Susceptibility Research Articles

Genomics and Proteomics in Epidemiology

ven a brief perusal of current journals and meeting programs shows the vibrant life and potential of in the 21st century. Even if no new epidemiologic methods or technologies were developed, we could still make major contributions to understanding the etiology of the many diseases that are underresearched, or are still poorly understood despite substantial research, or are newly emerging. There is still plenty to be achieved with the well-designed questionnaire, the optimization of response and follow-up rates, and the 2 X 2 table. However, this is also a time of rapid development of technologies that will facilitate epidemiologic research. Epidemiologists have always been opportunistic in the adoption of new technologies for exposure assessment or outcome definition, and many new tools have already become available in the last 25 years. In the early 1980s, Perera and Weinstein' extended the term molecular epidemiology from the study of characterization of infectious organisms to the study of exposure and suscep tibility relevant to cancer and other chronic diseases. For some exposure-disease rela tions, methods of exposure assessment have identified the etiologic culprits in a rogues' gallery of suspects-such as the association of human papillomaviruses with cervical cancer, after observational studies had strongly implicated aspects of sexual behavior as increasing risk, and seroepidemiologic studies had suggested associations with a number of other sexually transmitted infections. Similarly, the identification of somatic mutations characteristic of exposure to aflatoxin in the TP53 gene in liver tumors provided a crucial piece of evidence to bolster a previously disputed set of ecologic and dietary studies associating aflatoxin exposure with liver cancer risk.2 Application of novel biomarkers as measures of exposure, or to assess the misclassification associated with other methods, will offer new opportunities to define exposure-disease relations. Much of the rest of this article discusses the scale and accuracy of new methods to assess between-person inherited genetic variation. However, we (and the people who fund our work) should not forget the need to better assess environmental exposures, because these are often modifiable and remediable, unlike our inherited genotypes. In the last decade, the development of individual biomarkers has been revolution ized by -omics approaches. The suffix -omic is from the Greek meaning or every; thus, genomics is the study of all of the genes in an organism. The first genomic technology in widespread use was the expression array, which enabled the study of the degree of expression of all known genes in an organism (sometimes referred to as the transcriptome). The major application in large-scale human studies has been the analysis of tumors. The ability to measure the transcriptome of individual tumors permitted the description of different patterns of variation in gene expression within tumor types previously thought to be a single type based on conventional histology. These patterns have been shown to be associated with prognosis3 and treatment response.4 For some tumors, the different patterns may derive from different cells of origin.5

Investigation of magnetic properties at low temperatures on permanent magnetic N d60Al10Fe20Co10 bulk metallic glass

The temperature dependence of magnetic properties for Nd60Al10 Fe20Co10 bulk metallic glass is investigated. The re sults indicate that th e Nd60Al10Fe20Co10 bulk metallic gla ss exhibits permanen t magnetic behaviour at room temperature. The coercive force and the shape of hy steresis loops change markedly when temperature decreases. AC magnetic susceptib ility is measured and a peak at about 18K is found. The peak moves torwards high temperatures when the frequency is increased. This indicates that there are spi n glass structures in the bulk metallic glass.

Effect of scandium and titanium–boron on grain refinement and hot cracking of aluminium alloy 7108

The effect of scandium and titanium–boron (Tibor) additions on the solidification behaviour of castings and welds of aluminium alloy 7108 has been investigated. A circular patch test was adopted to evaluate the effects of these elements on the hot cracking suscepti bility of welds made on cast coupons treated with different grain refiner additions. It was observed that grain size, as well as cracking susceptibility, decreased with increasing amounts of scandium and that hot cracking was completely eliminated at scandium additions above 0·25 wt-%. A more pronounced grain refining effect in welds was observed with Tibor and, in addition, no hot cracking was observed with Tibor additions as low as 0·02 wt-%Ti (0·004 wt-%B). Castings, however, were more effectively grain refined with scandium, achieving a finer grain size than with Tibor.

Eolian evidence from the Chinese Loess Plateau: the onset of the Late Cenozoic Great Glaciation in the Northern Hemisphere and Qinghai-Xizang Plateau uplift forcing

On the basis of a newly-constructed record of magnetic susceptibility (SUS) and the depositional rate change of eolian loess-red clay sequences in the last 7.2 Ma BP from the hea Plateau, together with a cornperison of a record of °18O values from the equatorial East Pacific Ocean and eolian Quartz flux variations fmm the North Pacific Ocean, the evolutiomuy process of the Late Cenozoic Great Glaciation in the Northern Hemisphere can be divided into three stages: the arrival stage around 7.2–3.4 Ma BP, the initial stage at about 3.4—2.6 Ma BP, and the Great Ice Age since 2.6 Ma BP. The evolution of the East Asian monsoon is characterized by paid winter and summer monsoons, and it is basically composed of the initial stage of weak winter and summer monsoons, the transitional stage of simultaneous increase in intensity of winter and summer monsoons, and the prevailing stage of strong winter and week summer monsoons, or weak winter and strong summer monsoons. The Late Cenowic global tectonic uplift, paaicdarly the Qinghai-Xizang Plateau uplift and the associated CO2 concentration variation, controls the dng processes of the onset of Great Glaciation and the long-term changes of East Asian monsoom climate in the Northern Hemisphere to a large extent. The accelerating uplift of the Qinghai-Xizang Plateau between 3.4 and 2.6 Ma BP provided an important driving force to global climiatic change.

Pneumococcal Vaccination in the United States: Current Recommendations and Strategies to Improve Vaccination Coverage

S treptococcus pneumoniae is the most commonly identified cause of lower respirato1y tract infections, a common cause of sepsis and meningitis, and a major cause of morbidity and mortality worldwide. In the United States, pneumococcal infections may cause more deaths each year than any other vaccine preventable disease (1) . Mortality for pneumococcal pneumonia with bacteremia is about 20% among adults and as high as 40% among the elderly. In spite of the impressive public health burden of pneumococcal disease, vaccines aga inst pneumococcus re main largely underutilized. The recent emergence of drug-resistant S pneumoniae places a new emphasis on the need for vaccination against pneumococcal infections. Clinically significant pneumococcal isolates with decreased susceptib ili ty to penicillin were first identified in the United States in the 1970s but were uncommon until the early l 990s (2). Data from active, populationbased surveillance in the United States during 1995 and 1996 show that in some areas over 20% and 10% of isolates were no longer susceptible to penicillin and cefotaxime, respectively (3). Concurrent with the emergence of strains res istant to beta-lactams, pneumococci with decreased susceptibility to other classes of antimicrobial agents also have become more prevalent. The emergence of resistant strains makes empirical treatment decisions more cha llenging for clin icians; as pneumococcal infections become more difficult to treat, assuring that patients at risk receive adequate vaccination is more important than ever.

Simulations to Evaluate HIV Vaccine Trial Designs

Many HIV vaccine trials have been proposed to evaluate susceptibility of individuals. However, vac cines may also affect an epidemic's course at the population level by altering the infectiousness of vaccinated individuals who become infected. A vac cine trial design that does not estimate both suscep tibility and infectiousness might reject a proposed vaccine that is capable of halting the HIV epidemic. We describe a vaccine trial design called the Retro spective Partner Trial (RPT), which can quantify vaccine effects on both susceptibility and infectious ness. We describe HIVSIM, a simulation environ ment that generates simulated populations and al lows for empirical evaluation of the statistical power of the RPT. HIVSIM explicitly models a number of factors which influence transmission and preva lence, and which have proven difficult to model us ing standard models. These factors include the infec tion stage of infected individuals, partnership selec tion, the duration of partnerships and concurrence, and transmission of HIV. The simulation analysis indicates that the RPT design has substantially greater statistical power for identifying vaccines which, in spite of exhibiting poor protection against infection, are nonetheless capable of halting the HIV epidemic by substantially reducing the infectious ness of vaccinated individuals who become infected.

H-2 genes and resistance to infection with Heligmosomoides polygyrus in selectively bred mice

Two lines of mice bred selectively for high resistance (RH) and susceptibility (SL) to reinfection with Heligmosomoides polygyrus demonstrated disparate levels of resistance to infection but did not differ in the frequency of H-2 antigens when assayed with antisera against antigens of 5 inbred H-2 haplotypes. The selected RH and SL mice were crossbred with, and backcrossed to, the inbred CBA mice. F1 mice from crosses between RH and CBA were as resistant to reinfection with H. polygyrus as their RH parents. F1 mice from crosses between SL and CBA were more resistant than either of their parents. BC1 mice were either positive or negative for H-2 antigens from RH and SL mice. BC1 mice that were positive for RH H-2 antigens were more resistant to infection than their negative littermates, but they were significantly more susceptible to infection with H. polygyrus than their F1 parents. These results demonstrated that genes within and mapped outside H-2 complex control the level of resistance to H. polygyrus in the selected mice and suggested that selective breeding of mice for resistance fixed the relevent genes in and outside the H-2 complex.

Influence of Aluminum Grain Boundary Misorientation on Penetration by Gallium

Materials that undergo intergranular degradation processes, such as Stress Corrosioi Cracking (SCC) or certain types of Liquid Metal Embrittlement (LME), show variations in sus ceptibility with grain boundary character Samples with high fractions of “special” boundaries i.e. highly periodic boundaries with low-S Coincidence Site Lattices (CSL), exhibit higher resis tance to these types of attack[l,2]. Very useful comparisons have been drawn between low periodicity boundaries and high-periodicity boundaries; however, few attempts have been mad to date to explain variations in behavior between various “general” boundaries. The presen study employs the LME of aluminum by liquid gallium in an attempt to elucidate the variation in structure and properties of general grain boundaries.

Petrophysical investigations in the Southern Bohemian Massif (Austria): Data-acquisition, -organisation and-interpretation

The petrophysical parameters Density (p), Susceptibility (SUS), as well as Natural Remanent Magnetisation (NRM) and Koenigsberger ratio (Qn) were measured on approx. 2600 core samples (magmatic and a few metamorphic rocks) from the Southern Bohemian Massif. These and associated data have been organized into primary and subsidiary dBASE IV databases. The quantity and kind of information now available through the databases are described.

Continuous surveillance of antibiotic resistant Neisseria gonorrhoeae: A tool to forewarn emerging trends in resistance.

A DE CREASE IN THE IN CI DENCE OF GON OR RHOEA cases has been re ported in the past 20 years by sev eral west ern coun tries (1-4). Sta tis tics in Can ada show this de cline start ing in the early 1980s, from a peak of 56,336 cases re ported in 1981 to an es ti mated 4500 cases in 1994, a 92% de crease in the to tal number of cases over a 13year pe riod. Al though the in ci dence of gon or rhoea cases is drop ping, there is a con stant in crease in the number of re sis tant iso lates that par al lels the in tro duc tion of new an ti bi ot ics. The abil ity of the gono coc cus to de velop re sis tance to an ti bi ot ics has been shown re peat edly over the years. As early as 1976, chro mo somally me di ated re sis tance to peni cil lin and later mul ti ple re sis tance to other an ti bi ot ics were re ported along with plas mid me di ated re sis tance to peni cil lin (1,5-7). As a re sult, tet ra cy cline was cho sen as the al ter na tive treat ment for penicillinaseproducing Neis se ria gon or rhoeae (PPNG) un til tet ra cy cline re sis tant strains were char ac ter ized in the United States in 1985 and later re ported world wide (8-11). Cur rently, thirdgeneration cephalosporins and qui nolones are the most ef fec tive anti microbials against gon or rhoea (12,13). The de tec tion of these sus cep ti bil ity changes and the ac cu rate pre dic tion of up com ing re sis tance trends are pos si ble only if a con tinu ous sur veil lance pro gram is in ef fect.

Effects of Plant Epicuticular Lipids on Insect Herbivores

The primary role of epicuticular lipids on aerial plant surfaces is prevention of water loss, but their species-specific chemical composition and their vari­ able crystal morphology suggest other ecological functions. Among these functions is mediation of interactions between plants and insect herbivores. Epicuticular lipid extracts and individual lipid components enhance or deter oviposition, movement, and feeding. The physical structure of plant surface lipids can affect insect herbivore attachment and locomotion. Surface lipids may also affect herbivores indirectly by influencing predatory and parasitic insects. Glossy crop phenotypes are often less susceptible to insect herbivores than are normal phenotypes. The epicuticular lipids of glossy plants are usually reduced in amount and have dramatically different chemical compo­ sition and morphology. Study of the basis of the reduced suscept ibility of glossy plants can help elucidate the role of plant surface lipids in insect-plant interactions.

The prevalence and incidence of pressure ulcers in home care: Are patients at risk?

With the earlier discharge from the acute care setting, there may be an increased suscep tibility to the development of pressure ulcers in the home than ever before. A descriptive study was undertaken to determine pressure ulcer prevalence and incidence prior to in stituting prevention and treatment protocols. Study findings are presented in this article.

Olfactory bulb kindling in mice susceptible and resistant to ethanol withdrawal.

The relation between kindling and susceptibility to ethanol withdrawal seizures was investigated using withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice. These lines were developed by selective breeding to be prone and resistant, respectively, to handling-induced convulsions after chronic exposure to ethanol. Development of kindled seizures in response to electrical stimulation of the olfactory bulb was investigated in mice aged 2 and 8 months with no exposure to ethanol. Older WSP mice kindled more slowly than older WSR mice, requiring significantly more stimulations to reach the first stage 3 and the first stage 5 seizures. In younger mice, there was no significant difference between the two lines in the rate of kindling. The lower kindling rate in mature WSP mice is in contrast to their higher sensitivity to handling-induced convulsions on withdrawal from ethanol and other agents. This finding suggests that separate genetic factors underlie these two models of mouse seizures.

51V NMR study of the electronic correlation in layered perovskite compounds Sr n+1 V nO 3 n+1

NMR measurements have been made to study the electron correlation effect in metallic layered perovskite compounds Sr n+1 V n O 3 n+1 ( n =2, 3 and ∞). It has been found that the exchange enhancement of the spin susceptibil ity increases with decreasing n from ∞ to 2 within the random phase approximation.

Behaviour and fitness of γHCH/dieldrin resistant and susceptible female Anopheles gambiae and An.stephensi mosquitoes in the absence of insecticide

The effects of gamma HCH/dieldrin resistance genes on various fitness components of mosquito larvae and adult females in the absence of insecticide were investigated in backcrossed strains of Anopheles gambiae Giles and An.stephensi Liston. Among larvae, heterozygotes (RS) developed slightly but significantly faster than homozygotes for resistance (RR) or susceptibility (SS). The lifetime fecundity of RR females in population cages was only half to two-thirds that of SS and RS females despite similar longevities; several reasons were identified: RR gravid females were less responsive to oviposition-site stimuli, their spontaneous activity--as measured in an acoustic actograph--was only half that of SS or RS females, and RR females produced fewer eggs per unit bloodmeal. When inseminated females were recorded in LD 12:12, RR were again less active than SS or RS. When the lighting was switched to a regime simulating full-moonlight, the activity pattern of SS and RS changed and they flew for longer periods. In contrast, the activity of RR females was the same in LD 12:12 as in 'moonlight'. In a test simulation of potential predation, RR mosquitoes took to flight least readily. All component tests on adult females therefore point to RR as being the least fit of the three genotypes. The behavioural tests suggest that resistance has raised the response threshold of RR females to diverse stimuli. A possible physiological mechanism underlying RR behaviour is that a change in the cyclodiene receptor on the chloride channels has increased their permeability to chloride ions, causing hyper-inhibition of the nervous system.

Evidence of different magnetic phases in amorphous Fe xSi 1− x/Si multilayers

Some of the magnetic properties of sputtered amorphous Fe x Si 1− x /Si multilayers are reported. The composition and modulation length range between 0.60 ⩽ x⩽ 0.80 and 3 Å < d < 70 Å, respectively. From transverse biased initial susceptibil ity measurements, using the magneto-optic Kerr effect, we found evidence of the existence of two magnetic phases in these multilayers. The second phase may be constituted by Fe-rich interlayers, caused by the sample preparation method.

Effects of the lethal yellow (AY) mutation in mouse aggregation chimeras

The Ay allele is a recessive lethal mutation at the mouse agouti locus, which results in embryonic death around the time of implantation. In the heterozygous state, Ay produces several dominant pleiotropic effects, including an increase in weight gain and body length, a susceptibility to hepatic, pulmonary and mammary tumors, and a suppression of the agouti phenotype, which results in a yellow coat color. To investigate the cellular action of Ay with regard to its effects upon embryonic viability and adult-onset obesity, we generated a series of aggregation chimeras using embryos that differ in their agouti locus genotype. Embryos derived from Ay/a x Ay/a matings were aggregated with those derived from A/A x A/A matings, and genotypic identification of the resultant chimeras was accomplished using a molecular probe at the Emv-15 locus that distinguishes among the three different alleles, Ay, A, and a. Among 50 chimeras, 25 analyzed as liveborns and 25 as 9.5 day embryos, 29 were a/a in equilibrium A/A and 21 were Ay/a in equilibrium A/A. The absence of Ay/Ay in equilibrium A/A chimeras demonstrates that Ay/Ay cells cannot be rescued in a chimeric environment, and the relative deficiency of Ay/a in equilibrium A/A chimeras suggests that, under certain conditions, Ay heterozygosity may partially affect cell viability or proliferation. In the 25 liveborn chimeras, Ay/a in equilibrium A/A animals became obese as adults and a/a in equilibrium A/A animals did not. There was no correlation between genotypic proportions and rate of weight gain, which shows that, with regard to its effects on weight gain, Ay heterozygosity is cell non-autonomous.

Nutritional modulation of phagocyte function with special emphasis on the newborn

Alterations in nutritional status, including protein-calorie malnutrition in man and studies in animals models, lead to changes in phagocyte (polymorphonuclear neutrophil and mononuclear phagocyte, monocyte-macrophage) function.1–3,61,62 In these acquired immunodeficiencies neutrophils have altered modulation of adherence, decreased random and directed movement and impaired microbicidal activity. These functions may be restored following nutritional repletion. Mononuclear phagocyte studies have been more limited yet suggest effects on metabolic, secretory and microbicidal functions. The problem of early postnatal malnutrition in the newborn is a special one, which requires further intensive investigation. In this situation, malnutrition may compromise an already inadequate immune system and alter host sus ceptibility to infection. We believe that increased understanding of the role of nutritional and immune factors in resistance to infection should yield new insights into the control and prevention of neonatal morbidity and mortality.

EFFECTS OF ALLOYING ON THE MAGNETIC AND STRUCTURAL BEHAVIOUR OF CeFe2

EFFECTS OF ALLOYING ON THE MAGNETIC AND STRUCTURAL BEHAVIOUR OF CeFe₂

The Germanization of Lenin

The American school of Lenin interpretation is unable to approach the maker of the November 7 insurrection with any degree of objectivity and therefore much of the American writing on Lenin is distorted.1 One source of this myopia stems from the fate of American liberalism in the 1950's and 1960's and its relation to the Totalitarianism debate. Confronted by the images of Hitler and Stalin and accepting the Totalitarianism argument as put forth by German emigr? scholars to the United States such as Sigmund Neumann and Karl J. Friedrich, American liberal historiography approached Lenin as an expression of Caesarism. According to Neumann and Friedrich, German fascism and Soviet dictatorship were both manifestations of a more universal phenomenon ? political domination by a monolithic party. In essence, all political societies in the 20th century had demonstrated a sus ceptibility to hegemonic rule2, and thus Hitlerian racism and Stalinist Communism were bound together by a common denominator, the autocracy of a single party. The American school of Lenin interpreta tion became a mode of the Whig interpretation history, and thus Lenin was imprisoned within a dictatorial image.3 One consequence of the larger tactic of branding Lenin as the originator of current Kremlin totalitarianism, was to capture him within the narodnik syndrome. By the term narodnik syndrome I refer to that interpretation of Lenin as continuing the 19th-century Russian revolu tionary tradition which was synonymous with elitist conspiracy. An additional term for 19th Century narodnism is Russian Jacobinism, an adjective also applied to Lenin, which was exemplified by Ishutin and Tkachev who advocated conspiratorial political action led by a minority. Another activity of certain sections of the Russian narodniki was political terrorism, and to affirm that Lenin was a Russian Jacobin is to claim that Lenin also condoned terrorist activities.4 The narodnik