Osteoblastoma in the occipital bone: A case report of a rare tumor in the calvarium

Osteoblastomas infrequently occur in the calvarium, displaying a preference for temporal and frontal bones when it does. We present an unusual case of a large, expansile osteoblastoma in the occipital bone of a 23-year-old man who presented with a nontender lump at the back of his head. Initial computed tomography scan showed a large occipital bone mass, and after additional imaging, a gross total resection was performed. Histopathological examination revealed an osteoblastoma. Although these tumors are benign, overlapping imaging characteristics of lesions affecting the calvarium often present a diagnostic dilemma. This case emphasizes the importance of imaging in the management and work-up of these patients to decrease the risk of complications and assists surgeons in their preoperative planning

Genotoxicity profile of fexinidazole—a drug candidate in clinical development for human African trypanomiasis (sleeping sickness)

The parasitic disease human African trypanomiasis (HAT), also known as sleeping sickness, is a highly neglected fatal condition endemic in sub-Saharan Africa, which is poorly treated with medicines that are toxic, no longer effective or very difficult to administer. New, safe, effective and easy-to-use treatments are urgently needed. Many nitroimidazoles possess antibacterial and antiprotozoal activity and examples such as tinidazole are used to treat trichomoniasis and guardiasis, but concerns about toxicity including genotoxicity limit their usefulness. Fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining of public and pharmaceutical company databases, has the potential to become a short-course, safe and effective oral treatment, curing both acute and chronic HAT. This paper describes the genotoxicity profile of fexinidazole and its two active metabolites, the sulfoxide and sulfone derivatives. All the three compounds are mutagenic in the Salmonella/Ames test; however, mutagenicity is either attenuated or lost in Ames Salmonella strains that lack one or more nitroreductase(s). It is known that these enzymes can nitroreduce compounds with low redox potentials, whereas their mammalian cell counterparts cannot, under normal conditions. Fexinidazole and its metabolites have low redox potentials and all mammalian cell assays to detect genetic toxicity, conducted for this study either in vitro (micronucleus test in human lymphocytes) or in vivo (ex vivo unscheduled DNA synthesis in rats; bone marrow micronucleus test in mice), were negative. Thus, fexinidazole does not pose a genotoxic hazard to patients and represents a promising drug candidate for HAT. Fexinidazole is expected to enter Phase II clinical trials in 201

Einfluss einer kombinierten B-Vitamin- und Antioxidanziensupplementierung auf die ADMA-Plasmakonzentration bei Personen mit erhöhtem kardiovaskulären Risiko

[no abstract

A Physical Model of Moulin Evolution on the Greenland Ice Sheet

Nearly all proglacial water discharge from the Greenland Ice Sheet is routed englacially via moulins. Identification of these moulins in high-resolution imagery is a frequent topic of study, but the processes controlling how and where moulins form remain poorly understood. Because moulins may reasonably compose approximately 10-15% of the englacial-subglacial hydrologic system, the evolution and shape of moulins can alter both the timing and variability of meltwater inputs to the bed. This evolution can impact both the form of the subglacial hydrologic system and associated response of ice motion. Here, we develop a physical model of moulin formation and evolution to constrain the role of englacial processes in shaping the form and structure of the subglacial hydrologic system. Within this model, moulin geometry is controlled by a balance of viscous and elastic deformation and is dependent on that deformation, refreezing, and the dissipation of turbulent and sensible heat energy. All of which are dependent on the characteristics of the available supraglacial meltwater and the surrounding ice. We find moulin geometry is responsive to changes in these parameters over the course of hours to days, indicating that diurnal and multi-day variations in melt can substantially alter the geometry of a moulin and, consequently, the pressure-discharge relationship at the bed of the ice sheet. Therefore, there is no single moulin shape that can appropriately represent englacial storage across the Greenland Ice Sheet

A review of the tolerability of the candidate TB vaccine, MVA85A compared with BCG and Yellow Fever vaccines, and correlation between MVA85A vaccine reactogenicity and cellular immunogenicity

© 2012 Elsevier Ltd. All rights reservedBackground: The development of a new, more effective vaccine against tuberculosis (TB) for use in healthy and HIV-infected adults, children and infants, remains a global health priority. MVA85A is a candidate tuberculosis vaccine designed to enhance immunity to the existing vaccine, Bacillus Calmette-Guerin (BCG). MVA85A entered clinical trials in 2002 and has now progressed to Phase IIb proof-of-concept efficacy trials in infants and HIV-infected adults in Africa. Methods: A detailed analysis was conducted of the cumulative safety data of intradermal delivery of MVA85A in 112 healthy adult subjects in a series of open label, single arm, non-controlled, Phase I safety and immunogenicity clinical trials in the UK. The trials differed with respect to previous mycobacterial exposure, vaccine regime and dose. Objective safety measures (local reaction size and body temperature) were evaluated for correlations with adaptive antigen-specific immune responses. Results: All subjects in the combined mid-dose group developed a local reaction, of which 92% were mild, 8% were moderate and no reactions were severe. Around 90% of subjects in each group reported at least one systemic adverse event, most commonly headache, myalgia, malaise, feeling feverish, fatigue and arthralgia. Of all systemic adverse events in the combined mid-dose group, 96% were mild, 3% were moderate and 1% were severe (but none of these were judged to be vaccine-related). Pre-vaccination mycobacterial exposure did not affect the adverse event profile. The size of local reaction and frequency of systemic adverse events increased with MVA85A vaccine dose. There were no documented fevers in the low-dose group, whilst 3% of subjects in the combined mid-dose group and 21% in the high-dose group had documented fevers. Peak local reactions were larger after a second poxvirus vaccination, but other local and systemic adverse events were comparable to a single MVA85A vaccination. No severe systemic AEs or serious adverse events in any group were judged to be vaccine-related. Local AEs compared favourably to BCG vaccine-induced local AE and systemic AEs after MVA85A vaccination were comparable to those after the live viral Yellow Fever vaccine in similar populations. There were no correlations found between local reaction size or body temperature and adaptive immune responses (measured by ex vivo interferon gamma Enzyme Linked Immunospot). Conclusions: The candidate TB vaccine, MVA85A has been safely administered to over 100 healthy adults in the UK. Intradermal vaccination with MVA85A induced a transient, superficial reaction local to the injection site and mild short-lived viral symptoms. The local and systemic AE profile of MVA85A vaccination was comparable to published data of other intradermal vaccines and live viral vaccines respectively. Local reaction sizes and body temperature measurements did not correlate with the adaptive cellular immune response to MVA85A.Funded by charitable grants from Europe Aid; TBVAC (EU 6th Framework Programme); The Oxford Biomedical Research Centre and the Wellcome Trus

Some foundational and methodical problems of the empirical theory of literature

Kindt W. Some foundational and methodical problems of the empirical theory of literature. Poetics. 1981;10(4-5):483-513