The Importance of Analytical Chemistry to Food and Drug Regulation

The first thesis this Article postulates is that the history of food and drug regulation during the past twenty centuries has been the history of the development of analytical chemistry, not the history of the development of law and regulation. Statutory law during this period has remained relatively static, while general under-standing of analytical chemistry has leapt ahead with unparalleled achievement. Increased scientific enlightenment, largely achieved through analytical chemistry, has produced every important advance in food and drug regulation. Indeed, the overwhelming success of the field of analytical chemistry has created entire scientific disciplines as well as improvement in government regulation of food and drugs. The second thesis this Article presents is that the very nature of food and drug regulation requires that analytical chemistry will retain its central regulatory significance for the foreseeable future.The task that must be accomplished by analytical chemistry, in short, is far from completed, and stretches into the indefinite future. Before pursuing these two theses, it is necessary to dispose of one subsidiary matter. The past few years has witnessed intense debate concerning the scope of the term analytical chemistry. AOAC has, for example, discussed changing its name because of concern that the present title is not sufficiently broad to reflect the comprehensive purposes of the scientific field it represents. The plain meaning of the words themselves, however, quite adequately describes the scope of scientific inquiry represented by this field.Chemistry is defined as [t]he science of the composition, structure, properties, and reactions of matter. Analysis, as it relates to chemistry, is defined as [s]eparation of a substance into constituents or the determination of its composition. \u27 This Article approaches the subject of analytical chemistry in this comprehensive context

Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.National Institutes of Health (U.S.) (Grant HG007005

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Features and outcomes of unplanned hospital admissions of older people due to ill-defined (R-coded) conditions: retrospective analysis of hospital admissions data in England

BackgroundRising rates of unplanned admissions among older people are placing unprecedented demand on health services internationally. Unplanned hospital admissions for ill-defined conditions (coded with an R prefix within Chapter XVIII of the International Classification of Diseases-10) have been targeted for admission avoidance strategies, but little is known about these admissions. The aim of this study was to determine the incidence and factors predicting ill-defined (R-coded) hospital admissions of older people and their association with health outcomes.MethodsRetrospective analysis of unplanned hospital admissions to general internal and geriatric medicine wards in one hospital over 12 months (2002) with follow-up for 36 months. The study was carried out in an acute teaching hospital in England. The participants were all people aged 65 and over with unplanned hospital admissions to general internal and geriatric medicine. Independent variables included time of admission, residence at admission, route of admission to hospital, age, gender, comorbidity measured by count of diagnoses. Main outcome measures were primary diagnosis (ill-defined versus other diagnostic code), death during the hospital stay, deaths to 36 months, readmissions within 36 months, discharge destination and length of hospital stay.ResultsIncidence of R-codes at discharge was 21.6%, but was higher in general internal than geriatric medicine (25.6% v 14.1% respectively). Age, gender and co-morbidity were not significant predictors of R-code diagnoses. Admission via the emergency department (ED), out of normal general practitioner (GP) hours, under the care of general medicine and from non-residential care settings increased the risk of receiving R-codes. R-coded patients had a significantly shorter length of stay (5.91 days difference, 95% CI 4.47, 7.35), were less likely to die (hazard ratio 0.71, 95%CI 0.59, 0.85) at any point, but were as likely to be readmitted as other patients (hazard ratio 0.96 (95% CI 0.88, 1.05).ConclusionsR-coded diagnoses accounted for 1/5 of emergency admission episodes, higher than anticipated from total English hospital admissions, but comparable with rates reported in similar settings in other countries. Unexpectedly, age did not predict R-coded diagnosis at discharge. Lower mortality and length of stay support the view that these are avoidable admissions, but readmission rates particularly for further R-coded admissions indicate on-going health care needs. Patient characteristics did not predict R-coding, but organisational features, particularly admission via the ED, out of normal GP hours and via general internal medicine, were important and may offer opportunity for admission reduction strategies.<br/