Late-Life Depression: Essential Features, Assessment and Treatment

Key Points Major Depressive Disorder (MDD) not a normal part of aging. Age influences demographics, etiology, presentation, assessment, acute and maintenance treatment, and outcome. Depressive syndromes in later life are significant and very treatable and recent advances in psychotherapies and somatic therapies improve treatment effectiveness

An Efficient, Green Chemical Synthesis of the Malaria\ud Drug, Piperaquine

To provide a robust, efficient synthesis of the malaria drug piperaquine for potential use in resource-poor settings. We used in-process analytical technologies (IPAT; HPLC) and a program of experiments to develop a synthesis of piperaquine that avoids the presence of a toxic impurity in the API and is optimized for overall yield and operational simplicity. A green-chemical synthesis of piperaquine is described that proceeds in 92 – 93 % overall yield. The chemistry is robust and provides very pure piperaquine tetraphosphate salt (> 99.5 %). The overall process utilizes modest amounts (about 8 kg/kg) of 2-propanol and ethyl acetate as the only organic materials not incorporated into the API; roughly 60 % of this waste can be recycled into the production process. This process also completely avoids the formation of a toxic impurity commonly seen in piperaquine that is otherwise difficult to remove. An efficient synthesis of piperaquine is described that may be useful for application in resource-poor settings as a means of expanding access to and reducing the cost of ACTs

The ALMaQUEST Survey - V. The non-universality of kpc-scale star formation relations and the factors that drive them

ABSTRACT Using a sample of ∼15 000 kpc-scale star-forming spaxels in 28 galaxies drawn from the ALMA-MaNGA QUEnching and STar formation (ALMaQUEST) survey, we investigate the galaxy-to-galaxy variation of the ‘resolved’ Schmidt–Kennicutt relation (rSK; $\Sigma _{\rm H_2}$–ΣSFR), the ‘resolved’ star-forming main sequence (rSFMS; Σ⋆–ΣSFR), and the ‘resolved’ molecular gas main sequence (rMGMS; Σ⋆–$\Sigma _{\rm H_2}$). The rSK relation, rSFMS, and rMGMS all show significant galaxy-to-galaxy variation in both shape and normalization, indicating that none of these relations is universal between galaxies. The rSFMS shows the largest galaxy-to-galaxy variation and the rMGMS the least. By defining an ‘offset’ from the average relations, we compute a ΔrSK, ΔrSFMS, ΔrMGMS for each galaxy, to investigate correlations with global properties. We find the following correlations with at least 2σ significance: The rSK is lower (i.e. lower star formation efficiency) in galaxies with higher M⋆, larger Sersic index, and lower specific SFR (sSFR); the rSFMS is lower (i.e. lower sSFR) in galaxies with higher M⋆ and larger Sersic index; and the rMGMS is lower (i.e. lower gas fraction) in galaxies with lower sSFR. In the ensemble of all 15 000 data points, the rSK relation and rMGMS show equally tight scatters and strong correlation coefficients, compared with a larger scatter and weaker correlation in the rSFMS. Moreover, whilst there is no correlation between ΔrSK and ΔrMGMS in the sample, the offset of a galaxy’s rSFMS does correlate with both of the other two offsets. Our results therefore indicate that the rSK and rMGMS are independent relations, whereas the rSFMS is a result of their combination.ERC STF

Are galactic star formation and quenching governed by local, global, or environmental phenomena?

We present an analysis of star formation and quenching in the SDSS-IV MaNGA-DR15, utilising over 5 million spaxels from $\sim$3500 local galaxies. We estimate star formation rate surface densities ($\Sigma_{\rm SFR}$) via dust corrected $H\alpha$ flux where possible, and via an empirical relationship between specific star formation rate (sSFR) and the strength of the 4000 Angstrom break (D4000) in all other cases. We train a multi-layered artificial neural network (ANN) and a random forest (RF) to classify spaxels into `star forming' and `quenched' categories given various individual (and groups of) parameters. We find that global parameters (pertaining to the galaxy as a whole) perform collectively the best at predicting when spaxels will be quenched, and are substantially superior to local/ spatially resolved and environmental parameters. Central velocity dispersion is the best single parameter for predicting quenching in central galaxies. We interpret this observational fact as a probable consequence of the total integrated energy from AGN feedback being traced by the mass of the black hole, which is well known to correlate strongly with central velocity dispersion. Additionally, we train both an ANN and RF to estimate $\Sigma_{\rm SFR}$ values directly via regression in star forming regions. Local/ spatially resolved parameters are collectively the most predictive at estimating $\Sigma_{\rm SFR}$ in these analyses, with stellar mass surface density at the spaxel location ($\Sigma_*$) being by far the best single parameter. Thus, quenching is fundamentally a global process but star formation is governed locally by processes within each spaxel.ERC Advanced Grant: 695671 "Quench

How do central and satellite galaxies quench? - Insights from spatially resolved spectroscopy in the MaNGA survey

We investigate how star formation quenching proceeds within central and satellite galaxies using spatially resolved spectroscopy from the SDSS-IV MaNGA DR15. We adopt a complete sample of star formation rate surface densities ($\Sigma_{\rm SFR}$), derived in Bluck et al. (2020), to compute the distance at which each spaxel resides from the resolved star forming main sequence ($\Sigma_{\rm SFR} - \Sigma_*$ relation): $\Delta \Sigma_{\rm SFR}$. We study galaxy radial profiles in $\Delta \Sigma_{\rm SFR}$, and luminosity weighted stellar age (${\rm Age_L}$), split by a variety of intrinsic and environmental parameters. Via several statistical analyses, we establish that the quenching of central galaxies is governed by intrinsic parameters, with central velocity dispersion ($\sigma_c$) being the most important single parameter. High mass satellites quench in a very similar manner to centrals. Conversely, low mass satellite quenching is governed primarily by environmental parameters, with local galaxy over-density ($\delta_5$) being the most important single parameter. Utilising the empirical $M_{BH}$ - $\sigma_c$ relation, we estimate that quenching via AGN feedback must occur at $M_{BH} \geq 10^{6.5-7.5} M_{\odot}$, and is marked by steeply rising $\Delta \Sigma_{\rm SFR}$ radial profiles in the green valley, indicating `inside-out' quenching. On the other hand, environmental quenching occurs at over-densities of 10 - 30 times the average galaxy density at z$\sim$0.1, and is marked by steeply declining $\Delta \Sigma_{\rm SFR}$ profiles, indicating `outside-in' quenching. Finally, through an analysis of stellar metallicities, we conclude that both intrinsic and environmental quenching must incorporate significant starvation of gas supply.ERC STF

The ALMaQUEST Survey: The Molecular Gas Main Sequence and the Origin of the Star-forming Main Sequence

The origin of the star forming main sequence ( i.e., the relation between star formation rate and stellar mass, globally or on kpc-scales; hereafter SFMS) remains a hotly debated topic in galaxy evolution. Using the ALMA-MaNGA QUEnching and STar formation (ALMaQUEST) survey, we show that for star forming spaxels in the main sequence galaxies, the three local quantities, star-formation rate surface density (\sigsfr), stellar mass surface density (\sigsm), and the \h2~mass surface density (\sigh2), are strongly correlated with one another and form a 3D linear (in log) relation with dispersion. In addition to the two well known scaling relations, the resolved SFMS (\sigsfr~ vs. \sigsm) and the Schmidt-Kennicutt relation (\sigsfr~ vs. \sigh2; SK relation), there is a third scaling relation between \sigh2~ and \sigsm, which we refer to as the `molecular gas main sequence' (MGMS). The latter indicates that either the local gas mass traces the gravitational potential set by the local stellar mass or both quantities follow the underlying total mass distributions. The scatter of the resolved SFMS ($\sigma \sim 0.25$ dex) is the largest compared to those of the SK and MGMS relations ($\sigma \sim$ 0.2 dex). A Pearson correlation test also indicates that the SK and MGMS relations are more strongly correlated than the resolved SFMS. Our result suggests a scenario in which the resolved SFMS is the least physically fundamental and is the consequence of the combination of the SK and the MGMS relations

Towards robust determination of non-parametric morphologies in marginal astronomical data: Resolving uncertainties with cosmological hydrodynamical simulations

Quantitative morphologies, such as asymmetry and concentration, have long been used as an effective way to assess the distribution of galaxy starlight in large samples. Application of such quantitative indicators to other data products could provide a tool capable of capturing the 2-dimensional distribution of a range of galactic properties, such as stellar mass or star-formation rate maps. In this work, we utilize galaxies from the Illustris and IllustrisTNG simulations to assess the applicability of concentration and asymmetry indicators to the stellar mass distribution in galaxies. Specifically, we test whether the intrinsic values of concentration and asymmetry (measured directly from the simulation stellar mass particle maps) are recovered after the application of measurement uncertainty and a point spread function (PSF). We find that random noise has a non-negligible systematic effect on asymmetry that scales inversely with signal-to-noise, particularly at signal-to-noise less than 100. We evaluate different methods to correct for the noise contribution to asymmetry at very low signal-to-noise, where previous studies have been unable to explore due to systematics. We present algebraic corrections for noise and resolution to recover the intrinsic morphology parameters. Using Illustris as a comparison dataset, we evaluate the robustness of these fits in the presence of a different physics model, and confirm these correction methods can be applied to other datasets. Lastly, we provide estimations for the uncertainty on different correction methods at varying signal-to-noise and resolution regimes.STFC ER

The Adventure of Relevance: Speculative Reconstructions in Contemporary Social Science

At a time when the institutional and intellectual futures of the social sciences are under threat, there has been growing concern among researchers and policy makers around the question of how to foster and enhance the relevance of their knowledge-practices. This thesis problematises such demands by elaborating a concept of ‘relevance’ that renders it not the product of a subjective act of interpretation, but an event that is part and parcel of the immanent processes by which the facts that compose situations come (in)to matter. By expanding on the work of William Connolly, Gilles Deleuze, John Dewey, Donna Haraway, William James, Michel Serres, Isabelle Stengers and Alfred North Whitehead, among others, I follow the implications of the concept of relevance through a speculative exploration of modes of knowledge-making in contemporary social science. As I show, such an exploration requires a transformation of the ethos with which social scientific inquiries are identified. If the former could be characterised as an ‘ethics of estrangement’ whereby to inquire is to estrange oneself from an apparent reality in order to gain access to a realm of social causes and reasons, an ethos oriented by the concept of relevance must reject that bifurcation of reality and cultivate, instead, a deep empiricism that is both singularly attentive to the coming into matter of the facts that compose a situation, and inventive of propositions that may contribute to the possible transformation of those situations that demand inquiry. It is this latter ethos, one which I call an ‘adventure’, that my thesis develops

Molecular subgroups of medulloblastoma: the current consensus

Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause of morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication and stratification include clinical factors (age, presence of metastases, and extent of resection) as well as histological subgrouping (classic, desmoplastic, and large cell/anaplastic histology). Transcriptional profiling studies of medulloblastoma cohorts from several research groups around the globe have suggested the existence of multiple distinct molecular subgroups that differ in their demographics, transcriptomes, somatic genetic events, and clinical outcomes. Variations in the number, composition, and nature of the subgroups between studies brought about a consensus conference in Boston in the fall of 2010. Discussants at the conference came to a consensus that the evidence supported the existence of four main subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). Participants outlined the demographic, transcriptional, genetic, and clinical differences between the four subgroups. While it is anticipated that the molecular classification of medulloblastoma will continue to evolve and diversify in the future as larger cohorts are studied at greater depth, herein we outline the current consensus nomenclature, and the differences between the medulloblastoma subgroups

Promoting Pre-conceptional use of folic acid to Hispanic women: A social marketing approach

Objective: To develop a culturally appropriate communication initiative in an effort to promote the use of pre-conceptional folic acid among Hispanic women of childbearing age. The materials were designed to communicate information about the risks of neural tube defects and the value of folic acid supplementation before conception. Methods: The initiative was developed using a social marketing approach. A series of focus groups were conducted with Hispanic women, particularly Mexican and Mexican-American women, to gain an understanding of their knowledge, attitudes, and behaviors regarding birth defects and folic acid. Additionally focus groups assessed women's preferences for existing folic acid education materials. Qualitative analysis of coded transcripts revealed key themes which were incorporated into a multi-media initiative. Results: Critical themes of the research highlighted the need to include the role of partners and a sense of family in the promotions aimed at these groups. Another key component was the need to dispel myths which act as barriers to preconceptional folic acid use. Other important elements included in the media products were the need for Spanish and English versions, an explanation of neural tube defects, and a reference to the cost of the supplements. Conclusion: The final products of the initiative included Spanish and English versions of a brochure, photo-novella, and radio public service announcement. Pre-testing results showed women understood the message, thought the message was for women like them, and expected to begin taking a folic acid supplement. Results of the overall evaluation of the initiative are on-going