Meningococcal disease: has the battle been won?

Meningococcal disease is a worldwide life-threatening infection associated in many cases with debilitating long-term sequelae, both within the military and civilian populations. Military recruits are at a higher risk of acquiring this infection due to numerous factors, such as young recruits in the age group 18-25 years, high carriage rates of meningococci, communal and crowed living quarters and global deployment or training in regions with different meningococcal serogroup epidemiology. Although these increased risk factors among young recruits remain, the increased incidence of disease is now historic. Numerous outbreaks have been reported among military personnel, however although the incidence of the disease continues to decrease, there are still sporadic cases. The non-specific symptoms, sudden onset and rapid progression of the infection results in a limited time frame to both diagnose and successfully treat the patient. Many developments have been made in relation to the microbiological diagnosis of the disease, particularly in the era of molecular diagnostics, which have the potential to diagnose the infection more quickly. Developments in vaccinology, and in particular with relation to biotechnology and reverse vaccinology, have led to the availability of new meningococcal vaccines, further enabling disease prevention. This paper outlines the history of meningococcal disease in relation to the military and highlights the new developments in both diagnostics and vaccination, which have the potential to diagnose, treat and control meningococcal disease in a more efficient manner.

The high-pitch notched audiogram: a cohort of patients without causative noise-induced hearing loss.

BACKGROUND: One still encounters opinion that hearing loss with high-pitch notched audiogram is invariably due to noise-induced hearing loss. This paper tests this misapprehension. METHODS: A study was conducted of patients identified in a prospective manner with notched audiograms but no history of noise exposure occurring in an otolaryngological practice over a 20-year period. RESULTS: A cohort of 26 hearing loss patients, in whom notched audiograms were not associated with historical evidence of noise exposure, was documented. CONCLUSION: The findings confirm that a notched audiogram is not pathognomonic of noise-induced hearing loss.

Reproduction-longevity trade-offs reflect diet, not adaptation.

A tenet of life history evolution is that allocation of limited resources results in trade-offs, such as that between reproduction and lifespan. Reproduction and lifespan are also influenced proximately by differences in the availability of specific nutrients. What is unknown is how the evolution of the ability to use a nutritionally novel diet is reflected in this fundamental trade-off. Does the evolution of the ability to use a nutritionally novel food maintain the trade-off in reproduction and longevity, or do the proximate effects of nutrition alter the adapted trade-off? We tested this by measuring trade-offs in male milkweed bugs, Oncopeltus fasciatus, fed either an adapted diet of sunflower or the ancestral diet of milkweed. Sunflower-fed males lived longer but invested less in reproduction, both in mating and fertility. Milkweed-fed males invested in both mating and fertility at the expense of survival. The evolution of an expanded diet was not constrained by the existing trade-off, but instead was accompanied by a different trade-off between reproduction and longevity. We suggest that this occurs because diets differ in promoting germ line development or longevity.

Diet and social conditions during sexual maturation have unpredictable influences on female life history trade-offs.

The trade-off between gametes and soma is central to life history evolution. Oosorption has been proposed as a mechanism by which females can redirect nutrients invested in oocytes into survival when conditions for reproduction are poor. Although positive correlations between oocyte degradation and lifespan have been documented in oviparous insects, the adaptive significance of this process in species with more complex reproductive biology has not been explored. Further, environmental condition is a multivariate state, and combinations of environmental stresses may interact in unpredictable ways. Previous work on the ovoviviparous cockroach, Nauphoeta cinerea, revealed that females manipulated to mate late relative to sexual maturation experience age-related loss in fecundity because of loss of viable oocytes via apoptosis. This loss in fecundity is correlated with a reduction in female mate choice. Food deprivation while mating is delayed further increases levels of oocyte apoptosis, but the relationship between starvation-induced apoptosis and life history are unknown. To investigate this, virgin females were either fed or starved from eclosion until provided with a mate at a time known to be suboptimal for fertility. Following mating, females were fed for the duration of their lifespan. We measured lifetime reproductive performance. Contrary to predictions, under conditions of delayed mating opportunity, starved females had greater fecundity, gave birth to more high-quality offspring and had increased longevity compared with that of fed females. We suggest that understanding proximal mechanisms underlying life history trade-offs, including the function of oocyte apoptosis, and how these mechanisms respond to varied environmental conditions is critical.

Spatial organization of the assembly pathways of glycoproteins and complex polysaccharides in the Golgi apparatus of plants.

The Golgi apparatus of plant cells is the site of assembly of glycoproteins, proteoglycans, and complex polysaccharides, but little is known about how the different assembly pathways are organized within the Golgi stacks. To study these questions we have employed immunocytochemical techniques and antibodies raised against the hydroxyproline-rich cell wall glycoprotein, extensin, and two types of complex polysaccharides, an acidic pectic polysaccharide known as rhamnogalacturonan I (RG-I), and the neutral hemicellulose, xyloglucan (XG). Our micrographs demonstrate that individual Golgi stacks can process simultaneously glycoproteins and complex polysaccharides. O-linked arabinosylation of the hydroxyproline residues of extensin occurs in cis-cisternae, and glycosylated molecules pass through all cisternae before they are packaged into secretory vesicles in the monensin-sensitive, trans-Golgi network. In contrast, in root tip cortical parenchyma cells, the anti-RG-I and the anti-XG antibodies are shown to bind to complementary subsets of Golgi cisternae, and several lines of indirect evidence suggest that these complex polysaccharides may also exit from different cisternae. Thus, RG-I type polysaccharides appear to be synthesized in cis- and medial cisternae, and have the potential to leave from a monensin-insensitive, medial cisternal compartment. The labeling pattern for XG suggests that it is assembled in trans-Golgi cisternae and departs from the monensin-sensitive trans-Golgi network. This physical separation of the synthesis/secretion pathways of major categories of complex polysaccharides may prevent the synthesis of mixed polysaccharides, and provides a means for producing secretory vesicles that can be targeted to different cell wall domains.

Quantitative genetic variation in the control of ovarian apoptosis under different environments.

Fertility loss in otherwise healthy individuals can be an evolutionary conundrum. Most studies on the evolution of post-reproductive lifespan focus on the fitness effects of survival past the age of last reproduction. A complementary approach, which has been largely neglected, is to develop an understanding of the nature of variation in the mechanism underlying loss of fertility, ovarian apoptosis. Variation in the genetics underlying the regulation of ovarian apoptosis could hold the key to understanding the evolution of midlife fertility loss. We estimated quantitative genetic variation in the regulation of ovarian apoptosis in females of the cockroach Nauphoeta cinerea, an insect with reproductive cycles. We have earlier shown that delaying reproduction incites loss of fertility. Here, we forced females to delay reproduction under conditions of excess or limited food and examined apoptosis under both conditions. We found substantial additive genetic variation in levels of apoptosis when females experienced a limited period of starvation during sexual maturation but not when females had unlimited access to food. Hence, selection could act on the regulation of ovarian apoptosis to change the rate of fertility loss with age at least under some environmental circumstances. Our results suggest that an understanding of how loss of fertility evolves requires an understanding of the interaction between genes involved in the regulation of apoptosis and environmental factors such as diet.

Using path signatures to predict a diagnosis of Alzheimer's disease.

The path signature is a means of feature generation that can encode nonlinear interactions in data in addition to the usual linear terms. It provides interpretable features and its output is a fixed length vector irrespective of the number of input points or their sample times. In this paper we use the path signature to provide features for identifying people whose diagnosis subsequently converts to Alzheimer's disease. In two separate classification tasks we distinguish converters from 1) healthy individuals, and 2) individuals with mild cognitive impairment. The data used are time-ordered measurements of the whole brain, ventricles and hippocampus from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We find two nonlinear interactions which are predictive in both cases. The first interaction is change of hippocampal volume with time, and the second is a change of hippocampal volume relative to the volume of the whole brain. While hippocampal and brain volume changes are well known in Alzheimer's disease, we demonstrate the power of the path signature in their identification and analysis without manual feature selection. Sequential data is becoming increasingly available as monitoring technology is applied, and the path signature method is shown to be a useful tool in the processing of this data.

Random forest prediction of Alzheimer's disease using pairwise selection from time series data.

Time-dependent data collected in studies of Alzheimer's disease usually has missing and irregularly sampled data points. For this reason time series methods which assume regular sampling cannot be applied directly to the data without a pre-processing step. In this paper we use a random forest to learn the relationship between pairs of data points at different time separations. The input vector is a summary of the time series history and it includes both demographic and non-time varying variables such as genetic data. To test the method we use data from the TADPOLE grand challenge, an initiative which aims to predict the evolution of subjects at risk of Alzheimer's disease using demographic, physical and cognitive input data. The task is to predict diagnosis, ADAS-13 score and normalised ventricles volume. While the competition proceeds, forecasting methods may be compared using a leaderboard dataset selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and with standard metrics for measuring accuracy. For diagnosis, we find an mAUC of 0.82, and a classification accuracy of 0.73 compared with a benchmark SVM predictor which gives mAUC = 0.62 and BCA = 0.52. The results show that the method is effective and comparable with other methods.

Sperm competition within a dominance hierarchy: investment in social status vs. investment in ejaculates.

There is increasing recognition that male-male competition can take many forms, but as yet the form is not predictable a priori. Many recent studies have focused attention on how males in disadvantaged mating roles compensate through sperm competition. However, mating systems in which subordinate males are reproductively suppressed, particularly through the stress of social interactions, may limit the ability of males to respond by increasing investment in sperm quality. We examined the interaction between social status and ejaculate tactics in Nauphoeta cinerea, a cockroach that has a mating system with well-characterized dominance hierarchies. Both social experience with other males and social status influenced aspects of ejaculates. The stress of social interactions reduced the size of the ejaculate and number of sperm inseminated. In ejaculates formed prior to social experience, however, males that go on to become dominant inseminated more sperm than males that go on to become subordinate, suggesting innate differences among males. Our results show that though selection for increased success in sperm competition for subordinate males in a hierarchy can occur, both the traits and the way in which the balance between pre- and post-copulatory strategies is negotiated will depend on specific details of the mating system. These details will include how the physiological effects of social interactions may limit selection through male-male competition.

The 'modified triple staple' technique: a variant stapling technique for anastomosis after low anterior resection.

INTRODUCTION: Stapled techniques of coloanal anastomosis in anterior resection have gained widespread acceptance over hand anastomosis. We believe a modification of the 'triple staple technique' has ergonomic advantages over existing stapling methods and present our technique and experience here. METHODS: Fifty consecutive patients underwent anterior resection with a concomitant defunctioning ileostomy in 44 (86%) patients. A modified triple staple technique of side to end coloanal anastomosis was performed without the need of a purse string suture on the proximal and the distal segments. RESULTS: There were no major intra-operative complications. 2/50 (4%) clinical leaks and 2/37 (5.4%) radiological leaks were noted. A combined leak rate of 4/50 (8%) was reported. The incidence of anastomotic stricture encountered was 1/50 (2%). CONCLUSION: The modified triple staple technique for side to end anastomosis in anterior resection has ergonomic advantages and comparable safety to the existing techniques of stapling coloanal anastomosis. We believe this technique can be widely adopted as an added alternative to the current techniques of stapled anastomosis after anterior resection.

Distinguishing globally-driven changes from regional- and local-scale impacts: The case for long-term and broad-scale studies of recovery from pollution.

Marine ecosystems are subject to anthropogenic change at global, regional and local scales. Global drivers interact with regional- and local-scale impacts of both a chronic and acute nature. Natural fluctuations and those driven by climate change need to be understood to diagnose local- and regional-scale impacts, and to inform assessments of recovery. Three case studies are used to illustrate the need for long-term studies: (i) separation of the influence of fishing pressure from climate change on bottom fish in the English Channel; (ii) recovery of rocky shore assemblages from the Torrey Canyon oil spill in the southwest of England; (iii) interaction of climate change and chronic Tributyltin pollution affecting recovery of rocky shore populations following the Torrey Canyon oil spill. We emphasize that "baselines" or "reference states" are better viewed as envelopes that are dependent on the time window of observation. Recommendations are made for adaptive management in a rapidly changing world.

Sexual conflict and the evolution of female mate choice and male social dominance.

Conflicts between the sexes over control of reproduction are thought to lead to a cost of sexual selection through the evolution of male traits that manipulate female reproductive physiology and behaviour, and female traits that resist this manipulation. Although studies have begun to document negative fitness effects of sexual conflict, studies showing the expected association between sexual conflict and the specific behavioural mechanisms of sexual selection are lacking. Here we experimentally manipulated the opportunity for sexual conflict in the cockroach. Nauphoeta cinerea and showed that, for this species, odour cues in the social environment influence the behavioural strategies and fitness of males and females during sexual selection. Females provided with the opportunity for discriminating between males but not necessarily mating with preferred males produced fewer male offspring than females mated at random. The number of female offspring produced was not affected, nor was the viability of the offspring. Experimental modification of the composition of the males' pheromone showed that the fecundity effects were caused by exposure to the pheromone component that makes males attractive to females but also makes males less likely to be dominant. Female mate choice therefore carries a demographic cost but functions to avoid male manipulation and aggression. Male-male competition appears to function to circumvent mate choice rather than directly manipulating females, as the mate choice can be cryptic. The dynamic struggle between the sexes for control of mating opportunities and outcomes in N. cinerea therefore reveals a unique role for sexual conflict in the evolution of the behavioural components of sexual selection.

Clinical value of postnatal autopsy and genetics consultation in fetal death.

The aim of the present study was to investigate the clinical use of postnatal autopsy and genetics consultation in cases of fetal death in a teaching hospital. A retrospective analysis of medical records including pathology and genetics reports was performed in all cases of fetal death in which a woman delivered at Ben Taub General Hospital, Houston, Texas over a 2-year period. Cases were excluded when gestational age of the fetus was less than 20 weeks. Fetuses were only included when the 1- and 5-min Apgar scores were 0 and 0, respectively. There were 139 fetal deaths and 12,209 live born infants during the study period (stillbirth rate 1.125%). Although pathology services were used in 96.2%, a genetics consultation was obtained in only 12% of cases. Fetal autopsy provided a certain cause of fetal death in 19.4%, a probable cause for death in 36.3%, and was inconclusive in 44.3%. Among the cases in which a genetics consultation was obtained, a certain and probable cause for fetal death was found in 20% and 20% of cases, respectively. The utilization of genetics consultation was found to be independent of multiple clinical variables examined including ultrasound data, identification of maceration, and training level of resident. Our data show a frequent use of pathologic examination in cases of fetal death and an infrequent use of genetics consultation services. The request for genetics consultation seemed to have been made at random.

Pneumococcal endophthalmitis after corneal transplantation: control by modification of harvesting techniques.

Between January and September 1986, 61 patients underwent corneal transplantation at a university hospital, and three (4.9%) of the patients developed endophthalmitis. Cultures of the donor cornea were positive for Streptococcus pneumoniae. The transplant program was stopped and an investigation begun. Review of corneal transplants in 1985 showed that S pneumoniae was recovered from only 1 (1.5%) of 66 donor corneas compared with 6 (9.8%) of 61 in 1986 (P = 0.045; Fisher's exact test). Investigation showed that major changes had occurred in the corneal transplant program in 1986 as a result of a new state law. Coroner's cases had become the source of most corneas; younger donors were available, and corneas, instead of whole eyes, were collected in the coroner's office, often by part-time technicians. All of the infected corneas had been harvested by part-time technicians, instead of the regular eye bank technician, and came from younger donors (mean age 11.8 years v 27.2; P less than or equal to 0.02). Based on these observations, collection techniques were modified to reduce contamination of corneas during harvesting. This included the use of surgical drapes and gloves, collecting the cornea without interruption, saline irrigation of the eye, and inversion of the eye chamber to ensure complete contact of the cornea with the antibiotic-containing media. The program was restarted, and there were no corneal infections with S pneumoniae during a one-year follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescents and the contraceptive pill: the impact of beliefs on intentions and use.

OBJECTIVES: To determine which beliefs about the contraceptive pill predict adolescent females' intentions to use the pill and their actual pill use, and to examine how intentions toward other birth control methods influence adolescents' intentions to use the pill and their eventual pill use. METHODS: Three hundred forty-five adolescents were interviewed about their beliefs regarding the consequences of using the pill and about their intentions to use the pill and other contraceptive methods. Follow-up interviews were conducted 1 year later, during which subjects reported their sexual activity and oral contraceptive use over the course of the year. RESULTS: Concerns about health and physical appearance differentiated subjects who intended to use the pill from those who did not, those who reported actually using the pill at all from those who did not, and those who did or did not use the pill consistently. The impact of beliefs differed between sexually active subjects and those who first had sex after the initial interview. Intentions to use withdrawal were negatively related to subjects' use of the pill (beta = -0.19, P < .05), although intentions to use condoms were unrelated to pill use. Intentions toward abortion were unrelated to either intentions to use the pill or eventual pill use. CONCLUSIONS: Female adolescents' beliefs about the contraceptive pill predicted their initial intentions to use the pill and their actual pill use over the course of a year. Adolescents may view withdrawal-although apparently not condoms-as an alternative to pill use. Abortion appears to be a backup to pill use rather than a substitute.

Almitrine mimics hypoxia in fetal sheep with lateral pontine lesions.

Almitrine bimesylate is a potent and long-lasting respiratory stimulant in adult species. It acts by stimulating the peripheral chemoreceptors, where it has been shown to accumulate specifically, although its exact mechanism of action is uncertain. In the fetal lamb, however, it produces a profound inhibition of breathing even after denervation of the peripheral chemoreceptors. In this respect its action is similar to hypoxia. To investigate whether almitrine is hypoxia mimetic, we examined the effect of almitrine in nine fetal lambs of 120-130 days gestation. Five had lesions in the lateral pons that changed the fetal depressive response to hypoxia to one of stimulation. In the remaining four fetuses, the lesions did not bilaterally encompass the appropriate area of the pons; thus they still showed the normal fetal depressive response to hypoxia and so acted as controls. Almitrine (10 mg iv) caused a pronounced stimulation of breathing that lasted 406 +/- 26 min in all five fetuses with lesions that caused a stimulatory response to hypoxia. However, in the remaining four fetuses, in which the response to hypoxia was inhibitory, almitrine caused an inhibition of breathing that lasted 184 +/- 28 min. We conclude that the action of almitrine is like that of hypoxia and that, because it acts specifically on the chemoreceptors, it may prove to be a useful tool in the study of possible central chemoreceptor mechanisms.

Loa loa: experimental infection in two species of African primates.

Four species of primates, baboon (Papio anubis), patas monkeys (Erythrocebus patas), green monkey (Cercopithecus aethiops) and chimpanzee (Pan troglodytes) were inoculated with third-stage larvae of a human strain of Loa loa from Cameroon, West African. The baboon and patas monkeys developed patent infections after 135 to 148 days; the green monkeys and chimpanzee did not. In each animal which became patent, microfilaremia rose rapidly to high levels. In the baboon, but not in the patas monkeys, there was a suppression of microfilaremia during the 4th month of patency. After splenectomy, microfilariae reappeared in the peripheral blood in large numbers. In both baboon and patas monkeys, the microfilariae of Loa loa maintain the diurnal periodicity so characteristic of their behavior in man.