Determining how atmospheric carbon dioxide concentrations have changed during the history of the Earth

The reconstruction of ancient atmospheric carbon dioxide concentrations is essential to understanding the history of the Earth and life. It is also an important guide to identifying the sensitivity of the Earth system to this greenhouse gas and, therefore, constraining its future impact on climate. However, determining the concentration of CO2 in ancient atmospheres is a challenging endeavour requiring the application of state-of-the-art analytical chemistry to geological materials, underpinned by an understanding of photosynthesis and biochemistry. It is truly an interdisciplinary challenge

Current problems in the clinical physiology of the parathyroid and thyroid glands

Contemporary advances continue to develop in our understanding of the fundamental physiology of the control of secretion by the parathyroid and thyroid glands. The discovery of thyrocalcitonin and the early research on its mechanisms of action gives promise of defining many aspects of parathyroid control which have been obscure until now.Appreciation of central nervous system mechanisms influencing thyroid secretion and sensitive techniques for thyrotropin measurement give promise of continued development in understanding thyroid secretion control and the secretion disorders that commonly occur clinically. Direct, obvious and valuable therapeutic advances have resulted from the fundamental approaches used in the study of these endocrine glands. Such practical applications can be expected to continue to occur in the future.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33333/1/0000730.pd

Lockheed Martin: Dealing with Dependence on a Single Customer

Lockheed Martin is a giant in the aerospace and defense industry, and obtains more than four fifths of its revenues from governments for national defense. Budget deficits have caused the United States and other governments to carefully evaluate the amount they allocate to defense, and sharp cuts are anticipated. What can Lockheed Martin do to deal with reductions in demand from its most important customer

Rates of psychotropic medicine prescribing in paediatric populations in Australian general practice from 2000-2016

General practitioner (GP) prescribing of psychotropic medicines to paediatric patients is increasing across countries, sparking the need for additional research into this field. We examined prescribing rates, GP and patient characteristics and indications associated with prescribing psychotropic medicines to paediatric patients in Australian general practice, using data from the Bettering the Evaluation and Care of Health (BEACH) program. We extracted all encounters with children aged 3 to 17 from 2000 to 2016. Psychotropic medicines were defined as those in the ATC codes N05 (Psycholeptics) and N06 (Psychoanaleptics). Of the 144,397 encounters, GPs prescribed 1829 psychotropic medicines to paediatric patients at an average rate of 1.16 prescriptions per 100 encounters (95% confidence interval 1.09–1.23). We found that the rate of psychotropic medicines prescribed to paediatric patients in Australian general practice increased. Patients who were adolescent, female, socio-economically disadvantaged or from an English-speaking background were significantly more likely to be prescribed a psychotropic medicine. GP practices in remote or regional areas and Australian graduate GPs were more likely to prescribe psychotropic medicines to paediatric patients. Depression, attention deficit hyperactivity disorder, anxiety and autism were the most common psychiatric indications managed with psychotropic medicines. Antidepressants, psychostimulants, benzodiazepines, antipsychotics and other psychotropic medicines were prescribed, signifying a high rate of off-label use. Sertraline was the most common psychotropic medicine prescribed, followed by fluoxetine and methylphenidate. Future studies involving data from other prescribers, e.g. paediatricians and psychiatrists, and studies linking prescribed medicines to their indications may widen our understanding of psychotropic medicine prescribing in Australian paediatric patients

Rigorous biochemical criteria for the diagnosis of pheochromocytoma

Based on urinary studies of patients with pheochromocytoma as compared to hypertensives considered to be without this tumor, rigorous biochemical criteria for diagnosis are proposed. Free catecholamines in 90% and metanephrine metabolites in 100% of the pheochromocytoma patients' urine samples exceeded the normal (hypertensive) values by more than 5 SD. No patient without pheochromocytoma has falsely positive values in both free catecholamine and metanephrine metabolite determinations. No patient with a pheochromocytoma had a urine sample negative for metanephrine metabolites. The combination of these studies has given excellent accuracy for definitive diagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33926/1/0000193.pd

PORTAL VENOUS CATECHOL AMINES IN PORTAL HYPERTENSION

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32177/1/0000233.pd

Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle

AbstractPKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD

Investcorp

Investcorp is a publicly traded global alternative asset management company headquartered in Manama, Bahrain. It manages a huge hedge fund, along with other assets. The case describes Investcorp’s history, investment strategies, and major competitors. The company has a highly aggressive growth strategy, but it is also facing the retirement of its CEO