“At Home” In Georgia: The Hidden Danger of Registering to do Business in Georgia

Georgia law prohibits any foreign corporation—a corporation with an originating registration initiated in a state other than Georgia—from transacting business in the state until it obtains a certificate of authority from the Georgia Secretary of State. Attorneys advise foreign corporations to register as a matter of course, and business owners readily comply. Georgia is not unique in its registration requirement. Every state in the union has enacted such a statute. But very few states require a foreign corporation to forfeit the guarantees of due process as a condition for transacting business in the state. Georgia is one of them. In this article, the authors discuss the pitfalls of the current state of Georgia law, noting that it likely violates federal law

Sedatives and Analgesics Given to Infants in Neonatal Intensive Care Units at the End of Life

To describe the administration of sedatives and analgesics at the end of life in a large cohort of infants in North American neonatal intensive care units (NICUs)

Pharmacokinetics of Clindamycin in Obese and Nonobese Children

ABSTRACT Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size. The final model included TBW and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (liters/hour) = 13.8 × (TBW/70) 0.75 × [PMA 2.83 /(39.5 2.83 +PMA 2.83 )]; volume of distribution ( V ) was associated with TBW, albumin (ALB), and alpha-1 acid glycoprotein (AAG): V (liters) = 63.6 × (TBW/70) × (ALB/3.3) −0.83 × (AAG/2.4) −0.25 . After accounting for differences in TBW, obesity status did not explain additional interindividual variability in model parameters. Our findings support TBW-based dosing for obese and nonobese children

Vancomycin Cerebrospinal Fluid Pharmacokinetics in Children with Cerebral Ventricular Shunt Infections

This study described the cerebrospinal fluid (CSF) exposure of vancomycin in 8 children prescribed intravenous vancomycin therapy for cerebral ventricular shunt infection. Vancomycin CSF concentrations ranged from 0.06 to 9.13 mg/L and the CSF: plasma ratio ranged from 0 to 0.66. Two children out of three with a staphylococcal CSF infection had CSF concentrations > minimal inhibitory concentration at the end of the dosing interval

Pharmacokinetics and Safety of Fluconazole in Young Infants Supported with Extracorporeal Membrane Oxygenation

Candida infections are a leading cause of infectious disease-related death in infants supported with extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK), thus standard fluconazole dosing in children on ECMO may result in suboptimal drug exposure. This study determined the PK of fluconazole in infants on ECMO

Mapping policies and programmes: the use of GIS to communicate spatial relationships in England

It has long been acknowledged that there is a gap between the advancement of GIS in the research field and its application in planning practice. This paper demonstrates the potential for employing simple GIS mapping overlays as a way of communicating complex planning issues in a ‘language’ that is easily understandable and effective at stimulating policy debate, critical thinking and learning. The analysis focuses on capturing the synergies and conflicts in two key planning challenges in England, progrowth and housing delivery agendas. In a political context where spatial evidencebased policymaking has been eroded in recent years, the analysis demonstrates the need for policymakers to ‘think spatially, act spatially’ when developing different policies and programmes. The paper concludes that only by making spatial relationships of policies and programmes explicit in a manner that is easily understood by a range of actors, can different spatial scenarios and metaphors of future opportunities and challenges be developed to inform long-range development and planning

Geomorphic and stratigraphic evidence for an unusual tsunami or storm a few centuries ago at Anegada, British Virgin Islands

© The Author(s), 2010. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Natural Hazards 63 (2012): 51-84, doi:10.1007/s11069-010-9622-6.Waters from the Atlantic Ocean washed southward across parts of Anegada, east-northeast of Puerto Rico, during a singular event a few centuries ago. The overwash, after crossing a fringing coral reef and 1.5 km of shallow subtidal flats, cut dozens of breaches through sandy beach ridges, deposited a sheet of sand and shell capped with lime mud, and created inland fields of cobbles and boulders. Most of the breaches extend tens to hundreds of meters perpendicular to a 2-km stretch of Anegada’s windward shore. Remnants of the breached ridges stand 3 m above modern sea level, and ridges seaward of the breaches rise 2.2–3.0 m high. The overwash probably exceeded those heights when cutting the breaches by overtopping and incision of the beach ridges. Much of the sand-and-shell sheet contains pink bioclastic sand that resembles, in grain size and composition, the sand of the breached ridges. This sand extends as much as 1.5 km to the south of the breached ridges. It tapers southward from a maximum thickness of 40 cm, decreases in estimated mean grain size from medium sand to very fine sand, and contains mud laminae in the south. The sand-and-shell sheet also contains mollusks—cerithid gastropods and the bivalve Anomalocardia—and angular limestone granules and pebbles. The mollusk shells and the lime-mud cap were probably derived from a marine pond that occupied much of Anegada’s interior at the time of overwash. The boulders and cobbles, nearly all composed of limestone, form fields that extend many tens of meters generally southward from limestone outcrops as much as 0.8 km from the nearest shore. Soon after the inferred overwash, the marine pond was replaced by hypersaline ponds that produce microbial mats and evaporite crusts. This environmental change, which has yet to be reversed, required restriction of a former inlet or inlets, the location of which was probably on the island’s south (lee) side. The inferred overwash may have caused restriction directly by washing sand into former inlets, or indirectly by reducing the tidal prism or supplying sand to post-overwash currents and waves. The overwash happened after A.D. 1650 if coeval with radiocarbon-dated leaves in the mud cap, and it probably happened before human settlement in the last decades of the 1700s. A prior overwash event is implied by an inland set of breaches. Hypothetically, the overwash in 1650–1800 resulted from the Antilles tsunami of 1690, the transatlantic Lisbon tsunami of 1755, a local tsunami not previously documented, or a storm whose effects exceeded those of Hurricane Donna, which was probably at category 3 as its eye passed 15 km to Anegada’s south in 1960.The work was supported in part by the Nuclear Regulatory Commission under its project N6480, a tsunami-hazard assessment for the eastern United States

Inferring the Transcriptional Landscape of Bovine Skeletal Muscle by Integrating Co-Expression Networks

Background: Despite modern technologies and novel computational approaches, decoding causal transcriptional regulation remains challenging. This is particularly true for less well studied organisms and when only gene expression data is available. In muscle a small number of well characterised transcription factors are proposed to regulate development. Therefore, muscle appears to be a tractable system for proposing new computational approaches. Methodology/Principal Findings: Here we report a simple algorithm that asks "which transcriptional regulator has the highest average absolute co-expression correlation to the genes in a co-expression module?" It correctly infers a number of known causal regulators of fundamental biological processes, including cell cycle activity (E2F1), glycolysis (HLF), mitochondrial transcription (TFB2M), adipogenesis (PIAS1), neuronal development (TLX3), immune function (IRF1) and vasculogenesis (SOX17), within a skeletal muscle context. However, none of the canonical pro-myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6 and MEF2C) were linked to muscle structural gene expression modules. Co-expression values were computed using developing bovine muscle from 60 days post conception (early foetal) to 30 months post natal (adulthood) for two breeds of cattle, in addition to a nutritional comparison with a third breed. A number of transcriptional landscapes were constructed and integrated into an always correlated landscape. One notable feature was a 'metabolic axis' formed from glycolysis genes at one end, nuclear-encoded mitochondrial protein genes at the other, and centrally tethered by mitochondrially-encoded mitochondrial protein genes. Conclusions/Significance: The new module-to-regulator algorithm complements our recently described Regulatory Impact Factor analysis. Together with a simple examination of a co-expression module's contents, these three gene expression approaches are starting to illuminate the in vivo transcriptional regulation of skeletal muscle development

A Cell Cycle Role for the Epigenetic Factor CTCF-L/BORIS

CTCF is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation. CTCF-like, or BORIS, is thought to antagonise CTCF and has been found in normal testis, ovary and a large variety of tumour cells. The cellular function of BORIS remains intriguing although it might be involved in developmental reprogramming of gene expression patterns. We here unravel the expression of CTCF and BORIS proteins throughout human epidermis. While CTCF is widely distributed within the nucleus, BORIS is confined to the nucleolus and other euchromatin domains. Nascent RNA experiments in primary keratinocytes revealed that endogenous BORIS is present in active transcription sites. Interestingly, BORIS also localises to interphase centrosomes suggesting a role in the cell cycle. Blocking the cell cycle at S phase or mitosis, or causing DNA damage, produced a striking accumulation of BORIS. Consistently, ectopic expression of wild type or GFP- BORIS provoked a higher rate of S phase cells as well as genomic instability by mitosis failure. Furthermore, downregulation of endogenous BORIS by specific shRNAs inhibited both RNA transcription and cell cycle progression. The results altogether suggest a role for BORIS in coordinating S phase events with mitosis