From Collapse to Freezing in Random Heteropolymers

We consider a two-letter self-avoiding (square) lattice heteropolymer model of N_H (out ofN) attracting sites. At zero temperature, permanent links are formed leading to collapse structures for any fraction rho_H=N_H/N. The average chain size scales as R = N^{1/d}F(rho_H) (d is space dimension). As rho_H --> 0, F(rho_H) ~ rho_H^z with z={1/d-nu}=-1/4 for d=2. Moreover, for 0 < rho_H < 1, entropy approaches zero as N --> infty (being finite for a homopolymer). An abrupt decrease in entropy occurs at the phase boundary between the swollen (R ~ N^nu) and collapsed region. Scaling arguments predict different regimes depending on the ensemble of crosslinks. Some implications to the protein folding problem are discussed.Comment: 4 pages, Revtex, figs upon request. New interpretation and emphasis. Submitted to Europhys.Let

Fine Selmer Groups and Isogeny Invariance

We investigate fine Selmer groups for elliptic curves and for Galois representations over a number field. More specifically, we discuss Conjecture A, which states that the fine Selmer group of an elliptic curve over the cyclotomic extension is a finitely generated $\mathbb{Z}_p$-module. The relationship between this conjecture and Iwasawa's classical $\mu=0$ conjecture is clarified. We also present some partial results towards the question whether Conjecture A is invariant under isogenies.Comment: 20 page

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Assessment and management of anxiety disorders in children and adolescents

Anxiety disorders in childhood and adolescence are extremely common and are often associated with lifelong psychiatric disturbance. Consistent with DSM-5 and the extant literature, this review concerns the assessment and treatment of specific phobias, separation anxiety disorder, generalised anxiety disorder, social anxiety disorder, panic disorder and agoraphobia. Evidence-based psychological treatments (cognitive behaviour therapy; CBT) for these disorders have been developed and investigated, and in recent years promising low-intensity versions of CBT interventions have been proposed that offer a means to increase access to evidence-based treatments. There is some evidence of effectiveness of pharmacological treatments for anxiety disorders in children and young people, however, routine prescription is not recommended due to concerns about potential harm

Fungal vaccines and immunotherapeutics: current concepts and future challenges

Purpose of review The remarkable advances in modern medicine have paradoxically resulted in a rapidly expanding population of immunocompromised patients displaying extreme susceptibility to life-threatening fungal infections. There are currently no licensed vaccines, and the prophylaxis and therapy of fungal infections in at-risk individuals remains challenging, contributing to undesirable mortality and morbidity rates. The design of successful antifungal preventive approaches has been hampered by an insufficient understanding of the dynamics of the host-fungus interaction and the mechanisms that underlie heterogenous immune responses to vaccines and immunotherapy. Recent findings Recent advances in proteomics and glycomics have contributed to the identification of candidate antigens for use in subunit vaccines, novel adjuvants, and delivery systems to boost the efficacy of protective vaccination responses that are becoming available, and several targets are being exploited in immunotherapeutic approaches. Summary We review some of the emerging concepts as well as the inherent challenges to the development of fungal vaccines and immunotherapies to protect at-risk individuals.ThisworkwassupportedbytheNorthernPortugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (contracts IF/00735/ 2014 to A.C., and SFRH/BPD/96176/2013 to C.C).info:eu-repo/semantics/publishedVersio

Low intensity treatment for clinically anxious youth: a randomised controlled comparison against face-to-face intervention

Methods to deliver empirically validated treatments for anxious youth that require fewer therapist resources (low intensity) are beginning to emerge. However, the relative efficacy of low-intensity treatment for youth anxiety against standard face-to-face delivery has not been comprehensively evaluated. Young people aged 6–16 years with a primary anxiety disorder (N = 281) were randomly allocated to treatment delivered either face-to-face or in a low-intensity format. Face-to-face treatment comprised ten, 60-min sessions delivered by a qualified therapist. Low intensity comprised information delivered in either printed (to parents of children under 13) or electronic (to adolescents aged 13 +) format and was supported by up to four telephone sessions with a minimally qualified therapist. Youth receiving face-to-face treatment were significantly more likely to remit from all anxiety disorders (66%) than youth receiving low intensity (49%). This difference was reflected in parents’ (but not child) reports of child’s anxiety symptoms and life interference. No significant moderators were identified. Low intensity delivery utilised significantly less total therapist time (175 min) than face-to-face delivery (897 min) and this was reflected in a large mean difference in therapy costs ($A735). Standard, face-to-face treatment for anxious youth is associated with significantly better outcomes than delivery of similar content using low-intensity methods. However, the size of this difference was relatively small. In contrast, low-intensity delivery requires markedly less time from therapists and subsequently lower treatment cost. Data provide valuable information for youth anxiety services. Clinical trial registration information: A randomised controlled trial of standard care versus stepped care for children and adolescents with anxiety disorders; https://anzctr.org.au/; ACTRN12612000351819

Behavioural activation by mental health nurses for late-life depression in primary care: a randomized controlled trial

Background: Depressive symptoms are common in older adults. The effectiveness of pharmacological treatments and the availability of psychological treatments in primary care are limited. A behavioural approach to depression treatment might be beneficial to many older adults but such care is still largely unavailable. Behavioural Activation (BA) protocols are less complicated and more easy to train than other psychological therapies, making them very suitable for delivery by less specialised therapists. The recent introduction of the mental health nurse in primary care centres in the Netherlands has created major opportunities for improving the accessibility of psychological treatments for late-life depression in primary care. BA may thus address the needs of older patients while improving treatment outcome and lowering costs.The primary objective of this study is to compare the effectiveness and cost-effectiveness of BA in comparison with treatment as usual (TAU) for late-life depression in Dutch primary care. A secondary goal is to explore several potential mechanisms of change, as well as predictors and moderators of treatment outcome of BA for late-life depression. Methods/design: Cluster-randomised controlled multicentre trial with two parallel groups: a) behavioural activation, and b) treatment as usual, conducted in primary care centres with a follow-up of 52 weeks. The main inclusion criterion is a PHQ-9 score > 9. Patients are excluded from the trial in case of severe mental illness that requires specialized treatment, high suicide risk, drug and/or alcohol abuse, prior psychotherapy, change in dosage or type of prescribed antidepressants in the previous 12 weeks, or moderate to severe cognitive impairment. The intervention consists of 8 weekly 30-min BA sessions delivered by a trained mental health nurse. Discussion: We expect BA to be an effective and cost-effective treatment for late-life depression compared to TAU. BA delivered by mental health nurses could increase the availability and accessibility of non-pharmacological treatments for late-life depression in primary care. Trial registration: This study is retrospectively registered in the Dutch Clinical Trial Register NTR6013on August 25th 2016. © 2017 The Author(s)

Improving mental health and social participation outcomes in older adults with depression and anxiety: Study protocol for a randomised controlled trial

Background Increasing both the frequency and quality of social interactions within treatments for anxiety and depressive disorders in older adults may improve their mental health outcomes and quality of life. This study aims to evaluate the clinical efficacy and cost utility of an enhanced cognitive behavioural therapy (CBT) plus social participation program in a sample of older adults with depression and/or anxiety. Methods A total of 172 community-dwelling adults aged 65 years or older with an anxiety and/or depressive disorder will be randomly allocated to either an enhanced CBT plus social participation program (n = 86) or standard CBT (n = 86). Both treatments will be delivered during 12 weekly individual sessions utilising structured manuals and workbooks. Participants will be assessed at pre-treatment, post-treatment, and 12-month follow-up. The primary outcome evaluates mean change in clinician-rated diagnostic severity of anxiety and depressive disorders from baseline to post-treatment (primary endpoint) based on a semi-structured diagnostic interview. Secondary outcomes evaluate changes in symptomatology on self-report anxiety and depression measures, as well as changes in social/community participation, social network, and perceived social support, loneliness, quality of life, and use of health services. Economic benefits will be evaluated using a cost-utility analysis to derive the incremental cost utility ratios for the enhanced CBT program. Discussion Outcomes from this study will provide support for the establishment of improved psychosocial treatment for older adults with anxiety and/or depression. Study outcomes will also provide health systems with a clear means to reduce the impact of poor emotional health in older age and its associated economic burden. In addition to the empirical validation of a novel treatment, the current study will contribute to the current understanding of the role of social participation in older adult wellbeing

Aspectos económicos y ambientales de la producción de hidrógeno en la provincia de Córdoba, a partir de recursos eólicos

En este trabajo se presenta la Evaluación Económica y Ambiental del proyecto de instalación de un parque eólico en la provincia de Córdoba con fines de producción de hidrógeno. El potencial de hidrógeno eólico se analiza para cada departamento de la provincia, considerando los requerimientos energéticos del electrolizador y el factor de capacidad de los sitios analizados. Se analizaron cuatro aspectos del sistema: la evaluación del recurso eólico, el análisis del costo de producción de hidrógeno vía electrólisis, los requerimientos de energía eólica anual para producir hidrógeno y la evaluación de impacto ambiental del proyecto. Para ello se modela una planta que genera una potencia nominal de 60 MW. A partir del costo modelado de producción de la energía, se determina el de producción de hidrógeno. El presente análisis contribuirá a definir los desafíos y oportunidades para la producción de hidrógeno/eólico, que definirán una futura economía del hidrógeno.This paper presents the Economic and Environmental Project evaluation for installation of a wind farm in the province of Cordoba for the purpose of hydrogen production. The potential of hydrogen wind is analyzed for each department province, considering the energy requirements of the electrolyzer and the capacity factor of samples analyzed. We analyzed four aspects of system: hydrogen resource assessment, cost analysis of hydrogen production via electrolysis, wind energy requirements to produce hydrogen and annual assessment project's environmental impact. For this purpose a plant that generates a nominal power of 60 MW was modeled. From a model of cost production of energy the cost production of hydrogen was determined. This analysis should help to define the challenges and opportunities for the production of hydrogen / wind, defining a future hydrogen economy.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES