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Precipitation regime change in Western North America: The role of Atmospheric Rivers.
Daily precipitation in California has been projected to become less frequent even as precipitation extremes intensify, leading to uncertainty in the overall response to climate warming. Precipitation extremes are historically associated with Atmospheric Rivers (ARs). Sixteen global climate models are evaluated for realism in modeled historical AR behavior and contribution of the resulting daily precipitation to annual total precipitation over Western North America. The five most realistic models display consistent changes in future AR behavior, constraining the spread of the full ensemble. They, moreover, project increasing year-to-year variability of total annual precipitation, particularly over California, where change in total annual precipitation is not projected with confidence. Focusing on three representative river basins along the West Coast, we show that, while the decrease in precipitation frequency is mostly due to non-AR events, the increase in heavy and extreme precipitation is almost entirely due to ARs. This research demonstrates that examining meteorological causes of precipitation regime change can lead to better and more nuanced understanding of climate projections. It highlights the critical role of future changes in ARs to Western water resources, especially over California
Harmonic analysis of measured initial geometric imperfections in large spiral welded carbon steel tubes
Integrating the promotion of physical activity within a smoking cessation programme: Findings from collaborative action research in UK Stop Smoking Services
Background: Within the framework of collaborative action research, the aim was to explore the feasibility of
developing and embedding physical activity promotion as a smoking cessation aid within UK 6/7-week National
Health Service (NHS) Stop Smoking Services.
Methods: In Phase 1 three initial cycles of collaborative action research (observation, reflection, planning,
implementation and re-evaluation), in an urban Stop Smoking Service, led to the development of an integrated
intervention in which physical activity was promoted as a cessation aid, with the support of a theoretically based
self-help guide, and self monitoring using pedometers. In Phase 2 advisors underwent training and offered the
intervention, and changes in physical activity promoting behaviour and beliefs were monitored. Also, changes in
clientsâ stage of readiness to use physical activity as a cessation aid, physical activity beliefs and behaviour and
physical activity levels were assessed, among those who attended the clinic at 4-week post-quit. Qualitative data
were collected, in the form of clinic observation, informal interviews with advisors and field notes.
Results: The integrated intervention emerged through cycles of collaboration as something quite different to
previous practice. Based on field notes, there were many positive elements associated with the integrated
intervention in Phase 2. Self-reported advisorsâ physical activity promoting behaviour increased as a result of
training and adapting to the intervention. There was a significant advancement in clientsâ stage of readiness to use physical activity as a smoking cessation aid.
Conclusions: Collaboration with advisors was key in ensuring that a feasible intervention was developed as an aid to smoking cessation. There is scope to further develop tailored support to increasing physical activity and
smoking cessation, mediated through changes in perceptions about the benefits of, and confidence to do physical activity
Between pebbles and organisms: Weaving autonomy into the Markov blanket
The free energy principle (FEP) purports to provide a single principle for the organizational dynamics of living systems, including their cognitive profiles. It states that for a system to maintain non-equilibrium steady-state with its environment it must minimise its free energy. It is said to be entirely scale-free, applying to anything from particles to organisms, and interactive machines, spanning from the abiotic to the biotic. Because the FEP is so general in its application, it is for this reason that one might wonder in what sense this framework captures anything specific to biological characteristics, if details at all. We take steps to correct for this here. We do so by taking up a distinct challenge that the FEP must overcome if it is to be of interest to those working in the biological sciences. We call this the pebble challenge: it states that the FEP cannot capture the organisational principles specific to biology, for its formalisms apply equally well to pebbles. We progress in solving the pebble challenge by articulating how the notion of âautonomy as precarious operational closureâ from the enactive literature can be unpacked within the FEP. This enables the FEP to delineate between the abiotic and the biotic; avoiding the pebble challenge that keeps it out of touch with the living systems we encounter in the world and is of interest to the sciences of life and mind
Genetics of Amyotrophic Lateral Sclerosis
La sclĂ©rose latĂ©rale amyotrophique (SLA) est la maladie des neurones moteurs la plus frĂ©quente, affectant 4-6 individus par 100,000 habitants Ă lâĂ©chelle mondiale. La maladie se caractĂ©rise par une faiblesse et une atrophie musculaire suite Ă la dĂ©gĂ©nĂ©rescence des neurones du cortex moteur, tronc cĂ©rĂ©bral et moelle Ă©piniĂšre. Les personnes atteintes dĂ©veloppent les premiers symptĂŽmes Ă lâĂąge adulte et la maladie progresse sur une pĂ©riode de trois Ă cinq ans. Il a Ă©tĂ© rĂ©pertoriĂ© quâenviron 10% des patients ont une histoire familiale de SLA; 90% des gens affectĂ©s le sont donc de façon sporadique. La dĂ©couverte il y a 19 ans de mutations dans le gĂšne zinc/copper superoxide dismutase (SOD1), prĂ©sentes dans 15-20% des cas familiaux de SLA et environ 2% du total des individus affectĂ©s, a Ă©tĂ© lâĂ©vĂ©nement dĂ©clencheur pour la dĂ©couverte de variations gĂ©nĂ©tiques responsables de la maladie. La recherche sur la gĂ©nĂ©tique de la SLA a connu une progression rapide ces quatre derniĂšres annĂ©es avec lâidentification de mutations dans de nouveaux gĂšnes. Toutefois, mĂȘme si certains de ces gĂšnes ont Ă©tĂ© dĂ©montrĂ©s comme rĂ©ellement liĂ©s Ă la maladie, la contribution dâautres gĂšnes demeure incertaine puisque les rĂ©sultats publiĂ©s de ceux-ci nâont pas, Ă ce jour, Ă©tĂ© rĂ©pliquĂ©s. Une portion substantielle de cas reste cependant Ă ĂȘtre gĂ©nĂ©tiquement expliquĂ©e, et aucun traitement Ă ce jour nâa Ă©tĂ© dĂ©montrĂ© comme Ă©tant efficace pour remĂ©dier, attĂ©nuer ou prĂ©venir la maladie.
Le but du projet de recherche de doctorat Ă©tait dâidentifier de nouveaux gĂšnes mutĂ©s dans la SLA, tout en Ă©valuant la contribution de gĂšnes nouvellement identifiĂ©s chez une importante cohorte multiethnique de cas familiaux et sporadiques. Les rĂ©sultats prĂ©sentĂ©s sont organisĂ©s en trois sections diffĂ©rentes. Dans un premier temps, la contribution de mutations prĂ©sentes dans le gĂšne FUS est Ă©valuĂ©e chez les patients familiaux, sporadiques et juvĂ©niles de SLA. PrĂ©cisĂ©ment, de nouvelles mutations sont rapportĂ©es et la proportion de mutations retrouvĂ©es chez les cas familiaux et sporadiques de SLA est Ă©valuĂ©e. De plus, une nouvelle mutation est rapportĂ©e dans un cas juvĂ©nile de SLA; cette Ă©tude de cas est discutĂ©e. Dans un deuxiĂšme temps, de nouvelles avenues gĂ©nĂ©tiques sont explorĂ©es concernant le gĂšne SOD1. En effet, une nouvelle mutation complexe est rapportĂ©e chez une famille française de SLA. De plus, la possibilitĂ© quâune mutation prĂ©sente dans un autre gĂšne impliquĂ© dans la SLA ait un impact sur lâĂ©pissage du gĂšne SOD1 est Ă©valuĂ©e. Finalement, la derniĂšre section explique la contribution de nouveaux gĂšnes candidats chez les patients atteints de SLA. SpĂ©cifiquement, le rĂŽle des gĂšnes OPTN, SIGMAR1 et SORT1 dans le phĂ©notype de SLA est Ă©valuĂ©.
Il est souhaitĂ© que nos rĂ©sultats combinĂ©s avec les rĂ©cents dĂ©veloppements en gĂ©nĂ©tique et biologie molĂ©culaire permettent une meilleure comprĂ©hension du mĂ©canisme pathologique responsable de cette terrible maladie tout en guidant le dĂ©ploiement de thĂ©rapies suite Ă lâidentification des cibles appropriĂ©es.Amyotrophic lateral sclerosis (ALS) is the most common of motor neuron diseases, affecting 4-6 individuals per 100,000 individuals worldwide. ALS is characterized by muscle weakness and atrophy caused by the degeneration of neurons located in the motor cortex, brain stem and spinal cord. This fatal disease generally has an adult onset and progresses over a three to five year period. While 10% of patients affected have a family history of the disease, 90% of cases do not and are considered sporadic. The finding of mutations in the zinc/copper superoxide dismutase gene (SOD1) gene 19 years ago in about 15-20% of familial ALS (FALS) patients and approximately 2% of overall cases developed the interest of identifying rare genetics variants causing the disease. The ALS research field experienced a rapid progression during the last four years as mutations in new genes have been identified. While mutations in some of those new genes have been clearly linked to ALS, the role of others is still questionable and so far has not been positively replicated in other populations. Importantly, a significant portion of cases still need to be genetically explained and, unfortunately, there is still no effective treatment to cure, attenuate or prevent the disease.
The aim of this Ph.D research project was to identify new ALS mutated genes while analysing the causative role of other newly identified genes in a large familial and sporadic ALS cohort of different origins. The results presented here are categorized into three different sections. First, the contribution of FUS mutations to familial, sporadic and juvenile ALS is analysed. Specifically, new FUS mutations are reported in ALS cases and the proportions of variants present in the tested familial and sporadic ALS cohorts are assessed. In addition, a new mutation is reported in a juvenile ALS patient, and this interesting case is discussed. Second, new genetic avenues are explored for the SOD1 gene. Precisely, a new and complex SOD1 mutation is reported in a French ALS family. Moreover, the possibility that other ALS mutated genes influence SOD1 splicing events is evaluated. Third, the contribution of new candidate genes is evaluated. Precisely, the contribution of OPTN, SIGMAR1 and SORT1 genes to the ALS phenotype is assessed.
Hopefully, our different findings combined with recent developments in genetics and molecular biology will permit a better understanding of the pathological mechanisms involved in the disease and will lead to the identification of the right targets in order to develop appropriate therapeutics for ALS patients
Genetic mapping of a modifier locus affecting hypertension in soluble guanylate cyclase α1 deficient mice
Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis.
Women with osteoporosis treated for 36 months with twice-yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis to investigate the timing and precise location of denosumab versus placebo effects in the hips. We analyzed clinical computed tomography scans from 80 female participants in FREEDOM, a randomized trial, wherein half of the study participants received subcutaneous denosumab 60âmg twice yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24, and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualized and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control and to display the results on a 3D average femur model. Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over 3 years. One-third of the increase came from increasing cortical density, and two-thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12% at key locations such as the lateral femoral trochanter versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months. Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures observed in denosumab-treated women at increased risk of fracture.This study was funded by Amgen Inc., Thousand Oaks, CA, USA. Cambridge Bone Group is supported by Arthritis Research UK, The Evelyn Trust, and Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.232
Ten Simple Rules for Getting Help from Online Scientific Communities
The increasing complexity of research requires scientists to work at the intersection of multiple fields and to face problems for which their formal education has not prepared them. For example, biologists with no or little background in programming are now often using complex scripts to handle the results from their experiments; vice versa, programmers wishing to enter the world of bioinformatics must know about biochemistry, genetics, and other fields.
In this context, communication tools such as mailing lists, web forums, and online communities acquire increasing importance. These tools permit scientists to quickly contact people skilled in a specialized field. A question posed properly to the right online scientific community can help in solving difficult problems, often faster than screening literature or writing to publication authors. The growth of active online scientific communities, such as those listed in Table S1, demonstrates how these tools are becoming an important source of support for an increasing number of researchers.
Nevertheless, making proper use of these resources is not easy. Adhering to the social norms of World Wide Web communicationâloosely termed ânetiquetteââis both important and non-trivial.
In this article, we take inspiration from our experience on Internet-shared scientific knowledge, and from similar documents such as âAsking the Questions the Smart Wayâ and âGetting Answersâ, to provide guidelines and suggestions on how to use online communities to solve scientific problems
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