Ion Mobility-Mass Spectrometry with a Radial Opposed Migration Ion and Aerosol Classifier (ROMIAC)

The first application of a novel differential mobility analyzer, the radial opposed migration ion and aerosol classifier (ROMIAC), is demonstrated. The ROMIAC uses antiparallel forces from an electric field and a cross-flow gas to both scan ion mobilities and continuously transmit target mobility ions with 100% duty cycle. In the ROMIAC, diffusive losses are minimized, and resolution of ions, with collisional cross-sections of 200–2000 Å^2, is achieved near the nondispersive resolution of ~20. Higher resolution is theoretically possible with greater cross-flow rates. The ROMIAC was coupled to a linear trap quadrupole mass spectrometer and used to classify electrosprayed C2–C12 tetra-alkyl ammonium ions, bradykinin, angiotensin I, angiotensin II, bovine ubiquitin, and two pairs of model peptide isomers. Instrument and mobility calibrations of the ROMIAC show that it exhibits linear responses to changes in electrode potential, making the ROMIAC suitable for mobility and cross-section measurements. The high resolution of the ROMIAC facilitates separation of isobaric isomeric peptides. Monitoring distinct dissociation pathways associated with peptide isomers fully resolves overlapping peaks in the ion mobility data. The ability of the ROMIAC to operate at atmospheric pressure and serve as a front-end analyzer to continuously transmit ions with a particular mobility facilitates extensive studies of target molecules using a variety of mass spectrometric methods

Can CANVAS due to RFC1 biallelic expansions present with pure ataxia?

BACKGROUND: Biallelic expansion of AAGGG in the replication factor complex subunit 1 (RFC1) was identified as a major cause of cerebellar ataxia, neuropathy (sensory ganglionopathy, or SG) and vestibular areflexia syndrome (CANVAS). We wanted to clarify if RFC1 expansions can present with pure ataxia and if such expansions could be responsible for some cases where an alternative diagnosis had been made. METHODS: We identified patients with a combination of ataxia and SG and no other cause found, patients where an alternative diagnosis had been made, and patients with pure ataxia. Testing for RFC1 expansions was done using established methodology. RESULTS: Among 54 patients with otherwise idiopathic sporadic ataxia without SG, none was found to have RFC1 expansions. Among 38 patients with cerebellar ataxia and SG in which all other causes were excluded, 71% had RFC1 expansions. Among 27 patients with cerebellar ataxia and SG diagnosed with coeliac disease or gluten sensitivity, 15% had RFC1 expansions. CONCLUSIONS: Isolated cerebellar ataxia without SG makes the diagnosis of CANVAS due to RFC1 expansions highly improbable, but CANVAS is frequently the cause of the combination of idiopathic cerebellar ataxia with SG. It is important to screen patients diagnosed with other causes of acquired ataxia and SG as a small percentage were found to have RFC1 expansions

Individual freedom versus collective responsibility: an ethicist's perspective

Philosophical theories of collective action have produced a number of alternative accounts of the rationality and morality of self-interest and altruism. These have obvious applications to communicable disease control, the avoidance of antibiotic resistance, the responsibility of healthcare professionals to patients with serious communicable diseases, and the sharing of personal data in epidemiological research

Real-Time Studies of Iron Oxalate-Mediated Oxidation of Glycolaldehyde as a Model for Photochemical Aging of Aqueous Tropospheric Aerosols

The complexation of iron (III) with oxalic acid in aqueous solution yields a strongly absorbing chromophore that undergoes efficient photodissociation to give iron (II) and the carbon dioxide anion radical. Importantly, iron (III) oxalate complexes absorb near-UV radiation (λ > 350 nm), providing a potentially powerful source of oxidants in aqueous tropospheric chemistry. Although this photochemical system has been studied extensively, the mechanistic details associated with its role in the oxidation of dissolved organic matter within aqueous aerosol remain largely unknown. This study utilizes glycolaldehyde as a model organic species to examine the oxidation pathways and evolution of organic aerosol initiated by the photodissociation of aqueous iron (III) oxalate complexes. Hanging droplets (radius 1 mm) containing iron (III), oxalic acid, glycolaldehyde, and ammonium sulfate (pH ~ 3) are exposed to irradiation at 365 nm and sampled at discrete time points utilizing field-induced droplet ionization mass spectrometry (FIDI-MS). Glycolaldehyde is found to undergo rapid oxidation to form glyoxal, glycolic acid, and glyoxylic acid, but the formation of high molecular weight oligomers is not observed. For comparison, particle-phase experiments conducted in a laboratory chamber explore the reactive uptake of gas-phase glycolaldehyde onto aqueous seed aerosol containing iron and oxalic acid. The presence of iron oxalate in seed aerosol is found to inhibit aerosol growth. These results suggest that photodissociation of iron (III) oxalate can lead to the formation of volatile oxidation products in tropospheric aqueous aerosols

Lifespan extension and the doctrine of double effect

Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning

Effects of Reproductive Status, Social Rank, Sex and Group Size on Vigilance Patterns in Przewalski's Gazelle

Quantifying vigilance and exploring the underlying mechanisms has been the subject of numerous studies. Less attention has focused on the complex interplay between contributing factors such as reproductive status, social rank, sex and group size. Reproductive status and social rank are of particular interest due to their association with mating behavior. Mating activities in rutting season may interfere with typical patterns of vigilance and possibly interact with social rank. In addition, balancing the tradeoff between vigilance and life maintenance may represent a challenge for gregarious ungulate species rutting under harsh winter conditions. We studied vigilance patterns in the endangered Przewalski's gazelle (Procapra przewalskii) during both the rutting and non-rutting seasons to examine these issues.Field observations were carried out with focal sampling during rutting and non-rutting season in 2008-2009. Results indicated a complex interplay between reproductive status, social rank, sex and group size in determining vigilance in this species. Vigilance decreased with group size in female but not in male gazelles. Males scanned more frequently and thus spent more time vigilant than females. Compared to non-rutting season, gazelles increased time spent scanning at the expense of bedding in rutting season. During the rutting season, territorial males spent a large proportion of time on rutting activities and were less vigilant than non-territorial males. Although territorial males may share collective risk detection with harem females, we suggest that they are probably more vulnerable to predation because they seemed reluctant to leave rut stands under threats.Vigilance behavior in Przewalski's gazelle was significantly affected by reproductive status, social rank, sex, group size and their complex interactions. These findings shed light on the mechanisms underlying vigilance patterns and the tradeoff between vigilance and other crucial activities

An adaptable integrated modelling platform to support rapidly evolving agricultural and environmental policy

he utility of integrated models for informing policy has been criticised due to limited stakeholder engagement, model opaqueness, inadequate transparency in assumptions, lack of model flexibility and lack of communication of uncertainty that, together, lead to a lack of trust in model outputs. We address these criticisms by presenting the ERAMMP Integrated Modelling Platform (IMP), developed to support the design of new “business-critical” policies focused on agriculture, land-use and natural resource management. We demonstrate how the long-term (>5 years), iterative, two-way and continuously evolving participatory process led to the co-creation of the IMP with government, building trust and understanding in a complex integrated model. This is supported by a customisable modelling framework that is sufficiently flexible to adapt to changing policy needs in near real-time. We discuss how these attributes have facilitated cultural change within the Welsh Government where the IMP is being actively used to explore, test and iterate policy ideas prior to final policy design and implementation

Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury

Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the ‘social brain network’ (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2–8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems