cancer biology and 2) through the discovery of diagnostic markers indicative of discretesubtypes and stages of disease progression in breast cancer. The results reported herein detaildisease-specific protein abundance characteristics associated with neoplastic progression inbreast cancer that will benefit further expansion of the basic biological understanding of thisdisease and describes novel proteins for further evaluation as biomarker candidates for thediagnosis of breast cancer

Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer\u27s trial selection and disease monitoring

Blood biomarkers indicative of Alzheimer\u27s disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6 years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer\u27s Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments

Use of the online poisons information database TOXBASE and admissions rates for poisoned patients from emergency departments in England and Wales during 2008 to 2015

Background The impact of poison information services on patient care in hospital, particularly decisions on whether to admit patients after initial attendance at an emergency department (ED), is unclear. In the United Kingdom, the vast majority of poisons information is provided by use of the online poisons information database, TOXBASE. We investigated the relationship between rates of hospital access to TOXBASE and rates of poisoning admissions from EDs in England and Wales to begin to address the interactions between use of poisons information and patient management as reflected by hospital activity. Methods Data were obtained on attendances and admissions due to poisoning for individual National Health Service (NHS) Trusts in both England and Wales, together with data on the overall number of accesses to TOXBASE for drugs (pharmaceuticals and drugs of abuse), from 2008 to 2015. Rates of TOXBASE access and admissions per poisoning attendance in London were clearly different to the rest of England and Wales; London was therefore analyzed separately. Negative binomial generalized additive models were fit, incorporating an interaction effect, for accesses, attendances and admissions to check for variability according to hospital size. Additional models were then fit to assess whether there was any variation in association of overall TOXBASE use with rates of admission for 6 key drug subgroups: antidepressants, paracetamol, antipsychotics, opioids (including all medicines, but excluding heroin), heroin and non‐opioid drugs of abuse. Results Rates of TOXBASE use per Trust increased across the study period by 39.3% (95% confidence interval [CI] = 34.1%, 44.8%) in England and 76.9% (24.7%, 151.0%) in Wales, showing an increase in TOXBASE use which was substantially greater than the increase in poisoning attendances. Admission rates exhibited seasonality, with lower rates in January and February, increasing by 2.0% (1.0%, 3.1%) in England and 5.8% (5.5%, 5.9%) in Wales toward the middle of the year. The initial model fit indicated that the average proportion of poisoning patients admitted increased with both increasing attendances and increasing TOXBASE use (England and Wales overall, P < 0.0001; England and Wales excluding London, P < 0.0001; London, P < 0.0001). In England and Wales overall, and in London alone, increased TOXBASE access to non‐opioid drugs of abuse advice was associated with a significant decrease in admissions (England and Wales, −0.15% [−0.29%, −0.01%] [P = 0.032]; London, −1.02% [−1.53%, −0.50%] [P < 0.0001]). In contrast, increased access to heroin advice was associated with a significant increase in admissions in London (+2.03% [+0.11%, +3.99%] [P = 0.034]). Increasing access to TOXBASE for paracetamol advice was associated with lower admissions in England and Wales (England and Wales, −0.11% [−0.23%, −0.01%] [P = 0.036]; England and Wales excluding London, −0.18% [−0.30%, −0.06%] [P = 0.001]) but higher admissions in London (+0.52% [+0.03%, +1.01%] [P = 0.035]). Conclusions We have shown that greater overall use of TOXBASE by hospitals is associated with a higher proportion of poisoning attendances being admitted. Interestingly, looking at particular drug groups, we found significant associations in both directions between overall TOXBASE use and rates of admission for some drug groups. The current methodology is unable to determine whether such decisions might be appropriate or not. Mixed‐methods research is now required to gain a better understanding of how provision of poisons information affects decisions within the ED

Does Restricting Pack Size of Paracetamol (Acetaminophen) Reduce Suicides?

The authors discuss a new study that examined the change in deaths attributed to paracetamol poisoning in England and Wales in the six years before and after a legislated reduction in the maximum pack size

Cooling atoms, particles and polarisable objects using dissipative dipole forces

Optical cooling methods are generally applicable to a very restricted range of species. As a means of overcoming this problem, we explore the effect of the retarded interaction of any polarisable particle (an atom, a molecule or even a micromirror) with itself, similarly to cavity-mediated cooling. We use the transfer matrix method, extended to allow us to handle moving scatterers, to explore the most general configuration of a mobile particle interacting with any 1D combination of fixed optical elements. Remarkably, this model allows a solution in closed form for the force acting on the particle, without any a priori restriction on the nature of the particle.peer-reviewe