Participants in phase 1 oncology research trials: are they vulnerable?

Phase 1 oncology trials involve risk and offer a relatively low prospect of benefit to participants. Some claim that participants constitute a vulnerable population requiring special protections. We undertook this study to determine whether phase 1 oncology trial participants have demographic and health status characteristics of a vulnerable population. We reviewed participant demographic and health status data from phase 1 trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute that began between 1991 and 2002 and from 11 previously published studies. Main outcome measures were median age, sex, race/ethnicity, performance status, previous therapy, educational achievement level, and health insurance coverage. Almost 10 000 participants in trials sponsored by the Cancer Therapy Evaluation Program had a median age of 57 years, 90% self-identified as white, 93% had near-normal performance status, 85% had some form of health insurance, and 92% had been previously treated for cancer; 20 000 individuals from published studies had comparable profiles. The demographic and health status characteristics of phase 1 oncology trial participants are not those of a conventional vulnerable population and suggest little reason to assume that, as a group, they have a compromised ability to understand information or to make informed and voluntary decisions.     

CCL25 increases thymopoiesis after androgen withdrawal

Although studies have demonstrated that androgen withdrawal increases thymic size, molecular mechanisms underlying this expansion remain largely unknown. We show that decreased androgen signaling leads to enhanced immigration of bone marrow T-cell precursors, as manifested by both an early increase of early thymic progenitors (ETP) and improved uptake of adoptively transferred quantified precursors into congenic castrated hosts. We provide evidence that the ETP niche is enhanced after androgen withdrawal by proliferation of UEA(+) thymic epithelial cells (TEC) and increased TEC production of CCL25, a ligand critical for ETP entry. Moreover, the greatest increase in CCL25 production is by UEA(+) TEC, linking function of this subset with the increase in ETP immigration. Furthermore, blockade of CCL25 abrogated the effects of castration by impairing ETP entry, retarding immature thymocyte development, limiting increase of thymic size, and impairing increase of thymopoiesis. Taken together, these findings describe a cohesive mechanism underlying increased thymic productivity after androgen withdrawal.     

Scourge of life or an economic lifeline? Public discourses on khat (Catha edulis) in Ethiopia

Until the turn of the 20th century, only the religious and political elite of the city of Harer in eastern Ethiopia chewed khat. Its consumption has since spread to all regions of Ethiopia and all social groups, irrespective of religious affiliation, gender category, and age bracket, have taken up the habit. In a few decades khat has been transformed from a shrub grown for domestic consumption to the region's predominant cash crop; from a substance chewed on religious and cultural occasions to a visible and pervasive social habit; from a product sold in local markets to the most profitable commodity, whose trade involves millions of farmers, traders, and other service providers in the Horn of Africa and the Arabian Peninsula. The growing importance of khat has engendered a heated national debate in Ethiopia concerning the legal status of the plant. Opponents contend that khat is a health hazard with deleterious socioeconomic consequences and seek a complete ban to curb its "evil influence" on the country's youth and future. Others oppose any policy that ignores khat's micro- and macroeconomic benefits. This article outlines the positions the protagonists in this debate have staked out, critically evaluates their merits, and concludes by urging a public discourse on how to use the prosperity that the khat industry has generated to engender a sustainable economic development.     

Sero-epizootiological investigation of infectious laryngotracheitis infection in commercial poultry of Plateau State,north central Nigeria

Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens with outbreaks resulting in high economic losses due to increased mortality and drop in egg production. This study reports a survey of ILT virus antibody conducted in nine local government areas (LGAs) of Plateau State involving 67 randomly selected commercial poultry flocks. In all, 938 sera were tested using the Agar Gel Immuno-diffusion (AGID) technique. Overall prevalence of 1.2% (N = 11) was recorded. ILT virus antibody was found in 2.5% (n = 9) and 7.1% (n = 2) of the tested sera from Jos South and Langtang North LGAs, respectively. No detectable ILT virus antibody was found from the other seven LGAs. This is the first report of ILT infection in poultry from the North central part of Nigeria. It is therefore recommended that the economic implication of ILT infection in Nigerian poultry population be conducted in order to know if vaccination should be adopted for control.     

Altered Response Dynamics and Increased Population Correlation to Tonal Stimuli Embedded in Noise in Aging Auditory Cortex

Age-related hearing loss (presbycusis) is a chronic health condition that affects one-third of the world population. One hallmark of presbycusis is a difficulty hearing in noisy environments. Presbycusis can be separated into two components: alterations of peripheral mechanotransduction of sound in the cochlea and central alterations of auditory processing areas of the brain. Although the effects of the aging cochlea in hearing loss have been well studied, the role of the aging brain in hearing loss is less well understood. Therefore, to examine how age-related central processing changes affect hearing in noisy environments, we used a mouse model (Thy1-GCaMP6s X CBA) that has excellent peripheral hearing in old age. We used in vivo two-photon Ca²⁺ imaging to measure the responses of neuronal populations in auditory cortex (ACtx) of adult (2–6 months, nine male, six female, 4180 neurons) and aging mice (15–17 months, six male, three female, 1055 neurons) while listening to tones in noisy backgrounds. We found that ACtx neurons in aging mice showed larger responses to tones and have less suppressed responses consistent with reduced inhibition. Aging neurons also showed less sensitivity to temporal changes. Population analysis showed that neurons in aging mice showed higher pairwise activity correlations and showed a reduced diversity in responses to sound stimuli. Using neural decoding techniques, we show a loss of information in neuronal populations in the aging brain. Thus, aging not only affects the responses of single neurons but also affects how these neurons jointly represent stimuli.SIGNIFICANCE STATEMENT Aging results in hearing deficits particularly under challenging listening conditions. We show that auditory cortex contains distinct subpopulations of excitatory neurons that preferentially encode different stimulus features and that aging selectively reduces certain subpopulations. We also show that aging increases correlated activity between neurons and thereby reduces the response diversity in auditory cortex. The loss of population response diversity leads to a decrease of stimulus information and deficits in sound encoding, especially in noisy backgrounds. Future work determining the identities of circuits affected by aging could provide new targets for therapeutic strategies.     

Khat in the Horn of Africa: Historical perspectives and current trends

Aim of the study

This article looks at the history of the expansion of khat consumption from the traditional chew regions to Western countries and assesses the implication of possible international control for its use and trade in the Horn of Africa.

Materials and methods

Ten months of initial field work in Ethiopia, three follow up field work, archival work in Ethiopia and Europe, as well as study of available relevant literature.

Results

The debut of khat in the West in the 1980s was initially greeted with disdain and indifference. Authorities dismissed it on grounds that the mode of consumption, chewing the leaves for an extended period of time to extract a miniscule amount of the active ingredient, would not be appealing to Western users. Following the Mogadishu debacle of 1993, as depicted in the movie Black Hawk Down, authorities in the West began to express concern that khat was a new drug of abuse. Its trade was increasingly linked with terrorism because of its association with immigrants from the traditional khat use countries in the Horn of Africa and the Arabian Peninsula. Amid hysteria and moral panic, many Western countries classified khat as a highly potent controlled substance, rendering its possession, cultivation, and trade illegal.

Conclusion

This article argues that more and more Western governments, out of panic rather than definitive evidence of harm, will be instituting national laws banning the leaves, but khat will not be placed under international control because the scientific evidence of harm is unlikely to rise to a critical mass that would justify its illegalization. States in the source countries would continue to tolerate khat because banning it would be disastrous from an economic and social welfare standpoint. Because of its ambiguous legal position and the unstable nature of its active ingredient, cathinone, khat would not be successfully commoditized as a global commodity or transformed into a highly concentrated illicit drug. In this situation, khat would continue to be chewed in the traditional-use areas of the Red Sea littoral marketed by local syndicates who work with a large network of petty commodity traders.     

Measurement of the rate of myelination using a fluorescent analogue of ceramide

Fluorescence digital imaging microscopy was used to investigate the process of myelin formation by Schwann cells in neuronal cocultures. The uptake of the fluorescent ceramide analogue N-[5-(5,7-dimethyl BODIPY™)- 1-pentanoyl]D-erythro-sphingosine (C₅-DMB-ceramide) and its return to the plasma membrane as the corresponding fluorescent sphingomyelin and galactocerebroside analogues were measured. Through observation of this process it was possible to determine the rate of lipid synthesis in myelin internodes. The highest rate of synthesis of fluorescent sphingomyelin and galactocerebroside analogues was observed between days 3 and 7 after induction of myelination. This rate was approximately 5-fold greater than the steady-state rate of synthesis in fully myelinated internodes and 10-fold higher than the rate observed prior to myelination. The internode diameter increased during the first 3 days of myelination, but this was followed by a reduction in diameter and then an increase until the myelin sheath formation was completed. Internodes were found to be heterogeneous in terms of lipid distribution, with fluorescence intensities ranging 5-fold in myelinating cultures. Additionally, the rate of lipid transport along the internode was slow since there was a quicker increase in fluorescence intensity near the cell body of the Schwann cell than near the nodes of Ranvier. The results show that fluorescence digital imaging microscopy can be used to study the process of myelin formation and to determine the rate of formation, lipid transport, and heterogeneity of the myelin membrane. J. Neurosci. Res. 49:497–507, 1997. © 1997 Wiley-Liss, Inc.     

The Clinical Implications of Fatty Pancreas: A Concise Review

Fatty pancreas is a newly recognized condition which is poorly investigated until today as compared to nonalcoholic fatty liver disease. It is characterized by pancreatic fat accumulation and subsequent development of pancreatic and metabolic complications. Association of fatty pancreas have been described with type 2 diabetes mellitus, acute and chronic pancreatitis and even pancreatic carcinoma. In this review article, we provide an update on clinical implications, pathogenesis, diagnosis, treatment and outcomes.