Prediction of Axial Pile Capacity Based on Case Histories

A data bank containing records from 1000 load tests on driven piles was set up. A computer program was developed to access the data bank and perform capacity analyses using a variety of methods. Analyses using six methods in clay and three in sand are reported here. For piles in clay, the capacities were predicted with tolerable accuracy by all methods, whereas the scatter was large for all methods for piles in sand. Generally, capacities were higher for tapered piles then indicated by the analyses. Tensile and compressive side shear capacities were essentially the same. The capacities of open and closed ended pipe piles were predicted with equal accuracy. Limits on side shear and tip stresses were helpful in reducing overpredictions

Effects of Supplementing High Levels of Cu, Co, Mn, and Zn After Calving on Productivity of Two-Year-Old Cows

When cow management, health and nutrition are adequate. supplementation of trace minerals at high levels is not beneficial and may in fact be detrimental to reproductive performance

Erythromycin improves gastric emptying half-time in adult cystic fibrosis patients with gastroparesis

AbstractBackgroundGastrointestinal manifestations are frequently encountered in cystic fibrosis patients. Gastroparesis evidenced by a variety of diagnostic methods has been described in patients with cystic fibrosis, predominantly in children and in individuals with advanced lung disease. The presence of gastroparesis in adult patients with different degrees of lung involvement and its response to the acute and chronic administration of macrolides have not been reported.MethodsUsing the University of Florida Cystic Fibrosis database we identified symptomatic patients who had gastroparesis confirmed by a prolonged half-time during gastric emptying scintigraphy.ResultsOf 86 cystic fibrosis patients, periodically followed in our institution, we found five who had classical symptoms and prolonged gastric emptying half-time. Age 25.2±8 years, 80% females, BMI 22±9 kg/m2, HbA1c 5.8±0.6 g/dl, FEV1 53.2±15% of predicted. Gastric emptying half-time was 191.4±91.4 min (range 100–300 min) and decreased to 12.2±6 min (range 5–20 min) after IV administration of erythromycin (p=0.043). Patients were followed up for 3±2.1 years. All patients but one, who was taking opiods, had good clinical response to PO macrolides.ConclusionsGastroparesis occurs in patients with cystic fibrosis, even in patients with relatively preserved lung function and in those without cystic-fibrosis related diabetes. Macrolides may be an effective therapy in cystic fibrosis patients with gastroparesis when administered acutely or chronically

Human liver glycogen phosphorylase inhibitors bind at a new allosteric site

AbstractBackground: Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target.Results: The binding site in human liver glycogen phosphorylase (HLGP) for a class of promising antidiabetic agents was identified crystallographically. The site is novel and functions allosterically by stabilizing the inactive conformation of HLGP. The initial view of the complex revealed key structural information and inspired the design of a new class of inhibitors which bind with nanomolar affinity and whose crystal structure is also described.Conclusions: We have identified the binding site of a new class of allosteric HLGP inhibitors. The crystal structure revealed the details of inhibitor binding, led to the design of a new class of compounds, and should accelerate efforts to develop therapeutically relevant molecules for the treatment of diabetes

Psychedelics Promote Structural and Functional Neural Plasticity.

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders

What do general practitioners know about ADHD? Attitudes and knowledge among first-contact gatekeepers: systematic narrative review

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood disorder with international prevalence estimates of 5 % in childhood, yet significant evidence exists that far fewer children receive ADHD services. In many countries, ADHD is assessed and diagnosed in specialist mental health or neuro-developmental paediatric clinics, to which referral by General (Family) Practitioners (GPs) is required. In such ‘gatekeeper’ settings, where GPs act as a filter to diagnosis and treatment, GPs may either not recognise potential ADHD cases, or may be reluctant to refer. This study systematically reviews the literature regarding GPs’ views of ADHD in such settings. Methods: A search of nine major databases was conducted, with wide search parameters; 3776 records were initially retrieved. Studies were included if they were from settings where GPs are typically gatekeepers to ADHD services; if they addressed GPs’ ADHD attitudes and knowledge; if methods were clearly described; and if results for GPs were reported separately from those of other health professionals. Results: Few studies specifically addressed GP attitudes to ADHD. Only 11 papers (10 studies), spanning 2000–2010, met inclusion criteria, predominantly from the UK, Europe and Australia. As studies varied methodologically, findings are reported as a thematic narrative, under the following themes: Recognition rate; ADHD controversy (medicalisation, stigma, labelling); Causes of ADHD; GPs and ADHD diagnosis; GPs and ADHD treatment; GP ADHD training and sources of information; and Age, sex differences in knowledge and attitudes. Conclusions: Across times and settings, GPs practising in first-contact gatekeeper settings had mixed and often unhelpful attitudes regarding the validity of ADHD as a construct, the role of medication and how parenting contributed to presentation. A paucity of training was identified, alongside a reluctance of GPs to become involved in shared care practice. If access to services is to be improved for possible ADHD cases, there needs to be a focused and collaborative approach to training

The observed state of the water cycle in the early twenty-first century

Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 28 (2015): 8289–8318, doi:10.1175/JCLI-D-14-00555.1.This study quantifies mean annual and monthly fluxes of Earth’s water cycle over continents and ocean basins during the first decade of the millennium. To the extent possible, the flux estimates are based on satellite measurements first and data-integrating models second. A careful accounting of uncertainty in the estimates is included. It is applied within a routine that enforces multiple water and energy budget constraints simultaneously in a variational framework in order to produce objectively determined optimized flux estimates. In the majority of cases, the observed annual surface and atmospheric water budgets over the continents and oceans close with much less than 10% residual. Observed residuals and optimized uncertainty estimates are considerably larger for monthly surface and atmospheric water budget closure, often nearing or exceeding 20% in North America, Eurasia, Australia and neighboring islands, and the Arctic and South Atlantic Oceans. The residuals in South America and Africa tend to be smaller, possibly because cold land processes are negligible. Fluxes were poorly observed over the Arctic Ocean, certain seas, Antarctica, and the Australasian and Indonesian islands, leading to reliance on atmospheric analysis estimates. Many of the satellite systems that contributed data have been or will soon be lost or replaced. Models that integrate ground-based and remote observations will be critical for ameliorating gaps and discontinuities in the data records caused by these transitions. Continued development of such models is essential for maximizing the value of the observations. Next-generation observing systems are the best hope for significantly improving global water budget accounting.This research was funded by multiple grants from NASA’s Energy and Water Cycle Study (NEWS) program.2016-05-0

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors